The Project Gutenberg eBook of The diagnostics and treatment of
tropical diseases, by Edward R. Stitt
This eBook is for the use of anyone anywhere in the United States and
most other parts of the world at no cost and with almost no restrictions
whatsoever. You may copy it, give it away or re-use it under the terms
of the Project Gutenberg License included with this eBook or online at
www.gutenberg.org. If you are not located in the United States, you
will have to check the laws of the country where you are located before
using this eBook.
Title: The diagnostics and treatment of tropical diseases
Author: Edward R. Stitt
Release Date: April 29, 2023 [eBook #70667]
Language: English
Produced by: Chris Curnow, John Campbell, University of the
Witwatersrand Health Science Library, The Bodleian, The
London School of Hygiene & Tropical Medicine and the Online
Distributed Proofreading Team at https://www.pgdp.net
*** START OF THE PROJECT GUTENBERG EBOOK THE DIAGNOSTICS AND TREATMENT
OF TROPICAL DISEASES ***
TRANSCRIBER’S NOTE
Italic text is denoted by _underscores_.
Bold text is denoted by =equal signs=.
A superscript is denoted by ^x or ^{xx}, for example P^2O^5.
A subscript is denoted by _{x}, for example NH_{4}OH.
Basic fractions are displayed as ½ ⅓ ¼ etc; other fractions are shown
in the form a/b, for example 4/10 or 1/40.
The tables in this book are best viewed using a monospace font.
Some minor changes to the text are noted at the end of the book.
THE DIAGNOSTICS
AND
TREATMENT OF TROPICAL DISEASES
BY
E. R. STITT, A. B., PH. G., M. D., SC. D., LL. D.
REAR ADMIRAL, MEDICAL CORPS, AND SURGEON GENERAL, U. S. NAVY, GRADUATE,
LONDON SCHOOL OF TROPICAL MEDICINE; MEMBER NATIONAL BOARD OF MEDICAL
EXAMINERS; MEMBER ADVISORY BOARD, HYGIENIC LABORATORY. FORMERLY:
COMMANDING OFFICER AND HEAD OF DEPARTMENT OF TROPICAL MEDICINE,
U. S. NAVAL MEDICAL SCHOOL; PROFESSOR OF TROPICAL MEDICINE,
GEORGETOWN UNIVERSITY, PROFESSOR OF TROPICAL MEDICINE,
GEORGE WASHINGTON UNIVERSITY; LECTURER IN TROPICAL
MEDICINE, JEFFERSON MEDICAL COLLEGE; ASSOCIATE
PROFESSOR OF MEDICAL ZOOLOGY, UNIVERSITY
OF THE PHILIPPINES
FOURTH EDITION—REVISED
WITH 159 ILLUSTRATIONS
LONDON
H. K. LEWIS AND CO., LTD.
1922
COPYRIGHT, 1922, BY P. BLAKISTON’S SON & CO
PRINTED IN U. S. A.
BY THE MAPLE PRESS YORK PA
PREFACE TO FOURTH EDITION
In this revision it has seemed desirable to adhere to the original
plan of the manual as such an arrangement of the contents gives to
the student or tropical practitioner a concise and readily accessible
presentation of the subject.
Accepting the spirochaetal etiology of yellow fever, as worked out
by Noguchi, I have transferred the chapter on this disease to the
section dealing with protozoal diseases and have endeavored to
present the more important features of the recent extensive additions
to our knowledge concerning this scourge of the tropics.
There is not a chapter in the book that has not been carefully
revised and brought up to date. Of the revisions made, the most
important deal with advances in the study of food deficiency
diseases, as will be noted under beriberi and pellagra.
I have enlarged various paragraphs on treatment, the additions
including descriptions of the treatment of hookworm disease by carbon
tetrachloride and of the methods of administering arsphenamine and
antimony.
Six new chapters have been added to the book, viz. Epidemic jaundice,
rat bite fever, tularaemia, tables of helminthic and arthropodan
diseases, trench fever, in Part I, and, in Part II, a chapter on the
diagnostics of tropical joint, muscle and bone lesions.
Extensive additions have been made to Chapter XLIII, “Diagnostic
problems and procedures, together with cosmopolitan diseases in the
tropics”; and in the chapter on blood examinations will be found a
presentation of our latest views as to acidosis as well as a table
giving the significance of the findings in blood chemistry.
Many new illustrations have been added and some of the older ones
replaced by others of greater teaching value.
Every effort has been made to retain the feature of a pocket manual
but it has been necessary to increase the number of pages from 524
to 610. The illustrations in the third edition numbered 119; in this
edition, 159.
In particular I have to express my indebtedness to Commanders C. S.
Butler and H. W. Smith of the Naval Medical Corps for advice and
assistance in the preparation of this edition. Dr. G. W. McCoy,
Director of the Hygienic Laboratory, has given me valued suggestions
as to changes in some of the old chapters and in the preparation of
the new chapter on Tularaemia.
Lieutenant Commander Bunker, the head of the Chemical Laboratory of
the Naval Medical School, has made the revisions of the subjects
dealing with physiological chemistry. Others, who have given me
advice and suggestions, have been Lieutenant Commander Reed and
Lieutenants Harper and Chambers of the Naval Medical School.
To Lieutenant Peterson I am indebted for assistance in the
proofreading and preparation of the index as well as in going over
the recent literature of tropical diseases.
PREFACE TO FIRST EDITION
There is no more striking evidence of advance in general medicine
than the present attitude of the physician or rather internist in the
diagnosis of the cases met with in a modern hospital ward. Instead
of first considering the evidence obtainable at the bedside and
then noting the laboratory findings as something apart and entirely
subordinate, we now find the two aids to diagnosis so correlated
that it is as difficult to note one kind of information as bedside
and other as laboratory as it formerly was to separate signs from
symptoms in the study of a case.
In tropical medicine, however, we have for many years made our
diagnosis in the laboratory, the bedside playing a subsidiary
part—the laboratory diagnosis is controlled by the bedside findings.
It was originally my idea to prepare a book which would enable
students to have presented to them in intimate relation the
laboratory and clinical aids to the diagnosis of tropical diseases. I
was forced to abandon this plan as it did not seem possible to take
up clinical diagnosis prior to the obtaining by the student of a
comprehensive knowledge of the facts in connection with each separate
tropical disease. There was not the same difficulty attaching to a
book exclusively devoted to the diagnostic methods of the laboratory
so that in 1908 a laboratory manual was published. More recently it
has occurred to me that my methods in teaching tropical medicine
from the clinical rather than the laboratory standpoint might be of
assistance to those who are interested in this very important branch
of medicine.
When we consider that a knowledge of malaria, blackwater fever,
amoebic dysentery, bacillary dysentery, liver abscess, pellagra and
hookworm disease is just as important for the medical man in the
Southern States of the United States as for the physician in tropical
colonial possessions, it will be realized that there is more of a
practical side to tropical medicine than is usually admitted.
Although this is intended as a companion volume to the one on
laboratory methods yet, in order to make it complete in itself, there
has been prepared under each disease a paragraph dealing with the
laboratory diagnosis of the disease under consideration.
Furthermore, under the sections on the blood, faeces and urine in the
diagnosis of tropical diseases, the laboratory methods which are of
practical application have been given.
The chief feature of the book is in presenting in Part II the
clinical side of tropical diseases from a standpoint of the signs
and symptoms of these diseases which are connected with anatomical
or clinical groupings rather than from the side of the individual
disease. Thus in Chapter XLIV the diagnostic points which may be
obtained from a study of the temperature chart are given while in
Chapter LII the neurological manifestations, which may be noted in
various tropical diseases, are presented.
In Part I each individual tropical disease is treated as taken up
in any of the well-known books on tropical medicine. It has seemed
to me, however, that the paragraphs on epidemiology and prophylaxis
should receive especial attention. Again, in order to bring out
more strongly the symptomatology of each disease, I have followed
the paragraph on symptomatology in general with a section dealing
with the symptoms in detail, as shown in a consideration of the
circulatory, respiratory, digestive, nervous and other systems.
The paragraph devoted to the definition of each important disease has
been prepared with a view to giving the reader a brief description of
the disease in its clinical and etiological aspects.
Small type has been used rather to supply headings than for the
purpose of indicating less important matter because in a book so
condensed it has not seemed advisable to present any subject not of
practical value.
This book is written from the standpoint of the teacher who aims not
only to give the essential points but to present them in a manner so
cross-referenced that the student has the subject presented to him
from every angle.
It has been my custom in preparing my lectures to abstract the
various works on tropical medicine in order that special points in
one book, not noted in the others, would stand out prominently.
In this connection I am deeply indebted to the manuals of Manson,
Scheube, Castellani and Chalmers, LeDantec, Jeanselme and Rist as
well as to the monographs in Maladies Exotiques, Albutt’s System of
Medicine, Osler’s System of Medicine, Mense’s Tropenkrankheiten and
Traite Pratique de Pathologie Exotique.
In particular I am indebted to Ruge and zurVerth’s
Tropenkrankheiten, to Brumpt’s Precis de Parasitologie and to the
only work in the diagnosis of tropical diseases I have been able to
obtain, that of Wurtz and Thiroux, entitled Maladies Tropicales.
In the section on blood examination I have advocated the adoption of
the scheme of differential counting brought out in Schilling-Torgau’s
work on the blood in tropical diseases.
I have freely consulted the various journals dealing with the subject
of tropical medicine as to recent advances in this branch of medicine
and I would particularly express my indebtedness to the Tropical
Diseases Bulletin which should be in the hands of every student of
tropical medicine, not only as an index to original papers but as
a guide as to the advisability of consulting such papers. These
abstracts are prepared by authorities in the different tropical
diseases and many of the abstracts indicate the value or lack of
value of the paper abstracted.
The tropical diseases are classified under those due to protozoa,
those due to bacteria, those due to filterable viruses, infectious
granulomata and tropical skin diseases. Sprue is classified as a food
deficiency disease for the reason that the cure seems to rest solely
in dietary treatment. Certain diseases which did not definitely
belong to any of the above-named sections were taken up under
diseases of disputed nature or minor importance. The second part of
the book deals with the clinical diagnosis of tropical diseases.
CONTENTS
PART I
TROPICAL DISEASES AND THEIR TREATMENT
DISEASES DUE TO PROTOZOA
CHAPTER I.—Malaria, 1.
CHAPTER II.—Blackwater fever, 55.
CHAPTER III.—The trypanosomiases, 66; African trypanosomiasis, 66;
Brazilian trypanosomiasis, 80; Animal trypanosomiases, 84.
CHAPTER IV.—The tropical relapsing fevers, 86.
CHAPTER V.—Yellow fever, 97.
CHAPTER VI.—Infectious jaundice, 114.
CHAPTER VII.—Rat bite fever, 118.
CHAPTER VIII.—The leishmaniases, 121; Visceral leishmaniasis, 127;
Cutaneous leishmaniasis, 135.
CHAPTER IX.—General considerations of dysentery, 141.
CHAPTER X.—Amoebic dysentery, 147.
CHAPTER XI.—Liver abscess, 164.
DISEASES DUE TO BACTERIA
CHAPTER XII.—Bacillary dysentery, 174.
CHAPTER XIII.—Plague, 188.
CHAPTER XIV.—Tularaemia, 213.
CHAPTER XV.—Cholera, 218.
CHAPTER XVI.—Malta fever, 237.
CHAPTER XVII.—Leprosy, 246.
FOOD DEFICIENCY DISEASES
CHAPTER XVIII.—Beriberi, 268; Rice and beriberi, 272; Ship
beriberi, 285; Scurvy, 286; War oedema, 287.
CHAPTER XIX.—Pellagra, 291; The diagnostic triad, 302.
CHAPTER XX.—Sprue, 313; Hill diarrhoea, 316.
HELMINTHIC INFECTIONS
CHAPTER XXI.—Ancylostomiasis, 319.
CHAPTER XXII.—Filarial infections, 336; Filaria bancrofti, 341;
Loa loa, 352; Onchocerca volvulus, 354; Dracunculus medinensis,
355.
CHAPTER XXIII.—The schistosomiases, 357; Japanese schistosomiasis,
364.
CHAPTER XXIV.—Minor helminthic infections, 368; Paragonimiasis,
368; Clonorchiosis, 371; Intestinal distomiasis, 373;
Strongyloides stercoralis, 374.
CHAPTER XXV.—Table of important animal parasite diseases, 377;
Protozoal diseases, 377; Trematodes, 379; Nematodes, 380;
Cestodes, 381; Arthropodan diseases, 382.
INFECTIOUS GRANULOMATA OF THE TROPICS
CHAPTER XXVI.—Yaws, 384.
CHAPTER XXVII.—Gangosa, 395.
CHAPTER XXVIII.—Mycetoma, 399.
CHAPTER XXIX.—Granuloma venereum, 404.
TROPICAL SKIN DISEASES
CHAPTER XXX.—Tropical ulcer, 407.
CHAPTER XXXI.—Tinea imbricata, 411.
CHAPTER XXXII.—Tinea cruris, 414.
CHAPTER XXXIII.—Pinta, 416.
CHAPTER XXXIV.—Minor tropical affections of the skin, 418;
Dermatophiliasis, 418; Tropical impetigo, 419; Piedra, 420;
Cutaneous myiasis, 421; Creeping eruption, 422; Craw-craw, 424.
TROPICAL DISEASES OF DISPUTED NATURE OR MINOR IMPORTANCE
CHAPTER XXXV.—Verruga peruviana and Oroya fever, 425; Oroya fever,
425; Verruga peruviana, 428.
CHAPTER XXXVI.—Dengue, 431; Dengue-like fevers, 438; Phlebotomus
or Pappataci fever, 438; Seven-day fever, 440; Sand-fly and
three-day fever, 441; Six-day fever, 441.
CHAPTER XXXVII.—Tsutsugamushi or Japanese River fever, 442.
CHAPTER XXXVIII.—Spotted fever of the Rocky Mountains, 446.
CHAPTER XXXIX.—Typhus fever, 451.
CHAPTER XL.—Trench fever, 460.
CHAPTER XLI.—Heat stroke and heat prostration, 464.
CHAPTER XLII.—Climatic bubo, ainhum, goundou, juxta-articular
nodules and visceral mycoses, 469; Climatic bubo, 469; Ainhum,
471; Goundou, 472; Juxta-articular nodules, 472; Visceral
mycoses, 474.
PART II
DIAGNOSTICS OF TROPICAL DISEASES
CHAPTER XLIII.—Diagnostic problems and procedures, together with
cosmopolitan diseases in the tropics, 477.
CHAPTER XLIV.—Onset and the temperature chart in the diagnosis of
tropical diseases, 491.
CHAPTER XLV.—Blood examinations in the diagnosis of tropical
diseases, 504.
CHAPTER XLVI.—The circulatory, respiratory and lymphatic systems
together with anaemia, haemorrhages and oedema in tropical
diseases, 547.
CHAPTER XLVII.—Jaundice and the liver and spleen in tropical
diseases, 557.
CHAPTER XLVIII.—The cutaneous system and the organs of the special
senses, 561.
CHAPTER XLIX.—The urine and the genito-urinary apparatus in the
diagnosis of tropical diseases, 570.
CHAPTER L.—The faeces and the alimentary tract in tropical
diseases, 581.
CHAPTER LI.—The joints, bones and muscles in tropical diagnosis,
592.
CHAPTER LII.—Neurological considerations in tropical diseases, 598.
PART I
TROPICAL DISEASES AND THEIR TREATMENT
DESCRIPTION OF PLATE OF MALARIAL PARASITES
Benign Tertian Parasites
A1. _Schizonts._ 1. Normal red cell. 2. Young ring form. 3.
Amoeboid or figure-of-eight form showing Schüffner’s dots. 4.
Amoeboid form showing increased chromatin (twenty-four to thirty
hours). 5. Segmentation of nucleus. 6. Nuclear halves further
apart, red cells enlarged and pale. 7. Further division of nucleus.
8. Unusual division form. 9. Typical merocyte. 10. Rupture of
merocyte liberating merozoites.
A2. _Female gametes._ 1. Young form showing solid instead of
ring-form staining. 2. Half grown form. 3. Rapidly growing form
with compact nucleus and clear vacuolated zone. 4. Full grown
macrogamete showing eccentrically placed chromatin and much
pigment in deep blue stained protoplasm. _Male gametes._ 1. Young
form similar to female one. 2. Half grown form showing central
chromatin. 3. Full grown microgametocyte showing large amount of
centrally placed chromatin with light blue protoplasm surrounding.
4. Division of chromatin occurring in microgametocyte and
developing in wet preparation. NOTE.—Chromatin division in gametes
does not take place until blood is withdrawn. 5. Spermatozoon like
microgametes developing from the microgametocyte. This only occurs
in wet preparations or in the stomach of the mosquito.
Quartan Parasites
B1. _Schizonts._ 1. Normal red cell. 2. Young ring form. 3. Older
ring form. 4. Narrow equatorial band. 5. Typical band-form. 6. Oval
form showing division of chromatin. 7. Early stage merocyte. 8.
Daisy form merocyte.
B2. _Male gametes._ 1. Young solid form. 2, 3, 4. Developmental
stages microgametocytes. 5. Flagellated body in wet preparation
showing microgametes developing from microgametocyte. _Female
gametes._ 1. Young oval form. 2. Somewhat older stage. 3 and 4.
Mature macrogametocytes (same as benign tertian).
Malignant Tertian Parasites
C1. _Schizonts._ 1. Normal red cell. 2, 3, 4, 5, 6. Young ring
forms. These are hair-like rings and are the only forms besides
crescents to be found in the peripheral blood. _In very heavy
infections_ or in smears from spleen the following forms are found.
7. Beginning division of chromatin. 8 and 9. Further division. 10.
Merocyte.
C2. _Female gametes._ 1 and 2. Young macrogametes. 3. Older stage.
4. Development in red cell. 5 and 6. Fully developed female
crescents showing clumping of pigment and rich blue colour. _Male
gametes._ 1 and 2. Developing forms. 3 and 4. Fully developed
microgametocytes. 5. Flagellated body developed in wet preparation.
[Illustration: PLATE OF MALARIAL PARASITES]
SECTION I
DISEASES DUE TO PROTOZOA
CHAPTER I
MALARIA
DEFINITION AND SYNONYMS
=Definition.=—Malaria is a protozoal disease caused by three species
of _Plasmodium_. In the clinically benign types of malaria we have
that of benign tertian, due to _P. vivax_, with a tertian periodicity
and that of quartan, due to _P. malariae_ and showing a quartan
or seventy-two hour periodicity. The clinically malignant type of
malaria is due to _P. falciparum_, the parasite of malignant tertian
or aestivo-autumnal malaria.
The benign malarial fevers are characterized by a frank chill
and well marked distinctions of cold, hot and sweating stages.
In malignant tertian there is an indefinite or dumb chill with
prolonged hot stage. Diagnostic of malaria are periodicity,
parasites and splenic enlargement. The malignant tertian parasite
is the one responsible for the so-called cerebral and algid
manifestations of perniciousness. Man is the intermediate host of
the parasite while the sexual cycle or sporogony goes on in some
species of mosquito of the anopheline subfamily, the definitive
host.
=Synonyms.=—Remittent Fever, Intermittent Fever, Ague, Marsh Fever,
Paludism, Jungle Fever.
French: Paludisme. German: Wechselfieber.
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—Hippocrates, who considered malaria as intimately
connected with bile, divided the disease into quotidian, tertian
and quartan, differentiating such types of fever from continuous
fevers. It is interesting to note that Celsus recognized two types
of tertian fever, the one benign and similar to quartan fever, the
other far more dangerous, with a fever occupying thirty-six of the
forty-eight hours, not entirely subsiding in the remission, but
being only mitigated.
In the time of Caesar views were expressed by Varro that swamp air
might be the cause of malaria and furthermore that animals, so
small that the eye could not follow them, might transmit diseases
by way of the mouth or nose.
In the view of our present knowledge it is remarkable that Lancisi,
in 1718, should have associated marshes with the development of
gnats, which insects he thought could not only introduce with
their proboscides the putrefying organic matter of such swamps but
animalcules as well.
In 1638 Countess del Chinchon, the wife of the Viceroy of Peru, was
cured of an intermittent fever by the employment of the bark of
certain trees which bark was introduced into Europe in 1640. The
origin of the name cinchona is thus explained.
While Morton and Sydenham in 1666 noted the specific action of
cinchona in certain fevers it remained for Torti, in 1753, by the
use of cinchona, clinically to differentiate those fevers which
were cured by cinchona from those which failed to yield to this
specific. Quinine was not introduced until after 1820. Audouard, in
1803, was the first to draw attention to the splenic enlargement of
malaria.
The views of Nott and Beauperthuis as to transmission of malaria
and yellow fever by insects are considered under the latter disease.
In 1847 Meckel announced that the dark color of malarial organs
was due to a pigment and in 1848 Virchow noted that this pigment
was contained in cells. In 1875, Kelsch observed pigmented bodies
in malarial blood and in 1880 came to the conclusion that these
pigmented cells were diagnostic of malaria.
The year 1880 is the most important one in the history of malaria
for on November 6, 1880, Laveran, at Constantine, first saw the
parasites of malaria while carrying on investigations as to the
origin of the pigmented bodies and melaniferous leucocytes. He not
only noted the findings of spherical pigmented bodies but also of
crescents and in particular the flagellation of the male gamete
which demonstrated to him that these were living bodies.
The name _Oscillaria malariae_ was proposed on account of the
movements of the flagellate body, but had to be dropped as not
valid, the generic name _Oscillaria_ having been previously applied.
When these bodies were demonstrated to various Italian authorities,
in 1882, they were thought by them to be degenerated red cells.
It may be stated that at this time the Italians, influenced by
the work of Pasteur, were convinced that an organism, _Bacillus
malariae_, reported by Klebs and Crudeli (1879) to have been
isolated from water and soil of malarious districts, was the cause
of malaria. This bacillus was said to be cultivable on ordinary
media and to be capable, when injected into man, of producing
malaria.
By 1885 the Italians were convinced that the bodies discovered by
Laveran were the cause of malaria and Marchiafava, by staining with
methylene blue, noted the ring forms and the increase in size up
to that of the sporulating parasites. To Golgi we not only owe the
discovery that the malarial paroxysm coincides with the period when
the sporulating forms (merocytes) simultaneously reach maturity
but also the exact working out of the cycle of quartan malaria.
He even showed three stages of development of the parasites in a
triple quartan. It may be stated that Golgi, Marchiafava and Celli
are the ones to whom we owe our first knowledge of the existence
of different species of parasites for different kinds of malaria.
In these investigations they showed that as a rule they could
reproduce a certain type of malaria by injecting the blood of
such a case of malaria into a well man. Gerhardt, in 1884, was
the first to produce malaria by the injection of malarial blood.
Laveran insisted all this time that there was but a single species
of malaria. About this period a great deal of research was carried
on as to the origin of malarial parasites and it was found that
many animals harbored parasites similar to the malarial parasites
of man. In 1891 the chromatin staining method of Romanowsky was
introduced which by bringing out the variations in chromatin
distribution led to more accurate study of species and cycles.
Our present exact knowledge as to the existence of 3 species of
malaria is largely due to the careful examinations made by Koch of
fresh and stained malarial blood preparations.
[Illustration: FIG. 1.—Geographical distribution of malaria.]
In 1894 Manson formulated the hypothesis of the mosquito
transmission of malaria. He based this upon the fact that the
flagellation of the male gamete does not take place for several
minutes after the removal of the blood from the peripheral
circulation. He also suggested that larvae might feed upon infected
mosquitoes dying upon the water and thus acquire the disease.
Ross for two years had mosquitoes feed upon the blood of malarial
patients which contained crescents but as he used insects of the
genera _Culex_ and _Stegomyia_ he failed to observe development
in the tissues of the mosquitoes. In 1897 he used 8 dappled-wing
mosquitoes (Anopheline) and in two of these, upon dissection, he
noted pigmentary bodies different from anything he had observed in
hundreds of dissections of other mosquitoes. At this time he was
forced to discontinue this work for about six months.
In 1886 Metschnikoff from observation of sporulating parasites in
the brain capillaries at the autopsy of a malarial case considered
them to be coccidial in nature. In 1892 Pfeiffer, studying the
Coccidia showed that there was an endogenous cycle going on in
the epithelial cells as well as the long known exogenous cycle
connected with the ingestion of oocysts passing out in the feces
of an animal infected with coccidiosis. He suggested that malaria
might similarly have an exogenous cycle as well as the well-known
endogenous one. Opie noted hyaline and granular forms of parasites
in the blood of crows and MacCallum, working with this malaria-like
disease of birds (_Halteridium_), observed the fecundation of a
granular female parasite by the flagellum-like process of the
hyaline male cell.
In 1898, in India, working with a malarial disease of sparrows
(_Proteosoma_), Ross infected 22 out of 28 healthy sparrows by
mosquitoes which had previously fed on sick sparrows. He noted in
the culicine mosquito employed for transmission the same cycle of
development as that subsequently worked out for human malaria, in
anopheline mosquitoes, by Grassi and Bignami, in Italy.
Koch’s great work in connection with malaria was to demonstrate
that the malaria-like infections of other animals had no part in
the causation of human malaria and that the malarial parasite could
only circulate between man and certain mosquitoes.
In order to demonstrate conclusively the connection between
infected mosquitoes and malaria Sambon and Low lived for three of
the most malarious months of 1900, in one of the most malarious
sections of the Roman Campagna, in a mosquito screened hut and did
not contract malaria.
Infected mosquitoes were also sent to London from Italy and allowed
to feed upon Doctor P. T. Manson and Mr. George Warren. After
a period of incubation these volunteers came down with typical
malaria with parasites in the blood.
In 1911 Bass first cultivated the parasites of malaria.
=Geographical Distribution.=—Malaria is so widely distributed
over all parts of the tropical and subtropical world that it would
require too much space to give its geographical distribution other
than as given in the accompanying chart. The malaria belt may be
said to extend from 60° N. to 40° S. Many of the islands of the
Pacific are exempt.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—There are at least three species of animal parasites
which produce human malaria, _Plasmodium vivax_, the cause of
benign tertian, _P. malariae_ of quartan and _P. falciparum_ of
aestivo-autumnal. These parasites belong to the haemamoeba type of
the order Haemosporidia, of the class Sporozoa and of the phylum
Protozoa.
This type of Haemosporidia is characterized by invasion of red
cells, amoeboid movement, pigment production and the extrusion of
flagellum-like processes from the male sporont after the blood is
taken from the animal and allowed to cool.
Other Haemosporidia which are very important in diseases of
domesticated animals, but not for man, are those of the piroplasm
type.
These parasites of the red cells do not produce pigment and do
not “exflagellate.” It is to parasites of this type that some
authorities have ascribed the cause of blackwater fever, a
condition undoubtedly connected with malaria.
It has been thought proper by some to consider the malarial parasites
as belonging to two genera, the genus _Plasmodium_, characterized
by round sexual forms and including _P. vivax_ and _P. malariae_ and
the genus _Laverania_, characterized by crescent-shaped sexual forms
and including but one species _L. malariae_, that of aestivo-autumnal
malaria.
Craig recognizes a quotidian form and a tertian form for the
aestivo-autumnal parasite. Manson formerly held the view that three
different species of crescent-bearing parasites were concerned
in malignant infections; one, of tertian periodicity, _Laverania
malariae_, and two, of quotidian periodicity, _L. praecox_, a
pigmented form, and _L. immaculata_, a form in which pigment is
only observed in the crescent formation and does not exist in the
ring form schizonts. He has abandoned this view. Stephens has noted
a parasite which has more nuclear material than _P. falciparum_
(_P. tenue_).
_Malaria of Animals_.—Other Haemosporidia of the haemamoeba type
are found in birds, monkeys, bats, squirrels and possibly in
reptiles (the parasites of reptiles, while intracorpuscular and
pigment producing, do not exflagellate). Of particular interest is
the so-called bird malaria or _Proteosoma_, a parasite very similar
to the human malarial ones.
The life cycle of this parasite was demonstrated before that of the
malarial parasites of man.
Although Koch in his work showed that these malaria-like parasites
of other animals were not infectious for man, Fermi has recently
carried out well-controlled experiments, by feeding laboratory
bred anophelines on the blood of various animals showing such
infections, and subsequently on men, with invariably negative
results.
Accumulated experience shows that man is not susceptible to any of
the animal malarias and that the three human species can only exist
in man as an intermediate host and in certain species of anopheline
mosquitoes as definitive hosts. Culicine mosquitoes never transmit
malaria.
_Malaria-Transmitting Mosquitoes_.—In the United States,
_Cellia albimana_, _C. argyrotarsis_, _Anopheles crucians_,
_A. quadrimaculatus_ and _A. pseudopunctipennis_ are efficient
transmitters of malaria. Rather remarkable is the experience of
Beyer in New Orleans that _A. crucians_ will only transmit _P.
falciparum_ while _A. quadrimaculatus_ will transmit _P. vivax_ and
_P. malariae_, but not _P. falciparum_. Further experiments have
shown that _A. crucians_ will transmit _P. vivax_ as well as _P.
falciparum_.
As showing the uncertainty attaching to the question of a certain
anopheline species being efficient hosts for malaria may be cited
the case of _A. punctipennis._ This species has been frequently
reported as incapable of transmitting malaria and quite recently
Mitzmain reported experiments on 219 females of the species which
had fed on crescent containing blood and which were dissected
from three to thirty-eight days after such feedings with negative
findings in stomach and salivary glands. Furthermore, these
mosquitoes failed to transmit malaria to healthy persons. Control
experiments with _A. quadrimaculatus_ and _A. crucians_ were
successful. In June, 1916, Dr. King reported 33% of positive
findings after dissection of _A. punctipennis_ which had fed on
malignant tertian cases and 85% of success where the man bitten
had benign tertian malaria. These results showed as high a degree
of success as that obtained with the control _A. crucians_ and _A.
quadrimaculatus_.
From the above it must be evident that there are other factors
involved besides that of the host species as both Mitzmain and King
are expert epidemiologists.
A species which may be the chief transmitter in one country may
be unimportant, though present, in another country. Thus _Cellia
albimana_ is the chief malarial transmitter of Panama although _C.
argyrotarsis_ is present. In Brazil the conditions are reversed,
probably due to _C. albimana_ thriving best where slightly brackish
pools of standing water abound, as in Panama.
In the Philipines _A. febrifer_ seems the important transmitter. It
freely enters houses and is a vicious biter.
In India the species which seem most active in transmitting malaria
are _Myzomyia culicifacies_ and _M. listoni_; while in Africa, _M.
funesta_ is very efficient.
In Europe _A. maculipennis_ and _A. bifurcatus_ are important.
The following species of anophelines selected from the different
genera are important transmitters of malaria.
_Anopheles maculipennis_.—Wings with four spots located at bases
of both forked cells and of second and third longitudinal veins. No
costal spots. Palpi yellowish brown and unbanded. Legs unbanded.
_Anopheles punctipennis_.—Wings with black costa showing yellow
spots at apical third and at apex. The apical spot involves the
first long vein and upper branch of first fork cell. The larger
spot at the apical third passes through the first long vein and to
the second vein just before it branches. In _A. pseudopunctipennis_
the markings are as above but the fringe has yellow spots.
_Myzomyia funesta_.—Wings with four yellow spots on a black costa
and two black line spots on third longitudinal vein. Palps with
three white rings. Proboscis unbanded. Legs with faint apical bands.
_Pyretophorus costalis_.—Costa black with five or six small yellow
spots. Palps with two narrow white bands and white tip. Femora and
tibiae with yellow spots. Apical tarsal bands.
_Myzorhynchus pseudopictus_.—Black costa with two pale yellow
spots. Wing fringe unspotted. Black palps with four pale bands.
Apex of palps white.
_Nyssorhynchus fuliginosus_.—Black costa with three large yellow
spots. Numerous black dots on the longitudinal veins. Palpi black
with white tip and two narrow white bands. Last three hind tarsal
segments white.
_Cellia argyrotarsis_.—Black costa with two distinct and several
smaller white spots.
While anophelines are usually rural or at any rate preferring the
suburbs of cities yet we can differentiate between domesticated and
wild anophelines, these latter keeping away from man and consequently
not playing a transmitting rôle.
Another factor in their becoming an efficient host appears to rest
in the feeding habits of such anophelines, one which is voracious
and fills and then ejects by rectum the blood taken from the
malarial patient is more apt to be a transmitter than a species
less greedy.
By an _efficient host_ is meant a species in which full development
of the parasite takes place.
LIFE HISTORY OF THE MALARIAL PARASITE
Malaria can be transmitted by subcutaneous or intravenous injection
of the blood of a patient with the disease into a well person, the
same type being reproduced.
=Transmission of Malaria.=—Such a method of transmission is only of
scientific interest and the regular method is as follows: An infected
anopheline at the time of feeding on the human blood introduces
through a minute channel in the hypopharynx the infecting sporozoite
of the sexual cycle.
When man is first infected by sporozoites we have starting up a
nonsexual cycle (schizogony) which is completed in from forty-eight
to seventy-two hours, according to the species of the parasite.
The falciform sporozite bores into a red cell, assumes a round
shape and continues to enlarge (schizont). Approaching maturity,
it shows division into a varying number of spore-like bodies. At
this stage the parasite is termed a merocyte. When the merocyte
ruptures, these spore-like bodies or merozoites enter a fresh cell
and develop as before.
=Malarial Toxin.=—At the time that the merocyte ruptures it is
supposed that a toxin is given off which causes the malarial paroxysm.
Rosenau, by injecting, intravenously, filtered blood, taken from
a patient at the time of sporulation of the parasites caused a
malarial paroxysm. No parasites developed later. Another man who
received a small amount of unfiltered blood allowed a slight
paroxysm and four days later showed parasites in his blood. Hence
the parasite will not pass through the pores of a Berkefeld filter.
=Schizogony.=—The nonsexual cycle goes on by geometric progression
from the first introduction of the sporozoite, but it is usually
about two weeks before a sufficient number of merocytes rupture
simultaneously to produce sufficient toxin for symptoms (period of
incubation). This cycle is termed _schizogony_. It is considered
that there must be several hundred parasites per cubic millimeter
sporulating to be capable of producing symptoms.
=Gametes.=—After a varying time, whether by reason of necessity
for renewal of vigor of the parasite by a respite from sporulation,
or whether from a standpoint of survival of the species, sexual
forms (gametes) develop. Some think that sporozoites of sexual and
nonsexual character are injected at the same time. It is usually
considered, however, that sexual forms develop from preexisting
nonsexual parasites. The developing gametes are often termed
sporonts. Strictly, the sexual parasites in the blood should be
called gametocytes. The gametes take about twice as long to reach
maturity as schizonts. The life of a crescent has been estimated
as about ten days and that of the gametes of benign tertian and
quartan about one-half this period.
[Illustration: FIG. 2.—Sexual (sporogony in mosquito) and nonsexual
(schizogony in man) cycle of the malarial parasite. The sporogony
diagram to the left shows in lower portion the fertilization of the
female gamete by the microgamete. The vermiculus stage of the zygote
is shown boring into the walls of the mosquito’s stomach to later
become the more mature zygote packed with sporozoites as shown in
the upper diagram of the developmental processes in the mosquito’s
stomach.]
=Sporogony.=—The gametes show two types the one which contains
more pigment, has less chromatin, and stains more deeply blue is
the female—a macrogametocyte; the other with more chromatin, less
pigment, and staining grayish green or light blue is the male—a
microgametocyte. When the gametes are taken into the stomach of the
Anophelinae, the male cell throws off spermatozoa-like projections,
which have an active lashing movement and break off from the now
useless cell carrier and are thereafter termed microgametes.
These fertilize the macrogametes and this body now becomes a
zygote. (Following nuclear reduction with formation of polar
bodies the macrogametocyte becomes a macrogamete). This process
of exflagellation can be observed in a wet preparation under the
microscope. There is first seen a very active movement of the
pigment of the male gamete and finally long delicate bulbous-tipped
flagellum-like processes are thrown off (exflagellated) and push
aside the red cells by their progressive motion. MacCallum saw a
female _Halteridium_ fertilized by the microgamete, after which it
was capable of a worm-like motion (vermiculus or ookinete).
By a boring-like movement the vermiculus stage of the zygote goes
through the walls of the mosquito’s stomach, stopping just under
the delicate outer layer of the stomach or mid-gut. In three or
four days after fertilization the zygote becomes encapsulated and
is then often called an oocyst. It continues to enlarge until about
the end of one week it has grown to be about 50µ in diameter and
has become packed with hundreds of delicate falciform bodies. Some
only contain a few hundred, others several thousand.
=Zygotes.=—In some of his observations Darling has noted that the
zygote of benign tertian malaria grows larger and more rapidly
than that of aestivo-autumnal and that the pigment is clumped
rather than in belts or lines as with aestivo-autumnal. Darling has
also noted that mosquitoes do not tend to become infected unless
the gamete carrying man has more than 12 gametes to the cubic
millimeter of blood. Rouband notes that the oocysts of _P. vivax_
are feebly refractile with fine granules of gray pigment in loose
chains while _P. falciparum_ ones are highly refractile with large
grains of black pigment. At a temperature of 25°C. vivax completes
its cycle in 11 days while the zygote of the crescent requires 14
days. Apparently it is possible for a mosquito to carry both types
of parasites.
The capsule of the mature zygote ruptures about the tenth day
and the sporozoites are thrown off into the body cavity. They
make their way to the salivary glands and thence, by way of the
veneno-salivary duct, in the hypopharynx, they are introduced into
the circulation of the person bitten by the mosquito, and start a
nonsexual cycle. As the sexual life takes place in the mosquito,
this insect is the definitive host and man only the intermediate
host. The sexual cycle or _sporogony_ in the mosquito takes about
ten to twelve days.
=Efficient Mosquito Hosts.=—It must be remembered that only certain
genera and species of Anophelinae are known malaria transmitters;
thus Stephens and Christophers, in dissecting 496 mosquitoes of
the species _M. rossi_, did not find a single gland infected with
sporozoites.
With _M. culicifacies_, however, 12 in 259 showed infection. A
mosquito which is capable of carrying out the complete sporogonous
cycle is an efficient host and in the case of malaria the mosquito
is the definitive host (sexual life of parasite).
=Malarial Index.=—Mosquito dissection is one method of determining
the endemicity of malaria or the _malarial index_. There are two
other methods: 1. by noting the prevalence of enlarged spleens,
and 2. by determining the number of inhabitants showing malarial
parasites in the blood. This index is best determined from children
between two and ten years of age, as children under two show for a
general average too high a proportion of parasites in the peripheral
blood while those over ten years of age show too great an incidence
of enlarged spleens.
Barber working in the Philippines with children from five to ten
years of age obtained a spleen index of 13.3 and a parasitic index
of 11.
=As Before Stated there are Three Species of Malarial Parasites:= 1.
_Plasmodium vivax_, that of benign tertian—cycle, forty-eight hours;
2. _Plasmodium malariae_, that of quartan—cycle, seventy-two hours;
and 3. _Plasmodium falciparum_, that of aestivo-autumnal or malignant
tertian—cycle of forty-eight hours.
=Multiple Infections.=—Variations in cycles may be produced by
infected mosquitoes biting on successive nights, so that one crop
will mature and sporulate twenty-four hours before the second.
This would give a quotidian type of fever. In aestivo-autumnal
infections anticipation and retardation in the sporulation cause
a very protracted paroxysm, lasting eighteen to thirty-six hours;
this tends to give a continued or remittent fever instead of the
characteristic intermittent type.
=Plasmodium Vivax.=—In fresh, unstained preparations, taken at
the time of the paroxysm or shortly afterward, the benign tertian
schizont, or nonsexual parasite, is seen as a grayish white, round
or oval body, whose outlines cannot be distinctly differentiated
from the infected red cell. They are about one-fifth of the
diameter of the red cell and are best picked up by noting their
amoeboid activity. In about eighteen hours fine pigment particles
appear and make them more distinct. After twenty-four hours the
lively motion of the pigment and the projection of pseudopod-like
processes, in a pale and swollen red cell, make their recognition
very easy. When about thirty to thirty-six hours old the amoeboid
movement ceases. Approaching the merocyte stage the pigment tends
to clump into one or two pigment masses and one can recognize
small, oval, highly refractile bodies within the sporulating
parasite.
The gametes or sexual forms do not show amoeboid movement, but
the fully developed gamete, which is generally larger than the
red cells, has abundant pigment, which is actively motile in
the male gamete and nonmotile in the female. The male gamete
is more refractile, is rarely larger than a red cell and shows
yellow-brown, short rod-like particles of pigment. About fifteen
minutes after the making of a fresh preparation these male gametes
throw out four to eight long, slender, lashing processes, which
are about 15 to 20 microns long. These spermatozoon-like bodies
now break off from the useless parent cell and with a serpent-like
motion glide away in search of a female gamete, knocking the red
cells about in their passage through the blood plasma.
The female gamete is larger than a red cell, is rather granular and
has more abundant dark-brown pigment than the male.
=Stained Smears.=—In dried smears, stained by some Romanowsky
method, as that of Wright, Leishman or Giemsa, we note small
oval blue rings, about one-fifth of the diameter of the infected
yellowish-pink erythrocyte. One side of the ring is distinctly
broader than the rather fine opposite end, which seems to hold
a round, yellowish-brown dot, the chromatin dot, and has a
resemblance to a signet ring. These small tertian rings of the
nonsexual parasites (schizont) are seen about the time of the
commencement of the sweating stage of the paroxysm. Two chromatin
dots in the line of the ring are rare as is also true of more than
one ring in a red cell.
When the parasite is about twenty-four hours old we note that
it contains much pigment and has an amoeboid or multiple
figure-of-eight contour, is about three-fourths the size of a red
cell and that the infected red cell is about one and one-half times
as large as in the beginning and presents a washed-out appearance.
It is an anaemic-looking cell. We also note, as characteristic of
a benign tertian infection, reddish-yellow dots in the pale red
cell, which are known as Schüffner’s dots. These, practically, are
characteristic for benign tertian.
A few hours before the completion of its forty-eight-hour cycle the
contained pigment begins to clump, the chromatin to divide and,
finally, we have a sporulating parasite, in which the 16 to 20
small, round, bluish bodies, with chromatin dots, are irregularly
distributed over the area of the merocyte.
[Illustration: FIG. 3.—_Plasmodium vivax._ (Benign tertian)
Development of schizonts of nonsexual cycle in peripheral blood of
man. Red cell swollen and stains feebly. Note Schüffner’s dots. X
2200. (MacNeal after Doflein.)]
The gametes, or sexual parasites, show a thicker blue ring and have
the chromatin dot in the center of the ring. The pigmentation of
the half-grown gametes is more marked than that of schizonts of
equal size. The shape of the gametes is not amoeboid, as is that
of the twenty-four to thirty-six-hour-old schizont, but round or
oval. _The full-grown gametes have the pigment distributed and the
chromatin in a single aggregation—just the opposite of nonsexual
parasites._ The male gamete stains a light grayish blue and has
a very large amount of chromatin, usually centrally placed. The
female gamete stains a pure blue, has only about one-tenth as much
chromatin as plasma, with the chromatin often placed at one side.
The pigment of the female gamete is dark brown while that of the
male is yellowish brown.
[Illustration: FIG. 4.—_Plasmodium vivax_. (Benign tertian.) Double
infection of a red blood cell which is enlarged and shows Schüffner’s
dots. X 2200. (MacNeal after Doflein.)]
=Plasmodium Malariae.=—In fresh preparations the young quartan
schizont has only slight amoeboid movement and, as development
proceeds, the rather dark brown, coarse pigment tends to arrange
itself peripherally about the band-shaped or oval parasite.
The infected red cell shows but little change. At the end of
seventy-two hours the rather regular daisy form of the merocyte is
more distinct than that of the benign tertian merocyte.
The distinctions between the male and female gametes are similar to
those of the benign tertian gametes. In Romanowsky-stained smears
it is difficult to distinguish the young quartan schizont from
the benign tertian one but, after twenty-four hours, the tendency
of the quartan schizont to assume equatorial band forms across a
red cell of normal size and staining characteristics and without
Schüffner’s dots makes the differentiation easy. In the fully
developed sporulating parasite or merocyte the eight merozoites
assume a regular distribution, giving it a daisy appearance.
The gametes show practically the characteristics of the benign
tertian ones but are smaller.
=Plasmodium Falciparum.=—The young schizont of malignant tertian
is extremely difficult to detect in fresh preparations, there being
noted early in the rather long continued, hot stage, as small
crater-like dots, about one-sixth of the diameter of a red cell
which, however, show an active amoeboid movement.
[Illustration: FIG. 5.—_Plasmodium vivax._ Mature schizont and
merocyte. Found in the blood just before and at onset of chill. X
2200. (MacNeal after Doflein.)]
Malignant tertian blood tends to show rather marked vacuolation
of the red cells and these central vacuoles have a resemblance
to young ring forms. The malarial parasites are most often
peripherally placed and they do not enlarge and diminish in size on
focusing up and down as do the vacuoles.
[Illustration: FIG. 6.—_Plasmodium malariae._ (Quartan.) Development
of nonsexual parasite in blood of man. X 2200. (From MacNeal after
Doflein.)]
Later on in the hot stage these ring-like dots enlarge to become
about one-third of the diameter of a red cell, most often occupying
the periphery of the infected red cell. About this time, or at the
very commencement of the pigmentation, the schizont-containing red
cells disappear from the peripheral circulation so that the further
development is rarely observed in blood specimens.
The infected cell is brassy in color and shrunken in shape—it
shows evidences of degeneration. The gametes appear as
crescent-shaped bodies, which are absolutely characteristic of
malignant tertian, the male gamete being more hyaline and delicate
while the female one is more granular and larger.
[Illustration: FIG. 7.—_Plasmodium falciparum._ (Malignant tertian)
Nonsexual cycle in blood and internal organs of man. Note multiple
infections of single red cell. (From MacNeal after Doflein.)]
In Romanowsky-stained preparations we see, while the fever is
sustained, small hair-like rings, with geometrical outline, with
frequently two chromatin dots in one end of the ring and a single
red cell often showing two or more of these young rings. The rings
are often seen as if plastered on the periphery of the red cells
or as if having destroyed a rounded section of the rim of the
red cell. As the fever declines the rings tend to disappear from
the peripheral circulation. The infected red cells often show
polychromatophilia and distortion.
[Illustration: FIG. 8.—Tertian malarial parasite, one red cell
showing malarial stippling. (Todd.)
FIG. 9.—Estivo-autumnal malarial parasites, and small
ring forms and crescents. (Todd.)]
In old aestivo-autumnal cases, or those with severe infection, we
may see adult rings and merocytes, which latter are smaller than
those of benign tertian, show from 10 to 12 irregularly placed
merozoites and a sharply clumped mass of pigment.
The gametes are the striking crescent-shaped bodies and these show
the distinctions of blue-staining for the female, with lighter
gray-blue to purplish staining and abundance of chromatin for
the male. The chromatin staining of crescents does not stand out
so well as that of the round form gametes of benign tertian and
quartan.
The black pigment of the female tends to be clumped toward the
center while the rather generally distributed pigment of the male
is reddish brown rather than black in a stained preparation.
This variation of pigment color may be due to the effect of
chromatin staining, as the black of the pigment is the same in male
and female gametes in fresh blood preparations.
_Stained Smear Preferred._—As regards differentiation of species
and cycle the examination of stained smears is more satisfactory and
definite, as well as less time consuming. Still, one obtains many
points of differentiation in the fresh preparation and should study
such a preparation while carrying out the staining of his dried smear.
UNSTAINED SPECIMEN (FRESH BLOOD)
--------------+-------------------+------------------+--------------------
| P. vivax | P. malariae | P. falciparum
| (benign tertian) | (quartan) |(malignant tertian)
| | | (aestivo-autumnal)
--------------+-------------------+------------------+--------------------
Character of |Swollen and light |About the size and|Tendency to distor-
the infected | in color after | color of a normal| tion of red cell
red cell. | eighteen hours. | red cell. | rather than crena-
| | | tion. Shriveled
| | | appearance. (Brassy
| | | color.)
--------------+-------------------+------------------+--------------------
Character of |Indistinct amoeboid|Distinct frosted |Small, distinctly
young | outline. Hyaline. | glass disc. Very | round, crater-like
schizont. | Rarely more than | slight amoeboid | dots not more than
| one in r.c. Active| motion. | one-sixth diameter
| amoeboid movement.| | of red cell. Two to
| One-third diam. of| | four parasites in
| r.c. | | one red cell common.
| | | Shows amoeboid move-
| | | ment until appear-
| | | ance of pigment.
| | |
--------------+-------------------+------------------+---------------------
Character of |Amoeboid outline. |Rather oval in |Only seen in over-
mature | No amoeboid | shape. Sluggish | whelming infections.
schizont. | movement. | movement of | Have scanty fine
| | peripherally | black pigment
| | placed coarse | clumped together.
| | black pigment. |
--------------+-------------------+------------------+---------------------
Pigment. |Fine yellow-brown, |Coarse almost |Pigmented schizonts
| rod-like granules | black granules. | very rare in peri-
| which show active | Shows movement | pheral circulation
| motion in one- | only in young to | except in over-
| half-grown | half-grown | whelming infections.
| schizont. Motion | schizont. | Tends to clump as
| ceases in full- | | eccentric pigment
| grown schizont. | | masses almost black
| | | in color.
--------------+-------------------+------------------+---------------------
STAINED SPECIMEN
--------------+-------------------+------------------+---------------------
| P. vivax | P. malariae | P. falciparum
| (benign tertian) | (quartan) | (malignant tertian)
| | | (aestivo-autumnal)
--------------+-------------------+------------------+---------------------
Character of |Larger and lighter |About normal size |Shows distortion and
infected red | pink than normal | and staining. | some polychromato-
cell. | red cell. Shows | | philia and stippl-
| “Schüffner’s | | ing. Rarely we have
| dots.” | | coarse cleft-like
| | | reddish dots--
| | | Maurer’s spots.
--------------+-------------------+------------------+---------------------
Character of |Chromatin mass |Rather thick round| Very small sharp
young | usually single and| rings which soon | hair-like rings,
schizont. | situated in line | tend to show as | with a chromatin
| with the ring | equatorial bands.| mass protruding from
| of the irregularly| | the ring. Often
| outlined blue | | appears on periphery
| parasite. | | of red cell as a
| | | curved blue line
| | | with prominent
| | | chromatin dot.
| | | Frequently two
| | | chromatin dots.
--------------+-------------------+------------------+---------------------
Character of |Vacuolated or Fig. |More marked band | Not often found in
half-grown | 8 loop-like body | forms stretching | peripheral circula-
schizont. | with single | across r.b.c. | tion. Chromatin
| chromatin aggrega-| | still compact.
| tion. Schüffner’s | |
| dots. | |
--------------+-------------------+------------------+---------------------
Character of |Fine pigment rather|Coarse pigment |Very rarely seen in
mature | evenly distributed| rather peripher- | peripheral circula-
schizont. | in irregularly | ally arranged in | tion in ordinary
| outlined parasite.| an oval parasite.| infection. Pigment
| | | clumps early.
--------------+-------------------+------------------+---------------------
Character of |Irregular division |Rather regular |Sporulation occurs in
merocyte. | into 15 or more | division into | spleen, brain, etc.
| spore-like | eight or ten | Rarely in peripheral
| chromatin dot |merozoites--Daisy.| circulation. 6 to 10
| segments. | | irregularly placed
| | | merozoites. (In
| | | culture 32.)
--------------+-------------------+------------------+---------------------
Character of |Round deep blue. |Round, similar to |Crescentic, pure blue
macrogamete. | Abundant, rather | P. vivax but | pigment clumped at
| coarse pigment, | smaller. | center, chromatin
| chromatin at | | scanty and in
| periphery. | | center.
--------------+-------------------+------------------+---------------------
Character of |Round, light green-|Round like P. |More sausage-shaped
microgamet- | blue, pigment | vivax. | than crescent. Light
ocyte. | less abundant, | | grayish blue to
| chromatin abundant| | purplish. Pigment
| and located | | scattered
| centrally or in a | | throughout.
| band. | | Chromatin scattered
| | | and in greater
| | | quantity but diffi-
| | | cult to stain.
--------------+-------------------+------------------+---------------------
Central vacuolation of red cells is common in malarial anaemia and
may be mistaken for nonpigmented parasites.
Malarial rings are usually peripheral and do not vary in size as
one focuses up and down as do the central vacuoles.
_Quinine-affected Parasite._—A very puzzling but well-recognized
finding in cases treated with quinine or salvarsan is the so-called
quinine-affected parasite. Such parasites lack definiteness of
outline and show poor chromatin staining. The gametes do not seem
to show these effects from the drug.
=Certain questions connected with the life history of the malarial
parasite in man which are of interest.=
1. _Extracellular location._—It is usual to consider the parasite
as developing within a red cell and in this position to destroy the
red cell. Rowley-Lawson, however, thinks that the parasites are
exclusively extracellular and that they adhere to the red cells by
loop-like pseudopodia which encircle a portion of the red cell and
digest the haemoglobin of such an area.
2. _Relapses._—There are several views as to the etiology of
relapses in malaria. These views are taken up under relapses (see
page 35).
3. _Malarial toxin._—Nature of the toxic material thrown off by
the parasite at the time of simultaneous sporulation. Rosenau’s
experiments tend to show that there is a fever-producing toxin
thrown off at this time. Other authors have thought that a
haemolysin and an endotheliolysin were thrown off at the same
time. Brown considers that the pigment produced by the parasite,
in its metabolism of the haemoglobin of the red cell, may act as a
haemolysin, he having found that intravenous injections of haematin
were capable of producing marked anaemia. It is well known that
a far greater number of red cells are destroyed in a paroxysm
than would be accounted for by the actual percentage of red cells
destroyed by parasites. The endothelial cells take up actively this
malarial pigment or haemozoin and are damaged or destroyed thereby.
Haematin injections also tend to destroy leucocytes and platelets.
Rowley-Lawson is of the opinion that the greater red cell
destruction than would be represented by percentage of cells
showing parasites is explained by parasites migrating from cell to
cell so that many red cells may be destroyed by a single parasite.
4. _Transmission to larvae._—There has been an idea that
sporozoites might enter the ovaries and ova as well as the salivary
glands so that a second generation of mosquitoes might transmit
malaria. There is no proof that such a method is ever operative.
5. _Congenital malaria._—There has been some question as to the
possibility of congenital malaria. Heiser has recently reported the
case of an infant which showed crescents in its blood by the end of
one week from birth. The mother showed the same infection and the
child must have been infected through the placental circulation.
Clark in numerous examinations of the blood of the new-born
failed to find infection even when the mother’s blood teemed with
parasites. In one case where the child showed infection shortly
after birth there had been an accident to the placenta and he
believes that instances of so-called congenital malaria are to be
explained in this way.
6. _Cultivation of parasite._—As to cultivation of malarial
parasites. Bass takes from 10 to 20 cc. of blood from the malarial
patient’s vein in a centrifuge tube which contains 1/10 cc. of
50% glucose solution. A glass rod, or a piece of tubing extending
to the bottom of the centrifuge tube is used to defibrinate the
blood. After centrifugalizing there should be at least one inch
of serum above the cell sediment. The parasites develop in the
upper cell layer, about 1/50 to 1/20 inch from the top. All of the
parasites contained in the deeper-lying red cells die. To observe
the development, red cells from this upper 1/20 inch portion are
drawn up with a capillary bulb pipette.
Should the cultivation of more than one generation be desired,
the leucocyte upper layer must be carefully pipetted off, as the
leucocytes immediately destroy the merozoites. Only the parasites
within red cells escape phagocytosis. Sexual parasites are much
more resistant. Bass thinks he observed parthenogenesis. The
temperature should be from 40° to 41°C. and strict anaerobic
conditions observed. Aestivo-autumnal organisms are more resistant
than benign tertian ones. Dextrose seems to be an essential for the
development of the parasites.
Bass considers that _P. vivax_ has a disc-like structure which
enables it to squeeze through the brain capillaries while adult
schizonts of _P. falciparum_ have a solid oval form which causes
them to be caught in the capillaries.
The Thompsons have rather simplified the method of Bass. They draw
10 cc. of blood into a test tube containing the usual amount of
glucose solution. They then defibrinate the blood by stirring with
a thick wire for about five minutes and remove the wire with the
adhering clot. They then pour this defibrinated blood into several
small sterile test tubes, which should contain at least a one-inch
column. Rubber caps are adjusted over the cotton plugs and the
tubes placed in the incubator. They note the tendency of cultures
of _P. falciparum_ to agglutinate which is not true of _P. vivax_.
They think this agglutination the great cause of the plugging of
capillaries in pernicious malaria. They note 32 merozoites as
maximum number in sporulation of _P. falciparum_ while _P. vivax_
has usually 16 or more, but never as many as 32.
This would explain the shorter incubation period of malignant
tertian. The pigment of _P. falciparum_ clumps much earlier in the
developing schizont than that of _P. vivax_ and is much coarser and
more discrete.
While Bass thought he noted parthenogenesis in cultures others have
failed to observe any evidence of it.
7. _Immunity._—As to immunity. There is no real immunity to
malaria, it is a continuance of the infection, but the parasites
are not in sufficient numbers to give rise to fever. If, however,
the patient becomes chilled or fatigued or otherwise depressed,
fever results.
This apparent immunity is also kept up by reinfection, because
if natives leave the locality for a length of time they lose it.
Patients who show this apparent immunity to one form of malaria
have no such resistance to the other types. Bass states that immune
bodies are produced in malaria and that immune processes contribute
to control of the infection, but that it is not lasting and is not
effective against new infection.
8. _Perniciousness._—Causes of perniciousness. This is taken up
under perniciousness in malaria. (See page 31.)
9. _Quinine-affected parasite._—Effect of quinine on malarial
parasites. It is usually thought that the merozoites at the time
of being thrown off from the merocyte are most vulnerable, while
the gametes are only slightly affected, if at all. Still, the young
forms from which gametes develop are destroyed. Quinine causes
parasites to disappear from the peripheral circulation and produces
degenerative changes in such parasites as may remain. Bass thinks
that quinine makes the red cell permeable to the lytic action of
serum. Anaemia may cause degenerative changes in parasites similar
to that from quinine.
10. _Anaphylaxis and the paroxysm._—Abrami has brought forward
evidence in favor of the malarial paroxysm being due to the
outpouring of merozoites into the blood plasma which act as
foreign antigen. It is noted that the dissemination of merozoites
takes place some hours before the cold stage which is one of the
manifestations of anaphylactic shock. They note a leucopenia and
lowering of the blood pressure preceding the paroxysm as evidence
of a haemoclastic crisis.
The Anopheline Mosquito
The ova of culicine mosquitoes are usually deposited in a scooped-out
raft-like mass of about 250 eggs set vertically. The raft is easily
seen with the eye, being about ⅕ inch long. The anopheline eggs are
oval in shape with pleated air cell projections laterally. They are
laid upon the surface of the water, to the number of about 100, in
star, triangle or ribbon patterns. The egg stage is two to four days
but shorter, however, in the tropics.
The larval stage is the most important one to be acquainted
with because in this stage one can most readily distinguish the
anopheline or possible malaria transmitter from a culicine species.
One can more readily and quickly make a survey for anophelines by
examining the collections of water for larvae than in any other
way. The anopheline larva seems to prefer the surface, on which
it lies flat and out of the water. To keep it from turning over
on its long axis, it has little rosette-like hair tufts on the
dorsal surface of the 5 or 6 middle abdominal segments (palmate
hairs). There are feathered lateral hairs projecting from thorax
and abdominal segments. The head is very small in comparison with
the thorax and can be rotated with lightning-like rapidity. There
is no projecting breathing tube or syphon from the next to the last
abdominal segment, as is characteristic of _Culex_, _Stegomyia_ or
any other culicine genus.
In addition, culicine larvae do not float parallel to the surface
of the water, but hang suspended at an angle, with only the tip
of the syphon pushed upward to the surface. The lateral hairs or
bristles are not feathered and the head is much larger than that of
the anopheline larvae. It is the fact of the surface position of
these anopheline larvae which enables them to worm their way over
film layers of water or between blades of grass, in grass or rush
studded pools or swamps.
In the pupal stage it is rather difficult to differentiate
species of mosquitoes from each other, so that, other than to
recognize that the bloated shrimp-like body is a mosquito pupa, is
unnecessary.
[Illustration: FIG. 10.—In the above figure note the culicine egg
raft, 45° angle position of syphonate larva, parallel attitude of
resting mosquito, nonbulbous palpi of male and short palpi of female
as contrasted with the anopheline star or ribbon arrangement of eggs,
horizontal attitude of asiphonate larva, bradawl attitude of resting
mosquito, spotted wings, bulbous palpi of male and long palpi of
female mosquito. (From Jordan after Kolle and Hetsch.) MacNeal.]
DIFFERENTIATION OF CULICINAE AND ANOPHELINAE
It is impossible even for an entomologist to determine the species
of mosquitoes without recourse to elaborate keys and tables. It is
a comparatively easy matter, however, to decide as to whether the
mosquito is a probable malaria transmitter or not.
_The male anopheline._—While certain characteristics of the male
are used to separate the Aedinae from other subfamilies, yet it is
only with the female that we concern ourselves in differentiating
the Culicinae from the Anophelinae. Therefore, it is first
necessary to distinguish the male from the female. If the antennae
have not been torn off, this can be decided by the highly adorned
plumose antennae of the male, those of the female being sparsely
decorated with short hairs. The palpi of the male _Anopheles_ tend
to be clubbed, while those of the _Culex_ are straight. If the
antennae have been broken off, look for the claspers at the end of
the abdomen.
Male mosquitoes do not feed on blood but on fruits and flowers
instead. The puncturing parts of the male are not sufficiently
resistant to penetrate the skin.
_The female anopheline._—Having determined that the insect is
a female, we then proceed to place it either in the subfamily
Culicinae or Anophelinae by a study of the relative length of the
palpi to the proboscis. If the palpi are much shorter than the
proboscis, it belongs to the Culicinae; if about as long or longer,
to the Anophelinae. The palpi of the female Megarhininae are also
long, but the proboscis is curved.
Having settled on the subfamily, we separate the genera by
considering such points as character and distribution of scales on
back of head, wings, thorax, and abdomen; banding of proboscis, legs,
abdomen, and thorax, shape of scales on wings, and location of cross
veins.
[Illustration: FIG. 11.—Resting posture of mosquitoes; 1 and 2,
_Anopheles_; 3, _Culex pipienes_. (_After Sambon._) From P. H.
Reports.]
Anophelinae show abundant upright forked scales on occiput. The
mesothorax shows sparse hairs or scales with a smooth scutellum. As
a rule, the wings are spotted (dappled) and the location of these
spots gives the best clue to the different species of the genera.
With the exception of _Bironella_ the first submarginal cell is
large. This cell is longer than the second posterior one.
In the resting position _Culex_ allows the abdomen to droop, so
that it is parallel to the wall. The angle formed by the abdomen
with head and proboscis gives a hunchback appearance.
_Anopheles_ when resting on a wall goes out in a straight line at
an angle of about 45°. It resembles a bradawl.
The scutellum of _Anopheles_ is simple, that of _Culex_ trilobed.
_Anopheles_ has but one spermatheca; _Culex_ has three.
=Anophelinae=
{ 1. Scales on wings, large and lanceolate.
1. Scales on head only; { _Anopheles._ Palpi only slightly scaled.
hairs on thorax and { 2. Wing scales small and narrow and lanceolate.
abdomen. { _Myzomyia_. Only a few scales on palpi.
{ 3. Large inflated wing scales.
{ _Cycloleppteron._
2. Scales on head and {
thorax (narrow curved { 1. Wing scales small and lanceolate.
scales). Abdomen with { _Pyretophorus._
hairs. {
{ 1. Abdominal scales only on ventral surface.
{ Thoracic scales like hairs. _Myzorhynchus._
{ Palpi rather heavily scaled.
3. Scales on head and { 2. Abdominal scales narrow, curved or
thorax and abdomen. { spindle-shaped. Abdominal scales as tufts
Palpi covered with { and dorsal patches. _Nyssorhynchus._
thick scales. { 3. Abdomen almost completely covered with
{ scales and also having lateral tufts.
{ _Cellia._
{ 4. Abdomen completely scaled. _Aldrichia._
NOTE.—Of the above genera only _Cycloleppteron_ and _Aldrichia_
are unproven malarial transmitters.
The female anopheline mosquito alone bites man, the male feeding
on fruits and flower juices. The female absolutely requires blood
for the development of her eggs after fertilization by the male
mosquito.
The anopheline mosquito bites at night or toward evening and
selects some dark place or dark colored wall to sleep against
during the day. Hence the advantage of a buff colored wall
interior. It is well to remember that the malarial incidence may be
kept down by killing the mosquitoes inside of a house by striking
them with a folded paper or piece of wire gauze on a handle (fly
swatter).
It is not a bad plan to have a dark colored surface in a room to
attract them and make their destruction easy.
Anophelines do not like wind and seek protection of underbrush.
As regards distance of flight from breeding places Metz has noted
that _A. crucians_ were not distributed generally over 7000 feet
and rarely were found between 7000 and 9000 feet beyond which
distance they were not found. Some anophelines get accustomed to
feeding exclusively on animals. Mosquitoes may hibernate through
the winter and possibly cause new infections the following spring.
Cases of malaria in the spring are however usually due to relapses.
Mitzmain’s negative experiments with hibernating mosquitoes _prove
man_ to be the _winter carrier_.
[Illustration: FIG. 12.—Asiphonate (Anopheline) larva _Anopheles_. 2
Siphonate (Culicine) larva _Stegomyia_]
The malarial zygote will not develop in the stomach of the mosquito
if the temperature is below 16°C. (60°F.). It would seem that the
zygote of _P. malariae_ will develop at a lower temperature than
that of the other two species, _P. falciparum_ requiring the highest
temperature.
Our views as to temperature requirements for the development of
zygotes in the mosquito must be changed as King has recently shown
that _P. vivax_ sporonts will survive exposure to temperatures of
30°F. for two days and _P. falciparum_ temperatures of 35°F. for one
day. This proves that temperatures approximating freezing ones will
fail to destroy the parasites of hibernating mosquitoes.
Wenyon has found experimentally that mosquitoes which had fed on
malarial blood and kept at incubator temperatures for a week to
allow development of zygotes showed inhibition of development of
zygotes when kept at temperatures corresponding to hibernating
ones. This treatment did not kill the zygotes but complete
development took place when subsequently the mosquitoes were again
subjected to incubator temperatures. From this it would seem that
the zygotes remain viable during the winter hibernation. This is
at variance with Mitzmain’s views who regarded hibernation as
destructive to zygotes.
[Illustration: FIG. 13.—Anatomy of the mosquito. No. 6 shows various
types of scales.]
The mosquito does not seem to suffer from her malarial
infection—quite different from the serious affection that filariasis
causes in the mosquito.
=Epidemiology.=—This matter has been considered rather extensively
under the historical and etiological discussions.
It may be stated however that the requirements for the spread of
malaria are: (1) Men who have sexual forms of the malarial parasite
in their peripheral circulation; (2) efficient anopheline hosts, and
(3) an atmospheric temperature above 60°F. (16°C.).
[Illustration: FIG. 14.—_Anopheles maculipennis (quadrimaculatus)_,
female. (_Castellani and Chalmers, after Austen._) From P. H.
Reports.]
It is a well recognized fact in the tropics that the natives
seem to have an immunity to malaria yet may carry parasites in
their circulation and serve as carriers. The native children to
a striking degree harbour parasites and to them malaria is a
prime cause of death. After repeated infections, if not fatal, a
temporary immunity is acquired. Many localities in the tropics
owe freedom from malaria to an absence of anophelines, as for
instance Barbadoes. Again malaria-bearing mosquitoes may acquire
the habit of feeding on animal blood other than that of man. It is
well recognized that rural populations are more liable to malaria
than those of towns and as the population of a country moves to
the industrial centres human blood may become difficult to obtain
and the anophelines turn to other sources of blood supply. It has
been suggested that mosquitoes may suffer from other infections
which may be inimical to the development of malarial zygotes (black
spores of Ross). Anophelines bite chiefly at sunset and at night
from which fact there would seem to be some value in shutting the
windows towards nightfall as is the custom in many malarious parts
of the world.
Pools containing a border growth of grass or rushes are often
selected by anophelines for depositing eggs. The small fish
or tadpoles, which prey on the larvae, cannot work their way
through the obstacles and, again, petroleum oil cannot be easily
distributed in a network of grass. Anophelines of different species
and of different countries seem to vary in their selection of water
for depositing their eggs. We should not generalize but go out and
search for breeding places.
[Illustration: FIG. 15.—_Anopheles maculipennis (quadrimaculatus),
male._ (_After Castellani and Chalmers_.) From P. H. Reports.]
Anophelines seem to prefer small collections of water or sluggish
clear streams. The pools made by excavations following railway or
other similar construction are favorite breeding places. Proper
cultivation of rural districts makes the country more healthful and
Carter has stated that tile drainage is the key to rural malaria
control.
The most practical method for the identification of anopheline
species is to collect the larvae and later to study the adults
which develop from the pupae. On the whole culicines do not seem to
object to foul collections of water while anophelines avoid such
breeding places.
PATHOLOGY AND MORBID ANATOMY
The pathological lesions are those connected with the destruction
of enormous numbers of red cells, not only each infected red cell
being destroyed but others not so parasitised. There has been an
idea that at the time of sporulation and rupture of the merocyte a
pyrogenetic toxin was given off and along and with this there were
haemolysins and endotheliolysins. Following Brown we are justified in
thinking that the malarial pigment (melanin or haemozoin) can act as
a haemolysin and by being taken up by endothelial cells bring about
their degeneration with associated capillary haemorrhages. All three
factors—red-cell destruction by parasites, haemolytic action on red
cells and capillary haemorrhages lead to anaemia.
[Illustration: FIG. 16.—Digestive tract of _Anopheles_ the stomach
of which is covered with numerous zygotes or oocysts of _Plasmodium
falciparum_. _c_, cloaca; _mt_, malpighian tubules; _o_, oocyst; _s_,
stomach; _sb_, sucking bladders or pumping organ; _sg_, salivary
gland. (MacNeal from Doflein, modified after Ross and Grassi.)]
The brain has a leaden hue caused by the black pigment. As
discussed under pernicious manifestations the blocking of the
capillaries may be explained in several ways. When examining
sections of a malarial brain one often encounters punctiform
haemorrhages.
The spleen is enlarged and the surface dark. In acute cases it may
be diffluent instead of hard, as in ague cake. Microscopic sections
show a striking absence of pigment in the Malpighian corpuscles,
the haemozoin being pushed off into the surrounding spleen pulp.
Bone marrow is dark from deposit of pigment. In the liver the
endothelial and Kupfer cells are packed with black pigment. The
parenchymatous cells do not contain this pigment but may show
grains of a yellow pigment, haemosiderin, which gives the iron
reaction. Haemozoin, although it contains iron, does not give this
reaction. Haemozoin is soluble in alkalis, but not in alcohol while
haemosiderin is soluble in alcohol but not in alkalis.
The splenic blood is more rich in haemozoin than that of the other
vessels, this indicating the spleen as the place of destruction of
infected red cells or as the nursery for the development of malarial
parasites. As a matter of fact splenectomy may cure an old malarial
cachectic.
The finding of pigmented mononuclears or pigmented parasites in a
cross section of a blood vessel makes for a diagnosis of a malarial
infection.
Malarial manifestations are common in tropical autopsies and one
must be very chary about reporting malaria as the real rather than
contributing cause of death.
There is usually a marked increase in large mononuclears in malaria
and if this is noted along with a leucopenia it is very suggestive.
Melaniferous leucocytes occur in malaria only.
The kidneys may show degenerative changes and the presence of
urobilin in the urine is an important indication of latent malaria.
SYMPTOMATOLOGY
CLINICALLY, WE HAVE TWO TYPES OF MALARIAL PAROXYSMS, (1) _Those
presenting a cold stage, followed by a hot stage, with a terminal
sweating stage_. Such attacks are brought about by the benign
infections which include the benign tertian and the quartan. Owing to
the fact that in such paroxysms the temperature makes a critical fall
to normal or subnormal readings such fevers are frequently designated
_intermittent fevers_.
[Illustration: FIG. 17.—Diagram of the temperature chart of a
double tertian malarial fever showing the succeeding development of
two generations of parasites, causing thereby a quotidian fever.
The solid line, _A_, shows the development of the generation of
parasites first introduced and the dotted line, _B_, the cycle of the
generation introduced later on.]
While these benign infections rarely or never exhibit pernicious
manifestations, they may, equally with the more dangerous
aestivo-autumnal parasite, lead to the production of malarial
cachexia, in which the clinical manifestations are similar whether
produced by a benign or malignant species.
(2) _Those in which the succession of cold, hot and sweating stages
is lacking._ There is not the frank well-defined chill of the former
group, so that the term dumb chill is frequently applied. With
the possible exception of the first paroxysm the temperature tends
to remain well above normal giving a continuous, or at any rate a
remittent type of fever, instead of the intermittent temperature
curve of the benign infections. The designation _remittent fever_, is
often applied to such fevers. Clinically there is a resemblance to
typhoid fever.
Such malarial fevers are caused by the small hair-like ring
parasite with its crescent sexual forms. There are many
designations for this type of malarial fever of which the
best recognized are: _malignant tertian_, _subtertian_,
_aestivo-autumnal_ and _tropical_. It is preëminently the malarial
fever of the tropics and, from its appearing in temperate climates
chiefly in the late summer and through the autumn months, received
from the Italians the designation aestivo-autumnal.
Such fevers were called subintrant by Torti because the succeeding
paroxysm set in before the completion of the long-continued preceding
one. This type of fever was greatly dreaded. The designation
_malignant tertian_ is to be preferred as indicating the greater
seriousness of this type of malaria.
INCUBATION PERIOD
Depending in great part on the number of sporozoites introduced by
one or more infecting anophelines at the time of biting we have
with quartan fever (8-12 merozoites) a period of incubation of
approximately three weeks, for benign tertian (16-24 merozoites)
two weeks and for malignant tertian (32 merozoites in culture)
eight to twelve days. These periods however may be much longer.
PRODROMATA
There may be prodromata of the nature of malaise, vague muscular
pains, headache and anorexia, possibly showing a periodicity in their
appearance or intensity.
It is only when a sufficient number of parasites sporulate
simultaneously and pour out into the circulation sufficient toxic
material to cause a well-marked paroxysm that such occurs—with
less poison we may only have vague suggestions of an attack of ague.
In a large proportion of cases there are no prodromata, they begin
with a sudden onset.
Malarial paroxysms show a preference for the forenoon or at any rate
tend to occur in the early afternoon, rather than in the evening.
MIXED AND MULTIPLE INFECTIONS
When there are two generations of tertian parasites, each maturing
on successive days, we have a paroxysm every day—a quotidian
fever. Such a tertian infection is called a double tertian. In
quartan infections, with the seventy-two-hour cycle of development,
if we have two generations of parasites sporulating on succeeding
days, but with an apyretic day intervening, we have a double
quartan. If three generations of quartan parasites sporulate on
three successive days we have a triple quartan infection. When two
species of parasites are present in the same case we have a mixed
infection. Mixed infections of malignant tertian and benign tertian
are the most common, next, those of quartan and malignant tertian
and very rarely those showing quartan and benign tertian. All three
species have been found in a single individual.
CLINICAL TYPES
_A Typical Benign Tertian or Quartan Paroxysm._—(Other than for
the difference in periodicity the paroxysms of these two malarial
infections are alike.)
The ague attack generally commences with malaise and slight headache,
frequently accompanied by yawning and stretching. Chilly sensations
radiating from the spinal column to the extremities and the jaws give
way to actual chill with shaking body and chattering teeth, face
pinched and bluish and cutis anserina.
The pulse is frequent, small and of rather high tension, there is
increased frequency of urination and nausea and vomiting may be
present.
Notwithstanding the fact that the rectal temperature is steadily
rising five or six degrees during this cold stage there is a desire
on the part of the patient to cover himself with all the wraps
obtainable.
The cold stage, which usually lasts from twenty to sixty minutes, is
succeeded by the hot stage.
At first there is a feeling of slight relief from the misery of the
chill but this is soon lost sight of in the increasing headache and
feeling of intense heat.
The previously welcome blankets are cast aside. The face now becomes
flushed, the eyes shining, and the pulse more full. Epigastric
discomfort, nausea and vomiting are apt to become more prominent in
this stage. The patient often complains of a throbbing headache. It
is at this time that he may become slightly delirious. A sense of
tension or even pain may be experienced in the region of the spleen,
which organ will be found tender even if not already palpable. Herpes
about the nose and lips is almost as common as in lobar pneumonia.
An attending bronchitis is not uncommon.
The fever remains high, from 105° to 106°F., and continues so
elevated for from four to six hours to be succeeded by the sweating
stage. In this the dry skin becomes moist and perspiration breaks
out first on the forehead to be followed by a more or less marked
profuse sweating of the entire body. The pulse becomes slower, the
temperature falls rapidly and the patient falls asleep to awake
slightly exhausted but feeling well.
[Illustration: FIG. 18.—Typical fever charts of the 3 types of
malaria.]
This feeling of well-being continues during the fever-free day which
is often referred to by a patient as “my good day.”
The sweating stage lasts usually about four hours so that the
entire paroxysm of cold, hot and sweating stages occupies
approximately eight to twelve hours.
While most cases of the benign infections show the typical stages
yet we meet cases where the cold and sweating ones are absent or
but slightly marked.
Blood examination will show the parasites of the benign infections
to be in the peripheral circulation during the entire apyrexial
period. During the paroxysm we have a moderate leucocytosis
and during the afebrile period a leucopenia with an increased
percentage of large mononuclears.
Billet thinks that quartan paroxysms can be distinguished from
benign tertian ones by their showing a less abrupt fever rise and
a more rapid fall of temperature with a shorter duration of the
paroxysm, four or five hours as against eight to twelve hours for
benign tertian.
_A Typical Malignant Tertian Paroxysm._—The characteristic features
of the paroxysm are slight chilliness instead of a frank chill,
prolonged and intensified hot stage, lack of marked terminal sweating
and a tendency to exhibit a continuous or at least remittent fever
curve instead of the distinct intermittence, with an apyrexial
period, of the benign infections.
During the period of the remittence the patient fails to experience a
sense of well-being. He is sick and does not have a “well day.”
The temperature of a malignant tertian paroxysm may fall to
normal during the first attack but succeeding attacks only show
the tertian periodicity by an exacerbation of the more or less
continuous fever.
In these cases the temperature rise is gradual rather than abrupt and
the fall rather by lysis than crisis.
The paroxysm lasts from twenty to thirty-six hours instead of ten
hours.
To explain the continuous type of fever it is often stated that
anticipation and retardation are characteristic of malignant
tertian infections. This simply means that the new paroxysm tends
to come on before the tertian periodicity of forty-eight hours
has expired and, having appeared, tends to delay its termination.
At any rate there is an extreme irregularity in the course of the
paroxysm. These attacks are often termed “dumb chills” and are
greatly dreaded.
The onset is insidious, occurring as a rule in the forenoon or early
afternoon, with rarely a chill but only chilly sensations. The
headache and backache are severe, the face is flushed, the pulse
quickened and the thirst urgent.
The patient feels more prostrated and ill than does one in a benign
paroxysm and there is a distinct tendency to mental confusion or
delirium. Nausea and vomiting may be prominent features of an attack.
At times an apathetic state may suggest typhoid fever. In these
malignant malarial attacks the spleen is palpable and very tender.
There is also a sense of weight in the region of the liver.
In a blood examination one is not apt to find any other parasites
than the young hair-like ring forms which begin to appear a few
hours after the onset of the paroxysm. The rings may be observed
to broaden, but prior to that development in which pigment would
appear in the ring, the parasite-containing red cell is caught in
the capillaries of spleen or other organs. The finding of young
ring forms while fever continues is suggestive of a malignant
tertian infection.
In the absence of quinine administration the finding of parasites is
to be expected in benign tertian and quartan infections, but with
the tropical parasite a smear may fail to show any organisms where
a few hours previously a blood examination would have shown a large
percentage of infected red cells in every field of the microscope.
=Pernicious Manifestations of Malaria.=—These grave manifestations
arise almost exclusively in the course of malignant tertian
infections. In his study of malaria Stott had about 1% of his cases
showing well-marked pernicious symptoms.
[Illustration: FIG. 19.—Temperature chart of malignant tertian fever
showing how readily one might confuse such a chart with that of
typhoid fever. (From Jackson’s Tropical Medicine.)]
As explanations of perniciousness are given: (1) the very large
number of red cells infected and destroyed by the malarial
parasites; (2) the throwing off at the time of sporulation of
the merocyte of a large amount of toxic material owing to the
presence of such a large number of disintegrating merocytes, and
(3) from the plugging of the capillaries of important internal
organs by adult parasites. This may arise as the result of (_a_)
the sporulating parasites acting as emboli, being too large to
pass the lumen of the capillary; (_b_) from degenerative changes
or distension with pigment of the endothelial cells lining the
capillaries, or (_c_) as the result of an ovoid shape on the part
of the malignant tertian parasite there is an inability to pass
through capillaries which the flattened benign parasites can do by
infolding (Bass), or (_d_) resulting from the tendency of malignant
tertian parasites to agglutinate.
_Types of Pernicious Malaria._—It is customary to divide pernicious
malaria into the following divisions—(1) Cerebral, (2) Algid, (3)
Bilious Remittent and, possibly, also (4) Pneumonic and (5) Cardiac
types.
Blackwater fever is often included in the grouping but would appear
to be best considered as a separate disease although almost surely
brought about by malaria.
We do not understand why in one case sporulating parasites
should plug the capillaries of the central nervous system,
with the production of conditions resembling well-recognized
nervous diseases, while in another case the damage is done the
intestinal mucosa, pancreas or lungs. At any rate these pernicious
manifestations of malaria should always be kept in mind when a case
of sudden cerebral involvement or acute abdominal disease shows
itself in a patient in a malarious country and a blood examination
should be promptly made.
_Cerebral Manifestations of Pernicious Malaria._—Various authorities
give different clinical pictures but the more commonly accepted types
are:
(1) The hyperpyrexial, when the symptoms are those of heat stroke,
with a temperature going up as high as 110°F. or even higher. Such
patients rapidly become comatose and as a rule die.
(2) The delirious and comatose forms are apt to be associated, the
comatose condition following a delirious state. Such manifestations
may or may not set in with a chill. Cases belonging to this group
may arise from a typical malignant tertian infection in which the
headache and restlessness have been unusually marked. The pulse is
full and fast with sighing respiration, hot dry skin and flushed
face. There may be rigidity of the neck muscles.
(3) Such terms as epileptiform, tetanic, aphasic, cerebellar
and bulbar have been applied to malarial manifestations and are
self-explanatory.
Cerebral malaria may give rise to a delusional insanity. Various
psychoses or amnesia at times follow cerebral types of pernicious
malaria.
_Algid Manifestation of Pernicious Malaria._—In such cases we have
a small thread-like pulse and a cold clammy skin. There are signs of
collapse. The respiration is slow and shallow and the voice weak.
It is customary to consider some of these cases, when there is
vomiting and diarrhoea, with painful cramps of the legs and scanty
or suppressed urine, as of choleraic type, while other cases, with
blood and mucus in the stools and marked abdominal pain are termed
dysenteric. Most dysenteric types only show a diarrhoea with the
presence of blood.
The dysenteric type is more common but the question always arises
whether the case may not have been really dysentery lighting up
a latent malaria or the lowering of resistance from the malaria
favoring a dysenteric infection. Stott had five algid cases of
dysenteric type but not one of choleraic. The choleraic types have
often been reported during outbreaks of cholera.
When epistaxis and haemorrhages from the intestines or stomach are
marked features of an attack the cases are termed haemorrhagic and,
if a prostrating, collapse-producing sweat be a characteristic
feature, they are called diaphoretic.
Cases have been observed when the excessive sporulation was
apparently taking place in the pancreas, giving the symptomatology of
acute haemorrhagic pancreatitis.
_Bilious Remittent Fever._—This is the most common and the least
dangerous of the pernicious manifestations but tends rapidly to
produce malarial cachexia. Slight jaundice and bilious vomiting
may appear in the course of an ordinary malignant tertian paroxysm
and only severe types, with fatal tendency, should be classed as
pernicious. It sets in with marked nausea followed by bilious
vomiting and bile-rich stools. Jaundice shows itself by the second
day; earlier than in yellow fever, but much later than the rapidly
appearing jaundice of blackwater fever. The urine shows bile pigment
and a yellow foam. Epigastric distress and liver tenderness are
marked features and there may even be gastric haemorrhage.
_Pneumonic and Cardiac Types._—Other recognized types are when,
with the symptoms of a broncho-pneumonia, we find an element of
periodicity and a response to quinine—the so-called pneumonic
type.
Again, usually in elevated regions, dilatation of the right
heart and death have been noted as occurring in cardiac types of
pernicious malaria.
Another type is one in which the sweating stage is excessive, the
so-called diaphoretic type. These cases may result in collapse and
such a termination may be syncopal in character.
=Relapses.=—Relapses are distinct features of malarial diseases,
the tendency being most marked in quartan and least so in malignant
tertian. A relapse after an interval of two years is very rare in
malignant tertian but periods as long as nine years may intervene
between attacks of quartan fever.
Relapses are intimately associated with conditions which tend to
lower the body resistance, so that exposure to cold or wet or
hot sun may bring on an attack. Alcoholic or venereal excesses,
as well as errors of diet, may be provocative. Persons returning
home from the tropics often experience relapses as they approach
the cooler climate of the temperate zone. It has been well stated
that the old resident of the tropics owes his condition of health
rather to education than acclimatization—experience has taught him
discretion.
There are three explanations of relapses of which the one supported
by Ross and Bignami seems more reasonable and is that the
disappearance of nonsexual parasites is only apparent and that they
continue their cycle but in insufficient numbers to excite symptoms.
_Parthenogenesis._—Schaudinn thought that, either spontaneously
or as the result of treatment, there was a disappearance of the
nonsexual forms and the male gametes, the female gametes however
surviving and, eventually, through the process of parthenogenesis,
producing a set of spores or merozoites which set up a nonsexual
cycle. It would seem probable that Schaudinn saw red cells
containing a merozoite along with a female gamete and interpreted
his findings as a sporulating sexual form.
Craig thinks that as the result of the conjugation of two young
schizonts a more resisting parasite is evolved, which under
favorable circumstances for its development may start anew a
nonsexual cycle.
=Latent Malaria.=—The persistence of a malarial infection, in
the absence of clinical and to a great extent of laboratory
manifestations, is shown by the occurrence of relapses, so that
the section treating of malarial relapses applies equally to this
paragraph. In addition to the factors influencing relapses, such
as exposure to sun, rain and excesses of various kinds, we note
a particular tendency for a latent malaria to develop activity
following surgical operations and childbirth. In untreated latent
cases we may have delayed healing of surgical operations.
In another paragraph there is noted the importance of examining
placental smears for evidence of a latent malarial infection.
Persons returning to a cool climate from the tropics, who may not
have shown evidence of active malaria for months, may come down
with a paroxysm upon encountering cool weather (refrigeration).
Latency may be complete or there may be vague manifestations of ill
health such as anorexia, malaise, irritability, headaches, anaemia
and alimentary tract disturbances. Not infrequently tropical
residents without symptoms may show crescents in their blood and
such cases are of prime importance in connection with infection
of mosquitoes. To a certain extent they are the typical carriers
and should be actively treated from a standpoint of malarial
prophylaxis.
=Masked Malaria.=—While as a rule one should not accept such a
diagnosis, unless the possibility of some other explanation than
malaria is excluded, yet there are manifestations, chiefly neuralgic,
gastro-intestinal or in the form of varied skin eruptions which at
times show periodicity and which respond to treatment with quinine.
[Illustration: FIG. 20.—Abnormal malaria parasites. 1, Normal red
corpuscle; 2, gametocyte and schizont; 3, gametocyte and gametocyte;
4, gametocyte and schizont; 5, schizont and schizont, both undergoing
schizogony. (_After Dr. J. D. Thompson, “Jl. R. A. M. C.”_) By
permission from Manson’s Tropical Diseases.]
=Malarial Cachexia.=—As the result of repeated attacks of any type
of malaria a condition of anaemia and physical and mental incapacity
may be produced. The skin has a dirty earthy hue, particularly of
the face, and the sclerae show a yellowish tinging. The patient
is sensitive to the slightest cold and is the victim of mental
depression with deterioration of memory or at any rate lack of
concentration.
There may be long periods in which the temperature is normal or
subnormal but slight febrile accessions may occur from time to time
and at such times the blood may show parasites.
The spleen is enlarged as may also be the liver. Twisting of the
pedicle of the spleen or its rupture from even slight blows may
necessitate surgical intervention.
There is anorexia and alimentary tract disturbances. A very
important feature of malarial cachexia may be the occurrence of
haemorrhages, particularly serious being those from the retinal
vessels.
It is probable that hookworm infection has frequently been
confused with the anaemia of malarial cachexia as in both of these
conditions we may have a high-grade anaemia with swelling about
the ankles, palpitation of the heart and shortness of breath. Some
authorities have recently called attention to splenic enlargement
in hookworm disease, but this is not generally accepted. There may
be also ascites in malaria. Urobilinuria is an important sign in
malaria where other causes for red cell destruction are excluded.
=The Sequelae of Malaria.=—The anaemia and other manifestations of
malarial cachexia have been described above. The enlarged spleen not
only is a source of danger from rupture but it may cause sensations
of pain or tension. The skin of those with chronic malaria tends to
ulcerate from slight wounds and phagedenic lesions may occur. There
may be various disorders of the nervous system varying from mental
confusion or lack of mental concentration to melancholia. Neuritis
and possibly peripheral neuritis may have origin in repeated attacks
of malignant tertian malaria. Ulceration of the cornea is the most
frequent of the ocular sequelae although even this is rare. It only
occurs after many relapses. It is painful, heals slowly and tends to
recur with relapses. Iritis may accompany it. Abortions are frequent
unless the malaria is adequately treated.
Symptoms in Detail
_General Appearance._—In the cold stage of the benign infections
the face is pinched and blue to become decidedly flushed when the
hot stage sets in. In malarial cachexia there is an earthy color
with the pigmentation more marked about the face and knuckles. In
the algid forms of pernicious malaria the skin is pale, cold and
clammy, in a measure simulating cholera. Herpes labialis is very
common in the benign infections, but less so in the malignant
tertian ones. Jaundice is a feature of bilious remittent fever.
_The Temperature._—Even in the cold stage the temperature is
steadily rising and may have reached 105°F. or higher by the time
of onset of the hot stage. It remains elevated during the four to
six hours of the hot stage and then falls rapidly to normal during
the sweating stage. The paroxysm tends to occur in the forenoon or
early afternoon. In 793 typical paroxysms Stott found only 37% to
occur before noon. Intermittent fever curves are characteristic
of benign infections. In malignant tertian a prolonged hot stage
(fifteen to thirty-six hours) is a marked feature. The onset also
is more gradual and the fever tends only to remit or may remain
continuous over several days, but even with such a chart there are
apt to be indications of slight rises every other day.
In the hyperpyrexial form of cerebral perniciousness the
temperature may rise to 112°F. and the case resemble sun stroke. In
the algid forms the axillary and rectal temperatures are usually
elevated.
_The Circulatory System._—The pulse is small, rapid and of high
tension in the cold stage to become full and bounding in the hot
stage. A cardiac type of perniciousness in which the right heart
dilates has been referred to.
_The Alimentary Tract._—Nausea and vomiting are common
manifestations of malarial paroxysms and in bilious remittent fever
the bilious vomiting is an especially distressing feature.
So-called choleriform and dysenteric manifestations of
perniciousness of the algid type are rarely observed.
Cases with the clinical picture of acute haemorrhagic pancreatitis
have been reported as incident to excessive sporulation of malarial
parasites in the capillaries of the pancreas.
_The Respiratory System._—There may be a slight bronchitis
in ordinary types of malarial fever. In the cerebral types of
perniciousness the breathing may be markedly altered—even of
Cheyne-Stokes character.
[Illustration: FIG. 21.—Malarial cachexia. (Deaderick.)]
A broncho-pneumonia which shows a periodicity and responds to
quinine is often considered as a pernicious type of malaria.
_The Skin._—Herpes labialis is a common manifestation of benign
tertian and not rarely of malignant tertian infection. Urticaria
may also be noted. The skin of malarial cachexia is earthy. Of
course, one must always keep in mind the skin eruptions due to
quinine administered in treatment, and of these urticaria is
probably the most frequent.
_The Nervous System._—In both the benign and malignant infections
headache is a marked feature and is accentuated during the hot
stage. There may be a “flighty” condition in the hot stage of
benign tertian and quartan but in aestivo-autumnal infections there
may be actual delirium.
Delirious and comatose states are prominent features of cerebral
pernicious attacks. At times there may be an apathetic condition
suggesting typhoid fever.
Almost any type of central nervous system disease may be simulated
as the result of focal sporulation so that we have aphasic,
epileptiform, hemiplegic, bulbar and other clinical types.
Some authors have recorded cases of multiple neuritis of malarial
origin. Catto has recently examined the blood of a number of cases
of multiple neuritis in Jamaica and has obtained negative malarial
findings in every case. Neuralgic manifestations are features of
latent malaria. Some loss of memory may be apparent after severe
malaria.
_The Special Senses._—Plugging of the retinal arteries may lead to
blindness which may be either transient or lasting. The discs are
grayish red instead of white as is the case with quinine amblyopia.
The ringing in the ears is connected with the quinine treatment.
_The Genito-urinary System._—In the cold stage there is apt to be
frequent urination with increased secretion. Later on, there is a
scanty febrile urine.
Albuminuria is rather common in aestivo-autumnal attacks and true
nephritis occurs in about 2% of cases.
Plehn attaches great importance to the examination of the urine for
urobilin as showing malarial infection when parasites cannot be
found. The pigment particles in urinary sediment (Uriola) do not
give reliable information. Bile in the urine is an important sign
of bilious remittent fever.
Orchitis has been reported as a malarial complication.
_The Liver and Spleen._—There is very little of importance to note
in connection with the liver except tenderness and jaundice in
bilious remittent fever. The spleen, however, is the organ in which
centers the infection and its tenderness and enlargement are of
special diagnostic value in malaria.
Even in comatose conditions pressure on the spleen may bring about
indications of pain. The liability to rupture of the friable spleen
of aestivo-autumnal infections is a real danger and the patient
should not expose himself to injury.
_The Blood Examination._—This is of prime value in the recognition
of malaria, and one should examine both fresh blood preparations
and stained films as well. More information is gotten from the
stained films but we should also avail ourselves of the different
characteristics of the 3 malarial species, which can be noted in a
preparation made by taking up a small drop of exuding blood on a
cover-glass and allowing it to drop on a slide and run out without
any pressure on the cover-glass.
The crescents, when found, show a malignant tertian infection but
there may also be present one of the benign parasites. A stained
film should be used to identify malignant tertian young ring forms.
Pigmented rings are rarely observed in aestivo-autumnal fever,
such parasites being caught in the capillaries as they enlarge to
the stage where pigment begins to be present. Flagellated forms
only develop in fresh blood preparations, 15 to 20 minutes after
the taking of the blood. Of the greatest differential value is the
swollen pale infected red cell of benign tertian, the normal red
cell of quartan and the distorted shrunken red cell of malignant
tertian.
Quinine administration may cause parasites to disappear from the
peripheral circulation or it may so affect the parasite that the
staining would indicate a degenerated parasite—the so-called
quinine-affected parasite. It is difficult to diagnose the species
of malaria from such a parasite.
Large mononuclears and transitionals containing phagocytized
pigment (melaniferous leucocytes) are characteristic of
malaria—the pigment however must be in the leucocyte and not
free. There is a leucocytosis during the malarial paroxysm with
a leucopenia and increase in the large mononuclears during the
apyrexial period.
Among natives of India the large mononuclears and transitionals
averaged 21% in the apyrexial stage of malaria while healthy
natives rarely showed as much as a 10% count (Stott).
Some authorities have reported positive Wassermann reactions in
serum of malarial patients taken during a paroxysm. All agree,
however, that the serum of malarial patients at other times is
negative.
DIAGNOSIS
In the diagnosis of malaria the special points to consider are:
(1) presence of malarial parasites, (2) periodicity, (3) splenic
enlargement, (4) response to quinine therapy, (5) the presence of
melaniferous leucocytes and (6) a high large mononuclear percentage
when leucopenia is present. In the examination for parasites one
should not only consider the species of parasite present but, as
well, the stage of development and the presence of the sexual forms.
In an intensive investigation Bass has shown that 55.09% of those
showing parasites in the blood give a clinical history of malaria
while 44.91% of those with parasites in the blood fail to be
associated with clinical manifestations.
Blood platelets are the findings most frequently mistaken for
malarial parasites in stained blood, and the vacuoles in fresh
blood. Quartan and tertian periodicity is only found in malaria,
but quotidian periodicity is a feature of a host of diseases.
There are very few tropical diseases which have not been mistaken
for malaria and many of these have been considered as of malarial
etiology before the discovery of the real cause.
Of the cosmopolitan diseases, typhoid fever, septic conditions,
including malignant endocarditis, tuberculosis, influenza, pyelitis
and even syphilis are to be considered in a diagnosis of malaria.
As regards tropical diseases, kala-azar, Malta fever, liver abscess,
filariasis, trypanosomiasis, leprosy, relapsing fever and yellow
fever are to be thought of in differential diagnosis.
As was noted under the discussion of the pernicious manifestations
of malaria, scores of diseases may be simulated by the sporulation
of the malarial parasite in certain organs or areas of organs. One
should always keep in mind the possibility of pain in the appendix
region or in the gall bladder area as connected with malaria if in
the tropics. A polynuclear increase negatives malaria and indicates
appendicitis or cholecystitis. Malarial pancreatitis has been
referred to before.
[Illustration: FIG. 22.—A cluster of blood-plaques and two plaques
lying upon a red cell and simulating malarial parasites (× 1000).
(Todd.)]
With malarial cachexia we must in particular keep from mistaking it
for hookworm disease or other secondary anaemias due to intestinal
parasites.
_Provocative Measures._—Kohlbrugge’s recommendation to have
patients suspected of malaria climb mountains and drink copiously
of cold water, in order to bring on a relapse, is of value in the
diagnosis. (Effects of fatigue and refrigeration.) It must always
be borne in mind that quinine causes the parasites to disappear
from the peripheral circulation. It is interesting to note that
small doses of quinine given over ten days or two weeks may make
a latent case active. Other provocative agents are subcutaneous
injections of adrenalin (the best), or anti-typhoid inoculations.
Certain physical methods, as hot and cold douches or alternating
the hot air chamber at 55°C. for 10 minutes, followed by a cold
bath for 3 minutes have been recommended. After injection of
adrenalin the presence of parasites in the blood is at its height
at the end of an hour. Sunlight is a factor in relapse.
_The laboratory diagnosis_ of malaria has already been fully gone
into in the section on etiology and that on blood examination under
the heading of symptoms in detail.
The evenly spread stained film undoubtedly gives more accurate
information as to species and stage of cycle than any other
method. Still one should always examine a fresh specimen and if
the parasites are very scarce, a thick film preparation. The thick
film methods of Ross, Ruge and James are given under the chapter on
the blood in tropical diseases. During winter parasites tend to
disappear from the circulation regardless of treatment.
PROGNOSIS
The prognosis in benign tertian and quartan is most favorable when
proper treatment is instituted, as such infections are never fatal in
first attacks. Not only may malignant tertian kill in a first attack
but it leads rapidly to a cachexia while the cachexia following upon
benign infections is more gradual.
It is the tendency to perniciousness which makes us dread malignant
tertian as we can never be sure that a paroxysm may not develop
cerebral or algid manifestations and these show a very high death
rate, 25 to 50%, even when promptly treated.
As regards relapses quartan is the malarial fever which is most
apt to show this feature and aestivo-autumnal the least. Deaderick
gives the percentage of cases showing relapses in quartan, benign
tertian and aestivo-autumnal as 65, 55 and 45.
The great importance of malaria is rather its invaliding tendency and
by thus reducing the powers of resistance it makes the death rate
from intercurrent diseases higher. Tropical malaria does not seem to
affect the native as it does the European but the high death rate of
infants among the natives is undoubtedly largely connected with this
disease.
Statistics vary greatly as to the percentage of fatal cases in
malaria. Certain figures from tropical countries give fatal results
as occurring in from 2 to 10% of cases, while statistics from
temperate climates show a death rate below 1%. The mortality from
pernicious types of malaria is about 25%.
PROPHYLAXIS AND TREATMENT
=Prophylaxis.=—There are three methods in the prevention of
malaria, all of which may be combined, as was the case in the Canal
Zone region of Panama. These are: (1) Destruction of anopheline
mosquitoes; (2) protection of the individual from the bites of
mosquitoes, and (3) quinine prophylaxis.
It may be stated that it is frequently advisable to carry on the
mosquito warfare without regard to the question of the kind of
mosquitoes destroyed. In general terms the malarial mosquito breeds
in the suburbs of towns or in districts more distinctly rural,
while the transmitter of the more dreaded yellow fever, prefers
breeding places in the immediate vicinity of city houses.
Bentley has recently noted that, with improvement in agricultural
methods and utilization of marshy lands, malaria tends to disappear
as much from the physical improvement and thereby greater
resistance of the people as from the destruction of mosquitoes by
the draining of the swamps. The resulting greater prosperity makes
better food and shelter obtainable.
1. _Destruction of Mosquitoes._
Such measures may be directed either toward the larva or fully
developed insect.
(_a_) Measures against larvae. When practicable permanent measures
should be preferred to temporary ones and when agricultural
development goes along with drainage of swamps the cost is repaid.
The doing away with mosquito breeding places may be accomplished
by filling in pools or by making ditches with smooth sloping sides
to carry away the water. These ditches require a great deal of
attention to prevent their filling up with tropical vegetation and
thereby adding to breeding places. Subsoil drainage with tiled
drains is better. Care should be exercised that public works
operations do not raise the level of the subsoil water.
Anophelines tend to breed in sluggishly moving streams or in
stagnant pools especially where there is a luxuriant growth of
weeds or grass, and are not apt to be found in rapidly flowing
streams, hence the necessity for constant care of ditches and the
like to prevent their becoming obstructed by vegetation or silt.
When filling in or drainage is not practicable the method of oiling
the surface of the pool with crude petroleum is to be recommended.
One uses about ½ pint for every 100 square feet of surface and the
process should be repeated every two weeks.
In places where oil is not effective, Barber recommends Paris
green mixed with dust and so used as to form a scant surface
deposit. Anopheline larvae, being surface feeders, ingest it and
are killed. It does not affect Culex larvae. On account of its ease
of transportation, and adaptability to weedy places where oil does
not penetrate, Paris green dust will doubtless prove a valuable
selective larvicide. Mayne and Jackson recommend cresol as the best
larvicide. In 1 to 1,000,000 parts it is an effective larvicide,
and even in 1 to 1,000,000,000 it is destructive to young larvae.
Mixtures of soft soap and petroleum are better than petroleum alone.
Winds are apt to blow away the surface coating of oil and it is
difficult to oil the surface of a pool filled with grass. Wise
recommends crude carbolic acid, using 1 ounce to 16 cubic feet of
water.
In using any larvicide it is well to introduce it along the banks
of water collections with a long-spout can and mix it thoroughly
with a stiff reed broom.
There are many enemies of mosquito larvae, such as tadpoles,
water-beetle larvae and various small fish such as “millions.”
Terni suggests the using of such fish as carp and tench which have
a food value as well as a larvicidal one.
(_b_) Measures against the mosquito. The clearing away of grass and
brush from around houses exposes the mosquitoes to the sun in which
they cannot live long.
When inside the house they may be destroyed by sulphur fumigation, 1
or 2 pounds of sulphur for each 1000 cubic feet and with an exposure
of two hours.
It is usually stated that mosquitoes may hibernate during winter
following infection in the autumn and that cases of malaria in
early Spring may be explained by their bites. Examination of
hibernating mosquitoes for zygotes does not give strong proof to
this view but such mosquitoes, becoming active with a rise in
temperature, may bite gamete carriers in the house and thus spread
malaria.
Pyrethrum powder, which is set on fire with a little alcohol, may
be burned, using 2 pounds per 1000 cubic feet, and an exposure
of four hours. This does not certainly kill the insect and the
stupified mosquitoes should be swept up and burned.
Giemsa’s spray is now considered an excellent measure for killing
mosquitoes in rooms. The composition is as follows: Pyrethrum
tincture (20 parts powdered pyrethrum blossoms to 100 parts
alcohol), 480 grams; odorless potash soap, 180 grams; glycerine,
240 grams. Before using it dilute with 20 times its own weight of
water, and spray the walls of the room with a spray pump.
The use of a small square of wire gauze on a handle (fly swatter)
to kill mosquitoes as they rest on a wall is of great value in
keeping them down in a screened house.
2. _Protection of the Individual._
The house should be thoroughly screened with copper-wire screens
which should have 18 meshes to the inch. Mosquitoes can pass through
a 15 mesh screen. Screen doors should always open outward and close
automatically with spring hinges.
It is almost impossible to screen a ship’s hatches effectually.
Then too the screening of fan intakes and ports interferes with
free circulation of air, thus adding to the discomfort of the heat
of the tropics.
As malarial mosquitoes bite chiefly toward evening one should not
expose himself after sunset.
Houses should be far removed from native habitations.
Mosquitoes prefer the lower floors of a house so that the upper
stories are preferable for sleeping.
Mosquito nets at night, with protection by veils for the face or
coverings for the hands and ankles, when going out of the house,
are well-known measures.
It is stated that Emin Pascha always carried a mosquito net and
never suffered from malaria. He thought that the cause of malaria
was too large to go through the net.
Even when mosquito nets are intact and well tucked in there is the
weak point that a person sleeping on a narrow cot is apt to put his
arm or leg against the net, in which case the mosquitoes readily
bite the skin presenting at the open spaces.
Oil of citronella is often used to keep away mosquitoes.
Brooks recommends Neal’s method. In this daub a solution of 1 ounce
Epsom salts in 10 ounces of water on the exposed parts and allow to
dry.
Application of certain pine products used as mange cures will keep
away mosquitoes.
3. _Quinine Prophylaxis._
The ease of application of quinine prophylaxis, as compared with the
more permanent methods of mosquito destruction and screening, appeals
to the sanitarian, especially in the tropics.
It is just as easy to give quinine to a man in the tropics as it is
in temperate climates, but when one considers the propositions of
draining tropical swamps and shutting off circulation of air on a
torrid night with fine wire gauze in the windows and closely woven
mosquito nets around the bed, the question is decidedly different.
In consequence, the tendency is for the average man to despair
of accomplishing anything in the way of mosquito destruction and
screening and to seize eagerly on the inferior alternative, that of
quinine prophylaxis.
Ronald Ross presents this matter concisely and to the point when
he states that it is not a good policy to substitute a measure
which does not exclude infection, but is merely extirpative in
some cases, for positive prevention. From this it will be seen
that unless it is clearly recognized that quinine prophylaxis may
in some cases extirpate, but does not prevent, there might be a
tendency to adopt this measure and neglect the two proper ones.
As regards the relative merits of quinine prophylaxis and
protection from mosquitoes Celli gives the following figures:
Treatment Infected
Mosquito protection plus quinine prophylaxis 1.76 %
Mosquito protection alone 2.5 %
Quinine prophylaxis alone 20.0 %
No protection at all 33.0 %
With quinine prophylaxis, there is the possibility of producing
an immunity to quinine on the part of the parasites which have
been introduced by infected mosquitoes and held in check by the
prophylactic but not curative dose of quinine. Later on when the
quinine prophylaxis is discontinued the parasites begin to multiply
vigorously and seem to possess an immunity to quinine.
As an instance of this, 398 marines served in 1906 for about one
month on the Isthmus of Panama during which time they were given 9
grains of quinine daily as a prophylactic.
During this month there was only an occasional case of malaria
among the men. At the end of the month 298 of the original 398
returned aboard ship and sailed for the North. Two days later
20 cases of malaria developed, followed the next day by 53 and
the day following that by 45. The medical officer then resumed
10-grain prophylactic doses for those not down with malaria but
notwithstanding this there were 215 acute malarial paroxysms, some
of them of pernicious type, among the 298 men.
It was noted that these men did not respond satisfactorily
to quinine treatment even when the drug was administered
intramuscularly.
Of the greatest value have been the observations of Stott. Using
native Indian troops he gave one group (3931) prophylactic quinine
while the other (3906) did not take quinine prophylactically. He
continued this experiment one year giving 15 grains 3 times weekly
for five months, and 10 grains 3 times weekly for the remaining seven
months. Those taking quinine gave 170 primary admissions while those
not taking it gave 179 (43.2 per thousand strength for the former as
against 45.8 per thousand for those not taking quinine prophylaxis).
Further observations were that those taking quinine prophylaxis
showed a greater tendency to relapse, had somewhat longer fever, and
required more quinine for treatment.
Linnell states that he used quinine prophylaxis among 2000 coolies
for a year, giving 5 grains or more daily with most discouraging
results. It seemed to act as a slow poison and did not protect.
_Quinine Immunity._—Bignami thinks that malarial relapses
may be connected with insufficient initial treatment so that
quinine-resisting forms survive and later, when some factor lowers
the patient’s resistance, active multiplication of parasites, which
are not readily destroyed by quinine, follows.
While quinine prophylaxis may not be desirable on board ship, where
one is in a position to readily recognize and treat the onset
of malaria and to more or less efficiently carry out mosquito
protection methods, or in a wealthy seaport, where sufficient
interest in and funds for draining and screening exist, yet on
military expeditions or exploring trips in tropical or subtropical
countries it is the only practical method of keeping a force
efficient.
Of course, one should also utilize mosquito nets as assisting in
protection from malaria, and as effective for yellow fever, dengue
and filariasis.
_Methods of Prophylaxis._—There are innumerable methods of carrying
out quinine prophylaxis among which may be noted.
(_a_) Celli’s method. In this there is given 3 grains of quinine
each morning and 3 grains each night. Taken in this way Celli
thinks that harmful effects from quinine are avoided, that quinine
immunity does not occur and that there is no danger from quinine
haemoglobinuria. For children he recommends the tannate in
chocolate tablets.
(_b_) In 1909 Bertrand and other members of a French Commission
recommended two consecutive doses of 5 to 10 grains every
seventh and eighth day for benign infections and two consecutive
prophylactic doses of 10 to 15 grains every third and fourth days
where malignant tertian was prevalent.
(_c_) Ziemann gives 15 grains every fourth day with the idea that
the quinine is entirely eliminated in four days. Nocht gives about
12 grains on two succeeding days of each week in divided doses of
2 or 3 grains instead of the entire amount in one dose.
Koch gave 15 grains on tenth and eleventh days.
(_d_) Castellani’s method of 5 grains daily and a double dose once
a week is the one I recommend.
_Sterilization of Carriers._—In addition to quinine prophylaxis for
those not infected we also have quinine disinfection for native or
other carriers of malaria. For these infected persons Koch recommends
15 grains on two to three successive days of each week, the course
to be continued for three months. This plan of extirpation of the
parasites of _malarial carriers_ is of great practical application.
Gill uses 10 grains of quinine daily for six months after discharge
from hospital. The effect of tartar emetic on malarial gametes may
prove of value.
=Treatment.=—Cinchona bark was first introduced into Europe in
1640 and has its name from Countess Chinchon, wife of the Peruvian
Viceroy, who was cured of a fever by this bark in 1638.
Much of our knowledge of the therapeutics of cinchona bark is due
to Torti. In giving the drug he used a large dose the first day and
the same for the subsequent two days. After that he administered
smaller doses for a week and then still smaller doses for two or
three weeks. Quinine was not introduced until 1820.
At present quinine or some salt of the alkaloid is used in malaria
instead of preparations of cinchona bark.
_Toxic Effects of Quinine._—The most important untoward
manifestations of cinchonism are the very common scarlatiniform,
eczematous or urticarial rashes, gastric disturbances and vertigo.
Impairment of vision may be brought about by quinine and quinine
haemoglobinuria is a recognized possibility. In quinine amblyopia
the pupils do not react to light and the optic disc is very pale,
thus distinguishing the impairment of vision due to the plugging of
the retinal vessels by the malarial parasite, in which condition
the pupils do react to light and the disc is a grayish red.
_Quinine Idiosyncrasy._—Fortunately the taking of quinine is well
borne by the great majority of persons but in exceptional cases
we may have developing, even after doses as small as one grain,
of (_a_) severe nausea vomiting or diarrhoea, (_b_) various skin
eruptions, usually of a scarlatiniform or urticarial type, (_c_)
marked ringing in the ears, dizziness or deafness, (_d_) impairment
of vision, (_e_) dyspnoea and (_f_) malarial haemoglobinuria. To
determine an idiosyncrasy make a scratch on the flexor surface of
the forearm and apply a drop of a 1 to 10 solution of quinine.
Oedema with a wide zone of erythema in about 5 minutes shows
idiosyncrasy. A control with normal saline should be made. It is
well to make this skin test before giving quinine intravenously.
For desensitization we give 1/10 grain of quinine combined with 5
grains of bicarbonate of soda and in about 1½ hours we give 1 grain
with 5 grains of bicarbonate of soda.
The cheapest and most generally obtainable salt is the sulphate. It
is soluble in 720 parts of water and contains 74% of alkaloid. The
opinion now prevails that this is one of the less desirable of forms
for the administration of quinine. It is frequently obtained in pill
or tablet form and it must not be forgotten that such preparations
may be almost stone-like and pass through the alimentary tract
without absorption. If used it is best to give it in acid solution
made by dissolving 5 grains of quinine sulphate in one teaspoonful (1
dram) of water with one drop of concentrated hydrochloric acid.
_Dosage of Quinine._—The ordinary full dose of quinine for an
adult is 10 grains repeated three times in a day or 30 grains
daily. Some authorities recommend 15 grains three times daily (45
grains) at the commencement of treatment and such dosage seems to
be just as efficient as the larger dose of 60 grains in a day.
In cinchonism we have ringing in the ears, fullness in the head,
deafness and dizziness. For children Bass recommends 1/20 of the
adult dose for each year of age so that a child of 5 years age
would receive ¼ of the adult dose. Beyond 15 years of age the dose
is that of an adult.
There now seems to be a tendency to use the alkaloid itself instead
of its salts, it having been found that the alkaloid and its very
insoluble tannate are absorbed from the digestive tract equally as
well as the soluble salts. Quinine is almost insoluble in water
(1-1560) and hence has less bitter taste than the soluble salts. It
is also less haemolytic so that it may be used with greater safety
where blackwater fever is feared.
Euquinine or ethylcarbonate of quinine contains 81% quinine, and
is only soluble in 1-12,000 parts of water, hence its comparative
tastelessness. It is expensive.
Quinine tannate contains only about 30% of quinine and is
practically insoluble in water. It is often given to children in
chocolate tablet form. It can often be taken by those who suffer
disagreeable effects from other salts. The dose should be 2½ times
that of quinine sulphate.
Until recently the bimuriate (72% of alkaloid and soluble in 1 part
of water) or the chlorhydrosulphate (74% of alkaloid and soluble
in 2 parts of water) have been considered the most desirable salts
for hypodermic injections or oral administration. At present,
owing to its extensive use in local anaesthesia and incident
availability, bimuriate of quinine and urea is to be recommended
for intramuscular use. It contains 60% of quinine and is soluble in
an equal amount of water.
It has been found to have a slightly greater tendency to produce
amblyopia than other quinine salts and should not be used
intravenously.
In a very important series of experiments on prisoners,
MacGilchrist found that hydroquinine (a synthetic product of
quinine) was about 20% more efficient than quinine. Cinchonine was
about the same as quinine while quinidine was about one-half as
potent as quinine.
Acton has praised the value of cinchona febrifuge (the combined
alkaloids of cinchona) given in daily doses of 21 grains for ten
days.
Methods of Administration
_By Mouth._—This is the usual method and is the one to be preferred
in all cases where other methods of administration are not
necessitated.
Golgi believes that quinine is most effective at the time of
liberation of merozoites from the bursting merocytes, hence he
administered quinine four hours before the attack with a view to
having it in its greatest concentration in the blood at such times.
When given intravenously the full concentration is obtained in a
very few minutes but with other methods this is a matter of great
variation.
It is usual to give the quinine in capsules or cachets, the pills
and tablets being often so hard that they do not dissolve in the
alimentary tract.
The method usually in vogue in military services is to give quinine
sulphate in acid solution. This method is trying to the stomach.
_By Subcutaneous Injections._—This method is liable to be followed
by necrosis and abscess formation or fibrous indurations. Quinine
and urea hydrochloride is preferable either for subcutaneous or
intramuscular injection.
Cohen holds that quinine and urea hydrochloride controls malarial
infection more rapidly and efficaciously than any other salt of
quinine when given intramuscularly. In order to prevent tetanus or
other infections he is very careful about asepsis. He recommends
that a 10 to 15-grain dose be injected every day for a week, then
once a week for a month, then once every two weeks for another
month. He considers a 33% solution as best, thus one could give 10
grains in the contents of an all-glass 2 cc. syringe.
James has recommended very dilute solutions for subcutaneous
injections (1-150). There are practical objections to this method.
It is usual to give about 1 gram (15 grains) of a soluble salt in
10 cc. of water. _The present view is that subcutaneous injections
deserve condemnation._
_Intramuscular Injections._—It is now recognized that when quinine
is not well borne when given by mouth the two modes of administration
to be followed are either by intramuscular injection or introduction
of the drug into a vein. For intramuscular use we dissolve a soluble
salt of quinine, as the bimuriate or chlorhydrosulphate, in distilled
water or sterile saline. A 50% solution is commonly used and from 6
to 10 grains of quinine is injected into the gluteal muscles of one
side about 3 inches below the iliac crest. Repeat the injection on
the other side. Repeat this daily dose of 12 to 20 grains for 3 or 4
days; then give quinine by mouth.
The solution should be autoclaved before use and the skin at the
site of injection painted with iodine. Dudgeon has called attention
to the constant production of oedema and necrosis in the area of
the injection. This tissue necrosis occurs immediately and persists
for a long time. If the injection is made in the neighborhood of an
important nerve, neuritis may ensue. Repeated injections should not
be given in the same area.
Of course in the use of quinine salts through the medium of the
hypodermic needle everything must be sterile.
_Intravenous Injections._—Bass and many others think that when
quinine cannot be administered by mouth it should be given
intravenously. Not only is there the objection of inflammatory
reactions or necrosis when the drug is given subcutaneously or
intramuscularly but the absorption of the drug is so slow that the
patient may die before we obtain the desired effect. Ross condemns
the subcutaneous method and recognizes the advantages of the
intravenous method over the intramuscular one when rapidity of action
is desirable.
In giving quinine intravenously Bass thinks that 10 grains at one
time is sufficient and that a 20-grain dose is not without danger.
He does not think it necessary to give more than 30 grains daily
in this way. Intravenous quinine seems to be entirely eliminated
within twenty-four hours and most of it within twelve hours.
When used in cerebral malaria he repeats the 10 grains
intravenously in eight hours if the drug cannot then be given by
mouth. Bass thinks that theoretically amyl nitrite might relax the
cerebral capillaries which are obstructed by parasite-infected red
cells and thus enable the quinine in the circulation to reach such
cells.
The best known method of administering quinine intravenously is
that of Bacelli. In this method 1 gram (15 grains) of a soluble
salt of quinine is given in 10 cc. of water.
MacGilchrist has shown experimentally that such a strength of
quinine (1-10) will coagulate blood serum.
In my opinion this is a dangerous method if the injection is made
rapidly. There is no doubt as to the necessity for using the
intravenous channel in cerebral or algid types of perniciousness
when intramuscular injections do not give results. The generally
accepted method is to use a salvarsan technique with a dilute
solution of quinine, giving 1 gram (15 grains) of some soluble
salt of quinine in 250 cc. salt solution. Such injections should
be given cautiously. Quinine hydrochloride, which is soluble in
40 parts of water, is the salt usually recommended. MacGilchrist
considers the very soluble acid salts as haemolytic and prefers
to give quinine base—3 pints of a solution of the alkaloid,
containing about 12 grains.
McLean has used concentrated solutions of quinine intravenously
several hundred times in cases of malaria (6 being blackwater fever
ones) without any untoward results. He autoclaves his 10-grain
solution of hydrochlor-sulphate in 10 cc. of sterile water for
twenty minutes at 15 pounds, and injects it slowly into an arm vein,
allowing about two minutes for the injection. The patients complain
of a slight cough and hot feeling in the lungs with a succeeding
dizziness which rapidly disappears. He is opposed to intramuscular
injections and found intravenous ones diluted 1 to 250 often to cause
shock and collapse.
_Rectal Administration._—Some authorities recommend the
administration per rectum of a soluble salt of quinine in about 3
times the usual dose by mouth or hypodermically. It is considered
applicable in cases where there is marked vomiting. It certainly is
the least satisfactory way of giving quinine.
_Dosage and Length of Treatment._—In Panama the standard preliminary
treatment is to give from 3 to 5 grains of calomel followed by 1 or 2
ounces of 50% magnesium sulphate.
Fayrer holds that a torpid liver interferes with the efficient
action of quinine, hence the value of calomel and salts. I prefer
to give 2 or 3 grains of calomel, in divided doses, followed by
sodium phosphate, 2 drams, every two hours, for three or four doses.
_Standard Method._—The National Malaria Committee of the United
States recommends the following treatment: Give 30 grains of quinine
daily in three 10-grain doses. Keep this up for 4 days and follow
by 10 grains every night for 8 weeks. Where the infection does not
present acute symptoms give the 10 grains daily for 8 weeks.
_Canal Zone Treatment._—So soon as the diagnosis is made give 15
grains of quinine 3 times daily (45 grains in twenty-four hours) and
continue such treatment for a week or until the temperature has been
normal for five or six days. Then give 10 grains 3 times daily for
ten or twelve days.
It is considered that by employing such thorough treatment from the
beginning the tendency to latency or relapse is prevented—in other
words the disease is really cured. It is interesting to note that
Torti recommended large single doses at the commencement of treatment.
Espach has noted that he had frequent relapses in many cases
treated by this method. In my opinion the Canal Zone treatment
should be followed by 10 grain doses daily for 8 weeks.
Tonics of iron, arsenic and strychnine are valuable in treating the
anaemia, but it is not advisable to add small doses of quinine to
such tonic mixture.
_Repeated Small Doses._—In Nocht’s method we give the quinine in
small doses repeated several times in the day, as 3 or 4 grains
given 5 or 6 times daily. Such treatment is thought advisable when
there is a tendency to haemoglobinuria or when giving quinine to
pregnant women.
In giving the small doses one should see that they are given during
the night as well as the day.
_Quinine and Pregnancy._—There is frequently hesitancy in giving
quinine to a pregnant woman but unless the malaria is controlled
the patient will be apt to abort. Potassium bromide is thought to
control the ecbolic influences of quinine.
Clark states that the experience at Ancon Hospital would indicate
that quinine can be given with impunity to pregnant women. In
malarial subjects quinine after parturition is of value not only in
controlling a fever due to malaria but it also favors involution
and aids in the healing of perineal tears. The quinine also is
beneficial in improving the quality of the mother’s milk and does
no harm to the child.
_Manson’s Method._—In a benign malarial infection Manson prefers to
wait until the hot stage has been passed and the patient is beginning
to perspire, this idea being that the headache and other symptoms
are aggravated and that very little advantage is gained by treatment
during the early part of the paroxysm. He gives 10 grains at the
onset of the sweating stage and afterward 5 grains, 3 or 4 times
daily, for the following week. He then gives a daily tonic containing
arsenic and iron, with a quinine treatment every seventh day for
about two months.
For regularity he advises the quinine treatment on Sunday giving a
dose of salts in the morning followed by three 5-grain doses during
the day.
Manson notes the danger of large doses of quinine as producing
not only serious disturbances of sight and hearing but pronounced
cardiac depression as well.
There are many who speak highly of Warburg’s tincture in treatment.
It is both laxative and sudorific. The dose is ½ ounce (15 cc.)
which contains about 5 grains of quinine sulphate and 4 grains of
extract of aloes. As a rule it is better to give the quinine and
the laxative separately.
More recently the tendency has been to give large doses of
quinine, not only for its greater curative value but, as well, for
the prevention of relapses. Craig, however, states that in his
experience with aestivo-autumnal infections he has yet to see a
single case, in which treatment was promptly instituted, that did
not recover with a daily treatment of 30 grains.
_Koch’s Method._—Koch recommended 15 grains each day for a week,
then three days without quinine. Then three days with 15-grain doses
each day. Then one week without quinine, followed by three days of
treatment. This plan of a weekly interval followed by three days of
treatment is continued until not fewer than 30 15-grain doses are
given over nine or ten weeks.
_Drugs Other than Quinine._—Salvarsan and neosalvarsan have been
extensively used and with some success in benign infections but
without material effect in malignant tertian ones.
_Intermittent Treatment._—There are those who consider a treatment
in which days of quinine administration are followed by days
without quinine as equally efficient and less trying on the
patient. Some of the experiences of Stephens and his colleagues
indicated that 45 grains on two consecutive days of each week and
continued for 8 weeks gave better results than 30 grains daily over
such a period. In their experiments a dosage above 45 grains in a
day did not seem any more efficient than 45 grains, so that this
may well be considered as a maximum dose. On the whole however
there seems to be a greater tendency to relapse following an
intermittent treatment and Acton, as a result of his comparison of
intermittent and continuous methods, deprecates the intermittent
one.
Some have thought that salvarsan aided the specific action of
quinine.
Many physicians recommend arsenic in the form of Fowler’s solution
or as sodium cacodylate. It is most useful in chronic cases. Some
preparation of iron is, of course, indicated in malarial anaemias.
It has been claimed that radium and X-ray treatment, when directed to
the spleen, assist the action of quinine.
Methylene blue, next to quinine, has been considered as the most
valuable drug. It is given in 2-grain doses every four hours. It is
also given intravenously.
The form of methylene blue to use is that labelled “Medicinal.”
It is often stated that the opium fiends of the tropics are immune to
malaria and some physicians have claimed antiperiodic properties for
the drug. Dover’s powder is lauded by some as of value in symptomatic
treatment.
Surveyor has recommended picric acid in the treatment of malaria in
doses of 2 grains two or three times daily.
Recently hectine, a remedy somewhat similar to the cacodylates,
has been strongly recommended by the French. It is given
intramuscularly in 2-grain doses. It is said to be valuable when
there is a leucopenia as it has a tonic action. It has been
recommended to combine this treatment with quinine.
It is said to be a good substitute for quinine in blackwater fever.
Rogers has recently noted the value of tartar emetic injections in
eradicating the sexual parasites of carriers.
After rather extended trial of this drug for the above purpose and
as a method of treating ordinary infections the general opinion is
against its value.
_General and Symptomatic Treatment._—During the course of the
fever the patient should remain in bed and given only broths.
In the intermissions of the benign forms one may allow a more
generous diet. It is important that the patient be not allowed
to become constipated and as a laxative one grain of calomel in
divided doses followed by effervescing phosphate of soda is very
satisfactory.
For the nausea sips of an ice-cold alkaline mineral water or
cracked ice will generally prove effective. In more refractory
cases spirits of chloroform or even a hypodermic of morphine
may be necessary. Counterirritation to the epigastrium is often
a help. Phenacetine may be given for the headache although ice
water compresses are generally sufficient. In algid states hot
water bottles should be applied to the body. During convalescence
excesses in food or drink should be avoided as well as fatigue or
exposure to wet or cold.
CHAPTER II
BLACKWATER FEVER
DEFINITION AND SYNONYMS
=Definition.=—Blackwater fever is a disease of disputed etiology
but recently there has seemed to be rather general agreement that it
is connected with repeated attacks of malaria. It is prone to affect
the old European residents of parts of the tropics where malignant
tertian is rampant.
On the basis of lowered integrity of the red cells, by reason of
repeated attacks of malaria, we may have extensive lysis of the red
cells following the administration of a dose of quinine or as the
result of refrigeration, excessive exposure to the sun or great
fatigue.
Clinically we have a prostrating chill of asthenic type
associated with early jaundice and the passage of porter-colored
urine—haemoglobinuria.
=Synonyms.=—Haemoglobinuric Fever, Bilious Haemoglobinuric Fever,
Haemorrhagic Malarial Fever.
French: Fièvre Bilieuse Hemoglobinurique. German: Schwarzwasserfieber.
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—There is no reasonable doubt that the explanation of
the fact that blackwater fever was first brought to the attention
of the medical world, by Lebeau and other French naval surgeons,
in Madagascar, in 1850-1853, was due to the confusion of this
disease with the bilious remittent type of pernicious malaria as
well as with yellow fever. Even after the clinical picture was well
recognized, disputes as to the nature of the coloring matter of
the characteristic urine were frequent, some considering that the
dark color, which we now know to be due to haemoglobinuria, was due
to haematuria or that the color was due to bile. Blackwater fever
must have been the condition referred to in medical literature
of the period, 1850 to 1870, under the names “Fièvre bilieuse
haematurique,” “haemorrhagic malarial fever” and “febris remittens
haemorrhagica.”
It was first described in the U. S. by Cummings of Louisiana
in 1859. Other American physicians during the next ten years,
described the disease from various other Southern states.
Veretas noted the presence of the disease in Greece, in 1858.
It is rather remarkable that the disease was not noted by so keen
an observer as Torti, if it existed in his time, and Manson states
that it is strange that it should not have been recognized in India
if it had existed there prior to recent times. Some think that its
introduction into Africa has been of recent occurrence. There are
two explanations of the recent greater prominence of the disease in
Africa and other tropical areas, where malignant malaria prevails
extensively, which are (1) that there has been a great influx of
susceptible Europeans into such areas during the past twenty or
thirty years and (2) that the more frequent and excessive dosing of
malarial patients with quinine is responsible.
[Illustration: FIG. 23.—Geographical distribution of blackwater
fever.]
=Geographical Distribution.=—It is in tropical Africa that the
disease is of prime importance as a cause of death and invaliding.
Here it prevails chiefly in West, Central and East Africa from
about 12° N. to 12° S. latitude. It is less frequent in Northern
Africa although a considerable number of cases have been reported
from Algeria. It is unknown in Egypt, a country where malaria is
very rare in Europeans.
In India it occurs in several districts and Stephens states that
in the Duars (Bengal) he saw more cases in a fortnight than he
had seen in the same time in Africa. In Europe it occurs chiefly
in Southern Italy, Sicily, Sardinia and Greece. Blackwater fever
was frequently noted among the British forces in Macedonia and
Palestine during the World War.
It is common in Central America and Northern South America,
especially in the regions of the Amazon basin, in Brazil.
In the U. S. it is chiefly found in the most malarious sections of
Arkansas, Mississippi, Louisiana, Texas, Alabama, Georgia, Florida
and South Carolina. It would seem that it is becoming more rare in
the Southern States.
As a result of malarial prophylaxis among the Americans working in
the Panama Canal Zone it has almost disappeared among them although
still common among the white Europeans in the same region who
neglect quinine prophylaxis and mosquito protection.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—There seem to be cases where from very heavy infection
with the malignant tertian parasite, as from 12 to 20% of the red
cells, one can expect the appearance of a more or less dark urine,
the color of which is due to haemoglobinuria. Such cases give support
to the old view that haemoglobinuric fever was simply a type of
pernicious malaria.
Brem has proposed for such cases the designation, pernicious
malarial fever with haemoglobinuria.
The idea as to etiology which now seems most generally accepted
is that blackwater fever occurs almost solely in those who have
resided for considerable periods of time in districts where malignant
tertian malaria is very prevalent and intense and who have repeatedly
suffered from such malarial attacks. Rarely blackwater fever may
be connected with benign tertian infections or exceptionally with
quartan ones. As a result of the damage done the patient by the
malarial attacks there is a tendency on the part of his red cells
to haemolysis which may be due to the production of a hypothetical
autolysin or to anaphylactic sensitizations, as has been suggested
recently.
Malaria is the predisposing cause and the exciting cause may be
any of a number of different factors capable of lowering body
resistance such as the occurrence of another malarial attack,
the administration of quinine, particularly of the acid salts of
quinine in rather large doses, refrigeration, as brought about by
one’s clothes becoming wet and then later subjected to the chilling
influence of a sea breeze, to excessive fatigue or dietetic or
alcoholic excesses.
Quinine administration, particularly if associated with
refrigeration, is the most common exciting factor.
As regards the association of malaria and blackwater fever
Stephens, in a study of 390 cases of blackwater, found that 73%
of the cases showed malarial parasites on the day preceding the
haemoglobinuria, 47.5% on the day of the attack and 23% on the day
following the appearance of the dark urine. Other workers give
higher figures as 95, 70 and 20%.
Where one utilizes the methods of examining for increased
percentage of large mononuclears or for melaniferous leucocytes,
in those cases not showing malarial parasites, the percentage
of evidence of malaria is greatly increased. It is necessary to
understand that a small percentage of cases diagnosed as blackwater
fever do not show evidences of malaria at autopsy and cases are
recorded where blackwater has attacked persons who had never had
malarial fever, such instances, however being exceptional.
_The Quinine Theory._—This idea as to the causation of blackwater
fever first originated with Veretas, in Greece, in 1858. Later
Tomaselli supported this view in Italy and more recently it was
advocated by Koch. Just as in connection with the influence of
Koch’s great prestige much harm was done in prophylaxis against
bovine tuberculosis so in this matter of quinine in the causing of
blackwater the influence was unfortunate because many persons with
severe malaria now refuse to take the specific quinine for fear of
bringing on haemoglobinuria.
It may be stated that quinine alone, even in doses which are
capable of producing profound toxic effects such as disturbances
of sight and hearing, weak heart and collapse does not, other than
exceptionally, cause haemoglobinuria. It has even been stated
that quinine base and quinine tannate tend to prevent haemolysis,
haemoglobinaemia and haemoglobinuria. Blackwater fever may develop
without the previous administration of quinine.
_Theory as to Acidosis with a Damaged Liver Plus Malaria and Acid
Salts of Quinine._
MacGilchrist has recently advanced the idea that blackwater fever
is brought about by an acidosis in one with a damaged liver plus
malaria and the administration of acid salts of quinine. He thinks
that one can safely give the quinine when alkalis are being given
and that quinine base is protective against haemolysis.
_Theory as to Its being Caused by a Piroplasm._
Sambon has thought by reason of the clinical resemblance of
blackwater to certain haemoglobinuric diseases in cattle, dogs and
sheep that such a cause might be operative. These parasites of the
red cells are easily discernible in the animal infections but have
never been seen in blackwater fever.
_The Chlamydozoal Hypothesis._
Leishman has recently noted appearances in the large mononuclear
cells of the blood of blackwater patients of certain cell
inclusions which he thought to be of chlamydozoal nature and that
these chlamydozoa might be etiological factors. Such appearances
may not only be absent in marked cases of blackwater but may be
seen in conditions other than blackwater fever.
=Epidemiology.=—There seems to be a consensus of opinion that when
malaria is kept in check by proper and persistent quinine prophylaxis
or by other antimalarial measures blackwater fever becomes mild in
character or even nonexistent. It is those who are careless about
quinine prophylaxis or those who expose themselves to depressing
influences as cold, wet, excessive fatigue or alcoholic debauches in
whom blackwater shows itself.
Overexertion leading to fatigue and chilling seem to be the most
common exciting factors. Those in bad health from disease or lack
of proper diet seem more susceptible. A peculiar feature of the
disease is that it may not be present in a district for a number
of years and then assume almost epidemic proportions. Europeans
are usually exempt from attacks during their first year in endemic
tropical areas. Dudgeon obtained a malarial history in every one of
a hundred cases observed by him in the Balkans.
PATHOLOGY AND MORBID ANATOMY
As a result of the excessive destruction of red cells the liver
cannot convert the great amount of haemoglobin outpouring into bile
pigment so that haemoglobinaemia and haemoglobinuria result. It has
been estimated by Ponfick that if ⅙ of the red cells are destroyed
the liver is unable to dispose of the liberated haemoglobin and
haemoglobinuria results. A damaged liver would be less competent.
Various discussions as to autolysins and complement content of serum
have arisen.
Dudgeon has demonstrated active haemolysins in the tissues and
urine of blackwater fever cases which bodies he was unable to note
in other conditions including malaria. There was no evidence of
increased fragility of the red cells. There was no evidence of
auto-haemolysis. Bile pigment in the plasma occurred in most of the
cases which ended fatally.
As a rule we have the pathological findings which go with malaria.
As peculiarities of blackwater noted by Whipple and others may
be mentioned congestion of the kidneys with purple-colored
pyramids. In the spleen the Malpighian bodies are prominent and
sharply outlined. Very striking are the necroses of the Malpighian
corpuscles of the spleen and focal necroses of the liver. Whipple
considers that this speaks for a powerful circulating toxin in
blackwater fever which is not present in malaria.
The liver cells in the area of the central veins show the most marked
destruction. The myocardium shows fatty change and the fat lipoid
content of the adrenal is reduced.
The anuria is thought to be mechanical and due to the plugging up
of the tubules by haemoglobin casts.
The urine shows a reddish to black color and has a sediment made up
of granular débris with haematoidin crystals and only rarely a red
cell. It is not a haematuria.
The absorption bands of methaemoglobin are usually noted
spectroscopically.
Urobilin and albumin are present in large quantities.
SYMPTOMATOLOGY
=A Typical Case.=—In a person who has lived in an intensely
malarious region for one or two years or even long after he has left
such districts and who has had several malarial attacks, there comes
on what is considered as another malarial chill, which may or may not
definitely be connected with some resistance-lowering influence, as
exposure to tropical sun or rain, or indulgence in dietary or other
excesses, or following in one to six hours the accustomed dose of
quinine. This chill, however, is more prostrating than those formerly
experienced and upon passing his urine the patient notes its reddish
to black coffee color and himself makes the diagnosis of blackwater
fever. The attack comes on suddenly with a very severe chill, marked
prostration and pain over the region of the kidneys. The temperature
in a typical case rapidly goes up to 104° to 105°F.
Rather profuse sweating accompanies the fall of the fever and the
patient is markedly debilitated after the subsidence of the fever.
There may be a recurrence of the paroxysm the following day. The
fever course, however, may be more or less continuous or remittent.
In other words it tends to be irregular and atypical.
Nausea and bilious vomiting come on early with epigastric distress.
Almost as pathognomonic as the haemoglobinuria is the early and
intense jaundice. This comes on within a few hours or almost
simultaneously with the haemoglobinuria and usually lasts for two or
three days after the haemoglobinuria and fever have ceased. Itching
of the skin of this jaundice is not noticeable.
The spleen and liver are enlarged and tender. Albuminuria comes
on with the haemoglobinuria and shows from 1/10 to 4/10 of 1% of
albumen by weight.
The pulse is rapid, 110 to 120, from the first but soon becomes
feeble and of low tension. In severe cases the very rapid almost
thready pulse, with pallor and cold extremities, may resemble a
severe haemorrhage. Epistaxis is not uncommon. A very unfavorable
symptom seems to be hiccough. Another frequent cause of death and
the one against which we chiefly direct our therapeutic measures
is anuria with subsequent uraemic symptoms, such as coma and
convulsions. At times a nephritis may develop in the course of a
blackwater attack and the case subsequently run as one of severe
nephritis.
Very striking is the rapidly developing anaemia, some cases showing a
loss of two million red cells in twenty-four hours.
The mind is usually clear throughout an attack, the patient showing
restlessness and marked anxiety.
In mild cases the fever course and haemoglobinuria is over within
twenty-four hours leaving the patient far more prostrated than
would a malarial paroxysm. In severe cases, however, the fever
runs a remittent course over several days, with more marked
haemoglobinuria and jaundice.
There may be cases which only show haemoglobinuria. These apyretic
cases have been considered by some as quinine haemoglobinuria.
Symptoms in Detail
_Fever Course._—This resembles that of a malarial paroxysm and may
be intermittent in character or last several days as a remittent
fever. The rigor which accompanies the febrile rise is intense.
_The Liver and Spleen._—As a result of the marked blood
destruction the liver is unable to dispose of the haemoglobin
outpouring and icterus, which usually comes on in a few hours and
is intense, is almost constant together with epigastric distress,
bilious vomiting and tenderness and slight enlargement of the
liver. The spleen is also somewhat enlarged and quite tender.
_The Circulatory System._—At first the pulse is rapid with tension
but soon it becomes weak, compressible and of low tension. In
severe cases it may have a rate of 150 or more or even become
thready.
_The Genito-urinary System._—The dark colored urine is
pathognomonic of the disease and gives it its name. The reddish
to almost black color is due to haemoglobin and not to bile.
Bile pigments do not appear in the urine. There is but rarely
a red cell to be found in the granular débris with occasional
haematoidin crystals which forms the urinary sediment, hence it is
haemoglobinuria and not haematuria.
The urine resists decomposition for a long time. Albumin is present
in large amount and comes on with the onset of haemoglobinuria.
Casts are abundant and urobilinuria is marked. As a result of the
blocking up of the renal tubules with haemoglobin casts pain over
the loins and anuria may occur. There may be vesical tenesmus.
_The Blood._—Cases have been reported where as many as 2,000,000
red cells have been destroyed within twenty-four hours, so that
rapid and marked anaemia characterizes the disease. The blood is
thin and the serum tinged. The degenerative changes of the red
cells are not as commonly seen as one would expect but this is
probably due to the fact that degenerated cells are first destroyed
in the excessive haemolysis. Hb percentage reduction generally
parallels the reduction in red cells. Melaniferous leucocytes may
be found and during the leucopenia, which follows the paroxysm, the
large mononuclears and transitionals may be increased to 20%. There
is a reduction in the alkalinity and coagulability of the blood.
DIAGNOSIS
=Clinical Diagnosis.=—An unusually asthenic prostrating paroxysm,
similar to that of a malarial chill, but with more intense rigor,
during which haemoglobinuria, early jaundice and marked bilious
vomiting are features, makes for a diagnosis of blackwater fever.
The two diseases which are most likely to be confused with
blackwater fever are yellow fever and bilious remittent malarial
fever.
In infectious jaundice the jaundice does not appear for 48 to 72
hours, the pulse is slow, there is no haemoglobinuria, although
there may be a haematuria, and we have a polynuclear leucocytosis.
A case of paroxysmal haemoglobinuria occurring in a blackwater
district would be impossible to differentiate from a very mild
case of blackwater fever. Chlorate of potash or carbolic-acid
poisoning, or snake bite, or severe burns, may produce
haemoglobinuria.
-----------+-------------------+-------------------+--------------------
| Blackwater fever | Yellow fever | Bilious remittent
-----------+-------------------+-------------------+--------------------
Onset |Sudden but asthenic|Sudden but asthenic|Comes on more
| with marked | for two or | slowly.
| rigor. | three days. |
-----------+-------------------+-------------------+--------------------
Urine |Haemoglobinuria. |No blood in urine |Bile in urine.
| Pink foam to | before 3d or 4th | Yellow froth on
| urine. Albuminuria| day and then | shaking urine.
| from first day. | haematuria. | Albuminuria
| | Albumin from 2d | slight and
| | day. | not common.
-----------+-------------------+-------------------+--------------------
Icterus |Early and intense. |Does not appear |Jaundice develops
| Comes on in a few | before 3d day | slowly about 2d
| hours. | and gradually | day.
| | intensifies. |
-----------+-------------------+-------------------+--------------------
Spleen |Somewhat enlarged |No enlargement of |Splenic enlargement
| and tender. | spleen. | is marked; may
| | | have ague cake.
-----------+-------------------+-------------------+--------------------
Pulse |Rapid from start |Stationary pulse |Pulse not so rapid
| and becoming | with rising temp- | as in blackwater.
| more so as disease| erature or falling|
| progresses. | pulse with |
| | stationary temp- |
| | erature. (Faget’s |
| | law.) |
-----------+-------------------+-------------------+--------------------
Vomit |Early marked |Mucus-like followed| Bilious vomiting
| bilious vomiting. | by black vomit | and gastric distress
| | about 4th day. | less than in
| | | blackwater.
-----------+-------------------+-------------------+--------------------
Evidences |Usually present as |Negative unless |Some evidence at
of malaria| parasites or | yellow fever | some time almost
| melaniferous | occurs in a | always obtainable.
| leucocytes or | malarial case. |
| increased large | |
| mononuclear | |
| percentage. | |
-----------+-------------------+-------------------+--------------------
=Laboratory Diagnosis.=—Other than the noting of evidences of
malarial infection, rapid reduction in red-cell count and haemoglobin
percentage there is little information to be derived from the blood
which is thin and shows delayed coagulation time. It is difficult to
make good blood smears. In the urine we note the granular sediment of
débris of red-cell destruction with at times haematoidin crystals.
Spectroscopically we get absorption bands of methaemoglobin and more
rarely oxyhaemoglobin.
[Illustration: FIG. 24.—The most important clinical spectra.
(_Monographic Medicine._ D. Appleton and Co., New York.)]
Albumin is present in quantity and urobilin is usually present in
large amount.
One can examine the urine for blood by the haemin-crystals, guaiac
or benzidin tests.
Burkitt has noted that his cases of blackwater have shown a very
acid urine with large amounts of acetone bodies.
The serum shows haemoglobinaemia and may show reduced alkalinity.
PROGNOSIS
So far as statistics go the mortality rate would appear to be
influenced by the delicateness of the tests used for determining the
presence of haemoglobinuria. When a diagnosis is only made with the
presence of marked haemoglobinuria, showing porter-colored urine, the
mortality rate is, of course, higher than when slight haemoglobinuria
is taken into consideration.
In cases treated with quinine, Deaderick, in statistics of various
authorities, gives a death rate of 25.9%; in cases not so treated,
of 11.1%.
Marked and persistent vomiting and hiccough are very unfavorable
signs. In particular, however, it is anuria that gives us our
greatest concern in the care of a case. A severe attack is followed
by a marked anaemia and convalescence is usually protracted.
PROPHYLAXIS AND TREATMENT
=Prophylaxis.=—The view now generally entertained is that where
malarial prophylaxis is properly carried out there will not be any
blackwater fever. In persons who have had a previous attack of
blackwater fever quinine prophylaxis should be with quinine tannate
or quinine base, avoiding the acid salts of quinine.
In particular any exposure to chilling influences or conditions
which lower resistance should be avoided. As blackwater fever is
more prevalent among those who have been for 2 or 3 years in highly
malarious, tropical regions than among recent arrivals, the former
should exercise the greater care as to errors in diet, alcoholic
excesses, exposure to wet and irregularity in quinine prophylaxis.
=Treatment.=—There is less unanimity of opinion as to the
advisability of giving quinine during an attack of blackwater fever
than exists as to any other therapeutic measure.
Of course if it be true that quinine base is devoid of haemolytic
influence the fear of increasing haemolysis by giving quinine would
not have to be considered. At any rate any red cells containing
parasites will surely be destroyed in the general haemolysis and
with them their contained parasites, so that it does not seem
reasonable to give quinine during the first day or two of the
attack. Quinine, if given, should not be by mouth for fear of
increasing the nausea and vomiting. The majority of authorities
hold that if parasites persist after two or three days from the
onset quinine is indicated. Some give quinine during the first day
if parasites are present but otherwise they withhold quinine.
Absolute rest in bed, avoidance of chilling and good nursing are the
prime considerations in treatment.
The patients should be given alkaline waters freely, as Vichy
or water containing 30 grains of bicarbonate of soda to the
pint. Cracked ice often tends to lessen the nausea and vomiting.
Albumin water or barley water may be retained better than milk or
broths. As the condition is so asthenic one cannot disregard the
nourishment of the patient during the first two or three days as is
true of the sthenic first stage of yellow fever. Hot fomentations
to the loins are indicated for relief of pain and the effect on the
renal congestion.
Saline enemata are of particular value and may suffice in mild
cases. In severe cases subcutaneous or intravenous saline
injections are necessary. Sorel recommends the intravenous
injection of lactose or glucose solutions in quantities of about
300 cc. (Crystallized glucose 47 grams, water 1000 cc. or C. P.
lactose 92.5 grams, water 1000 cc.) He also uses these sugar
solutions as enemata. Dry cupping or hot fomentations over the
loins are the usual remedies in threatened suppression of the
urine. If blackwater fever should be shown to be accompanied by
diminished alkalinity of the serum then the intravenous injection
of a 1 or 2% solution of bicarbonate of soda would be indicated.
Some have recommended calcium lactate in doses of 20 grains every
four hours. There is little evidence however to indicate that it
is of value. Transfusion of blood has been practised but reports
of such treatment indicate that while temporary improvement occurs
yet this is followed by a return of haemoglobinuria. From Dudgeon’s
work it would seem that the existing haemolysins would destroy the
foreign red cells.
Burkitt claims excellent results by intravenous injections of
alkaline solutions, similar to those recommended under “cholera.”
He also finds neosalvarsan of the greatest value in treatment, as
cases so treated convalesce most rapidly.
Hearsey advocates a mixture in which there is contained 10 grains
of bicarbonate of soda and 1/30 grain of bichloride of mercury in
each dose, to be given every two hours.
Cholesterin has been given in 15-grain doses in suspension in thick
milk every four hours with the idea that it is anti-haemolytic. The
dose is repeated 2 or 3 times.
Calomel in large doses has been recommended by some tropical
practitioners but it would seem advisable only to use calomel to
keep the bowels open and then in small divided doses.
Antipyretics should not be used from their depressing action on the
heart.
For the urinary suppression, Wallace recommends salines as hot
as can be borne, administered high in the colon by a double-flow
tube. Since he found this treatment effective after intravenous and
rectal injections had failed, it is to be inferred that the results
obtained were due not to the further administration of fluid but to
the action of heat applied directly to the splanchnic area.
CHAPTER III
THE TRYPANOSOMIASES
DEFINITION AND SYNONYMS
=Definition.=—African trypanosomiasis is an important protozoal
disease of Central and West Africa, due to a flagellate, _Trypanosoma
gambiense_, and transmitted by a tsetse fly, _Glossina palpalis_.
The trypanosome undergoes a developmental cycle in the fly which
does not become infective until after about twenty days. The period
of incubation is about two or three weeks, after which an irregular
fever with approximately normal morning temperature and high evening
rise appears, attended with a rapid pulse rate at all times. This is
called the stage of trypanosome fever and may show trypanosomes in
the peripheral blood. Later on the glands enlarge and gland juice
shows trypanosomes. With the appearance of a fine tremor of the
tongue, a state of apathy or lethargy, known as sleeping sickness,
sets in, attended with trypanosomes in the cerebro-spinal fluid.
Gradually increasing mental deterioration marks the almost invariable
course to death. A more virulent type of trypanosomiasis is found in
Rhodesia.
In Brazil there is a disease caused by a flagellate,
_Schizotrypanum cruzi_, which resembles a trypanosome and is
transmitted by a bug, _Lamus megistus_. The disease runs an acute
course with a high fever and great mortality in infants showing
chiefly manifestations of involvement of brain or thyroid gland. In
adults it runs a chronic course showing neurological manifestations
or signs of myxoedema or even of Addison’s disease.
=Synonyms.=—Sleeping sickness; Negro lethargy. French: Maladie du
sommeil. German: Schlafkrankheit. For the Brazilian trypanosomiasis,
Schizotrypanosomiasis; Chagas’ disease.
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—In describing sleeping sickness, in 1803, Winterbottom
brought out the importance of enlargements of the posterior
cervical glands (Winterbottom’s sign).
In 1880 Evans had found a trypanosome in the blood of horses
affected with surra and several years afterward Bruce discovered
that nagana, a fatal disease of cattle, was due to a trypanosome,
_T. brucei_. In 1890 Nepveu found a trypanosome in the blood of a
man in Algeria but owing to vagueness of description the discovery
did not attract attention.
[Illustration: FIG. 25.—Geographical distribution of African
trypanosomiasis.]
In 1901, Forde found a parasite in the blood of a patient in the
River Gambia Colony who had a fever and in 1902 Dutton recognized
the parasite as a trypanosome and gave it the name _T. gambiense_.
In 1902, Castellani, finding a trypanosome in the cerebro-spinal
fluid of a patient with sleeping sickness, brought about the
establishment of the connection between the trypanosome in the
blood (trypanosome fever) and the trypanosome in the cerebro-spinal
fluid (sleeping sickness). In 1903, Bruce and Nabarro reported that
this disease was spread by a tsetse fly, _Glossina palpalis_.
In 1910 Stephens and Fantham brought forward the existence of a
more virulent trypanosome, _T. rhodesiense_.
=Geographical Distribution.=—The disease exists on the West Coast
of Africa, from Senegal to Mossamedes. It is also present in the
Congo basin and particularly in Uganda. The more virulent form is
found in Rhodesia.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—The African trypanosomiases follow infection with two
species of trypanosomes; the more virulent type of the disease,
occurring in South Central Africa, being due to _Trypanosoma
rhodesiense_, transmitted by _Glossina morsitans_ and that of
less severe type, but of more general distribution, being due to
_T. gambiense_ and transmitted by _Glossina palpalis_. The very
important _Trypanosoma brucei_, which is the devastating agent in the
African horse, dog and cattle disease, nagana, is also transmitted
by _Glossina morsitans_ and there exists the opinion that this
trypanosome is identical with _T. rhodesiense_.
Macfie has reported a new trypanosome, _T. nigeriense_, from
young persons in Nigeria. It is said to be less virulent than _T.
gambiense_, and to be transmitted by _Glossina tachinoides_.
[Illustration: FIG. 26.—_Trypanosoma gambiense_ (slide presented by
Professor F. G. Novy) (From Todd.)]
Bruce considers _T. nigeriense_ as being _T. gambiense_. Macfie
noted many short stumpy forms in animals inoculated with _T.
nigeriense_.
These trypanosomes are blood flagellates and are typical of the
Binucleata in possessing two chromatin-staining areas, the larger
and more centrally situated mass being the tropho or macronucleus
and the smaller, but more deeply staining one, the kineto or
micronucleus (Blepharoplast). Trypanosomes have a fusiform or
fish-shaped body which stains blue. Near the less pointed,
nonflagellated end, usually called the posterior end, is the deeply
stained blepharoplast. Adjoining this is a vacuole and, taking
origin from this part of the trypanosome, is the flagellum. This
borders an undulating membrane attached to the body and then,
carried along to the other extremity, projects free as a long,
whip-like flagellum.
In fresh preparations the body of the trypanosome progresses in the
direction of its flagellated end, although occasionally it will be
observed to move in the opposite direction.
Some trypanosomes show granules at certain stages and it has been
observed that the extrusion of these granules precedes disintegration
of the trypanosome. It has been suggested that such granules might
be infective, explaining the infectivity of blood from which
trypanosomes were absent. In the separation of trypanosomes into
groups and species Bruce relies upon morphology, action on animals,
and manner of development in the tsetse fly. He does not consider
serum diagnosis and cross inoculation methods as reliable for
differentiation. The human trypanosomes are polymorphic.
_T. gambiense_ varies much in length and breadth. The normal
type, as found in the blood, varies from 14 to 20 microns, while
longer forms, 20 to 24 microns, are growth ones and, in the
longest ones (23 to 33 microns), we have those preparing to divide
longitudinally. The normal short forms are the ones from which
the development takes place in the tsetse fly. In width these
flagellates are from 1.5 to 2 microns. The blepharoplast is oval
and the nucleus situated about the center.
[Illustration: FIG. 27.—_Glossina palpalis_ in natural resting
position and with wings outstretched. (MacNeal after Doflein.)]
With _T. rhodesiense_ the nucleus is typically located almost
adjacent to the blepharoplast. As a matter of fact it may require
the passage of this trypanosome through rats to bring out these
“posterior nuclear forms,” the nuclear location being at times almost
entirely that of _T. gambiense_. In addition to the characteristic
of nucleus being near the blepharoplast, this trypanosome is more
virulent for laboratory animals than _T. gambiense_, agreeing in this
respect with the more severe clinical course in man.
When the tsetse fly, _Glossina palpalis_, feeds on a man in whose
peripheral circulation there are normal type trypanosomes we
have an accumulation of such forms in the middle and posterior
portions of the gut. From the eighth to the eighteenth day long,
slender forms develop and pass forward into the proventriculus.
None of the intestinal forms can cause infection when injected
into animals. These proventricular types work their way into the
salivary ducts and thence into the salivary glands, where further
development takes place. Here we have shorter forms developing,
which are similar in morphology to the normal blood type. It is at
this stage that the fly becomes infective by the passing of these
trypanosomes down the salivary ducts and through the channel in the
hypopharynx to the subcutaneous tissues of the person bitten. High
temperatures, 75 to 85°F., are favorable to development, while low
temperatures, 60 to 70°F., are inimical to development, but do not
kill the ingested trypanosomes. This explains the long period which
at times elapses before a fly becomes infective. Under favorable
conditions a fly becomes infective in twenty to thirty-four days
and remains infective the rest of its life, up to 185 days. The
infection is not transmitted to the pupa. This is an inoculative,
cyclical or indirect type of infection. It is usually considered
that a tsetse fly whose proboscis has just been contaminated with
trypanosome blood is capable of transferring the infection for a
few hours. This would be a mechanical or direct method of infection
and such power for infection only lasts for a few hours.
There are other groups of trypanosomes, not important for man,
in which the cyclical development does not include the salivary
glands. In the _T. pecorum_ group of small monomorphic trypanosomes
development takes place only in intestines and proboscis, while in
the _T. vivax_ group this occurs in the proboscis alone.
[Illustration: FIG. 28.—_Glossina morsitans_ before and after
feeding. Lateral view. (From Doflein after Austin.) MacNeal.]
When tsetse flies feed on animals infected with trypanosomes only
from 2 to 6% become infective. Again, it has been shown that where
the wild animals on which tsetse flies feed may show an infection
of from 16 to 50% yet not more than 2 out of every 1000 tsetse
flies, caught and tried out on susceptible animals, show themselves
infective.
Both of the human trypanosomes of Africa have been cultured by
using the N.N.N. medium in which rat’s blood was substituted for
that of the rabbit. Human blood will also serve as a substitute.
Growth however is not constant.
=Epidemiology.=—Practically the only method of transmission of the
disease is by the bite of infected tsetse flies. The female gives
birth to a single, yellowish brown, motile larva, which is almost as
large as the mother and which, upon reaching the ground, bores its
way into a coarse, sandy soil for a depth of about two inches and
then becomes a pupa. The larval stage in the mother lasts about two
weeks and the pupal stage about a month.
The tsetse fly is much like _Stomoxys_, but has a branching of
the feathering of the arista, long palps, a bulb to the proboscis
and a characteristic upbending of the fourth longitudinal vein
to meet the mid-cross vein. The female deposits her larva near a
shady place upon loose, dry, sandy soil. Moisture and sunlight are
not favorable for pupal development, the sun being particularly
injurious, so that pupae, buried only an inch deep and away from
shade, are killed. This fact has been utilized in prophylaxis by
cutting down the trees. The trouble is that the bush growth which
soon follows is favorable as providing shade for the pupae.
Male and female flies bite and transmit the disease. They bite in
the daytime, usually from 9 A.M., to 4 P.M., and will bite in the
sunlight.
It has been stated that tsetse flies are attracted by persons
wearing khaki clothing.
With a view to eradication of the disease certain areas have been
depopulated, but upon examining the flies caught in the district a
year or more later, infected flies have been obtained. This would
indicate some other reservoir than man. It is now generally conceded
that the trypanosome strain in the antelope is the same as _T.
rhodesiense_, both being transmitted by _G. morsitans_.
Taute, however, believes them different as he not only injected
blood containing such trypanosomes into himself, with negative
result, but also allowed flies which had fed on antelopes, which
were infective for laboratory animals, to feed on himself, likewise
with negative result. It is a well-known fact that men in good
condition are refractory to trypanosome infection so that this
courageous experiment does not prove the antelope strain to be
different from the human one.
One measure that has been proposed is to kill off the big game from
a certain area with a view to depriving the flies of their main
source of infection.
The probabilities of an animal reservoir for _T. gambiense_ however
is not so well settled. Many think that we may have trypanosome
carriers and that such persons in the enjoyment of health may act
as reservoirs of the virus. Koch suggested that crocodiles were
important factors in the life of the tsetse flies and recommended
the destruction of the crocodile eggs.
Koch noted the infection of 15 women in a fly-free district and
considered their infection as coming from sexual intercourse with
their husbands, who had returned home from fly districts where they
had contracted trypanosomiasis.
This same method of infection of prostitutes has quite recently
been brought to notice by Bernard.
It will be remembered that dourine, a trypanosome disease of
horses, caused by _T. equiperdum_, is transmitted by the sexual act.
All observations however indicate that the spread of the disease is
almost exclusively through the medium of the tsetse fly. Professor
Lanfranchini was infected in his laboratory by a strain which was
supposed to be _Trypanosoma brucei_.
PATHOLOGY
The chief pathological findings are the enlargements of the lymphatic
glands. The dura mater may be adherent in places and the pia mater
may show areas of thickening. The cerebro-spinal fluid is increased
in amount. The pathological process is a chronic polyadenitis which
is followed by a chronic inflammation of lymphatics of brain and
spinal cord.
We have a meningo-encephalitis in which the most characteristic
feature microscopically is a widespread perivascular infiltration
of small round cells surrounding the vessels of the pia-arachnoid
of both brain and cord. The process is most marked about vessels
of pons and medulla. The nerve cells are but little affected other
than those of the bulbar nuclei.
[Illustration: FIG. 29.—Temperature chart of trypanosome fever.]
SYMPTOMATOLOGY
_The Period of Invasion._—After an incubation period which may be
as short as ten or twelve days, following the bite of an infective
tsetse fly, the trypanosomes may be found in the blood or in gland
juice. One case has been reported where an official of the Belgian
Congo showed trypanosomes less than four weeks after his arrival in
the colony. His first symptoms were noted about ten days after his
arrival.
In natives, trypanosomes may be present in the blood for long
periods of time during which they may do heavy work; thus 7 of
Koch’s 52 native porters showed trypanosomes. In Europeans however
the course of the disease is rarely so insidious but rapidly enters
upon the stage of trypanosome fever.
_The Stage of Trypanosome Fever._—Although fever may be absent in
natives until the onset of the period of sleeping sickness, yet in
Europeans there are usually noted febrile paroxysms, lasting for a
few days, and followed, by afebrile periods varying from a few days
to two or three weeks.
The temperature curve is of a markedly remittent type, approaching
normal in the morning and going up to 103°F. or higher in the
evening—a wide daily range. Very characteristic is a low-tension
rapid pulse which often is as rapid when the temperature
approximates the normal as when it is higher. Early in the disease
there are evidences of involvement of the nervous system, as shown
by headache insomnia, difficulty of concentration for mental work
and cardiac instability.
[Illustration: FIG. 30.—Rash of human trypanosomiasis. (Photo: R.
McKay.) By permission from Manson’s Tropical Diseases.]
_Winterbottom Sign._—Very important are the glandular enlargements,
particularly of the glands of the posterior cervical triangle
(Winterbottom’s sign), which upon puncture may show trypanosomes when
the blood examination fails to reveal them. The glands are discrete,
soft, usually painless and may show but very slight enlargement.
Oedematous swellings, especially about the eyes or joints or in
localized areas upon the trunk, may be rather prominent in some
cases. In Europeans pinkish erythematous rings appearing early in
the infection may make one think of syphilis. These erythematous
patches are not visible on the skin of natives. A dryness of the skin
is rather constant and, especially in natives, papules which itch
greatly may be present. Rarely such manifestations as orchitis or
choroiditis may be observed.
[Illustration: FIG. 31.—Swelling of the glands of the posterior
cervical triangle—Winterbottom’s sign. (Ruge and zur Verth after
Koch.)]
_Kérandel Sign._—Recently great prominence has been given to a
deep hyperaesthesia, which shows itself as a lively pain, often
retarded, after some slight blow upon a bony projection of the
body. Kérandel, who suffered from trypanosomiasis, noted that
the fear of striking against objects became with him an absolute
obsession. It is called the Kérandel sign. It is during this first
stage, when the trypanosomes are to be found only in the blood or
gland juice that the disease would appear to be curable. Upon the
appearance of the trypanosomes in the cerebro-spinal fluid (second
stage) we have practically a hopeless prognosis.
There may be a latent period of several months in which health
seems normal, to be followed by the sleeping-sickness stage. It has
also been noted that untreated cases, as well as those receiving
more or less treatment, may remain in good health for periods up to
several years. There is therefore reason to believe that certain
cases may not enter upon the sleeping sickness stage.
[Illustration: FIG. 32.—Cases of trypanosomiasis showing the edema
especially about eyes. (Ruge and zur Verth after Koch.)]
_The Stage of Sleeping Sickness._—In this stage the mentality
becomes more weakened. The native from being happy and willing to
work becomes morose and apathetic. This change of disposition is
frequently the first thing to be noted in a patient by his family.
There is a tendency to gaze into the distance. The speech is rather
low and tremulous like that of a tired, sleepy child. The tongue
especially shows a decided tremor which may also be present in the
lips and hands.
The gait is one of weakness and apathy—a shuffling gait. The
reflexes may be exaggerated. Romberg’s sign may be present but
the Argyll-Robertson pupil has not been noted. There may be an
alternation of periods of crying and laughing which with the
occasional exhibition of intention tremor and rarely nystagmus may
make one think of multiple sclerosis. The patient tends to sleep
even when lying in a bright sunlight. Again he may go to sleep
with a morsel of food in his mouth. Notwithstanding the apparent
stupid state of the patient, he will, when aroused, answer fairly
intelligently but with apathy and retardation. The hebephrenic and
catatonic manifestations of dementia praecox may be exhibited in
some cases.
Finally the patient becomes weaker and more emaciated. The pulse
becomes rapid and feeble, the blood pressure being extremely low.
The mouth becomes dry, the teeth covered with sordes and bed sores
develop. There may be convulsions. The coma and general weakness
become more marked and the patient dies. Frequently terminal
pneumonias or dysenteries bring about the end.
The sleeping sickness stage rarely lasts longer than a year and
even with treatment not more than two years.
The Symptoms in Detail
_The Nervous System._—Headache and lack of mental concentration
may be early features of the disease. Deep hyperaesthesia, or
Kérandel’s sign, often present. Patients tend to be morose and
apathetic. Tremor of tongue and lips are rather constant signs
about the commencement of the stage of sleeping sickness. Early
insomnia gives way to the drowsiness that characterizes the second
stage. There is very little disturbance of sensory or motor
functions until near the end. Epileptiform convulsions may be late
manifestations. Coma deepens as the end approaches.
_The Temperature Curve._—The febrile paroxysms, which may not be
present in natives until the sleeping-sickness stage, show great
irregularity of course and a marked remission in the morning. The
fever may be absent for several weeks to return later. Trypanosomes
are more apt to be present in the peripheral circulation during the
fever than when the temperature is normal.
_The Circulatory System._—The pulse tends to run from 90 to 120
beats per minute and is fast even without fever. The tension is
low and the systolic pressure tends to be extremely low during the
later stages of the disease.
_The Lymphatic System._—Most important in diagnosis is the
enlargement of the lymphatic glands, especially those of the
posterior cervical triangle (Winterbottom’s sign). Other enlarged
glands may be the supraclavicular, epitrochlear and axillary
glands. The inguinal glands suffer enlargements so frequently
as the results of wounds and infections of the foot that their
enlargement is of less diagnostic value. The natives of certain
parts of Africa not only attach great diagnostic importance to
gland enlargement but they imagine they cure the disease by
removing the glands with various primitive cutting tools. The
glands are not painful, do not become matted together and rarely
suppurate. Our best means of diagnosing trypanosomiasis is by
withdrawing gland juice with a syringe and examining the smears.
_The Skin._—Erythematous areas may be present in Europeans.
Localized oedemas are rather marked features. The skin may be very
dry and itch markedly.
_Other Manifestations._—The spleen may be enlarged, the
respirations may be more rapid than normal and the blood show a
secondary anaemia. In a blood examination the large mononuclears
show an increase with a normal white count.
The eye may show keratitis or irido-cyclitis in trypanosomiasis.
Trypanosomiasis seems to favor abortion and still-births, in this
respect resembling syphilis.
DIAGNOSIS
In making a survey of a native population Schwetz considers gland
palpation as almost as reliable as gland puncture and of course more
expeditious. The typical gland should be large and soft or elastic
although he admits trypanosomes may be found in small hard glands.
When the glandular enlargement is distinct, with the erythema and
headache, there is much that suggests syphilis. Another point of
confusion is that positive Wassermann tests are often obtained in
sleeping sickness.
The increase in large mononuclears goes with malaria, kala-azar and
syphilis as well as with trypanosomiasis so that such findings are
of little assistance in differential diagnosis.
An early history of attacks of fever, with marked fluctuation of
temperature, associated with rapid pulse, even with the apyrexial
morning fall, is suggestive. Then with the glandular enlargements
we think immediately of laboratory examinations. As with pellagra
the history is very important in the diagnosis of trypanosomiasis.
_For the laboratory diagnosis_ we may use peripheral blood with
some thick film method. The examination of preparations from the
peripheral blood is usually very discouraging. Very much better
results (in fact some prefer this method to any other) can be
obtained by taking 10 to 20 cc. of blood in about 25 cc. of citrated
salt solution, centrifuging 2 or 3 times and examining the sediment
of the third centrifugalization. Dutton and Todd prefer to centrifuge
citrated blood and to collect the leucocyte layer for examination as
is done in opsonic work.
_Gland Puncture._—The English workers usually prefer the gland
puncture method, using a sterile but dry hypodermic needle. Water
in the needle distorts both leishman bodies and trypanosomes.
In the sleeping-sickness stage trypanosomes can almost constantly
be found in the cerebro-spinal fluid.
In a diagnostic study of 336 cases Broden obtained 87% of positives
from gland puncture, 80% from centrifugalizing the supernatant
fluid left from the second centrifugalization of the blood and 4.5%
from spinal fluid examinations.
Some prefer to inoculate susceptible animals, particularly the
guinea pig or monkey, with blood or gland juice from the suspected
case. A very satisfactory material is an emulsion from an excised
gland which may be inoculated intraperitoneally into white rats.
The further course, after animal inoculation, is the examination of
the blood of these animals for trypanosomes. Usually at the time
the guinea pigs die we find numerous trypanosomes.
Other tests are: (1) Trypanolysis, when unheated suspected serum
and trypanosomes are incubated together for one hour. Normal serum
may occasionally cause disintegration and treated cases give it in
only about 45% of cases. Unfavorable untreated cases give it in
about 80% of cases.
(2) The so-called auto-agglutination test is not of much value.
In this the red cells of the blood of a trypanosomiasis case come
together in clumps when one makes a wet preparation. It is not
a rouleaux formation. (3) The attachment test is made by making
a mixture of inactivated serum, leucocytes and trypanosomes and
allowing them to be in contact for 20 minutes. A positive test
shows attachment of the trypanosomes to the leucocytes.
PROGNOSIS
If the patient cannot be removed from the infected district or cannot
receive the atoxyl or atoxyl-tartar-emetic treatment the prognosis is
almost surely that of a prolonged but fatal end.
There is very little hope of cure if the disease has gone on to the
sleeping-sickness stage.
PROPHYLAXIS AND TREATMENT
=Prophylaxis.=—The question of depopulation of districts and
destruction of the big game therein, when the area is infected with
_Glossina palpalis_, has been fully considered under epidemiology.
Isolation, in the fly-free districts, of infected natives has
not proven a very practical measure but that of rendering their
peripheral blood free of trypanosomes by atoxyl injections would
seem more desirable. In this we aim to cure the patient as well as
render him safe to others.
The most practical measure is that employed in Uganda of clearing
the plant and tree growth for at least fifteen feet from the
streams of water, it having been noted that the tsetse flies
confine themselves to a narrow strip not more than fifteen feet
from the water’s edge. The tsetse fly requires considerable
moisture for its existence.
The catching of flies in traps or with a sticky lime does not offer
much encouragement.
As regards personal prophylaxis, white clothes are to be worn as the
tsetse fly, along with mosquitoes, prefers dark-colored garments.
The legs should be protected by leggings and possibly one could
consider the wearing of gloves or veils. As a matter of fact,
however, the heat of the tropics precludes these latter measures. As
the fly only bites in the daytime one should choose the night for
going about, if practicable.
=Treatment.=—The general opinion is that trypanosomiasis is only
curable at a time prior to the appearance of trypanosomes in the
cerebro-spinal fluid. Consequently, the stage of sleeping sickness
offers little chance of cure by treatment.
Such cases have been treated with injections of 10 cc. of 1 to 1000
solution of neosalvarsan into the spinal canal, after withdrawing
about 15 cc. of spinal fluid, but without appreciable curative
effect. On the assumption that trypanosomes invading the central
nervous system are protected from drug action, Marshall proposed
the injection of salvarsanized serum intrathecally. Three hours
after the administration of 0.6 gm. of salvarsan enough blood is
withdrawn from a vein to give about 20 cc. of serum. Following
the withdrawal of a slightly greater amount of cerebro-spinal
fluid from 5 to 20 cc. of the serum is injected in its place.
Yorke in a critical article on the claims for this treatment is
of the opinion that there is no satisfactory evidence that such
a method sterilizes the infected cerebro-spinal fluid. He cites
cases where the trypanosomes disappeared from the spinal fluid
after ordinary treatment and where cases lived for extended periods
after trypanosomes were found in their spinal fluid. Corbus
and associates have described a new method of obtaining a high
medicinal content in the cerebro-spinal fluids. Their work was done
with neo-arsphenamine, but there seems to be no reason why other
drugs may not be similarly administered.
The basis of the method is the observation that hypertonic salt
solution, injected intravenously, will dehydrate the central
nervous system, and that restoration of fluid begins at about
the sixth hour. If a drug is injected into the circulation just
at the time when the restorative formation of spinal fluid is
taking place, it appears that a large quantity is carried into the
subarachnoid spaces with the fluid, as on a flood tide.
Method:
1. 8 A.M. Patient is put to bed.
2. 10 A.M. Intravenous injection of 100 cc. of 15% saline, warmed
and administered slowly by gravity. The symptoms produced by this
injection are mild and transitory.
3. No food is permitted at midday.
4. 4 P.M. Neo-arsphenamine is injected with the usual technic.
5. 8 P.M. Light nourishment is allowed. Patient is kept under
observation, preferably in bed, for the ensuing thirty-six hours.
_Atoxyl._—The first drug to offer hope of cure was sodium
arsanilate, atoxyl, which contains about 26% of As. This is best
given in doses of about 0.5 gram (7½ gr.) in about 15 cc. of
sterile distilled water intramuscularly. Several cases of optic
neuritis were reported but the drug is still a standard treatment.
We give the atoxyl at intervals of five days, Manson gives 3 grains
every third day.
Probably the best treatment is one in which three doses of atoxyl
are followed by from 10 to 15 daily or every other day injections
of 0.1 gram (1½ gr.) of tartar emetic. The course is repeated after
an interval of three weeks. It is advisable to give a hypodermic of
caffein a few minutes before the tartar emetic to lessen depression.
Kérandel received the atoxyl-tartar-emetic double treatment and
ascribed his cure to the tartar emetic. Tartar emetic is also given
intravenously, 0.1 gram in 150 cc. water.
Intravenous injection of arsenophenylglycin, in doses of about
1.0 gram. (15 gr.) intravenously has been highly recommended.
Recent reports from German East Africa state that of 35 treated
with this drug six died of the effects of the drug. Salvarsan and
neosalvarsan have been used but apparently without particular
success.
A combination of treatments in which salvarsan, sodium salicylate
and ethyl-hydrocuprein (a quinine derivative) have been used has
been favorably reported by Morganroth where the action of a single
drug was of little value.
Very remarkable claims in experimental animals have been made for
“trixidin,” a preparation of antimony trioxide which is given
intramuscularly. Even inunctions with this preparation have been
quite successful in curing infected mice. In larger animals abscess
formation is an objection.
Daniels has reported good results from the injection of oxide of
antimony. The preparation used is Martindale’s injectio antimonii
oxidi given subcutaneously in 30 minim doses (1/20 grain of the
oxide). Masters gives this preparation intramuscularly and notes
its greater efficiency than any other drug or combination of drugs.
He gives 3/100 grain every other day until 40/100 grain has been
given. If trypanosomes continue present he gives a .77 gram dose
of soamin. Soamin is a drug similar to atoxyl but said to be less
toxic.
In the treatment of 18 cases of _T. rhodesiense_ infections Newham
notes that tartar emetic alone was as effective as the combined
treatment with atoxyl. He gave the tartar emetic injections twice
weekly intravenously commencing with 1 grain and going up to 3
grains. An organic antimony preparation, “Stibenyl,” has been
recommended. See kala-azar.
Very favorable reports have been made from the use of galyl and
ludyl, arsenical compounds.
A drug which is reported to have exceptional trypanocidal effect
on animals infected with both human trypanosomes is “Bayer 205.”
Dogs infected with the dourine parasite and showing oedema
and eye symptoms have been cured by the injection of the drug
intravenously. A dose of 0.5 mg. causes disappearance of parasites
in mice. It is stated that the drug produces a protection against
reinfection which lasts for months.
BRAZILIAN TRYPANOSOMIASIS
=General Considerations.=—In 1909, Chagas reported the finding
of a flagellate in the intestines of _Conorhinus megistus_ or,
more properly, _Lamus megistus_. He was also able to transmit the
flagellate to laboratory animals and could culture it on blood agar.
[Illustration: FIG. 33.—_Schizotrypanum cruzi_ in blood of child
with acute type of Brazilian trypanosomiasis. (MacNeal from Doflein
after Chagas.)]
In investigating the matter of the importance of this flagellate,
_Schizotrypanum cruzi_, in Minas Geraes, Brazil, where the
above-named bug was present in great numbers in the cracks of the
houses of the poor he associated this flagellate infection, which he
at first considered trypanosomal, with a disease of the children of
that section.
The bug is a vicious feeder and, from its biting chiefly about the
face, has been called barbeiro or barber by the natives. Both the
male and female of _Lamus_ bite and can transmit the disease and
although the parasite is not transmitted hereditarily the nymph is
capable of sucking blood and becoming infected.
[Illustration: FIG. 34.—_Conorhinus megistus_, the insect carrier of
_Schizotrypanum cruzi_. (From Doflein after Chagas.)]
It requires several months for the insect to go through the egg,
larval and pupal stage to maturity. Some consider this bug to
belong to the genus _Triatoma_. The insects may live for more than
a year and tend to remain in the same house where they may have
become infected but leave such house if it be abandoned by man.
Brumpt thinks that the bedbug may also transmit the disease. A
large proportion of armadillos in the endemic areas are infected
with _S. cruzi_ but do not seem to be affected thereby. It has been
suggested that this animal may be a reservoir of virus.
[Illustration: FIG. 35.—_Schizotrypanum cruzi_ developing in the
tissues of the guinea pig. 1. Cross-section of a striated muscle
fibre containing _Schizotrypanum cruzi_: Note dividing forms. 2.
Section of brain showing a _Schizotrypanum_ cyst within a neuroglia
cell, containing chiefly flagellated forms. 3. Section through the
supra-renal capsule, fascicular zone. 4. Section of brain showing a
neuroglia cell filled with round forms of _Schizotrypanum_. (From
Low, in Sleeping Sickness Bulletin, after Vianna.)]
_S. cruzi_ is found in the blood of children during the acute febrile
stage but at other times in children, and as a rule in adults, it is
rarely present in the peripheral blood. The early blood forms are
narrow and very motile. They increase in size and slacken in motility
when they become about 20 microns long. _S. cruzi_ is characterized
by a very large blepharoplast. Dividing forms are never seen in the
blood. The common site of multiplication is in the cells of the
voluntary muscles and heart and also in the cells of the central
nervous system, adrenals, and bone marrow. In these tissues the
flagellate takes on a rounded form and undergoes binary division.
Continued division converts the infected cell into a cyst. It is this
process going on in various important structures that accounts for
the extreme variation in symptomatology and pathology.
Chagas thinks that the gametes for the cycle in _Lamus_ arise
from parasites developing in the lungs of the vertebrate host.
Flagellated parasites enter the lungs, lose the flagellum and
become oval in shape, later on dividing into 8 parts. These assume
an elongated form and enter the red cells of the host. Against this
is the statement of various observers that the flagellates are only
to be found free in the plasma, never within red cells. The forms
taken up by _Lamus_ multiply in the intestine and then pass to the
salivary glands after about 8 days. The bug is then infectious when
it bites. Brumpt notes that infection may occur from inoculation of
the faeces passed by the bug, especially through the conjunctiva.
=Symptomatology.= _Acute types._—This form of the disease usually
occurs in children under one year of age. The period of incubation is
about ten days. It is attended by a high continued fever which may
show a slight morning drop. There is marked puffiness of the face and
enlargement of the thyroid. The lymphatic glands and spleen are also
enlarged. The case may give the picture of a meningitis in which form
the disease is exceedingly fatal. During the febrile period parasites
are to be found in the blood but in the afebrile intervals which
alternate with the febrile ones parasites are not present.
_Chronic Types._—The type of the disease as seen in adults is
mainly chronic. They often show enlargement of the thyroid and
manifestations of myxoedema. The lymphatic glands are enlarged. Where
the adrenal is attacked we have the syndrome of Addison’s disease.
In the cardiac types there are present various forms of cardiac
irregularities.
In the cerebral types various neurological manifestations may be
noted.
An irregular fever may accompany the signs of involvement of the
various important organs.
The disease is attended by a marked anaemia.
=Diagnosis.=—In the laboratory diagnosis of those cases not showing
the flagellates in the blood the usual method is to inoculate a
guinea pig with the blood and in about two weeks _S. cruzi_ may be
found in the blood of the animal. The parasites may not appear,
however, in the blood, when one should resort to culturing the guinea
pig’s blood or more surely examine sections of muscle of the animal
for the forms in the muscle cells undergoing binary division.
Brumpt has recently advocated the xenodiagnostic method. Thus, in a
number of guinea pigs infected with _S. cruzi_, parasites could not
be found, but by having third stage larvae of _Conorhinus_ feed on
these animals the parasites developed in the bugs. He regards the
alimentary tract of these bugs as a most favorable culture medium.
=Prophylaxis and Treatment.=—Other than destroying the bugs by
sulphur fumigation or whitewashing there is little to note. The bugs
show a liking for leather articles, as old harness.
The same plan of treatment as for African trypanosomiasis may be
tried but such treatment is not effective with infected animals.
In the myxoedema types thyroid extract is indicated.
NOTE: Escomel has reported the finding of a trypanosome 20 to 40
microns by 3 to 4 microns which had a flagellum as long as the
body and with a very small but distinct blepharoplast (unlike _S.
cruzi_) in the blood of a native of Peru. The patient at the time
of the blood examination was afebrile and showed a generalized firm
oedema. There was noted anaemia, prostration and somnolence. This
may be a new species.
TRYPANOSOMIASES OF ANIMALS
=Trypanosoma brucei.=—This trypanosome causes a surely fatal
disease in horses and one from which few cattle recover. It is
called “nagana” or the fly disease, from being transmitted by
the tsetse fly, _Glossina morsitans_. All animals except man and
possibly the goat seem susceptible. The disease is characterized
by fever, oedematous areas about neck, abdomen and extremities,
progressive anaemia and emaciation. It is an important disease of
domesticated animals of many parts of Africa.
=Trypanosoma evansi.=—This is the cause of a very fatal disease
of horses in India and the Orient and known as “surra.” It also
affects camels and even cattle. It is thought to be transmitted
by biting flies (_Stomoxys_). The symptoms are fever, emaciation,
oedematous areas and great muscular weakness.
=Trypanosoma equinum.=—This trypanosome causes a fatal disease in
horses in South America. There is paralysis of the hind quarters of
the horse which gives the disease the name “mal de caderas.”
=Trypanosoma equiperdum.=—This trypanosome causes a disease of
horses in many parts of the world. It is known as “dourine” and is
transmitted by coitus. The genital organs show marked oedema which
is followed by anaemia and paralysis.
=Trypanosoma dimorphon.=—This trypanosome causes a disease of
horses in Gambia. It is also found in horses and cattle in other
parts of Africa. The parasite shows marked variation in morphology.
=Trypanosoma lewisi.=—Rats in many parts of the world show this
infection which is rarely fatal to them. It is transmitted by the
rat flea by a process of regurgitation. It can also be transmitted
by the rat louse.
CHAPTER IV
THE TROPICAL RELAPSING FEVERS
DEFINITION AND SYNONYMS
=Definition.=—There is a group of tropical fevers more or less
identical clinically with European relapsing fever and caused by
spirochaetes closely allied to _Spironema recurrentis (Spirillum
obermeieri)_. It seems probable that the relapsing fevers of East
and West Africa are caused by a single species, _S. duttoni_, which
is transmitted by a tick, _Ornithodoros moubata_, while that of
Northern Africa is caused by another species, _S. berbera_, which
is transmitted by lice, either _Pediculus vestimenti_ or _Pediculus
capitis_. Another species of spirochaete, _S. carteri_, is supposed
to cause the relapsing fever of India and it seems probable that its
transmission is brought about by infected lice.
Besides the above species of spirochaetes others have been
reported, as _S. novyi_ for American and _S. persica_ for Persian
relapsing fever. The view taken by Nuttall, that these various
names may be of convenience in the study of relapsing fevers but
that there is no adequate morphological difference to justify them
as species, seems worthy of acceptance. It has been shown that the
separation of these spirochaetes on the basis of susceptibility
of laboratory animals and cross immunity reactions is untenable.
Agglutination of certain strains by their specific sera, however,
is a reliable means of separation. As with European relapsing
fever, these fevers are characterized by a sudden onset, intense
frontal headache, and pain of back and limbs. This fever remains
high for three to five days and falls by crisis, to be succeeded
by an apyrexial interval of approximately one week. There may be
several of these alternating febrile and afebrile periods. The
spirochaetes are in the peripheral circulation during the febrile
period but not in the afebrile one. The spleen is enlarged and
tender. Cases showing jaundice seem more grave.
=Synonyms.=—Febris recurrens. Tick fever. French: Typhus recurrent.
German: Rückfallfieber.
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—Although Hippocrates described the clinical features of
relapsing fever quite accurately this knowledge seems to have been
lost until about the eighteenth century.
The causative spirochaetes were first seen by Obermeier in the
blood of a patient in 1868 but he did not publish his discovery
until 1873.
Ross and Milne, in 1904, found that African tick fever was a
spirillar fever while Dutton and Todd established the fact of its
transmission by ticks.
=Geographical Distribution.=—Relapsing fever was epidemic in the
U. S. in 1869, since which time it has not reappeared. There have
been many epidemics in Ireland, Russia, Turkey and other parts
of Europe. It was a disease of importance during the Balkan War
of 1912-1913. China and India have frequently been visited by
epidemics as well as the Philippine Islands and the Dutch East
Indies. Uganda, Congo State and German East Africa, as well as
Egypt and Algeria, are important centers. There is also a relapsing
fever of Colombia and Central America.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—Relapsing fevers are caused by organisms generally
considered as protozoal in their nature and belonging to the
flagellates.
[Illustration: FIG. 36.—Spirochaetes of relapsing fever from blood
of man. (Kolle and Wassermann.)]
_Transmission by the tick._—The generic name _Spiroschaudinnia_
is preferred by some to the more commonly accepted _Spirochaeta_.
Recently, authorities give these organisms the name _Spironema_.
East and West African relapsing fever, or tick fever, is caused
by _Spironema duttoni_ and the transmission is through the bite
of an argasine tick, _Ornithodoros moubata_. Not only does the
tick itself become infected by the taking in of blood-containing
spirochaetes but likewise transmits the infection to its progeny.
Leishman considers that when the spirochaetes are taken into
the alimentary tract of the tick there is a breaking up of the
spirochaetes into small granules which reach the Malpighian
tubules. They also invade the ovary and the ova. It was thought
that these granules were the infecting agents and that they were
excreted in the fluid of the coxal glands or passed out with the
faeces. More recently it has been claimed that these granules have
no relation to the infection, which is due to spirochaetes as such.
It may be stated that spirochaetes as such may be found in the
secretion of the coxal glands as well as in the faeces. This
coxal fluid dilutes the thick faeces and makes an emulsion which
is smeared out by the body of the tick in the area of the bite
puncture.
[Illustration: FIG. 37.—_Spirochaeta novyi._ (Todd.)]
At any rate this infection of man seems to be the contamination
method, the material from faeces and coxal glands being rubbed
into the wound made by the tick-bite. The ticks hide in the cracks
about the old native huts and bite the sleeping inmates. There
may be quite a local reaction at the site of the bite. _Spironema
duttoni_ has been cultured by Noguchi, by utilizing his methods
for culturing the organism of syphilis. In such cultures he has
noted longitudinal division rather than transverse, this fact
rather favoring a protozoal as against a bacterial nature. This
spirochaete is from 24-30 microns long, about 0.45 micron broad and
has a corkscrew motility. It is readily transmissible to a number
of laboratory animals, as monkeys, white rats, etc. The spirochaete
of Northern African relapsing fever, _S. berbera_, causes the
disease as seen in North Africa and Egypt. It is transmitted by
lice, Nicolle and others having shown that the spirochaetes make
their way from the alimentary tract to the body cavity of the
louse. They have shown that the bite alone of an infected louse is
innocuous and also that the faeces are non-infective, when injected
into monkeys. Emulsions of infected lice, however, when rubbed into
wounds, produce the disease in monkeys.
_Transmission by the Louse._—The spirochaetes taken in by a louse
disappear in a few hours and the insect remains harmless until
about the fifth day, when it becomes infectious, and so remains
until the twelfth to fifteenth day. Spirochaetes reappear in the
coelomic fluid of the louse about the sixth day and continue
present until about the twentieth day.
A striking fact is that infection can be brought about a day
before spirochaetes appear and that after a period of a few days
these spirochaete-containing lice lose their power to infect. It
would seem that the infecting stage was an invisible one. Have we
then a symbiosis between a spirochaete and an invisible virus,
possibly filterable? Wolbach has shown that certain spirochaetes
will pass through a Berkefeld filter as spirochaetes but this would
not affect the possibility of the existence of some granule or
chlamydozoal stage. It may be that the infecting stage is not an
invisible one but a granule one.
_Mode of Infection._—It is by crushing the louse, by scratching
or otherwise, that the spirochaetes contained in the coelomic
fluid reach and penetrate the wound of the bite. This is therefore
a contaminative method of infection. Mackie has shown that the
Indian relapsing fever, which is caused by _S. carteri_, is
probably transmitted by the louse, and it is probable that the
conditions under which the infection takes place are similar to
those occurring with _S. berbera_ infections. With the European
relapsing fever, bedbugs may possibly act as transmitting agents.
The probabilities however are that this infection is transmitted by
lice alone.
[Illustration: FIG. 38.—_Ornithodoros moubata._ (Murray from
Doflein.)]
A relapsing fever of Persia is transmitted by a tick of the
genus _Ornithodoros_, which is also true for the relapsing fever
of Panama. There is great variation in the description of the
different spirochaetes, and frequently measurements are given for
short forms and long forms. They also vary from wave-like lines to
corkscrew spirals. Again, different species have different types
and different activities of movement. As a rule they are about 20
× 0.4 microns. The spirochaetes of the relapsing fever of Panama
varied in length from 4.6µ to 22µ. Of these the most common were
those measuring 13µ. Transverse division of the longest forms was
seen in dark-field preparations. The monkey is susceptible to all
species of relapsing fever spirochaetes. White mice and white rats
are readily infected by _S. duttoni_ and the Panama spirochaete but
are refractory to _S. recurrentis_ except after passage through
monkeys. _S. carteri_ causes only a transient infection in these
small rodents.
=Epidemiology.=—With tick fever the epidemiology rests upon the life
history of the tick _O. moubata_. This tick infests the rest houses
along the route of travel, hiding in the crevices of floors and walls
during the day and coming out at night to bite the sleeping inmates.
The feeding occupies a long time, more than an hour. Both sexes bite
man. The female lays about 100 eggs, from which nymphs emerge in
about twenty days. The larval stage takes place in the egg. Shortly
after emerging the nymphs suck blood. An important fact is that the
female transmits the spirochaete to its ova, so that the ticks from
such ova may transmit the disease.
[Illustration: FIG. 39.—Siphunculata and Rhynchota. 1. _Pediculus
capitis._ 2. _Pediculus vestimenti._ 2_a_. Protruded rostrum of
_Pediculus_. 3. _Phthirius pubis._ 4. _Acanthia lectularia._ 5. _A.
rotundata._ 6. _Conorhinus megistus._]
Natives seem to suffer severely from tick fever in childhood but
in adult life possess a sufficient degree of immunity so that
the disease shows itself in a very mild form in those harboring
spirochaetes.
The immunity conferred by an attack is not lasting and a second
infection may occur within a year. Such second attacks, however,
do not present the relapses so important in a clinical diagnosis.
As a matter of fact there may be no symptoms and such cases with
spirochaetes in their blood make ideal carriers for the infection
of ticks or lice. Ticks can be infected by these carriers. In some
of the rest houses 50% of the ticks may be infected. While the
tick does not tend to leave its habitation it may be transported
in the bundles of native porters. The transmitting agent of the
North African relapsing fever and probably of the Indian type is
the louse. The body louse deposits about 75 eggs in the clothes of
the host, which hatch out in about four days and become adults in
about two weeks. The head louse deposits its eggs or nits on the
hair of the host’s head. Hagler has noted that, in Servia, typhus
fever disappeared when lice were gotten rid of but relapsing fever
continued to prevail until they also exterminated the bedbugs.
_The Relapsing Fever of Panama._—Bates, Dunn and St. John have
demonstrated that a tick, _Ornithodoros talaje_, transmits the
relapsing fever of Panama. This tick seems to prefer the crevices
and open joints of bamboo beds, laying its eggs and moulting in
the hiding places. It comes out at night to feed on the occupants
of the bed. Two white rats were inoculated with an emulsion made
from ticks taken from a suspected bed. Both rats developed a
spirochaete infection. A man inoculated with blood of one of these
rats developed relapsing fever on the sixth day. A second man was
inoculated subcutaneously with an emulsion of ticks collected from
a bed and showed spirochaetes in his blood on the eleventh day.
Another man was bitten by ticks from the same source and was
instructed not to scratch the bite. The ticks engorged in about 15
minutes, some of them secreting coxal fluid which mixed with blood
from the bite made a scab. This man was positive for spirochaetes
on the fifteenth day.
PATHOLOGY AND MORBID ANATOMY
The spirochaetes disappear from the peripheral circulation during
the apyrexial period, notwithstanding which such spirochaete-free
blood, when injected into monkeys, may bring about infection. Either
a granule stage or an invisible stage of the parasite may be present.
The relapse is probably due to the existence of resistant strains
which are not destroyed by the lytic substances, developed during the
attack.
Agglutinating and lytic substances show themselves chiefly during
the apyretic intervals.
The spleen is enlarged and soft. There are frequent infarctions.
The spirochaetes are found phagocytized in the macrophages of the
spleen and elsewhere. Parenchymatous degeneration of kidney and heart
muscle, and especially of liver, may be noted.
SYMPTOMATOLOGY
_East and West African Relapsing Fevers._—In African tick fever
after a period of incubation of from three to ten days the disease
sets in rather suddenly with dizziness, marked headache and general
body pains. The temperature quickly rises to 104°-105°F. and remains
elevated during this primary febrile period, except for slight
morning remissions. Vomiting is quite a feature of this disease and
may be bilious in character.
There may be rather marked praecordial oppression and a bronchial
catarrh. The pulse in particular and the respiration in less
degree are accelerated. Herpes and epistaxis may be noted. The
bronchial manifestations seem to occur chiefly in the first
febrile accession. The spleen is somewhat enlarged and tender
but in many cases this is not noted. Spirochaetes are found in
the peripheral circulation during the febrile accessions but not
during the apyrexial intervals. There is great variation as to the
abundance of spirochaetes. In some cases we may have to search
several hundred fields before finding a single spirochaete. Severe
cases may show them in abundance. A rather marked leucocytosis
may be present in cases showing high fever and bronchitis. After
about four days the fever falls by crisis, often below normal, and
possibly with great prostration and cardiac weakness.
A critical sweat is a feature of this rapid fall of temperature.
During the afebrile period, which lasts from three or four days to
eight to ten days, the patient feels much better and his appetite
and strength return. With the onset of the second pyrexial wave the
severe symptoms of the first days are repeated, as with the first
febrile period. This second one terminates by crisis. Iritis is not
uncommon. Manson and Thornton have reported transient cranial nerve
involvements coming on late in the course of the disease.
In European relapsing fever the second febrile accession is usually
shorter and of less severity than the first. Furthermore there are
rarely more than 2 or 3 relapses. In tick fever, however, there may
be as many as 10 of these febrile recurrences, although there are
usually only 4 or 5. In natives there is usually only one febrile
period, this probably being due to an immunity resulting from
previous infections.
_North African Type._—In the relapsing fever of North Africa the
attacks are less severe and the number of relapses rarely exceeds
three. A fever of Egypt, generally known as the _bilious typhoid of
Griesinger_, is believed to have been a form of relapsing fever. In
this there was marked bilious vomiting with great tenderness of the
liver, late jaundice, albuminuria, bone pains, especially about the
knees, and a high death rate. The symptoms rather suggest yellow
fever but this disease has never been reported from Egypt.
_Indian Type._—In the relapsing fever of Asia there is a marked
tendency for the patient to collapse at the time of the crisis.
There are rarely more than two relapses and in probably 25% of
cases there is no relapse. There seems to be a greater tendency
to liver complications in the Asian types than elsewhere and such
cases form a large part of the death rate from this disease.
Bilious vomiting and jaundice, with a typhoid-like state and the
occurrence of various inflammatory complications, especially
parotiditis, are noted. The mind is usually clear, but delirium may
be present in severe cases.
_Relapsing Fever of Panama._—In three experimental cases the
temperature of the first accession varied from 102°F. to 104.5°F.
Frontal headache and general body aches were the chief symptoms.
Vomiting was noted in one case. The spleen was not enlarged. The
first relapse was cut short in each case by arsphenamine.
The Symptoms in Detail
_The Temperature Curve._—This is the chief point in the clinical
diagnosis of relapsing fever. The onset of the first febrile
accession is abrupt and the temperature rapidly rises to 104°F.
or higher. After a continued high temperature for three or four
days the fever drops by crisis, which is at times productive of
collapse. Following an apyrexial period of four to eight days we
have a second febrile accession, and there may be several of these
wave-like alternations of fever and apyrexia.
_The Nervous System._—Very marked frontal headache is a striking
feature and the pains in back and limbs may be of great severity.
Cranial nerve involvement has been noted. There may be apathy, but
on the whole the mind is clear.
_The Digestive System._—Anorexia and vomiting are features of the
febrile periods to cease in the fever-free periods. In some types
bilious vomiting may be marked.
_The Circulatory and the Respiratory System._—The pulse rate is
much accelerated, and there may be some praecordial distress.
A bronchial catarrh is frequently present in the first febrile
paroxysm.
_The Liver and Spleen._—Splenic tenderness and moderate
enlargement are fairly constant features. The liver may suffer
severely in the so-called bilious typhoid and marked jaundice may
ensue with a typhoid state.
_The Blood Examination._—This is the most important point in
diagnosis. The spirochaetes, which are only found in the peripheral
circulation during fever periods, are not so numerous in tropical
relapsing fevers as in the European forms. When spirochaetes are
scarce it is more satisfactory to examine Romanowsky-stained
specimens, especially with the Giemsa staining. The spirochaetes
show a varying number of undulations. There is no chromatin
staining in the line of the spirochaetes. The disease when severe
shows a well-marked polymorphonuclear leucocytosis, with at times
an increase of large mononuclears. This latter, however, may be
connected with malaria or amoebiasis.
DIAGNOSIS
The disease most likely to be confused with relapsing fever is
malaria and for this differentiation the finding of the parasites of
either disease is of first importance.
The blood of a suspected case even during the apyrexial period
should be injected into a mouse or white rat (guinea pigs are
refractory to infection). Spirochaetes should appear in the blood
of the mouse in about twenty-two hours and persist for about two
days. Relapses occur but recovery is the rule.
Dengue may be suspected, but the leucopenia, lack of splenic
tenderness, lack of tendency to vomiting and presence of post-orbital
pains should differentiate. As there is a leucocytosis in both
relapsing fevers and smallpox, and similar headache and backache,
confusion might exist were the parasites not found.
Yellow fever has many features in common with the bilious type of
relapsing fever, but there is no leucocytosis in yellow fever, and
there is no characteristic albuminuria and slow pulse in relapsing
fever. Influenza has many points in common with relapsing fever.
In a case of relapsing fever with jaundice confusion might arise with
Weil’s disease inasmuch as a blood smear might show spirochaete-like
organisms.
Typhus fever shows a less abrupt onset and the marked mental
symptoms (stupor) and dark macular eruptions about the trunk, on
the 4th to 6th day, should differentiate. If the case is first seen
in the apyrexial period one may take a drop of blood from a case
showing spirochaetes and one from the suspected patient. After
incubation for thirty minutes the spirochaetes should lose motility
and agglutinate if the case be one of relapsing fever (Lowenthal’s
Reaction).
In blood examinations we may use the dark-field illumination,
although the spirochaetes stain readily with Wright’s stain. The
India ink method is a good one. Hagler recommends smearing out a
mixture of one loopful of blood and a collargol preparation made
by diluting one part collargol with two parts water. The diluted
collargol should stand 24 hours and be filtered before use.
PROGNOSIS
The mortality is usually given as about 2 to 5% with the exception
of the very serious form in which jaundice is present when the death
rate may exceed 50%.
A serious feature of the disease is the length of its course, this
often extending from six weeks to two months.
Since salvarsan and neosalvarsan have been found to be practically
specifics in the treatment of the disease the mortality has been
reduced to exceedingly low figures.
PROPHYLAXIS AND TREATMENT
=Prophylaxis.=—The sole question is the avoidance of places infested
with ticks, bedbugs and lice. In Africa, the habitations of the
natives, where infected ticks may hide themselves in cracks in floors
and walls, are to be especially avoided. As the tick feeds at night a
night light is of value.
Destruction of the spirochaetes by salvarsan injection is important
prophylactically as well as therapeutically—the reservoir of
infection for lice or ticks being gotten rid of.
=Treatment.=—We have in salvarsan, or neosalvarsan, a specific. The
drug should be given so soon as the spirochaetes are found—in the
period of onset of the fever. If given at the end of the fever it may
intensify the critical manifestations, especially collapse. Unless
given early it does not abort the relapse. Neosalvarsan, being less
toxic, is better adapted to the treatment of the icteric type of the
disease. Atoxyl has practically no value in treatment and the same is
true of antimony.
Conseil has treated cases with galyl and ludyl, in doses of 4 to
7 grains, with results as good or better than with salvarsan.
The pains in the head and back are relieved by aspirin, although
a hypodermic of morphine may be necessitated. Cool sponging and
fresh-air treatment are desirable. On the whole, treatment, other
than the specific one, is symptomatic.
_Administration of the Arsphenamines._—Although arsphenamine
(salvarsan) is probably the drug of choice when immediate
therapeutic effect is desired, neo-arsphenamine is more popular
because it is more simply prepared and administered, is tolerated
better by the patient and has a slightly higher therapeutic index.
It is, however, less stable, and both the powder and its solutions
should be inspected carefully for signs of decomposition, namely,
a darkening in color, a strong odor, and insolubility. Ampules
containing either drug should be immersed in 95% alcohol for 15
minutes in order to detect any crack. Should a breach be found, or
suspected, the ampule should be rejected.
Myocarditis, advanced non-syphilitic renal or hepatic disease,
advanced arteriosclerosis and Addison’s Disease are regarded as
generally contra-indicating the employment of these drugs. Cases in
which the syphilis is of long standing should receive mercurials
for at least a week prior to the first injection of arsenic, in
order to avoid the possibility of activating lesions in vital
organs (Herxheimer), and should be closely questioned regarding the
occurrence of symptoms following previous injections (idiosyncrasy).
Prior to each injection, a patient should have a complete
uranalysis, receive a cathartic on the evening preceding, and be
allowed only liquids for the meal preceding. Subsequently to the
injection, he should be allowed only liquids for the succeeding
meal, and be retained under observation for at least twelve hours.
Untoward symptoms following the injection are treated usually with
epinephrin solution (0.6 to 1.2 cc.) or atropin.
Arsphenamines are administered intravenously, usually in the median
cephalic or the median basilic vein at the bend of the elbow. This
method requires aseptic technic throughout. All apparatus should
be thoroughly washed before sterilization, since it is believed
that symptoms may arise from substances extracted from glassware
and rubber tubing. The water used must be distilled, preferably
twice, and freshly boiled. The dose of arsphenamine is 0.3 to 0.6
gm., that of neo-arsphenamine is 0.3 to 0.9 gm. Until tolerance is
ascertained, the dose should be small and not repeated in less than
a week.
NEO-ARSPHENAMINE
1. Only a single ampule should be dissolved at a time. The powder
should be dusted over the surface of a small portion of the water
and permitted to dissolve without agitation. The solution is then
made up to bulk. Specimens which do not dissolve readily are to be
rejected.
2. Cold water only is to be used.
3. The solution should not be stronger than 0.1 gm. of the drug in
2 cc. of water.
4. A very small needle should be used, and the time of the
injection should not be less than five minutes.
ARSPHENAMINE
1. _Cold Water Should be Used in all Cases._—(Exception.
“Arsenobenzol” requires hot water. Consult instructions issued
by individual manufacturers for possible departures from these
directions.)
2. _Neutralization and Alkalinization of the Solution._—With
a graduated pipette or burette add 0.9 cc. of normal NaOH,
standardized against normal acid, for each 0.1 gm. of the drug.
The alkali should be added all at once, the amount specified being
slightly in excess of that required to redissolve the flocculent
precipitate first formed.
3. _Concentration of the Drug._—It is important that the
concentration of the drug is not greater than 0.1 gm. to 30 cc.,
_i.e._, 180 cc. of water for the usual dose of 0.6 gm.
4. _Method of Injection._—The gravity method only should be
employed. When several patients are to be injected from the same
solution, the container for the solution should be graduated. A
glass stopcock is of value in controlling the flow of solution,
but in its absence the rate of injection can be governed by the
elevation of the fluid and by the size of the needle. A needle of
18 or 20 B. & S. gauge is best.
5. _Rate of Injection._—Operators should pay particular attention
to the rate of administration since it is believed that rapidity
of injection accounts for more unfavorable results in the use of
arsphenamine than any other one thing. In no case should the rate
exceed 0.1 gm. of drug (30 cc. of solution) in two minutes, _i.e._,
twelve minutes for the average dose of 0.6 gm.
CHAPTER V
YELLOW FEVER
DEFINITION AND SYNONYMS
=Definition.=—Yellow fever is an important epidemic disease of the
West Coast of Africa and tropical America caused by a spirochaetal
organism, _Leptospira icteroides_. The spirochaete is contained
in the peripheral blood only during the first three days of the
disease. A mosquito, _Stegomyia calopus_ (_Aedes calopus_), biting
a patient during this period of his illness, takes in the organism
which undergoes some developmental cycle of the nature of which we
are ignorant, but we do know experimentally that a minimum period of
twelve days is requisite for the completion of the cycle which makes
the mosquito infectious for man.
When a susceptible individual is bitten by an infected mosquito
there develops, after a period of incubation of from two to five
days, a rapid rise of fever, with markedly congested face and
severe pains of back and head. About the end of the third day the
sthenic manifestations are succeeded by asthenic ones in which
jaundice, haemorrhages, particularly black vomit, and anuria are
the important features.
Faget’s sign of a lack of accordance between pulse and temperature
is of great diagnostic importance.
=Synonyms.=—Febris Flava, Typhus Icteroides. Spanish: Fiebre
Amarilla, German: Gelbfieber, French: Fièvre Jaune.
History and Geographical Distribution
=History.=—It would seem probable that yellow fever was the
disease from which those of Columbus’ second expedition suffered
in San Domingo, in 1495. At the same time the first definite
description of the disease was that of Dutertre, in Guadaloupe, in
1635. There has been much discussion as to whether the West Coast
of Africa may not have been the original endemic centre and the
importation to the West Indies the result of the slave traffic.
While there is very little support given this view the recent
recognition of the extent and importance of the African endemic
area, as brought out by Boyce, is somewhat suggestive. Spinden
advances evidence to show that a devastating epidemic disease,
attended with bleeding from the mouth and nose, raged among the
Mayas and Aztecs in pre-Columbian periods. One such epidemic is
recorded as of 1454. There have been numerous severe outbreaks
in the United States, that occurring in Philadelphia, in 1793,
being the most celebrated and that centering in Memphis, in 1878,
probably the most terrible. Yellow fever has been a scourge in
Brazil since its introduction in 1849, until quite recently. Lisbon
experienced severe outbreaks of the disease in 1723 and in the next
century in 1850 and 1856. Many of the Spanish cities have also
suffered from time to time.
The history of the connection between yellow fever and the mosquito
is discussed under etiology.
[Illustration: FIG. 40.—Geographical distribution of yellow fever.]
=Geographical Distribution.=—As will be seen from the chart the
chief epidemic centers are the islands and coasts of the Gulf of
Mexico and the West Coast of Africa. The disease has at times
extended down the West Coast of South America and is now rather
prevalent in Ecuador. The last epidemic in the United States was
that in New Orleans.
The disease has never invaded Asia or Australia and there is fear
that the opening of the Panama canal may bring this about.
Guiteras, who has recently returned from an investigation of the
problem of yellow fever on the West Coast of Africa, was unable to
find evidence of its existence there at the present time. He notes
an absence of the extreme heat and abundance of mosquitoes which
are features of yellow fever ports of South America.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—It is now generally accepted that the cause of yellow
fever is a spirochaete, _Leptospira icteroides_, which is very
similar to but slightly smaller than _L. icterohaemorrhagiae_ of
infectious jaundice. Noguchi injected 74 guinea pigs with about
5 cc. of blood from 27 cases of yellow fever. The blood from 6 of
these cases proved infectious, producing in 8 guinea pigs fever,
conjunctival injection, albuminuria, a leucocytosis followed by
leucopenia and, after a few days, a subsidence of the fever to normal
or subnormal. At this time jaundice and haemorrhages occurred.
[Illustration: FIG. 41.—Dark-field view of _Leptospira icteroides_
in a culture 16 days old. × 1000. (After Noguchi.)]
Autopsies of the guinea pigs showed a fatty and yellow liver with
nephritis. Some of the injected guinea pigs showed only fever
but seemed to have acquired an immunity to subsequent injections
of a virulent virus. In the blood, liver and kidneys of the
animals showing the jaundice and albuminuria Noguchi was able
to demonstrate spirochaetes by dark-field illumination. He also
obtained cultures from such animals. Leptospiras were demonstrated
in the blood of 3 out of 27 human cases but only after prolonged
search. Cultures have been obtained from human yellow fever
blood. For culturing, a medium is used consisting of 1 part of
serum and 3 parts of Ringer’s solution made semisolid with 0.3%
agar and contained in tall tubes. One cc. citrated yellow fever
blood is introduced into the lower part of the medium. A thin
layer of liquid petrolatum is poured on the top of the medium. We
need partial oxygen tension but not anaerobiasis. Optimum growth
temperature is 33°C. _L. icteroides_ is from 4 to 9 microns long
by 0.2 wide and tapers gradually to extremely thin sharp points.
These organisms will pass the pores of V and N Berkefeld filters
thus placing them in the group of filterable viruses. The virulence
of different strains varies, with some strains as little as 0.00001
cc. of culture proving fatal for guinea pigs. Monkeys, rabbits and
birds were not susceptible to infection but the marmoset and puppy
seemed to respond as did the guinea pig.
By having _Stegomyia_ (_Aedes calopus_) feed on infected guinea
pigs as well as the human case of yellow fever, and subsequently
allowing these mosquitoes to bite normal guinea pigs, the disease was
transmitted in a few cases. In certain infected mosquitoes Noguchi
found leptospiral organisms with dark-field illumination. Mosquitoes
fed on infected guinea pigs became infectious in 8 days, this shorter
period over human feedings being due, probably, to the greater
abundance of organisms in the blood of the infected guinea pigs over
human yellow fever blood.
Guiteras doubts the etiological relation of Noguchi’s leptospira to
yellow fever on the ground that in view of the susceptibility of
animals to this organism the disease should exist as an epizootic,
which is improbable in view of the ease with which yellow fever is
eradicated when measures applied solely to man and the mosquito are
practiced. Among other points of objection he notes the recovery
of the spirochaete from the blood later than the third day of the
disease.
[Illustration: FIG. 42.—_Leptospira icteroides_ in blood of a guinea
pig inoculated with a culture × 1000. (After Noguchi.)]
_Infection by Injection of Blood._—The subcutaneous injection of as
little as 0.1 cc. of the blood of a yellow fever patient in the first
three or four days of the disease, or the serum of this blood, which
has passed through the pores of a Chamberland filter (F but not B
according to the French Commission), will bring about the infection
of a susceptible person after an incubation period of from one day
and fifteen hours to twelve days and eighteen hours.
In the natural method of transmission the mosquito, _Stegomyia
calopus_, is the intermediary. In order that the female of this
culicine species may transmit the disease it is necessary that
she bite a yellow fever patient in the first three days of his
illness, after which a period of approximately twelve days must
elapse before the mosquito can transmit the disease. In such case
the period of incubation varies from two days one hour to six days
two hours. Carroll was bitten by a mosquito which had fed on a
yellow fever patient twelve days previously, and four days later
experienced a very severe attack, this fact being against the views
of the French Commission that the disease shows a less severe form
in those who may be bitten in the first period of the infectivity
of the mosquito. A second case bitten five days later by the same
mosquito that infected Doctor Carroll had a mild attack. Persons
bitten by experimentally contaminated mosquitoes before an interval
of twelve days had elapsed escaped infection.
Prior to the investigations of the American Commission our views as
to the incidence and spread of yellow fever were chaotic.
Rush, in 1793, thought that the Philadelphia epidemic originated
from “damaged coffee which putrefied on a wharf near Arch Street.”
In 1883, Doctor Friere reported that yellow fever was caused by
a coccus, _Cryptococcus xanthogenicus_ and claimed that he could
confer immunity by vaccination with attenuated cultures. Carmona
y Valle of Mexico and Carlos Finlay of Havana considered that the
_Micrococcus tetragenus_ was the cause but Sternberg, investigating
these claims, showed that these cocci had nothing to do with
yellow fever. In his work Sternberg isolated an organism which he
designated “X.”
=Bacillus Icteroides.=—In 1897, Sanarelli isolated an organism which
he named _Bacillus icteroides_. In investigating this organism Reed
and Carroll found that it was closely related to the hog cholera
bacillus. Certain American investigators substantiated the claims of
Sanarelli. Sternberg, however, doubted these findings.
To further investigate the relation of _B. icteroides_ to yellow
fever Army surgeons were sent to Cuba in 1900.
=American Commission.=—In addition to Reed and Carroll, Lazear and
Agramonte were also members of the Commission.
The Commission first cultured the blood of 18 yellow fever patients
with negative results for _B. icteroides_ in every case.
_B. icteroides_ grows as readily on culture media as does the
typhoid organism.
It was also shown that yellow fever blood, which was negative
for _B. icteroides_, could produce yellow fever when injected
subcutaneously. In 11 autopsies made shortly after death cultures
from various viscera were negative for _B. icteroides_. It was
then decided to abandon, as fruitless, further investigations as
to Sanarelli’s organism, and to take up the mosquito transmission
theory.
=Mosquito Transmission.=—In 1848, Doctor Nott, of Mobile,
strongly advocated the insect transmission of yellow fever but not
specifically incriminating the mosquito.
Riley from a study of Nott’s original paper, thinks that the author
had in mind invisible forms of insect life, which could act as
disease producers, and simply cited the mosquito to illustrate his
views. In 1853, Dr. Beauperthuis, in Guadeloupe, noted that malaria
and yellow fever ceased to exist in regions which from their
altitude fail to nourish “insectes tipulaires.”
He also thought that the virus of these diseases was introduced by
the channel of insect inoculation. Furthermore he stated that the
variety, zancudo bobo (_Stegomyia_), had white stripes on the legs
and was in a way the domestic species. However, there is a question
whether his zancudo bobo was _Stegomyia_ and furthermore if we
translate the expression _inoffensif_ as without result it would
negate the connection between this mosquito and disease production.
From 1881 Doctor Carlos Finlay had been advocating the transmission
of yellow fever by _Culex fasciatus_ (Synonym for _Stegomyia
calopus_).
In 100 experiments made by Finlay 13 cases of yellow fever
developed.
In no instance had these experimental mosquitoes fed on a yellow
fever patient more than six days previous to their biting and,
knowing that a period of at least twelve days must elapse, the
infections in the 13 cases could not have been brought about by
these experimental mosquitoes.
=Extrinsic Incubation.=—An observation by Carter influenced the
Commission in their investigations. Carter, in 1898, noted that a
period of about two weeks generally elapsed between the appearance
of the first case and the group of cases resulting from this first
case. He termed this period the “extrinsic incubation” and we now
know this as synonymous with the twelve-day period of incubation in
the mosquitoes infected by the first case plus the two to five days
of the period of incubation in man.
The American Commission obtained ova from Doctor Finlay and from
these ova mosquitoes were hatched for the experimental work. Of 11
susceptible persons, bitten by contaminated mosquitoes, the first 9
remained uninfected while the two volunteers, bitten subsequently
(Aug. 27 and 31), developed the disease. One of these cases was
that of Doctor Carroll, whose infection was brought about by one
of these laboratory reared mosquitoes which had fed on 4 cases
of yellow fever, two of which were severe cases and two mild.
This mosquito had fed on one of the severe cases just twelve days
previously. The other case was bitten by 4 contaminated mosquitoes,
one of which was the one that had infected Doctor Carroll.
Of the 9 negative cases 6 were bitten by mosquitoes which had fed
on yellow fever patients from the fifth to the seventh day of
the disease and the remaining 3 failures were where the interval
between contamination and biting the volunteer was from two to six
days only.
At this time the medical mind was obsessed with the idea that
yellow fever was transmitted by fomites.
It had been forgotten that Cathrall, in 1800, had failed to infect
himself with black vomit and that Ffirth, in 1804, in order to
obtain material for a graduation thesis, swallowed black vomit
and smeared it, as well as blood, upon wounds he had made on
his skin with negative result. (It will be remembered that the
fourth proposition of the French Commission was that application
of infectious serum to the abraded skin would not produce the
disease—the hypodermic injection being required.)
=Fomites.=—To settle the question of the relative importance of
fomites and infected mosquitoes the Commission caused two houses,
14 × 20 feet, to be erected, one well ventilated for the infected
mosquitoes and the other poorly lighted and ill ventilated for the
black vomit contaminated clothes, sheets and blankets (fomites).
A medical officer and two privates of the Hospital Corps slept in
this room for twenty days in most intimate contact with the infected
material. No infections resulted.
There were other experiments with similar results.
One of the occupants of the fomites building was afterward
inoculated subcutaneously with 2 cc. of blood taken from a patient
in the first day of the disease and developed yellow fever after
four days of incubation. This proved that he was susceptible to
yellow fever.
Blood from this patient, taken in the first three days of his
attack, was injected into a third man who also developed yellow
fever. This experiment was to prove that the production of the
disease was due to a virus capable of multiplying rather than to a
toxin. Of course, it would be impossible to conceive of a toxin so
potent that it could produce symptoms in a third man when diluted
in the circulation of the second man.
In the other building there was a screen partition dividing the
space into two compartments, one containing 15 contaminated
mosquitoes, the other with the same air but without mosquitoes.
Controls occupying the mosquito free section remained free
from yellow fever, while those exposing themselves in the
mosquito-containing compartment developed yellow fever. One of
these cases was bitten by mosquitoes contaminated thirty-nine days
previously, a second one with fifty-one day insects and a third,
who developed a severe case, was bitten by mosquitoes contaminated
fifty-seven days previously.
As above stated the Commission inoculated men subcutaneously with
blood, taken from yellow fever patients in the first three days of
the disease, with positive results. It was also found that if the
blood was heated to 55°C., for ten minutes the virus was destroyed
and, finally, it was found that the filtrate from a Berkefeld
filter was infectious, thus showing that the virus was so minute
as to pass through the pores of a filter which would hold back the
smallest known bacterium (_filterable virus_).
_Experiments of Guiteras._—During the summer of 1901 Doctor
Guiteras, with a view to immunity production, repeated the
experiments of the Army Commission and infected 8 persons, 3 of
whom died. Gorgas thinks the greater severity of these infections
may be explained by greater virulence of the virus developing
in the mosquito during the hot season. It is known that the
development of this virus requires fifteen to twenty days in winter
as against the twelve days for summer.
_Note._—Doctor Lazear, who had charge of the mosquito work of the
Commission, tried to infect himself with experimental insects prior
to his applying a twelve-day mosquito to Doctor Carroll. About
three weeks later he was bitten by a mosquito which he did not at
the time consider a _Stegomyia_. The attack of yellow fever which
resulted from this bite ended fatally.
_To summarize, the American Commission found:_
1. That _B. icteroides_ had nothing to do with yellow fever.
2. That fomites was a negligible factor.
3. That _Stegomyia calopus_, when fed on the blood of a yellow fever
patient, in the first three days of the disease, became contaminated
and, after a period of twelve days, but not before, was capable of
transmitting the disease to a susceptible person. Once infectious the
mosquito so remained for the rest of life.
[Illustration: FIG. 43.—_Aedes calopus_ (_Stegomyia calopus_),
female. From P. H. Reports.
FIG. 44.—_Aedes calopus_ (_Stegomyia calopus_), male.
From P. H. Reports.]
4. The blood of a yellow fever patient in the first three days, which
was sterile for _B. icteroides_, was capable of producing the disease
when injected subcutaneously. If heated to 55°C. for ten minutes
the virus was destroyed however. Furthermore, infectious blood when
passed through a Berkefeld filter remained infectious, thus showing
that the virus is a filterable virus.
The French Commission verified these findings and in addition
brought out the following points.
1. Cutaneous vaccination with infective serum is without result.
2. Infectious serum loses its yellow fever-producing power in
forty-eight hours unless preserved under liquid petrolatum when it
remains virulent for five days.
3. Infectious serum if heated for five minutes at 55°C. loses its
virulence but has prophylactic and curative power.
4. Besides the method of hypodermic inoculation yellow fever can
only be transmitted by the bite of a mosquito in which the virus
has remained for at least twelve days.
5. In one instance it was thought that the progeny of infected
mosquitoes transmitted the disease. Rosenau and Goldberger, in 38
experiments, failed to obtain such result.
_Paraplasma flavigenum._—In 1909, Seidelin reported certain minute
protozoa as existing in the red cells of yellow fever patients.
He considered them as related to the piroplasms and gave the name
_Paraplasma flavigenum_. It is stated that the parasite has been
found as late as the fourteenth day from the onset of the attack.
The idea is advanced that there may be carriers of yellow fever.
These claims are generally denied.
=Epidemiology.=—There are numerous records which attest the almost
universal susceptibility to yellow fever. In the Orwood epidemic,
Carter has reported that of 46 persons entering an infected house,
“Gray Mansion,” 45 contracted yellow fever.
On the “Lombardia,” with a complement of 249, there were 242 cases
and 134 deaths. The 7, who escaped, were immunes.
The idea that the colored race possesses immunity is now thought
to be connected with the contraction of the disease in infancy
or childhood, attacks at this period of life being very mild and
difficult of diagnosis.
_Immunity._—As proof that such immunity is not racial we may note
that in Ecuador the natives of the endemic area about Guayaquil
possess an immunity due to mild attacks in childhood, but the natives
of Quito, 300 miles distant, where there is no yellow fever, do not
possess it, and many residents of Quito have contracted the disease
when passing through Guayaquil to take steamer to Europe.
There has been some inclination to question the immunity conferred
by an attack of yellow fever but Carter has shown that in
quarantine practice we can admit such immunes with perfect safety.
Thirty thousand such immunes were allowed to enter Key West and
Tampa from Havana between 1888 and 1898 and no case of yellow fever
developed from them. During the same period 450 non-immunes from
Havana gave 13 cases in the quarantine stations.
_The Yellow Fever Mosquito._—A knowledge of the life history of
_Stegomyia calopus_ explains the epidemiology of yellow fever.
This culicine species is widely distributed in the tropical
and subtropical world, extending from 38° north to 38° south
latitude. It is rarely found at a greater altitude than 3000 feet.
Petropolis, a railway-connected suburb of Rio, has an altitude of
2300 feet, with cool nights, at times about 9°C, and a freedom
from _Stegomyia_. Persons having occupation in Rio during the day
but returning to Petropolis in the afternoon escape yellow fever.
In this connection it is generally accepted that the female
_Stegomyia_ only bites between 5 o’clock P.M. and midnight. While
the first feeding may occur earlier in the day, all subsequent
feedings, which alone could be infectious, occur late in the
afternoon or at night. (Recent observations show _Stegomyia_ to
bite in daytime,—not at night.)
These views, which were advanced by Marchoux, would explain the
apparent freedom from infection of those leaving infected areas
by the early afternoon. Seidelin, however, claims that these
mosquitoes will continue to bite in the day after numerous feedings
of blood.
It is recognized that railways are unimportant factors in
transporting these mosquitoes, differing in this respect from ships
which offer better conditions.
The _Stegomyia_ is preëminently a house mosquito and a town mosquito.
It is the domesticated one, while the malaria-transmitting ones are
rural and feed in natural plant-containing bodies of water instead of
the water in old tin cans, roof gutters, cisterns or other utensils
surrounding the house which are preferred by the yellow fever
mosquitoes.
_Stegomyia_ seem to prefer water for breeding that is slightly
tainted with sewage, although developing equally well in fresh
water. They will also develop in brackish water.
When once this mosquito takes up its residence in a certain room
of a house it rarely leaves it and thus is explained the danger of
occupying a room which has been occupied by a yellow fever patient.
Then too, the warning sound, so characteristic of the approach of
most mosquitoes, is not given by _Stegomyia_.
The female lays about 70 eggs in small groups and not in a compact
egg raft as with _Culex_. The eggs are therefore difficult of
detection. The eggs do not suffer after rather prolonged drying.
Even temperatures approximately 0°C. do not seem to destroy the
viability. It would seem probable that it is this stage in the
metamorphosis of _Stegomyia_ which is responsible for the survival
of the species under unfavorable conditions.
The eggs the American Commission received from Finley had been
deposited thirty days previously on the edge of some water in a
basin. The water had meanwhile evaporated and the eggs were dry.
Notwithstanding this the eggs promptly hatched out when water was
poured in the basin.
The most favorable temperatures for these mosquitoes range from 29°
to 31°C. Under 20°C. the eggs do not hatch out.
The larvae, which hatch out in about two days, develop into pupae
in approximately one week. In about two days the fully developed
insect breaks out of the pupal case. It will thus be seen that
a period of ten to fourteen days suffices for a generation. The
insect is almost black and has a silvery lyre or Jew’s harp pattern
marking on the thorax. The legs and abdomen also have silvery
bands. The female lays several batches of eggs and has been
observed in one instance to live 154 days. The French Commission
kept a female alive 106 days. They consider that life under normal
conditions is much shorter in duration than in captivity. If
deprived of water the adult insect only lives about five days. In a
refrigerator, Guiteras was able to keep mosquitoes alive, without
food or water, for eighty-seven days.
On fruit and sugar vessels the conditions for the development of
_Stegomyia_ are exceptionally favorable.
These mosquitoes are prone to remain in the same house where they
have been feeding. Carter has pointed out that yellow fever rarely
spreads more than 75 yards from an infected house so that it is
improbable that infected mosquitoes fly, or are carried by the
wind, any great distance.
The same authority has also noted that ships in Havana harbor lying
about 400 yards from shore never become infected when the crew have
not been ashore or where infected ships have not been anchored near
by.
It is probable that they are carried aboard ships in connection
with coaling or provisioning rather than blown aboard by prevailing
winds.
[Illustration: FIG. 45.—Temperature chart of Yellow Fever. A,
Mild case with recovery. B, Severe case showing the saddle-back
temperature curve similar to that of dengue. C, Chart of fatal case
of yellow fever.]
PATHOLOGY AND MORBID ANATOMY
The toxic effects are chiefly borne by the liver and endothelial
linings of the capillaries. The cloudy swelling of the liver cells
obstructs the bile canaliculi, causing jaundice, and the more
advanced fatty degeneration of these cells brings about disturbances
caused by interference with the important liver functions. The
degenerative changes in the endothelial cells lining the capillaries
bring about the haemorrhages so much a feature of yellow fever.
The icterus is apt to be more marked after death, and is especially
prominent about the neck and eyelids. Dutroulau considers the
absence of icterus in a cadaver as negativing yellow fever.
The liver is of a boxwood or chamois skin color and on section is
very oily. Haemorrhagic patches may be seen dotting the yellow cut
surface.
A midzonal fatty degeneration of the liver cells may be noted in
cases dying by the 4th and 5th day but later there is degeneration of
the entire lobule.
The stomach and intestines contain disintegrated blood. Petechiae
and erosions are common in the cardiac end of the stomach. The
upper part of the duodenum shows changes similar to those seen
in the stomach but the other portions of the intestines are
essentially negative.
The spleen does not show any particular change. The kidneys are
enlarged, congested and on microscopical examination show fatty
degeneration of the renal epithelium.
The adrenals often show fatty degeneration, especially of the
cortex.
Haemorrhagic infiltrations are marked features in skin and mucous
and serous membranes.
SYMPTOMATOLOGY
=A Typical Case.= _Sthenic Stage._—With very slight or absent
prodromata, often during the night, the disease sets in rather
abruptly with chilly sensations and the temperature rapidly rises
to about 104°F. The face is flushed, dusky and swollen, the eyes
injected. Very severe frontal and orbital headaches with marked
rachialgia of the lumbo-dorsal region are peculiarly characteristic.
The pulse is of high tension and the rate from 90 to 110. The
systolic pressure is increased—at times as high as 175. These are
the early manifestations of the _first or sthenic period_ of the
disease.
Vomiting, first of mucus and bile, comes on very early. About the
second day albumin appears in the urine and by the 3d or 4th day
this is present in large amount and is associated with the presence
of hyaline and granular casts. The temperature remains fairly
high for three or four days, with morning remissions and evening
exacerbations. Of great diagnostic value is _Faget’s law_ as to
lack of correlation of temperature and pulse, in that by the 2d
day, notwithstanding the high temperature, the pulse rate becomes
less and by the 3d or 4th day it has probably decreased 20 to 40
beats from its initial rate.
_Stage of Remission._—About the close of the 3rd day or upon the
4th day there may occur a fall in the temperature and a decided
amelioration of the symptoms. This however is frequently not
noted and even when present may last only for a few hours. It
is often called the _stage of remission or calm_. By the 3d day
the congestion of the facies and other sthenic manifestations
have disappeared and, possibly preceded by the short period of
remission, there is ushered in the _second or asthenic stage_.
_Asthenic Stage._—It is at this time that we have the appearance
of the most characteristic features of yellow fever—the jaundice
and the haemorrhages. The jaundice is first noted in the sclerotics
and rapidly spreads over the body as a lemon to orange yellow
tinging. Swelling and bleeding of the gums are the earliest signs
of the damage to the capillaries. This may go on to bleeding from
the nasal mucosa, the intestines and, best known and most dreaded,
the coffee ground vomiting or black vomit of gastric haemorrhage.
Epigastric tenderness is often marked. In very severe cases
haemorrhagic extravasation into the skin may appear. The mind
is peculiarly clear, the patient alert and suspicious. At times
patients may be delirious even to the extent of wild struggling to
throw themselves out of bed.
In favorable cases the temperature rapidly falls to normal,
associated with an unusually slow pulse rate, even below 45.
In the first few days there is a normal white count, with an increase
in the percentage of the polymorphonuclears and later on an increase
in the large mononuclears.
[Illustration: FIG. 46.—Temperature chart from one of the
experimental yellow fever cases reported by the U. S. Army Yellow
Fever Commission. A severe case with recovery.]
Besides the typical course we may have cases so mild that the
albuminuria is insignificant and the jaundice and haemorrhages
entirely absent. On the other hand we may have fulminating cases
with jaundice and black vomit setting in by the end of the 3rd day
and rapidly going on to a fatal termination.
=Symptoms in Detail=
_The Temperature._—This rises abruptly, reaching its maximum by
the 1st day. Very high temperatures are not a feature of yellow
fever. There is nothing characteristic in the further course of
the fever chart and it should be borne in mind that the so-called
intermission is transient and deceitful.
_General Appearance._—On the 1st day the face is swollen and
congested. This florid congestion, which may extend down the neck
to the upper part of the chest, is more marked in yellow fever
than in any other disease. The eyes are shining, the conjunctivae
injected and there is photophobia.
About the end of the 2d day the facial congestion disappears to
be succeeded by an earthy tinging and subicteroid tinting of the
conjunctivae. The jaundice does not appear until about the fourth
day. This may be noted somewhat earlier if one blanches the skin by
pressure with a glass slide. Petechial eruptions may be prominent
in the later stages. The jaundice is best seen at a distance of 5
to 6 feet.
_The Circulatory System._—Of peculiar value in diagnosis is
_Faget’s law_—a falling pulse rate with constant temperature or a
constant pulse rate with a rising temperature.
A markedly slow pulse, between 40 and 50, is often recorded about
the time of the period of remission.
It is interesting to note that the pulse of yellow fever made
a great impression upon Benjamin Rush, who called it the
indescribable or sulky pulse. The systolic blood pressure is high
at first, but by the 2d day begins to fall, becoming quite low in
the asthenic stage (even below 70 mm.) due probably to supra-renal
involvement rather than to cardiac weakness.
Haemorrhages, especially from gums, nose and intestines, are
common. Black vomit is the best known of these haemorrhages.
_Blood Examination._—This has generally been considered as varying
but slightly from normal findings.
Noc states that in the first stages of the disease there is
an increase of the polymorphonuclear percentage with a marked
diminution or disappearance of eosinophiles while later on,
from the 3d to the 6th day, there is an increase in the large
mononuclears.
_The Alimentary Tract._—The tongue may be coated in the
center. Vomiting often appears early and consists of whitish or
bile-stained mucus. It must be remembered that if black vomit
should appear it almost never comes on before the 4th day. There is
usually marked epigastric tenderness. Bleeding from the gums and
intestinal canal are not rare.
_The Nervous System._—The mind is unusually clear, the patient
often mentally alert and suspicious. There is often insomnia. The
severe cephalalgia, often frontal or supraorbital, as well as the
severe loin pains (_coup de barre_) are striking features. There
may be a marked hyperaesthesia. A delirious state may be present.
_The Liver and Spleen._—There is no special alteration in the
size of either liver or spleen. There may be tenderness about the
liver region. The jaundice of the asthenic stage is incident to
the pressure of the swollen degenerating liver cells on the bile
capillaries while the fatal issue is connected with the loss of the
urea formation function. It has been claimed that an acidosis may
occur. The spleen is not affected.
_The Genito-urinary System._—Albuminuria begins to appear about
the second day and tends steadily to increase in amount. Various
types of tube casts, often bile-stained, are abundant. The urine
shows neither bile nor blood cells except in the later stages
of the disease. The reaction is very acid. It is of the utmost
importance to note the quantity of urine voided, as scanty
secretion, leading to anuria, makes for a very grave prognosis.
DIAGNOSIS
The main points to consider in the diagnosis are: (1) the facies, (2)
the severe cephalalgia and rachialgia, (3) the early albuminuria, (4)
the epigastric tenderness, (5) Faget’s law of lack of correlation
between pulse and temperature, (6) the absence of clouding of the
consciousness, and finally the late appearance of the jaundice and
haemorrhages.
Of the greatest importance is the history of the case as to recent
whereabouts and associates. Also careful questioning as to prior
attacks of jaundice or albuminuria related to hepatic or renal
diseases. Influenza in its sudden onset and fever and pains has much
in common with yellow fever. Weil’s disease is much like yellow fever.
The diseases with which yellow fever is most apt to be confused are:
_Aestivo-autumnal Malaria._—In ordinary aestivo-autumnal malarial
paroxysms the search for the malarial parasite is of great
importance, although the finding of a malarial infection does not
exclude yellow fever. Albuminuria is not a feature of tropical
malaria.
In that type of tropical malaria known as bilious remittent fever
the clinical picture is rather asthenic and bile pigment in the
urine is an early feature. Again jaundice comes on fairly early and
the slow pulse is absent. The spleen is enlarged and tender.
_Blackwater Fever._—This is an asthenic disease with marked
and very early jaundice. The haemoglobinuria (Blackwater) is
pathognomonic. Splenic tenderness is marked.
_Smallpox._—The early headache, backache and vomiting of smallpox
may well confuse one before the eruption of variola appears.
_Dengue._—This is probably the most difficult disease to diagnose
from yellow fever. The facies, orbital pains and backache of yellow
fever and dengue are similar. Dengue also shows a slowing of the
pulse. The high blood pressure of the onset is not present in
dengue. There is no albuminuria in dengue and there is a marked
and early leukopenia with reduction of the polymorphonuclear
percentage, which does not exist in yellow fever. The jaundice of
yellow fever and the eruption of dengue do not show themselves
until after the first three days.
Relapsing fever, typhus fever and plague have been considered by
some authorities as possible of confusion with yellow fever.
_Bilious Typhoid of Egypt._—In 1851 Griesinger described a
disease he called bilious typhoid of Egypt in which there was a
sudden onset with marked chill and rise of temperature in four or
five hours to 103° or 104°F. Rachialgia and bilious vomiting were
marked. There was splenic enlargement. The temperature fell on
the fourth or fifth day with at about this time the appearance of
icterus. Relapses were the rule and the mortality was very high.
Bone pains, especially about the knee, were common and severe. This
disease is now considered a relapsing fever. It is this disease
which affected the troops of Napoleon in Egypt and which was
thought by some authorities to have been yellow fever. Others think
it may have been epidemic jaundice.
PROGNOSIS
This is bad with advancing years and possible lesions of liver or
kidneys. It is difficult to make a statement as to the average
mortality. Thus, in the epidemic of 1853, one of the most virulent
that ever visited New Orleans, the mortality was estimated at 85%,
while that of 1897, one of the mildest epidemics on record, only gave
a mortality of ½%.
As a general rule the earlier in the year an epidemic starts the
more virulent the disease; thus the 1853 epidemic, just referred
to, started in May.
High temperatures and excessive albuminuria, as well as early
appearance of jaundice, are bad signs. The mortality may be
considered as averaging about 20%.
PROPHYLAXIS AND TREATMENT
=Prophylaxis.=—By screening a patient during the first three days of
the disease we prevent the infection of _Stegomyia_ (_Aedes_).
It must be remembered that this mosquito not only breeds near human
habitations but that it tends to remain in the same room where it
has been feeding. Consequently we should use sulphur fumigations or
Giemsa’s spray or killing by hand to destroy insects. The larvae
breed by preference in old tin cans near the house door. To kill
these one should empty every old receptacle of water, and oil or
cover other collections of water.
All receptacles used for collecting and storing water draining from
roofs should be carefully screened with fine copper wire gauze. Of
particular importance is it to treat every suspicious case as it if
were one of yellow fever and screen the patient as well as destroy
any mosquitoes in the room or house occupied by such patient.
Noguchi reports success in prophylaxis by the injection of 2 cc.
of a killed culture of _Leptospira icteroides_. Immunity is not
conferred until after the tenth day. He notes that among 3607
persons vaccinated in Salvador there were no cases of yellow fever
while among the unvaccinated 181 cases occurred. Killed cultures of
_Leptospira icteroides_ were first used for protective inoculation
in 1918 when 427 vaccinations were carried out.
=Treatment.=—At the onset one should give calomel in small doses,
repeated every twenty minutes, until about 2 grains are taken, as
8 doses of ¼ grain calomel with soda. Magnesium citrate or sodium
phosphate should follow the calomel. Some prefer castor oil in large
doses (2 ounces). This treatment should not be repeated, it is only
indicated at the onset of the disease, so that if the case is not
seen until after the second day the laxative or purgative measures
should be withheld.
During the first three days of the disease no nourishment whatever
should be given. The patient should be allowed an abundance of
fluid, of which the best is Vichy, of which may be given a couple
of ounces every twenty minutes or so, iced or just cool, as the
patient prefers. Water, to which 30 grains of bicarbonate of soda
to the pint has been added, makes a good substitute. It is of vital
importance to put the patient to bed and keep him quiet. When
vomiting is severe cracked ice or iced champagne may be of value.
Alkaline enemata are indicated when the patient cannot retain the
Vichy. There would seem to be an acidosis in yellow fever.
A mustard foot bath is best given in bed, the feet and legs of the
prone patient being immersed in a foot tub half full of warm water
into which a pound of freshly ground mustard has been stirred.
Every few minutes there should be added a quart of very hot water
so that the bath may be very hot—just short of burning the feet.
The blankets are kept over the patient and the foot tub, so that we
also give a vapor bath which causes free sweating. This treatment
relieves the headache and backache. This foot bath can be repeated
2 or 3 times in the first twenty-four hours. After the bath, the
sweating patient must be thoroughly dried. Cold spongings are
important means of keeping down fever. For anuria use dry cups
to the loins or hot fomentations. Strychnine may be indicated in
the asthenic stage and camphor in oil hypodermically for extreme
cardiac weakness. The Sternberg treatment is 150 grains of sodium
bicarbonate and ⅓ grain of bichloride of mercury in a quart of
water. The dose is 1½ ounces every hour.
Any exertion causing a rise in blood pressure may be fatal. It
is possible that the stimulation of the circulation incident to
the taking of food may explain the dangers of allowing food to a
patient. As before stated no food should be given for the first two
or three days. Then commence with albumin water and thin barley
gruel. Later on wine jelly and easily digestible broths. Even when
convalescence sets in we should be very careful as to diet.
Noguchi has produced an immune serum to his spirochaete by
injecting horses. He has records of 170 cases of yellow fever
treated with this serum with a mortality of 13.6%, while untreated
cases gave a death rate of 52%. He notes that the serum must be
given before the third day of the disease to be of any value—best
results in the first day. He believes also that though salvarsan
and neosalvarsan have some leptospiricidal action they are both too
damaging to the kidney to supplant serum in treatment.
CHAPTER VI
INFECTIOUS JAUNDICE
DEFINITION AND SYNONYMS
=Definition.=—Infectious jaundice is a spirochaete infection, caused
by _Leptospira icterohaemorrhagiae_. This spirochaete is a common
parasite of rats in various parts of the world and man possibly
receives his infection from this source. There is a sudden onset
with rather high fever, headache and vomiting. The jaundice appears
about the third or fourth day when the urine shows albumin and bile.
Haemorrhages, especially epistaxis, are common and the liver rather
than the spleen shows enlargement. A polymorphonuclear increase is a
feature.
=Synonyms.=—Epidemic jaundice. Spirochaetosis icterohaemorrhagica.
Typhus bilieux. Weil’s disease.
HISTORY AND GEOGRAPHICAL DISTRIBUTION
[Illustration: FIG. 47. FIG. 48.
FIG. 47.—Showing _Leptospira_. (After Noguchi in Journal of
Experimental Medicine.)
FIG. 48.—A group of _Leptospira icterohaemorrhagiae_ from a culture.
(After Noguchi in Journal of Experimental Medicine.)]
=History.=—This disease was probably the form of jaundice noted in
the forces of Napoleon during the Egyptian campaign. It was first
recognized as a distinct disease by Weil, in 1886, who described
it as a peculiar form of acute infectious disease characterized by
jaundice, swelling of spleen and nephritis. Inada and his Japanese
colleagues discovered the causative spirochaete in 1915 and noted
the frequency of this parasite in rats. Infectious jaundice was an
important disease of the soldiers of the recent war.
=Geographical Distribution.=—Japan and Egypt may be considered as
the parts of the world in which the disease is most common. It is
endemic in West Africa and cases have frequently been reported from
the shores of the Mediterranean.
During the Russo-Turkish war (1877) cases of jaundice seen in
the Balkans by Sandwith were probably infectious jaundice as the
disease was frequently noted in that region during the recent war.
Cases were noted in Flanders during the war. A few cases have been
reported from the United States.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—The spirochaete causing infectious jaundice, _Leptospira
icterohaemorrhagiae_, is the type species of a genus described by
Noguchi as having minute elementary spirals running throughout the
body and failing to show either flagella or undulating membrane. The
caudal portion of the spirochaete is remarkably flexible and when
in motion the whole body seems drawn into a straight line except
for the hook formation of one or both terminal portions. Propulsion
seems to occur by the rotary motion of the hook and progresses in the
direction of the straight end. If both ends become curved progression
ceases.
[Illustration: FIG. 49.—Four specimens of _Leptospira icterohaemorrhagiae_. (After
Noguchi in Journal of Experimental Medicine.)]
[Illustration: FIG. 50.—A leptospira viewed under the dark-field microscope. (After
Noguchi in Journal of Experimental Medicine.)]
It is insoluble in 10% saponin thus differing from the other
blood spirochaetes. The constituent spirals are closely placed
and the total length may reach 15 to 20 microns. The dark-field
illumination is preferable for its demonstration although it shows
up well by various staining methods. To culture use a medium of
one part of rabbit’s serum with three parts of Ringer’s solution
inoculating with citrated plasma. The organism is found in the
blood during the first three or four days of the disease. It is
also present in the urine. Young guinea pigs are particularly
susceptible and in them we have, following injection of the blood
of a case, jaundice, albuminuria and haemorrhages. At autopsy the
spirochaetes are best demonstrated in a liver emulsion. Infection
with this spirochaete is common among rats in various parts of the
world so that it may be considered a natural infection of rats, but
they do not seem to suffer from it.
=Epidemiology.=—It is considered that the infection is transmitted
through the urine of infected rats or men. The spirochaetes may
gain entrance through the skin or by mouth. The fact that the
spirochaetes seem to die in urine within 24 hours makes infection
by the contaminated urine questionable but experiments with various
arthropods have failed to indicate their connection with the
transmission of the disease.
In Japan it has been noted that the disease is most common in wet
mines, disappearing when the mines are pumped dry. Before we knew
the cause of the disease attention was directed to the connection
between the infection and working about defective sewers. Trench
warfare, with the accompanying rats and wet conditions, seemed to
favor infection.
PATHOLOGY
The liver shows enlargement and fatty degeneration, but less marked
than in yellow fever. The organisms are found in the liver and also
in the kidneys, which latter show an intertubular congestion together
with haemorrhages in this region. Haemorrhagic areas may be present
in various portions of the alimentary tract and elsewhere.
SYMPTOMATOLOGY
After an incubation period of from 5 to 7 days the disease sets in
abruptly with rigors, headache, muscular pains and vomiting. The
patient is prostrated and has the appearance of extreme illness;
the face flushed and the conjunctivae injected. There is fever of
an irregular type usually running between 102° to 104°F. for the
first three or four days, when it begins to fall by lysis although
occasionally by crisis about the fifth day. Following a few days
of moderate fever or normal temperature there is a tendency for a
second rise toward the end of the second week, which continues for
approximately another week when a slow convalescence sets in in
favorable cases. The secondary fever shows rather marked oscillations.
Jaundice appears about the third or fourth day with marked
tenderness of the liver and slight or moderate enlargement of the
spleen. The urine is scanty and high colored showing albumin and
bile pigments. Early in the second week urine of a low specific
gravity is excreted in large amounts. The pulse is rapid at first
to become slow with the appearance of the jaundice. There is a
tendency to sleeplessness and nocturnal delirium and in unfavorable
cases the “typhoid state” comes on. Pains in the nape of the neck
and calf muscles are common features.
Haemorrhages, starting as epistaxis, are commonly observed.
Next to epistaxis intestinal haemorrhage is the most frequent.
Haematuria is rarely observed. The red cells and the haemoglobin
fall in percentage with an increase in the polymorphonuclears. The
leucocytosis runs about 15,000.
The spirochaetes may be found with the dark-field illumination
early in the disease in a blood examination and later on in the
urine.
DIAGNOSIS
It must be remembered that the causative spirochaete is very scarce
in the blood of this disease which is usually not the case with
relapsing fever showing jaundice. It is best to inject 2 to 4 cc.
of blood into young guinea pigs intraperitoneally and after the
development of the infection in the animal we find the spirochaetes
rather abundantly in preparations made from liver emulsions and
examined with dark-field illumination. Noguchi cultured the organism
from the blood early in the disease but found it difficult. Wataguchi
states that when the blood is simply diluted with water and kept at a
temperature of about 25°C. growth may be obtained by the fourth day,
reaching a maximum by the second week.
Agglutinins appear in the blood about the end of the first week and
cultures may be agglutinated by such serum diluted as high as 1 to
500.
Bilious remittent fever shows earlier jaundice, a more rapid pulse
rate and malarial parasites.
In yellow fever there is more marked rachialgia and earlier and
more marked albuminuria. The marked leucocytosis of Weil’s disease
should be of differentiating value.
The early jaundice and haemoglobinuria of blackwater fever should
distinguish this disease.
Prophylaxis and Treatment
=Prophylaxis.=—As the infection appears to be transmitted through
the medium of the urine and faeces, sterilization of these discharges
from those sick with the disease should be practised. Extermination
of the rat, the host of the parasite, is the important method of
eradication of the disease.
=Treatment.=—This would appear to be solely symptomatic.
Arsphenamine has no effect on the infection. Hexamethylenamine has
been recommended. A serum against the organism has been prepared and
seems to show protective value.
CHAPTER VII
RAT BITE FEVER
DEFINITION
Rat bite fever is a relapsing type of fever following the bite of
rats infected with _Leptospira morsus-muris_, which brings about
the infection of man with this spirochaete. Following the healing
of the wound we have developing in the cicatrix inflammatory signs
with lymphangitis and swelling of the tributary lymphatic glands. The
onset is sudden with rigors and fever, which latter continues for
several days to then fall to normal and after an apyrexial period to
be followed by relapse. Numerous relapses follow during the following
weeks, months or even years of the disease. In Japan the disease is
known by the name of Sodoku.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—In a study of this disease Futaki and others discovered
a spirochaete in the tissues of the bite area and the adjacent
lymphatic glands (1915). These spirochaetes were about 10 microns
long. In the blood of man and infected animals shorter and thicker
spirochaetes are found (3 to 6 microns). When cultivated in the media
used for other _Leptospira_ we have longer forms up to about 20
microns. The shorter forms are considered as young organisms.
_Leptospira morsus-muris_ is found in the blood of infected
mice, rats or guinea pigs during the first two weeks and then
becomes distributed in the connective tissues especially that
of the lips, bridge of nose and tongue. They are not secreted
in the saliva but the transfer seems to occur by a break in the
spirochaete-containing tissues and thus inoculated into the bite
wound. The organism may possibly be excreted in the urine.
=Epidemiology.=—It has been found that about 3% of house-rats in
Japan are carriers of the disease. It is less frequent in other
countries although reported from various European countries, America
and especially China. The disease has also been reported from
Australia. It seems probable that the construction of the Japanese
houses gives greater opportunity for the occurrence of bites of rats
than elsewhere.
[Illustration: FIG. 51.—_Spirochaeta (morsus) muris_ in lung of
mouse inoculated with blood from human rat bite fever. Silver
impregnation. × 1500. (From MacNeal. After Futaki, Takaki, Taniguchi
and Osumi.)]
[Illustration: FIG. 52.—_Spirochaeta (morsus) muris_ in blood of
guinea pig with experimental-rat-bite fever. Giemsa’s stain. × 1250.
(From MacNeal. After Futaki and associates.)]
PATHOLOGY
In infected guinea pigs there is swelling of the lymphatic glands
and the spleen with the presence of spirochaetes. The liver is
congested and may show a few spirochaetes. In human autopsies there
are degenerative changes in the liver and kidneys. The infection is
rarely fatal in experimental animals although it causes about a 10%
mortality in man.
SYMPTOMATOLOGY
Following a rather long incubation period of from six to eight weeks,
although cases have been reported where not more than two weeks had
elapsed from the time of injury, during which time the wound of
the rat bite heals, we have a rather sudden onset with headache,
nausea and marked weakness. The cicatrix now becomes inflamed and
the surrounding tissues show oedema and at times vesicle formation.
Leading from the inflamed areas is a line of tender lymphatics which
extend to a group of swollen lymphatic glands.
The onset is often characterized by chills and malaise. A rapid
pulse and prostration are present during the pyrexial period.
The fever rises rapidly to 101°F. or 102°F. and within two or three
days has reached about 104°F. and remains high for two or three more
days. About this time it falls rapidly to normal, attended with
profuse sweating. The temperature remains normal for a few days,
during which time the local swelling and inflammation subside. An
eruption of purplish spots may accompany the fever, appearing chiefly
on chest and arms. There may be urticarial lesions. Joint pains,
together with motor and sensory disturbances, may be noted.
Symptoms of nephritis may appear.
After the critical fall of temperature there is usually an
apyrexial period of several days during which time the local
manifestations about wound and glands subside. The fever again
comes on, to later disappear and reappear.
The successive paroxysms are usually of less severity.
The fever is suggestive of the relapsing fevers. The pulse is
rapid and weak. There may be as many as twelve of these febrile
accessions and the course of the disease may extend over several
months. There is an eosinophilia and during the febrile paroxysm
a leucocytosis of about 15,000. The spirochaetes should be looked
for in the blood during the early febrile periods. The dark-field
illumination is the best method for their demonstration.
TREATMENT
Treatment is entirely symptomatic. Some success seems to have
followed the administration of salvarsan.
Strychnine for the heart weakness and tonics during convalescence
are recommended.
Aspirin is often necessary to relieve the headache and joint pains.
As prophylactic measures the same precaution should be taken as to
cauterization of the wound as one would observe in rabies.
CHAPTER VIII
THE LEISHMANIASES
DEFINITION AND SYNONYMS
=Definition.=—Under this designation we group three diseases, two
of which are general infections and one a cutaneous affection. It
is now thought that the visceral leishmaniasis of adults or Indian
kala-azar and that of young children or infantile kala-azar are one
and the same disease. The cutaneous leishmaniasis of the Near East
or oriental sore and the various leishmania ulcerations of tropical
America are grouped with the others solely by reason of their cause,
this being a protozoon of the same genus, _Leishmania tropica_ for
the skin leishmaniases, and _L. donovani_ for the visceral ones. Most
authorities assign to infantile kala-azar a distinct species, _L.
infantum_.
The visceral leishmaniases are characterized by a chronic course,
marked splenic enlargement, progressive anaemia and emaciation
together with leucopenia. The cutaneous leishmaniases can only
surely be differentiated from other tropical sores by the finding
of the leishman bodies from smears made from the granulomatous
tissue of the sore.
=Synonyms.=—Dum-Dum Fever, Tropical Splenomegaly (for Indian
Kala-azar), Splenic Anaemia of Infants, Ponos (for infantile
kala-azar), Oriental Sore, Biskra Button, Bagdad Boil, Bouton
d’Orient, Aleppo Boil, Granuloma Endemicum (for the Eastern cutaneous
leishmaniasis), Espundia, Bubas Braziliana, Uta, Forest Yaws (for the
American cutaneous leishmaniasis).
GENERAL CONSIDERATIONS OF HISTORY, ETIOLOGY AND RELATIONSHIP
=History.=—In 1869 the English medical authorities in India
became familiar with a very fatal disease among the natives of
Assam but regarded it as a very malignant form of malaria. The
native designation for the disease was kala-azar. In 1889 Giles
investigated this disease and finding hookworm ova in almost all of
the cases he came to the conclusion that it was ancylostomiasis.
Rogers (1896) and Ross (1898) after studying the disease were of
the opinion that it had to do with malaria, the former regarding it
as a malignant form of malaria and the latter that it was malaria
plus some secondary infection.
Owing to the very similar temperature charts and misled by
agglutination tests of the serum of kala-azar patients, which he
regarded as showing agglutinins for the _Micrococcus melitensis_,
Bently, in 1902, claimed that kala-azar was a malignant form of
Malta fever.
In 1903 Manson suggested that the disease might be caused by a
trypanosome, the absence of malarial parasites and non-response to
quinine being against the then usually accepted malarial etiology.
A few months later in the same year, May, 1903, Leishman reported
findings which he considered as degenerated trypanosomes in the
spleen pulp of a soldier who died in 1900 at Netley Hospital
of dum-dum fever. Although first noting the peculiar bodies
in 1900, at the time of making the autopsy, he was at a loss
to explain their significance but in 1903, while examining a
trypanosome-infected rat, he came to the conclusion that there was
a similarity in the parasites of the two infections and published
his paper entitled “On the possibility of the occurrence of
trypanosomiasis in India.”
[Illustration: FIG. 53.—_Leishmania donovani._ Smear from juice
after puncture of spleen of case of Indian Kala-azar. (MacNeal from
Doflein after Donovan.)]
In July, 1903, Donovan reported the finding of similar parasites in
material from splenic puncture of cases of dum-dum fever and taken
during life.
There was much discussion as to the true nature of these leishman,
or leishman-donovan bodies, Laveran regarding them as piroplasms
while others thought them to be trypanosomes.
In 1904 Rogers succeeded in cultivating these parasites in citrated
salt solution and noted that the cultural forms were those of
flagellates. In 1903, Wright, of Boston, found similar parasites
in the granulation tissue of a tropical ulcer in a little Armenian
girl.
In 1905, Pianese found leishman bodies in smears from liver and
spleen of children dying with infantile splenic anaemia in Italy.
About the same time Laveran in examining spleen smears made by
Cathoire from an infant dying of an undetermined disease in Tunis
found these bodies. Later investigations have shown this infantile
leishmaniasis to be rather prevalent in the Northern part of Africa
and Southern part of Europe.
Quite recently it has been determined that not only is the classical
oriental sore a form of leishmaniasis but, as well, certain skin
ulcerations found in South and Central America, such as espundia and
uta in Peru, bubas in Brazil and forest yaws in the Guianas.
=Etiology.=—The parasites which cause a general infection in
kala-azar and leishmania infantile splenic anaemia but a local one in
oriental sore are usually separated as distinct species, _Leishmania
donovani_ for kala-azar, _L. infantum_ for infantile splenic anaemia
and _L. tropica_ for oriental sore.
These parasites are grouped with the haemoflagellates and
occur in their vertebrate hosts exclusively as small, oval,
cockle-shell-shaped bodies, measuring 2.5 × 3.0 microns. The
protoplasm stains a faint blue and contains a rather large
trophonucleus which is peripherally placed and gives the appearance
of the hinge of the cockle shell. Besides this macronucleus we have
a second chromatin-staining body which is often rod-shaped and set
at a tangent to the larger nuclear structure. It is called the
blepharoplast or micronucleus and stains a more intense reddish
than the rather fainter stained pinkish macronucleus. One or more
vacuoles are common in the cytoplasm.
Some consider these nonflagellated bodies, which are usually found
packed in endothelial cells of spleen, liver, lymphatic glands and
bone marrow, as resting stages, the flagellate existence occurring
in some other host than its vertebrate one. Patton has carried on
an immense amount of experimental work with the bedbug and has
noted the development of flagellate forms from the 5th to the 8th
days in bugs which fed on kala-azar patients showing leishman
bodies in their peripheral circulation. If the bugs are allowed
a second feeding after the infecting blood meal the flagellates
disappear within twelve hours, so that for full development in the
bedbug a single feeding is requisite. He states that the flagellate
forms change to post-flagellate ones by the twelfth day. At the
same time, although much evidence exists in favor of the bedbug as
host for the flagellate forms, it has not been shown experimentally
that the bedbug is definitely connected with the transmission of
the disease.
Donovan is disposed to incriminate _Conorhinus rubrifasciatus_ as
the transmitting agent and furthermore he feels that there has not
been sufficient investigation of mosquitoes along this line.
_Canine Leishmaniasis._—In the regions where leishmaniasis of
infants occurs there is also found a similar disease of dogs and
Basile has claimed that the disease is transmitted from dog to dog by
the dog flea. As the dog has been regarded by some as the reservoir
of the virus, so naturally the transmission of the disease from dog
to child through the flea has been considered.
Wenyon, however, tried to infect two young dogs with great number
of fleas which had previously fed on dogs infected with canine
leishmaniasis and at autopsy, five or six weeks later, was unable
to find parasites in smears from spleen, liver or bone marrow and
did not succeed in obtaining cultures from this material inoculated
into tubes of N. N. N. medium.
Basile states that a temperature of 22°C. is necessary for
the development of the parasite in the flea and that negative
experiments have been due to their not having been conducted in
the winter. Patton has had fleas feed on a heavily infected dog,
whose peripheral blood showed hundreds of parasites per film. These
experiments were made in the winter and although examining 200 of
these fleas he failed to find any evidence of the flagellates after
eight hours.
Views have been entertained that the canine infection is one with
a flea herpetomonad distinct from _Leishmania_, but as dogs can be
infected with _L. infantum_ and then show manifestations similar to
canine leishmaniasis the parasites are probably the same.
Patton fed great numbers of fleas on a dog experimentally infected
with _L. donovani_ and found that the flagellates had entirely
disappeared from the alimentary tract of fleas dissected after
eight hours, although fleas dissected within four to six hours
showed degenerating _Leishmania_.
As regards oriental sore Wenyon has found that bedbugs and
_Stegomyia_ will feed from the sores and take up parasites which
develop into flagellate forms in the gut of the insects.
Proof of transmission by these agents however is lacking and others
are inclined to suspect the house fly or some species of moth midge.
In Brazil there exists some evidence that the cutaneous
leishmaniasis found there may be transmitted by species of the
tabanid family.
It must be understood that there is always a suspicion that the
flagellate forms noted in arthropod experiments may be those of
nonpathogenic herpetomonad or crithidial species as such forms are
common in arthropods and are difficult to distinguish from the
flagellate stage of leishman bodies.
_Cultural Forms._—Very definite is our knowledge of the cultural
forms of _Leishmania_. Rogers first cultured material from splenic
juice of kala-azar patients in 10% sodium citrate solution at a
temperature of 17° to 24°C. The medium was slightly acidulated
with citric acid. There was no satisfactory development at blood
temperature. In forty-eight hours the oval parasites have developed
into herpetomonad flagellates, from 20 to 22 microns long by 3½
microns broad, with a 20-micron flagellum which takes origin from
the blunt anterior end of the body near the blepharoplast. The
peripheral blepharoplast and centrally placed macronucleus are at
a distance from one another as opposed to the approximation of the
crithidial blepharoplast to the centrally placed nucleus in a body
with pointed anterior end.
Formerly it was thought that there were differences in the three
species of _Leishmania_ from the standpoint of growth on various
culture media, _L. donovani_ not growing on N. N. N. medium while _L.
infantum_ grew well on N. N. N. medium but not in citrated blood. It
is now known that both species will grow on these two media.
It is absolutely essential in culturing _L. donovani_ or _L.
infantum_ that the blood agar or citrated blood be sterile, as
any bacterial contamination prevents growth. With the parasite
_L. tropica_, however, bacterial contamination does not inhibit
development and statements have even been made that growth is
favored by a staphylococcal symbiosis. _L. tropica_, it would seem,
will develop into flagellated forms in cultures at 28°C. while it
will be remembered that Rogers in his original experiments failed
to obtain other than commencing signs of division at 27°C., 22°C.
being the temperature necessary for the development of flagellate
forms.
_L. tropica_ from South American cutaneous leishmaniases seems to
grow more luxuriantly on N. N. N. medium than does that of oriental
sore of Asia and Africa.
Giugni tried N. N. N. media made with human, rabbit and dog blood,
respectively. The parasites grew well on dog and rabbit blood media
but not on that made with human blood. He found growth best when
he added salt in quantity from 5 to 9 grams per liter. When red
corpuscles are laked in a medium the growth is less favorable.
While differences in development on different culture media may
obtain not only with different species but with different strains
of the same species, it would appear that such variations cannot be
utilized as a means of separating the three species.
_Animal Inoculation._—With animal inoculations we formerly thought
that the parasite of kala-azar could be differentiated from that of
infantile leishmaniasis by the fact that dogs could not be infected
with _L. donovani_, while they were susceptible to infections
with _L. infantum_. Recently Donovan and Patton have successfully
inoculated dogs with kala-azar splenic material. Patton found the
parasites in the liver, spleen and lymphatic glands as well as bone
marrow of the inoculated dogs. Consequently we cannot separate the
two visceral leishmaniases from a standpoint of susceptibility
of the dog. Monkeys are susceptible to both diseases. It is
important to recognize the fact that animal inoculations, even with
spleen-juice, rarely give rise to infection.
As regards separating oriental sore from the visceral leishmaniases
Gonder has shown that white mice may be infected with both
kala-azar and oriental sore, there being produced in each case a
general infection with the presence of parasites in spleen and
liver. A point of difference, however, is that the oriental-sore
mice develop lesions on feet, tail and head which was not observed
with the kala-azar mice. There are some reasons for thinking that
in human cutaneous leishmaniasis a generalized infection may
precede the local manifestations.
Dogs and monkeys can be infected with _L. tropica_ as well as mice,
but in them we have only cutaneous lesions produced. Inoculation
should be made intraperitoneally.
A very interesting point is that the dogs in India never show a
natural infection with _L. donovani_, while in the regions where _L.
infantum_ is responsible for human infections the natural infection
of dogs is not uncommon, indeed many think the dog the reservoir of
virus for both _L. infantum_ and _L. tropica_. It has been suggested
that the dogs of India, where kala-azar prevails, may be immune.
_Morphology._—As regards morphology it is usually stated that the
parasites of the three species of _Leishmania_ are practically
identical. In cultures it has been noted that the flagella of _L.
tropica_ are longer and more twisted than those of _L. infantum_.
Again it has been observed that the parasites of the Oriental
and South American skin lesions may at times show a flattened or
band-like trophonucleus instead of the constant round or oval one
of the visceral leishmaniases.
Escomel has reported the finding of flagellated _Leishmania_ in the
South American sores.
_Relationship._—Within the past year the view has been generally
accepted that Indian kala-azar and infantile kala-azar are one and
the same disease, the points of difference between _L. donovani_
and _L. infantum_ which had been advanced from cultural and animal
inoculation standpoints having been disproved.
It has been suggested that the Mediterranean basin may have been
the original focus of visceral kala-azar and that it spread thence
to India by way of Greece and the Russian Caucasus, cases having
been reported from districts which would join the two foci.
Just as children bear the brunt of malaria in old malarious
districts and adults suffer in places in which the disease has been
more recently imported, so by analogy we may consider the disease
as of more recent introduction in India. We now know that visceral
leishmaniasis is widely distributed in China, north of Yangtse, as
well as in the Sudan, and quite recently a case of kala-azar has
been reported from South America, in an Italian, who had lived in
Brazil from 1897 to 1910.
In the Mediterranean basin there is a natural canine leishmaniasis
and some think the human form may be contracted from the dog
through the medium of the flea. This dog kala-azar exists in two
types, one acute and the other chronic.
Some entertain the view that the virus of oriental sore is that of
a modified visceral leishmaniasis and there has been experimental
work along the line of determining whether the cutaneous infection
immunized against the visceral or vice versa as with vaccinia and
small pox.
Manson has suggested that as oriental sore is common in camel-using
countries it might be that a passage through the camel lowered
the virulence of the parasite as passage through the bovines does
variola, so that such an infection was of a mild type.
More recently there has been some evidence to indicate that
oriental sore may simply be a manifestation of a visceral infection
as shown in Gonder’s work with mice and from the fact of the long
period of incubation in oriental sore with the appearance in some
cases of general symptoms as well as the cutaneous ones.
The South American leishmaniases differ clinically from oriental
sore in that, following the primary lesions, ulcerating
granulomatous processes of nasal and buccal cavities frequently set
in subsequently, at times even after the primary manifestations
have healed.
VISCERAL LEISHMANIASIS
=General Considerations.=—There are two types of kala-azar, as
the visceral leishmaniasis is termed, one the Indian kala-azar,
which prevails in Assam, Madras, Indo-China, China and the Sudan
and characterized by a subacute or chronic febrile course and
splenomegaly in older children or adults and the other, the infantile
type, which in over 90% of cases occurs in children under four years
of age.
In 195 cases reported from Assam, by Mackie, 100 were in children
between six and ten years of age so that it is hardly true to call
Indian kala-azar a disease of adults.
The infantile type, which occurs chiefly in the countries bordering
the Mediterranean, is usually stated to be caused by _Leishmania
infantum_ while the adult type is said to be caused by _L. donovani_.
If, as is now thought, the two parasites are identical it will be
necessary to drop the name _L. infantum_.
=Epidemiology.=—Whether Indian kala-azar is transmitted by the
bedbug or infantile kala-azar by the flea are points which have not
been experimentally proven. It must be admitted that epidemiological
evidence supports the bedbug transmission view for the former.
On the other hand, Mackie dissected 322 bedbugs which he had fed on
kala-azar cases with practically negative results. He also injected
material from 588 bugs into two monkeys with negative results.
Mackie was likewise unsuccessful with lice, mosquitoes and sand
flies.
Rogers, investigating the disease in Assam, found that the usual
history in the villages was that someone with the disease came to
a village and subsequently other cases appeared. It was shown that
where a village escaped while others near at hand suffered there
was a history of nonintercourse with the infected villages. The
natives took extreme steps to eradicate the infection, it having been
reported that the Garos even burned the patients as well as their
huts. All evidence shows that the infection is contracted by sleeping
in an infected house. House epidemics and family epidemics are often
noted.
At the same time various observers have frequently noted instances
where an advanced case may associate intimately with his relatives
for months or years and yet none of these develop the disease.
There is little to support the view that it is a contact infection,
as such does not occur in hospitals where verminous insects are
absent. By isolating the sick and moving the uninfected to new
houses, only a short distance away, there is no spread of the
disease. The disease practically appears only in those Europeans
who live with or among natives.
In view of the fact that _Leishmania_ may be found in the
intestinal ulcerations or in the kidneys there have been
suggestions that the disease may be spread through the medium of
faeces or urine. There is not the slightest evidence that the
parasites could live in water which they might contaminate and the
view that some sort of transmitting host might take up parasites
from the faeces or urine is improbable, as the parasites have never
been found in faeces or urine.
The fact that a distance of 300 yards seems to suffice for
permanent protection of the uninfected excludes from consideration
such transmitting agents as the mosquito or house fly.
The tendency of some to incriminate soil factors can be explained
by the well-known fact that bedbugs can live for months without
food, being ready to bite those entering an infected house even
after long disuse as a habitation of man.
Infantile kala-azar may possibly be connected with the disease in
dogs and may be transmitted by the agency of the flea but there is
nothing like the evidence for this view that obtains for the bedbug
theory in Indian kala-azar.
=Pathology.=—At autopsy there is noted marked emaciation with
greatly enlarged spleen and liver, dropsical effusions and ulceration
of the large intestine. The spleen is often enormously enlarged,
rather firm but quite friable. The liver may at times show cirrhosis
but the usual change is a distention of the endothelial cells of the
intralobular capillaries with great numbers of parasites, as many as
100 or more parasites being at times found in a single cell. Not only
do the endothelial cells of the liver contain parasites but those of
the spleen, particularly the cells lining the venous sinuses as well
as those of the pulp cords, the lymphatic glands and bone marrow.
The parasites are present in the intestinal ulcerations of the
terminal stages. Less frequently they are found in kidneys, adrenals,
testicles, pancreas and lungs. Rarely, parasites may not be found
at the autopsy of advanced cases. It is possible that the finding
of coccus-like bodies in the cells of such cases may represent
degenerated leishman bodies. The mesenteric and prevertebral lymph
glands are swollen. The bone marrow is red.
When the phagocytic endothelial cells rupture the parasites
are taken up by other cells and if by large mononuclear or
polymorphonuclear cells may appear in the peripheral circulation.
In possibly 80% of cases the parasites may be found after prolonged
search in smears of peripheral blood. The leucopenia and large
mononuclear increase are the blood features.
SYMPTOMATOLOGY
_Indian kala-azar._—As with all diseases tending to a chronic course
it is difficult to be sure of the length of the period of incubation
of kala-azar and various authorities have given it as from two to
three weeks to several months. Manson states that one of his cases
developed the initial fever of the disease ten days after arriving in
the endemic area. As a rule the period of onset is rather indefinite.
There may be a history of daily rigors, so that malaria is suspected,
but it is found that the fever does not respond to quinine. The fever
is usually of a low remittent type, rarely a low continued fever, in
which the temperature does not exceed 101°F. At times however in the
early stage the remittent fever is of a high type, the temperature
reaching 104°F.
[Illustration: FIG. 54.—Fever chart of a case of kala-azar reported
by Bassett-Smith. This chart shows how easily one might confuse the
temperature curve of this disease with that of Malta fever.]
Rogers attaches particular importance to the fact that four-hour
charts will show a double or even triple rise of fever in the
twenty-four hours instead of the single one in typhoid fever.
The patients also show a striking absence of typhoid malaise and
apathy often stating that they feel well when the temperature may
approximate 104°F.
The febrile accessions last from two to six weeks to be followed by
periods of apyrexia and apparent improvement. Then follow further
waves of fever and apyrexia so that the fever chart may resemble that
of Malta fever.
In the early stages of the disease the loss of weight is apt to be
marked. Later on, owing to improvement in appetite and increase in
spleen, this is not so manifest.
The spleen begins to enlarge early in the disease and has usually
reached the level of the umbilicus by the third month. In some
cases there is little if any enlargement of the spleen even in
the chronic stages. At times we note only an irregular fever with
weakness, anaemia and emaciation. The liver does not usually become
distinctly enlarged until about the sixth month.
The course of the disease in India is chronic often covering a
period of one or two years. In the Sudan, however, Bousfield noted
that the symptoms ran an acute course, the average duration being
only about 5 months. Rarely he encountered chronic cases with
greatly enlarged spleen.
As the disease progresses anaemia and emaciation become marked so
that the bulging spleen and liver in a dusky or earthy colored,
skeleton-like native (black fever) make a striking picture. The
lymphatic glands of cases in North China show enlargement.
Symptoms referable to intestinal ulcerations, such as diarrhoea or
dysentery, are often noted at the end. Bleeding from the gums and
nose is not infrequently noted.
The marked leucopenia, with accompanying decrease in the
polymorphonuclears (the bacterial phagocytes), makes septic
infections and pneumonia especially common in the course of kala-azar.
These complications frequently bring about a fatal termination so
that we do not get the typical terminal cachexia with emaciation,
exhaustion, dry brittle hair, petechiae, oedema and ascites. On
the other hand the tendency of a bacterial infection to cause a
leucocytosis may bring about a cure.
_Infantile kala-azar._—The symptoms on the whole are similar to
those of the adult type of kala-azar and differ only to the extent
that might be expected in a disease occurring in very young children
instead of in those older.
The onset is insidious with some fever and gastro-intestinal upset.
The spleen enlarges, the child becomes apathetic, anaemic and
emaciated. Irregular attacks of fever occur and the child often
suffers from epistaxis, bleeding from the gums or haemorrhages into
the skin. According to Nicolle a peculiar pallor of the skin is
characteristic. Ulcerations of the intestines and noma may bring
about a fatal termination. The liver does not enlarge to the extent
that the spleen does. The finding of the parasites is necessary for
the distinction of this infantile splenomegaly from those of other
origin. The lymphatic glands are not usually enlarged.
Symptoms in Detail
_Onset and Fever Chart._—The disease commences in a rather
indefinite manner, often with gastro-intestinal symptoms or
possibly daily rigors. The fever chart is that of a remittent
fever with rather marked oscillations and in particular a double
rise in the 24 hours, which Rogers regards as characteristic. The
absence of a high continued fever and this double daily rise assist
in differentiating typhoid. Waves of fever separated by apyrexial
periods often simulate the fever chart of Malta fever.
_The Spleen, Liver and Lymphatic Glands._—The splenic enlargement,
which may reach the umbilicus by the third month, is the most
characteristic clinical sign of kala-azar. The diagnosis was
formerly made by spleen puncture but owing to many fatalities
the liver puncture is to be preferred, although the results of
such exploratory examinations are often negative, the liver being
involved to a less extent than the spleen and rarely showing
appreciable enlargement before the third month. It is during the
pyrexial periods that the spleen and liver enlarge.
Cochran has brought forward the importance of examining smears from
excised lymph glands for the parasites and others have shown that
gland puncture is of value. The glands in the infantile type of the
disease often do not show enlargement.
_The Blood._—Marked anaemia is only found in the later stages and
the color index is about normal. The number of red cells rarely
falls below 2,000,000.
Leucopenia is characteristically marked, this having been below
2000 in 62% of Rogers’ cases. This authority considers the finding
of 1 white to 1000 red cells, in a case of fever, very significant
of kala-azar.
There is also an increase in the large mononuclear percentage which
would aid in differentiating typhoid.
The coagulability of the blood is decreased and this may be a
factor in the fatal results which at times follow spleen puncture.
Parasites are found in the peripheral circulation in about 80% of
cases, after prolonged search, and may be phagocytized by either
large mononuclears or polymorphonuclears.
Patton found parasites in the peripheral blood in the examination
of a single slide in 42 out of 84 cases and with three slides in 25
of those not showing parasites with the first slide. By repeated
examinations up to the seventeenth slide, he got positive results
in all 84 cases.
The Sudan commission found that the alkalinity of the serum of
their patients was diminished.
Rogers has noted an acidosis in unfavorable cases of kala-azar
while those showing improvement only showed slight or no acidosis.
_Respiratory and Circulatory Systems._—There is very little that
is constant, the lungs being quite normal in 90% of Rogers’ cases.
The pulse rate is rather variable, although usually accelerated.
Diagnosis
_Clinical Diagnosis._—Cases of kala-azar are usually diagnosed as
malaria and it is in the lack of response to quinine that we have our
best point of differentiation.
In children showing splenomegaly the probability of the case being
kala-azar rather than malaria is indicated if the case has shown
progressive deterioration of health.
Malta fever shows a rather similar succession of febrile and
afebrile periods but the spleen of the former rarely shows marked
enlargement and the bronchial catarrh, sweatings, transient joint
swellings and neuralgic manifestations are characteristic of Malta
fever. Kala-azar may show muscular pains and slight sweatings and
the differentiation has at times only been made by the laboratory
diagnosis.
Typhoid and the paratyphoids are best differentiated clinically by
the presence of a continued fever, the absence of a double daily
rise and the existence of a more marked apathy.
The recent statements that hookworm disease may show enlargement of
the spleen would make this a condition to differentiate. Hookworm
ova and an eosinophilia indicate ancylostomiasis but there is
always the question here as with malaria as to the existence of
kala-azar and some other affection.
_Laboratory Diagnosis._—The leukemias can be easily differentiated
by the blood picture, an important matter because the spleen of
spleno-myelogenous leukemia is very friable and the danger from
splenic puncture is far greater in this condition than in kala-azar.
Banti’s disease with its leucopenia shows a rather similar blood
picture and can only be surely differentiated by the finding of
leishman bodies in kala-azar.
While malaria may at times show a leucopenia below 4000, a
polynuclear percentage below 50 and a large mononuclear one of 20
or more, yet the simultaneous appearance of all three is rare in
malaria while common in kala-azar.
Malta fever, typhoid and the paratyphoids are best differentiated
by blood cultures or agglutination tests.
Until recently it was recommended that for diagnosis our best
procedure was to make a splenic puncture. Manson and others have
pointed out the dangers from splenic puncture in kala-azar and have
rather preferred puncture of the liver, although recognizing that
the chances of obtaining parasites from a liver puncture, are less
than from a splenic one.
Statistics have been given where a mortality approximating 1% has
followed spleen puncture. Bousfield, however, using an all-glass
syringe with a 1½ inch needle did not have a fatality in 120 spleen
punctures.
For diagnosis the spleen or liver juice, rather than pure blood, is
smeared on a slide and stained by some Romanowsky method, preferably
that of Giemsa.
Cultures on N. N. N. medium can also be made.
Human blood seems to inhibit growth so that N. N. N. medium for
cultivating _Leishmania_ should be made from rabbit blood.
The culture should be kept at a temperature of about 22°C.
One should always first examine a smear of the peripheral blood for
parasites in polymorphonuclear or large mononuclear leucocytes. The
Sudan Commission found leishman bodies in the peripheral blood of
13 out of 15 cases so examined, but rarely did they find more than
one parasite-containing leucocyte to a slide.
It is well to select a time when some pyogenic infection causes a
leucocytosis.
Quite recently Wenyon and others have noted the desirability of
culturing the peripheral blood in N. N. N. medium. Diagnosis may be
made in this way, provided one wait from two to three weeks before
reporting negatively as to the presence of flagellated _Leishmania_
in the cultures. As before stated, strict asepsis and a room
temperature are requisite for flagellate development.
It has been noted that artificial pustulation might assist in
diagnosis by giving a multitude of polymorphonuclear leucocytes for
examination for phagocytized _Leishmania_.
Cochran has recently noted the advisability of excising a lymphatic
gland and making gland smears to examine for _Leishmania_. Others
have reported success with gland puncture as utilized in the gland
of trypanosomiasis.
Animal inoculation has no place in diagnosis as such a procedure is
but rarely successful. Ray has recently proposed a turbidity test
in which about 2 drops of blood are added to 20 drops of distilled
water. Instead of giving a clear solution of haemoglobin we have a
turbidity followed later by a white flocculent precipitate. It is
now thought that this turbidity is due to excess of serum globulin
in the blood of this disease and the test can be carried out with
serum instead of whole blood.
=Prognosis.=—Kala-azar is a chronic disease in the great majority
of cases although both the adult and infantile types may show cases
rapidly running to a fatal termination. Marked intestinal disturbance
makes for a bad prognosis as does also a low large mononuclear
percentage. A marked leucopenia is a bad sign particularly when
associated with such low polymorphonuclear percentages as ten to
twenty. Rogers notes that in children the polymorphonuclears several
times did not give more than 5% of the total leucocyte percentage.
The mortality is usually given as about 95% although Rogers states
that he has reduced this to 75% by large doses of quinine. The
action of antimony is that of a specific. Patients often succumb to
complicating septic conditions or pneumonia.
Prophylaxis and Treatment
_Prophylaxis._—The best results in India have been obtained by
abandoning infected houses and establishing new ones for the
non-infected villagers, which need not be more than 300 yards from
the old ones, thus showing that mosquitoes and flies are probably
not concerned in transmission. Measures directed against the bedbug
seem to offer the best chance of success. Often, however, the bugs
are so deeply located in cracks of thick-walled houses that they may
not be reached by sulphur fumigation. Flaming of such crevices with a
plumber’s lamp has been recommended.
_Treatment._—Rogers has recommended quinine in doses of 60 to 70
grains daily, claiming thereby to have reduced the mortality of the
disease to 75%.
Castellani recommends a combination of quinine and atoxyl, while
Manson has reported success with atoxyl in 2 cases, giving 3 grains
intramuscularly every other day.
Salvarsan has been tried, but without much success, as is also true
of X-rays.
Some have tried cinnamate of soda with the idea of increasing the
leucocytes.
With the purpose of increasing leucocytes Rogers has tried
hypodermic injections of sodium nucleate and killed staphylococcus
vaccines as well as splenic substance tablets. The sodium nucleate
injections were most painful and did not increase the leucocytes.
He had some success with tabloids of spleen substance.
If the blood serum shows a lessened alkalinity the intravenous
injection of solutions of bicarbonate of soda should be tried.
Rogers reports very favorable results from the administration of
alkalies by mouth.
Recently hectine has been recommended in infantile kala-azar.
Following the successful employment of intravenous injections of
antimony tartrate in American leishmaniasis it has been used in
Indian and infantile kala-azar.
Rogers has used the same treatment in Indian kala-azar with a
considerable degree of success. He has also used a 5% ointment of
finely divided antimony. The treatment should be continued until
the temperature has been normal several weeks and the leucocyte
count approach the normal.
Antimony may now be considered as a specific in the treatment of the
leishmaniases.
Knowles, at Shillong, has had long experience and striking success
with the intravenous administration of tartar emetic in kala-azar.
The heavy powder alone should be used—not the light powder. A 1%
solution is prepared in normal saline and the solution autoclaved
for 10 minutes at 110°C. If there is any opalescence or deposit
discard the solution. Knowles begins with the intravenous injection
of 3 to 4 cc. for an adult and gives the injections on alternate
days, increasing the dose until we are giving from 10 to 12 cc.,
the maximum dose. It will be noted that the dosage ranges from 3
to 10 centigrams (½ to 1½ grains). The amount of drug given for a
complete course of treatment is 200 cg. (33 grains). In the latter
part of the course of treatment the effects on the patient are more
marked so that caution must be observed, and it may be necessary
to lengthen the interval or reduce the dose. The injections
should not be given within two hours of a meal. Organic disease
of the heart or kidneys contraindicates the antimony treatment.
Coughing, a metallic taste in the mouth and constriction of the
chest are frequently noted following the injection. Nausea, colic
and diarrhoea show that the limit of the drug has been reached
and albuminuria and jaundice are signs of warning to decrease the
dose or stop the treatment. Christopherson considers that 5 to 8
grains will cure oriental sore, but for kala-azar 60 grains may be
necessary. This authority considers 3 grains of tartar emetic as
the maximum dose intravenously. For children under 1 year of age
the intravenous dose of the 1% solution is ¼ to 1 cc., from 1 to 5
years old 1 to 3 cc. and from 5 to 10 years of age 1 to 5 cc.
Manson-Bahr has reported the successful use of an
organic preparation of antimony, the sodium salt of
p-acetylaminophenylstibinic acid. It is a powder, readily soluble
in water and has the trade name of “stibenyl.” It can be injected
intravenously up to 0.8 gram. The drug contains 36% of antimony.
Knowles advises the use of tonics and, when indicated, of
anthelminthics. He also recommends cod liver oil to increase the
weight.
CUTANEOUS LEISHMANIASIS
=General Considerations.=—There is good reason to believe that much
that was written about oriental sore prior to our knowledge of its
etiology referred to tuberculous, syphilitic and other ulcerative
skin lesions. As regards the work done in the investigations as to
etiology Cunningham, in 1885, described deeply staining bodies in
cells which were larger than lymphocytes. Later, in 1901, Firth
confirmed the findings of Cunningham, but considered the bodies as
degenerative changes in the cells rather than entertaining the view
of Cunningham that they were parasitic protozoa. The name _Sporozoa
furunculosa_ was given these parasites. As previously stated, Wright,
in 1903, using his modification of the Romanowsky stain, found round
or oval bodies, from 2 to 4µ in diameter, packed in the cytoplasm of
endothelial cells, in smears from an oriental sore in a child from
Armenia. He called the parasites _Helcosoma tropicum_.
[Illustration: FIG. 55.—_Leishmania tropica._ Smear from granulation
tissue of Delhi boil or oriental sore. (MacNeal from Doflein after J.
H. Wright.)]
As the result of our knowledge that such lesions are caused by
leishman bodies, _Leishmania tropica_, we have been forced to
include among such sores clinical types entirely different from the
classical oriental sore of Fayrer or Tilbury Fox. Even a keloid
type of lesion described by the workers in the Sudan is known now
to be caused by leishman bodies. In 1909 leishman bodies were
demonstrated in ulcerative processes from Brazil and since that
time we have divided cutaneous leishmaniasis into two groups,
according to geographical distribution, that of the East, or
oriental sore, and that of the West, or American leishmaniasis.
Oriental sore is found chiefly in North Africa, Asia Minor, Syria,
Persia and India, and more recently cases have been reported from
Italy and Greece and New Caledonia. American leishmaniasis is found
chiefly in Central America, Brazil, Peru and the Guianas.
=Epidemiology.=—There is nothing definite known as to the
epidemiology of cutaneous leishmaniasis. The fact that oriental sore
almost always occurs on the uncovered parts of the body would suggest
transmission by some insect as the house fly or mosquito rather than
by the body louse, flea or bedbug, these latter showing no special
preference for the uncovered skin.
There has been a great deal written about the origin of the disease
in drinking water, various inorganic constituents having been
incriminated as factors. In certain places, as Delhi, oriental sore
has decreased among the British troops with the discontinuance of
the use of water from certain city wells. We know that oriental
sore is rather easily inoculable, it having been stated that
certain people of Bagdad inoculated their children in order to
insure against the possible appearance of the sore on the face with
the resulting scar disfiguration. Wenyon found that the virus would
not pass through the unabraded skin.
The disease is most prevalent about the end of summer and in the
autumn. It is a disease of towns. Some have thought that it might
be transmitted through the medium of the laundry. Not only can man
be infected by inoculation but this is also possible with monkeys
and dogs when a scarified area about nose or over eyebrows is
inoculated with virus from a sore.
The lesions are similar to those in man but last a shorter time.
It has been suggested that the dog may be the reservoir of this
virus as well as for that of infantile kala-azar. There is some
experimental evidence to show that an animal which has recovered
from a visceral leishmaniasis is immune to a cutaneous one.
There has been an idea that lizards or snakes might serve as
the reservoir of virus for oriental sore and that species of
_Phlebotomus_ feeding on these reptiles might take in the
flagellates and subsequently transmit them to man. Laveran,
however, has been unable to infect lizards with _L. tropica_.
Patton’s observations point to infection from the crushing of
infected sandflies when biting the exposed surfaces of the skin.
The natural infection of man with oriental sore produces a rather
lasting immunity.
As regards the American sores there is a great deal of difference
of statement as to the probable transmitting agent. These sores
seem to occur in forest regions where clearing of the trees is
going on. Infections occur in late summer or autumn. Marshy
districts appear to favour infection. Brumpt thinks the fact that
dogs, which are susceptible as well as monkeys to inoculation with
the American leishmaniasis, are often bitten by ticks without
the production of the sore, is against the view that ticks act as
transmitting agents. He rather favors a tabanid fly and in a case
reported by Darling the patient incriminated a tabanid fly.
Five cases are reported by Cerqueira as following the bite of
_Phlebotomus lutzi_.
The disease seems to occur naturally in the dog in the infected
regions.
=Pathology.=—In oriental sore there is an infiltration of the corium
and its papillae with plasma and lymphoid cells as well as with large
phagocytic cells packed with leishman bodies which cells Wright
regards as endothelial cells. There is atrophy of the epidermis.
In the keloid type of leishmaniasis noted by the Sudan Commission
epithelial cell nests were characteristic although there was no
other evidence of epithelioma.
In the American leishmaniasis there is rather constant involvement
of the lymphatic glands and often lymphangitis. Histologically the
appearance is rather that of granulation tissue with occasionally
giant cells.
SYMPTOMATOLOGY
_Oriental Sore._—Wenyon inoculated a scarified area on his arm which
became infected with pyogenic organisms but eventually healed. It was
thought that this inflammation would destroy any _Leishmania_ which
might have been present. About six months later he became ill and
had fever up to 103°F. for a week with malaise and gastro-intestinal
upset. At this time a small red papule was noted upon the site of the
original scarification which subsequently enlarged and was found to
contain leishman bodies.
The period of incubation is usually given as about two months,
although in some instances it may be as short as a week. Usually
the earliest appearance of the sore is similar to that of a
mosquito bite. The papule continues to enlarge, becoming purplish
in color with a glazed surface. It somewhat resembles an inflamed
acne lesion. Growing larger, the surface of the blind boil-like
lesions now becomes covered with brownish scales and, either from
scratching of the rather pruriginous spot or from the development
of vesicles, it becomes covered with a yellowish crust, beneath
which is an ulcer with raised edges and discharging a thin
offensive pus.
The ulceration does not generally occur before the third or
fourth month. The ulcer is painless and may be an inch or more
in diameter. Healing comes on in about seven to ten months, the
yellowish unhealthy granulations giving place to healthy pink ones.
The sore tends to run a course of about one year, hence the French
designation _bouton d’un an_.
According to Weber’s statistics about 85% of the sores were located
on the upper or lower extremities and about 10% on the face, while
the trunk served as the location for only about 5% of the sores.
There are generally 2 or 3 sores.
According to Déperet and Boinet the number of sores to a case was
one sore in 30%, 2 to 4 sores in 50% and from 4 to 20 in about 20%
of cases.
[Illustration: FIG. 56.—Oriental sore. (Ruge and zur Verth after
Cardamatis.)]
_American Leishmaniasis._—Under a number of names such as
_espundia_, _uta_, _bubas_ and _forest yaws_ there has been found in
many parts of Central and South America an ulcerating sore, more or
less resembling oriental sore, but often associated with ulcerating
granulomatous lesions of nasal and buccal mucosae. Da Silveira
states that in Brazil about 20% of cases develop the mucous membrane
lesions. He notes an incubation period of two to three months. In
Venezuela the mucous membrane lesions are more rare.
The lymphatic glands and lymphatics are commonly affected.
Just as with oriental sore one or more pruriginous papular lesions
appear on the uncovered parts of the body. In a few days it
develops a pustular summit. This undergoes ulceration and after
several months or even after the primary lesions have healed
nodules may make their appearance in nose and mouth.
These ulcerate and form fungoid granulations. Even the larynx may
be involved. The nasal septum and other cartilaginous portions
of the nose are often destroyed and the overlying tissues
become swollen and often eroded by ulceration, so that the
patients present the appearance of similar cases where syphilis,
tuberculosis or leprosy may be the cause.
A point of distinction between syphilitic and leishmaniasis lesions
of the nasal mucosa is that the latter do not involve the bony
structures.
Rabello noted that a positive Wassermann may be present in
cutaneous leishmaniasis which is in agreement with Sutherland’s
findings of 27% positives in cases of kala-azar.
The patients suffer from fever, joint pains, bronchitis and general
symptoms. After a long period of ten to twenty years, during which
they often die of some intercurrent affection, there may be a
terminal cachexia.
[Illustration: FIG. 57.—A case of _Leishmaniasis_ from Brazil
showing lesions in the mouth. (After Carini; from Mense.)]
=Diagnosis.=—The diagnosis in either oriental sore or in
American leishmaniasis can only be made surely by the finding of
_Leishmania_, either by scrapings from the edges of the ulcer or by
culturing in N. N. N. medium the blood from the immediate site of the
sore. Cultures were once obtained from the blood of a finger where
the sore was located on the arm of the same side but usually the
parasites are absent from the peripheral circulation. Gland puncture
in American leishmaniasis may give positive findings of parasites.
=Prophylaxis and Treatment.=—Knowing that the application of
material from a sore to a scarified surface will bring about
infection, it would seem advisable to cover any abrasions or open
wounds with flexible collodion or other protectives so as to prevent
flies, which may have fed on oriental sores, from having access to
the wound.
It has been recommended to paint the spot of insect bites with
tincture of iodine.
Atoxyl and salvarsan have been tried in oriental sore and American
leishmaniasis without any particularly striking curative results.
Attempts have been made to excise the early lesions but unless one
goes well beyond the infected area, severe recurrences may result.
Bier’s passive congestion method has been tried without success.
An expectant treatment is usually resorted to, the crusts being
softened and removed with antiseptic fomentations with subsequent
disinfection of the ulcer with bichloride or potassium permanganate
solution and the application of some antiseptic ointment or powder.
Thorough cauterization with pure carbolic acid followed by rapid
neutralization with alcohol can be tried. The injection of killed
cultures of _Leishmania_ does not seem to have been effective.
Wenyon has had good results from an ointment of equal parts of
methylene blue, lanoline and vaseline in an American sore.
Carbon dioxide snow has been shown by Mitchell to be an efficient
local application for oriental sore.
The remarkable effect of antimony on the parasites of leishmaniasis
was first noted in the treatment of the cutaneous types. The
treatment is similar to that described under kala-azar. The effect of
the drug is less pronounced on the lesions of the mucous membranes.
CHAPTER IX
DYSENTERY
DEFINITION AND SYNONYMS
=Definition.=—The designation dysentery refers to a symptom-complex
of (1) small, frequently passed mucous or muco-sanguinolent stools
and (2) pains connected with spasm of the sphincter ani (tenesmus) or
intestinal gripings (tormina).
The condition may be set up by numerous causes but of these two so
outweigh the others that it is usual to have in mind either bacillary
or amoebic dysentery when the term is employed.
=Synonyms.=—The Bloody Flux. French: Dysenterie. German: Ruhr.
GENERAL CONSIDERATIONS
As will be noted in the sections dealing with amoebic and bacillary
dysentery our present knowledge of these conditions is of recent
date. There was so much that was etiologically, epidemiologically
and clinically contradictory that the subject was impossible of
elucidation until the existence of a group of dysentery bacilli was
generally accepted, following the reporting, in 1898, by Shiga, of
his bacillus of dysentery.
Although Hippocrates was the first accurately to describe the
disease we now know as dysentery yet there is good ground for
believing that the disease existed in Egypt and India for centuries
before Christ.
Many of the older writers failed to differentiate conditions which
showed admixtures of mucus and blood in the stools from those with
blood alone.
Commencing with the last century, authorities have considered
the association of mucus with the blood as essential in clinical
diagnosis.
It is interesting that with a better knowledge of etiology we are
now recognizing as of dysenteric nature diarrhoeal conditions in
which there is an absence of the typical stool of dysentery.
Our views as to the etiology and epidemiology of bacillary
dysentery have been fairly definite for at least twenty years,
while those relating to amoebic dysentery, notwithstanding the
important researches of Kartulis, Councilman and Lafleur, Schaudinn
and others have remained rather chaotic until quite recently.
_The Term Dysentery._—By the term dysentery we understand a
symptom-complex of more or less characteristic stools and more or
less characteristic pains.
As a rule the stool is composed of one or more teaspoonfuls of
greenish yellow or dirty brown mucus, the altered blood being
intimately admixed with the mucus, or we may have a whitish to
grayish muco-purulent mass with streaks or flecks of blood on the
outside. These mucoid masses may be found suspended in serous,
sanguineous or more or less feculent discharges which are usually
small in amount and passed with much frequency.
The terms tormina and tenesmus are the ones used to designate the
characteristics of the pains of dysentery, tormina for the griping
colicky pains, which center about the umbilicus or run in the
direction of the large intestine, and tenesmus for the painful
spasmodic contractions of the sphincter ani to which is due the
sensation of lack of ability to complete the act of defecation
leading to straining and justifying Manson’s description “glued to
the commode.”
It is usually stated that the nearer the dysenteric process is to
the rectum, the greater the tenesmus and the nearer to the caecum,
the greater the tormina.
THE MODERN CLASSIFICATION OF DYSENTERIES IS BASED ON ETIOLOGY RATHER
THAN UPON CLINICAL MANIFESTATIONS
Owing to the great importance of the two main kinds of dysentery,
amoebic, or that caused by _Entamoeba histolytica_, and bacillary,
or that caused by some strain of _Bacillus dysenteriae_, we shall
consider them separately from the other causes of the dysenteric
symptom-complex.
=A. Dysenteries caused by animal parasites.=
_Protozoal dysenteries._
1. Amoebic dysentery (_Entamoeba histolytica_).
2. Flagellate dysenteries (_Lamblia intestinalis_, _Trichomonas
intestinalis_ and _Chilomastix mesnili_).
While in adults these intestinal flagellates usually cause only
a diarrhoea, with at times marked nervousness, they may produce
dysenteric symptoms in young children. The onset in children under
three years of age may be insidious and attended with fever. The
stool contains much mucus with only a little blood.
In cases of amoebic dysentery, the diarrhoeal attacks, which at
times occur, are often associated with an abundance of flagellates,
which may well be the cause of the complication. Cases of dysenteric
diarrhoea have been reported from Gallipoli in which _Lamblia
(Giardia)_ were apparently the only parasites involved. Such stools
are often of a yellow ochre color. Relapses are common features
of _Lamblia_ infections. _Lamblia_ is an inhabitant of the upper
intestine while _Trichomonas_ and _Chilomastix_ belong to the
large intestine, especially in the region of the caecum. While
these last named flagellates are often found in the stools of those
convalescent from dysentery there is a general opinion that they
are nonpathogenic. These organisms may be present in diarrhoeal
conditions in which case it is common to designate such diarrhoeas as
flagellate diarrhoeas. Fantham and Porter have reported 187 cases of
pure lambliasis.
In diagnosis it is important to recognize the encysted _Lamblia_.
These are oval cysts, about 10 × 7µ and show a curved central line,
with two lateral dots. When stained these dots show as chromatin
areas. These cysts may be found in the faeces in great numbers. The
vegetative _Lamblia_ has 4 pairs of flagella, is about 15µ long and
has a tumbling motion. Calomel alone or calomel and ipecac give
good results at times. Enemata of organic silver salts may be of
benefit.
Porter recommends bismuth salicylate. Low has noted the tendency of
lambliasis to recur and thinks many of the reported cases of cures
are only temporary. His experience with bismuth, salol, thymol and
cyllin has not been encouraging.
It is well known that lambliasis is of rather frequent occurrence
in mice and rats so that these rodents may be factors in spreading
the infection through the agency of their faeces deposited about
human food.
Of other drugs recommended in treatment Dobell and Low have had no
success with methylene blue, turpentine or beta-naphthol. These
authors failed to find any increase in either large mononuclears or
eosinophiles in a case of the infection.
Since Lamblia inhabit the upper parts of the small intestine, it
may be that the administration of drugs by the duodenal tube will
prove an effective method of treatment. Owens reports successful
results in the treatment of amoebic dysentery from ipecac so
administered. Stiles has recommended sulphur in lambliasis.
3. Ciliate dysenteries (_Balantidium coli_).
While various ciliates may cause a severe type of dysentery it is
very exceptional that others than _Balantidium coli_ do so. This oval
ciliate is from 60 to 100 microns long by about 50 to 70 microns
broad. It is a commensal of hogs and the disease in man is usually
found in those having the care of hogs. Infections have been reported
from various parts of the world, temperate as well as tropical
regions. These ciliates may be found in the faeces of persons
apparently well but in such cases symptoms may eventually appear. The
parasites multiply in the submucosa and the pathologic process is
similar to that observed in the large intestine in amoebic dysentery.
The parasite is so large and has such an active motility that
it would be impossible to fail to detect it in a microscopic
examination of the faeces. Encysted parasites are round. The
onset is rather insidious with diarrhoea which may be followed by
dysentery. A severe form of anemia may be noted.
Ipecac, emetine, arsenic and quinine appear to be of little
value in the treatment, but Walker considers the organic silver
compounds, as protargol, etc., of value. Methylene blue enemata
(1-3000) and 2-grain pills by mouth have been recommended.
[Illustration: FIG. 58.—Important pathogenic Protozoa of the
intestinal tract. (1a) Motile _E. coli_. Note large amount of
peripheral arrangement of chromatin in nucleus. (1b) Encysted _E.
coli_. Note larger size than _E. histolytica_ cyst, 8 ring form
nuclei and absence of chromidial bodies. (2) Motile _E. histolytica_
from acute dysenteric stool. Note histolytica nucleus with scanty
chromatin. (3) Tetragena type of _E. histolytica_ from case of
chronic dysentery. Note greater amount of chromatin and central
karyosome with centriole. (4a) Preëncysted _E. histolytica_ from
carrier. Note small size and heavy peripheral ring of chromatin in
nucleus making this feature of chromatin in nucleus similar to the
larger _E. coli_. (4b) Encysted _E. histolytica_ from dysentery
convalescent. Note small size, 4 ring nuclei and a dark chromatin
staining mass, “chromidial body.” (5a and 5b) Motile and encysted
cultural amoebae from Manila water supply. (6a and 6b) Oocyst and
sporozoite production in 4 spores of _Eimeria stiedae_. (7a and
7b) Oocyst with 2 sporoblasts and oocyst with 2 spores containing
4 sporozoites of _Isospora bigemina_. (8a and 8b) Vegetative
and encysted _Trichomonas intestinalis_. (9a and 9b) Vegetative
and encysted _Lamblia intestinalis_. (10) _Balantidium coli._
Illustrations of amoebae from Walker—others from Doflein.]
4. There are also dysenteric manifestations noted in the terminal
stages of kala-azar (_Leishmania donovani_) and in algid pernicious
malaria (_Plasmodium falciparum_). These conditions are taken up
under the diseases kala-azar and malaria.
Wenyon noted a case of coccidial infection (_Isospora hominis_)
in which there was a dysenteric syndrome. There have been about
seventy cases of infection with this parasite reported, chiefly
from soldiers serving in Gallipoli. The usual opinion is that they
are nonpathogenic parasites. The oocysts are ovoid, with one end
narrowed, and measure 28 × 14 microns. There are two sporocysts,
each of which contains four sporozoites. The cyst when first passed
is unsegmented.
_Helminthic dysenteries._—1. In addition to the protozoal causes
above noted we may have dysenteric symptoms following infections with
trematodes, especially _Schistosoma mansoni_ and _S. japonicum_. In
these cases we have mucus coating the stool with more or less clotted
blood in which mucus we may find the diagnostic ova. A rather high
eosinophilia is present.
2. Infections with _Gastrodiscus hominis_ also give rise to
dysenteric manifestations.
3. A very small cestode, _Heterophyes heterophyes_, has been noted
to cause a condition suggestive of dysentery.
4. In 1902, Brumpt noted the finding of a nematode,
_Oesophagostomum brumpti_, in the large intestine of an African
native, which caused dysenteric symptoms and, more recently,
another species, _O. stephanostomum_, has been reported as causing
a fatal dysentery in a Brazilian at Manaos.
5. There have also been reported cases with dysenteric
manifestations which were apparently connected with intestinal
myiasis.
=B. Dysenteries caused by bacteria.=
1. Those caused by either the more toxic, nonacid mannite strain of
Shiga, or the less toxic, acid mannite strains of the Flexner group.
2. Morgan has reported as the cause of certain bacillary dysenteries
a bacillus known as B. Morgan No. 1. It is motile, produces indol,
and in glucose bouillon gives a very slight amount of gas. It does
not change mannite and does not produce a primary acidity in litmus
milk. This organism is a frequent cause of summer diarrhoea of
children. Flies from houses with such cases often show Morgan’s
bacillus.
Paratyphoid infections may give the clinical picture of a colitis
and such cases at times show a large amount of blood in the
dysenteric stools. Usually the symptoms are rather those of an
entero-colitis or a gastro-enteritis.
3. In Japan, dysentery-like epidemics of a very fatal disease, termed
_ekiri_, occur among young children. The organism is very motile,
producing gas and acid in glucose, but not in lactose media. It is
reported at times to show indol production. Apparently a member of
the Gärtner group.
4. Spirillar dysentery. LeDantec has reported a type of dysentery
which shows the presence of great numbers of spiral forms. These
are Gram negative and noncultivable. It is in question whether they
belong to the bacteria. There is no fever in this type of dysentery.
5. Other bacterial causes. Cases of dysentery have been reported
as caused by _B. pyocyaneus_, streptococci, atypical _B. coli_ and
organisms of the Gärtner group.
In a _Pyocyaneus_ infection the color of the stools would be
suggestive. This cause should be borne in mind in the dysenteric
infections of debilitated children in the tropics. Some of the
cases of so-called ptomaine poisoning due to members of the Gärtner
group have clinical similarities to dysentery especially at the
commencement of the attack.
=C. Dysenteries resulting from mechanical irritants or poisonous
substances.=
A very interesting form of poisoning which gives rise to serious
illness or death and is attended with marked abdominal pain and
manifestations of dysentery is that reported from North China
through the use of short lengths of bristles which are given mixed
with the food.
Various irritant metallic poisons as arsenic, antimony and mercury
may give rise to dysenteric symptoms. In cancer and syphilis of the
rectum there may be a suspicion that the process is an ordinary
dysenteric one.
Intussusception shows marked tenesmus with bloody rather than
muco-sanguineous stools.
While dysenteric symptoms may be present in the terminal stages
of various chronic diseases, especially tuberculosis and cardiac
affections, yet it is in chronic nephritis, leading to uremia, that
we may see symptoms of a marked catarrhal or even diphtheritic
colitis.
CHAPTER X
AMOEBIC DYSENTERY
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—Lambl, in 1859, was the first one to note the presence of
amoebae in man, these being found in the stools of a child affected
with diarrhoea. It was Lösch, however, who, in 1875, first accurately
described the parasite which he found in the intestinal ulcerations
as well as in the stool of a patient with chronic dysentery and was
able to produce dysenteric ulcerations in the dog, by injecting
amoebae-containing faeces into the dog’s rectum.
In 1879 Grassi noted the encysted forms of amoebae, but as he
found them in well people, he denied their pathogenic importance.
Cunningham found amoebae in the stools of cholera patients and
Perroncito in those of typhoid cases, both of these authorities,
however, viewing the question of their pathogenicity as did Grassi.
This was the general attitude of the medical mind until Koch, in
1883, while investigating cholera in Egypt, was impressed with the
striking penetration of amoebae in the walls of intestinal ulcers
and considered that this fact favored the view that amoebae were
pathogenic.
Kartulis continued the work of Koch and in 1886 published his
findings in 150 cases of dysentery, noting the presence of amoebae
in the stools of all these cases. In 1887 he noted the presence
of amoebae in liver abscess. In 1891, Lutz noted that amoebae in
dysentery contained red cells. In the same year Councilman and
Lafleur came to the conclusion that there were two species of
amoebae in man, one harmless and the other, which was found in
the submucosa of intestinal ulcers, pathogenic, Casagrandi and
others put forward the view that amoebae only acted as carriers for
bacteria, but in 1893 Kruse and Pasquale injected all the bacterial
species isolated from a dysenteric stool into a cat’s rectum with
negative result. Hlava and Kartulis first produced dysenteric
lesions in cats by injecting per rectum, amoebic stools. Kruse
and Pasquale produced dysentery in cats by injecting per rectum
bacteria-free pus from a liver abscess which however contained
amoebae.
A stumbling block as to the connection between amoebae and
dysentery was the fact that many cases of typical dysentery failed
to show amoebae. In 1898 Shiga settled this matter by reporting
a group of bacilli which were concerned in the production of
dysentery. His findings were confirmed all over the world and the
distinction gradually obtained of cases of dysentery from bacillary
as well as from amoebic infections.
In 1903 Schaudinn reported the existence of two species of amoebae,
one harmless and named _Entamoeba coli_, the other pathogenic and
named _E. histolytica_. In 1907 Viereck described a pathogenic
amoeba which, by reason of its four nuclei in the encysted stage,
he called _E. tetragena_.
As the result of the work of Hartmann, Whitmore, Darling, Wenyon and
the recent conclusive findings of Walker we now hold the view that
Schaudinn was working with _E. tetragena_ and not with a separate
species, so that by the law of priority we must drop the name _E.
tetragena_ and accept _E. histolytica_.
=Geographical Distribution.=—Amoebic dysentery seems to be
especially prevalent in Indo-China, China and the Philippines, as
well as in parts of India. It is also very common in Egypt and
Northern Africa. In South America, especially Brazil, it is common,
as is also true of the West Indies and Central America. It is an
important disease in the Southern States of the United States, as
well as in Italy and other parts of Southern Europe. On the whole
it is probable that it exists in greater or less degree in most of
the tropical and subtropical parts of the world.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—For a long time the authorities in Manila held that
it was impracticable to differentiate between a pathogenic and
nonpathogenic species, taking the view that the principal factor
in the production of dysentery was that of symbiosis between
amoebae and suitable bacteria, it having been thought that they
observed in cultures of amoebae evidences of both symbiosis and
antagonism on the part of amoebae to certain species of bacteria.
They furthermore were convinced that pathogenic amoebae could be
cultured on a medium of about 1/10th the strength of ordinary
nutrient bouillon or agar and that dysentery could be produced
by such cultural amoebae. Such views had an important bearing on
epidemiology as it was thought that where amoebae could be cultured
from green vegetables, fruit, or water supply there was positive
evidence of the possibility of infection with amoebic dysentery
from such a source.
The above views are no longer entertained and, due to Walker, working
in Manila with experiments on man, we now know that cultural amoebae
are without effect in the production of dysentery and that there are
certainly two well known species of amoebae having man for a host,
the one pathogenic, _Entamoeba histolytica_, and the other a harmless
commensal, _Entamoeba coli_. Two other species, _Endolimax nana_ and
_Iodamoeba bütschlii_, have recently been described but are generally
considered nonpathogenic.
Some authorities prefer the generic names _Löschia_ and _Endamoeba_
to _Entamoeba_.
Schaudinn, in 1903, described the pathogenic amoeba, which he named
_E. histolytica_, as follows: 1. Distinct, highly refractile and
tenacious ectoplasm. He considered this tough external portion of
the cytoplasm as the explanation of the ability of the pathogenic
amoeba to bore its way into the intestinal submucosa. 2. Eccentric
nucleus which was indistinct by reason of little chromatin. 3.
Reproduction by peripheral budding in which small aggregations of
chromatin reached the periphery of the cytoplasm and, enclosed in a
resistant capsule, broke off from the parent amoeba and constituted
the infecting stage.
[Illustration: FIG. 59.—_Entamoeba histolytica_. The same living
individual drawn at brief intervals while moving. (From Doflein after
Hartmann.)]
For the nonpathogenic _E. coli_ he noted: (1) No distinction
between a granular endoplasm and refractile ectoplasm; (2)
centrally placed and sharply outlined nucleus, rich in chromatin;
and (3) encystment with the formation of eight nuclei, which cysts
with their nuclei or amoebulae form the infecting stage.
The pseudopodia of _E. histolytica_ are actively projected as long
finger-like processes which show the ectoplasm quite distinctly,
while the pseudopodia of _E. coli_ are lobose and sluggishly
projected and show a uniformly opaque grayish color. In dysenteric
stools _E. histolytica_ tends to show contained red cells. _E.
coli_ never contains them but instead shows bacteria and food
particles.
In 1907 Viereck and later Hartmann recognized a pathogenic amoeba
with four nuclei in its encysted form, to which was given the name
_E. tetragena_.
All authorities now consider that Schaudinn made an error in
observation as to the existence of peripheral budding for _E.
histolytica_, so that we recognize but two types of encystment, one
with a larger cyst and thicker cyst wall, with eight nuclei and an
absence of chromidial bodies—_E. coli_—the other, smaller, with
a thin cyst wall one to four nuclei and chromidial bodies in the
encysted stage, the pathogenic amoeba, _E. histolytica_. Synonym,
_E. tetragena_.
In the vegetative stage the human amoebae are best differentiated
by the nuclear structure as shown in stained specimens. In _E.
coli_ the nucleus is vesicular with a thick nuclear membrane
and the chromatin chiefly deposited on the under surface of the
nuclear membrane. This chromatin often seems deposited in quadrant
aggregations. The karyosome is eccentric.
For the pathogenic amoeba we recognize a _histolytica_ type of
nucleus, which is found in dysenteric stools, and a _tetragena_ type,
which is found in diarrhoeal or more or less normal stools. Dobell
does not recognize this differentiation.
[Illustration: FIG. 60.—The more important intestinal amoebae of man
showing nuclear structure when stained. 1. _E. histolytica._ 1(a).
_E. histolytica_ cyst. 2. _E coli._ 2(a). _E. coli_ cyst. 3. _E.
nana._ 3(a). _E. nana_ cyst. 4. _I. bütschlii._ 4(a). _I. bütschlii_
cyst. (After Dobell.)]
The histolytica nucleus has a thin nuclear membrane and is poor in
chromatin while the tetragena nucleus has more chromatin, showing
radial projections from the inner surface of the nuclear membrane,
and a loose central spherical karyosome, which contains a central
chromatin dot or centriole, with a clear halo surrounding it.
Dobell states he has not been able to note this centriole.
The preëncysted _E. histolytica_ has a nucleus resembling that of _E.
coli_. The smaller size and chromidial bodies are differentiating.
Animal experimentation upon kittens with _E. coli_ by Schaudinn,
Craig and Wenyon have been unsuccessful as to production
of dysenteric manifestations. On the other hand all of
these experimenters produced typical lesions and dysenteric
manifestations in kittens injected rectally or fed with material
containing pathogenic amoebae.
Wenyon as previously stated produced a liver abscess in one of his
experiments.
Darling has been so successful in his experimental work with
kittens that he compares the colon of a kitten to a test tube and
suggests the procedure of rectal injections of material containing
amoebae as a means of differentiating the two human amoebae.
On the other hand Walker was unable to infect kittens and
monkeys with material containing pathogenic amoebae and he makes
the statement that such failures would indicate the greater
susceptibility of man to infection, as he was able to infect 17 out
of 20 men with one feeding of such material.
Sellards and Baetjer note that inoculation of kittens per rectum
or by feeding dysenteric stools rich in amoebae has resulted in
infection in about 50% of experiments.
By inoculating the material directly into the caecum they were
able to infect every one of their kittens. They were also able
to propagate a strain of amoebae through a series of animals for
several months.
The intracaecal inoculations yielded positive results in diagnosis
of human amoebiasis when the clinical manifestations were obscure
and the amoebae in the discharges so few and atypical as to make
such an examination unsatisfactory.
_Other Intestinal Amoebae._—It is a remarkable fact that one of
the most common of the intestinal amoebae, _Endolimax nana_, has
only recently been reported (Wenyon and O’Conner in 1917). In the
examination of the stools of American soldiers Kofoid found it
present in 28% of his examinations while _E. coli_ was present
in 23% of cases and _E. histolytica_ in 9.3%. In examining 156
British soldiers Dobell noted its presence in 33% of them. The
general view is that it is not pathogenic but its great importance
is in the possibility of its being mistaken in its cyst form for
_E. histolytica_. The living amoeba averages about 8 microns but
in stained specimens it is somewhat smaller. In freshly passed
faeces the amoeboid motion is sluggish and the nucleus indistinct.
This amoeba is best identified by haematoxylin stained specimens
when the nucleus shows a measurement of about 2 microns with a
large eccentric karyosome which exhibits a variety of form. Unless
perfectly fresh material is stained the degenerative changes in the
amoebae may give a signet ring appearance of karyosome and ring
nucleus. Such an appearance may suggest the limax nucleus. The
mature cysts are usually oval, but sometimes round, and contain
4 nuclei, but when newly formed may only have one nucleus. The
nucleus is large in the uninucleate form (up to 3 microns) but
in the quadrinucleate forms it is about 1.2 microns with a large
eccentric mass of chromatin. Chromidial bodies are rarely, if ever,
present in these cysts.
_Iodine Cysts._—These bodies which stain a deep brown colour when
treated with iodine are now recognized as amoebae and have been
named _Iodamoeba bütschlii_. They are most probably nonpathogenic.
It is a small amoeba (9 to 13 microns, rarely up to 20 microns)
and shows the sluggish movements of _E. coli_. The nucleus is very
difficult to discern, thus differing from _E. coli_. In stained
specimens it has a vesicular nucleus about 2 microns in diameter
with a fairly large central karyosome. The cysts are spherical
or oval, often of irregular outline and are about 10 microns in
diameter. The nucleus is large and eccentrically placed and has a
karyosome which tends to show as a peripherally placed mass. There
is almost always present a large glycogen mass in the cyst which
stains intensely with iodine.
_Dientamoeba Fragilis_ (Jepps and Dobell 1918).—A rare binucleate
amoeba averaging 8-9 microns in size. Nuclei show a fairly large,
central granular karyosome and no peripheral chromatin. Strands
of linin may be seen radiating from karyosome to nuclear wall.
This organism is said to be frequently mistaken for Blastocystis
when the vacuoles coalesce leaving a thin ring of cytoplasm. Cysts
unknown. Considered nonpathogenic. Recently Kofoid and Swezy
reported another species of amoeba parasitic in man, _Councilmania
lafleuri_. The adult and cystic stages resemble in many respects
the _E. coli_. Adult said to ingest red blood cells. Stated to be
pathogenic but that more evidence is needed on this point.
=Human Experiments.=—Recently Walker and Sellards have published a
most important paper.
The experiments were made in men who had been under observation
for years at Bilibid Prison, whose food was cooked and the water
they drank distilled. Moreover, there were complete records of
examination for intestinal parasites, including entamoebae. They were
under complete control and the existence or possibility of natural
infection with amoebae was reduced to a minimum. All the men fed
pathogenic amoebae were volunteers and each signed, in his native
dialect, an agreement to the conditions of the experiment.
The first series of experiments was with cultural amoebae, in
order to refute statements that amoebae cultivated from water or
other nonparasitic sources, as well as from dysenteric stools, are
capable of living in man parasitically or of producing dysenteric
symptoms. Twenty feeding experiments on ten men were made by Walker
and Sellards with cultures of amoebae without the development in a
single instance of dysentery or the finding of such amoebae in the
stools upon microscopical examination. In 13 cases they recovered
the amoebae in cultures from the faeces from the first to the sixth
day, but never afterwards. They stated definitely that cultural
amoebae are nonpathogenic.
The next experiments were with _Entamoeba coli_. In the 20 cases
fed with material containing _Entamoeba coli_ there was a uniform
failure to recover them culturally and in no instance was dysentery
produced. Seventeen became parasitized as the result of a single
feeding in from one to eleven days, the entamoebae being found
in the stools and persisting in their appearance in the stools
for extended periods. They concluded that _Entamoeba coli_ is an
obligate parasite, nonpathogenic, and cannot be cultured.
The third series of 20 feedings, carried on by Walker alone, was
with _Entamoeba histolytica_. The material was mixed with powdered
starch or magnesium oxide and given in gelatin capsules. In these
experiments they obtained tetragena cysts in the stools of men
fed only motile _Entamoeba histolytica_, and motile _Entamoeba
histolytica_ in the stools of men who were fed only tetragena
cysts and, finally, an alternation of motile _E. histolytica_ and
tetragena cysts in the stools of a man having a recurrent attack of
amoebic dysentery.
=Results.=—Seventeen of the men became parasitized after the first
feeding; 1 required three feedings, and 2, who did not become
parasitized at the first feeding, were held as controls. The
average time for parasitization was nine days. Only 4 of the 18
parasitized men developed dysentery, which came on after twenty,
fifty-seven, eighty-seven, and ninety-five days, respectively,
after the ingestion of the infecting material.
In 4 cases fed with material from acute dysenteric stools or
from amoebae-containing pus from liver abscess, and containing
motile amoebae, there was no resulting dysentery, the 4 cases of
experimental dysentery resulting from feeding of material from
normal stools of carriers.
As regards the cases which became parasitized, but did not develop
dysentery, it is suggested that the amoebae live as commensals in
the intestine of the host and only penetrate the intestinal mucosa
and become tissue parasites when there occurs depression of the
natural resistance of the host or as the result of some lesion of
the intestine. That the pathogenic amoebae are more than harmless
commensals, however, is shown by the fact that they alone, and not
the nonpathogenic _Entamoeba coli_, are capable of penetrating a
possibly damaged intestinal mucosa.
=Epidemiology.=—The chief factor in the spread of amoebic dysentery
would seem to be the encysted amoebae in the stools of convalescents,
or symptomless carriers, rather than the motile amoebae in dysenteric
stools. When such carrier has to do with the preparation of food, he
becomes a particular source of danger.
This probably explains the endemic rather than the epidemic
characteristics of the spread of amoebic dysentery because, if the
innumerable vegetative amoebae in dysenteric stools were equally
operative with the more sparsely eliminated cysts, there would
be epidemics of amoebic dysentery similar to those of bacillary
dysentery. The old idea that water, fruit or vegetables, from
which one can isolate amoebae on culture, are sources of infection
must be abandoned, as such cultural amoebae are known to have no
pathogenic relation to man.
Vegetative amoebae undergo disintegration in a short time after
the stool is passed, so that they are probably rarely concerned in
amoebic infections but the resisting cysts may be washed from a
dried stool into a water supply or even be transported in dust to
lodge on unprotected foodstuffs.
Flies may possibly act as transmitting agents. As bearing on the
probable importance of such flies as _Musca domestica_ and _Fannia
canalicularis_ in transmitting amoebic infections may be noted
the findings of Wenyon that the faeces of such flies, as well as
_Lucilia_ and _Calliphora_, after feeding on cyst-containing human
faeces, teem with such cysts. In a dissection of 1027 house flies
caught in Mesopotamia Buxton found ova of parasites of man in
4.09%. The percentage of infection with _E. histolytica_ cysts was
O.3%.
PATHOLOGY
Wenyon thinks that the pathogenic amoebae work their way into the
tubular glands of the intestines and multiply and subsequently,
either by pressure of their pseudopodia or through the disintegrating
action of some toxic substance elaborated by them, they force their
way into the underlying submucosa. In this location they produce a
gelatinous, oedematous necrosis, which shows a marked absence of
polymorphonuclears, but a proliferation of connective tissue cells.
The process is regenerative rather than inflammatory.
Small hemispherical elevations of the overlying mucosa mark
the location of the deeper-lying necrotic process. With the
multiplication of the amoebae and the extension of the necrotic
process in the submucosa we have thrombi formed in the terminals of
the portal vein and possibly in those of the mesenteric arteries,
which in the former case may result in emboli being swept up the
portal vein to lodge in the liver and form a starting point for a
similar necrosing process there or, as the result of interference
with the blood supply of the overlying mucosa, cause this to
undergo necrosis and be cast off as a slough, leaving an oval or
irregular ulcer with deeply undermined edges and a floor formed by
the muscular coat. The ulcers may be no larger than a pin’s head or
they may be 1 or 2 inches in diameter or by coalescence be still
larger. The gelatinous necrosis in the submucosa always extends
beyond the limits of the necrosis of the mucosa, thus explaining
the undermining. At times the muscular coats of the intestines are
involved thus leading to a slough which involves all coats except
the serous one. Bacterial infection, with coagulation necrosis of
the mucosa overlying the amoebic process, is also responsible for
some of the tissue destruction.
The amoebic ulcerations rarely extend above the ileo-caecal valve but
may involve the entire large intestine. Rogers and Lafleur found the
lesions most often in the caecum and ascending colon, often limited
to this area.
The appendix was involved in 7% of the Manila autopsies. Often mild
cases may only show lesions in the caecum. When there is a tendency
to perforation the omentum will often be drawn over to the location
of the threatened perforation. There is often thickening of the
intestine in one place with cicatricial contraction of the lumen
and thinning in another, so that there is an appearance of great
irregularity.
SYMPTOMATOLOGY
The great majority of cases of amoebic dysentery run a chronic course
with periods of improvement alternating with recurrences of pains and
dysenteric stools. From Walker’s experiments the period of incubation
would appear to be from one to three months. The onset in such cases
is very insidious and the patient may complain more of diarrhoeal
than dysenteric manifestations. Such patients often give a history
of passing three or four pultaceous stools daily and complain of
tenderness in the region of the caecum or along the course of the
large intestine. One may determine some thickening of the colon in a
thin subject.
Fever is absent and there are very few of the toxic manifestations
which often accompany bacillary dysentery, such as headache, nausea
and a mildly delirious state. There is progressive loss of weight
and strength with the development of neurasthenic symptoms. The
skin becomes dry and earthy and we have the picture of a more or
less marked secondary anaemia. It is in these cases that we should
be on the lookout for grayish green or grayish brown mucoid masses
which can usually be found during an exacerbation. Sloughs of the
gelatinous-like necrosis in the submucosa usually contain amoebae.
The X-ray has been utilized to give location of amoebic ulcerations.
Bismuth is used for several days prior to taking the photograph and
fills the sites of ulceration.
Such cases usually show a moderate leucocytosis in which the
percentage of large mononuclears is increased and a very
important point is that with tenderness about the caecum, plus a
leucocytosis, one may diagnose appendicitis and operate on a normal
appendix. Autopsy records however have shown that the appendix is
not infrequently invaded by amoebae but in some of these cases,
other than finding amoebae in the lumen of the appendix, I have
been unable to note any change. Cases of amoebiasis confined to
caecum and ascending colon may only show symptoms of slight anaemia.
Besides the more common insidious chronic type we may have amoebic
dysentery setting in quite acutely with severe griping and frequent
scanty grayish green to reddish brown mucoid stools.
Such cases may show anorexia and nausea with some fever but there
is not present the manifestations of toxemia one associates with a
severe case of bacillary dysentery in the tropics.
Very confusing cases are those in which a bacillary dysentery
sets in upon an amoebic one and this possibility should always be
thought of when a severe bacillary dysentery does not respond to
serum therapy or an amoebic one to emetine.
Gangrenous lesions may occur in amoebic dysentery although more
common in bacillary infections. Such cases will show extreme
prostration and even give the clinical picture of cholera.
=Complications.=—By far the most important and serious complication
of amoebic dysentery is liver abscess, which occurs in about 20%
of cases. This condition is treated of separately. Besides liver
abscess quite a number of cases of amoebic abscess of the brain
have been reported, 26 such cases occurring in Egypt alone. These
abscesses almost always occur in those cases which have developed
liver abscess and may appear after the liver abscess has healed.
The pus of such abscesses is viscid and blood-tinged, resembling
liver abscess pus. The amoebae are found in the abscess wall.
The symptoms are those of brain tumor, meningitis not occurring.
Necrotic processes of skin and muscles have also been reported in
which amoebae have been found.
Perforation of the large intestine is not rare, Strong having noted
12 perforations in 77 autopsies. These usually occur in the region
of the sigmoid flexure.
Adhesions are common complications of amoebic dysentery.
DIAGNOSIS
=Clinical Diagnosis.=—In the clinical diagnosis it is well to
remember that many cases of chronic tropical diarrhoeas are really
due to amoebic ulcerations of the intestines.
We can as a rule differentiate bacillary from amoebic dysentery by
the more sudden and acute onset of the former together with fever
and other evidences of toxaemia. The pulse rate is more rapid in
bacillary than amoebic dysentery. Again the number of stools in
bacillary dysentery is usually greater and the amount of each
stool less in quantity. The stool of bacillary dysentery is of a
milky whiteness from the large number of pus cells or composed
of gelatinous, reddish mucus, while that of amoebic dysentery is
tinged with disintegrated blood giving it a grayish-green or brown
color. The mucopurulent mass in bacillary dysentery may be flecked
or streaked with blood. The therapeutic results following emetine
injections are of value in diagnosis.
Gangrenous types of dysentery are similar whether due to bacillary
or amoebic infection. Chronic dysentery of bacillary origin is much
like amoebic dysentery clinically.
Manson-Bahr and Gregg recommend the use of the sigmoidoscope in
the diagnosis of chronic amoebic ulcerations. In the evening the
patient takes ½ ounce of castor oil and the next morning a soap and
water enema is given followed by 15 minims of laudanum. The patient
is put in the lithotomy position. No anaesthetic is used. The pain
in introducing the instrument is greater in chronic bacillary
ulceration cases than in amoebic ones. Scrapings can be made for
microscopic examinations. Nisbet has reported the diagnosis of a
case of balantidial ulceration by use of the sigmoidoscope.
=Laboratory Diagnosis.=—The mucoid mass of amoebic dysentery is
often brownish. The pathogenic amoeba shows active finger-like
processes and in acute attacks often shows contained red cells.
In the fresh specimen of the milky mucopurulent mass of bacillary
dysentery one observes large numbers of pus cells and particularly
very large phagocytic cells which greatly resemble amoebae. Upon
staining with Gram’s stain one may find numerous Gram-negative
bacilli in the cytoplasm of this cell.
These large cells which resemble amoebae are often vacuolated, thus
intensifying the similarity. They are nonmotile, however, and do
not show the small ring nucleus which is so characteristic of the
vegetative human amoebae. The nucleus of the confusing cells is
also larger, approximating one-fourth the size of the cell.
Bacillary dysentery stools show an absence of Charcot-Leyden
crystals which are often present with amoebic stools.
For bringing out the nuclear characteristics of human amoebae
Walker recommends fixation of thin moist smears in Giemsa’s
sublimate alcohol (absolute alcohol 1 part, sat. aq. sol.
bichloride 2 parts) for 10 to 15 minutes. These smears are then
well washed with water and stained with alum haematoxylin for five
minutes. The nuclear characteristics are noted under etiology. In
such staining the preparations, which are best made on cover-slips,
should never be allowed to become dry.
An excellent iron haematoxylin method is that of Rosenbusch:
Rapidly smear out with a toothpick a small particle of faeces or
other material containing protozoa and, while still moist, fix by
Giemsa’s method and, after getting rid of the mercury with iodine
solution followed by 95% alcohol, treat smears with a 3.5% solution
of iron-alum in distilled water for one-half hour or overnight,
then wash thoroughly in distilled water.
Then stain from five to twenty minutes in the following
haematoxylin stain: (1) 1% solution of haematoxylin in 95% alcohol.
It takes at least ten days to ripen. (2) A saturated solution of
lithium carbonate. Add to 10 cc. of the haematoxylin solution
5 to 6 drops of the lithium carbonate one. Next wash well and
differentiate with about 1% solution of the iron-alum. Again wash
in water, pass through alcohols to xylol and mount in balsam. With
vegetative amoebae I have obtained beautiful results with vital
staining which can best be done by tinging the faeces emulsion with
a 1% aqueous solution of neutral red. I have also had good results
by emulsifying the faeces in a drop of 1 or 2% formalin and then
adding a drop of 2% acetic acid. The mixture is then tinged with
either neutral red or methyl green.
For distinguishing the encysted form of _Entamoeba coli_ one can
obtain excellent results by emulsifying the faeces in Gram’s iodine
solution. Owing to the glycogenic reaction given by _E. coli_, the
round amoeba, with its 8 nuclei stands out very distinctly.
For diagnosing the 4-nucleated cyst of the pathogenic amoeba one
gets better results with haematoxylin as this brings out not only
the 4 nuclei but the chromidial bodies as well. It was formerly
customary to recommend the administration of salts prior to examining
for amoebae. Walker warns that such a procedure gives us amoebae
which are difficult to differentiate, the nuclear characteristics of
_E. coli_ and the tetragena nucleus of _E. histolytica_ being much
alike as they both contain much chromatin. In a dysenteric stool the
histolytica type of nucleus, containing but little chromatin, does
not resemble the nucleus of _E. coli_.
He prefers the examination of formed stools obtained without a
purgative.
DIFFERENTIATING CHARACTERISTICS OF PATHOGENIC AMOEBAE
(AFTER DOBELL AND O’CONNOR). MOTILE STAGE
-----+----------------+-----------------+----------------+----------------
| Entamoeba | Entamoeba coli | Endolimax nana | Iodamoeba
| histolytica | | | bütschlii
-----+----------------+-----------------+----------------+----------------
Size | 20-30µ | 20-30µ | 6-12µ | 9-13µ
-----+----------------+-----------------+----------------+----------------
Moti-|Very character- |Usually sluggish |Slow progressive|Slight motility
lity| istic. Flows in| but may show | movement when | with movements
| almost straight| considerable | freshly passed.| similar to
| line across | activity when | Later slight | E. coli.
| field. Later | freshly passed. | changes of | Quickly
| becomes less |The movement | shape. Soon | degenerates
| active pushing | consists chiefly| rounds and | and dies.
| out a few, | in changes of | dies. |
| large blunt, | shape without | |
| blade-like | progression. | |
| pseudopodia | | |
| which are per- | | |
| fectly hyaline | | |
| being composed | | |
| entirely of | | |
| ectoplasm. | | |
-----+----------------+-----------------+----------------+----------------
Cyto-|Endoplasm finely|Endoplasm had a |Endoplasm finely|Endoplasm finely
plasm| granular and | bulky granular | granular with | granular and
| uniform in | appearance and | numerous minute| homogeneous.
| appearance. May| contains numer- | food vacuoles |Usually contains
| contain red | ous food | containing | numerous food
| blood cells but| vacuoles charged| bacteria. |vacuoles charged
| bacteria | with bacteria |No sharp line as| with minute
| probably never | and vegetable | a rule between | bacteria. Cysts
| seen in normal | débris. Never | the endoplasm | of this amoeba
| individuals. | contains red | and ectoplasm. | have previously
|Ectoplasm clear | blood cells. No | | been described
| and well | sharp line be- | | been described
| developed. | tween endoplasm | | as “iodine
| | and ectoplasm. | | cysts.”
-----+----------------+-----------------+----------------+----------------
Nuc- |4-7µ. A delicate| 4-7µ. |1-3µ. Vesicular |2-3.5µ. Small
leus | vesicle incon- | Distinguishable.| with delicate | vesicle with
| spicuous or | Stained shows | membrane. | distinct mem-
| invisible. | larger beads of |Stained shows | brane. Stained
|Stained shows | chromatin lining| wall free from | shows wall free
| fine beads of | wall. Karyosome | chromatin. All | from chromatin
| chromatin | spherical, | chromatin cont-| as a rule.
| lining wall. | eccentric and | ained in large,|Typically
|Karyosome small,| larger than | irregular, | chromatin cont-
| spherical and | that of | eccentric | ained in large,
| central. | E. histolytica. | karyosome. | central
| | |Variations in | spherical
| | | shape of | karyosome. Zone
| | | karyosome | between nuclear
| | | characteristic.| wall and
| | | | karyosome
| | | | filled with
| | | | single layer of
| | | |small granules.
-----+----------------+-----------------+----------------+----------------
(Part 1 of 2)
-----------------------------------------------------------------
ENCYSTED STAGE
-----------+------------------------+---------------------------+
| Entamoeba histolytica | Entamoeba coli |
-----------+------------------------+---------------------------+
Size | 7-15µ | 15-20µ |
-----------+------------------------+---------------------------+
Shape | Round. | Round. |
-----------+------------------------+---------------------------+
Wall | Thin. | Thicker than E. |
| | histolytica. |
-----------+------------------------+---------------------------+
Nuclei |Typically shows four |Typically shows eight |
|nuclei. May show one to |nuclei. May show one to |
|four. Nuclei at rest |twenty. Structurally |
|structurally similar to |similar to adult nucleus. |
|that of adult nucleus. | |
| | |
-----------+------------------------+---------------------------+
Chromatoids|Large chromatoids |Large chromatoids may be |
|common. |present but usually absent.|
-----------+------------------------+---------------------------+
Glycogen |Diffuse but not |Relatively abundant in the |
|abundant. |early stages. Scanty or |
| |absent in mature cysts. |
-----------+------------------------+---------------------------+
(Part 2 of 2)
-----------------------------------------------------------------
ENCYSTED STAGE
-----------+---------------------------+-------------------------
| Endolimax nana | Iodamoeba bütschlii
-----------+---------------------------+-------------------------
Size | 7-9µ | 9-12µ
-----------+---------------------------+-------------------------
Shape | Usually oval. | More or less rounded.
-----------+---------------------------+-------------------------
Wall | Thin. | Relatively thick.
| |
-----------+---------------------------+-------------------------
Nuclei |Very small. May show from |One relatively larger
|one to four nuclei. Rarely |nucleus. Differs struct-
|eight. Structurally similar|urally from the adult
|to adult type of nucleus. |type in that the granules
| |in the clear zone become
| |massed at one pole giving
| |an eccentric karyosome.
-----------+---------------------------+-------------------------
Chromatoids|Absent. |Absent.
| |
-----------+---------------------------+-------------------------
Glycogen |Rarely present. |Dense glycogen mass is
| |characteristic.
| |
-----------+---------------------------+-------------------------
Walker also notes the advantages of examining a specimen with a
⅔ inch objective as encysted amoebae are easily picked up. In
opposition to the usual recommendation of text-books to report
only on motile amoebae, he recommends the making of a differential
diagnosis on nonmotile encysted forms. This however is now
generally accepted by experienced workers as true.
The preëncysted _E. histolytica_ has a nucleus much resembling that
of _E. coli_. The presence of the same chromidial bodies one notes
in the cysts is an aid in recognizing this stage. The 4 nuclei of
the cysts are much smaller than the nucleus of the preëncysted or
vegetative stage.
PROPHYLAXIS AND TREATMENT
=Prophylaxis.=—The main consideration is a knowledge of the
importance of the carrier problem. The stools of all persons
preparing food in localities where amoebic dysentery is prevalent
should therefore be examined for the 4-nucleated cyst of the
pathogenic amoeba. It must be remembered that while emetine controls
the dysenteric manifestations of amoebiasis it does not seem to cause
the disappearance of the parasite, so that patients who have had
amoebic dysentery tend to become carriers.
As a matter of fact there is a question as to the possibility
of the emetine treatment acting as a factor for the increase of
carriers.
Vedder considers that while emetine will kill the amoebae deeply
placed in the submucosa it has no effect on the more superficially
located cysts and suggests that it may be possible to treat
carriers by colonic irrigations with quinine or silver salts.
Emetine bismuth iodide has recently been highly recommended as our
best agent for eradication of _E. histolytica_ cysts of carriers.
=Treatment.=—The emetine treatment may now be considered as the
specific one for amoebic dysentery. In Brazilian ipecac about
72% of the total alkaloids is emetine, so that it is better than
Carthagena ipecac which contains only about 40% of emetine. Emetine
was recommended for dysentery as long ago as 1817, but owing to
the impossibility of differentiating between bacillary and amoebic
dysentery, until recently, this method of treatment was little
advocated.
In 1910 Vedder found that emetine was practically without power in
its action on dysentery bacilli but that it would kill amoebae,
even in dilutions of 1 to 100,000. He also found that deëmetized
ipecac was quite inert in its action on amoebae.
In 1912, Rogers, who had for years been an ardent advocate of
the ipecac treatment of amoebiasis, took up the treatment of
amoebic dysentery and its liver complications with emetine.
Reports from all over the world now attest the value of this drug
in the treatment of the acute manifestations of amoebiasis but
unfortunately note the inefficacy of this treatment on the encysted
forms of amoebae.
It is usual to give from ⅓ to ⅔ grain of emetine hydrochloride,
dissolved in sterile saline, by hypodermic injection into the
subcutaneous tissues. Some now give as high as 1 grain daily for
about ten days, but Vedder prefers ⅓ grain repeated 3 times daily. In
these doses there is practically no nausea.
It was found by Baermann and Heinemann that subcutaneous injections
of from 2 to 2½ grains daily caused indisposition and anorexia. The
subcutaneous injections are less painful than the intramuscular
ones.
Rogers has used emetine intravenously in doses of 1 grain without
bad effect.
Vedder calls attention to the fact that the minimal fatal dose
of emetine is several times less when administered to rabbits
intravenously than when given subcutaneously, so that after seeing
rabbits die with what was apparently centric paralysis immediately
after intravenous doses of comparatively small amounts of emetine
hydrochloride he would hesitate before administering 1 grain
intravenously in a human case.
Levy and Rowntree think emetine should not be given intravenously
except in extreme cases. Among ill effects of emetine they note
peripheral neuritis. Kilgore has reported such cases where even
wrist-drop was seen.
Low has treated cases successfully with keratin-coated tabloids of
emetine hydrochloride, giving ½ grain every night. Vedder has not
obtained satisfactory results with the drug by mouth.
Rogers considers that 15 grains of emetine is the fatal dose for
an adult man and as there is possibly a cumulative action it would
seem safer to continue the drug only for ten days and then later
repeat the course of hypodermics. Of course emetine cannot cure the
ulcerative lesions of amoebic colitis and as bacillary infections
are apt to set in when damaged tissues are present and, as such
infections do not yield to emetine, one must be prepared for failure
in treatment of symptoms in such cases.
Recognizing the great importance of immediate treatment to prevent
extension of the ulcerative process, as well as against abscess, the
rule was adopted in the medical care of the English forces, in the
Mediterranean, to give emetine so soon as a case of dysentery was
seen, not waiting for a determination of etiology. The treatment
ordered was 1 grain of emetine, hypodermically, every day for ten
days, or ½ grain morning and evening for ten days. There must not be
any intermission of a single day.
Before the introduction of emetine the usual treatment was with
ipecac.
It was customary to give 20 to 50 grains of powdered ipecac in
capsule, cachet or keratin-coated pills to a patient with an empty
stomach and who had had a dose of morphine or laudanum about 20
minutes before the time for giving the ipecac. The salol-coated
ipecac pills are generally used in America. The patient should be
in bed and should try to yield to the soporific influences of the
opiate. Any flow of saliva should be removed with gauze as its
swallowing would provoke nausea. Some use a mustard poultice to the
epigastrium. It is remarkable the change which this treatment will
effect in the number and character of the stools.
Many now think it advisable to give emetine hypodermically to reach
the amoebae deeply seated and, at the same time, to give ipecac by
mouth to destroy more superficially situated ones, or those in the
lumen of the gut. Alcresta ipecac has been recommended as a good
method of giving ipecac by mouth.
We do not have now the same confidence in emetine injections that
we formerly entertained. In Egypt the combination of emetine
injections with ½ grain keratin coated tablets of emetine by
mouth seemed to give better results in the more chronic stages of
amoebiasis.
Very favorable reports have come from the use of emetine bismuthous
iodide. This drug is given by mouth in doses not exceeding 3 grains
in a day. It is put up in gelatine capsules and a course of treatment
is one 3 grain capsule each night for 12 nights. It is supposed that
there is no action on the drug in the stomach as it is insoluble in
dilute acid but as a matter of fact nausea and vomiting frequently
occur and slight purging is common after its administration. During
the twelve-day course of treatment the patient should remain in bed
and be given a milk diet.
We have recently had success with the administration of ipecac by the
duodenal tube and it might be that bismuthous emetine iodide could be
given in the same way.
Ross thinks that the flushing action of salines, thus washing away
amoebae and necrotic material, is of advantage in amoebic as well as
in bacillary dysentery. He also thinks liquid petrolatum of value.
Some advise the bismuth treatment recommended by Deeks of giving a
large teaspoonful of bismuth subnitrate, in a glass of water, 3 or 4
times during the day.
A decoction made by boiling for 15 minutes one teaspoonful of
powdered chaparro in 8 ounces of water and given one-half hour before
each meal has been reported on favorably. The powdered roots, stems
and leaves of “Chaparro amargosa” are used. This is a plant of Texas
and is named _Castela nicholsoni_. A decoction of about one-half
strength of that taken by mouth is recommended for enemata. Simaruba
bark is recommended by some practitioners. Its action is similar to
chaparro. Benzyl benzoate is recommended for the pains and tenesmus
of amoebic dysentery as well as bacillary dysentery. Twenty drops of
the 20% alcoholic solution are given three times daily.
Many drugs have been recommended for colon irrigation of which the
favorite is probably quinine muriate in dilution of 1 to 1000 or 1
to 2500. Inject 2 or 3 pints slowly by gravity. Protargol in 1 to
500 solution is better than silver nitrate in 1 to 2000. Emetine
enemata do not seem to be of much value.
In very serious cases, particularly when gangrenous change in
the mucosa may be present, the operation of appendicostomy seems
indicated, following which a catheter is inserted and the large
intestine irrigated with a 1% solution of bicarbonate of soda to wash
away the mucus and later with a boracic acid solution of 1 to 125 or
1 to 10,000 of potassium permanganate.
In a discussion as to certain surgical considerations in connection
with appendicostomy Muller notes that the right rectus incision
is to be avoided on account of danger of gangrene from pressure
of rectus on the stitched-up appendix. He also thinks that
appendicostomy is much safer than caecostomy on account of the
frequent thinning of the walls of the caecum. For irrigation he
prefers a 1 to 500 solution of collargol.
In treating dysentery cases rest in bed and the use of a
nonirritating diet are advisable.
The return of the increase of large mononuclears to normal may be
used as an index to cure.
Walker and Emrich have recently reported success in treatment of cyst
carriers by giving oil of chenopodium in 3 hourly doses of 16 minims,
followed by castor oil and preceded by a dose of magnesium sulphate.
CHAPTER XI
LIVER ABSCESS
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—Although Hippocrates noted the method of evacuating
abscess of the liver by caustics there was very little known about
the condition until during the last century.
The history in connection with the finding of amoebae in liver
abscesses is of very recent date (1887) and is taken up under the
history of amoebic dysentery.
=Geographical Distribution.=—Concisely one may state that the
distribution of liver abscess is in relation to the existence of
amoebic dysentery. It is particularly prevalent in those centers
of amoebic infection where there are many white men having little
knowledge of the conditions necessary for the maintenance of health
in the tropics.
In liver abscess, as with blackwater fever, it is education rather
than acclimatization that brings about a diminution of these
tropical diseases.
For several years subsequent to the American occupation of the
Philippines amoebic dysentery and liver abscess were common but in
more recent years liver abscess has become rare in Americans and
amoebic dysentery much reduced in prevalence.
More temperate living results in less storing up of fat in the
liver and an organ more resistant to infection.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—The dislodgment of amoebae-containing material from
amoebic intestinal ulcerations and the plugging of the portal
capillaries by such emboli give us the starting point of a liver
abscess. The exciting cause is _Entamoeba histolytica_ which in the
liver continues the same production of a gelatinous necrosis as is
carried on in the submucosa of the large intestine or appendix.
This pathogenic amoeba is fully described under amoebic dysentery.
As to obtaining a history of amoebic dysentery in liver abscess
cases we have the following statistics:
500 cases with dysentery findings in 60% (Kartulis).
444 cases with dysentery findings in 59% (Zancarol).
500 cases with dysentery findings in 85% (Kelsch and Kiener).
63 cases with dysentery findings in 90.5% (Rogers).
38 cases with dysentery findings in 85% (Seamen’s hospital
autopsies).
Amoebic liver abscess is exceedingly rare among children and
probably 10 times less common among women than men.
Of 40 cases of liver abscess Waring noted intemperance in 67.5% and
authorities generally insist upon the importance of the abuse of
alcohol as a predisposing factor.
Natives of India very rarely develop liver abscess but it has been
noted that when they begin to follow the customs of Europeans, as
to eating and drinking, such lesions become more common in them.
As to the proportion of cases of amoebic dysentery which give
rise to liver abscess only the statistics of those who have
differentiated between bacillary and amoebic dysentery are of any
value. Such statistics would indicate that about 20% of the cases
of amoebic dysentery are complicated by liver abscess.
Liver abscess may be present without demonstrable lesions in the
large intestines, such lesions having healed or the intestinal
involvement having been so slight as not to have caused other than
microscopic changes.
It is a well-known fact that liver abscess may set in years after a
patient has left the tropics and years after the occurrence of any
dysenteric manifestations.
PATHOLOGY
There seems little doubt but that the amoebae in the thrombosed
terminals of the portal vein are carried by way of the upward current
into the liver where they lodge in the liver capillaries, Councilman
and Lafleur having found amoebae in such emboli.
Another view is that the amoebae may wander across the abdominal
cavity and enter the liver in this way. This seems as improbable as
that view which considers a possible entrance by way of the bile
duct. Bile is toxic to amoebae and it would be difficult to explain
their presence in the small intestines.
In 639 cases Roux found the abscess in the right lobe in 70% of the
cases.
Other statistics give about 75% for the right lobe, 10% for the
left lobe, 4% for the lobus Spigelii and in about 10% of cases
abscesses are found in both right and left lobes.
In 562 cases Zancarol found a single abscess in 60% of the cases.
In 288 cases Waring found a single abscess in 61.5%, double abscesses
in 11.5% and multiple abscesses in 27%. The favorite site of liver
abscess is the superior and posterior part of the right lobe and near
its surface.
The abscesses vary enormously in size, some being no larger
than a walnut while others may contain a quart or more of pus,
exceptionally as much as a gallon. The pus is typically of a
chocolate color and contains degenerated liver cells, granular
débris and often haematoidin and Charcot-Leyden crystals. There is
an absence of polymorphonuclears. It may however be creamy in color.
In Strong’s cases about 50% of the abscesses showed bacteria upon
culturing, the organisms noted being staphylococci, streptococci,
_B. coli_ and _B. pyocyaneus_.
The walls of liver abscesses are rather shaggy and the amoebae are
found deeply located.
It is probable that the necrotic process, set up by the amoebae,
begins in the interlobular capillaries although it may at times
begin within the lobule.
Microscopically, the necrotic abscess wall shows amoebae in its
depths but necrosis of the surrounding tissue beyond the zone of
the amoebae is noticeable which would suggest the elimination
by the amoebae of some toxic substance. There is an absence of
polymorphonuclear infiltration around the abscess.
Surrounding the abscess wall there is a zone of marked hyperaemia.
Amoebae may be found in this area as well as in the abscess wall.
If the liver abscess is not treated by emetine or with this drug
and some surgical procedure the tendency is for rupture to occur
and Cyr’s statistics show that of 159 cases rupture occurred
as follows: lungs 59, pleural cavity 31, peritoneal cavity 39,
intestines 8, stomach 8, vena cava 3, kidneys 2, bile ducts 4,
pericardium 1 and externally 2.
SYMPTOMATOLOGY
Although the statistics would indicate that a history of amoebic
dysentery has been obtained in only from 60 to 90% of cases of liver
abscess, yet, when we consider that amoebic lesions of the large
intestines have been frequently noted at autopsy in those who had
never shown symptoms of dysentery during life, we are forced to
believe that amoebic lesions of the appendix or large intestines are
necessary factors in the production of liver abscess. Consequently, a
history of amoebic dysentery is one of the most important points to
consider in the making of a diagnosis of tropical liver abscess.
=Tropical Liver.=—There is also much evidence to be obtained from
statistics and otherwise to support the view that the amoebic
infection of the liver is only possible in a person whose liver
has been functionally impaired. To this condition the designation
tropical congestion of the liver or simply tropical liver has been
applied. There is much to support the view that, in the tropics,
the intestines and liver take the place of the thoracic organs
in being subject to congestion. In temperate climates excesses
and exposure to debilitating influences result in coryza or
pneumonia. In the tropics we have diarrhoea and congestion of the
liver. Tropical liver is recognized by vague digestive troubles,
high-colored urine, loss of energy, irritability, with a sensation
of fullness in the region of the liver which is generally described
by the patient’s statement that he feels his liver. There may be
pain referred to the right shoulder and the liver may be tender on
palpation.
By the discontinuance of alcohol and highly spiced foods, with
treatment by phosphate of soda or sodium sulphate, together with
general care of the health, the patient may recover completely.
Rogers recognizes a condition which he terms the _pre-suppurative
stage of amoebic hepatitis_ in which the amoebae from dysenteric
lesions have lodged in the portal terminals of the liver but in
which abscess formation has not taken place.
At this stage we have a leucocytosis in which the
polymorphonuclears are but little increased in percentage with a
low remittent fever. At this time Rogers considers that the disease
may be cured by emetine or ipecac and liver abscess avoided.
=A Typical Case of Liver Abscess.=—Following a case of amoebic
dysentery, during the period of convalescence or subsequently, a
rather irregular type of fever is noted, which shows an evening rise
with sweatings which tend to become colliquative. From a marked
feeling of weight in the region of the liver there may later develop
tenderness or pain upon palpation of the liver. Of importance is
the fact that there is no associated splenic enlargement. In the
majority of cases the right side of the liver enlarges in an upward
direction. A tape-measure will often show enlargement of the right
side. Pain referred to the right shoulder is often complained of when
the abscess is located in the upper convex part of the liver but,
when nearer the inferior concave surface, there may be pain referred
to the region of the appendix. When located in the left lobe the
symptoms may be considered as of gastric origin.
The upward enlargement of the liver as shown by X-rays is of great
value in diagnosis, but an abscess located in the center of the liver
is not indicated by such rays.
There is a marked tendency to splint the liver so that the patient
tends to lie towards the right side and when walking applies his
right arm and forearm to his side, which led Koch to remark, “It is
as if he carried his abscess under his arm.” The right rectus often
shows rigidity.
Auscultation of the base of the right lung reveals a moist
crepitation which, together with a dry cough (tussis hepatica),
the fever, evening sweats, anaemia and emaciation, may suggest
tuberculosis. The respirations are shallow as deep inspiration tends
to cause pain. It must be remembered that cases of liver abscess
have been reported where there were practically no symptoms.
Insomnia is a marked feature in many cases. Jaundice is rare,
but an earthy color or subicteroid tinging is often noted. The
superficial veins may be enlarged.
The urine is scanty and high-coloured, frequently with a marked
increase in the ammonia nitrogen. Urobilin may be present in
considerable amount.
There is a rather constant but low leucocytosis of from 12 to 20
thousand, which shows only about 70% of polymorphonuclears with an
increase in large mononuclears up to 10 to 15%.
The final proof is the obtaining of the chocolate-coloured or anchovy
sauce-like pus by exploratory puncture.
[Illustration: FIG. 61.—Temperature chart of liver abscess.]
This pus does not contain pus cells but only granular débris,
cholesterin crystals and is often bacteriologically sterile. The
amoebae, being in the abscess wall, are not apt to be found when
pus is at first withdrawn. Owing to the tendency of liver abscess
to rupture into the lungs the first indication of the true nature
of a prolonged hectic fever may be obtained when the characteristic
pus is expectorated by the patient.
Attended with progressive emaciation and exhaustion the patient,
as a rule, after a prolonged illness, dies, unless operative
procedures cure him or some intercurrent disease brings about his
death.
Symptoms in Detail
_Onset and the Fever Chart._—The onset is at times so insidious
that there may be no symptoms and yet a liver abscess be found at
autopsy. Usually following convalescence after amoebic dysentery an
irregular fever sets in which becomes hectic in character. Profuse
sweats accompany the evening rise. The morning temperature is
frequently normal and there may be frequent apyretic intervals.
_The Respiratory System._—Crepitation at the right base, a dry
cough (tussis hepatica) and shallow respirations are features of
the disease.
_The Nervous System._—Pains in the right shoulder are connected
with irritation of the branches of the phrenic nerve.
The patient is irritable and often complains of insomnia.
The right rectus tends to be somewhat rigid and decubitus is dorsal
or toward the right side.
_The Liver and Spleen._—The liver is tender and as the abscess in
nine-tenths of the cases is located in the right lobe and generally
toward the upper convex surface we have an enlargement upward.
There is very rarely any jaundice.
The urine shows an excess of urobilin and of nitrogen eliminated
as ammonia. When the abscess is in the left lobe the condition is
apt to be considered as some gastric disturbance. The spleen, as a
rule, shows no enlargement.
_Examination of the Blood._—There is usually a moderate
leucocytosis with normal polymorphonuclear percentage and increase
in the large mononuclears.
[Illustration: FIG. 62.—Liver abscess. X-ray photograph taken from
the side and showing upward enlargement of liver. (Ruge and zur Verth
after Béclére.)]
DIAGNOSIS
=Clinical Diagnosis.=—Of greatest importance is a history of a
previous dysentery although it must be remembered that liver abscess
may appear in one who has never had dysenteric symptoms. Fever
of a hectic type with crepitation at right base, pain and upward
enlargement of the liver are most significant.
The X-ray may confirm the diagnosis of upward enlargement which may
be as high as the angle of the scapula. The majority of conditions
causing enlargement of the liver give a downward enlargement.
The amelioration of symptoms by giving emetine hypodermically for two
or three days is diagnostically exceedingly important.
Syphilitic gummata may give the picture of liver abscess,
especially as regards the fever and loss of weight. Iodide of
potash is said to be of use in differentiating, as it controls the
fever of syphilis. The gummatous enlargement, however, is irregular
and projects downward.
Suppurative pylephlebitis generally arises from infections of the
colon or appendix. This condition as well as pyaemic (multiple)
abscesses of the liver is apt to show jaundice.
In suppurative cholangitis and cholecystitis we get a history of
biliary colic, jaundice and usually a marked point of tenderness
at the tip of the ninth rib and a tumor in the region of the gall
bladder. Abscess of the left lobe may give the symptoms of gastric
trouble.
In differentiating empyema we usually have a history of pleurisy or
pneumonia.
Suppurating hydatid cyst which may be confused with liver abscess
is most surely differentiated by finding echinococcus hooklets.
Then too the complement fixation test for hydatid disease will
differentiate.
Tuberculosis is often thought of, particularly when a liver
abscess ruptures through the lungs. Malaria is also usually
suspected. Abscess in the kidney or perinephritic region may be
very confusing. In an abscess of the abdominal wall an exploring
needle does not move up and down with respiration as it does when
penetrating a liver abscess cavity.
=Laboratory Diagnosis.=—The chocolate-colored pus of a liver
abscess, when there has been no bacterial contamination, shows an
absence of polymorphonuclears and does not at first show amoebae.
These appear in the pus coming from the drainage tube about the
third day. Cholesterin and haematoidin crystals may be found in the
granular débris of a fresh drop of pus used for examination for
amoebae.
Liver abscess usually shows a moderate leucocytosis with a normal
polymorphonuclear percentage and an increase of large mononuclears
and transitionals to about 12 to 20%.
According to Schilling-Torgau we may have a perfectly normal white
count and polymorphonuclear percentage and yet have evidence of the
presence of liver abscess in his modification of Arneth’s index, so
that in an apparently normal differential count we may find that
½ or more of the polymorphonuclears are of a less mature type and
in cases where there are many immature polymorphonuclears we have
indications which force a very cautious or unfavorable prognosis.
Thus a differential count of 33% band-form polymorphonuclears
and 39% of normal nucleated ones would make us give a cautious
prognosis, while one with 1% myelocytes, 22.5% immature
polymorphonuclears, 21% band-form nucleated ones and 30% of normal
ones would make for a very bad prognosis. We have a displacement to
the left. Normally there are 63% of normal polymorphonuclears, 4%
of band-form and no immature ones or myelocytes.
One may find an iodophilia in liver abscess.
Of the functional liver tests we may determine the ammonia
quotient, the percentage of N eliminated as ammonia being increased
in abscess of the liver. The same is true of the lipase test.
Probably the most specific test for disturbances of the hepatic
function is that for urobilinogen. The test is made by adding 5 to
10 drops of Ehrlich’s aldehyde reagent to 5 cc. of perfectly fresh
urine when a positive reaction gives a fine cherry-red color.
PROPHYLAXIS AND TREATMENT
=Prophylaxis.=—The prophylaxis is the same as that for amoebic
dysentery plus avoidance of anything which reduces the functional
power of the liver, such as overfeeding, alcoholic excesses, etc.
It is well to remember that abscesses may occur months or even two
or three years after an attack of amoebic dysentery, consequently
it is well to give a grain of emetine on two or three successive
days of each month following an acute attack.
=Treatment.=—Leaving out of consideration the pre-suppurative stage
of amoebic hepatitis which, according to many authorities, responds
to injections of emetine, it may be stated that the treatment of
liver abscess is entirely surgical and such treatment should be
instituted the moment the diagnosis is made. The earlier a liver
abscess is drained the less run down will be the patient, the more
rapid the convalescence and the better the prognosis.
Until recently surgical authorities condemned severely the trocar
and cannula method of operation, but with the introduction of
emetine there are now those who believe that such a procedure may
suffice and a more radical operation not be necessitated.
Prior to introducing the trocar and cannula the usual procedure
is to use an aspirating needle of about ⅛ inch bore and 3½ inch
length. If the needle happens to be longer it should not be passed
deeper than 3½ inches, in a person with a 32-inch chest, in order
surely to avoid the vena cava. If there are no distinct localizing
signs the needle should first be introduced in the eighth or ninth
interspaces in the anterior axillary line and pushed backward,
inward and slightly upward. Manson recommends at least 6 punctures
before abandoning exploration. Cantlie does not think that a
moderate degree of haemorrhage from the puncture of the liver will
do harm in a case which is simply a liver congestion. One should
always be ready to operate in case pus be found in the exploring
needle. Leaving the needle in situ a small skin incision is made
and a 4 or 5 inch by ⅜ inch trocar and cannula introduced along
the line of the needle. Withdrawing the trocar some of the pus is
allowed to escape through the cannula and there is then introduced
a 6 × ½ inch piece of strong rubber drainage tubing, one end of
which has lateral fenestrations but a closed tip in order that a
long steel pin may put the tubing on the stretch so that it passes
the smaller lumen of the cannula.
The cannula is then slipped out over the tubing and the external
stretched end of the tubing released so that the contracting rubber
fills the puncture. The steel pin used for introducing the rubber
tube is then withdrawn and the tubing transfixed close to the skin
with a safety pin.
After the cavity has drained of pus a dressing is applied. There
are some who advocate aspiration alone without subsequent drainage.
The dressing should be changed frequently and a connecting tube,
draining into an antiseptic-containing bottle, should be attached
to the tube in the cavity in order to obtain a syphoning action.
Some aspirate and inject into the cavity about 2 ounces of 1 to
1000 emetine solution.
Some report favorably from the use of 1 to 1000 quinine
irrigations. At present the hypodermic use of emetine will probably
obviate the necessity of any irrigation.
There are those who think that a preliminary aspiration, followed
by incision, after a few days of improvement in general condition,
is the best method in serious cases.
It is usual to recommend a general anaesthetic when introducing the
aspirating syringe or trocar and cannula. Local anaesthesia with
quinine and urea hydrochloride, however, will usually suffice and
lessen the dangers of shock in bad cases. Rib resections and even
intra-abdominal procedures are best done under local anaesthesia
provided the operator is familiar with the technic.
Newman has recently warned against the use of the small aspirator
for diagnosis, pointing out that it is unreliable and that the
diagnosis should be made by other diagnostic aids, including
hypodermic use of emetine. He notes the occurrence of death from
internal haemorrhage, the interference of the needle with the
surgical incision and, further, the obscuration of the field of
operation by pus where no adhesions exist and, finally, the danger
of general peritoneal infection from a leak. He notes that the
cavity may be under tension and that the pus may force itself along
the track of the needle. He recommends incision and packing with
gauze where adhesions do not exist and the exploration of the liver
with dressing forceps instead of cutting into the liver with the
knife.
USUAL OPERATION FOR LIVER ABSCESS
Either a vertical incision about the middle of the right rectus
(Bevan) or a Kocher incision, parallel with the costal margin, may
be used. The latter incision favors hernia if prolonged drainage is
required. The hand is introduced into the abdominal cavity and the
liver palpated. Often the borders of the site of a liver abscess give
a hard feeling on palpation. If adhesions are not present the area
should be packed off with gauze and the cavity opened by a dressing
forceps, haemostat or thermo-cautery. It is often advisable to
introduce a trocar and cannula and to drain off the excess of pus.
Where the abscess is situated far back or high up in the liver
the transpleural route is to be preferred to the abdominal one.
Make a 3 or 4 inch incision over the 9th rib with its center in
the line of the angle of the scapula. Excise about 2 inches of
rib subperiosteally. An assistant presses a roll of gauze against
the tissues above the line of incision to prevent air entering
the pleural cavity. Later the upper flap may be sutured to the
endothoracic fascia. Even if the pleural cavity should be opened
and air enter no serious result will follow although it is an
accident to be avoided if possible. The diaphragm is now cut
through and the liver exposed and after packing gauze around the
area to be opened, the abscess cavity is entered and drained as
previously described.
McDill prefers to resect 2 or 3 inches of both 9th and 10th ribs
in the midaxillary line. The muscle wounds made in resection are
then closed by catgut. This movable wall is now forced against the
diaphragm with a roll of gauze pressed inward by an assistant.
A 3-inch incision is now made through this bone-free wall near
the upper border of the 11th rib, going through diaphragm and
exposing the liver. The edges of the wound in the thoracic wall
and diaphragm are now clamped together by haemostats to close off
the pleural cavity. Later catgut sutures are substituted for the
forceps. The liver often bulges into the wound. Finding the abscess
by a palpating finger as a rather firm area in a less resistant
liver surface we introduce a forceps or aspirating needle or trocar
and proceed as above noted.
There are indications that the use of emetine subcutaneously may
make the more radical operations unnecessary. In a recent symposium
on liver abscess many of the papers would indicate a preference for
aspiration without drainage coupled with emetine subcutaneously.
Rogers, in a recent article, notes that a case of liver abscess was
cured by emetine without any form of operation. Recent experience,
however, would indicate that it is necessary to evacuate the pus to
effect a cure.
SECTION II
DISEASES DUE TO BACTERIA
CHAPTER XII
BACILLARY DYSENTERY
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—Epidemics of dysentery have been noted since ancient
times, the widespread and fulminating nature of such outbreaks in
times of war and famine having impressed observers in all ages. The
disease is mentioned in the Ebers Papyrus (1600 B. C.).
Herodotus referred to an epidemic of dysenteric nature in the
Persian Army and Hippocrates described the dysenteric syndrome. It
has been known in India since remote times.
While the etiology of amoebic dysentery was thoroughly investigated
and its connection with amoebae fairly well established during the
decade from 1880 to 1890 it was not until 1898 that Shiga isolated
the causative organism of bacillary dysentery. It is true that
Chantamesse and Widal drew attention to a bacillus isolated from
large intestines, mesenteric glands and spleen of cases of tropical
dysentery but the organism was not clearly differentiated from
_Bacillus coli_. Celli isolated an organism which coagulated milk
and produced gas in glucose media. This organism which Celli called
_B. coli dysentericus_, differs culturally from _B. dysenteriae_.
=Geographical Distribution.=—Bacillary dysentery differs from the
amoebic form in that it tends to appear in extensive epidemics
spreading over temperate as well as tropical and subtropical parts
of the world.
It is peculiarly liable to follow the movements of armies in any
part of the world and like typhoid fever its distribution is one of
hygienic rather than geographical influence.
Infections with various strains of dysentery bacilli are important
factors in morbidity among infants and young children in whatever
part of the world the question has been investigated. The disease
is prone to prevail in lunatic asylums whether in temperate or
tropical parts of the world.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—During a very fatal epidemic of dysentery in Japan
Shiga isolated an organism, _Bacillus dysenteriae_, from dysenteric
stools of 36 cases, which bacillus he found to be agglutinated by the
serum of the patients. He reported this work in 1898. In 1900, Kruse
isolated an organism from patients in an epidemic of dysentery in
Germany which corresponded to that of Shiga. In 1900, Flexner, Strong
and Musgrave, working in Manila, not only encountered an organism
similar to that of Shiga but also an organism of wider fermentative
action. Dysentery has resulted from accidental laboratory infections
and Strong produced dysentery in a prisoner condemned to death
through ingestion of cultures.
In 1903, Hiss and Russell isolated an organism from a fatal case of
diarrhoea in a child to which they gave the name “Y”.
On the whole, dysentery bacilli correspond culturally with the
typhoid bacillus except in showing slightly weaker fermentative
action on carbohydrates. The main point of difference however is
their absolute nonmotility.
The characteristic of nonmotility is of greatest differentiating
value and the reports of slight motility are probably from
misinterpretation of molecular movement as motility. The dysentery
bacilli do not form those thread or whip-like filaments so
characteristic of typhoid cultures and are somewhat plumper. The
dysentery bacillus is not found in the blood and hence is not
eliminated in the urine, although recently there have been reported
rare cases where dysentery bacilli were isolated from the blood. It
is found in mesenteric glands. In dysentery patients agglutination
phenomena do not show themselves until about the tenth day from
the onset. Hence, this procedure is of no particular value in
diagnosis. It is of value, however, to identify an organism
isolated from the stools at the commencement of the attack, using
serum from an immunized animal or a human convalescent for the
agglutination test.
There seems to be only moderate agglutination power in the serum
of convalescents from Shiga strains. Flexner strains give higher
agglutinations, but early in convalescence the serum is not apt to
have a titre of more than 1-150.
Dysentery bacilli produce a coagulation necrosis of the mucous
membrane of the large intestine and occasionally of the lower
part of the ileum. Polymorphonuclears are contained in the fibrin
exudate.
It was formerly thought that these lesions were of local origin,
but the present view is that toxins are produced which, being
absorbed, are eliminated by the large intestine with resulting
necrosis. Flexner, by injecting rabbits intravenously with a toxic
autolysate, produced characteristic intestinal lesions. The toxin
withstands a temperature of 70°C. without being destroyed. The
toxin may cause joint trouble.
There are two main types of dysentery bacilli:
1. Those producing acid in mannite media—the acid strains
(Flexner-Strong types).
2. Those not developing acid in mannite (Shiga-Kruse types). The
Shiga type is very toxic in cultures, while the Flexner type seems to
be less so. An organism resembling the Shiga bacillus but producing
indol is the Schmitz bacillus. It does not appear to be pathogenic.
In immunizing horses for the production of antidysenteric serum it
is customary to use both Flexner and Shiga strains, thus producing
a polyvalent serum.
Lentz recognizes 4 types of dysentery bacilli for the
differentiation of which he uses mannite, maltose and saccharose
bouillon with litmus as an indicator.
------------+-------------+---------+--------+-------
| Shiga-Kruse | Flexner | Strong | “Y”
------------+-------------+---------+--------+-------
Mannite | Blue | Red | Red | Red
Maltose | Blue | Red | Blue | Blue
Saccharose | Blue | Blue | Red | Blue
------------+-------------+---------+--------+-------
The following table gives the more important cultural
characteristics of the intestinal bacilli which might be confused
with the various strains of dysentery bacilli.
Key for column headings:
A - Motility
B - Milk coagulation
C - Glucose
D - Maltose
E - Lactose
F - Mannite
G - Saccharose
H - Glucose neutral red bouillon
I - Butt
J - Slant
K - Indol
------------------+---+---+-------+---+---+---+---+---+----+--------+---
| | |Litmus | | | | | | |Russel’s|
| | | Milk | | | | | | | Medium |
| | |-------| | | | | | |--------|
| | |1st|3d | | | | | | | |
| A | B |day|day| C | D | E | F | G | H | I | J | K
------------------+---+---+---+---+---+---+---+---+---+----+---+----+---
B. faecalis | | | | | | | | | | | | |
alkaligines | + | - |Alk|Alk| O | O | O | O | O | O | O | O | -
------------------+---+---+---+---+---+---+---+---+---+----+---+----+---
B. typhosus | + | - | A | A | A | A | O | A | O | O | A |Alk | -
------------------+---+---+---+---+---+---+---+---+---+----+---+----+---
B. dysenteriae | | | | | | | | | | | | |
(Shiga-Kruse) | - | - | A |Alk| A | O | O | O | O | O | A |Alk | -
------------------+---+---+---+---+---+---+---+---+---+----+---+----+---
B. dysenteriae | | | | | | | | | | | | |
(Flexner-Strong) | - | - | A |Alk| A | A | O | A | O | O | A |Alk | -
------------------+---+---+---+---+---+---+---+---+---+----+---+----+---
B. dysenteriae | | | | | | | | | | | | |
“Y” | - | - | A |Alk| A | O | O | A | O | O | A |Alk | +
------------------+---+---+---+---+---+---+---+---+---+----+---+----+---
B. Morgan No. 1 | + | - | O | O |A G| O | O | O | O | G | | | +
------------------+---+---+---+---+---+---+---+---+---+----+---+----+---
B. paratyphosus A | + | - | A | A |A G|A G| O |A G| O | G |A G|Alk | -
------------------+---|---+---+---+---+---+---+---+---+----+---+----+---
B. paratyphosus B | + | - | A |Alk|A G|A G| O |A G| O |G Fl|A G|Alk | -
------------------+---+---+---+---+---+---+---+---+---+----+---+----+---
B. enteriditis | | | | | | | | | | | | |
(Gaertner.) | + | - | A |Alk|A G|A G| O |A G| O |G Fl|A G|Alk | -
------------------+---+---+---+---+---+---+---+---+---+----+---+----+---
B. coli | + | + | A | A |A G|A G|A G|A G| O |G Fl|A G| A | +
------------------+---+---+---+---+---+---+---+---+---+----+---+----+---
B. lactis | | | | | | | | | | | | |
aerogenes | - | + | A | A |A G|A G|A G|A G|A G|G Fl|A G| A | -
------------------+---+---+---+---+---+---+---+---+---+----+---+----+---
B. cloacae | + | + | O | A |A G|A G|A G|A G|A G|G Fl|A G|Alk | +
------------------+---+---+---+---+---+---+---+---+---+----+---+----+---
B. proteus | | | | | | | | | | | | |
vulgaris | + | | O |Alk|A G|A G| O | O |A G| G |A G|Alk | -
------------------+---+---+---+---+---+---+---+---+---+----+---+----+---
Of the above tabulated nonspore bearing, Gram-negative, intestinal
bacilli only _B. lactis aerogenes_ shows capsules and only _B.
cloacae_ and _B. proteus vulgaris_ liquefy gelatin. In the table +
= positive, - = negative, O = no change, A = acid, Alk = alkaline,
G = Gas and Fl = fluorescence in neutral red bouillon.
=Epidemiology.=—There is probably no disease, with the possible
exception of cholera, where those attending a patient are so liable
to have their hands contaminated with infectious material.
The terrible frequency of the stools and the tendency of the
mucilaginous mucoid mass to become smeared over the buttocks and
clothing of the patient make it onerous for an attendant to carry
out methods of personal protection. In a family, where the mother
may have to care for a sick child, and prepare food for the other
children and herself, the opportunities for the spread of the
infection in the family are great. In military barracks, as well
as in other institutions where large numbers make use of the same
water-closet accommodations, the chances of contamination of the seat
by a patient responding to the frequent and imperious demands for
evacuation are most probable, with subsequent transference of the
infectious material to others. Bacillary dysentery is peculiarly an
institutional disease and tends to spread in jails, orphan asylums
and the like. A carrier is a particular source of danger in such an
institution.
Not only is there the danger from a patient ill with bacillary
dysentery but as well that from the convalescent or chronic
carrier. Such carriers are particular sources of danger where they
take part in the preparation of food for others. It is now thought
that the striking prevalence of the disease in insane asylums is
associated with the difficulty of making such patients observe the
proper care of their hands as well as their persons.
Friedmann has recently noted an outbreak of dysentery due to the
Shiga type of bacillus which was instituted by a soldier returning
to the barracks from a furlough.
There resulted 86 cases in the man’s regiment of which 49 belonged
to his own squadron. The spread of the disease was traced to the
latrines. The epidemic was suppressed by the enforcement of the
most rigid rules of cleanliness especially as regarding washing of
the hands after leaving the latrines.
The stools of the convalescents were examined and no man was
discharged from hospital until his stools were negative for
dysentery bacilli upon 3 successive tests in fourteen days.
Isolation of the bacilli from convalescents was obtained in 40
patients only for periods under fourteen days while with 27 others
such carrying of bacilli lasted from two weeks to one month.
As the dysentery bacillus does not invade the blood stream we do
not find it in the urine so that to a certain extent the dysentery
bacillus carrier is less dangerous than the typhoid one.
There have been reports of isolation of Flexner and “Y” type
bacilli from monkeys and rabbits but there is nothing to indicate
that any other host than man is of importance.
Flies are undoubtedly of as much importance in the spread of
bacillary dysentery as of typhoid.
The possibility of infection through the medium of soiled clothes,
sent out for washing, is to be thought of.
There have been several instances of transference of the disease by
the water supply.
In times of war, with large forces of soldiers, bacillary dysentery
tends to become the most important disease encountered by military
surgeons. During the Civil War there were 285,000 cases of dysentery
in the Federal army.
It is possible that infectious material may be disseminated as dust
and thus contaminate food.
PATHOLOGY
Injection of dysentery bacilli into the peritoneal cavity of guinea
pigs causes a muco-sanguinolent diarrhoea with congestion of and
haemorrhage into the caecum. There is also a haemorrhagic peritoneal
exudate.
In the rabbit lesions similar to those in man are obtained as well
as paralysis of the limbs.
It is therefore thought that there are two toxins concerned in the
pathology of bacillary dysentery, one a neurotoxin which may cause a
peripheral neuritis or joint trouble and the other a toxin which acts
on the lower bowel, especially the caecum, with the production of
congestion and coagulation necrosis of the mucosa.
Cases have been reported where the adrenals showed congestion and
necroses, as if subjected to the action of a toxin.
In man we have an acute inflammation of the mucosa of the large
intestines and, in the tropics, we frequently find the lower
third of the ileum involved as well. In amoebic dysentery the
process rarely extends beyond the ileo-caecal valve. A catarrhal
process with hyperaemia and sero-purulent exudate is first noted,
to be succeeded by fibrin formation in the mucosa, a process of
coagulation necrosis. When the process invades the ileum there
is no involvement of Peyer’s patches. Virchow noted the greater
intensity of the process in the region of the rectum, sigmoid
flexure and ileo-caecal valve.
As a rule, however, the entire large intestine is grayish red,
looking like lustreless red velvet. Later on we may have irregular
islands of grayish membrane formation surrounded by the red swollen
congested gut. The solitary glands are usually swollen and may
soften and ulcerate, having the submucosa as a base. Ulceration in
bacillary dysentery is superficial rather than deep as with amoebic
dysentery. The ulcers of bacillary dysentery involve the free folds
of the intestine and extend transversely while amoebic ulcers run
longitudinally. The intervening mucosa is unaffected in amoebic
ulcerations while in bacillary ones it is inflamed.
Microscopically we note marked congestion of the blood vessels
of the mucosa and submucosa with dilated lymph spaces full of
polymorphonuclear cells.
In the mucosa we find an outpouring of pus cells which are
entangled, along with the glandular structures of the mucosa, in a
fibrinous exudate which causes necrosis of the mucosa (coagulation
necrosis).
In chronic bacillary dysentery, according to Rogers, the lesions
are limited to the lower portion of the large gut and rarely extend
above the descending colon.
In this region one finds serpiginous ulcerations separated by
islands of mucosa. Willmore and Savage have noted autopsy findings
of what was practically a large granulating surface over the whole
large intestine, in cases which had apparently recovered, with the
exception of a prolonged convalescence.
SYMPTOMATOLOGY
Bacillary dysentery usually runs an acute course, rarely relapsing
and but occasionally going on to a chronic condition. The period of
incubation is usually from two to seven days although accidental
infection with bacilli in the laboratory has given an incubation
period approximating twenty-four hours. Periods of incubation longer
than a week can probably be explained as for cholera, such cases
being in those who are healthy carriers, but by reason of some
gastro-intestinal upset the quiescent bacilli take on pathogenic
activity.
In temperate climates and in particular when the infecting organism
is a Flexner type the case may appear as a watery diarrhoea
associated with colicky pains and anorexia. The stools soon become
more scanty in amount, frequent in number and associated with
straining. This is followed by mucous stools more or less tinged
with blood. The temperature is normal or but slightly elevated and
the patient does not seem ill.
In the tropics and in temperate climates where the Shiga type
bacillus is the infecting organism the onset is usually rather
sudden with malaise, abdominal pain and a diarrhoea, which only
temporarily relieves such pain. This initial diarrhoea is soon
followed by the characteristic dysentery stool and the pains, which
latter tend to centre about the umbilicus and to become continuous.
There is usually loss of appetite and slight nausea and the patient
may at times show a very slight tendency to flightiness. The mind
however is usually clear. Fever of moderate degree is not uncommon
and it may be quite marked,—up to 104°F. Ingestion of food or
drink or any movement of the body brings on a desire for defecation.
The number of stools, which in mild cases number 15 to 30, may become
excessive, even more than one hundred in twenty-four hours, and the
tenesmus most torturing, so that excoriations around the anus and
at times prolapse of the bowel intensify the distressing clinical
picture. In acute cases the stool may be almost pure blood with only
an admixture of mucus.
Vesical tenesmus may be present and the urine may be diminished in
amount.
There is a toxic effect on the heart so that the pulse tends to
become accelerated and weak. Bacillary dysentery may show a moderate
leucocytosis with increased polymorphonuclear percentage instead of a
large mononuclear one as with amoebic dysentery.
At times, however, the lymphocytes may be the leucocytes showing
the greatest relative increase.
_Collapse Types._—In the most severe types of dysentery we may have
an abrupt onset with rigors and vomiting and a high fever. This fever
gives way to a subnormal temperature and the patient shows signs of
collapse and such a case may die without having passed dysenteric
stools. The abdomen is rigid and very tender on palpation.
_Entero-dysentery._—In those cases where the process extends to
the lower portion of the small intestine the general symptoms are
much more severe although the tenesmus is less and the stools less
frequent and more voluminous. They contain much blood and mucus mixed
with feculent material. Shiga calls such cases entero-dysentery.
In severe cases of the more typical dysentery or colodysentery, as
designated by Shiga, the stools may change from the mucopurulent
mass to a serous discharge which is very rich in albumin and of an
albuminous odor. In such cases emaciation of the patient is very
rapid. Such cases may show signs of collapse with cold clammy skin
and the clinical picture one associates with cholera.
It has been suggested that such cases may be due to action of the
dysentery toxins on the adrenal.
This serous fluid may contain the flesh-like particles which the
French liken to gut scrapings. During convalescence there may be an
arthritis, which however does not impair the function of the joint.
=Complications.=—In addition to the arthritis there may be neuritis,
which, in severe cases, may go on to muscular atrophy. In the
arthritis the knee joint is that most frequently involved. This
complication appears late in the course of the attack. Arthritis may
be frequent in one epidemic and absent in another. The joint swelling
usually clears up completely. Some of the reported joint involvements
are undoubtedly serum reactions from antidysenteric serum treatment.
Rarely in Shiga infections we may have an irido-cyclitis. Subnormal
temperature may follow severe attacks.
In some epidemics of dysentery gangrenous manifestations have been
common. This is a very fatal type and is recognized by the passage
of dark-brown serous discharges containing ashy gray to black
sloughs or even tubules of gangrenous mucosa, the stool having a
putrid odor. The general symptoms are pronounced, there being a dry
glazed tongue, and low muttering delirium with a thready pulse. It
is the typhoid state.
It is usual to consider bacillary dysentery as a self-limited
disease, running on to convalescence within ten days or two weeks.
Rogers has called attention to the importance of bearing in mind
a chronic condition as well as the acute one. In these chronic
cases the ulcerations are usually located in the descending
colon, sigmoid flexure or rectum and give rise to frequent stools
containing blood and mucus and causing a progressive loss of
strength and weight. There is marked digestive disorder and the
patient becomes weak, anaemic and neurasthenic.
DIAGNOSIS
In the presence of the dysenteric syndrome of tormina, tenesmus,
frequent scanty stools of muco-purulent or muco-sanguinolent
character, one must keep in mind the various conditions which may
give rise to such manifestations of dysentery and not diagnose a
bacillary dysentery until we have excluded tuberculous, cancerous and
syphilitic processes as well as those connected with schistosome or
other helminthic infections.
=Clinical Diagnosis.=—Amoebic dysentery is differentiated clinically
from bacillary dysentery by the usual absence of manifestations of
toxaemia and by its insidious onset and chronic course.
It is important however to remember that either bacillary or
amoebic dysentery may show gangrenous manifestations and in such
cases the clinical picture of the typhoid state is the same
whether the process is amoebic or bacillary. Fulminant bacillary
dysenteries may greatly resemble cholera in its algid stage.
Tropical liver abscess is a complication exclusively occurring in the
amoebic form of dysentery while joint manifestations and evidences
of multiple neuritis may be noted in some epidemics of bacillary
dysentery. Again, the toxins of the dysentery bacilli have a tendency
to damage the myocardium. At present we consider the good effects
of the administration of emetine as important in the diagnosis of
amoebic dysentery.
It is important to remember that chronic dysentery may result from
bacillary as well as amoebic infections, although a chronic process
is more a feature of amoebic dysentery.
The muco-purulent stool of bacillary dysentery is more of a milky
whiteness and flecked or streaked with blood or a very viscous bright
blood-tinged mucus rather than the homogeneous, grayish brown,
gelatinous mixture of disintegrated blood and mucus of the amoebic
one. The odour is apt to be foetid in amoebic stools but rather
albuminous with bacillary dysentery ones.
=Laboratory Diagnosis.=—The chief point is to determine whether we
are dealing with an amoebic or bacillary infection. While these two
kinds of dysentery may coexist it is practical to consider a case in
which amoebae with long, rapidly extruded, finger-like pseudopodia
and containing red blood cells are found, as one of amoebic dysentery.
A fresh specimen of the muco-purulent stool of bacillary dysentery
shows, in addition to pus cells, numerous large, phagocytic
cells, which may show vacuolation and strikingly resemble
amoebae. Such cells never show motility but, under conditions of
lowered temperature of specimen or from prolonged standing and
beginning disintegration, the amoebae too fail to show motility.
If mounted in Gram’s iodine solution these large cells show a
much larger nucleus than that of amoebae and take the yellow
staining of iodine more intensely. The best method, however, is
to make a smear, fix it by heat and stain by Gram’s method or
with Loeffler’s blue or dilute carbol fuchsin. These confusing
cells stain easily and perfectly and in the Gram specimen we note
the Gram-negative bacilli in the cytoplasm. Giemsa’s stain, with
methyl alcohol fixation, or the usual Wright or Leishman technique
answer equally well. On the other hand it is rather difficult to
obtain satisfactorily stained amoebae in this way, it usually
being necessary to fix moist thin smears of the stool with some
bichloride fixative, as Zenker’s fluid, and then carry out the
staining with haematoxylin.
_The Stained Smear._—The presence of pus cells as well as
endothelial cells in a stained smear of material from a bacillary
dysentery stool is of value in differentiating from an amoebic
stool smear in which pus cells are rarely seen. The amoebic
dysentery smear gives more the picture of granular débris.
We should always examine a stool as soon after it is passed as
possible.
If the microscopical examination indicates a bacillary infection
we should take a small mass of the stool, wash it in sterile
water and then drop it in a tube of sterile bouillon or salt
solution. After emulsifying in this tube of bouillon we take up 2
or 3 loopfuls of the emulsion and deposit them on a poured plate,
later smearing out with a glass rod, either by successive parallel
strokes or by revolving the plate while smearing the surface with
the glass rod. It is in the first two or three days of an attack
of acute dysentery that we obtain the best cultural results, often
noting a pure culture of dysentery bacilli from proper material
taken at the onset. Manson-Bahr states that he has never recovered
true dysentery bacilli from a purely faecal stool. Even faecal
contamination of the mucoid mass makes it difficult to recover the
organism. Dysentery bacilli rapidly die out if the stool is acid so
that it has been recommended to make the stool strongly alkaline
where it has to be sent to a laboratory from a distance.
It has seemed to me that litmus lactose agar gives results more
surely than the more restraining faeces-plating media. Still I
generally use Endo’s fuchsin agar because it is always at hand
for typhoid or paratyphoid culturing and gives good results. The
dysentery bacillus colonies on this medium are like those of
typhoid—grayish white. In England they prefer MacConkey’s neutral
red bile salt agar while others use the Conradi-Drigalski medium.
We are now using the Teague medium, which is taken up in the
chapter on Faeces. On all these media the colonies resemble those
of typhoid and the differentiation is most easily made by examining
for motility. At the same time one not infrequently finds lack of
motility in bacilli from colonies just isolated on Endo’s medium
which later on in subculture show motility and are found to belong
to the typhoid or paratyphoid group. For the sure determination
of dysentery bacilli or for differentiating the Flexner and Shiga
strains one should carry out agglutination tests.
The isolation of dysentery bacilli from chronic cases or from
convalescents is more difficult as a rule and agglutination tests may
be more practical. A trouble is that an agglutinating effect may be
connected with a prior infection.
Although some observers have noted the appearance of agglutinins
in the serum of cases of acute bacillary dysentery within three or
four days from the onset of the disease, yet it is usual not to
obtain agglutination with the patient’s serum before the tenth day.
With the Shiga strains agglutinating power in 1 to 50 is usually
accepted as evidence of specificity but for Flexner strains we
generally have a higher titre so that a dilution of 1 to 150 should
be required for the test.
Ritchie has recently tested the sera of 792 normal persons and found
that 30% of these individuals agglutinated Shiga bacilli in 1 to 32,
while with Flexner strains 41% agglutinated in 1 to 64 and 30% in 1
to 128. For comparison Ritchie’s results with typhoid showed that
only 6% agglutinated such bacilli in 1 to 16. There is some evidence
that typhoid vaccination increases the agglutinating power of the
serum against dysentery organisms. These findings are remarkable, as
the usual advice is to consider an agglutination of 1 to 30 as fairly
specific for Shiga infections and 1 to 100 for Flexner ones.
Willmore and Savage tried heating serum to 56°C. for thirty
minutes, but found that such a procedure was of no practical
value with dysentery, thus differing from Malta fever serum where
such a procedure is of value in destroying coagglutinins and thus
increasing the specific action. The work of Ohno would indicate
that we should trust to the acid-producing effect on mannite
for differentiating Flexner and Shiga strains rather than on
agglutination because it was found that agglutinins for an acid
strain were not always more specific for such strains than for
nonacid ones.
At the same time it is the rule for a Flexner type bacillus to
show specificity for its serum and the Shiga type for the serum of
the more toxic, nonacid-fast Shiga strain cases. The statement of
Willmore and Savage that the differentiation of bacillary dysentery
infections is a refinement of technique seems a proper view because
with a polyvalent serum for treatment one only needs to know that
the case is one of bacillary dysentery for proper treatment. Of
course with a monovalent serum, effective only for the Shiga
bacillus, one would have to determine whether the organism
producing the dysentery was of that strain.
As a matter of fact it takes considerable time and laboratory skill
to carry out reliable cultural and serological tests.
From a practical standpoint we can use the therapeutic polyvalent
serum for agglutination and any organism recovered on the plate
made from the faeces which agglutinates in 1 to 50 or 1 to 100
may be considered as diagnostic of bacillary as against amoebic
dysentery. Often one does not see a case of dysentery until late
in the disease and then, provided the condition is serious and the
diagnosis points to a bacillary infection it would be better to
inject the curative serum rather than await laboratory confirmation.
PROPHYLAXIS AND TREATMENT
=Prophylaxis.=—The ease with which water-closet seats may be
contaminated should make us pay great attention to their disinfection
during an outbreak of bacillary dysentery. The same applies to the
bedclothes of such patients sent out for laundering.
Great care should be given to the washing of one’s hands prior to
eating. The greatest care must be taken with rectal tubes when
used for treatment. It is better to make an invariable rule to
confine the use of a single tube to a single patient, as the rubber
tubes are difficult to disinfect other than by boiling and such
treatment, especially in the tropics, soon ruins the tube. For
disinfecting tubes a 5% solution of liquor cresolis compositus is
good. The tubes should be thoroughly washed of the disinfectant
before using again. For disinfection of faeces one can use an
equal portion of the above disinfectant to a similar amount of
stool leaving the disinfectant to act on the stool at least one
hour before emptying the receptacle. Soiled clothes should be
disinfected in a 2½% solution of the compound cresol solution.
Flies must be kept in mind and water and milk supplies boiled. The
carrier is of as great importance here as in typhoid or cholera,
especially when assisting in preparing food.
=Vaccination.=—Vaccination against dysentery does not seem to have
made much headway owing to the very severe reactions following
injections of killed cultures of the Shiga bacillus. By injecting
such bacilli treated with an immune serum (sensitized) the reaction
is less severe.
Dean reports the value of treating the emulsion of organisms with
an equal amount of 1 to 1000 eusol. Gibson treated a suspension of
dead organisms with an equal amount of serum, mixing in the syringe
at the time of injection. Although this method was used during the
war its immunizing value was not settled.
The question of the best method of preparing vaccines for
prophylactic use is still unsettled. The greatest difficulty has
been experienced in making vaccines of the Shiga bacillus on
account of the great toxicity of such preparations.
The serum alone is used almost exclusively for curative rather than
prophylactic purposes.
=Treatment.=—In the treatment of bacillary dysentery absolute rest
in bed is important to keep up the strength of the patient and also
to protect the heart which tends to be more or less damaged by the
toxic action of the Shiga bacillus. Some prefer to prop up the
patient in bed, considering a strict dorsal decubitus as undesirable.
It is important to use sufficient covering on the patient to avoid
chilling. A light wool blanket spread over the abdomen is often all
that is needed in the tropics.
Some authorities deal with the subject of treatment without
referring to any other means than the administration of serum.
This probably is the proper attitude when the very fatal Shiga
type infections are encountered. It must be remembered that
certain epidemics, which as a rule are associated with the Shiga
type bacillus, give a very high mortality (20 to 40%) while other
epidemics seem associated with a less virulent strain of this
bacillus.
At any rate when a case is seen early it would seem advisable
to give about 2 grains of calomel in divided doses of ¼ grain
every half hour and then follow it up with saline treatment. Most
authorities recommend a preliminary dose of castor oil. During
the first day or two enemata of normal saline, boric acid or 1½%
sodium bicarbonate solution in 2 pint amounts would seem indicated
as assisting the salines in the elimination of toxic material.
After that time the tenesmus and rectal irritation make the use of
the rectal tube too trying to the patient. I have used the Murphy
protoclysis method with a certain degree of success, but this
procedure cannot be kept up long. Hot fomentations to the belly
relieve the griping pains.
The saline treatment is highly recommended by Buchanan who gives
60 grains of sodium sulphate every two or three hours until the
dysenteric character of the stool disappears.
Bahr in the Fiji islands treated 53 consecutive cases, of which
41% had marked constitutional symptoms, with a mortality of 13.2%.
He gave 1 dram of sodium sulphate every hour for the first day and
subsequently the same dose every four hours.
In a second series of 106 cases, of which 42% had marked
constitutional symptoms, he treated 34 with salines plus the
administration of capsules of cyllin. The remaining 72 cases
received in addition to this treatment injections of a polyvalent
serum obtained from the Lister Institute. The mortality in this
series was 1.8%. He notes that 5 of the cases in this second series
were of the severest type as evidenced by the gangrenous stools
and toxic condition and yet not one of these five serum-treated
cases died. He notes that the stools of those who received serum
injections became normal in five days for an average while for
those treated with saline alone the average period was eight days.
Bahr strongly recommends the combined treatment of salines and
serum. In very severe cases Bahr used 50 to 70 cc. of the serum but
ordinarily 20 cc. for adults and 10 cc. or less for children.
Willmore and Savage think one obtains the best results by injecting
from 80 to 120 cc. of a polyvalent serum into the subcutaneous
tissues of the flank or abdomen or intravenously. They think that
anaphylaxis is less liable to follow a massive initial dose of serum.
In the use of serum Shiga recommends a dose of 10 cc. for a mild
case or two injections of 10 cc. at intervals of ten hours for
cases of medium severity, while in very toxic cases he uses 60 cc.
in 3 daily doses of 20 cc. each. It is important to use serum early
as it has little or no effect if used after the 7th day (Klein).
The best known sera are those of Shiga, Dopter and that prepared by
the Lister Institute.
Animal charcoal and bolus alba are considered of value by some
physicians. Opium should be avoided. Intravenous saline injections
are of value in cases showing collapse signs. Again, such cases,
from the standpoint of possible adrenal insufficiency, may be
helped by adrenalin. Where there is a very small rapid pulse with
marked cardiac weakness injections of camphor in oil may be of
value.
Subcutaneous injections of ordinary or hypertonic saline containing
about 10 drops of 1 to 1000 adrenalin solution is of value in
collapse.
Ross considers opium as of value in dysentery and states that he
regards ipecac as of value not only in amoebic but in bacillary
dysentery as well. I have often given salol-coated pills containing
1 grain of ipecac and ⅙ grain of calomel every two hours to cases
of bacillary dysentery with apparent benefit.
For the diet of cases of acute bacillary dysentery albumin water
or barley water sweetened with lactose is to be preferred to milk,
which is usually not well borne by such patients. Kendall has noted
the value of sugar of milk in lessening the toxicity of various
organisms. Tea sweetened with lactose is usually well borne. Meat
juice expressed from a piece of lightly broiled steak is good.
Various jellies or sago pudding are of value. Willmore and Savage
praise yoghurt.
Unless given in small amounts liquid diet is apt to increase
evacuations and some cases seem to do better on ordinary diet.
In the tropics there are many brands of sterilized natural milk and
these can be inoculated with a culture of _B. bulgaricus_.
In chronic bacillary dysentery Rogers recommends 1 to 1½ pint
enemata of albargin in strength of 1 to 500. Protargol seems to
be equally efficient in the same strength. Owing to the effect
of organic material on silver nitrate this salt does not seem
so reliable as the organic silver compounds. It has also been
recommended to flush the colon with warm boric acid solution.
Another recommendation is to use milk for this purpose. Vaccine
treatment has been employed, in cases of chronic bacillary
dysentery. Either eusol-treated organisms or those sterilized by
0.25% trikresol are to be preferred.
CHAPTER XIII
PLAGUE
DEFINITION AND SYNONYMS
=Definition.=—Plague is primarily a disease of rats or other
rodents and is caused by a bacterium of the haemorrhagic septicaemia
group, _Bacillus pestis_. The disease exists in the rodent in both
an acute and chronic form. Acute plague of the rat is apt to be
septicaemic, so that when certain species of fleas which infest the
rat feed on the blood of their host they ingest plague bacilli.
These seem to multiply in the region of the proventriculus and cause
thereby an obstruction to the stomach. As a result the flea makes
vigorous and repeated but ineffectual efforts to feed. Regurgitation
of the contents of the oesophagus occurs, thereby inoculating
plague bacilli. When the rats die these fleas will attack man and
cause human plague. The ordinary type in man is bubonic plague,
characterized by extremely tender glandular enlargements. This form
of the disease is thought to be exclusively transmitted from man to
man by fleas or possibly bedbugs. A second type is pneumonic plague
which is a surely fatal pneumonia which is transmitted from man to
man by droplets of sputum expelled in coughing. Either the bubonic or
pneumonic types may become septicaemic or this form may exist from
the start.
Plague shows a marked clouding of the consciousness from the onset
and is characterized by toxic action on the heart and endothelial
lining of capillaries.
=Synonyms.=—Oriental Plague, Black Death, Pestis. French: La Peste.
German: Die Peste.
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—Ancient writers were accustomed to apply the
designation “plague” to any disease which was epidemic in character
and attended with great mortality. This explains why the plague of
Athens and that of Marcus Aurelius, which epidemics did not possess
the characteristics of oriental plague, were so designated. There
exist however writings which show that fatal epidemic diseases
attended with buboes and prostration were noted prior to the
Christian era.
It is probable that the biblical description of a disease among the
Philistines which was attended with buboes and killed the mice of
the field referred to plague.
In the 6th century, during the reign of Justinian, a disease
which was unmistakably plague started from Egypt and reaching
Constantinople caused the death of 10,000 persons in one day. It
spread throughout the entire Roman empire.
_The “Black Death.”_—The most noted epidemic of plague was that of
the “Black Death” of the 14th century. The disease seems to have
originated in the East, possibly in China, and eventually invaded
Asia Minor, Egypt and Europe. The disease was called “Black Death”
in Germany, on account of the petechial spots or “tokens” and in
Italy, the “Great Mortality.”
In the records of the epidemic we note that it was attended with
great stupefaction, the sick losing their speech from palsy of the
tongue. Others noted buboes of groins and arms while some noted a
putrid inflammation of the lungs with the expectoration of blood.
In the plague at Avignon it was noted that at first, for six or
eight weeks, the sick expectorated blood and that to come near them
was certain death. Afterwards buboes appeared in groin and axilla
and some of the sick recovered.
_Quarantine._—It was during this epidemic that quarantine became
a recognized procedure in Europe. The adoption of a period of
detention of forty days probably originated in the medical idea
that the 40th day was the last day of ardent diseases, this being
one of the critical days. The lazarettos, where strangers were held
in quarantine, appear to have first been established on some island
near Venice, in 1485.
It has been estimated that one-fourth of the population of Europe
succumbed to the “Black Death,” but estimates in certain parts
of Europe would indicate a mortality approaching 70% of the
inhabitants.
In 1665 occurred the Great Plague of London, during which year it
was estimated that approximately 60,000 out of a population of
450,000 died. It was thought that this epidemic was introduced from
the Levant by way of Holland.
There was much plague in Europe in the 18th century but it would
seem to have completely disappeared by 1841 and only to have
returned with the present pandemic.
_The Present Pandemic._—The plague epidemic with which all parts
of the world are now so concerned is supposed to have originated
in China, in the province of Yunnan, and from that center to have
reached Canton, in 1894, causing the death of 60,000 people in a
population of 1,500,000. In the same year it extended to Hong Kong
and from that great seaport has spread over the entire world. India
has suffered more than any other country, there having been years
when the plague deaths exceeded 1,000,000.
In a recent article by Low it is noted that the highest death rate
was reached in 1907 when 1,315,892 persons died. From the time of
the introduction of plague into India to the end of 1917 there were
9,841,396 deaths from this disease.
In its spread it has invaded Europe, Egypt, South Africa,
Australia, Japan, Philippine Islands, California and parts of
Central and South America. It has recently made its appearance in
New Orleans.
=Geographical Distribution.=—At present there are only two
important foci of endemicity, one Mesopotamia and another in the
region of the Himalayas (India, Thibet and Yunnan). There also
seem to be less important centers in Uganda, in Africa, and in the
trans-Baikal region of Siberia. In view of the rather widespread
infection of the California ground squirrels, from which rodents
the disease has from time to time spread to man, it would seem
probable that California might be considered another focus of
plague.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—The bacillus of plague was first isolated by Yersin
from a plague bubo, in 1894, at Hong Kong. It is true that Kitasato
reported a bacillus which he had isolated from the blood of a plague
patient, on July 7, 1894 (Yersin’s report was made July 30, 1894).
Kitasato’s bacillus was motile, Gram-positive, coagulated milk and
gave a turbidity in bouillon, characteristics which were just the
opposite of those of the organism reported by Yersin.
[Illustration: FIG. 63.—Pest bacilli from spleen of rat. (Kolle and
Wassermann.)]
As now recognized the plague bacillus, when in smears from
pathological material, shows the form of an oval bacillus, the ends
of which stain more intensely than the central portion (bipolar
staining). When cultured on ordinary agar, the morphology is more
rod-shaped with a tendency to pleomorphism.
These agar cultures are very sticky and mucilaginous. If 3% of
NaCl is added to the agar, this pleomorphism is exaggerated, there
occurring coccoid, root-shaped and various bizarre involution forms.
For obtaining the involution-form appearance on 3% salt agar one
should transfer liberally from the ordinary agar growth to the salt
agar rather than planting direct from the pathological material.
A bouillon culture, upon the surface of which there has been
deposited drops of oil or melted butter, shows a string-like
downward growth from the under surface of the oil globules. This
“stalactite” growth is very fragile and is difficult to obtain.
Ordinary bouillon cultures show a rather powdery deposit at the
bottom and a hanging-drop preparation from such a culture shows
chains of plague organisms resembling streptococci. Gelatine is not
liquefied. _Bacillus pestis_ grows readily at room temperature as
well as at 37°C, and one may be struck with the fact that colonies
on agar plates may show variations in degree of development so
that the suspicion of a contaminated culture may arise. Human
plague material for cultures or smears is best obtained from the
bubo prior to suppuration in bubonic plague, from the blood in
septicaemic plague and from the watery sputum in pneumonic plague.
_Plague in the Rat._—With acute plague in the rat one finds marked
injection of the subcuticular surface of an exposed abdominal flap;
certain glands, especially the neck ones, show marked congestion,
haemorrhagic necrosis and periglandular infiltration; the pleural
cavity contains much fluid; the liver has a yellow mottled appearance
liberally sprinkled with discrete, yellowish-white granules about
the size of a pin’s head, while the spleen is enlarged. Smears from
the spleen or affected glands, as a rule, show the bacilli in great
numbers. The San Francisco findings in plague rat autopsies varied
somewhat from those noted above, which held for Indian plague rats.
_Confusing Organisms._—Other organisms which may be obtained
from plague-suspected material are those of the proteus or colon
group, which may show bipolar staining, but culturally are quite
different. Klein has noted that a nonmotile rod, which gives a
striking bipolar staining and named _Bacillus bristolensis_, may be
mistaken for the plague bacillus. Its growth in bouillon is similar
to that of _B. coli_ and it coagulates milk.
An organism, _B. pseudotuberculosis rodentium_, resembles the
plague bacillus in a striking manner but is without virulence for
rats. It is virulent however for guinea pigs and these animals can
be immunized against plague with this closely related organism.
Litmus milk cultures of plague show a very slight acidity while
with _B. pseudotuberculosis rodentium_ there is a high degree of
alkalinity produced.
Wherry has reported two cases of ulcerative conjunctivitis with
lymphadenitis of cervical glands, fever and marked prostration,
due to infection with _B. tularense_, occurring in persons who had
handled rabbits which had died of this plague-like infection. The
organism was first noted by McCoy in squirrels in California. The
symptoms and lesions in these animals are those of plague. Guinea
pigs succumb after the cutaneous inoculation of material and show
lesions markedly resembling plague. The organism, however, will
not grow on ordinary simple media as does the plague bacillus. As
will be noted in the chapter on Tularaemia the disease has a very
limited geographical distribution.
The _crucial test_ for any plague material is the power of the plague
bacillus to infect a rat or guinea pig, when the material is rubbed
on the shaven skin of the animal. _B. tularense_ will also pass
through intact shaven skin and it produces lesions in the guinea
pig similar to those of plague. Other organisms, however which might
infect through intact skin produce lesions unlike those of plague. As
a practical point it may be stated that cases showing a profusion of
oval, bipolarly staining bacilli, in smears from glands or sputum,
and with clinical manifestations of plague, are not likely to be
other than plague; still, to be conservative, one should always
inoculate animals cutaneously or subcutaneously.
[Illustration: FIG. 64.—Plague bacillus involution forms produced by
growing on 3% salt agar. (Kolle and Wasserman.)]
=Epidemiology.=—Plague is primarily a disease of rodents, usually
rats, and man contracts his infection from these animals. With the
exception of pneumonic plague which, under certain circumstances, is
transmitted directly from man to man, plague infections originate
from the bite of fleas which have become infected from feeding on the
blood of plague rats. Infected fleas act as intermediaries in plague
epizootics among rats. It is true that a rat might become infected
from bites received in a fight with an infected rat, or man might be
infected through a cut on a finger while handling plague material,
but such methods play but a small part in plague epidemiology.
_Fleas and Plague._—In 1897, Ogata infected mice by inoculating
them with an emulsion of crushed fleas taken from plague rats. In
1898 Simond showed that if a rat, dead of plague, were placed in a
large bottle and a healthy rat confined in a small cage introduced
into the bottle and suspended above the dead rat, so that there
could be no contact between the dead and the living animal, the
well rat would contract the disease. If however the fleas were
removed from the dead rat, before the introduction of the caged
rat, no infection took place.
By reason of claims that the rat flea would not bite man these
convincing experiments were in a measure disregarded. The complete
confirmation of the correctness of this view, as to transmission of
bubonic plague, was brought about by the Indian Plague Commission.
In a large number of experiments it was shown that when healthy and
plague-infected guinea pigs were confined together in spaces where
there were no fleas, there were no plague infections of any of these
well animals.
[Illustration: FIG. 65.—1 and 2, male and female _Xenopsylla
cheopis_. 3, Head of _Ceratophyllus_. 4 and 5, male and egg-distended
female of _Sarcopsylla penetrans_.
_Xenopsylla cheopis_ is the most important plague transmitter of the
flea family as it is the common rat flea of India where there is so
much plague.
_Sarcopsylla_ or _Dermatophilus penetrans_ is an important factor in
a disabling skin disease, especially of the feet, in many parts of
the tropics.]
On the other hand in 35 experiments, when fleas had access to
the spaces, plague infections were the rule. Again, guinea pigs
in cages which were suspended only two inches above a plague
flea infected floor, became infected, but other animals, which
were suspended so high that the fleas could not jump up to them,
remained well. Two cages, each containing a monkey, were placed in
a plague flea infected room. One was surrounded with a protecting
zone of 6 inches of “tanglefoot” fly paper, this being the limit
of the distance a flea can jump, while the other cage was not
so protected. The monkey in the cage without the sticky paper
contracted plague while the second monkey remained well. It is
only when there is a great incidence of plague among rats that
we have outbreaks of bubonic plague in man, and it has been noted
that the greater the epizootic, the more heavily infected was the
blood of the sick rats with the plague bacilli. A flea with a
stomach capacity of about ½ c.mm. could take in several thousand
plague bacilli in a feeding on a rat whose blood was teeming with
bacilli. The blood of a rat dying with plague may contain as many
as fifty million bacilli to the cc. Human blood rarely contains
more than a million to the cc. There is a multiplication of the
organisms in the flea, so that when it defecates, thousands of
plague bacilli are deposited near the puncture wound made by the
flea when subsequently feeding on a man. The infected faeces are
rubbed into the wound by the man in scratching the site of the
bite, so that we have here an instance of a contaminative method of
infection as contrasted with the inoculative method by the mosquito
in malaria.
[Illustration: FIG. 66.—1, _Ctenocephalus felis_. 2, _Ceratophyllus
fasciatus_. 3, _Hoplopsyllus anomalus_. 4, _Ctenopsylla musculi_.
5, _Xenopsylla cheopis_. 6, _Pulex irritans_. 7, Internal anatomy
of flea. (After Fox.) (_a_) Maxillary palpus; (_a_-1) epipharynx;
(_a_-2) mandible; (_a_-3) labial palpi; (_a_-4) maxillae; (_a_-5)
basal elements of rostrum and mandibles; (_b_) salivary pump;
(_c_) hypopharynx; (_d_) aspiratory pharynx; (_e_) muscles of the
aspiratory pharynx; (_f_) eye; (_g_) oesophageal ganglia (brain);
(_h_) thoracic ganglia; (_i_) oesophagus; (_j_) salivary duct;
(_k_) gizzard; (_l_) salivary gland; (_m_) stomach; (_n_) aorta;
(_o_) ovaries; (_p_) malpighian tubules; (_q_) pygidium; (_r_)
rectum showing rectal glands; (_s_) anus; (_t_) intestines; (_u_)
bursa copulatrix; (_u_-1) ductus obturatorius (blind duct); (_v_)
receptaculi seminis or spermatheca; (_w_) ducts of spermatheca; (_x_)
vagina; (_y_) uterus; (_z_) abdominal ganglia.]
Bacot and Martin have shown that while infection may take place as
the result of the faeces being rubbed into the wound made at the time
of feeding yet the ordinary way is probably by regurgitation from the
oesophagus of the flea at the time of feeding.
Upon taking in plague septicaemia blood the bacilli multiply
about the site of the proventriculus as well as distending the
oesophagus. This makes an obstruction to the entrance of the
stomach resulting in starvation of the flea. This naturally makes
the flea more voracious and in the ineffectual muscular efforts
to take in blood, regurgitation of the contents of the oesophagus
occurs, thereby infecting the person upon whom the flea is trying
to feed. This obstruction apparently may be overcome in some way as
the plague-infected flea does not necessarily die. Still from lack
of sufficient fluid such fleas are liable to be killed off if the
relative humidity is low, as in dry weather. Further investigations
have shown that the proventricular plug may be channeled, but in
such case valve action is lost and the contents of the stomach are
regurgitated, thus making such a flea more dangerous than one with
an obstructed proventriculus. Such fleas may continue infectious
for 67 days.
Very interesting in this connection is the fact that Heiser found
plague-infected fleas in the desk of a European at Manila who died
of plague. A mummified rat was found in one of the drawers of
this desk, from which successful animal inoculations for plague
were made. Heiser notes that data would indicate that these fleas
probably remained alive 2 weeks after the death of the rat which
brought about their infection. Another very striking finding during
the same Manila plague outbreak (1912-1913) was that bedbugs found
on the sleeping mat of a human victim of plague showed bipolarly
staining bacilli.
Bacot has carried on experiments in which fleas infected two months
previously and kept in a cool place could transmit plague. This
would indicate the danger from plague-infected fleas which had been
held in material packed away in boxes.
_Method of Spread._—The spread of plague epizootics among rats seems
to be rather by the fierce brown sewer rat, _Mus norvegicus_. The
more delicate black house rat, _Mus rattus_, usually receives its
infection from the sewer rat. When the rat dies the fleas leave the
dead body and seek a new host, preferably one similar to the one just
abandoned. The sewer rat reaching the basement of houses and dying
of plague is deserted by his fleas. These will attach themselves to
the house rats which go from basement to roof of the house and later
these dying are abandoned by the fleas which, in the absence of a
rodent host, will feed on man and infect him.
The house rat is rarely found in Europe while in many parts of the
tropics it is common and in close association with man. The fact
that the sewer rat avoids the upper portions of houses probably
explains the greater infrequency of plague epidemics in Europe
where this rodent is common. In former ages when the house rat was
prevalent in Europe we had great epidemics there. _Mus (Rattus)
norvegicus_ is of stout build with a blunt nose and small opaque
ears which barely reach the eyes when laid forward. The tail is
shorter than the length of the head and body together (89% of such
length). With _Mus rattus_ we have a delicately built rat with a
slender head and sharp nose. The ears are translucent and large
and reach beyond the middle of the eye when extended. The rather
delicate tail is about 25% longer than the length of the head and
body taken together.
Recently it has been found that a guinea pig set free in a house
suspected of having plague fleas becomes infected if such fleas are
present. The fleas would probably prefer the guinea pig to man and
such a measure would in some degree be protective to man. It is
however for the detection of plague infection that the measure is
employed and the guinea pig is termed the “Plague barometer.” In
Madras there is practically an absence of _Mus norvegicus_ although
_Mus rattus_ is present in numbers and the comparative freedom of
the city from plague is striking.
The principal rat flea of the Orient is _Xenopsylla cheopis_. This
flea is without combs like _Pulex irritans_, the human flea, but
is of a lighter color and has an ocular bristle near the upper
margin of eye and two bristles posterior to the antennae. In Europe
and the United States _Ceratophyllus fasciatus_ is the common rat
flea. Many other species of fleas transmit plague and it is also
possible that the bedbug may play a part in spreading infections
from man to man. Vergbitski has transmitted plague from man to the
rat by infected bedbugs. In Siberia, a marmot, the tarabagan, is
supposed to play the part of the rat in plague transmission. In
California, the ground squirrel, _Citellus beecheyi_, has become
infected and may transmit the disease by its flea, _Ceratophyllus
acutus_. In the Tropics plague tends to prevail only at times when
the temperature is between 10° and 30°C. It is the effect on the
flea of cold weather which causes the disappearance of bubonic
plague at such times. The bacillus of plague can withstand freezing
temperatures. Sunlight and drying are the especially inimical
factors for _B. pestis_. Dry seasons are inimical to the spread of
plague and it is especially in very rainy seasons that epidemics
rage.
_Chronic Plague in Rats._—The Indian investigators have called
attention to the existence of a chronic plague in rats. In this we
have chronic buboes, areas of necrosis in spleen and abscesses of
the spleen. It is chiefly in the spleen that the lesions occur, thus
differing from the acute plague in rats above described. Of 27,699
_M. norvegicus_, examined in Bombay, O.57% showed signs of chronic
plague.
In the necrotic material plague bacilli can be found in
approximately one-half of these rats although frequently the
bacilli are nonvirulent. It is possible that this chronic plague
in rats may serve as the reservoir of infection which keeps up
plague epizootics from year to year. Plague in India, according to
White is less virulent now than formerly and this is attributed to
a greater immunity of the rats.
_As regards pneumonic plague_ the origin of such epidemics is
probably from pneumonia occurring secondarily in cases of bubonic
plague. Provided the conditions are favorable, particularly as to
moisture in the air of the room, the infection spreads directly from
man to man as a result of the droplets of heavily infected sputum
being sprayed into the air in the act of coughing on the part of the
patient. It is an instance of _Flügge’s droplet method of infection_.
In the recent epidemic of pneumonic plague in North China, it was
at first thought that the hunting of the tarabagan for its valuable
skin, which led some of the Chinese to even capture tarabagans,
possibly sick with plague, was the origin of the epidemic. This
view is no longer held and we now know that the outbreak was
independent of any disease in rats, tarabagans or other animals.
Strong has shown that the bacillus which was isolated from these
cases of pneumonic plague was identical with that isolated from
cases of bubonic plague; its virulence was no greater and animals
infected cutaneously or subcutaneously died of bubonic plague.
Experiments by Teague and Barber, with emulsions of plague bacilli,
showed that with a room temperature of 32°C. plague bacilli were
quickly destroyed when the air was comparatively dry. In such an
atmosphere, saturated with moisture, the viability would be greatly
prolonged. In the plague wards in Manchuria the extreme cold which
prevailed, together with the saturation of the atmosphere of the
unventilated rooms by the moisture of the breath of the patients,
made conditions most favorable for the viability of the plague
bacillus. They note that in the plains of India, although about 3%
of bubonic cases assume a pneumonic type, yet epidemics of plague
pneumonia do not occur; this is probably due to the fact that
the higher temperatures and open rooms make evaporation occur 30
times more rapidly there than was the case in the plague wards in
the bitter cold weather of the Manchurian winter. The possibility
of carriers of plague bacilli in those who might go on to
convalescence need not be considered, as practically all cases of
plague pneumonia die. Other material from the patient than sputum
does not seem to be a source of danger in the spread of plague,
so that there is no need for the disinfection of urine and feces.
There has recently been an outbreak of septicaemic plague in Ceylon
in which there was an absence of plague in the rats. The infection
was possibly transferred directly through bedbugs or human fleas.
As a matter of experience the transference of plague from place to
place generally occurs from infected rats or infected fleas which
have been transported by ships. A case of bubonic plague in a ward
with other patients would not be a source of danger provided there
was freedom from fleas and a lack of development of secondary
pneumonias. It is very doubtful as to infection ever taking place
by way of the alimentary canal, although there is some evidence
that rarely the tonsil may be primarily involved. Monkeys are very
susceptible to plague and the possibility of an epizootic among
them should be thought of during plague epidemics.
PATHOLOGY
It is rare that one finds the primary vesicle marking the site of
entrance of the plague material. Thus in 13 cases where plague was
contracted by direct cutaneous inoculation of those performing
autopsies on plague victims only two showed evidences of local
reaction as shown by the formation of a primary vesicle.
The chief points noted in a plague autopsy are: (1) The marked
involvement of the lymphatic system as shown by intense congestion
and haemorrhagic oedema of the lymphatic glands. Not only are
the glands tributary to the site of inoculation involved, thus
forming the primary bubo, but there is secondarily more or less
inflammatory change in all the lymphatic glands of the body.
There is also a marked periglandular oedema, with haemorrhagic
extravasations of the connective tissue surrounding the primary
bubo, this mass being made up of a group of glands matted together
by this periglandular exudate.
(2) The destructive effect of a toxic product of the plague
bacillus, which may be designated an endotheliolysin, upon the
endothelial cell lining of blood vessels as well as lymphatic ones.
This causes the extensive blood extravasations so characteristic of
plague as shown by petechial spots, not only of the skin but of the
serous and mucous membranes as well.
There is a general congestion of all organs of the body.
The meninges of the brain are deeply congested and there may be
haemorrhagic extravasations in the brain substance itself. Crowell
has reported two cases of plague meningitis in which plague bacilli
were found in the ventricular pus. The spleen is generally markedly
congested and enlarged to 2 or 3 times its normal size.
There may be haemorrhagic extravasations throughout the spleen
pulp. The bacilli are chiefly scattered throughout the venous
sinuses.
There is also active congestion of the liver. The kidneys are
intensely congested and we often find fibrin thrombi in the tufts
of the Malpighian bodies.
The plague toxin has a marked effect on the cardiac muscle so that
we usually find dilatation of the right side of the heart with fatty
degeneration of the muscle fibers.
In a study of the pathology of primary pneumonic plague Strong
noted pericardial and pleural ecchymoses with fibrinous pleurisy
over the affected lung areas.
The process was at first lobular but later involved the entire lobe.
There was marked congestion of the bronchial mucosa with
involvement of the bronchial glands. The larynx and trachea are
also intensely congested. Microscopically there is a distension of
the alveoli and bronchial passages with a haemorrhagic exudate.
There is practically no fibrin in the alveolar exudate. The process
seems to extend by continuity along the bronchi and bronchioles.
Plague bacilli pack the exudate found in the bronchi and
bronchioles.
In a report on the autopsy findings of septicaemic plague in Ceylon
in cases where plague bacilli were demonstrated in smears and
cultures from spleen and blood, Castellani noted that other than
meningeal congestion and some splenic enlargement there was nothing
abnormal.
SYMPTOMATOLOGY
In a clinical study of plague it is customary to consider the disease
as manifesting itself in a mild form (Pestis minor) and a severe form
(Pestis major).
=Pestis Minor.=—Pestis minor, which is sometimes termed pestis
ambulans, is that form of plague in which there is only slight fever
and comparatively little physical prostration or mental hebetude.
These cases usually show moderate enlargement and tenderness of some
group of lymphatic glands. It is in this mild form of plague that we
are most apt to find the primary vesicle or phlyctenule at the site
of the flea bite.
Ordinarily, man is so susceptible to plague that there is no
reaction at the site of inoculation but in these mild cases there
is an inflammatory reaction resulting in a vesicle or pustule,
which may teem with plague bacilli. In such cases it is extremely
important to search for such primary vesicles and examine for
plague bacilli. It is usually stated that only about 5% of cases of
bubonic plague show these vesicles.
=Pestis Major.=—Pestis major can certainly be divided clinically
and epidemiologically into two types, pestis bubonica, or bubonic
plague, which is the common type of plague, and pestis pneumonica,
or pneumonic plague, the contagiousness of which is extreme and the
mortality practically 100%.
Both of these types of plague tend finally to show an invasion
of the blood stream with plague bacilli, the case then becoming
one of septicaemic plague. Many authors, however, recognize an
overwhelming plague septicaemia in which the manifestations of
buboes or pneumonia are absent and such cases are designated
septicaemic plague, or _pestis siderans_.
In all forms of pestis major there stand out the characteristics of
rather sudden onset, rigors or chilly sensations, rapidly rising but
irregular fever, marked giddiness, great prostration, the mental
state and speech of an intoxicated person and extreme weakness of the
heart with a rapid weak pulse.
Typhus fever alone shows an equal degree of early mental hebetude,
so that it is stated that Clot Bey, who had seen much plague
in Egypt, when elsewhere shown cases of typhus with parotid
involvement, remarked “In Egypt one would call such cases plague.”
=A Typical Case of Bubonic Plague.=—After a period of incubation
of from three to seven days the disease may set in quite abruptly,
or after a prodromal stage, in which malaise, giddiness, mental
hebetude and pains in the back and limbs may be present. With the
onset of the attack the effects of the toxaemia upon the nervous
system are the most striking. The patient has a pale, drawn, anxious
countenance, with injection of the conjunctivae toward the inner
canthus.
The speech is thick and difficult, the gait is staggering, so that,
with the stupid mental state and tendency to wander aimlessly
about, one has the symptom-complex of an alcoholic intoxication. In
some cases a delirious tendency may be marked, especially as the
disease develops. After a few hours, or within a day, the fever
begins to rise rapidly and is often associated with shivering
attacks. The face now becomes hot and flushed, the conjunctivae
markedly injected, the pupils dilated, and the eyes rather staring.
The temperature is as a rule from 102° to 104°F., occasionally
higher, with a tendency to rather marked remissions and, on the
whole, of great irregularity of the fever curve. The pulse is rapid
and shows early indications of the extreme toxic effect exercised
upon the heart. Cardiac weakness is a marked feature of plague.
The urinary secretion is diminished but there is rarely more than a
slight amount of albumin.
_The Pathognomonic Bubo._—About the second or third day the
development of an extremely painful bubo practically gives the
diagnosis.
About 70% of these buboes are of the inguinal region, the femoral
glands being more frequently invaded than those above Poupart’s
ligament. The axillary glands are involved in about 20% and the
submaxillary and cervical ones in from 5 to 10% of cases.
There is a question whether the tonsil ever serves as the site of
infection from which cervical buboes result. It would seem that
the greater frequency of inguinal buboes is because a greater area
of skin drains into these glands. There may be multiple buboes
and it must not be forgotten that the lymphatic glands of any
region may become enlarged. There may also be lymphangitis. Only
one gland of a group may be involved or the whole group may show
enlargement. Very characteristic for plague buboes is the oedema
of the periglandular tissues, which is largely responsible for the
great size of some of these buboes; they may vary from the size of
an almond or walnut to that of a child’s head. The patient tends to
assume an attitude to relieve any tension on the very painful bubo.
Particularly over these buboes, but at times elsewhere, the skin
may show areas of inflammation, often several inches in diameter.
Necrosis of this area occurs and a slough separates. These lesions
are often termed carbuncles but are really not such, but only
gangrenous patches of skin.
When these areas of cutaneous necrosis are a marked feature the
designation of _cellulo-cutaneous plague_ is at times given.
Petechiae or large purpuric spots may be conspicuous in some
epidemics and it was from these “tokens,” as they were called, that
plague received the designation “black death.”
As the case progresses, the anxious countenance gives way to one of
apathy, the control of speech and cerebration become more and more
impaired and the patient may go into a typhoid state.
Cases with buboes in the axillae give the gravest prognosis, as
for example, 80% mortality for axillary, and 70% for inguinal.
The buboes may suppurate towards the end of a week or they may
undergo a slow resolution. Secondary broncho-pneumonia may develop
in the course of bubonic plague. Pulmonary congestion is however
not infrequent and may cause dyspnoea, accelerated respiration and
cough. Owing to the tendency to degeneration of the endothelial
lining of capillaries, various haemorrhagic manifestations, other
than those of the skin, may be observed, such as epistaxis,
haematuria, etc. There is usually a rather marked leucocytosis in
which the increase is chiefly of the polymorphonuclears.
[Illustration: FIG. 67.—A, Temperature chart of fatal case of
bubonic plague. B, Chart of case of bubonic plague going on to
recovery but with suppuration of plague bubo. C, Chart of fatal case
of pneumonic plague.]
=A Typical Case of Pneumonic Plague.=—Besides those cases where
pulmonary involvement sets in during the course of an attack
of bubonic plague and which are classified as secondary plague
pneumonias we have sporadic cases and epidemics when the clinical
course of the disease is predominantly and primarily pulmonary.
Although the characteristics of pulmonary involvement, with
expectoration of blood, were noted by many observers of the
14th century and later as manifestations of plague, yet in the
present pandemic, which started in 1894, such cases were at first
overlooked as being plague. The recognition of a primary pneumonic
plague was made by Childe in 1897. The onset is sudden, with a
rise of temperature to 103°F., or higher, during the first day.
The marked physical exhaustion and clouding of the consciousness,
characteristic of any type of pestis major, are intensified in
pneumonic plague. In fact the occurrence of manifestations of such
profound toxaemia in the presence of only slight physical signs,
should make one suspicious. Crepitation over small areas, without
demonstrable dulness on percussion, may be the only sign. There is
often early dyspnoea and rapid shallow respiration. Cough, with the
expectoration of rather abundant watery sputum, which soon becomes
blood-stained or absolutely sanguineous, may be present by the
second day.
[Illustration: FIG. 68.—Axillary Bubo. (Reproduced from Simpson’s
Treatise on Plague, 1905.) From Jackson’s Tropical Medicine.]
There is never the rusty, tenacious sputum of lobar pneumonia. Herpes
never appears, according to Childe. Heart failure is a very prominent
feature of plague pneumonia.
It is fortunate that this watery sputum teems with bacilli early
in the disease as smears from such sputum give an early and sure
diagnosis of this terribly contagious and fatal malady. The
knowledge that this infection is transmitted from man to man by
the droplets of sputum expelled in coughing demands the protection
by some form of mask of anyone coming near such a patient. Some
observers noted splenic enlargement and tenderness over the
superficial lymphatic glands. Strong has noted that the course of
the disease rarely extends beyond the fourth day and that death is
the invariable termination.
In 1919 thirteen cases of plague pneumonia occurred in California
starting from an at first unrecognized case of bubonic plague of
squirrel origin. These pneumonias were diagnosed as influenza
pneumonias but later the true diagnosis was determined. McCoy notes
in this connection that there is a strong tendency to pulmonary
localization of plague in the squirrel which is not true of the rat.
=Septicaemic Plague.=—As regards the clinical manifestations of
septicaemic plague, if such be considered as a separate type, Choksy
states that there is no clinical sign by which such a septicaemia
can be recognized without the help of the laboratory, although the
presence of a thready or imperceptible pulse, in one showing the
characteristic toxaemia of plague, should cause suspicion.
The patient may be so overwhelmed from the start that there may be
only a slight rise of temperature. Occasionally, plague bacilli may
be recognized in blood smears, a finding that practically never
obtains in any other bacterial disease. At the same time blood
cultures are solely to be depended upon in diagnosis and even such
examinations may be negative. Liston has noted that plague patients
always die if more than 40 bacilli per cc. are present in the
blood. In a recent outbreak of septicaemic plague in Ceylon the
only clinical manifestations were intense headache, and fever. The
patients died within forty-eight hours. Until properly diagnosed
bacteriologically the disease was thought to be pernicious malaria.
The Symptoms in Detail
_General Appearance._—The face is at first drawn and pallid, the
eyes injected and the expression one of fear or anxiety. As the
temperature rises the pallor is succeeded by a flushed and dry hot
skin. Later on in the disease the expression is more one of apathy.
The staggering gait and the tendency to wander give the impression
of alcoholic intoxication.
_Temperature Curve._—The fever course of plague is very irregular.
The temperature usually rises rapidly to 103° to 104°F., but tends
to exhibit marked remissions by the third day. After a fall, it may
rise to a very high degree just before death. Cases which recover
often show a fall by lysis.
_Nervous System._—Very characteristic for plague is the intense
and early disturbance of the mental condition. The patient presents
the characteristics of alcoholic intoxication, thick speech, lack
of mental concentration and giddiness which causes a staggering
gait. Later on an apathetic or stuporous stage may ensue or there
may be delirium.
Rarely a case of bubonic plague may show marked involvement of the
meninges, giving the clinical picture of meningitis.
_Circulatory System._—The pulse is at first soft, dicrotic and
rapid, 110 to 120 beats per minute. Later on, as the heart begins
to show the toxic effects of the disease, the pulse becomes thready
and irregular, to be followed by cardiac failure. There is a
marked tendency to congestion of various internal organs and to
haemorrhages from the capillaries.
_Respiratory System._—Pulmonary congestion and even
broncho-pneumonia may supervene in bubonic plague. In pneumonic
plague, however, the lungs seem to be the primary seat of the
bacterial development. Plague pneumonia is characterized by intense
toxaemia and few physical signs. The abundant, watery sanguineous
sputum is loaded with plague bacilli. Dyspnoea and cyanosis appear
early.
[Illustration: FIG. 69.—Plague Carbuncle. (Reproduced from Simpson’s
Treatise on Plague 1905.) From Jackson’s Tropical Medicine.]
_The Lymphatic System._—It is the presence of the plague bubo
which differentiates bubonic plague. There is no relation between
the size of the bubo and the severity of the attack. Axillary
buboes are the most fatal. A characteristic of these buboes is
their extreme tenderness, the pain causing the patient to draw up
the legs or assume any attitude which will relieve tension upon the
bubo. The size is mainly due to the periglandular infiltration or
oedema, which causes the glands of a group to be matted together.
The elevation of a plague bubo is rather diffuse, not pointed as
with venereal buboes. Femoro-inguinal buboes are about 6 times as
frequent as cervico-maxillary ones. There may be lymphangitis as
well as lymphadenitis.
_Cutaneous System._—The skin over the buboes often tends to become
necrotic and slough off. This however may occur elsewhere and
such lesions are termed “carbuncles.” Capillary haemorrhages of
the skin may cause petechiae and when the area is large they have
been designated “tokens.” In about 5% of cases there is a small
vesicle or pustule at the site of the flea bite as an indication of
reaction. The contents teem with plague bacilli. It is often termed
the primary lesion.
_The Liver, Spleen and Alimentary Tract._—The spleen may show
enlargement and tenderness on deep pressure, as may also the liver,
these organs being markedly congested. The tongue at first is
coated, with clean tip and sides. Nausea and vomiting frequently
occur and, as a rule, there is constipation. Haemorrhages from the
bowel may occur.
DIAGNOSIS
=Clinical Diagnosis.=—It is well to remember that we have a sure and
simple means of diagnosis by bacteriological means so that in the
first cases during an epidemic we should rest the determination of
the case as one of plague solely upon such methods.
One should be suspicious of any case of fever of rapid onset
in which there is marked dulling of intellect and impairment
of speech, as of one intoxicated, together with evidences of
rapidly developing heart weakness. In septicaemic plague we
practically have no other symptoms to guide us—there is not the
exquisitely tender bubo of bubonic plague nor the abundant, watery,
sanguinolent sputum of pneumonic plague.
Typhus fever probably more nearly resembles plague at its onset than
any other disease. There is marked clouding of the consciousness and
intense prostration as with plague and the eruption does not appear
before about the fourth day.
An influenza pneumonia may show the general prostration and cardiac
weakness of plague. In influenza pneumonia we have an onset
with the features of ordinary influenza, which, however, in the
influenza epidemic in 1918 was often short. In plague pneumonia
we have pneumonia from the start. The pulse in plague is early
weak and rapid and the tendency to a stuporous state more marked.
The early appearance of thin watery sputum, which quickly becomes
blood-tinged and always contains plague bacilli is noted in plague
pneumonia. Only a few hours elapse before we have bloody sputum
which in influenza is a later and not constant sign. The dyspnoea
is earlier and much more pronounced in the pneumonic plague. At
autopsy Crowell notes the almost invariable presence of pleural
exudates in plague while an acute vesicular emphysema is a feature
of influenza pneumonia.
Malaria and septicaemic conditions may be confused with septicaemic
plague. The sudden onset and prostration of relapsing fever may
make one think of plague.
Many have thought climatic bubo a form of ambulant plague but the
gradual onset, only slight tenderness of the swollen glands and
slight prostration should differentiate. Venereal bubo cases are
apt to be regarded with suspicion during epidemics.
Markedly toxic cases of typhoid fever with an exceptionally rapid
onset may give rise to confusion.
=Laboratory Diagnosis.=—If the patient has a bubo we should
introduce a hypodermic syringe needle into the swollen, oedematous
glandular mass in order to obtain some of the gland juice. Smear a
drop of this on a slide, stain with Loeffler’s blue or dilute carbol
fuchsin and examine for bipolarly stained oval bacilli. When the bubo
begins to soften we may not obtain plague bacilli.
Probably the best stain for plague bacilli is that recommended by
Archibald. There are two solutions, one made by dissolving 0.5 gram
of thionin and 2.5 grams phenol crystals in a 1% aqueous solution of
formalin; the other solution is made by dissolving 0.5 gram methylene
blue and 2.5 grams phenol crystals in a 1% formalin solution. Let
these stock solutions stand 24 hours before using and then mix equal
parts of each solution; filter, and stain smear for 10 seconds. Wash
and dry.
In a case of suspected pneumonic plague we stain the smear of
watery or thin blood-tinged sputum as above.
The same procedure may be followed with a rather heavy blood smear of
a drop of the 5 or 10 cc. taken from a vein for culturing in a case
suspected of septicaemic plague.
Plague is practically the only bacterial disease where there
is likelihood of finding the causative organism in smears. In
septicaemic plague the blood culture is the proper procedure and
one should take 5 to 15 cc. of blood in 15 to 25 cc. of normal
saline containing 1% of sodium citrate. This prevents coagulation
and at one’s leisure 1 or 2 cc. can be added to tubes of melted
agar and plates poured or other portions added to bouillon or 3%
salt agar. This same blood emulsion can be used to infect guinea
pigs subcutaneously or to infect them cutaneously by rubbing on the
shaven surface.
In smears from material from buboes, from sputum, or in blood
smears, as well as from blood or spleen smears from experimental
animals, we obtain the typical morphology of a cocco-bacillus (1.5
× 0.5 microns) with very characteristic bipolar staining, there
being an intermediate, unstained area. Very characteristic also
is the appearance in these smears of degenerate types which stain
feebly and show coccoid and inflated oval types. The presence
of these involution forms associated with typical bacilli is
almost diagnostic for one with experience. Inoculating tubes of
plain agar and 3% salt agar with this same material, we obtain
in plain agar cultures organisms which are, typically, small,
fairly slender rods, which do not stain characteristically at
each end and are not oval. The smear obtained from the salt agar
presents most remarkable involution forms—coccoid, root-shaped,
sausage-shaped forms, ranging from three to twelve microns in
length, more resembling cultures of moulds than bacteria. Another
point is that on the inoculated plain agar we are in doubt at the
end of twenty-four hours whether the dew-drop colonies are really
bacterial colonies or only condensation particles. By the second
day, however, these colonies have an opaque grayish appearance,
so that now, instead of questioning the presence of a culture, we
consider the possibility of contamination.
Blood cultures in septicaemic plague may show from 5 to 500,000
bacilli per cc. Smears from the blood in such cases are positive in
only about 17%.
The plague bacillus grows well at room temperature—its optimum
temperature being 30° instead of 37°C., as is usual with pathogens.
Next to the salt agar culture, the most characteristic one is
the stalactite growth in bouillon containing oil drops on its
surface. The culture grows downward from the under surface of the
oil drops as a powdery thread. These are very fragile, and as the
slightest jar breaks them, it is difficult to obtain this cultural
characteristic.
Albrecht and Ghon have shown that by smearing material upon the
intact, shaven skin of a guinea pig, infection occurs. This is the
crucial test. Smear the material on a shaven surface about 1 inch
square.
A pocket made by cutting the skin of a guinea pig with scissors
and extended subcutaneously with scissors or forceps, into which
a piece of the suspected plague tissue is thrust with forceps, is
more practical than injecting an emulsion with hypodermic syringe.
Mice inoculated at the root of the tail succumb quickly. Rats, this
being primarily a disease of rats, are of course susceptible.
When a guinea pig is inoculated with plague material the animal
should be placed in a galvanized iron garbage can or other similar
container and the opening covered with cheese cloth to prevent the
fleas or other vermin which it might harbor from escaping. Again a
6-inch band of tanglefoot fly paper should be attached around the
interior of the upper part of the can to further prevent escape of
fleas. It must be remembered that every precaution must be taken
in the laboratory to prevent the escape of plague-infected fleas.
The guinea pig usually dies in from two to five days and shows
glandular enlargements, and marked congestion of viscera with a
swollen spleen, smears from which may show a profusion of plague
bacilli.
The subcutaneous tissues about the site of inoculation show a
haemorrhagic oedema.
If guinea pigs are not available one may use white mice which die
within forty-eight hours or white rats which live about as long as
guinea pigs.
One of the most important points in fighting plague is the
detection of plague in the rats and, from noting the locality in
which such plague-infected rats were caught, to direct our rat
destruction efforts to that particular section of the city. These
dead rats should be dropped into a bichloride solution or petroleum
preparation in order to destroy the rat fleas. In the laboratory
they are dissected and plague-infected ones most easily recognized
by the marked subcutaneous injection of the widely reflected
skin flap. Oedematous or haemorrhagic glandular swellings are
characteristic. The liver shows a yellowish appearance, and as
if sprinkled with small whitish dots and the spleen is swollen
and congested. There may be effusion into the pleural cavities.
Material from the swollen glands or spleen should be stained,
cultured and inoculated into animals as for a human case.
If glandular, splenic or other material from human or rat autopsies
has to be sent to a distant laboratory the specimen should be placed
in a strong salt mouth bottle containing 20% glycerine in water with
2% calcium carbonate.
Agglutination is not very practical owing to the frequent absence
of agglutinins from the serum of plague patients. Then, too, there
is a marked tendency to spontaneous agglutination on the part of
the plague bacilli. Strong states that culturing at 37°C. lessens
this tendency to spontaneous agglutination. Again, even when
present, the titre of plague-agglutinating sera is usually quite
low so that one must work with dilutions of from 1 to 10 or 1 to 20.
PROGNOSIS
Pneumonic and septicaemic plague give an almost absolutely
unfavorable prognosis, many stating that every such case dies.
As regards bubonic plague the mortality averages 75%. The Egyptian
epidemic of 1900 gave an average mortality of 50%. The mortality
in natives is much higher than that among Europeans, these latter
often showing death rates under 25% while in the same epidemic
natives show from 75% to 95% mortality. Plague pneumonia, however,
is absolutely fatal for Europeans as well as natives.
PROPHYLAXIS AND TREATMENT
=Prophylaxis.=—In pneumonic plague it is the human patient and not
the rat which has to be considered. The infection is spread by means
of droplets of plague bacilli-laden sputum which are sprayed from the
mouth of the patient in the act of coughing. As a result any person
entering a ward containing plague pneumonia cases is extremely liable
to contract the pneumonic form of plague.
The attendants are protected by bag-like masks or successive layers
of gauze and cotton wool applied as bandages over face and neck.
Motoring goggles make a good protection for the eyes and small
rolls of cotton should be placed along the sides of the nose to
absolutely prevent the possibility of bacilli being drawn down to
the entrance of nose or mouth. These masks should not have any weak
spot in their armor.
_Spread of plague pneumonia_.—It has been noted that when
secondary pneumonia develops in the course of bubonic plague in
India, the Philippines, or other hot countries, it is not followed
by primary plague pneumonia outbreaks. This is thought to be due to
the fact that the windows are wide open and the relative humidity
low, conditions which are the opposite of those which existed
in Manchuria where the intense cold made the closing of windows
necessary and where the air of rooms or wards was saturated with
the moisture from the occupants. As the main consideration for the
spread of pneumonic plague seems to be high relative humidity it
would seem that hospital wards could be constructed so that the air
supplied by artificial ventilation would be very dry.
The recent outbreak of septicaemic plague in Ceylon at a time
when there was no plague noted in rats would indicate that other
transmitting agents than infected rat fleas were operative. The most
probable transmitting insects to be suspected would be the bedbug and
human flea.
_Spread of bubonic plague_.—With bubonic plague, unless it should
in its course become pneumonic or septicaemic, there is almost
solely the question of the rat and its fleas. Many authorities
consider that pure bubonic plague can be treated safely in a
general ward of a hospital provided there is sure freedom from
bedbugs or other verminous insects.
The various species of fleas which the rat may harbor may be
attacked by the use of various petroleum preparations containing
naphthalene. One preparation known as pesterine, which consists of
kerosene 20 parts, soft soap 1 part and water 5 parts, the soap
being dissolved in the water and the oil being gradually stirred
into the hot mixture, is often recommended as a flea insecticide. A
5% solution of compound cresol to which naphthalene has been added
is also of value.
It is always well to combine flea destruction with rat extermination
because, as rats are reduced in numbers, there are fewer hosts,
so that man is more liable to infection with fleas deprived of a
sufficient number of rat hosts.
This may explain why a high death rate among rats, as the result of
a plague epizootic, may act as a factor in the outbreak of human
plague.
_Rat destruction_.—As a matter of fact, however, it is best to
attack the problem from the side of rat extermination which, it
must be understood, is most difficult owing to the highly developed
suspicious nature of the rat. A successful rat catcher or rat
exterminator must have the mind of a detective.
The first measure in rat extermination is the regulation of the
disposal of garbage. It is most important that only cans with
securely fitting tops be used so that rats cannot secure any food
from the contents of the can. Again no particle of food should be
left accessible to the rat. Unless the ordinary food supply of the
rat is denied him he will not eat poisoned bait or bait in traps.
Again rats are not only carnivorous but will eat any kind of cereal
or vegetable, in fact they will eat almost anything and in addition
are cannibals. In a plague outbreak especial attention should be
directed to flooring in stables, under surfaces of board walks,
sealed-in attics of houses, wharves and sewers. Where sewers have
catch-basins at street openings the rat has a means of egress from
the sewer. These sedimenting catch-basins also serve as a breeding
place for mosquitoes. It has been estimated that a sewer rat can
jump 2 feet but not 3 feet.
In rat-proofing houses, double walls should be eliminated and
houses raised well from the ground—at least 18 inches. In
plugging up rat holes with concrete we should add broken glass to
the concrete. Sheets of galvanized iron driven down several feet
have been used as a protecting barrier around grain elevators or
warehouses. Concrete is the proper material to use in rat proofing.
Where rats are on board ship fumigations with sulphur dioxide, carbon
monoxide or funnel gases are usually employed.
Hydrocyanic acid gas is a most efficient destroyer of rat and flea
life. The great objection to its use is its danger to those using
it in fumigation. Liston allows this gas, developed from ½ ounce
KCN, to act for four hours in a space of 100 cubic feet. The great
danger from the use of this gas in holds of ships is that it tends
to collect in detached spaces or pockets and remains following
ventilation of the hold so that persons entering such spaces
suffer the poisonous effects of the gas. Some cargo ships have a
rat-run built to extend fore and aft and leading to a receptacle
in which the rats are caught. Rats naturally choose a tube or
similar opening so they get into this little passageway which is so
constructed that their return is obstructed. This scheme is used
in setting traps, either covering the traps with hay and leaving
a small opening or placing the trap under an inclined plank or
placing it at the end of an iron or terracotta pipe. There is not
much danger of rats getting aboard a ship lying out from the dock.
It is when a ship goes alongside a dock that we can expect rats to
come aboard.
Phosphorus paste made up with a glucose base and containing about
4% of phosphorus is spread on pieces of stale bread, 1 inch square
and ¾ inch thick. Whatever poison is used, whether strychnine,
arsenic or phosphorus, it should be placed in boxes which have
openings large enough to let the rats in but too small for
domesticated animals. Barium carbonate is a useful rat poison.
Cats will very rarely attack the fierce sewer rat.
_Danysz virus._—Many workers, during plague outbreaks, have tried
to exterminate rats by impregnating bread or other bait with
bacterial cultures. The best known of these viruses, as they are
called, is that of Danysz. The organism is closely related to _B.
enteriditis_ of Gaertner and is supposed to bring about a fatal
infection in the rats. As a matter of fact the cultures quickly
cease to be virulent and their use has been generally abandoned.
Simpson, however, thinks well of this measure and employed it with
success in South Africa. He kept up the virulence of his cultures
by frequent passage through animals.
In rat extermination it is advisable to employ Heiser’s Manila plan.
In this, the location in the city of the plague rats brought into
the laboratory is noted and radiating lines made from such foci.
Plague-infected rats are rarely found more than a few squares from
the focus. The periphery of the infected area is then considered as
an outer zone for the fight and the house-to-house extermination is
carried on toward the center of the area. If, on the other hand, one
should start at the center and work peripherally the infected rats
might be spread all over the city.
_Prophylaxis by Immunization._—The best-known bacterial prophylactic
is that of Haffkine. Stalactite bouillon cultures are grown in flasks
for five to six weeks. The organisms are then killed by heat at
65°C. for one hour. Phenol (½%) is then added and from 0.5 to 4 cc.
injected according to the age and size of the individual. Ten days
later a still larger amount is injected. The reaction following these
injections is apt to be quite severe.
Recent reports show that of 118,148 inoculated persons the plague
incidence was approximately 8 per 1000 while among 321,621
noninoculated the incidence was 34 per 1000.
Statistics from Sagaing show 19 cases with 7 deaths among 4284
inoculated persons while there were 134 cases and 128 deaths among
4467 not inoculated.
The plague mortality in cases which had previously been inoculated
was 40% while that among the noninoculated was 78%.
From the above it will be seen that incidence is reduced to about
one-fourth and mortality about one-half as the result of the use of
Haffkine’s prophylactic.
Besides this killed culture other material has been used. Lustig
and Galleotti used the nucleo-proteid from plague bacilli for
subcutaneous injection. Kolle and Strong have recommended a vaccine
of living but nonvirulent plague bacilli. A higher degree of
immunity seems to be conferred by this living vaccine but there are
certain dangers in the use of living organisms which outweigh the
advantage noted above.
Yersin’s antiplague serum, which is prepared by injecting horses at
first with killed cultures and later with living plague bacilli,
may be used as a prophylactic as well as in treatment. One point
to consider is that such serum, if used immediately after taking
from the horse, might contain living plague bacilli. The phenol
preservative prevents this. It must be remembered that this is a
passive immunization as against the active one with Haffkine’s
prophylactic, hence the protection is very short, only ten days
or two weeks as against the more enduring immunity of a year or
so following Haffkine’s prophylactic. It must be remembered that
anaphylactic manifestations may follow the repeating of the dose
of Yersin’s serum. It is probably advisable for one who is to be
exposed to plague for a short time only to receive an injection of
the serum. As regards pneumonic plague there seemed to be little
protection attaching to either active or passive immunization.
=Treatment.=—It may be stated that the only treatment which has any
curative value is that with antiplague serum. This would appear
to be of considerable value in bubonic plague provided it is
administered in the first day or two of the disease. It must be given
in large amounts, from 50 to 100 cc. or even to the extent of 250
cc. Then too such enormous doses apparently require to be repeated.
Intravenous administration gives a better chance for success in
desperate cases. In septicaemic and pneumonic plague the use of serum
has been without result.
Salvarsan, as might be expected, has been tried but did not prove
of any value.
Connor has reported success with the intravenous injection of one
dram of a dilution of 1 part of tincture of iodine in 10 parts of
sterile water. He gave 6 such injections to a severe case with good
result.
In the way of symptomatic treatment one should use ice-bags to head
and cold sponging to the body.
Morphine seems to be the best drug to calm the patient. Cardiac
stimulants, especially strychnine, are indicated for the heart
weakness so much a feature of plague. Some consider incision or
enucleation of the bubo of value in treatment but it has always
seemed to me that the going into the periglandular exudate might
serve to set up a septicaemic condition when otherwise it might not
supervene.
CHAPTER XIV
TULARAEMIA
DEFINITION AND SYNONYMS
=Definition.=—This is a plague-like disease of various rodents,
transmissible to man, caused by an organism _Bacterium tularense_,
which is not closely allied to any other species. A number of human
cases have been reported from Utah, where the disease is prevalent
among the jack rabbits, and the transmission to man is through the
bite of a horsefly, _Chrysops discalis_, which has previously sucked
the blood of infected jack rabbits.
The site of the bite in man is usually marked by a punched-out
ulcer, which is associated with swelling and suppuration of the
glands draining the area. The general symptoms are sudden onset,
with rigors, followed by an irregular fever of three or four weeks’
duration and by a prolonged convalescence. Several cases have been
reported in the middle west due to handling infected rabbits. There
have been a number of infections in laboratory workers where the
local signs have been absent. In man death rarely results from the
disease.
=Synonyms.=—Deer-fly fever (in man). Plague-like disease (in
rodents).
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—In 1911 McCoy and Chapin discovered the _B. tularense_
in a plague-like disease, first described by McCoy in the
California ground squirrel. They described the organism, succeeded
in cultivating it on special media, transmitted the infection to
various rodents by feeding, nasal inoculation and injection of
infected blood, and demonstrated the probable natural mode of
transmission by the squirrel flea.
In recent publications, Francis, Lake and Mayne, and Wayson have
recorded the transmission of the disease experimentally by the
house fly (_Musca domestica_), the horsefly (_Chrysops discalis_),
the stable fly (_Stomoxys calcitrans_), the rabbit louse, the mouse
louse and the bedbug, and have shown that the freshly recovered
organism can be grown on other than the special media previously
recommended.
=Geographical Distribution.=—The first case of infection occurring
in man was reported from Ohio by Wherry and Lamb in 1914. Since
then a number of cases have been reported by Francis among rural
residents of Utah and by Francis and Lake among laboratory workers
handling animals infected with _B. tularense_.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—_Bacterium tularense_ is a small nonmotile Gram-negative
cocco-bacillus, from 0.3 to 0.7µ long and gives the appearance in
stained preparations of being surrounded by capsular material. It is
very difficult to cultivate and until recently it has been grown only
on coagulated egg yolk as used by McCoy and Chapin.
[Illustration: FIG. 70.—_Chrysops discalis._ The transmitting agent
of tularaemia.]
Recently Francis has shown that the organism will grow scantily on
serum or blood agar. However, by adding a piece of fresh sterile
spleen to such media he has obtained a more satisfactory culture
medium, although for routine work the egg yolk medium is preferred.
The organism refuses to grow on ordinary media such as nutrient
broth or agar. Material from a culture, or pus from bubo, or an
emulsion of the spleen of an infected guinea pig, when rubbed into
the abraded skin of an experimental animal brings about infection,
in this respect showing a similarity to plague infection. Upon
autopsy of such an experimentally infected guinea pig we find
haemorrhagic oedema at the site of inoculation with caseation of
lymph glands and small necrotic foci in spleen and liver. Smears
from the spleen show the organism in varying numbers. In infected
rodents the organism is often found abundantly in the blood and in
man a bacteriaemia may occur.
=Epidemiology.=—The infection of ground squirrels with this
organism was noted by McCoy in his plague work in California.
Francis in studying the disease in man in Utah found infection of
the jack rabbits and ground squirrels of the region and showed that
the transmission of the disease could be carried out by a biting
fly (_Chrysops discalis_) and reported this fly as the common
transmitting agent of the human infection. He regarded the sick and
dying jack rabbits as the reservoir of virus. Tularaemia is chiefly a
disease of the rural population attacking those at work in the fields.
As a result of accidental laboratory infections it would seem that
almost 100% of those carrying on extensive animal experimentation
with this organism become infected.
The louse infesting jack rabbits _Haemodipsus ventricosus_, can
transmit the infection from rabbit to rabbit so that the infection
in the jack rabbits is probably kept up by this agency. Recent
experiments have shown that the infection in white mice can be
transferred by the bites of the mouse louse and also by bedbugs.
Again if the mice are fed on infected bedbugs transmission is found
to take place by such feeding experiments. The faeces of such
bedbugs prove infectious. Guinea pigs injected subcutaneously with
the urine of white mice suffering from the disease die acutely with
typical lesions of tularaemia.
Mice fed on the liver of a rabbit dying of the disease succumbed to
the infection within five days.
As noted under etiology the most important method of spread of the
disease to man is by the bite of an infected horsefly (_Chrysops
discalis_). From experimental studies it would seem that any biting
arthropod might prove a transmitting agent. In view of the fact that
the infected deer fly tends to lose its infectivity after about five
days Francis is of the opinion that the fly is only a mechanical
transmitter of the organism.
Wherry reported the infection as manifested by conjunctivitis with
glandular involvement and due to handling infected wild rabbits.
Lake and Francis have reported that of six investigators from
the Hygienic Laboratory working with this infection all have
contracted the disease. There were fortunately no fatalities. Such
an experience demonstrates the great infectivity of this virus and
must lead to the conclusion that the few cases so far reported of
the disease do not represent the importance of tularaemia in man.
With a knowledge of the existence of such an infection and with
satisfactory methods of laboratory diagnosis we shall probably
have other reports of the infection. We now know that the ground
squirrels of California and Utah, the jack rabbits of Utah and the
wild rabbits of the middle west furnish important reservoirs of
virus.
PATHOLOGY
In experimental animals we have lesions which cannot well be
differentiated from those of plague. There is not sufficient data for
a statement as to the pathology in man.
In experimental animals we have a definite bacteriaemia but in man
the organism has only in rare instances been obtained from the
blood.
SYMPTOMATOLOGY
It has been difficult to determine the period of incubation but in
one laboratory infection the disease set in seven days after the
patient began tularaemia work. There do not seem to be any prodromata.
[Illustration: FIG. 71.—Temperature chart of a case of laboratory
infection (tularaemia.)]
In Utah most of the cases showed local lesions at the site of the
fly-bite and subsequent swelling and suppuration of adjoining lymph
glands. The local lesions were generally observed about the head or
on parts of the body not covered by the clothing. There is a rather
sudden onset with chilliness or rigors, generally associated with
dizziness, prostration and malaise. Headache is usually present
and there may be complaints of pains in the back and limbs. The
temperature rises rapidly and when first taken during the rigors may
reach 103° or 104°F. An irregular fever course follows for two or
three weeks. There is practically no apathy, thus differentiating
the mental state of typhoid fever or the marked clouding of the
consciousness of plague. At times we may have rhinitis and epistaxis.
Physical examination is almost invariably negative. The spleen is
not palpable. The pulse is rather rapid and the blood pressure
uninfluenced.
The white and differential counts vary but little from normal.
The main feature of the disease, aside from local lesions when
these are present, is prostration and this continues marked during
the several weeks or months of convalescence.
It is a disabling illness rather than a dangerous one though a fatal
case is recorded.
In the six laboratory infections above referred to, there were no
local lesions except in the case of one man who had had previously
an attack of the disease. In the second attack, two years after the
first one, there was noted a papule on one finger with subsequent
involvement of the epitrochlear and axillary glands. A guinea pig
inoculated with blood taken from the papule became infected and
showed the typical lesions of tularaemia.
There was no fever or malaise in this second attack, thus showing
a degree of immunity. In cases showing conjunctival ulcerations
with glandular involvement Wherry and Lamb obtained cultures of _B.
tularense_ from inoculated animals.
DIAGNOSIS
There is very little in the clinical picture, other than the local
lesions, to indicate a diagnosis.
Material from ulcers or glands should be inoculated into guinea
pigs or white mice. The organism is almost invariably absent
from the blood of human cases so that blood cultures or animal
inoculation from such blood are almost always negative.
Complement fixation and agglutination tests are the methods of
diagnosis to be relied on. In the Hygienic Laboratory an antigen
is prepared by washing off the 72 hour growth from egg yolk
medium with small amounts of saline. The suspension is heated for
30 minutes at 56°C. and then preserved by the addition of O.3%
tricresol. Such an antigen is used for each type of test.
PROGNOSIS
This disease is but rarely followed by death. It is however a most
incapacitating disease by reason of the three or four months of
convalescence during which time the strength and energy of the
patient are markedly affected.
PROPHYLAXIS AND TREATMENT
=Prophylaxis.=—In view of the very great liability to infection
of those carrying on autopsies of animals experimentally infected
with the disease it would seem advisable to wear rubber gloves when
doing such work. It would appear that house flies, stable flies
and horseflies may transmit the disease in nature and we know that
bedbugs and lice can transmit the disease among experimental animals.
When we consider the natural infection of ground squirrels and jack
rabbits in California and Utah and wild rabbits in the middle west,
the problem of prophylaxis looms to great proportion.
=Treatment.=—At present treatment is entirely symptomatic. Those who
go to bed at once and remain in bed during the stage of fever seem to
be less seriously affected.
CHAPTER XV
CHOLERA
DEFINITION AND SYNONYMS
=Definition.=—Cholera is a disease caused by a spirillar type of
bacterium, _Spirillum cholerae asiaticae_. The organism multiplies in
the small intestines and, undergoing lysis, liberates an endotoxin,
which is responsible for the desquamation of the epithelium of the
mucosa and other manifestations of the disease. Cholera appears to
be endemic in the delta of the Ganges and the various world-wide
epidemics can generally be traced to that source. The rice-water
stool of cholera teems with the spirilla, and infections of water or
food supplies can be traced to such a contamination. The importance
of the cholera carrier has been thoroughly demonstrated from the time
of the Hamburg epidemic of 1892. The clinical course of the disease
is divided into a stage of evacuation, in which we have diarrhoeal
discharges of rice-water character along with very painful cramps of
the muscles. Following increasing cyanosis we have almost a cessation
of circulation often associated with anuria, the algid stage. With
the return of activity of circulation and urinary secretion we have
the stage of reaction.
=Synonyms.=—Cholera Asiatica.
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—Although the word χολέρα, meaning flow of bile, is found
in the writings of Hippocrates, it certainly does not refer to the
disease we now recognize as cholera. The older writers noted the
characteristics of bilious discharges in the disease they termed
cholera, which could not apply to the bile-free rice-water discharges
of what we now term cholera. Koch rather doubted the antiquity of
cholera but Susruta, in India, in the 7th century A. D., described a
disease in which there were diarrhoea and vomiting, stabbing pains,
cyanosed lips and nails, with sinking in of the eyes and weak voice.
Detailed accounts of the presence of cholera in India were
published from the 16th to 18th centuries when the Portuguese,
English and French were carrying on their wars of conquest in
India. These wars naturally spread the disease all over India.
It is thought that true cholera did not exist in China until 1669
when it was carried there from India. It is first described from
Japan in 1821 although an epidemic which devastated Tokyo in 1718
may have been cholera.
A great pandemic of cholera started in India, in 1817, extending
over Asia but not invading Europe. The second great pandemic is of
importance as being the first to invade Europe. It started in India
in 1826 and advancing slowly reached Persia in 1829, going thence
by way of Astrakhan to Russia, Sweden, Northern Europe and England.
By 1832 it had spread over the whole of Europe.
In the same year, 1832, it reached Canada and thence spread to Fort
Dearborn where it infected the soldiers who subsequently carried
the disease down the Mississippi valley. It was also introduced
into New York and spread thence South and West so that by 1836
cholera was present all over the U. S., not disappearing until
1838. It disappeared from Europe in 1839.
The next European outbreak or third pandemic lasted from 1846 to
1862 and was traced to India by way of land and sea, that by land
following the caravan route by way of Persia and Russia and that
by sea from Indian pilgrims going to Mecca and there causing the
infection of Mahommedan pilgrims from Egypt and European Turkey.
This pandemic reached the U. S. in 1848, starting at New Orleans
and going up the Mississippi valley. Central and South America and
the West Indies were also invaded by the third pandemic.
The fourth great pandemic invaded Europe by the usual routes and
continued from 1863 to 1875. During its continuance there were two
outbreaks in the U. S., one in 1867 and another in 1873.
That in 1873, when it was introduced into three widely separated
parts of the country, was the last appearance of cholera in the U. S.
The fifth pandemic began in 1883 and affected particularly the
Mediterranean seaports of France, Spain and Italy. It was during
this epidemic, in 1883, that Koch, working in Egypt, discovered the
cause of cholera, the _Spirillum cholerae asiaticae_.
A very serious outbreak of cholera, which originated in 1891, in
pilgrims from the delta of the Ganges, reached Europe in 1892,
almost a million deaths occurring in Russia. It was during this
epidemic that cholera appeared in Hamburg and gave opportunity for
those careful studies as to transmission of the disease to be later
referred to.
It is usual to recognize a sixth pandemic which began in 1902
and spread over India, China and the Philippines. This pandemic
continuing was a cause of great mortality among the soldiers
of the recent Balkan war. During the World War there was much
cholera among the Austrian forces in Galicia. It also prevailed in
Bulgaria, Greece and Turkey.
=Geographical Distribution.=—Practically every pandemic when
studied can be traced back to India and particularly to the delta
of the Ganges, which may be considered the enduring focus of the
disease.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—The cholera vibrio, _Spirillum cholerae asiaticae_, was
discovered by Koch in 1883 and is a short curved organism which,
from its shape, is often called the comma bacillus. In addition to
single spirilla there may be “S” shapes from attachment of pairs.
In cultures in peptone solutions long filamentous forms may be
seen which however are exceedingly rare in the rice-water stools.
A stained smear from a fleck of mucus gives the fish-in-the-stream
appearance. Besides comma-shaped organisms we may have coccoid or
rod-shaped forms. In old cultures marked pleomorphism is often seen.
[Illustration: FIG. 72.—Cholera vibrios, short forms. (MacNeal from
Kolle and Schurmann after Zettrow.)]
It is Gram-negative and stains best with a dilute (1-10) carbol
fuchsin. There is a single terminal flagellum, which endows
the organism with great motility, which may best be termed
scintillating. It has been estimated that its motility is five
times greater than that of the typhoid bacillus. It grows best on
media with an alkaline reaction (—0.4%) and it is this tolerance
for media of high alkalinity that permits the separation of the
cholera spirillum from the ordinary faecal bacteria by the use of
Dieudonne’s alkaline blood agar or similar media. This is equal
parts of defibrinated ox blood and N/1 NaOH, 3 parts of which
are added to 7 parts of nutrient agar. It thus has 15% of normal
sodium hydrate, instead of the 1% acid reaction of the usual media.
Unfortunately, other spirilla tolerate this high alkalinity.
The cholera organism is strongly aerobic and grows quickly and
luxuriantly in the upper part of a tube of Dunham’s peptone
solution, this property enabling one to separate it from other
organisms of faeces by taking up loopfuls from the surface layer
to plate out on agar of about 0 or -0.3% reaction. When grown in
peptone solution the cholera spirillum produces a nitroso body so
that one obtains an indol reaction (cholera red) by simply adding 5
or 6 drops of concentrated H_{2}SO_{4}.
When this test is employed it is necessary to determine whether the
peptone used is suitable for the reaction. As a matter of fact this
test is now rather discredited. Blood serum is digested. Recently
much discussion has arisen as to the value of the haemolytic power
possessed by noncholera vibrios on blood agar plates.
It is true that the digestive action which true cholera has on
the red cells of the medium may give the appearance of a zone of
haemolysis. Therefore, for the demonstration of this haemolytic
action of noncholera spirilla, fluid blood media should be used.
The El Tor spirillum, isolated from Egyptian pilgrims without
symptoms of cholera, is haemolytic, but gives the immunity
reactions of the true cholera vibrios which are not haemolytic.
Gelatine is liquefied and the stab shows an air bubble liquefaction
at the summit of the stab. On gelatine plates a powdered glass
center with an encircling zone of liquefaction was formerly
considered characteristic of cholera, but at the present time
gelatine cultures have been almost abandoned in practical work.
As a rule animals cannot be infected by feeding them cholera
material unless the acidity of the gastric juice be neutralized
and intestinal peristalsis checked by opium (procedure of Koch).
Injected intraperitoneally, the cholera vibrio produces a fatal
peritonitis. Recently monkeys have been infected after purgation
with sulphate of soda and administration of bicarbonate of soda.
They died in from one to forty-eight hours with symptoms of cholera.
There have been instances where cholera has been caused in laboratory
workers by the accidental ingestion of cholera cultures, thus Orgel
was infected from sucking up peritoneal fluid in doing Pfeiffer tests
for bacteriolysis and died.
Emmerich and Pettenkofer swallowed cholera cultures, the former
experiencing a severe attack of cholera and the latter a diarrhoea
in which cholera spirilla were present. On the other hand similar
experiments have resulted negatively but this is what should be
expected from the epidemiological facts as to carriers.
The virulence of the cholera vibrio can be exalted by passage
through guinea pigs—successive culturing of the peritoneal exudate
of intraperitoneally infected animals alternating with culture
media growth inoculations. Such a fixed virus, the virulence of
which cannot be exalted, is the material used by Haffkine in
his cholera vaccine. The toxicity of cholera is supposed to be
due to an endotoxin which is set free when the vibrios undergo
disintegration when lying between the basement membrane and
epithelial lining of Lieberkühn’s glands. Others think the vibrios
may enter the blood stream, there to be immediately disintegrated
with toxin production. The usual idea, however, is that the cholera
spirilla never invade the blood stream—they are confined to the
alimentary canal. Macfadyen obtained the endotoxin by grinding the
frozen spirilla. This toxin was destroyed by a temperature of 60°C.
The spirillum of cholera has but little resistance to disinfecting
agents or to drying. It is also rapidly overgrown by putrefactive
bacteria and tends to disappear from sewage-contaminated water in a
short time. In stools the vibrio dies in about one or two days in
summer and in about a week in winter.
The inoculation of animals by cholera cultures tends to produce an
immune serum which is remarkable for its high agglutinating power,
the titre at times going as high as 1 to 20,000. For agglutination
tests in proving spirilla isolated from stools to be true cholera
ones we use a serum of at least 1 to 4000 for its specific vibrio.
Such a serum should agglutinate any true cholera spirillum in a
1 to 500 or 1 to 1000 dilution. The occurrence of bacteriolysis,
when a small loopful of the culture emulsified in 1 cc. of 1 to
1000 dilution of the immune serum and then introduced into the
peritoneal cavity of a guinea pig, is the surest proof that a
suspected organism is that of cholera.
This is shown when, upon removing a drop of the peritoneal fluid
fifteen to twenty minutes afterward, there is noted an absence
of motility and disintegration of the spirilla (_Pfeiffer’s
phenomenon_).
Complement fixation tests, using the rice-water stools or peptone
solution cultures as antigen, are of less value than those above
noted. Agglutination is the practical test and is almost as
specific as that for bacteriolysis.
=Epidemiology.=—Until recently our attention as to the methods
of transmission of cholera was directed almost exclusively to the
water and food supply, with a certain degree of consideration of
danger from fomites, especially to that connected with clothing
soiled by cholera discharges, it having been noted that those who
wash such clothing showed a high incidence of infection. Later on
the importance of flies in the spread of the disease was strongly
insisted upon. At the present time we consider the cholera carrier
the most important factor in cholera epidemiology and it is to the
detection and isolation of such persons that we now chiefly direct
our attention in the keeping out of a country of this dread disease.
It will be remembered that Pettenkofer and Emmerich insisted upon
the factors of soil and ground water in the spread of cholera.
Emmerich now admits that the spirilla excreted by carriers can
produce cholera but that such transference never gives origin
to epidemics. For this to take place he thinks that the vibrios
excreted by a carrier must come in contact with a soil which has
been impregnated with a suitable medium drawn to the surface from
the deeper layers of the soil by capillary suction. In such medium
the vibrios flourish and acquire the property of actively producing
nitrites from nitrates.
Emmerich considers that the symptoms of cholera are those of
nitrite poisoning so that only such organisms as possess this
nitrite-forming function in high degree can produce virulent
outbreaks of cholera.
All facts in connection with the spread of cholera by land or water
routes can be best explained by the cholera carrier; the individual
who is excreting vibrios, while in apparent health, being far more
dangerous than the one excreting such organisms in the rice-water
stools of a well-recognized case of the disease.
_Water Transmission._—There are two types of outbreaks of cholera
according as the general water supply is contaminated or when such
contamination is localized to certain wells, cisterns or other
nongeneral supplies. In the former the onset is explosive and cases
occur almost simultaneously and with equal distribution in all parts
of the city, to disappear with almost equal suddenness.
In the latter mode of infection, cases will appear from day to day
and often peculiarly localized to certain definite districts of a
city or to certain definite users of a particular water supply.
[Illustration: FIG. 73.—An instructive contrast between Altona and
Hamburg before the latter filtered its water, having learnt its
lesson from a sharp outbreak of cholera. (After G. E. Armstrong.)]
As an example of the first type of outbreak the Hamburg epidemic of
1892 is most instructive.
During a period of only about two months cholera attacked about
17,000 persons causing 8605 deaths in a city with a population of
600,000. This outbreak was attributed to the washing of clothes in
the water of the Elbe River by Russian immigrants. These immigrants
had come from cholera-infected districts and among them there
undoubtedly were cholera carriers.
The water supply of Hamburg was taken directly from the river.
The adjoining city of Altona, with a population of 140,000, is
further down the river but filtered its water by a slow sand
process. Although the water as taken from the river contained
the sewage of Hamburg yet there were only 328 deaths or 2.1 per
thousand as against 13.4 per thousand for Hamburg. There were many
interesting points in connection with the exemption of certain
places in Hamburg, of which may be noted the instance of the entire
freedom from cholera of a group of houses (Hamburg Hof), with 345
occupants. This was the only section of Hamburg which was supplied
with Altona water. As Hamburg and Altona are only separated by the
width of a street and hence practically form a single city, the
factor of food and contact transmission could easily explain the
cases in Altona.
To illustrate the second type of water transmission we have the
well-known incident of the Broad Street pump.
This was about the first definitely proven connection between water
and cholera. In 1854 it was noted that cholera was about 10 times
as prevalent in Golden Square as in other adjacent parts of London.
Various factors, such as previous droughts, stagnation of lower
strata of the atmosphere, sewerage defects and subsoil drainage
were found to be the same in Golden Square as elsewhere. It was
noted that the number of cases increased in the neighborhood of
the Broad Street well. The employees of a cartridge factory where
this well water was used gave a large number of cases while an
adjoining brewery, which had a well of its own and served out beer
to its employees, did not furnish a single case. Very striking was
the case of a lady living at Hampstead, a section of London which
was then free from cholera, who had acquired a liking for the
water of this well and had brought out to her regularly bottles of
water from the well. This lady drank some of the water on August
31 and was seized with cholera the next day. A niece drank of the
same water and died of cholera as well as the aunt. A servant also
contracted the disease but recovered.
Macnamara has noted the circumstance of a vessel of water, which
became contaminated with cholera stools, but which at the time it
was drunk by 19 persons did not show anything suspicious in odor,
color or taste. One person was stricken one day afterward, two on the
third day and two others came down with cholera on the fourth day. It
will be noted that only 5 of the 19 were attacked. A similar lack of
susceptibility of a certain proportion of people, equally exposed,
has been noted in all cholera outbreaks. It is probable that of those
of the 19 who did not contract cholera there were developed a certain
number of cholera carriers.
_Food Transmission._—Food contaminated by dejecta from cholera
patients or carriers is dangerous in proportion to its condition of
moisture. Drying and the development of inimical organisms are the
two chief factors in destroying the cholera vibrio. Temperature and
sunshine are operative in assisting the drying process.
Lettuce and celery are particularly dangerous because of the
favorable condition of moisture in their folds and imbrications.
Furthermore these vegetables are eaten uncooked and may have been
fertilized with night soil (human excrement) which material, if
containing cholera dejecta, would infect the plants. Milk is a
splendid culture medium for cholera vibrios but, upon becoming
acid, sterilizes itself of these vibrios. In sterilized milk,
however, they live for extended periods, as long as sixty days
and, even when such milk is contaminated by faecal material
containing other organisms besides the cholera vibrio, the vibrios
live much longer than they do in raw milk.
Milk is liable to be contaminated by flies which have been in
contact with cholera stools. Water that has been boiled and food
that has been cooked should subsequently be scrupulously protected
from flies or other contaminating agents. Uncooked shell fish are
peculiarly dangerous in cholera outbreaks.
In India, sun-dried fish, which are frequently covered with flies
during the curing process, are a factor in the spread of cholera.
_Transmission by Carriers._—This is now universally recognized as
the most important factor in the spread of cholera. Dunbar was the
first to draw attention to the presence of virulent cholera spirilla
in the faeces of apparently healthy persons during the Hamburg
epidemic of 1892.
Since that time these observations have been generally confirmed.
In some instances as many as 20% of those who have been in
immediate contact with a cholera patient have become carriers,
some showing symptoms of cholera but a larger proportion excreting
cholera spirilla while continuing in health.
While cholera prevailed in Manila, McLaughlin found from 6 to 7% of
carriers among healthy persons living in the infected districts.
Pottevin has recently reported that of 13,000 pilgrims examined 1.7
per thousand carried cholera vibrios. The carriers were especially
common among the dysenteric patients. During the Naples epidemic
of 1911 it was found that on the average 10% of healthy people in
contact with cholera cases became carriers. It was estimated that
90% of the cases in this epidemic were infected by sick or healthy
carriers.
Sergeant has recently reported the case of a healthy carrier who
continued to excrete cholera vibrios for two months and during this
time was in contact with 8 persons, 7 of whom became infected and 4
died. In Manila it was found that many of the children reported as
dying of meningitis or infantile beriberi were cholera cases.
The vibrios are rarely excreted in the faeces of the cholera patients
longer than seven to ten days. Frequently they disappear in three or
four days.
With healthy cholera carriers the period of the continuance of
vibrio excretion is equally short but cases have been reported
where periods of from three weeks to two months have been noted. It
is usually stated that 97% of carriers become vibrio free within a
month.
Greig has found infection of the bile of the gall bladder or ducts
in 80 cases in 271 cholera autopsies. When living organisms are
injected into the ear vein of a rabbit they pass into the bile.
An examination of the epithelial layers of the gall-bladder of
such a rabbit shows destruction of the cells and the presence of
vibrios in the underlying tissues. While cholera spirilla are soon
crowded out by intestinal bacteria, thus explaining the short
period during which cholera spirilla are excreted by convalescents,
this is not true when the cholera vibrio gets into the bile ducts
or gall bladder. Greig found one cholera convalescent excreting
cholera vibrios forty-four days after the attack. Of 27 persons who
had been in contact with cholera patients 6 were excreting cholera
vibrios although apparently well.
A very important matter is that persons who fail to show
cholera vibrios may begin to excrete such organisms after the
administration of a purgative or following some intestinal
disorder. In fact purgatives may set up an attack of cholera in a
cholera carrier.
The spread of cholera is intimately connected with the great
religious festivals and pilgrimages of Oriental people. Not only
do those of India keep up the dissemination of the disease there
but pilgrims going from the delta of the Ganges to Mecca carry the
infection and transmit it to their fellow pilgrims from Egypt and
Algiers. Greig examined a number of cholera convalescents who were
about to return to their homes in India and found 30 per cent of
these pilgrims excreting cholera vibrios in their stools.
In India cholera accounts for about 1 to 1.5 deaths per 1000 of
population. Malaria and plague are other great causes of death.
The intimate commercial relations between Europe and Egypt and
Algiers make the introduction of the disease into European ports an
easy matter. Of particular importance is the fact that so many sick
people make pilgrimages, these being peculiarly liable to act as
carriers.
Excesses in eating, often of badly prepared or decomposing food,
following periods of religious fasts, predispose the natives of
India to cholera.
Lowered resistance, as from disease or from gastric disorder,
increases the susceptibility to cholera. Errors in diet and in
particular the effects of alcoholic excesses markedly predispose to
infection.
PATHOLOGY
The cholera spirillum does not produce a soluble toxin, the toxic
principle being intracellular. The organism rarely penetrates
more deeply than just under the epithelial layer of the glands of
Lieberkühn. As a result of the outpouring of the fluid into the lumen
of the gut we have an increase in the red cells (7,000,000 per cu.
mm.) and leucocytosis of from 12,000 to 50,000. The specific gravity
of the blood is greatly raised, 1073 to 1078, and the alkalinity
diminished. The blood pressure is markedly lowered, 60 mm. in very
severe cases and 75 mm. in less severe ones.
The lower portion of the small intestines is the favorite location
for the action of the endotoxin of cholera. Early and marked
postmortem rigidity is a striking characteristic of the cholera
cadaver. Muscular contractions, causing odd positions of the
limbs, have at times given a basis for the idea that the victim had
been buried alive.
Besides marked rigor mortis the emaciation, leaden hue of skin and
shrivelled hands are noteworthy.
In opening up the body there is a striking dryness of all the
structures. The dry and dark-red muscles stand out prominently.
The lungs are dry and shrunken. The right heart is full of a dark,
jelly-like, viscid blood. The leading changes are found in the
abdomen. The omentum is dry, sticky and shrivelled looking. The
intestines have a ground glass appearance with a lilac-pink color of
the small intestines which is in contrast with the normal color of
the large intestines.
There is congestion of the affected intestinal mucosa and the lumen
is filled with the alkaline rice-water material. If the case is of
some days standing we have a rather brownish, foul-smelling bowel
content. There is usually a parenchymatous nephritis and on section
the medullary portion is much congested.
Crowell gives the following points as indicating cholera upon
autopsy: (1) Cyanotic finger nails, (2) dry tissues, (3) dry and
sticky peritoneum with pink serosa of ileum, (4) contracted and empty
urinary bladder, (5) shrunken dry spleen and liver, (6) rice-water
intestinal contents and (7) prominence of lymphoid tissues in the
ileum.
In his studies of the pathology of cholera Greig drew attention to
the frequency of the involvement of the gall-bladder. He also noted
the presence of small areas of consolidation in the lungs of those
developing pneumonia during the early days of convalescence. In the
exudates of such areas cholera vibrios could be seen thus showing
their penetration of the lung. Although rare instances of recovery
of the cholera spirillum from the blood have been reported Greig
was unable to accomplish this in any instance. In his opinion the
spirilla travel by way of the lymphatic system. In eight cases out
of fifty-five cases he recovered the spirilla from the urine.
SYMPTOMATOLOGY
=A Typical Case of Cholera.=—The so-called prodromal or premonitory
diarrhoea is not a feature of the onset of _cholera gravis_, the type
of the disease which characterizes the cholera epidemic.
The period of incubation is usually from one to five days. Longer
periods are possibly explained by some exciting intestinal disorder
in a cholera carrier. The course of the disease is conveniently
divided into a stage of evacuation, an algid one and a stage of
reaction.
_The Stage of Evacuation._—A profuse and frequent diarrhoea comes on
without colic or tenesmus. In fact the stools are voided with a sense
of relief as when an enema is gotten rid of.
The striking feature, however, of these movements is the sensation
of prostration which accompanies them.
The faecal character of these diarrhoeal stools is soon lost and the
typical rice-water stool is now passed. This designation is very apt
and the flocculi of intestinal epithelium, in a watery, slightly
opaque fluid, suggests rice-water. The odor is slightly albuminous.
Early in this stage cramps of the muscles set in. The muscles of
the legs, especially the calf muscles and those of the feet, are
particularly liable to these very painful contractions which may
cause the patient to cry out for relief. The muscles of the abdomen
and back may also be involved as may at times the muscles of the
entire body.
Vomiting, at first of the contents of the stomach and later of
rice-water material, is a distressing feature to the patient and by
reason of the manner in which it often gushes from the patient’s
mouth is liable to contaminate the attendants.
Along with the excessive loss of fluid the tissues, especially
of the face, become shrunken, the eyeballs with their congested
conjunctivae sink back in the orbits, and the nose becomes pinched.
The pulse becomes more and more feeble and there is a steady
diminution in the secretion of urine. An increasing duskiness
of the skin, which is cold and clammy to the touch, denotes the
setting in of the algid stage.
_Algid Stage._—In this stage there is almost complete cessation of
circulation, even the incision of a vein is only followed by a drop
of black tarry blood. Anuria is practically complete.
The vomiting, purging and cramps may or may not subside and in the
patient, with his great thirst, intense exhaustion and cadaveric
appearance, with mental faculties fairly well preserved, we have
an example of a living death. The temperature of the sodden,
inelastic, clammy skin is markedly depressed, even below 90°F.,
while the rectal temperature may approximate normal or be elevated.
Some authorities consider a marked difference between the
superficial and rectal temperatures as of bad prognosis.
The voice becomes husky and finally so feeble that the patient can
only whisper and the breath feels cold.
The sodden shrivelled hands, as those of a washerwoman, are very
characteristic. Thirst is intense.
The patient now falls into a listless, motionless state in which,
however, the apathy is more apparent than real. The algidity may
deepen and death ensue or the stage of reaction may set in. The
algid stage may last from a few hours to two or three days.
Collapse and uraemia are the two most frequent causes of death.
_Stage of Reaction._—The pulse returns, urine is again secreted and
the duskiness and coldness of the skin give way to normal conditions
and a favorable convalescence sets in. At other times, however, the
rise of surface temperature and restoration of the circulation are
not attended by urinary secretion.
In such cases a typhoid state ensues with accelerated respiration,
dry, brown tongue and muttering delirium.
It is customary to divide the types of cholera cases into:
1. _Cholera gravis._ The type above described.
2. _Cholerine._ In this there is a more or less marked stage of
evacuation with possibly the appearance of rice-water stools. The
urine, however, does not become suppressed and the algid stage is
not entered upon.
3. _Cholera sicca._ This type of the disease is more apt to be seen
in old or debilitated people. The patient dies of collapse without
showing symptoms of vomiting or diarrhoea. At the autopsy one may
find the bowels distended with rice-water contents.
The so-called _cholera ambulans_ is simply another designation for
the more or less ill cholera carrier.
=Sequelae.=—Following an attack of cholera we may have abscess of
the parotid gland or gangrene of various parts of the body. There may
be ulceration of the cornea. In pregnant women the disease almost
invariably causes abortion. Post-choleraic pneumonias and renal
inflammations are to be considered.
Symptoms in Detail
_General Appearance._—A typical case of cholera, with its
cyanosed, drawn, pinched face, cold, clammy skin and the eyes
deeply sunken in the orbits, makes a picture rarely seen in other
conditions. The washerwoman’s hands appearance should always be
looked for.
_Temperature Record._—The temperature of the skin surface is
lowered from the normal while that of the rectum may be normal or
even elevated. There may be a difference of 10° or more between
rectal and surface temperature. In the stage of reaction the
temperature may continue to rise to high fever points and this
so-called hyperthermic type is very fatal.
_Circulatory System._—The pulse is rapid and feeble in the stage
of evacuation to become imperceptible in the algid stage. The
circulation is practically at a standstill so that only a few drops
of black tarry blood, which does not coagulate readily, flow from
a wound of a vein when giving an intravenous injection. The blood
is concentrated and has a specific gravity of 1072 to 1078. The
systolic pressure falls greatly, even to 60 mm. of mercury in a
severe, or 75 mm. in a less serious case. The red cell count is
increased to 7 or 8 million red cells per c.mm. and the leucocyte
count reaches 15,000 to 50,000.
_Nervous System._—The mind is clear, even when the patient seems
profoundly apathetic. The muscle cramps are characteristic of the
disease.
DIAGNOSIS
=Clinical Diagnosis.=—It is customary to state that cholera
nostras and infections with virulent meat poisoning bacteria of the
paratyphoid group show bile in the intestinal discharges and not the
typical rice-water stools of true cholera. It must be remembered
that these affections can at times show as marked muscular cramps,
emaciation, cyanosis and weak voice as cholera so that only the
bacteriological examination can differentiate.
Algid pernicious malaria generally shows a rather high axillary
temperature and the stools are rarely so profuse as in cholera.
In ptomaine or mushroom poisoning the vomiting usually precedes the
diarrhoea—the opposite of the order in cholera.
Acute intestinal obstructions may simulate but here we have faecal
vomiting and constipation.
With irritant poisons as arsenic or antimony there is the metallic
taste and the pains are chiefly colicky rather than muscular and
the stools rather dysenteric.
I have seen severe cases of bacillary dysentery which could not
be differentiated clinically from cholera, and it is interesting
to note that many cases of cholera occurring in the Balkan war
were diagnosed as bacillary dysentery. In children cerebral
manifestations are very common so that in the Philippines many such
cholera cases were diagnosed as meningitis.
=Laboratory Diagnosis.=—Agglutination is the practical aid in
diagnosis. The serum from cholera convalescents, or those vaccinated
against cholera, show agglutinins. It has been stated that properly
vaccinated cases show a titre of from 1 to 2 thousand in about
70% of cases. Normal human serum does not agglutinate in a higher
dilution than 1 to 20. Greig has found that fatal cholera cases
rarely give higher than 1 to 40. In cases recovering he found
well-marked agglutinating power by the 6th day, titres of 1 to 500
or 1 to 1000 being frequently obtained. Janoue and Watanabe found
the agglutinating power of the sera of convalescents to fall rapidly
after the third week. As a rule the titre varied from 1 to 100 to 1
to 400. The highest titre noted was 1 to 10,000.
It is well to first make a microscopical examination of the stool
by taking one of the whitish epithelial flakes from the rice-water
material and making a straight smear which is then dried and fixed
with heat. This may be stained best by a dilute carbol fuchsin (1
to 10). Methylene blue makes a good stain, or more differential
is that by Gram’s method which shows the Gram-negative spirilla
stained by the bismarck brown counterstain, giving the appearance
of fish parallel to one another in a stream. According to Koch a
diagnosis can be made in this way of one-half the cases during an
epidemic.
The scintillating motility of cholera spirilla may strike one in the
examination of the stool in hanging drop.
Dunbar has a quick diagnostic method in which epithelial flakes
from the stool are emulsified in peptone solution. Then on a
slide, according to the method to be later described, is deposited
a drop of 1 to 50 normal serum dilution and on the same slide a
second drop of 1 to 500 dilution of cholera serum. A loopful of
the suspected stool emulsion is rubbed up in each of these serum
dilutions and we should have cessation of motility and clumping in
the cholera immune serum provided the organisms in the stool are
true cholera spirilla.
In case of an autopsy on a suspected case of cholera one should
tie off, between double ligatures, at least two 5-inch sections
of small intestines, one just above the ileo-caecal valve and one
taken from about the middle of the ileum. These portions of gut
should be dropped into sterile salt mouth bottles, well stoppered
and sent to a bacteriological laboratory as soon as possible. As
the cholera spirilla, when associated with faecal bacteria, tend
to die off within twelve to twenty-four hours it would probably be
advisable to inoculate an agar or blood serum slant with material
from the ileum at the same time the sections of gut are removed.
For diagnosis of a cholera carrier with a normal stool or a cholera
suspect with a diarrhoeal one inoculate 2 or 3 tubes of peptone
solution with 2 or 3 loopfuls of material from the stool. With
suspected carriers who are constipated and to whom one should not
give purgatives we may insert into the rectum a rubber tube or a
throat swab in order to obtain material immediately. The cholera
spirilla grow rapidly and being strong aerobes, they grow on the
surface of the fluid so that by taking a loopful from the surface,
we may in three to eight hours obtain a pure culture. Should there
be a pellicle present, this should be avoided in transfer by
tilting the tube slightly, so that the material near the surface
be obtained without touching the pellicle. Inoculate a second
tube from the surface of this first and, if necessary, a third
(_enrichment method_).
Smear the three-hour surface growth of a peptone culture on a
dry agar surface in a Petri dish. From colonies developing make
agglutination and, if desired, cultural tests. It is by immunity
reactions and not by cultural ones that we identify cholera
spirilla. The surface moisture of plates is best dried by the
filter-paper top.
The cholera colony is easily distinguished from the ordinary faecal
bacterial colonies by its transparent, bluish gray, delicate
character.
A practical quick method is to make smears from suspicious
colonies, stain for one minute with dilute carbol fuchsin and if
vibrios are present to make 2 vaseline rings on a single slide
allowing ample space at one end for handling the preparation
safely. Inside of one ring deposit with a platinum loop a drop of
salt solution and inside the ring nearest the end which is to be
held by fingers or forceps deposit a loopful of 1 to 500 or 1 to
1000 dilution of cholera serum. The emulsion in the salt solution
remains uniformly turbid and under a low power of the microscope
(⅔-inch) shows a scintillating motility. The emulsion made into
the drop of serum quickly shows a curdy agglutination and upon
examination with the ⅔-inch objective shows clumping and absence of
motility. Cover-glasses placed over the two vaseline rings assist
in the study of the preparation.
The best-known selective medium for plating out cholera material is
that of Dieudonne which is referred to under etiology. Apparently
a more satisfactory medium is that proposed by Goldberger, this
medium being transparent.
First prepare a 100% meat infusion by treating 500 grams of finely
chopped lean beef with 500 cc. water and after three hours strain
the infusion, adjust reaction to neutral with 5.3% anhydrous sodium
carbonate, then add to each 100 cc. 2½ cc. of the 5.3% anhydrous
sodium carbonate, sterilize in Arnold for one-half hour and filter.
Next prepare a 3% meat extract agar and mix one volume of the
alkaline meat infusion with 3 volumes of the hot melted 3% meat
extract agar. Pour plates and cover with a piece of filter-paper
and place in incubator for one-half hour until they are quite dry.
The necessity for a surface without moisture applies to Dieudonne’s
and Krumwiede’s alkaline egg media as well as this one. On this
medium cholera grows well while faecal bacteria are restrained.
The cholera colony is clear, round and shows a brownish center but
is without that striking bluish opalescence shown on ordinary agar
plates.
While peptone solution is a more favorable enrichment medium and
answers perfectly when cholera organisms are fairly abundant yet,
when scarce, selective enrichment media may be desirable. Of these
the best known is Ottolenghi’s alkaline bile. Goldberger prefers an
alkaline egg peptone solution made as follows:
Shake up an egg with an equal quantity of water and add to this
egg solution an equal quantity of a 5% solution of anhydrous
sodium carbonate. Steam one hour. Then add 1 part of this alkaline
egg medium to 9 parts of peptone solution, filter and sterilize.
Recent reports on _Aronson’s cholera medium_ would indicate its
great value in stool examination for cholera. The organisms taken
from such plates emulsify easily and there is no interference with
their agglutinability. To prepare it add to 100 cc. of 3% nutrient
agar, 6 cc. of 10% solution of exsiccated sodium carbonate and
steam in Arnold sterilizer for fifteen minutes. Then add 5 cc. of
20% saccharose solution, 5 cc. of 20% dextrin solution, 0.4 cc.
saturated alcoholic basic fuchsin and 2 cc. of 10% sodium sulphite.
A precipitate forms which quickly settles and plates can be poured
from the supernatant fluid. Cholera colonies develop in twelve
hours and show as red colonies in fifteen to twenty hours.
Test for _cholera red_ reaction. Add from three to five drops of
concentrated chemically pure sulphuric acid to the first or second
peptone culture after eighteen to twenty-four hours growth. Some
specimens of peptone do not give the reaction. At times we only get
the cholera red when we have a pure culture of cholera.
PROGNOSIS
There is the greatest variation in the mortality in different
epidemics as is true of most other epidemic diseases. At any rate 50%
may be considered an average mortality.
Young children and old people give a very high mortality rate as is
also true of alcoholics and those with kidney disease.
PROPHYLAXIS AND TREATMENT
=Prophylaxis.=—Of all the quarantinable diseases cholera is the one
in which personal prophylaxis is apparently of greatest influence in
protection from infection.
In the presence of cholera one should not only drink recently
boiled water, which has been protected from the contaminating
influence of flies, but all forms of uncooked food should be
avoided. In the first rank of prohibited foods should be raw shell
fish and uncooked salads. Such articles as lettuce and celery are
particularly dangerous on account of the moisture retained. Fruits
such as bananas and oranges can be made safe by covering them with
boiling water for two or three minutes and subsequently peeling.
Care must be taken that native servants do not put fish, which may
have been contaminated with cholera-infected water, on the ice in
an ice box and through such a source to have the butter, etc.,
infected. The most scrupulous attention should be given the matter
of the care of the ice-box in the tropics.
If conditions are such that boiled water cannot be obtained the
water may be treated with good quality chlorinated soda. As a
stock solution we use 1 teaspoonful of chlorinated soda to 1 pint
of water and of this 1 teaspoonful to 2 gallons of the water
to be disinfected. Pottevin recommends six hours contact with
hypochlorite of soda, 1 mg. per liter.
Besides care of the food and water ingested particular attention
should be paid to the washing of the hands before eating and if in
contact with cholera cases careful disinfection of the hands.
Experience in cholera epidemics has shown the importance of avoiding
anything which might lower resistance. In particular are fatigue,
excesses in alcohol or the taking of any kind of indigestible foods
to be avoided. It must be remembered that the use of purgatives may
set up cholera in a cholera carrier so that this possibility should
be thought of.
Tea has been recommended as a prophylactic, as has also eucalyptus
oil, 10 minims twice daily.
As acids have an inimical effect on the cholera spirilla some have
recommended the use of acid drinks but as a matter of fact the best
prophylactic is the normal gastric juice and there is a possibility
that the use of such acid drinks might upset the digestion and thus
defeat the object desired.
As to municipal measures for the control of a cholera outbreak the
most important one is to diagnose cholera carriers, such cases often
occurring in those associated with a cholera case. Such carriers
should be isolated and their stools disinfected until at least
2 negative examinations show them to have ceased being cholera
carriers. Of course a cholera case should be isolated and kept in a
fly-screened room.
For disinfection of stools one requires an equal amount of a 5%
compound cresol solution which when mixed with the same amount of
stool becomes a 2½% solution. This should be in contact with the
stool at least one hour before emptying the container. Chlorinated
lime, 1 pound to 4 gallons, makes a splendid disinfectant for
stools—equal parts of this 1 to 16 chlorinated lime solution and
stool.
Bed clothing or other material contaminated by vomitus or faeces
should be immersed in a 2½% compound cresol solution. All food
utensils should be disinfected by boiling.
Persons attending cholera cases should wear gowns and remove the
same upon leaving the room. Particular care should be exercised in
hand disinfection after attending a cholera case.
There is no danger from aerial conveyance of infectious material
other than the possibility of one’s coming within the danger zone
of a vomiting patient. Therefore, for disinfection of a room
occupied by a cholera patient we need not use formaldehyde gas but
washing of floors and lower part of walls with 2½% compound cresol
solution is sufficient. The stock solution of chlorinated lime, 1
pound to 4 gallons, is suitable for mopping floors and walls.
_Vaccination prophylaxis_ against cholera has been less used than
has been the case with plague or typhoid fever. The anti-cholera
sera have no practical value prophylactically and the same statement
applies to the use of such sera in treatment of cholera.
Ferran, in 1885, was the first one to use cholera vaccines in
prophylaxis. Haffkine, in 1893, adopted the use of a preliminary
subcutaneous injection of an attenuated cholera organism to be
succeeded later by one, the virulence of which had been exalted by
passage through animals to a fixed virulence. (Pasteur’s anthrax
method.) He now only uses the fixed virulence vaccine. This vaccine
is not killed by heat.
The statistics indicate quite a reduction in susceptibility on
the part of vaccinated persons (probably 8 to 1) but only slight
lessening of mortality rate. Of 5549 nonvaccinated 198 contracted
cholera and 124 died. Of 5778 vaccinated 27 contracted cholera and
14 died.
In the recent Balkan war (1913) Kolle’s vaccine was employed with
considerable success. This vaccine is killed by exposure to 58°C.
for one hour. It was found that this vaccine was not only of value
prophylactically but diminished case mortality as well. With 91,224
persons vaccinated and 8,968 not vaccinated, the case rate among
the inoculated was 0.7% and the death rate 10.2%, while among the
noninoculated the case rate was 9.3% and the death rate 27.5%.
Ottolenghi prefers to sterilize with a temperature of 53°C. He
gives 500 million at the first injection and 2 billion at the
second.
Among 72,653 soldiers, having 2 inoculations of this vaccine, the
incidence of cholera was about 13 times less than among 14,332 who
were not vaccinated.
Of 2897 Greek sanitary corps men inoculated 0.45% were attacked
while of 114,805 combatants, not inoculated, about 2% were attacked
by cholera. One would naturally consider the greater exposure of
the sanitary forces.
Cholera vaccines made from killed cultures are the ones now
generally used.
During the World War a Roumanian regiment numbering 4,500 soldiers,
had 386 cases of cholera develop in the course of six days, with
166 deaths. Vaccination was commenced and during the interval
between the first and second injections, new cases continued to
appear. Two days after the second injection the epidemic ceased. In
another regiment the commandant refused to have his men vaccinated.
A group of Jewish soldiers, 200 in number, insisted on being
vaccinated, which was done. Later the regiment was stricken by
cholera and 450 cases developed. None of the vaccinated Jewish
soldiers contracted the disease.
Some prefer sensitized living cultures for prophylaxis but such
vaccines are less practical.
There is much to indicate that Strong’s cholera autolysate is of
value prophylactically. In this cholera cultures are killed at
60°C. The killed culture is then allowed to digest itself in the
incubator at 37°C. for three or four days (peptonization). The
preparation is then filtered and from 2 to 5 cc. of the filtrate is
injected.
=Treatment.=—Many of the older authorities recommended the use
of various astringent medications for the checking of suspicious
diarrhoeas and most of these prescriptions contained opium in some
form, such as lead and opium pills or aromatic sulphuric acid and
laudanum. In view of the fact that for the infection of animals
Koch had to employ opium for checking peristalsis in addition to
neutralization of gastric juice it would seem very undesirable to
use opium by mouth. Calomel in divided doses and continued over one
or two days, but not exceeding 7 or 8 grains, has been recommended.
At present the treatment which is thought to give the best results is
the permanganate one proposed by Rogers. In this the patient is given
calcium permanganate water ad libitum and 2-grain pills of potassium
permanganate every half hour until the stools become more faecal in
character. These pills are made up with vaseline and coated with a
mixture of a 1 part salol and 5 parts of sandarach varnish.
Reports as to the use of kaolin in treatment and as a prophylactic
have been favorable. The suspension in water is given as a drink
and as an enema.
Rogers has recently been administering 1/100 of a grain of atropine
sulphate morning and evening. His statistics would indicate a
reduction in mortality of about one-half. Cases treated with
atropine also rarely show collapse. Injections of adrenalin
solutions have been recommended.
A great objection to any form of oral medication is the tendency to
vomiting. This can in a measure be controlled by cracked ice or by
a small hypodermic of morphia. The latter drug also relieves the
very painful cramps.
One danger which must always be borne in mind in giving more than
one dose of any drug subcutaneously is that with the slowing or
cessation of circulation, coming on with the algid state, we have
no absorption but, when the stage of reaction sets in and the drug,
whether morphine or toxic stimulant, begins to be taken up, there
may ensue a fatal poisoning.
However the views of authorities may conflict as to special forms
of treatment, there is universal acceptance of the employment of
intravenous injections of fluid to combat collapse. Normal saline
is the fluid usually used, but Rogers recommends his hypertonic
solution which consists of 120 grains of sodium chloride, 6 grains
of potassium chloride and 4 grains of calcium chloride to the pint of
water.
In the Philippines the normal saline seemed to answer as well as
the hypertonic solution.
Sellards had success in combating anuria, which is one of the most
dangerous conditions encountered in cholera, and at the same time
answered equally well with normal saline in relieving collapse, by
giving 2% sodium bicarbonate injections.
There is a marked acidosis in cholera and this form of treatment
seems indicated.
The objection to using sodium carbonate is that the salt has
a lytic action on red cells in vitro and furthermore Sellards
found that it tended to cause convulsions in one of his cholera
cases. Sodium bicarbonate, even in 4 or 5% concentration, does
not have any haemolysing effect on the red cells. Of course it is
true that in sterilization the bicarbonate tends to be converted
into carbonate but Sellards found that by sterilization in an
autoclave connected with live steam, at 7 pounds pressure, this was
minimized, only about 25% of the bicarbonate being converted into
carbonate after 1 hour.
If the temperature by rectum is about normal or slightly below, the
temperature of the fluid should be 102° to 104°F. and one usually
gives about 2 quarts.
Owing to the collapse of the veins it is usually necessary to cut
down on them instead of inserting the needle through the skin as for
salvarsan injections. The same apparatus as for salvarsan injections
is suitable but with a somewhat larger container as we give from 1 to
2 quarts of fluid. At least fifteen minutes should be taken up for
the introduction of 1 quart of fluid.
To determine the necessity for intravenous infusion in cholera
Rogers has recently recommended the employment of small bottles
containing aqueous solution of glycerine with specific gravities
varying from 1048 to 1070, increasing the specific gravity in each
successive bottle by 2°.
Drops of blood from the cholera patient are deposited at the
center of the surface of the fluid in the bottles from a capillary
pipette. If the specific gravity of the blood is 1062 at least a
liter of saline or sodium bicarbonate solution is needed. If 1066,
at least 2 liters. Formerly he estimated the indications by blood
pressure, considering a pressure of 80 in Europeans or of 70 in
natives as indicating intravenous injections.
On the whole the reports from the use of anti-cholera sera are
not very encouraging. Savas, however, was favorably impressed by
such treatment during the Balkan war. It should be administered
intravenously and early in the attack and given in doses of 50 cc. Of
61 severe cases, so treated, the mortality was 55.7%. Of 17 severe
cases, not receiving serum treatment, all died.
Hot water bottles should be used to keep up the body heat. No food
should be given during the first thirty-six hours but after that
time we may give broths or albumin water.
CHAPTER XVI
MALTA FEVER
DEFINITION AND SYNONYMS
=Definition.=—Malta fever is a septicaemic condition due to the
presence of the specific organism, _Micrococcus melitensis_, in the
blood and various organs, especially spleen. It runs a protracted
course, averaging three or four months, but is attended with very
slight mortality (2%). Rare cases may run an acute course and show a
high death rate. The fever course resembles that of a typhoid fever
with two or more relapses, in that a step-like rise of fever for ten
or twelve days is followed by a similar fall during the succeeding
week or ten days, an afebrile interval of a few days then ensuing, to
be followed by a second or third or even tenth febrile wave with the
separating days of apyrexia. The course of the disease may last for
a year or more attended with progressive anaemia and manifestations
of neurasthenia. Very characteristic are sudden swellings of various
joints which subside in a few hours to entirely disappear in a few
days. Neuralgic manifestations, especially sciatica, are prominent
features of the disease. It is chiefly spread by the milk of infected
goats and can best be prevented by boiling such milk.
=Synonyms.=—Febris undulans (from the wave-like monthly accessions
of fever). Mediterranean, Gibraltar or “Rock,” Neapolitan, Cyprus
fever (from the geographical distribution). Febris sudoralis (from
the night sweats). Mediterranean phthisis (from the bronchitis,
anaemia and night sweats resembling phthisis). Melitensis
septicaemia. Febris melitensis.
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—It is generally considered that a disease described by
Hippocrates, in which there was an irregular febrile course without
crisis but showing relapses and running a very prolonged course, was
probably Malta fever.
In 1861 Marston showed on clinical and pathological grounds that
the disease was different from typhoid fever.
In 1887, Colonel Bruce isolated the causative organism from the
spleen at autopsy and established the demands of Koch’s postulates
by reproducing the disease in monkeys with cultures from the spleen
and then recovering the organism from the monkeys.
Our present accurate knowledge of the epidemiology of Malta fever
and its connection with the use of the milk of goats is due to the
work of a Commission appointed to investigate the disease—1904 to
1907.
[Illustration: FIG. 74.—Geographical distribution of Malta fever.]
=Geographical Distribution.=—It is usual to consider Malta as the
focus of the disease, with the cities of the Mediterranean shores
showing quite a degree of infection. It is probable that the spread
of the disease has been in part connected with the importation
of Maltese goats, these animals being desirable on account of
their superior yield of milk. It is now known that outside of the
Mediterranean basin the disease exists in India, East and South
Africa as well as Northern Africa, China, North and South America
and the West Indies.
Mohler has shown that the disease under the names of “slow fever”
and “mountain fever” has existed in Texas and New Mexico for at
least twenty-five years.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—The causative organism, _Micrococcus melitensis_, is
a small coccus, rather oval than round and about 0.4 micron in
diameter. In morphology it is quite variable and may occur in pairs
or in short chains and is Gram-negative. It emulsifies evenly and
rapidly in a hanging-drop preparation and is nonmotile. Possibly on
account of its showing a rather active Brownian motion there has been
a reporting of slight motility by some authorities. Very striking is
the characteristic of very slow growth so that cultures on agar fail
to show colonies before the fourth day.
These minute transparent colonies become somewhat opaque and about
1/10 inch in diameter by the tenth day. Gelatine is not liquefied
and litmus milk is not altered. The optimum reaction of media
is about +0.75 to phenolphthalein and it grows best at the body
temperature. It has great powers of resistance to drying so that it
survives in dust for long periods.
Horses, cows, asses, as well as goats, are susceptible. It is very
difficult to infect rabbits, mice and guinea pigs. Monkeys have
been chiefly utilized in experimental work.
It would appear as if there were other organisms closely related
to _M. melitensis_ and a great deal is now being written as to
confusing serum reactions from the use of _M. paramelitensis_.
Evans and others have studied the relationship between _Bacillus
abortus_ and _M. melitensis_. Morphologically and culturally these
organisms are quite similar and Evans has demonstrated a marked
degree of cross-agglutination. This is a probable explanation of
the finding by Kennedy of agglutinating power in the sera and milk
of certain cows, but inability to isolate _M. melitensis_ from the
agglutinating milk.
=Epidemiology.=—Many experiments have failed to show any mosquito,
biting fly or louse as a probable factor in the transmission of
the disease. The infection is readily transmitted by subcutaneous
inoculation so that in a case in goat or man, with the cocci in the
peripheral circulation, it is reasonable to suppose that a biting
insect might transfer the infection by going directly from one
animal to another. There have been several laboratory infections,
but when we consider that of the great number of cases treated at
Haslar hospital and elsewhere in England, with frequent elimination
of the organism in the urine, and practically no infections among
the friends or attendants, it would seem as if usual methods of
infection were inoperative. There does not seem to be a carrier
problem in this disease. Urine showing bacterial contamination,
when dried and mixed with dust, has caused infection and
contaminated urine applied to the glans penis of a monkey caused
the disease.
As a large proportion of the prostitutes of Malta showed infection
and as _M. melitensis_ was found in urine and vaginal discharges
of many of these it is possible that sexual intercourse may be a
factor in transmission.
The Commission noted many cases of Malta fever among the goatherds.
By agglutination tests it was found that one-half of the goats
showed agglutinins in their serum. Of 28 monkeys given infected milk
26 became infected. Very conclusive was the case of the “Joshua
Nicholson,” which ship carried 65 Maltese goats from Malta to the
United States. Of ten of the crew who drank goats’ milk on the
voyage, eight became infected. Two who boiled the milk escaped
infection. It is reported, that when the goats reached the United
States and were quarantined, a woman drank of their milk and became
infected.
What may be deemed proof positive is the practical disappearance of
the disease among the naval and military forces of Malta, as the
result of boiling the milk, while still continuing among native
civilians. Bassett-Smith has noted that in 1905 there were 798 cases
among civilians and 245 naval cases. In 1907 there were 457 cases
among civilians and only 12 cases in the naval forces.
There are however occasional cases which Shaw has considered as due
to carriers. As the organisms are excreted in faeces as well as in
urine, and as the course of the disease is so protracted, as well
as the convalescence, it would seem that the carrier factor should
be of more importance than facts would justify.
Mohler has noted that in Texas, where the disease has existed for
twenty-five years, the Mexican goatherds boiled their milk and hence
were rarely infected.
Gentry and Ferenbaugh, in Texas, noted that cases of Malta fever were
most common in the spring and early summer months when the goats were
in full milk and the ranchmen were caring for the kids and teaching
them to suckle. The disease in certain areas was called “goat fever”
and in others “dust fever,” this latter name coming from the idea
that the dust-filled goat pens had to do with the disease.
The souring of milk does not destroy the germs of the disease,
hence transmission may be brought about by butter and cheese.
Malta fever was stamped out of Port Said by destroying all infected
goats.
Infection may occur: (1) By the stomach atrium (usual); (2)
contaminated dust reaching lungs; (3) by subcutaneous injection.
PATHOLOGY AND MORBID ANATOMY
The germs are found early in the blood and spleen; and are also
present in lymphatic glands and kidneys.
The blood is most apt to contain them at the height of the fever
curve and a striking feature is the appearance in waves of the
organisms in blood, urine or milk. While serum immunity reactions are
striking features, there is some question as to the conference of
immunity by an attack.
At postmortem we have an enlarged, congested, soft spleen with
swollen Malpighian bodies. The kidneys may show a nephritis and
the mesenteric glands be swollen. The intestines fail to show the
characteristic lesions of typhoid fever.
There may be evidences of myocarditis.
SYMPTOMATOLOGY
_A Typical Case._—Following a period of incubation, varying from
ten to fifteen days, headache, malaise and anorexia set in with a
step-like rise of fever from day to day.
The tongue is not heavily coated and is red at the tip and sides.
Constipation is the rule and there is an early tenderness and
enlargement of the spleen. There is much to suggest typhoid fever in
the gradual ascent of the remittent fever for about ten or twelve
days and the gradual descent during the succeeding ten or twelve
days, but the lack of apathy and slighter evidences of toxaemia
differentiate. The patient is dejected rather than apathetic.
There is often a slight bronchitis, with cough, which, when
associated with a profuse sweating at night, may suggest phthisis.
[Illustration: FIG. 75.—Temperature chart of Malta fever. (After
Scheube.)]
Following the initial period of fever there is usually a short
afebrile interval of a few days to be succeeded by a second, third
or many of these febrile waves, thereby making one of the names,
undulant fever, appropriate. Anaemia becomes marked and cardiac
weakness, as shown by palpitation and rapid, irregular pulse,
apparent.
The symptoms which aid us most in diagnosis are joint
manifestations and neuralgic pains. These may come on quite early
in the course of the disease or be delayed until succeeding febrile
waves set in. Swelling and pain, but without redness, of a single
joint may come on rather suddenly, to have the acute symptoms
subside in a few hours and to be entirely normal in three or four
days.
Pains in the sacro-iliac region or pains resembling those of
hypertrophic arthritis of the spine may be noted.
It is however the peripheral nerves, even more than the joints,
for which the toxic effects of _M. melitensis_ show a preference.
The sciatic nerve seems to be most often involved and sciatica may
set in suddenly and acutely, to pass off in two or three days,
leaving a soreness over the course of the nerve and a tendency to
recurrence. Orchitis may occasionally set in. There is usually
albuminuria.
Insomnia is usually quite a prominent feature of the disease and
there is a great tendency for nervous prostration to develop.
The usual course of the disease runs for three or four months but may
last almost a year.
=Other Clinical Types.=—(1) _The Malignant Form._—In such cases
instead of the insidious onset we have the characteristics of a
severe acute infection with high temperature from the beginning,
ranging from 103° to 105°F. Such cases may show vomiting and
early diarrhoea. This is followed by a typhoid state with cardiac
manifestations in the way of irregularity of the pulse. An ordinary
type of case may assume this malignant form and such cases may
develop a broncho-pneumonia.
(2) _The Intermittent Form of Hughes._—Here we have a type of case
similar to the typical one but less severe. It is a subacute form
which from time to time shows an intermitting fever. These cases
may fail to show evidence of serious illness and the patient may
continue his work although noting a progressive deterioration of
health. Some very mild cases which only rarely show slight fever of
a few days’ duration have been reported as _ambulatory_ cases.
(3) _The Disease in Infants._—Di Cristina and Maggiore have
described various forms of the disease as observed in infants in
Palermo. They note a hyperpyrexial type and an undulant type. A
type with anaemia and marked cachexia is very severe. Another form
shows cyanosis, irregular pulse and irregular respiration with
marked sweats. Again the symptoms may be those of a cerebro-spinal
meningitis.
=Sequelae and Complications.=—It should be borne in mind that
while not serious from a standpoint of mortality this disease is
to be dreaded by reason of the possibility of invalidism. The
neuralgic pains, insomnia and mental depression render patients
liable to the morphine habit. In pregnant women there is a tendency
to abortion. In rare cases we may have intestinal haemorrhages with
asthenic manifestations. Bassett-Smith has reported a case with
extensive purpura. The same author in paramelitensis cases has
noted the susceptibility to secondary streptococcal infections.
SYMPTOMS IN DETAIL
_Temperature Chart._—Except in the malignant form of the disease,
when the temperature may be rather continuous, the fever course is
a step-like ascent with daily remissions for about ten days and
then a similar descent. Following an evening rise of temperature
night sweats may be noted.
It is the wave-like succession of such courses of fever, separated
by afebrile intervals, that suggests the name undulant fever.
_Circulatory System._—The disease shows rather a toxic effect on
the heart as shown by palpitation and irregularity and rapidity of
pulse rate.
In the beginning of the fever, however, the pulse rate is not very
fast. Anaemia is a rather marked feature.
_Respiratory System._—A slight bronchitis with cough tends to
suggest phthisis in those cases which show rather marked night
sweats.
_Nervous System._—The organism seems to have a selective action
on the nervous system as shown by headache, various neuralgias,
insomnia, apathy and neurasthenia. Sciatica is probably the most
common peripheral nerve involvement.
_Joint Symptoms._—Very characteristic are the sudden and painful
swellings of various joints, especially hip, shoulder, ankle and
knee. Not rarely the costo-sternal articulations may be involved.
The acute symptoms subside in a few hours and the joints become
normal in a few days.
_Alimentary Tract Symptoms._—The tongue may have a slight furring
but the edges and tip are quite clean and red. Although anorexia
exists with the fever the appetite tends to return with apyrexia.
Constipation is usual. There is frequently tenderness of the
epigastric region.
_Genito-urinary System._—Other than for albuminuria and the
presence at intervals of the causative bacteria in the urine, there
is nothing of note, except the occurrence of orchitis in about 3
per cent. of cases.
_The Blood._—The white count is about normal or slightly
reduced—6500 on the average. The cells of lymphocyte type tend to
show an increase in percentage with a corresponding reduction of
polymorphonuclears.
There is a secondary anaemia.
The spleen shows early enlargement and tenderness.
DIAGNOSIS
=Clinical Diagnosis.=—The diseases most apt to be confused with
Malta fever are typhoid fever, malignant tertian malaria, liver
abscess, influenza, phthisis and kala-azar.
Besides the agglutination, complement fixation or blood culture
aids, we rely upon the sudden onset of joint involvement or
neuralgic manifestations as indicating Malta fever.
Usually the splenic enlargement about corresponds with that of
typhoid fever but at times it may be so marked as to equal that of
malaria or even kala-azar.
The presence of rose spots as well as the marked apathetic state
and the tendency to diarrhoea should aid in differentiating
typhoid. Unfortunately for diagnosis the leucopenia and polynuclear
percentage reduction is similar in the two diseases.
In kala-azar the double temperature rise in 24 hours with the
_Leishmania_ bodies in spleen puncture material, instead of _M.
melitensis_, are differentiating.
The short course and more sudden onset of influenza and the more
marked pulmonary symptoms of phthisis should prove diagnostic aids.
Liver abscess and empyema with their tendency to anaemia and
sweating may prove confusing, but the history, leucocytosis and
location of pain should differentiate. Then too the joint and nerve
manifestations of Malta fever are absent.
=Laboratory Diagnosis.=—Eyre obtained cultures from blood from the
2d to 300th day of the disease. He recommended the taking of at
least 5 cc. from a vein and that this be done at a time when the
fever is at its maximum point—the days when the fever is at its
maximum and in the evening of that day. By taking 20 to 30 cc. in an
equal amount of citrated salt solution, as described in chapter on
blood examination, one should have as great success as had Eyre—158
positives in 235 cases or 65.4 per cent.
It must be remembered that the colonies only appear about the
fourth day, becoming quite distinct by the tenth day.
Bassett-Smith takes about 10 cc. of blood in the afternoon during
pyrexial waves and distributes this blood in several tubes of
broth. He makes plates from these tubes every day. He also
recommends the taking of 1 cc. of blood which he allows to clot and
subsequently removes the serum and adds bouillon (clot culture).
Agglutination is the chief reliance in diagnosis. As result of two
infections in his laboratory Widal uses emulsions killed by ¾% of
formalin. He uses the microscopic method in the test with dilutions
not exceeding 1 to 200. Such emulsions keep for at least a year.
In connection with agglutination tests Nicolle recommends that the
serum be separated at once and removed from the clot and Nègre
has shown that by heating the serum to 56°C., for thirty minutes,
reactions are not obtained with nonspecific sera.
Some workers prefer the macroscopic agglutination.
Complement fixation methods are of value but the application of
such tests is confined to large laboratories.
PROGNOSIS
The mortality is usually reported as 2% but there have been epidemics
where the mortality, owing to the frequency of the very fatal
malignant type, has exceeded 10%. It must be remembered however
that the invaliding connected with the long course of the disease
and protracted convalescence makes Malta fever a serious affection.
Neurasthenia, susceptibility to neuralgias, cardiac weakness and
formation of morphine habit may result from the disease.
PROPHYLAXIS AND TREATMENT
=Prophylaxis.=—The danger from carriers seems slight but should be
considered.
Disinfection of excreta, in particular urine, is important.
Boiling of goat’s milk or killing of infected goats is a prime
consideration.
A rapid method of detecting infected goats is by carrying out a
macroscopic agglutination of _M. melitensis_ with the milk obtained
from goats. The lacto-reaction should be confirmed by a serum one.
=Treatment.=—There is no specific treatment generally recognized as
efficient. Recently, an anti-melitensis serum, from animals injected
with the nucleo-proteid material from the organisms, has been used
with some success.
A serum prepared by injecting horses intravenously with the
specific organism has been recommended by Sergent in doses of 50 cc.
Bassett-Smith recommends an autogenous vaccine, during the afebrile
period, in doses of from 50 to 200 millions. He thinks that the
best results are obtained with sensitized vaccines. During acute
phases the vaccine treatment is detrimental—it is only in chronic
cases that such treatment is of value. Some prefer to give doses of
10 million or so at short intervals. He also thinks yeast in 2-dram
doses to be of value. Phenacetin or aspirin may be given, but the
heart weakness makes extensive use of these analgesics dangerous.
The diet should be that for any acute disease but the protracted
course makes it necessary to have regard to an adequate food value.
Care should be taken to avoid chilling or fatigue.
Some recommend moderate use of alcoholic stimulation but this
treatment is questionable.
Cold sponging and local applications to joint or nerve involvements
are indicated.
Morphine should be employed with great caution.
CHAPTER XVII
LEPROSY
DEFINITION AND SYNONYMS
=Definition.=—Leprosy is a very chronic, almost incurable disease,
with a protracted period of incubation (two to ten years), which
sets in with indefinite prodromata of malaise, and irregular febrile
attacks associated with sweating and somnolence. In nerve leprosy
there may be vague manifestations of neuritis as prodromata. There
are two well-recognized types of the disease. The type characterized
by granulomatous proliferations in corium and subcutaneous tissues,
as well as lymphatic glands, is known as nodular or skin leprosy. It
shows spots and nodular infiltrations, chiefly about lobes of ears,
alae of nose and region of eyebrows, with falling out of hairs of
eyebrows and bearded region, and also involves extensor surfaces of
forearms, dorsal surfaces of hands and feet. The palms of hands and
soles of feet are almost never invaded. The other type is known as
nerve or maculo-anaesthetic leprosy and is characterized by nerve
thickenings, flat anaesthetic spots, chiefly of the covered region
of the body, muscular palsies and atrophies, with trophic changes
leading to contractures and mutilations. When the two types are
associated we have mixed leprosy.
The disease is caused by an acid-fast bacillus, which has not
surely been cultivated or inoculated into animals with pathogenic
result, and which is found in extraordinary abundance in the
granulomatous subepithelial tissues of nodular leprosy and in
scanty numbers or not at all in the perineurium and endoneurium of
the ulnar, facial or perineal nerves.
=Synonyms.=—Lepra. Elephantiasis Graecorum. Leontiasis. Satyriasis.
French: La Lèpre. German: Aussatz.
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—There are those who consider India as the home of
leprosy, a condition corresponding to the disease having been
described in the Rig Veda, of date of 1400, B. C.
Others regard Egypt as the original focus, a disease similar to
leprosy having been described in the “Ebers papyrus” of date of
about 1300, B. C.
Any one reading chapter xiii, Leviticus, must be convinced that
the disease there described as leprosy was of a different nature.
We find statements to the effect that where the hair in the spot
is white and the spot deeper than the skin of the flesh that it
is leprosy; again, if there be a white or red rising it is not
leprosy, but if lower than the skin it is leprosy.
According to Unna the term Zaarath had a theological rather than
a medical meaning. At the same time other references in the Bible
would indicate that leprosy was more or less prevalent among the
Jews of that period.
It is very probable that the ancients confused leprosy with many
other diseases where ulceration and nodular disfigurement were
conspicuous features.
From the fact that leprosy was called the Phoenecian disease it
would seem that Asia was the real home of the disease.
[Illustration: FIG. 76.—Geographical distribution of leprosy.]
It is well established that leprosy was introduced into Europe,
from Egypt, in the first century, B. C., by the returning legions
of Pompey.
As a result of the crusades, leprosy was spread widely over Europe
by the crusaders, so that in the 14th century the disease was so
prevalent, that it required approximately 20,000 leper asylums to
care for the lepers. In France alone there were about 2000 such
leprosaria.
As a result of the most drastic measures of isolation the disease
began to decrease in the 14th century and had practically
disappeared from Europe, as a whole, by the 15th century.
=Geographical Distribution.=—With the exception of a limited and
steadily diminishing number of cases in Norway and Sweden, with
an uncertain number in the Balkan region and Turkey, leprosy has
almost disappeared from Europe. Parts of Brittany and Provence in
France show cases and there are a considerable number in Portugal
and Spain.
Africa is heavily infected with the disease, especially in Central
and East Africa. In certain portions of the Cameroons (Banyang) it
is so common that one in every four persons suffers from leprosy.
Asia has many important leprosy centers, there being a very great
number in China and India. There are about 100,000 lepers in Japan
and about 3000 in the Philippines.
In 1902 there were 278 lepers in the United States, of which number
145 were native born. In 1912 there were only 146 distributed
chiefly in three centers: (1) That of the Great Lakes, there
being now 13 cases in Minnesota as against 27 in 1900; (2) among
the Orientals of the Pacific Coast, and (3) in the Gulf region,
especially about Louisiana and Florida.
There are 696 lepers in Hawaii and 28 in Porto Rico.
In South America, the disease is found in Columbia, Venezuela and
Brazil as is also true of Mexico and Central America.
In Australia the disease is found in Queensland and New South Wales.
It also prevails in New Caledonia and the islands of the Pacific.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—Leprosy is caused by an acid-fast bacillus, _Bacillus
leprae_, which rather closely resembles the tubercle bacillus
morphologically as well as tinctorially. It was first discovered by
Hansen in 1871 and fully reported in 1874. Much of our knowledge of
its characteristics is due to Neisser (1879).
The leprosy bacilli are found in profusion in the granulomatous
tissue of the corium and subcutaneous structures of the leprous
nodules, chiefly within cells called “lepra cells” and also within
endothelial and connective-tissue cells as well as lying free,
packed in lymphatic channels, the so-called “globi.”
The leprosy bacillus may be distinguished from the tubercle bacillus
by the following points:
1. The presence ordinarily of huge numbers of bacilli often grouped
in packets like a bundle of cigars tied together.
It will be remembered that it is very difficult to find even a
single tubercle bacillus in a skin lesion. Leprosy bacilli form
palisade groups but not chains.
2. The leprosy bacilli stain more solidly and when granules are
present they are coarser and more widely separated than the fine
granulations of the tubercle bacillus.
3. They do not stand decolorization quite as well as the tubercle
bacillus. With 20% sulphuric acid in water they hold their color
almost as well as tubercle bacilli but with 3% HCl in alcohol they
decolorize in about two hours as against twelve to twenty-four
hours for the tubercle bacillus.
4. Leprosy bacilli have neither been surely cultivated nor surely
inoculated with pathogenic results into guinea pigs or other
experimental animals and it is by the negative results upon
cultivating or animal inoculation that we have our surest method of
differentiation from tubercle bacilli.
Leprosy bacilli are chiefly spread through the lymphatics, but
in nodular leprosy, their occurrence in the blood stream during
the febrile accessions is so constant that this route may also be
of importance. Next to the corium they are most abundant in the
lymphatic glands. They stain readily by Gram’s method.
A great amount of work has been done within recent years in
attempting to cultivate the leprosy bacillus.
In 1900 Kedrowsky culturing material from 3 cases of leprosy
obtained diphtheroids from two and a streptothrix from one.
A rabbit was inoculated first intracerebrally and later
intraperitoneally with this nonacid-fast streptothrix and, when
killed six months later, showed peritoneal nodules, from which
both diphtheroids and acid-fast bacilli, but not a streptothrix,
were recovered culturally. Injections of cultures of the acid-fast
bacilli and diphtheroids into rabbits and mice produced nodules
which when cultured showed acid-fast organisms or diphtheroids.
In 1901 he cultivated a diphtheroid from a fourth case of leprosy.
Fraser and Fletcher working with Kedrowsky’s culture produced
peritoneal nodules with the killed as well as the living organism.
They were able to produce the same results with _B. phlei_. With
emulsions of leprous nodules, rich in leprosy bacilli, they could
not produce similar lesions in the experimental guinea pigs.
Rost obtained a culture on a salt-free medium from which he
prepared his _leprolin_ by a process similar to that used for
old tuberculin. It was claimed that leprolin had marked curative
power in leprosy. Recently Williams and Rost have cultivated a
streptothrix on a medium containing milk.
Clegg, by inoculating his medium with cultural amoebae, obtained
growth of a diphtheroid organism, with acid-fast tendencies, from
the spleen pulp of lepers.
Duval, by using media containing amino-acids, as result of tryptic
digestion, brought forward two organisms, one of which was a
diphtheroid and grew luxuriantly while the other showed a slow
scanty growth and was acid-fast.
Bayon, by using placental media, isolated an organism rather
resembling that of Kedrowsky. These organisms alone responded to
immunity tests when such were made by Bayon and they alone gave
rise to tissue changes resembling those of leprosy when injected
into animals.
Professor Deycke obtained a streptothrix-like growth from the
granulomatous tissue of excised leprous nodules. The ethereal
extract from this culture gave a neutral fat which he called
_nastin_ and which is the basis of a leprosy treatment.
Quite recently and after working for eighteen months, with material
from 32 nonulcerative cases of nodular leprosy, not only with media
as recommended by Duval, Rost and Bayon, but with blood and serum
culture media, both by aerobic and anaerobic procedures, Fraser has
been unable, in a single instance, to obtain any evidence of growth
from this wealth of leprosy material.
As being opposed to the possibility of culturing the human leprosy
bacillus, it may be stated that most of the experiments along this
line with rat leprosy, a disease occurring naturally in rats and
caused by an organism almost identical, as to lesions produced,
with the leprosy bacillus, have been negative. Bayon, however,
states that he has cultivated the bacillus of rat leprosy.
=Epidemiology.=—There is a consensus of opinion that every case of
leprosy owes its origin to contact, direct or indirect, with some
other case, but evidence as to the manner in which the disease is
transmitted, or even the proof of transmission, is to a great extent
lacking.
Every book refers to the inoculation experiment by Arning, of a
freshly excised leprous nodule sewn into a skin incision of the arm
of a condemned criminal. In this case a neuritis developed shortly
after the inoculation and the patient showed fully developed
leprosy three years later. Unfortunately for the value of the
experiment the man was a native of Hawaii and had lepers in his
own family. Against this experiment are the numerous instances
where physicians have inoculated themselves and others with leprous
material with invariably negative results.
Danielson inoculated himself and nine others with leprous material
and later Profeta repeated the same, but without success in a single
instance.
As regards those living for a long time in attendance on lepers
there have been a very few instances of the contraction of leprosy
as in the case of Father Damien at Molokai, and two instances in
Sisters of Mercy. Such cases however are most exceptional, as the
hundreds of attendants on the unfortunates continue their work for
years without showing any signs of leprosy.
It is stated that there has never been an instance of transmission of
leprosy to any attendant at the Saint Louis Hospital, Paris.
There are two cases which show that those who live in close
relation to lepers may develop the disease; in one, a leper
returned to Ireland and his brother, who had never been in a
leprosy country, but who had occupied the same bed with the leper
and worn his clothes, developed the disease in about five years. A
similar case is reported from Germany.
As showing that even with intimate contact, infection is rare, it is
stated that of 225 healthy Hawaiians, living in the same houses with
lepers, only 4½% contracted leprosy. Even when married to lepers only
9 out of 181 healthy people contracted leprosy from their leprous
mates.
In Japan, 7% of children of lepers contract the disease, 3.8% of
those married to lepers and 2.7% of people living in the same house
with lepers.
Just as with tuberculosis, in which all evidence points to the
predominance of infection in early life and its infrequency in
adult life, so does it seem to be true of leprosy. Among 10,000
lepers in the Culion leper colony, Denny notes that 35% were
brothers and sisters, 27% were cousins, 11% were children of
lepers, 7% parents of lepers, and only 1% husband and wife. This
would indicate that the relationships involving intimate contact in
childhood are etiologically most important.
One of the strongest proofs that leprosy is at least feebly
contagious is that based on the disappearance of the disease
following isolation of the lepers. The best instance is that of
Europe, in the thirteenth and fourteenth centuries, where, with
20,000 leper asylums for isolation, the disease disappeared by the
fifteenth century. In Norway, there were 2833 cases in 1856, while in
1907, there were only 438 left.
At the end of 1913 there were only 285 cases, 181 of these being
interned and 104 in their own homes. The reduction is attributed to
isolation.
This might have occurred without isolation because Hansen in
investigating the descendants of 160 known Norwegian lepers, who
immigrated to the North-western States of America, was unable to
find trace of a single leper among their descendants.
This and other facts militate against the views that leprosy may be
inherited and the idea is generally held that if a child be taken
away from its leprous surroundings after birth there is little or no
likelihood of its developing leprosy.
Again, it is a well-recognized fact that leprosy is more than
twice as common among men than among women. It is probable that
the greater opportunity for contact with lepers by man is the
explanation of the greater frequency.
_Views as to Mode of Transmission._—It may be stated that nothing
definite is known. There has been an idea that itch mites might
transmit the disease but no proof has been advanced. Lebouf found
leprosy bacilli in the stomachs of flies, which had been feeding on
leprotic ulcerations, and did not find acid-fast rods in flies which
had fed on persons with nerve leprosy or upon those not showing open
lesions. He thinks that flies may deposit faeces containing bacilli
about the nasal orifices or upon wounds of well persons, bringing
about thereby their infection.
Skelton was unable to find evidences of leprosy bacilli in bedbugs
living in the beds of lepers. Paldrock also was unable to find any
evidence of leprosy bacilli in bedbugs a few hours after feeding on
leprous tissue, but did find acid-fast rods in cockroaches which
had fed on leprosy nodules, even fourteen days after the feeding.
A. J. Smith fed bedbugs on Duval’s organism and recovered acid-fast
bacilli for considerable periods. The question arises, however, as
to the significance of Duval’s bacillus for leprosy.
Acid-fast bacilli have been reported from head lice and mosquitoes,
when the insects have been feeding on leprous tissue, but little or
no evidence of any multiplication has been obtained.
For many years Jonathan Hutchinson insisted that leprosy was caused
by the eating of imperfectly cured or decomposing fish, a view
which now has no supporters.
For a time it was considered that the initial lesions of leprosy were
to be found in the nasal mucosa and especially in ulcerations of
the nasal septum and that it was by the atrium of the nasal mucous
membrane that infection occurred.
There is no question but that the examination of the nasal mucus
for leprosy bacilli is of prime importance in diagnosis and it may
be that cases showing ulcerations of the septum are especially
dangerous when sneezing, but very few believe that leprosy is to
any extent contracted through this channel. de Azevedo examined
smears from the nasal mucosa in 59 persons who were in close
contact with lepers without finding acid-fast bacilli in a single
instance.
With a period of incubation covering from two to ten years it is
of course manifestly difficult to arrive at any correct idea as
to transmission but there is a growing belief that the free and
frequent use of soap is a decided factor in preventing infection
which may, like rat leprosy, be best brought about by continued
contact with a skin surface more or less abraded. There has been a
suspicion, but no proof, that sexual intercourse may bring about
infection.
_Rat Leprosy._—A disease occurring naturally among rats was first
observed by Stefansky, in Odessa, in 1903.
There are two types: (1) Of skin and muscles, and (2) of the
lymphatic glands. In the skin form areas of alopecia are present
with thickening of the site invaded. These areas are most often on
the back of the head. Just as in human leprosy the epithelium is
unaffected, the corium however being filled with cells packed with
acid-fast bacilli, exactly similar to the picture in human leprosy.
Ulceration of these subcutaneous nodules is common.
In the glandular type the glands are enlarged and the lymph sinuses
packed with the causative bacilli.
In rat leprosy it has been found that infection of other rats takes
places as readily through slight abrasions of the skin as when
material is injected subcutaneously.
The idea is that natural infection occurs by way of the skin and
through the lymphatics. There is no evidence that insects play a
part in transmission.
Rat leprosy prevails extensively in Europe, Asia and America.
Although similar etiologically and pathologically there does not
seem to be any connection between the disease in rat and in man, as
is the case with human and rat plague.
The prevalence of rat leprosy in the various parts of the world
varies greatly; thus in Odessa 4 to 5% of the rats are infected
while in San Francisco only ⅕ of 1%.
PATHOLOGY AND MORBID ANATOMY
In whatever way introduced the leprosy bacilli tend to invade and
multiply in the lymphatics of the corium and subcutaneous tissues.
In response to irritation, cells of disputed type, possibly plasma
cells, appear and phagocytize the bacilli in large numbers, so that
eventually the outline of the cell, as brought out in acid-fast
staining, is that of a mass of red bacilli.
These red-staining bodies are called _lepra cells_. In addition,
endothelial cells phagocytize the bacilli and these with their
bacilli, together with the free lying masses of bacilli in the
lymphatic sinuses, make the so-called “globi” when seen in transverse
section. The toxicity of the lepra bacillus is only slight so that
we may have very large giant cells of the Langhans type and this
probably explains the absence of caseation in leprosy. The arteries
of the leproma, as the granulomatous mass is termed, undergo an
arteritis with thickening of their walls.
[Illustration: FIG. 77.—Section of spleen showing lepra cells and
lepra bacilli. × 800. By permission from Manson’s Tropical Diseases.]
The leproma is a mass of cells of varying sizes and types in a
connective-tissue framework. The infiltrations are chiefly about
the hair bulbs, sweat glands and arteries. The epidermis is
separated from the leproma by a connective-tissue layer and is
uninvolved except for a thinning out of the layer and obliteration
of the interpapillary epithelial pegs.
Incision of a leprous nodule shows a smooth glistening cut of a
yellowish to slate gray color.
In nerve leprosy the cellular proliferations in the region of the
blood vessels and later in the perineurium and endoneurium cause
pressure on the axis-cylinder with consequent degeneration. The
affected nerves are swollen and reddish-gray in color. It is now
thought that an axonal degeneration involves the cells of the
anterior horns so that this, as well as the peripheral neuritis, is a
factor in the muscular atrophies which are features of the disease.
The sensory fibres are destroyed before the motor ones.
Leprous changes are common in the anterior part of the eye,
as of conjunctiva, cornea and iris, but rare in the posterior
eyeball. The mucosa of tongue, larynx and, pharynx is often
involved. Cartilage and bone are destroyed through pressure of the
granulomatous tissue.
The ovaries and testes may show connective-tissue increase.
Nephritis is rather common in leprosy but there is considerable
doubt whether the lungs are invaded by leprosy, except most rarely.
Next to skin, mucous membrane and nerves, the lymphatic glands show
the greatest involvement.
The liver not uncommonly in nodular leprosy and more rarely the
spleen may show connective tissue or cellular infiltrations.
SYMPTOMATOLOGY
The period of incubation of leprosy is peculiarly prolonged and is
at any rate from two to five years and may extend over many years,
Hallopeau having recorded a case where the disease did not develop
for twenty-seven years after the patient left the infected district.
The early manifestations are vague and indefinite, consisting chiefly
of malaise, weariness and mental depression.
There are often noted (_a_) irregular accessions of fever (leprotic
fever), attended with rather profuse sweating, so that the onset
may be mistaken for a malarial infection; (_b_) progressive
weakness, the patient being easily fatigued with a tendency to
somnolence; (_c_) alternating attacks of dryness and hypersecretion
of the nasal mucous membrane, with frequent attacks of epistaxis,
and (_d_) various neuralgic manifestations or paraesthesias as well
as headache. These prodromal manifestations usually precede but may
accompany the outbreak of the spots.
It is the prominence of the nasal manifestations that has caused
Sticker to insist that the primary lesion of leprosy is of the
nasal mucosa, the general view, however, being that this view
is without sufficient foundation and as a matter of fact some
have recently suggested that the disease first manifests itself
in the lymphatic glands, punctures of such structures showing
bacilli rather frequently, although in less proportion than upon
examination of the nasal mucosa.
All authorities recognize two well-separated clinical types of
leprosy, one the nodular, skin, hypertrophic or tubercular form and
the other the smooth, nerve, maculo-anaesthetic or atrophic form.
These fairly distinct types tend to run into one another and in
such cases we have the mixed form of the disease.
Following Manson I use the terms nodular and nerve leprosy. It is
usually stated that in Northern climates nodular leprosy forms about
70% of cases while, in the tropics, the larger proportion is made up
of nerve leprosy.
At one time a classification of the 239 lepers at San Lazaro
Hospital, Manila, P. I., showed 97 cases of nodular, 42 of nerve
and 93 of mixed leprosy, with two cases of doubtful nature.
NODULAR LEPROSY
_A Typical Case._—After more or less indefinite and uncharacteristic
prodromata the definite onset is by an outbreak of brownish red spots
which later become pigmented and thickened. These spots are at first
erythematous and tend to come out in crops, attended with attacks of
irregular fever. They soon have the appearance of limited areas of
sunburn. They vary in size from 1 or 2 millimeters to a blotch the
size of the palm of the hand.
They are raised and have a preference for appearing on the lobes of
the ears, the nasal alae, the forehead, eyebrows, cheeks and chin.
The extensor surfaces of the forearms, thighs and buttocks are also
favorite sites for the indurated spots. The palms of the hands,
soles of the feet, hairy scalp, groin and axillary regions are
almost never attacked.
These spots may be hyperaesthetic at first but soon show loss
of pain and temperature sense with retention of touch sensation
(dissociation of sensation). These spots do not sweat, they remain
dry even in a general perspiration.
Following successive febrile accessions and reappearances of spots we
have developed reddish-brown nodular masses, usually on the sites of
the spots.
When the nodules are grasped between the fingers one usually finds
them elastic to touch. As the result of active sebaceous secretion
these nodules have a greasy appearance.
These protruding nodules may give the face a leonine appearance,
hence the name leontiasis, or that of a satyr, hence satyriasis. With
the development of the nodules the hair falls out of the eyebrows and
bearded face. Nodules develop in the mucous membranes of the nose,
mouth and larynx, giving rise to foetid discharges and obstruction of
the nares, difficulty in mastication as well as in breathing and a
raucous voice.
The eye is involved with frightful frequency in this form of
leprosy, there being infiltrations of the eyelids, conjunctivae,
cornea and iris, with subsequent ulcerations and loss of sight.
The nodules on face, backs of hands, buttocks, etc., may disappear
by resolution but the tendency is for them to ulcerate and produce
various contractions and deformities.
[Illustration: FIG. 78.—Nodular leprosy. Advanced stage with
ulceration. Leontiasis. (Van Harlingen.)]
The glands in the region of the lesions become enlarged but do not
tend to suppurate.
Visceral involvements are not common but serious lesions of the liver
have been reported.
The course of the disease is essentially chronic and if some
intercurrent affection does not carry off the patient, the end
comes in a cachexia in about ten years, the temperature gradually
falling and a state of somnolence ushering in the end.
When nerve leprosy sets in upon a nodular type the life of the
patient seems to be prolonged.
Nerve Leprosy
_A Typical Case._—The prodromal manifestations are characterized
by the results of irritation of the granulomatous tissue upon the
nerve fibers and are chiefly neuralgic pains or signs of sensory
disturbances as formication, paraesthesias, etc. In particular, are
the ulnar, peroneal and facial nerves attacked, the process very
rarely extending above the knee or elbow.
[Illustration: FIG. 79.—Nerve leprosy. Perforating ulcer of the
foot. (U. S. Naval Medical Bulletin.)]
Anaesthesia of the region supplied by the ulnar nerve with
contractures of the fourth and fifth fingers may be signs directing
our attention to the true nature of the disease and in those cases
where the appearance of smooth yellowish-brown spots precedes the
neuritis manifestations we may here also find anaesthesia, provided
the eruption has lasted for some time.
In brief the fully developed case of nerve leprosy shows anaesthetic
spots, trophic lesions of the skin and bone, together with muscular
palsies. The spots often appear singly and may be from ½ to several
inches in diameter. They are not raised, have a sunburnt color and do
not sweat. Instead of having a preference for the exposed parts they
most frequently appear on the covered portion of the body or limbs as
trunk, buttocks, scapular region, thighs or arms, although the first
appearance of spots may be on the face.
[Illustration: FIG. 80.—Nerve leprosy, showing deformities,
perforating ulcer, etc. (From U. S. Naval Medical Bulletin.)]
These spots often look like ringworm lesions, as they have an
erythematous border with a paler center, but they are oval in
outline rather than round and there is no scaling. Bullous
eruptions, which are most frequently noted about the knuckles, are
rare manifestations of nerve leprosy. They are often followed by
ulceration.
[Illustration: FIG. 81.—Nerve or maculo-anaesthetic leprosy showing
anaesthetic spots on back (U. S. Naval Medical Bulletin.)]
About this time the nerve trunks begin to enlarge, especially
the ulnar at the elbow and the great auricular as it crosses the
sterno-mastoid muscle. The characteristic nerve enlargement is
spindle-shaped or beaded.
These nerve enlargements are at first tender but later become
painless and we have extensive areas of anaesthesia and trophic
changes of the skin and nails of fingers and toes such as felons,
glazed skin, bullae, which latter on rupturing leave ulcers.
We also have absorption of the bones of the phalanges.
The phalangeal bones may be completely absorbed and a distorted
nail cap the end of the metacarpal bone (_lepra mutilans_). Owing
to the anaesthesia lepers often burn or injure their fingers and
toes. Perforating ulcers are more common in leprosy than tabes.
Muscular palsies, atrophies and contractures are more common in the
face and upper extremity than in the lower extremity. We may have
changes quite similar to those of progressive muscular atrophy, the
thenar and hypothenar, as well as the interossei, undergoing atrophy
and resulting in the claw hand. There is extension of the first joint
and flexion of the two distal joints of the fingers. Such hands may
function quite well. Wrist-drop is not uncommon but foot-drop is
rare. Rarely Charcot’s joint condition may be observed.
Of the facial muscles the orbicularis palpebrarum is most apt to
show paralysis. The eyes are affected much less frequently in nerve
leprosy than nodular, 45% as against 85% for nodular leprosy. The
most common changes in nerve leprosy are ectropion of the lower lid
and subsequent corneal ulceration.
=Mixed Leprosy.=—In mixed leprosy we simply have a combination of
the manifestations of the two main types and as a matter of fact
the majority of cases tend eventually to assume a mixed type.
SYMPTOMS IN DETAIL
_Temperature Course._—On the whole leprosy runs an afebrile
course except for the accessions of irregular fever at the time
of the appearance of the successive crops of spots. This leprotic
fever lasts for a few days or a week or so and then the course
becomes afebrile. At such times sweating may be present and suggest
malaria. In the final stages of leprosy the patient may run a high
fever for long periods, associated with profuse sweating and loss
of weight.
_Skin._—The raised spots of nodular leprosy tend to come out in
numbers on lobes of ears, over eyebrows and on cheeks, as well as
backs of hands and forearms and on buttocks and feet. Soles of
feet and palms of hands almost never show spots. In nerve leprosy
the spots are often single and flat and often appear on parts
of body covered by the clothing, as trunk, thighs or arms. The
spots of leprosy are anaesthetic, often showing dissociation of
sensation. The indurated spots of nodular leprosy are succeeded by
tubercle-like growths. The hair falls out of the areas occupied by
the spots.
_Mucous Membranes._—The nasal mucosa is in particular studded with
nodules which later undergo ulceration. An ulcer of the septum is
often the first place from which leprosy bacilli may be obtained.
The pharynx and larynx are also involved early.
_Nervous System._—Besides the characteristic anaesthesia we have
various manifestations of neuritis, especially involving the ulnar,
facial and peroneal nerves. The affected nerves show a fusiform
enlargement and are tender. Later we have trophic changes in
skin, bone and nails of the fingers and toes. Absorption of bones
and perforating ulcers are common. Muscle palsies and atrophies,
especially the main-en-griffe, are common. The orbicularis
palpebrarum is not infrequently paralyzed. The olfactory, optic
and auditory nerves are rarely if ever involved. The reflexes are
slightly exaggerated.
Patients often complain of a sensation of cold. Some authorities
have called attention to the frequency of a mental and moral apathy
in lepers.
_The Circulatory System._—Honeij considers a high pulse rate,
especially in the morning, as characteristic of progressive stages
of leprosy.
_The Eye._—In nodular leprosy eye lesions, chiefly leprotic
nodules in conjunctivae or iris, with subsequent ulceration, are
met with at some time in the course of the disease in almost 90%
of cases. In nerve leprosy, corneal ulcerations, chiefly resulting
from paralyses of the facial muscles, with ectropion, give eye
symptoms in about 45% of cases.
_Genito-urinary Symptoms._—Atrophy of the testicles with increase
of connective tissue often result in males but data would indicate
that the procreative power of the female is but little diminished.
Lepers often die of renal complications, the kidney lesions being
rather those of amyloid change. Bacilli may be eliminated in the
urine during accessions of fever.
_The Lymphatic Glands._—These tend to enlarge and show bacilli,
but rarely suppurate.
The inguinal and cervical glands are most often enlarged.
_The Blood._—The changes, other than those of a secondary anaemia
as the disease progresses, are not characteristic. Bacilli are
present in the blood of cases of nodular leprosy quite constantly
but less so in that of cases of nerve leprosy. The bacilli are more
apt to be found in the blood at the time of febrile accessions.
DIAGNOSIS
=Clinical Diagnosis.=—It must be remembered that leprosy is very
slow in development, so that for months or even years there may be
but slight indications of the disease, as an anaesthetic spot or the
palsy of an orbicularis palpebrarum. One should always run over the
lobes of the ears or region of the eyebrows to feel for shot-like
nodules.
In the making of a diagnosis the information as to possible exposure
to the disease is of first importance.
The leprous spots are at first rather oily from increased action
of the sebaceous glands but subsequently become dry. In ancient
times the hypersecretion of sebaceous material about the facial
spots of nodular leprosy served as the basis of a test for leprosy,
the suspected eruption being dashed with water. If the surface was
not wetted it was a point in favor of leprosy. Of prime importance
however is the pin prick for anaesthesia, which is the most
important distinguishing characteristic, next to the finding of
the bacilli, for a leprous spot. The anaesthesia is more marked
in the center of the spot and may show dissociation of sensation.
It is very important to examine for enlargement of the ulnar or
great auricular and the earliest signs of a nerve leprosy may be
anaesthesia and a slight contraction of the ring and little finger.
Of the general diseases, which may be confused with leprosy, we have
the circumscribed form of scleroderma. Such spots however are dead
white in color and are not anaesthetic. The prodromal manifestations
with fever and sweatings simulate malaria. Elephantiasis and Madura
foot have been confused with leprosy but the marked tendency to
limitation to the lower extremities and absence of anaesthesia should
differentiate. Probably the most difficult disease to differentiate
from leprosy is syringomyelia. Morvan’s disease is only a form of
syringomyelia in which the neuralgic pains, anaesthesia of the skin
and painless whitlows, with tissue loss, are features. In fact
Zambaco has advanced the idea that Morvan’s disease is leprosy.
In syringomyelia the dissociation of sensation is marked, as
with leprosy. In syringomyelia, however, the upper extremities
are, as a rule, alone affected and the muscular atrophy is more
of the scapulohumeral type, with involvement of trunk muscles
causing scoliosis, than of the thenar and hypothenar eminences, so
that while the fingers may be more contracted and rigid than in
leprosy we do not get the main-en-griffe. The anaesthetic areas
of syringomyelia continue to sweat, and we may also get spastic
symptoms and speech defects in syringomyelia.
Raynaud’s disease has also been confused with leprosy.
Of the skin diseases the most important confusing lesions are
the cutaneous manifestations of tuberculosis and syphilis. In
lupus the tubercles are very much smaller, show the apple jelly
appearance, the lesion spreads peripherally, is rather purplish and
is not anaesthetic. Syphilitic ulcerations are more punched out,
do not affect the same sites and respond to syphilitic treatment
immediately. You do not find nerve enlargements in syphilis.
There is great lack of agreement as to the frequency of the
Wassermann reaction in leprosy, some reporting a positive test
as common in nodular leprosy while others have reported negative
findings where there was not ground for suspecting syphilis. Nerve
leprosy does not often give a positive test.
Fletcher obtained 22% positives in 100 cases of leprosy—28% in
nodular and 17% in nerve cases. One-third of the cases gave a
history of syphilis.
Sutherland and Mitra obtained 17 positive Wassermann reactions
in 34 nodular cases, 16 positives in 52 anaesthetic cases and 8
positives in 14 cases of mixed leprosy. The sera of 12 children of
leprous parents were negative.
The luetin reaction is negative in leprosy.
Mycosis fungoides has not the characteristic location about the
face and itches markedly and does not show anaesthesia.
Vitiligo shows an abrupt margin and is not anaesthetic.
=Laboratory Diagnosis.=—The usual procedure is to scrape a spot
or nodule with a scalpel until the epidermis has been gone through
and then smear out the serous exudate on a slide and stain by the
Ziehl-Neelsen acid-fast method or by Gram’s stain. Twenty per
cent. sulphuric acid is less apt to decolorize than the 3% acid
alcohol, the leprosy bacilli being less resistant to acid alcohol
decolorization than to aqueous acid solutions. There is a great
variation in the resistance to decolorization of leprosy bacilli,
a preparation from one case holding its color almost as well as
tubercle bacilli, while material from another case may decolorize
very easily.
I am partial to Tschernogabow’s technique. In this, one punctures
the subepithelial granulomatous tissue with a capillary pipette,
the end of which has been broken off by tapping the point in order
to give a cutting point, and the serum which exudes is smeared out
and stained.
Some prefer emulsifying a piece of the tissue and centrifuging and
staining the sediment. Quite recently the antiformin method of
treating leprous tissue, as for tuberculous tissue, has been used.
Many insist that the best method is to cut out small sections of
the lesion, going well into normal tissue, and putting through
paraffin and cutting thin sections and staining. Gram’s method,
counterstaining with bismarck brown, gives beautiful preparations.
For acid-fast staining first stain with haematoxylin to obtain
a histological background and then steam with carbol fuchsin,
decolorize very briefly with acid alcohol, then through absolute
alcohol and xylol.
Of the greatest diagnostic value is the staining of the nasal mucus
or scrapings from ulcerations on nasal septum for leprosy bacilli.
These are often found in the characteristic cigar package bundles or
engulfed in lepra cells. A standard procedure is to give 60 grains of
iodide of potash to cause a drug coryza, in the secretions of which
leprosy bacilli may be found. However, one will have better success
if the nasal secretion be obtained at a time when a natural coryza
exists.
Thibault examined the nasal mucus, gland juice and blood of 30
lepers. He obtained leprosy bacilli in the nasal mucus of 20, in
the gland puncture juice of 18, and in the blood of 7.
Hollman detected leprosy bacilli in the nasal mucus of 90% of 58
nodular cases, of 67% of 6 mixed leprosy and of 45% of anaesthetic
cases, after making 329 examinations.
Leprosy bacilli are apt to be found in the blood of nodular cases,
especially at the time of the febrile accessions. The blood is
best taken in 5 or 10 cc. quantities into 1% sodium citrate in
distilled water. After centrifuging, the sediment is treated with
10% antiformin, at 37°C. for one hour. Again centrifuging, and
washing, the sediment is smeared out on a slide and stained. The
bacilli are not apt to be found in the blood of cases of nerve
leprosy.
Smith and Rivas add 10 vols. of 2% acetic acid to 1 vol. blood,
centrifuge and make smears.
Gland puncture has recently been considered as an important
diagnostic procedure in leprosy.
It must not be forgotten that while the finding of leprosy bacilli
is usually very easy in the nodules of nodular leprosy it is a
painstaking and discouraging procedure with the spots of nerve
leprosy. Even the affected nerves, at autopsy, often fail to show
bacilli. For nerve leprosy the examination of nasal mucus is of prime
importance.
The _Roentgen ray_ has been utilized in the recognition of the very
early, trophic changes in bone, showing the commencing absorption
of phalanges. Neve has reported a case in which there were no
satisfactory indications of leprosy other than slight deformity of
toes and fingers but showing marked changes in the phalanges, even
to disappearance of terminal phalanx of some toes when examined
with X-ray.
PROGNOSIS
The progress of the disease is so slow that it is difficult to
estimate improvement or cure. At present the possibility of a cure,
with the new methods of treatment, is encouraging. There is no doubt
but that many of the reported cures have simply been instances of
remissions in the course of the disease for periods covering months
or even three or four years. It would seem that the earlier treatment
is instituted the greater the possibility of cure. There were 38
cases officially reported as cured, in Norway, from 1881 to 1885.
Nodular leprosy runs its course much more quickly than does nerve
leprosy. It is in nodular leprosy particularly that intercurrent
affections carry off the patients. Tuberculosis carries off about
23% of cases and nephritis almost 30%, while a combination of
tuberculosis and renal disease about 10%. In the remainder, the
cachexia or accidents of leprosy itself are responsible for a
large portion of the deaths. Cases of nodular leprosy are more
often carried off by kidney disease than those with nerve or mixed
leprosy.
It must not be forgotten that lepers, especially those with the
nerve form, may live for twenty to forty years.
PROPHYLAXIS AND TREATMENT
=Prophylaxis.=—As was noted under epidemiology there seems to
be little evidence to show that insects play any part in the
transmission of leprosy. Nevertheless it would seem advisable
to prevent flies from becoming contaminated with the discharges
from leprous ulcerations which so often teem with leprosy bacilli.
This possible method of transmission would seem more deserving of
attention than the question of the taking up of bacilli from the
blood by mosquitoes, bedbugs or biting flies, as the leprosy bacilli
are found in the blood of nodular leprosy chiefly during the febrile
accessions and very rarely in the blood of cases of nerve leprosy. In
all of the ordinary insects the bacilli seem to disappear in a very
short time, with the exception of the cockroach, for which reason it
would seem advisable to destroy these pests, which can be easily done
by sprinkling around a little sodium fluoride.
There is some evidence that scabies favours infection so that this
disease should be looked for and actively treated in endemic areas.
Leprosy tends to spread where there is marked personal
uncleanliness and close contact with lepers in overcrowded
quarters. Many authorities consider the free use of soap and water
the most important means of avoiding infection. While segregation
is generally considered the one proven prophylactic measure there
are those who question its value. There does not seem to have been
any very marked influence on the spread of leprosy among the native
Hawaiians through the enforcement of isolation of such cases.
Partial segregation at their homes has given very satisfactory
results. Where a leper is not excreting bacilli, or where acid-fast
organisms cannot be found after careful search there is no danger.
Such patients, however, should report for examination every few
months. Evidence as to contact indicates that all young children
are particularly liable to the infection, as has been noted for
children of lepers and brothers and sisters. Even if segregation
of lepers is not carried out as regards adults, it should be the
rule for children, so that infants and young children should be
separated from their leper parents or parent. A very remarkable
feature in connection with leprosy is the hysterical dread that
many communities have of a leper, when they must know or could
easily learn, that the contagiousness of the affection is so
slight, that notwithstanding our efforts, we can scarcely point to
a single instance to prove undoubted transmission of the disease
from one person to another. At any rate knowing that immense
numbers of the bacilli are given off from ulcerations and the nose,
we should guard against the dissemination of leprosy bacilli from
such sources.
=Treatment.=—Many so-called specific products, whether of the nature
of extractives, as leprolin or nastin, or of bacterial vaccines, have
been tried with results which have not tended to gain the confidence
of conservative men. The product which has been given most general
trial is nastin. This is a neutral fat, extracted from a streptothrix
growth, obtained by Deycke from leprous nodules. It is combined
with benzoyl chloride and is contained in ampoules containing from
one-half to one-fifth of a milligram.
Wise and Minett treated 244 cases with nastin for periods of from
one to two years, the treatment having been at first supervised by
Deycke himself. It was stated that nodular cases did not seem to be
improved and that anaesthetic leprosy was not apparently influenced.
Minett mentions the efficiency of a 2½% solution of benzoyl
chloride as a nasal spray and as an application to leprous ulcers,
this treatment causing the bacilli rapidly to disappear from the
discharges of nose or ulcers. On the other hand Scott, in Assam,
reports practically 50% of cures, or cases greatly improved, in
patients treated with nastin for a year or more. He gave nastin B1
injected intramuscularly at two weeks intervals.
Salvarsan does not seem to have been of any value in leprosy.
The standard treatment for leprosy is chaulmoogra oil given
internally, in capsules, in doses of 5 to 10 minims increased
gradually, according to stomach tolerance, to 40 to 60 minims.
For hypodermic use Heiser makes a mixture of 60 cc. each of
chaulmoogra oil and camphorated oil with 4 grams resorcin.
Injections are made weekly, commencing with 1 cc. This dose is
increased steadily according to tolerance, but in some patients
marked reaction in the lesions, with fever, occurs after a dose of
only a few cubic centimeters has been reached.
Rogers has for some time been giving subcutaneous injections of
sodium gynocardate, the sodium salt of the lower melting-point
fatty acids of chaulmoogra oil. Finding that large doses of sodium
gynocardate could be administered to animals with safety he has
recently given intravenous injections and has substituted this
method for the subcutaneous one. For use in the treatment of
leprosy he prepares a 2 or 3% solution in distilled water and,
after sterilization in an autoclave, adds ½ per cent. carbolic
acid. The solution should be quite clear. He starts with one-tenth
of a grain and increases the dosage by one-tenth with each
successive injection up to four-fifths of a grain. He states that
this method has as great superiority over the subcutaneous one
as that has over the administration of chaulmoogra oil by mouth.
Rogers now uses a solution of 3% sod. gynocardate with 1% phenol
and 1% sod. citrate. At first the intravenous injection is with 0.5
cc. thrice weekly, which dose is gradually increased up to as much
as 5 cc.
It is possible that sodium morrhuate (cod-liver oil) may be as
efficacious as the gynocardate salt. Rogers has used _Hydnocarpus_
instead of the true chaulmoogra oil and thought he obtained better
results. One explanation of the uncertainty of success with
chaulmoogra oil is the difficulty of securing oil obtained from
proper sources. The standard treatment of leprosy in Honolulu, as
reported by McDonald, is the weekly injection of the ethyl esters
of the entire fatty acids of the whole chaulmoogra oil, with 2% by
weight of iodine, chemically combined. The treatment begins with 1
cc. injected intramuscularly, increased by 1 cc. at every second
or third injection, until a dose of from 2 to 6 cc. is reached,
according to age and weight of patient.
For internal use the mixed fatty acids, carrying 2½% iodine,
chemically combined, are given in capsule. The dose by mouth is
0.25 grams per 100 lbs. weight, three times daily, an hour or two
after meals. This is gradually increased every two weeks until a
maximum dose of 1 gm. per 100 lbs. weight is reached.
Dyer combines hydrotherapy with the administration of chaulmoogra
oil. He gives a daily bath as hot as can be borne, and, in addition
to the specific treatment, gives 1/60th grain of strychnine three
times daily.
Antileprol, a preparation of chaulmoogra oil, which is more
satisfactory than oil, may be given in doses approximating 120 grains
by mouth daily or 60 grains subcutaneously. Such drugs as arsenic
salicylate of soda and bichloride of mercury have been used.
Thyroid extract has seemed to benefit cases of anaesthetic leprosy
in rare instances. The high frequency current with the needle
applied to the nodular lesions has been recommended by Unna. Radium
and X-rays have also been employed. There have been reports as to
the value of the antimony treatment in leprosy.
Leprosy is a disease in which improvement often occurs when the
patient is placed under more favorable conditions as to food,
climate, etc. Again, there is at times a tendency for the disease to
abort or ameliorate without relation to treatment or environment.
Surgical treatment is frequently of use, as nerve stretching for
the leprous neuralgias. Various eye operations are necessitated
by the ectropion or leprotic iritis. The amputations of the area
involved in perforating ulcer is recommended. Tracheotomy is often
demanded for the laryngeal stenosis.
McCoy has combined carbon dioxide snow local treatment with
chaulmoogra oil. The lesions showed decrease in size but remained
bacteriologically positive.
SECTION III
FOOD DEFICIENCY DISEASES
CHAPTER XVIII
BERIBERI
DEFINITION AND SYNONYMS
=Definition.=—Beriberi is a food deficiency disease due to the
absence from the dietary of a neuritis-preventing vitamine. It is
particularly important among the people of the Orient whose diet
is preponderatingly one of rice. In milling the grain the outer
vitamine-containing layers are rubbed off and this polished rice,
when the chief constituent of a dietary, is capable of causing, after
a period of two or three months, a peripheral neuritis.
This neuritis not only involves the nerves of the extremities but,
as well, the pneumogastric, and it is the manifestation of cardiac
disturbances which best differentiate this form of neuritis from
those due to alcohol or arsenic.
The disease is usually described under two types: (1) a wet or
dropsical beriberi, in which the vasomotor nerves are affected with
resultant general oedema and (2) a dry atrophic or paraplegic type,
in which muscular palsies and atrophies are the leading features.
Pathologically, we have a Wallerian degeneration of the peripheral
nerves with possibly axonal degeneration of the cells of the neuron
involved.
=Synonyms.=—Neuritis Multiplex Endemica, Polyneuritis Endemica,
Hydrops Asthmaticus. Japanese: Kakke.
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—While modern knowledge of beriberi may be said to
date from the writings of Bontius, in 1642, yet the disease is
distinctly described by Chinese writers of the seventh century and
treated in writings of the second century and possibly referred
to in writings as ancient as B. C. 2697. It is probable that the
disease described by Strabo as occurring in a Roman army while
invading Arabia, in 24 B. C., was beriberi. While mention of the
disease may be found in Japanese writings of the ninth century it
is thought by Scheube that this relates to the disease in China and
that beriberi first appeared in Japan about the eighteenth century.
Bontius described the atrophic form of the disease, Rogers, in
1808, the serous effusions, and Marshall, in 1812, noted two types,
barbiers, when the paralysis predominated, and beriberi, when the
dyspnoea and oedema were leading features.
In 1835 Malcolmson noted that cases of beriberi assumed the type of
barbiers and vice versa, from this time the view has obtained that
the two affections belong to one disease.
The disease seems to have first made its appearance in Brazil in
1866.
[Illustration: FIG. 82.—Geographical distribution of Beriberi.]
=Geographical Distribution.=—Reference to the chart will show
3 markedly endemic centers for beriberi, one embracing Japan, a
second the Dutch East Indies (Java, Borneo, Sumatra), and a third,
involving the Eastern coast of Brazil. In somewhat less degree the
disease prevails in India, Indo-China, Malay Peninsula, Eastern
China, and the Philippine Islands. It is also found in the regions
of the East and West Coasts of Africa, and was devastating to the
laborers on the Congo railway. It has been reported from many parts
of the world among coolies from Asiatic countries. A disease of
similar nature has been noted in asylums in England and America.
Beriberi occurred among the British soldiers in Mesopotamia during
the recent war—more than 300 cases in 1915. It is interesting
to note that scurvy, and not beriberi, occurred among the Indian
troops in Mesopotamia at this time. There was no scurvy in the
British troops.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—There is probably no disease about which there exist so
many views as to etiology as with beriberi. Many of those formerly
advanced are so negatived by recent investigations that it would
seem hardly worth while to mention them. While the cause is still
unsolved attention is at present almost exclusively directed to some
deficiency of a neuritis-preventing substance in the dietary and
such studies have in large part centered about the question of such
deficiencies in certain kinds of rice.
Reserving until the last the discussion of the rice theories we may
briefly dismiss such views as those assigning bacterial or protozoal
causes with the exception of those of Manson and Hamilton Wright.
_Manson’s Theory._—Under conditions of overcrowding, filth,
warmth, moisture and lack of ventilation, as would obtain in the
forecastle of a ship carrying a native crew, the development of a
hypothetical germ is favored. This germ in its growth gives off
emanations which like alcohol act as toxins upon the peripheral
nerves. The germ itself does not infect the patient.
_Wright’s Theory._—According to this view a bacillus which was
given off in the faeces was ingested and locating in the duodenal
mucosa gave off a toxin similar to that of the diphtheria bacillus.
Instead of developing its soluble toxin in the membrane of the
region of the throat this action took place in the upper part of
the small intestines.
Of the bacterial causes may be mentioned: (1) The coccus of
Pekelharing and Winckler. This organism was supposed to be short
lived in the body and repeated infections were necessary to produce
the disease.
(2) Dangerfield held views somewhat similar to those of Pekelharing
and thought a coccus in the alimentary canal the cause.
(3) Isuzuki regarded a coccus isolated from the urine as the cause.
(4) Okata and Kokubo thought a coccus obtained from the blood to be
the infecting agent.
Various bacilli, other than that incriminated by Wright, have been
brought forward as pathogenic agents but it may be stated without
further discussion that the claims of the advocates of bacterial
causes have not been verified and are solely of historical
interest. The same statement will hold for the plasmodium-like
protozoon of Glogner which was found in the splenic blood.
_Of the chemical theories_ may be mentioned; (1) Arsenic poisoning.
In an outbreak of arsenical neuritis in England, from arsenic
contained in the glucose used in making beer, Ross diagnosed the
illness as beriberi. Subsequently, arsenic was found in the hair of
certain patients with beriberi, hence the theory which has never
been substantiated. It may be stated that a careful study of this
epidemic by Reynolds and Bury indicated that the alcoholic factor
was also operative as persons taking an equal amount of arsenic but
without alcohol, did not develop neuritis.
(2) Treutlein’s oxalate theory.—This was based on the fact that
polyneuritis gallinarum could be produced in fowls by feeding them
oxalic acid.
_Of the food deficiency theories_, the most prominent is (1) that
of Takaki, generally designated the _nitrogen deficiency_ theory.
As the result of increasing the proteid constituents of the ration
of the Japanese Navy from 109 to 196 grams, the disease was largely
eliminated (from about 32% incidence to less than 0.5%).
In the old ration the ratio of N to C was as 1 to 17—32, in the
new ration, 1—16. In looking over the constituents of the new
ration the addition of about 100 grams of beans is noted. These are
rich in vitamines.
(2) According to Fales the hypothetical germ of beriberi can only
live in body fluids deficient in potassium carbonate. The high
content of potash in potatoes made him greatly increase the amount
of this vegetable in the dietary he recommended. Fales noted scurvy
as well as beriberi in the Bilibid prisoners on a diet deficient in
potash.
(3) Deficient fat. (4) Deficient phosphorus.—It was Schaumann’s
idea that the phosphorus contained in the outer layers of the rice
grain was essential in the prevention of beriberi. While it is
now known that the beriberi-preventing substance does not contain
phosphorus, yet the idea has proven of practical value as giving an
index of beriberi-producing power of rice.
_P_{2}O_{5} Index of Beriberi-producing Rice._—If a rice contain
under 0.4% of phosphorus pentoxide it is liable to produce beriberi.
Schaumann now considers that the antineuritic substance in rice
polishings acts as an activator in the metabolism of phosphorus.
_Vitamine Deficiency._—Grijns was the first to insist that beriberi
was due to the absence in the diet of some substance essential to
proper metabolism of the peripheral nerves. His views were along the
line of our present _vitamine deficiency ones_. There are undoubtedly
many different vitamines, varying as to nature of protective
power, temperature at which destroyed, solubility, etc. McCollum
emphasizes the importance of a fat soluble A and a water and alcohol
soluble substance B for proper metabolism. This latter, usually
designated “Water soluble B,” is generally considered the same as the
anti-neuritis vitamine but there is recent evidence that this may not
be the case. The antiscorbutic vitamine is water soluble C.
_Food Poisoning as Cause._—There are other theories as to
intestinal parasites causing the disease and in particular views as
to relation of fish eating to the disease, which are (1) that it is
caused by the ingestion of raw fish, or again (2) from the eating
of certain poisonous fish.
Miura, who is the great advocate of a fish intoxication, believes
that this comes about from eating fish belonging to the Scomberidae
family. As proving this, he cites the absence of beriberi in
prisons in Japan, where no fish is allowed. He does not recognize
that it is the diet of barley 6 to rice 4 parts which is the
prophylactic factor. Barley is rich in vitamines.
RICE AND BERIBERI
There are a few points in connection with rice which should be
understood. The larger part of the rice grain is starch and
covering this central starch core we have the rather thin aleurone
layer containing the proteid and fat constituents of the grain.
Externally there is an adherent layer, the pericarp, which varies
in color from red to white according to the kind of rice. The
pericarp contains the salts. The grain is covered by the husk which
is always removed to render the rice suitable for food. Unhusked
rice is called _padi_ in India and _palay_ in the Philippines. In
the process of removing the husk (milling) the pericarp and more or
less of the aleurone layer may be rubbed off the grain. When the
milling process is carried to the extent that but little remains
except the starch the rice is termed _polished_, _highly milled_,
or _white_ rice. A process of parboiling causes the husk to be more
easily detached and the pericarp to adhere more firmly to the grain
and when milled there is less loss of the anti-neuritis principle,
which is contained in the outer layers. Such rice is called
_cured_ rice. The embryo also contains the anti-neuritis vitamine
as well as the fat soluble A one. It is also lost in milling. The
scale-like dust is termed _rice polishings_ and has curative value
for those who have developed beriberi under a diet of polished
rice. When the milling process is less complete the rice so treated
is called _undermilled_ rice or _red_ rice. Polished, highly milled
or white rice contains as a rule less than 0.4% of phosphorus
pentoxide while the beriberi-preventing rices contain more than
0.4% of this compound for which reason legislation has required
rice to have more than 0.4% phosphorus pentoxide.
Siam rice is a polished white rice which contains about 0.25%
phosphorus pentoxide and has more often been associated with severe
outbreaks of beriberi than Rangoon rice, which has about 0.32%,
this latter, however, being a well-recognized beriberi-producing
rice. Unpolished rice contains about 0.55% of phosphorus pentoxide.
Natives generally prefer the polished rice because it is clean and
free from weevils, while the undermilled kind is dirty. Parboiled
rice has a disagreeable odor.
Voegtlin has recommended a P_{2}O_{5} requirement of 0.5% for corn
products and 1% for wheat ones. Thus whole wheat contained 1.12%
while highly milled flour had only 0.114%. Fowls fed on this flour
developed polyneuritis in twenty to thirty-two days.
Whole corn contains 0.76% P_{2}O_{5}, while highly milled corn
grits has approximately 0.2%, and highly milled corn meal about
0.3%. These highly milled corn products produced polyneuritis
within from thirty to thirty-five days.
With rock ground corn meal, containing 0.7% P_{2}O_{5} the fowls
remained well.
_Experiment of Fraser and Stanton._—While there have been numerous
instances reported to show the connection between polished rice and
beriberi, when such rice was the predominating article of diet, it
will suffice to refer to the experiments of Fraser and Stanton and of
Strong.
In 1909, Fraser and Stanton experimented with 493 Javanese coolies
who were employed in building a road far removed from any village
which might introduce the factor of bacterial etiology into the
problem. They noted that the Javanese prefer white rice, and
reference is made to the fact that many cases of beriberi occurred
among these laborers in 1906, which outbreak ceased upon requiring
them to eat parboiled rice at the suggestion of Doctor Braddon.
They state that they informed the coolies of the danger of white
rice but, notwithstanding, they all expressed a preference for the
white rice over parboiled rice. For the purpose of comparison, only
one-half were allowed the white rice diet. The two parties were
quartered in virgin jungle and were isolated from each other by an
interval of 7 miles. Of 220 individuals on white rice there were 20
cases of beriberi recorded while among 273, who lived on parboiled
rice, no cases occurred.
_Prolonged Continuation of Faulty Diet Necessary._—It appeared that
a considerable period of continuance of white rice diet was necessary
before the appearance of the disease (eighty-seven days). As against
the infectious nature of the disease they note that contact of
persons on a parboiled rice diet with the beriberi cases was without
result. Substitution of parboiled rice for white rice brought about a
cessation of the outbreak.
The Philippine scouts, numbering about 5000 natives, gave 618 cases
of beriberi in 1908 and 550 cases in 1909. In 1910 undermilled rice
was substituted for polished rice and they were required to eat 1-6
oz. beans daily. No other change in their mode of living was made.
By 1913 beriberi had disappeared among them, although the disease
still prevailed among the native population in contact with them.
_Experiment of Strong and Crowell._—Strong and Crowell stated that
the object of their study was to determine whether beriberi, as it
occurs in the Philippines, is an infectious disease or whether it is
one which has its origin in disturbances of metabolism, due chiefly
to the prolonged use of polished rice as a staple article of diet.
The experiments were carried out in Bilibid prison. Prisoners, who
had been condemned to death, were informed of the nature of the
experiment and were told of the diet on which it was proposed to
place them. They were also told that they might contract beriberi.
Twenty-nine volunteered and each signed a statement in his own
dialect that he undertook the experiment voluntarily.
In general, the groups were fed for the greater part of the time
occupied by the experiments as follows: Group (1) “White rice and
extract of rice polishings and special diet.” Group (2) “White rice
and special diet.” Group (3) “Red rice and special diet.” Group (4)
“White rice and special diet.”
Of 6 men on the Group 1 diet, 2 developed beriberi. The symptoms
however, were not marked, being chiefly loss of weight,
tachycardia, slight oedema of legs and tenderness of muscles of
calves. Four of the 6 men of Group 2 developed beriberi and 6 out
of 11, in Group 4, showed symptoms of beriberi. In Group 3, only 2
in 6 developed symptoms and these consisted in case No. 13 only in
tenderness of epigastrium, paraesthesia, cardiac disturbance and
marked diminution of knee jerk. In case No. 18 there was noted only
slight cardiac disturbance and epigastric pulsation. In none of
the cases was the complete picture of beriberi obtained except in
those in which the white polished rice formed the staple article of
diet, but in one case, fed on red rice, the diagnosis of beriberi
was almost definite.
The results of their experiments with the addition of rice polishings
to the diet would indicate that whatever may be the results obtained
with extracts from this material in preventing polyneuritis of fowls
or in curing it after it has developed it is not as efficient in man
as the cheaper and more readily obtainable mongo or katjangidjo bean
or yeast.
Evidently symptoms of beriberi may also sometimes occur in
individuals fed on red rice as a staple article of diet when the
diet is very monotonous, comprising few articles and continued
for long periods of time. From the experiments it is evident that
beriberi may be produced by the prolonged consumption of white rice
as a staple diet. Of 17 individuals fed on such diet 8 developed
beriberi, all with distinct loss of knee jerk, as well as with
other marked symptoms of the disease. Symptoms appeared within 61
to 75 days after the commencement of the diet.
Vedder thinks that the red rice used in these experiments may not
have been sufficiently undermilled, as it was found most difficult
to obtain such a beriberi-preventing rice for the Philippine
scouts. As regards the lack of success with extract of rice
polishings the same author considers that a sufficient amount of
alcohol for the extraction of the vitamines was not used in the
above experiments, as he found it necessary to use 30 litres of
alcohol to 5 kilos of rice polishings. Strong and Crowell used only
14 litres of 95% alcohol to 5 kilos of polishings.
_Braddon’s views._—Prior to the investigations of Fraser and
Stanton the importance of the rice factor in the etiology of
beriberi was insisted upon by Braddon who thought that a poison
was elaborated by some organism which poison was contained in the
beriberi-producing rice. This development was thought to occur
in rice stored in damp places, but Vedder has shown that storing
undermilled rice in a damp place for a year does not cause it to
lose its anti-beriberi-producing properties.
_Endocrine Gland Disturbances and Beriberi._—We owe in particular
to the researches of McCarrison our appreciation of the important
rôle of the endocrine glands in deficiency diseases. With dietaries
deficient in vitamines he noted in birds and other animals
hypertrophy of the adrenals, atrophy of the thyroid, thymus,
testicles and ovary. The pituitary was unaffected. Vitamine
deficiency seems to impair the activity of the thyroid and to thus
favor the action of products of intestinal bacteria. It is now
accepted as important this secondary factor of bacterial infection
in all types of food deficiency pathology. Dietaries rich in fats
and proteins with sufficiency of vitamines bring about thyroid
hyperplasia. In a diet too rich in carbohydrates and deficient in
vitamines marked endocrine disturbances are noted.
The adrenals show hypertrophy on a vitamine-deficient diet and this
hypertrophy is associated with increase of the adrenalin content of
the glands. Oedema seems to be associated with adrenal hypertrophy.
McCarrison believes the oedema to be associated with increased
intracapillary pressure from the effect of adrenalin but others
dispute the explanation. The adrenalin content of the enlarged
adrenals varies; it is in excess with a diet rich in carbohydrates
and deficient in proteins and vitamines, but is below normal when the
diet is scurvy-producing. Butter, probably from its fat soluble A
content, seems to protect against oedema.
_Polyneuritis gallinarum._—The work of Eijkman in showing that
polyneuritis could be produced in fowls by feeding them on polished
rice and prevented when a diet of rice polishings was added to
the neuritis-producing rice opened the way for a vast amount of
experimental work. As regards the nature of the neuritis-preventing
substance in the rice polishings it was soon found that it had no
relation to the phosphorus content. Funk has isolated a substance he
calls _vitamine_, a pyramidine base precipitated by phosphotungstic
acid, which is present in rice polishings and seems to possess
extraordinary curative properties in polyneuritis gallinarum. Heart
muscle, egg yolk and yeast are rich in this anti-neuritis substance,
which is also present in lentils and barley.
_Various Vitamines._—The anti-neuritis vitamine is soluble in
water and alcohol and is comparatively thermostable (destroyed by
a temperature of 120°C. in two hours). It is affected by alkaline
reaction but is stable in acid solution. The water soluble B vitamine
does not seem to be destroyed by a temperature of 120°C. for two
hours, hence it may be different from the anti-neuritis one. The
antiscorbutic vitamines differ in being thermolabile, these factors
in certain foods being destroyed by a temperature of 60°C. Another
vitamine, fat soluble A, found particularly in butter, seed embryos
and leaves of plants, is a food essential. Its absence from a diet
causes xerophthalmia. Cod-liver oil and glandular organs of animals
contain it.
Schaumann considers malt as richer in the anti-neuritis vitamine
than any other article of diet, rice bran coming next. Many think
that vitamines have not as yet been separated but that they are
intimately combined with some mother substance in the food.
There is, in all probability, a large number of vitamines present
in various animal and vegetable foods, the deficiency of which in a
diet may lead to vague disorders or to well-recognized diseases,
such as scurvy, ship beriberi, beriberi or pellagra.
Schaumann considers the curative principle to be of the nature of
an activator. An increase in the ingestion of carbohydrates and
necessarily in the vitamine as well seems to produce neuritis more
rapidly than where a smaller amount is given, this indicating the
importance of these vitamines in carbohydrate metabolism.
There are those who deny this carbohydrate metabolism function of
vitamines and it is a fact that polyneuritis of fowls will develop on
a diet from which carbohydrates are excluded.
In epidemics of beriberi it has been observed that those who eat
most rice are more often attacked, thus men more frequently than
women. A temperature of 120°C. destroys the vitamine. Owing to the
absence of rice as a constituent of other than slightest importance
in the dietary of Brazilian cases of beriberi, as well as from
numerous reports of the occurrence of the disease in nonrice-eating
persons, the view that is now entertained is that not only polished
rice, but any predominating carbohydrate article of diet, which
is deficient in the neuritis-preventing substance, can produce
beriberi. Wellman and Bass have shown that such articles of diet as
sago, boiled white potatoes, corn grits and macaroni practically
parallel polished rice in the production of polyneuritis in fowls.
=Predisposing Causes.=—There does not seem to be any racial
predisposition other than that associated with the more varied
and the more neuritis-preventing diet of the white race. For the
same reason beriberi is more prevalent among the poor than among
the prosperous classes of countries where the disease exists
extensively.
It is customary to consider as predisposing causes bad hygienic
surroundings, such as occur in jails, camps, etc., as well as
the influence of warmth and dampness of the atmosphere. Beriberi
is more common among men than women and affects most commonly
individuals between 15 and 30 years of age. Physical exhaustion,
excessive grief, digestive derangements, abuse of alcohol and
tobacco are considered to have a bearing in the production of
the beriberi symptoms. Surgical operations may be followed by
manifestations of the disease.
=Epidemiology.=—Inasmuch as the experiments of Strong force us to
the conclusion that the disease is not infectious, the study of the
prevention of the disease would appear to rest almost exclusively in
the question of a neuritis-preventing dietary.
In this connection Heiser, in the Philippines, has reported that
with a diet in which polished rice was contained the monthly death
rate at the leper colony at Culion was approximately 100, the
majority of these deaths being from beriberi. As a result of the
substitution of unpolished rice, about 1909, the monthly death rate
fell to less than 20 and of these none were from beriberi.
Toward the close of 1911 there was a great shortage of the rice
crop and the Philippine government bought quantities of rice in
order to protect the people from extortionate dealers. Much of
this rice was polished rice. The use of this polished rice was
commenced at Culion in November, 1911. In January, 1912, there
were 35 deaths, of which 2 were from beriberi. In February 86
deaths with 36 from beriberi and in March 82 deaths with 60 from
beriberi. In February the use of polished rice was discontinued
and unpolished rice substituted. In April the deaths had fallen to
25 with 3 from beriberi and, subsequent to that month, deaths from
beriberi cases developing at Culion ceased to be reported.
As regards the length of time necessary for the production of
the symptom-complex, Strong’s experiments show that beriberi was
produced in from sixty-one to seventy-five days. In Fraser and
Stanton’s work no case developed under eighty-seven days and many
of the cases did not develop for 120 to 160 days. Hamilton Wright
considered that the incubation period for his toxin-producing
bacillus was ten to thirty days.
PATHOLOGY AND MORBID ANATOMY
In polyneuritis gallinarum, Vedder and Clark are of the opinion
that there may be two vitamines involved, the absence of one from
the dietary causing the neuritis, while that of the other leads to
general prostration and cardiac degeneration, so that there may be
other factors in the production of beriberi than the degeneration of
the peripheral nerves and involvement of the vasomotors.
Furthermore, extract of rice polishings rapidly cures the cardiac
condition as well as the dropsy, but not the paresis; while Funk’s
vitamine base, which will cure the paralysis, will not affect the
cardiac disorder.
The blood of beriberics in the acute stage, has been shown to
contain a substance capable of profoundly influencing the vasomotor
functions, causing venous engorgement and a fall of blood pressure.
In deaths from wet beriberi the tissues are very moist so that
incisions tend to fill with fluid. There are generally present
pleural and in particular pericardial effusions. Serous fluid
in the abdominal cavity may also be present. The lower end of
the stomach and the upper portion of the small intestines, in
particular the duodenum, show marked congestion with more or less
abundant haemorrhagic extravasations. Some authorities do not admit
the existence of this duodenal congestion so insisted upon by
Wright.
The oesophagus is usually congested as may be also the pharynx and
the larynx.
Next to the peripheral nerve degenerations, to be later considered,
the most important lesions are found in connection with the heart.
All chambers of the heart show a dilatation with hypertrophy
as well as dilatation of the right ventricle in cases that
have lasted for some time. The heart muscle has the faded-leaf
appearance indicative of fatty degeneration. Microscopically there
are segmentation and vacuolation of the fibres. The lungs show
congestion and at times present the characteristics of pulmonary
oedema. The kidneys are congested but show only exceptionally
parenchymatous or interstitial changes. As would be expected, the
back pressure in the right heart gives a dilatation of the central
vein of the liver lobules which at times is productive of atrophy
of the adjacent liver cells. The muscles supplied by the affected
peripheral nerves show more or less atrophy according to the
duration of the disease.
Microscopically, the affected fibres show a loss of striation
with a colloid degeneration. These changes are more marked in
beriberic residual paralysis. The key to the disease is in
the changes present in the peripheral nerves. While these may
appear normal yet histological examination shows varying nerve
degenerations from slight medullary degeneration in a few fibres to
complete destruction of the nerve, giving a Wallerian degeneration
(vacuolation and formation of myelin droplets in the medullary
sheath with fragmentation of the axis-cylinder).
While it is usually stated that the central nervous system (brain
and cord), remains uninvolved yet we note axonal degeneration in
the cells of the nuclear centres of the affected peripheral nerves
as shown by convexity of the cell sides, dislocation of the nucleus
and disappearance of the tigroid substance. The striking feature of
the pathology of beriberi is the involvement of the vagus nerve and
there is evidence of degenerative changes in the cells of the vagal
origin in the floor of the fourth ventricle.
Various investigators have shown that in fowls marked peripheral
neuritis can exist long before clinical manifestations appear
and that typical cases of beriberi may show striking improvement
following vitamine administration, notwithstanding the continued
existence of peripheral nerve degeneration. For such reasons Vedder
thinks the more important changes to probably belong to cells of
cord and brain.
McCarrison has noted striking changes in the endocrine glands in
avian polyneuritis, particularly hypertrophy of the adrenals and
atrophy of the other glands of internal secretion. He attributes
the oedema to increase in adrenalin content. Shimbo has reported
adrenal hypertrophy in 14 human cases of beriberi.
SYMPTOMATOLOGY
It is well to remember that beriberi is but a form of multiple
neuritis which in many cases shows only motor and sensory
disturbances of the lower portions of the upper and lower extremities.
In fact an extensive epidemic of arsenical neuritis, or, to be more
exact, a neuritis in which both alcoholic and arsenical factors
were operative, was regarded by eminent authorities as beriberi.
The key to beriberi, however, is the peculiar and striking selection
of the vagus nerve in the degenerative processes as well as those of
the peripheral nerves of the extremities. It is vagal involvement,
giving disturbances of heart particularly and lungs in less degree,
which chiefly differentiates beriberi from other forms of multiple
neuritis.
Another peculiarity of beriberi is the tendency to vasomotor
involvement as shown in the patchy areas of oedema.
_Epidemic Dropsy._—Beriberi is typically a nonfebrile disease.
There is, however, a disease with fever, called epidemic dropsy,
which seems to have a similar etiology to beriberi. It also shows
the symptoms of a peripheral neuritis plus cardiac disturbances. In
fact Pearse has maintained the identity of the two diseases. Greig
considers epidemic dropsy as resembling ship beriberi.
The first record of epidemic dropsy was during a famine in Southern
India in 1877. Outbreaks again occurred in 1902 and 1907. The fact
that it is a disease which often shows a house infection has caused
the advancing of a theory that the bedbug transmits the disease.
While greatly resembling beriberi clinically the following points
of difference are usually noted by those who hold that it is a
distinct disease entity.
1. The presence of fever, which rarely exceeds 102°F. and is
usually only about 99° to 100°F.
2. An erythematous rash upon the oedematous portions of the
extremities.
3. The frequent generalized oedema, which suggested the designation
dropsy for the disease, cannot be differentiated from wet beriberi.
4. The neuritis manifestations are slight or absent. There may
be formication of the feet but anaesthesia is wanting. The vagal
involvement gives cardiac disturbances. There is anaemia.
_Infantile Beriberi._—There is also a condition in nursing infants
which would be difficult to recognize if unaware of the existence of
this type of beriberi. It is called _infantile beriberi_.
In 1898 Hirota first noted the existence of a condition in infants
nourished by beriberi mothers which has more recently been
carefully studied by McLaughlin and Andrews and to which the name
infantile beriberi is now generally given. In the Philippines it is
called “taon.” Clinically there is restlessness, vomiting, altered
voice, increased heart action, oedema and cyanosis. After death
there is found a marked hypertrophy and dilatation of the right
side of the heart with no change of the left side. The peripheral
nerves also show the lesions of beriberi of adults but of less
intensity.
The disease most often shows itself in an acute form, the child
rather suddenly being seized with great pain, crying constantly and
soon becoming cyanosed. Death, which may occur in a few minutes or
hours, is often thought to be due to meningitis, although there is
no fever or true convulsions. There is only rigidity of the body.
Less frequently the disease appears in a chronic form in which
vomiting and constipation are most marked. There is often a history
of the loss by the mother, who herself may have only a rudimentary
beriberi, of several children from this disease.
The infants improve rapidly when other infant feeding is
substituted for the mother’s milk. An extract of rice polishings
gives striking results in these cases.
_Asylum Beriberi._—The beriberi outbreaks which have frequently
been reported from European and American camps, prisons and
asylums do not differ from the cases one may see in the
classical distribution of the disease among the rice-eating
populations of the Orient. The cause is the same, a deficiency
in beriberi-preventing vitamines, and the symptoms are similar.
These vitamines may be deficient in the rice or other cereal or
proteid food supplied. Again they may have originally been present
in sufficient quantity but later destroyed by too great heat or
otherwise.
=Types of Beriberi.=—The ordinary clinical division of beriberi
is into (1) _wet or dropsical beriberi_ and (2) _dry or atrophic
beriberi_. At the same time, in a typical case, we find such
a combination of the vasomotor disturbances which lead to the
oedematous or dropsical manifestations of wet beriberi, and likewise
of those of peripheral nerve involvement causing more or less
development of muscular palsies or atrophies, as seen more strikingly
in dry or atrophic beriberi, that it does not seem advisable to
employ such a division.
In fact typical cases of wet or dropsical beriberi after a profuse
diuresis may change in a short time, as Manson has so aptly stated,
from a bloated carcass to little more than skin and bones and
assume all the appearance of a case of dry or atrophic beriberi.
Even Vedder, who states that from a theoretical standpoint wet and
dry beriberi may be considered separate pathological processes
(deficiency in the anti-cardiac degeneration vitamine rather than
the anti-neuritis one), is inclined to believe it inadvisable, from
a clinical standpoint, to consider the one type apart from the
other.
One sees cases which combine the features of dry and wet beriberi
which can best be designated _typical beriberi_. Again we see cases
where the vagal and vasomotor involvement is so marked that the
patient resembles a man with acute nephritis plus all the evidence
of extreme cardiac decompensation. Such cases may be designated
_fulminating_, _pernicious_ or better _cardiac_.
Again we observe cases which from the start show little if any
oedema and very slight cardiac involvement, but with marked motor
disturbances as shown by muscular atrophies and palsies. The
sensory changes are not so marked as the motor ones. Complete
anaesthesia is rarely present, it is rather paraesthesia and
blunting of sensation which characterize the sensory phenomena.
This is usually designated the _atrophic_ or _paraplegic_ type.
_Rudimentary or Larval Beriberi._—Scheube recognizes a rudimentary
type and it must have been the experience of every one in the tropics
that these indefinite types of beriberi are quite common.
In such cases there may be nothing more than some weakness of the
legs with vague manifestations of blunting of the sensation or
variation of the reflexes. At times there may be marked anaesthesia
in the region over the shin bones.
Many of these cases show cardiac palpitation on exertion and at
times we may note slight evidences of oedema about the lower part
of shin bone or dorsum of the foot. It is the frequency of such
cases that causes physicians in the tropics to consider almost
any affection showing neurological manifestations as of beriberi
nature. A careful study of the neurological features of cases in
the tropics will show that many of these cases are not beriberi but
rather the common cosmopolitan diseases of the nervous system.
=A Typical Case of Beriberi.=—The patient first complains of
weakness and heaviness of the legs, particularly after fatiguing
work. There is also noted a sense of fullness and tenderness in
the epigastric region. The slightest exercise brings about cardiac
palpitation and more or less dyspnoea.
As the symptoms of peripheral neuritis become more prominent we
have hyperaesthesia of the calf muscles so that squeezing these
muscles gives rise to rather marked pain. The thenar muscles or
those of the forearm may also be more or less hyperaesthetic.
Attention has been called to a circumoral anaesthesia.
An examination at this time will probably show an active patellar
reflex, some oedema over the shin and malleoli, possibly extending to
the dorsum of the foot, with partial anaesthesia in the oedematous
areas. It is a blunting of sensation as though a layer of cotton
were interposed between the skin and the examining instrument. Other
favorite sites for the oedema are the sacral and sternal regions.
Occasionally sharply defined oedematous patches may be observed,
particularly on the arms.
The exercise attendant upon the physical examination will probably
cause a rather marked cardiac palpitation. The pulse is usually rapid
and its rate is markedly affected by the slightest exertion. The
systolic pressure is low.
The anaesthesia noted in the lower extremities soon tends to show
itself about the back of the hands and the finger tips, so that it
may be difficult for the patient to button his coat. There is also
weakness of the grip. The temperature is normal and the mind is
entirely clear. The results from a blood examination are practically
negative, although later on there is the blood picture of a secondary
anaemia.
In cases where the oedema is more marked and generalized and when
pericardial or other effusions are developing we find a diminution
in the amount of urine, but with an absence of albuminuria.
Later the case may show a dropsical condition more or less resembling
nephritis, but with only slight scrotal oedema. At the same time
there will be found a dilatation of the right heart with blowing
systolic murmurs and equal spacing of the heart sounds. There may be
marked pulsation of the veins of the neck. At this time the patellar
reflex may be diminished and the anaesthetic areas more extensive.
This condition of wet, dropsical or oedematous beriberi may be
fairly rapidly succeeded by a disappearance of the oedema with, as
a result, the making more striking of the muscular atrophy incident
to the neuritis of the peripheral nerves. In this, the atrophic,
dry or paralytic beriberi, the _jongkok test_ is of value. With the
hands over the head the patient squats down on the calves of his
legs and attempts to rise—something impossible for the beriberic.
At this time the patellar reflex probably cannot be elicited and
later on there will be found foot and wrist-drop with atrophy of
muscles. With complete foot-drop, the reactions of degeneration
will be found.
A combination of the dry and wet types of beriberi is often described
as the mixed type.
It must always be remembered that the course of the ordinary case
of beriberi is essentially chronic, running over months or years.
=Acute Pernicious Beriberi.=—This is the fulminating type of
beriberi in which the marked involvement of the vagus overshadows
the other but less manifest phenomena of the disease. In some cases
the signs of peripheral neuritis may be quite prominent before the
fulminating onset of the cardiac manifestations, there being almost
a total lack of disturbance of the vasomotor system. Again we may
have slight if at all demonstrable motor or sensory disturbances but
with marked oedema. It should be borne in mind that this development
of cardiac disturbance with its fatal tendency may develop even
in a case of rudimentary beriberi. It is a common experience that
cases considered as mild types may, in a few hours, show cardiac
involvement and terminate fatally with striking suddenness.
There is apt to be marked epigastric tenderness or even distress
coming on with the onset of the acute cardiac involvement. It may
be so extreme that the patient dreads the slightest palpation of
his epigastrium. From a marked palpitation and praecordial distress
evidences of the dilatation of the right heart become prominent.
Indications of tricuspid insufficiency are seen in the pulsating
jugulars and cyanosis. The cardiac dullness is greatly increased
to the right and various abnormalities of sounds and rhythm may be
observed. There is also dyspnoea and a sensation of constriction
of the chest (beriberic corset). These are the cases which give
as horrible a picture of death as one ever sees. In the final
struggle for breath and praecordial agony of the last stages of
decompensation in old heart lesions we have a more gradual course
in a more asthenic patient. Acute pernicious beriberi may run its
course in a strong, vigorous patient in a few hours. In some cases
we have paralysis of the diaphragm.
=Paraplegic and Rudimentary Types.=—The rudimentary type has
already been considered and it would be impossible to draw a line
between slightly developed paraplegic cases and rudimentary ones.
The paraplegic cases show the weakness of feet and hands going on
to wrist and foot-drop. There is also marked blunting of sensation
of feet and hands which gives one the impression of ataxia when the
patient tries to button his coat.
[Illustration: FIG. 83.—_A_, Mixed Beriberi. _B_, Wet Beriberi. _C_,
Dry Beriberi. (From Jackson’s Tropical Medicine.)]
There is atrophy of muscles so that the grip of the patient
is enfeebled. This partial anaesthesia also accounts for the
pseudoataxic gait in which the element of muscular weakness is
prominent as opposed to the vigorous heel stamping gait of the
ataxic tabetic. The patient drags the toes and leans forward on a
cane when walking, thus suggesting the tripod.
It is the typical steppage gait of degeneration of the lower motor
neurones. It is a flaccid, atrophic paralysis of the muscles.
There is no involvement of the sphincter.
_Beriberic Residual Paralysis._—Hamilton Wright has used the term
beriberic residual paralysis to indicate cases which, in the course
of convalescence and favorable regeneration of axis-cylinders and
more or less return to a normal condition, become subject to some
factor lowering the vital forces and body resistance and experience
a return of the beriberi manifestations. To use a common expression
the patient has a set-back and the favorable progress to complete
recovery is temporarily in abeyance.
Symptoms in Detail
_Nervous Symptoms._—The most common symptoms are those connected
with degenerations involving the peripheral nerves of the
extremities. The motor nerves are more involved than the sensory
ones, there being rarely complete anaesthesia, but rather a
blunting of sensation as though a piece of cloth were interposed
between the examining instrument and the skin. At first there is
weakening of the muscle power as shown by the grip of the hand
or weakness of foot muscles. In more advanced cases we may have
foot and wrist-drop. Hyperaesthesia of the muscles is prominent,
especially that of the calf muscles. The unsteadiness of gait is
not true ataxia as the patient does not clearly show the Romberg
sign. It is muscular weakness rather than incoördination.
The Argyll-Robertson pupil is absent. The gait is the steppage
one of peripheral neuritis, the patient walking as if extracting
one foot after the other from clinging mud. Later on, when other
muscles than the foot extensors are involved, the gait becomes a
shuffling one. The mind is entirely clear. The vasomotor phenomena
are often marked as shown by patchy or most extensive development
of oedema and serous exudates. The knee-jerk is usually absent.
Fibrillary twitchings may be observed in beriberi as well as in
progressive muscular atrophy. The extensors of arms and legs are
more markedly affected than the flexors. The cardiac symptoms are
really connected with vagal involvement.
_The Cardio-respiratory Symptoms._—Owing to involvement of
the vagus the inhibitory apparatus is deranged so that we have
palpitation and rapid pulse rate both of which are markedly
increased by the slightest exertion.
The blood pressure is below normal. Shortness of breath is the
earliest feature of respiratory trouble. This may go on to marked
thoracic oppression and dyspnoea.
Aphonia may be present in acute pernicious beriberi and probably
indicates laryngeal palsies. Such cases are usually fatal.
Pulmonary congestion and oedema always accompany the terminal right
side dilatation of the heart which is responsible for the cyanosis,
pulsating jugulars and various murmurs. The pulmonic second sound
is accentuated and may be reduplicated. The rhythm of the heart
sounds is replaced by the equal spacing of embryo-cardia. The
diaphragm may be paralyzed as may also happen to the intercostal
muscles.
_Digestive and Urinary Symptoms._—Those who considered beriberi
as an acute infectious disease were disposed to note frequently
evidences of toxaemia as manifested by nausea, vomiting and
epigastric distress. As a matter of fact these symptoms only become
very prominent in pernicious beriberi and may well be connected
with the cardiac decompensation. However caused vomiting is of
unfavorable prognostic import.
The amount of urine is markedly decreased when oedema is advancing
but is succeeded by a polyuria when this diminishes. If albumin
should be present it is not connected with beriberi but some other
condition.
_Other Features._—There is nothing characteristic about the blood
other than a slowly developing anaemia.
Oedema is the most striking feature of wet beriberi. When slight
this oedema may only involve the pretibial-region or sternum.
Circumscribed areas of oedema may be present on the upper parts of
the body as neck and trunk.
Hydropericardium is the most frequent of the exudates into serous
cavities. Fever is almost always absent except in epidemic dropsy.
DIAGNOSIS
When the case is one of mixed type with the oedema, cardiac
involvement and signs of peripheral neuritis the diagnosis is
readily made. A diagnosis of nephritis is often given the wet type
of beriberi and locomotor ataxia the dry form, by those who have not
in mind the possibility of the disease existing in an oriental crew
after a long voyage.
The urine in beriberi is as a rule normal and there are no
peripheral nerve disorders in nephritis. Chagas has noted that a
quartan form of malaria gives rise to oedema about the ankles and
is often mistaken for beriberi by the physicians of the Amazon
region.
The cardiac manifestations of beriberi differ from those of
valvular disease in that the murmurs are muffled and there does not
exist the definite areas for the location of the murmurs of the
various valvular lesions. The rapid development of a pericardial
effusion is also against valvular heart disease.
The absence of lancinating pains, typical Romberg sign and
Argyll-Robertson pupil should differentiate from tabes.
The tripod gait of beriberi takes its name from the wide separation
of feet and use, with the hands, of a cane in front. It is a steppage
gait instead of the ataxic one of tabes. On account of the lack of
power to raise the toes in walking, the beriberic lifts the hip and
swings to one side in order to avoid scraping his toes.
In progressive muscular atrophy the palsy attacks the hand first
and in a more advanced case showing the main-en-griffe there would
also be deltoid involvement. Of course beriberi may show the
main-en-griffe characteristic but the greater involvement of the
feet with vagal phenomena differentiates.
_Ship Beriberi._—A disease of importance on Scandinavian sailing
ships to which the designation “ship beriberi” has been given
resembles beriberi in that we have oedema particularly of the lower
extremities and at times generalized so that a case would appear to
be one of wet beriberi.
More or less dyspnoea and cardiac palpitation are features of
the disease as of beriberi. In fact death often is the result of
acute cardiac paralysis. The striking point of difference is the
generally reported absence of manifestations of neuritis and Nocht
in an autopsy of a case failed to find evidence of degeneration of
the peripheral nerves.
Another point of distinction is that once the ship arrives in port
and a diet of fresh meat and vegetables is substituted for the one
of sterilized canned meats and desiccated and preserved vegetables,
the patient recovers rapidly so that in one or two weeks there is
no sign of the disease remaining. Beriberics improve at once when
put on a curative diet but the damage done the peripheral nerves
makes complete recovery a matter of weeks or months. Nocht is of
the opinion that ship beriberi is closely related to scurvy as he
found sore gums and haemorrhages into muscles in some of his cases.
He also notes that even in true scurvy there may be cases of dropsy
without the spongy gums and haemorrhages. Dropsy plus sore gums is
not infrequently noted in the beriberi-like affection of the men of
the French fishing fleet off the Newfoundland banks.
Schaumann believes that ship beriberi is due to an acute deficiency
in phosphorus, a chronic deficiency causing beriberi. It is
probable that this disease is caused by a deficiency in certain
vitamines, these being destroyed in the sterilization of canned
meats or by drying vegetables.
_Scurvy._—It will be remembered that in scurvy, which is the classic
food deficiency disease, we have spongy, swollen gums, loose teeth,
oedema about ankles and, in particular, haemorrhages into skin at
site of hair follicles and tumor-like haemorrhages into subcutaneous
and muscular tissues. Haemorrhages into the mucous membranes are not
uncommon. The heart shows marked palpitation and weakness.
The scurvy vitamine is much less stable than the beriberi one. It
is contained in fresh foods only, drying destroying it.
In connection with the question of multiplicity of vitamines
monkeys fed on rice will develop beriberi while if fed on a bread
deficiency diet they develop scurvy.
In Mesopotamia the Indian troops suffered greatly from scurvy
but not from beriberi while the British troops had many cases
of beriberi. From July to December there were 11,445 cases of
scurvy among the Indian forces and 104 cases of beriberi among the
British. During this period the British ate white biscuits, tinned
meats and horse flesh. This latter protected them from scurvy but
the Indian troops would not eat the fresh meat but ate barley flour
instead. The antiscorbutic vitamines are sometimes designated as
water soluble C vitamines.
_Rand Scurvy._—In investigating the endemic scurvy on the Rand,
in South Africa, Darling noted hypertrophy and dilatation of right
heart. Such cases often showed vagal degeneration. Pathologically,
these cases were closely related to beriberi, but clinically, they
showed spongy gums, and haemorrhages elsewhere. The knee-jerks were
always exaggerated.
_Infantile Scurvy._—As differing from infantile beriberi, we have
in infantile scurvy, which is attributed to the use of sterilized
milk instead of fresh milk, a tendency to separation of the
epiphyses from the shafts of the bones and extreme sensitiveness
to any movement particularly of the legs. A markedly anaemic and
asthenic condition is also characteristic. The chief lesion is a
subperiosteal blood extravasation.
Milk contains several vitamines some of which, as the growth
vitamine, are, destroyed in boiling; others, however, are not
destroyed until subjected to a temperature of about 120°C.
_War Oedema._—In those areas of Europe where famine conditions
were approached during the great war a condition of weakness and
oedema was noted by many observers and to this symptom-complex
various designations were applied such as war dropsy, war oedema,
etc. The oedema was more marked than would be true in ordinary
cases of starvation so that such factors as consumption of large
amounts of water and salt in the thin soups so prominent in the
dietary, plus hard work, must have been additional causes.
The oedema was most common in the feet and legs, at times extending
to the thighs and trunk, and in about one-half the cases involving
the face. Marked muscular weakness and alimentary disturbances
were common. There was dyspnoea on slight exertion with a slow
pulse, but cardiac disturbances were not features of the disease.
The urine was pale, of low specific gravity and free of albumin.
There was reduction of red cells and a tendency to leukopenia.
These cases showed marked emaciation upon the disappearance of
the dropsy. As is well known the deficiency in fats was marked
in Central Europe so that it was to be expected that ocular
manifestations should be frequently noted, deficiency of fat
soluble A being the exciting cause of xerophthalmia. The cases
tended to recovery under proper diet and hospital care.
Probably the most important conditions to consider in differentiation
of beriberi are the peripheral nerve involvements caused by alcohol
and arsenic.
In alcoholic neuritis there is the history of alcoholic excesses,
long-standing digestive disorders and tremors of hands, lips and
tongue. Chiefly characteristic, however, is the mental involvement,
such cases almost always showing loss of memory and defective
mental concentration.
Mental symptoms and tremors are practically absent in beriberi and
we have here the marked feature of vagal involvement plus vasomotor
phenomena.
In arsenical neuritis we have an early puffiness under the eyelids
and pigmentation of the skin which first shows itself in areas
normally pigmented. A dysenteric syndrome may also be present.
There would be less chance of confusing lead palsy as this chiefly
involves the upper extremity. Punctate basophilia, lead colic and
the blue line on the gums should differentiate.
In diphtheritic palsies the muscles of the soft palate are involved
in more than 75% of cases. Ocular palsies are also not infrequent.
In lathyrism we have a history of the eating of the chick-pea
(Lathyrus sativus) or other vetches, as may occur in times of famine.
Pain in the back, weakness of the legs and symptoms of spastic
paraplegia appear. The spasticity differentiates. The heart is not
affected.
It may be stated that there is no laboratory diagnosis for beriberi.
PROGNOSIS
There is no disease in which one should be more conservative in
making a favorable prognosis than in beriberi. A case which seems
to be progressing toward recovery may suddenly develop cardiac
disturbances and die in a very short time.
We now know that a change to a beriberi-preventing diet is
practically curative.
The mortality rate varies in different countries and in different
epidemics, so that we have death rates varying from less than 2 per
cent. to those exceeding 50 per cent. In acute pernicious beriberi
the prognosis is almost surely fatal.
The epidemic of beriberi which prevailed at Manila in 1882 seems to
have been attended by a great mortality, this having been as high
as 60% during the early part of the outbreak.
PROPHYLAXIS AND TREATMENT
=Prophylaxis.=—It must be remembered that not only is rice, from
which the neuritis-preventing vitamine has been removed by excessive
milling, productive of beriberi but that the same applies to other
cereals which have been similarly deprived of their vitamines.
The same result may be obtained by the employment of excessive
sterilization for canning.
Fresh meat is as valuable as fresh vegetables in prophylaxis but if
either kind of food be subjected to excessive heat, as is the case
with tinned meats, etc., they not only do not prevent beriberi but in
a negative way are beriberi-producing.
While boiled beef is heated throughout, with more or less complete
destruction of vitamines, roast beef does not sustain a temperature
above 70°C. in its interior, hence the greater portion of the
vitamine content is present in such meat.
It is possible that moulds may deprive cereals of their vitamines
so that spoiled cereals may be beriberi-producing. There have been
many reports both from asylums and prisons which would indicate
that the employed and the patients or prisoners lived on the same
ration yet the guards or nurses failed to develop beriberi, which
disease was prevalent among the inmates. Such statements rarely
stand the test of investigation. The same is true of pellagra.
Many of the reported outbreaks of beriberi among those who were
enjoying an abundant ration have been found to be connected with the
almost exclusive consumption of expensive canned meats and vegetables.
As the beriberi vitamine is apparently important in carbohydrate
metabolism, a greater ingestion of carbohydrates demands more
vitamine, hence an increase in carbohydrates, without corresponding
increase in vitamine-containing foods, may bring on beriberi where,
before the increase in carbohydrates, there was an absence of
beriberi.
In connection with the development of beriberi it must always
be kept in mind that debilitating conditions such as unhygienic
quarters and overexertion, as well as disease conditions (malaria,
ancylostomiasis, etc.) are factors of importance. In military forces
excessive drills should be stopped. The fatigue factor is to be kept
in mind in this as in other food deficiency diseases.
A combination of barley, which is rich in vitamines, with the rice
is important in oriental countries, thus a diet containing 6 parts
barley to 4 parts rice and used in Japanese prisons, on account of
its cheapness, not only prevented beriberi but cured the disease in
beriberics entering prison.
There is no doubt but that legislation against rice which contains
less than 0.4% of P_{2}O_{5} is a valuable measure of prophylaxis.
Polished rice has lost in P_{2}O_{5} as well as in vitamines.
Heiser has proposed that an excessive tax be placed on polished
rice with free entry for the unpolished article. The following
suggestions of Vedder in connection with prophylaxis would seem to
be worthy of consideration in pellagra as well as in beriberi.
1. In any institution where bread is the staple article of diet, it
should be made from whole wheat flour.
2. When rice is used in any quantity, the brown, undermilled, or
so-called _hygienic rice_ should be furnished.
3. Beans, peas, or other legume, known to prevent beriberi, should
be served at least once a week. Canned beans or peas should not be
used.
4. Some fresh vegetable or fruit should be issued at least once a
week and preferably at least twice a week.
5. Barley, a known preventive of beriberi, should be used in all
soups.
6. If corn meal is the staple of diet it should be yellow meal or
water-ground meal, i.e., made from the whole grain.
7. White potatoes and fresh meat, known preventives of beriberi,
should be served at least once a week, and preferably once daily.
8. The too exclusive use of canned food must be carefully avoided.
McCarrison has noted the value of onions even in a diet in which
protein and vitamine constituents are sufficient. The onions seem
to inhibit the growth of putrefactive bacteria.
=Treatment.=—The most important treatment is that of the
substitution of a diet containing the essential vitamines for the
beriberi-producing one. In carrying this out regard must be had
for the customs and tastes of the race concerned. Thus fresh beef
may be excellent for some people but objectionable to others.
Eggs, particularly the yolk, are very valuable as is also true of
unsterilized milk. Extract of rice polishings has given splendid
results in infantile beriberi but does not seem to have been as
efficacious in the disease in adults. Yeast has great curative value.
An extract of yeast known as _marmite_ has achieved reputation
when given in doses of 20 grains daily. Seidell has recently used
an autolyzed brewers’ bottom yeast. By treating this material with
Lloyds’ reagent he has extracted the vitamines so that instead of
having to give 200 cc., a dose of 10 grams of the concentrated
product suffices.
Malt extract is very rich in vitamines and liver seems to have a
higher content than beef muscle. Fat soluble A vitamine is abundant
in glandular organs but scarcely present in the beef of our
markets—this is probably true of water soluble B. Heart muscle is
about on a par with liver. Germinating wheat and beans seem to have
special value in treatment as well as prophylaxis.
In the treatment of a case care must be had not to allow a patient
with any cardiac involvement to sit up in bed as this may cause
sudden death. Braddon considers atropine hypodermically as of value
in cardiac types of cases.
Amyl nitrite inhalations or injections of 1% solution of
nitroglycerine are indicated when there is evidence of extreme
cardiac dilatation. Venesection is also to be kept in mind. Cardiac
tonics are of less value than rest, diet and venesection.
In the feeding of such patients only small amounts should be given
at a time to avoid epigastric distress. Again carbohydrates should
be restricted as there is evidence that excess of carbohydrates as
well as vitamine deficiency may be concerned in the disease. The
bowels should be kept open with salines. Mineral oil tends to keep
down intestinal putrefaction which is a factor of importance.
Strychnine is usually given as a routine treatment in the less
acute cases. With muscular atrophy massage is of prime importance.
Electrical stimulation is also usually employed. With the palsies
there is great danger of contractures so that even the bed clothing
should not rest upon the paralyzed feet. Even splints may be
necessitated.
CHAPTER XIX
PELLAGRA
DEFINITION AND SYNONYMS
=Definition.=—For a time it seemed as if the old idea that pellagra
was connected with a dietary defect, chiefly as regarded some factor
in a preponderating diet of maize, had been replaced by one assigning
as cause some infectious process, probably protozoal, possibly
bacterial.
The important advances recently made in the study of beriberi have
tended once more to swing the pendulum to the food deficiency
etiology. The latest views assign to food deficiency the basic
etiology, but regard some other factor, possibly an infectious one,
as secondarily operative.
The disease is essentially chronic with periodic exacerbations but
may run a rather acute course with a rapidly fatal termination. The
trend of symptoms consists of (1) mild neurasthenic manifestations
in the winter to be followed in the spring by (2) disturbances of
the alimentary tract, consisting of stomatitis, burning sensations
going up the oesophagus, gastric eructations and recurring
diarrhoeas. (3) In addition to the neurological and alimentary
tract symptoms we have the third and diagnostically the most
important group, those of the cutaneous system. The pellagrous
eruption is characterized by strikingly symmetrical, sharply
delimited patches of erythema, resembling sunburn. The sites of
preference are backs of hands, extending up the forearms, bridge of
nose or neck. The neurasthenia tends to pass into a toxic psychosis
or even a confusional insanity.
=Synonyms.=—Maidismus, Alpine Scurvy, Asturian Leprosy, Mal de la
Rosa, Mal del Sole.
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—Strambio considers some of the references of
Hippocrates to refer to pellagra but Castellani and Chalmers state
that after searching the writings of Hippocrates they have been
unable to find any references to a disease showing a resemblance to
pellagra.
The first definite description of the disease is generally credited
to Casal who, in 1735, described the disease as it existed in the
Asturias.
In his writings he notes that the peasants lived chiefly on corn
and that they rarely had fresh meat.
Casal’s paper was not published until 1762 but Thitery, who visited
Spain and was shown cases of pellagra by Casal, described the
disease in 1755 and gave full credit to Casal for the recognition
of the disease. The name of the disease was given it by Frapolli,
in 1771, the derivation being from pelle—skin, and agra—rough.
The disease had then existed in Italy for a considerable time.
Casal called the disease mal de la rosa.
In 1810, Marzari insisted that the two diseases, pellagra and
Alpine scurvy, which had a few years previously been recognized as
identical, were caused by the consumption of maize and from this
time on the maize theory as to etiology has been supported in Italy.
Later on (1872 to 1909) Lombroso elaborated the maize theory of
etiology and so strongly presented this view that it is impossible
for us lightly to set aside the arguments of this great physician.
While the zeists, as the advocates of the maize etiology are
termed, insist that pellagra made its appearance in Europe
following the introduction of Indian corn, after the voyages of
Columbus, there does not seem to be any evidence that pellagra ever
existed among the North American Indians. In 1905 Sambon insisted
that pellagra was a protozoal disease and in 1910 claimed that it
was probably transmitted by a midge, _Simulium reptans_.
About 1907 pellagra was found to be an important disease of the
Southern States of the United States and since that time the number
of cases has steadily increased so that it is now estimated that
there have been approximately 200,000 cases in the United States.
It is generally conceded that isolated cases of pellagra had
occurred in the United States prior to 1907, but they generally
were diagnosed differently.
=Geographical Distribution.=—In Europe it is most prevalent in
Italy, Balkan States, Greece, Turkey, Spain and Portugal. In
Roumania there were about 100,000 cases in 1906. The disease has
decreased in incidence and virulence in Italy, there having been in
1910 only 33,869 cases, as against 104,607 cases in 1881.
The disease was first recognized in Egypt by Sandwith in 1893 and
is now known to be widespread in Lower Egypt. It is rare in Upper
Egypt where they live on millet instead of maize. It exists in
Algiers.
It has been reported from India and the Straits Settlements and
prevails extensively in the West Indian Islands as well as in
Mexico and Central America.
The disease in the Southern States of the United States is of a
more fatal type than elsewhere, the average mortality having been
39.10%. The death rate in the United States has fallen, thus the
rate in Mississippi for the years 1914 to 1916 was only ten per
cent.
At present the Italian mortality is only about 3% although formerly
it was much higher.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—Like other diseases of unknown etiology the views in
this connection are innumerable.
_Zeists and Anti-zeists._—It is customary to divide the adherents
of the different views as to the cause of the disease into two
groups, the zeists, who advocate a connection between maize or
Indian corn (_Zea Mays_) and the disease, and the anti-zeists, who
claim that corn has nothing to do with pellagra.
_Food Deficiency._—Before taking up the better known considerations
noted above it may be stated that many now believe that pellagra,
along with beriberi and scurvy, belongs to the group of “food
deficiency” diseases. Just as beriberi is caused by the absence of a
neuritis-preventing substance or vitamine in the dietary, so is the
symptom-complex of pellagra brought about by the absence from the
dietary of some vitamine or vitamines essential to proper metabolism.
There are various ideas as to the factor which eliminates the
pellagra-preventing vitamines.
Some claim that in the process of milling maize the
vitamine-containing outer portion (bran) has been taken off just as
with beriberi-producing white rice, from which the pericarp with
its neuritis-preventing vitamine has been more or less completely
removed.
From analyses of milled maize and millings Funk has recently
suggested that pellagra in different countries is in relation
to the degree of milling. Just as with rice and maize so does
excessive milling of wheat get rid of vitamines, therefore, bread
made from highly milled flour is dietetically deficient.
Again, as brought out by Voegtlin, alkalis tend to destroy any
remaining vitamines in such bread. The practice of using sodium
bicarbonate in preparation of bread is a further factor in the food
deficiency problem. With the use of baking powder or buttermilk
the alkaline carbonate of soda is neutralized so that there is no
destructive effect on vitamine content.
The vitamine deficiency of highly milled flour and highly milled
corn meal runs parallel with the phosphorus pentoxide content of
such products. Whole wheat shows about 1.1% P_{2}O_{5}, while
highly milled flour contains only about 0.1%. Whole corn has about
0.76% P_{2}O_{5}, while milled corn meal has only about 0.3%.
Highly milled rice has under 0.4% P_{2}O_{5}.
Others think that as the result of bacterial or mould diseases of
the corn grain these important vitamines are destroyed. Then too,
as with rice and beriberi, the prevailing idea is that while there
is a striking association between a maize dietary deficient in the
pellagra-preventing vitamine and the occurrence of pellagra, yet this
deficiency may be supplied by other foods.
Beriberi seems rather definitely to be associated with a deficiency
in the anti-neuritis vitamine, which is probably the same as water
soluble B., and in pellagra-producing diets a similar deficiency
may be noted. More striking however is the deficiency in fat
soluble A in such diets. This vitamine is abundant in butter fat
and egg yolk, articles of diet of which pellagrins are deprived.
Leaves of plants contain it in abundance, while with seeds it is
present in less degree and then contained in the embryo, which
latter is lost in milling. Millet contains an exceptionally large
amount of fat soluble A and it is well known that in Egypt those
living on millet instead of maize escape pellagra. The protein of
millet has a high biological value which is the reverse with that
of maize. It should be noted that besides vitamine and protein
deficiencies the lack of inorganic salts should be considered.
_Protein Deficiency._—Animal protein is a superior protein and
maize protein an inferior one. Wilson grades proteins according to
their assimilability and taking meat protein as 1 he assigns to
maize protein a relative value of 3.4, which means that one must
consume 3.4 times as much maize protein as that of meat to obtain
the necessary protein requirements. Thirty grams of animal protein
daily is sufficient to maintain nitrogenous equilibrium but Wilson
considers 40 as a minimum B. P. V. (Biological protein value). We
should have to consume 136 grams of maize protein to obtain a B. P.
value of 40. Where hard labour is required the B. P. V. should be
50 and when associated with chronic intestinal disease it should be
as high as 60.
Wilson noted a B. P. V. of 23 for males in the diet which caused an
outbreak of pellagra in Armenian refugees at Port Said. The diet of
the pellagrous Turkish prisoners in Egypt had a B. P. V. of 33.5.
It may be stated that zein, the protein of maize, is deficient in
tryptophane and lysine, two important amino-acids necessary for
proper nutrition. Chick apparently produced pellagra in a monkey
fed on a low protein diet (Total protein 8.2 grams, of which all
but 2.7 grams was from zein.). The monkey was given an abundance of
accessory food substances in butter, marmite and orange juice.
_Amino-acid Deficiency._—In a recent paper Goldberger and Tanner
note that a low biological protein value is not necessarily
indicative of a pellagra-producing diet. In a series of experiments
the deficiency of vitamines did not seem to be related to pellagra
production and the same was true of the mineral elements. In
studying the nature of low protein biological values they were of
the opinion that this rested in certain amino-acid deficiencies in
the proteins consumed by the pellagrins. Benefit seemed to result
from administering cystine to two cases of pellagra and in a third
case there was steady improvement following the giving of both
cystine and tryptophane.
It is a question whether zein, the principal protein of maize,
contains any cystine.
Goldberger and his colleagues, after a careful investigation of
pellagra epidemiology, decided that such facts as the complete
absence of the disease among the nurses and attendants of the
pellagrous insane, or among the prison guards of institutions where
pellagra prevailed extensively, as well as among those caring for
pellagrous orphans, indicated that a dietary factor rather than
an infectious one was operative in the disease. Even where it was
stated that attendants and inmates of institutions had the same
dietary investigation indicated that as a matter of fact the insane
and the prisoners were not as well fed as the other group. Then too
the insane frequently fail to avail themselves of the food provided.
A study of the records of the Army and Navy of the United States
failed to show that a single case of pellagra had ever developed
among the personnel, although large numbers of the men came from
pellagrous districts of the South. This exemption they thought due to
the generous service ration.
In an investigation of the diet of the workingman’s family in the
North and South it was found that the southern one consumed much
larger quantities of starches and fats than the northern one, but
less fresh meat. In the family of the cotton mill operative, a
class showing a great incidence of pellagra, corn bread, flour
biscuits, and fat pork were the chief articles of diet. There is
a great deal of ancylostomiasis among these cotton mill people
and the debilitating effect of this disease may predispose to
pellagra. The general rise in the cost of food and, in particular,
the disproportionate increase in price of meats over cereals, since
1907, may explain the greater incidence of the disease since that
time. The wages of southern mill operators have also suffered on
account of frequent periods of financial depression during the last
ten years, thus causing them to buy cereals rather than meats.
_Goldberger’s Experiment._—In February, 1915, Goldberger started
a “pellagra squad,” consisting of 11 prisoners on a diet of wheat
flour (patent), corn meal, corn grits, corn starch, polished rice,
granulated sugar, cane syrup, sweet potatoes, fat fried out of salt
pork, cabbage, collards, turnip greens and coffee. Baking powder was
used for making biscuits and corn bread. The food value of each man’s
diet averaged 2952 calories.
A control was carried out with prisoners on a normal diet. The
experiment was continued until Oct. 31, 1915. Of the 11 volunteers
on the excessive carbohydrate diet six developed symptoms. Loss
of weight and strength and mild neurasthenia were early symptoms.
Definite cutaneous manifestations appeared only after five months.
The skin lesions were first noted on the scrotum, later appearing
on backs of hands in two cases and back of neck in one case.
There are those who believe that the methods of preserving foods,
cereal or proteid, by sterilizing at high temperatures, destroy
the vitamines so essential to proper metabolism so that people
who subsist extensively on canned vegetables and preserved meats,
instead of fresh meats and vegetables, may develop pellagra.
Evidence of this sort is obtainable in the mill villages of the
Southern States of the United States where pellagra is so very
prevalent.
We are now beginning to recognize that slight and vague digestive
trouble may be pellagrous in nature although never going on to the
development of the cutaneous, neurological and alimentary tract
diagnostic triad of symptoms.
Again there would appear to be efficient resistance to pellagra
in those who are in good physical condition, but when reduced
by illness, or the effects of poor diet and defective hygienic
surroundings, they may develop it. There are those who think that
hookworm disease is an important factor in predisposing to pellagra.
Not only does alcoholism, when coexistent with pellagra, make for
a bad prognosis but there are many who think that any abuse of
alcohol predisposes to pellagra. Against this however is the fact
that pellagra in the United States is about five times as common
among women as among men. It is generally recognized that pregnancy
and lactation predispose to pellagra.
_Pellagra in Turkish and German Prisoners._—There were (up to
the close of 1919) 9257 cases of pellagra among 105,668 Turkish
prisoners (1 in 11) and 79 cases among 7606 German prisoners (1
in 96). The Turkish prisoners had been on a deficient diet before
capture and the diet after capture had a B. P. V. of 33.5. The
labour group of the prisoners had a B. P. V. of 36.8 and the
disease was much more prevalent among them than in those not
working. Hammond-Searle notes that the diet of the nonworking
European prisoners was probably insufficient to prevent pellagra.
On the average the disease appeared among the German prisoners 4½
months after capture. They stated that while in Turkey their diet
had been excellent but almost all had suffered from dysentery or
malaria. In the Turkish prisoners diarrhoea was a prominent feature
and Bigland suggests a possible toxin action resulting from a
damaged intestinal mucosa. Stools from pellagrous Turkish prisoners
showed organisms similar to _B. perfringens_ in 90% of cases while
such organisms were not found in the stools of healthy prisoners.
_The Zeistic Views._—The idea which was at one time entertained
that maize, whether good or bad, brought on pellagra has now been
generally abandoned, owing to investigations, which proved that corn
possessed a fair nutritive value and was easily assimilable, together
with evidence to show that where care was taken in the maturing of
the grain and the prevention of decomposition by moulds or bacteria,
pellagra was either nonexistent or diminished in a district where
such measures were instituted.
The statement is frequently seen that pellagra did not make its
appearance in Europe until after the introduction of maize,
subsequent to the discovery of the New World. There are authors who
think Casal was suspicious of a maize dietary.
The zeistic views now incorporate some additional factor with the
basic one of a rather exclusive maize dietary.
1. The verderame theory of Ballardini. From noting on the corn
grains a covering with a greenish mould, Ballardini in 1845
advanced the view that pellagra was due to this mould and from
this time on we have the so-called zeitoxic views, which hold that
pellagra is caused by spoiled corn. Ceni and Fossati regard a toxin
elaborated by various moulds as causative. The fungi toward which
attention has been chiefly directed are _Aspergillus fumigatus_ and
_A. flavescens_ as well as certain species of _Penicillium_ and
_Mucor_.
2. The Lombroso view that as a result of the action of moulds or
bacteria, toxins are elaborated which, when ingested, give rise to
the disease.
3. That the toxins have origin in the action of various organisms,
especially _B. coli_, on the ingested corn, while in the intestines.
4. Recently views have been brought forward that pellagra is an
anaphylactic phenomenon connected with sensitization to the maize
proteins.
5. Rabitschek has brought forward a photodynamic theory which is
that pellagra is due to a preponderating maize or possibly other
cereal dietary which results in certain photodynamic substances
being introduced into the circulation. These substances become
toxic under the influence of sunlight. Hirschfelder has failed to
find any fluorescent body in the serum of five patients suffering
with severe pellagra.
Among arguments in favor of the maize etiology of pellagra may be
mentioned the following:
(_a_) Among the natives of Upper Egypt, where millet instead of
maize is the staple cereal, pellagra is rare, while in Lower Egypt
where much maize is eaten the disease is far more prevalent.
(_b_) While the natives of Corfu, prior to 1857, grew their own
maize and ate only sound grains there was no pellagra but later,
when the corn crop was less profitable, and the grain was imported
from Roumania, much spoiled maize was brought in and pellagra made
its appearance.
(_c_) Alsberg has shown that in recent years new methods of
harvesting corn have become common in the Southern States of the
United States. Instead of topping the corn it is cut and shocked
with the result that conditions are more favorable for the spoiling
of the corn. He also notes that varieties of corn are now planted
which have a greater oil content, which means a larger embryo, and
that it is this embryo which most easily spoils. Again he notes
that much corn is now raised in Northern States where the season
is shorter, so that there is a greater probability of immature
corn being marketed. All of these facts might explain the recent
appearance of pellagra in the U. S. and its previous nonexistence.
Thomas has shown that where 30 grams of a _superior protein_, such
as that of meat, would suffice, it would require 102 grams of corn
protein, an _inferior protein_. This inferiority is due to a lack
of assimilability of the amino-acids of corn protein. Protein
deficiency is the outstanding feature of a pellagra-producing diet
and in the corn protein we have one of inferior value.
_The Antizeistic Views._—As a rule the advocates of nonimportance
of maize in the production of pellagra hold that we are dealing with
an infectious disease and that it can only come into existence by
transmission from some other case.
1. The Thompson-McFadden Commission, while holding a very
conservative attitude, feel that certain faecal bacteria may be the
etiological factors.
2. Alessandrini believes that the causative factor may be present
in certain waters.
These views are that colloidal silica in water is responsible
for the disease. Voegtlin noted the great amount of aluminium
in certain vegetables and suggested this as the toxic causative
substance. A mixture of colloidal alumina and silica in water is
supposed to be operative as well as silica alone. Against the
colloidal silica hypothesis is the statement of Sandwith that the
water of the Nile, the drinking water of Egypt, is low in colloidal
silica content.
3. Long has suggested that amoebae may be the cause.
4. Tizzoni has incriminated a streptobacillus which he stated he
found in the blood and organs of pellagrins as well as growing on
maize.
=Epidemiology.=—As the result of very careful epidemiological
studies the Thompson-McFadden Pellagra Commission came to the
conclusion that there was evidence against the transmission of
pellagra by ticks, lice, bedbugs, cockroaches, fleas, mosquitoes and
buffalo gnats (_Simulium_).
They were rather disposed to consider that the disease showed a
greater prevalence where the disposal of faeces was unhygienic, as
in unsanitary privies, and that the existence of an efficient water
sewerage system prevented pellagra. If faecal bacteria should act
as infectious agents then the house fly would possibly be worthy of
suspicion.
Many of the peculiarities of sex and place distribution could be
explained by the stable fly, _Stomoxys calcitrans_, a fly which
bites viciously in the district in which they worked. This fly
bites only by day and is intimately associated with human dwellings
so that the greater incidence of the disease in the women, who stay
at home, as against an incidence five times less in the men who
work in the mill during the day might be explained by _Stomoxys_
bites.
At the same time their failure to transmit pellagra to monkeys by
injections of defibrinated pellagra blood would militate against any
infectious agent existing in the blood. It may be stated that Harris
has claimed to have produced a disease resembling pellagra in two
monkeys by injecting filtrates from emulsions of brain, skin and
intestinal tract of cases dying of pellagra.
Lavinder and Francis injected 79 monkeys and 3 baboons with varying
material from pellagra autopsies. Some of the animals were injected
with emulsions or Berkefeld filtrates of such emulsions made from
brain and cord. Other monkeys were inoculated with material from
skin similarly prepared, others with stomach and mouth mucosal
emulsions, and still others with intestine and faeces emulsions.
Blood, urine and cerebro-spinal fluid were also injected. Feeding
experiments were also carried out. With one exception, and that one
only suggestive of pellagra, the experiments were negative.
Sixteen volunteers, working under Goldberger, tried to infect
themselves with blood, nasopharyngeal secretions, epidermal scales,
feces and urine from pellagrins. Various atria of infection were
tried according to material; blood by intramuscular injection,
excreta by mouth. After a period of six months all the subjects of
the experiments remained well. _This evidence is certainly against
the infectious nature of the disease._
_Greater Prevalence in Women_.—Now that we attach no weight to
insect transmission of pellagra we have only the debilitating effects
of menstruation, pregnancy and lactation to explain the marked
susceptibility shown by women of from seventeen to forty years of
age. Before and beyond these ages the incidence in males and females
is about the same.
Before Goldberger began his experiments he was struck by the
relation poverty had to pellagra epidemiology, and as diet is the
chief element differentiating poverty and affluence, he chose this
line of research with the results recorded under etiology. His
explanation of the greater incidence in adult females, especially
wives and mothers, was their act of denying themselves the more
desirable parts of the food.
Sandwith has noted the great frequency of pellagra in hookworm
patients, thus of 300 such cases in Egypt, 46% had pellagra.
The Thompson-McFadden Commission was unable to note any evidence
that would distinctly point to corn, good or bad, as giving rise to
pellagra outbreaks. They did note, however, a very limited use of
fresh meats.
PATHOLOGY AND MORBID ANATOMY
There is nothing very constant or characteristic in the pathological
changes of pellagra. In the second stage the urine shows an
indicanuria and the faeces an abundance of skatol. The examination of
the gastric contents gives findings of anacidity and deficiency in
pepsin. The HCl deficiency probably causes disturbance of pancreatic
efficiency leading to mal-assimilation of fats and proteins.
The blood shows a moderate lymphocytosis but not an increase in the
percentage of the large mononuclears as has been claimed by the
adherents of the protozoon theory.
At autopsy we find rather marked emaciation. The wasting of all
organs seems to be greater than in any other wasting disease. The
skin lesions show degenerative changes in the corium with slight
cellular infiltration. In the epidermis there is superficial
atrophy but still some thickening in the stratum granulosum.
Warthin states that the lesions are those of a chronic
intoxication. The spleen shows atrophy and in the follicles there
is necrosis of germ cells as well as hyaline changes. The liver and
kidneys often show fatty change. In general the changes are those
of a senile character. There is atrophy of the mucosa of the small
intestines and there may be small ulcers present.
The mesenteric glands are enlarged. Roaf has noted the presence
of involvement of the adrenals and the Committee investigating
pellagra in Turkish prisoners found a marked supra-renal inadequacy.
Macroscopically no changes are seen in the central nervous system but
histologically we often note chromatolysis with bulging of borders,
eccentric nucleus and disappearance of tigroid substance in various
nerve cells, especially those of the anterior horn, posterior
ganglia, Clark’s column and Betz cells of cortex. There is an absence
of chronic meningo-encephalitis and meningo-myelitis which should be
present in the general type of protozoal infective lesions.
Degenerations in the posterior columns and crossed pyramidal tracts
have been reported from certain autopsies.
The cell count of the cerebro-spinal fluid is normal and there is
usually an absence of globulin increase with a negative Wassermann.
The blood chemistry findings in pellagra appear solely to be low
nonprotein nitrogen and urea values.
SYMPTOMATOLOGY
There is probably no other disease which shows such a multiplicity of
symptoms and such variations in these symptoms.
Upon questioning a patient who has developed a pellagra eruption in
the spring months there is often obtained a history of more or less
prolonged neurasthenic manifestations during the preceding winter,
chiefly dizziness, insomnia, apprehension, occipital heaviness and
muscular fatigue. There may also have been previous sensitiveness of
the mouth and slight epigastric discomfort. Along with the appearance
of the eruption we may have more marked alimentary tract disorders
consisting of stomatitis, gastric disturbances, especially pyrosis,
with a recurring diarrhoea. Upon examining the eruption we note
localized, sharply delimited, strikingly symmetrical skin lesions of
those parts of the body which are chiefly exposed to the sun’s rays.
This erythema is very similar to sunburn but often follows
inadequate exposure to the sun and the erythema persists instead
of fading. Desquamation continues for weeks or months instead of
healing. The dry scaling area usually shows a striking pigmentation
at the borders even after the central portions of the erythema have
cleared up. The skin lesions instead of being dry and atrophic as
is usual may more rarely be moist and oedematous.
From a vague neurasthenia we have now more distinct neurological
manifestations such as variations in the reflexes, tremors,
especially of tongue, head and upper extremities and a depressed
mental state with lack of mental concentration or lapses of memory.
Later on we may have a toxic psychosis in which mutism is often noted
in a mental state characteristically melancholic.
[Illustration: FIG. 84.—Marked symmetry of all lesions. Illinois
case. (From Lavinder and Babcock.)]
A final cachexia, with dementia, loss of control of the vesical
sphincter and a terminal diarrhoea, marks the end. Recurrences of
clinical manifestations each spring, or possibly skipping a year,
are striking features of the disease. While the skin and alimentary
tract disturbances are usually in abeyance in the winter, this
holds to less degree with the nervous symptoms.
THE DIAGNOSTIC TRIAD
We may then state that in a typical case we have the diagnostic
triad or pellagrous symptom-complex of (1) symmetrical sharply
delimited erythemas of certain portions of the skin surface exposed
to the sun with (2) alimentary tract disturbances of stomatitis,
epigastric and substernal soreness and burning, with pyrosis and a
recurring diarrhoea and (3) neurological manifestations in which a
prodromal neurasthenia is followed by paraesthesias, in which burning
sensations are prominent, at times leading to suicide by drowning,
with alterations of deep reflexes, tremors and, in more advanced
stages, a confusional insanity.
Burning sensations are noted in mouth, gullet and stomach as well
as of the skin. Then too a burning sensation may be complained of
in the area formerly the seat of a pellagrous eruption. The palms
of the hands and soles of the feet often give a burning sensation.
One of the characteristic features of pellagra is the periodic
recurrences in spring, with almost complete cessation of skin and
alimentary tract symptoms in the winter and, again, the tendency
in many cases for one group of symptoms to overshadow the symptoms
which usually accompany them. These periodic recurrences may well
be associated with seasonal variation in diet.
=Stages in Pellagra.=—For many reasons it is peculiarly difficult
to recognize stages but for convenience many authors describe the
disease under a prodromal, 1st, 2d and 3d stage.
These stages have reference solely to the degree of severity of the
manifestations and a case may never progress beyond the 1st stage,
although recurring for a number of years. Again a case may rapidly
progress to the 2d stage and even run through the 3d or cachectic
stage in a few months. We must not consider these stages as tending
to follow in sequence as we do in connection with the stages of
syphilis.
_The prodromal manifestations_ of neurasthenia, malaise, loss of
weight, loss of strength, vertigo and digestive disturbances would
be suited to many other diseases, especially tuberculosis, and they
are rarely recognized as belonging to pellagra until the appearance
of typical skin or other symptoms brings about their association with
pellagra. There is little definite information as to the period of
incubation although Sandwith places it at from nine to twelve months.
In Goldberger’s cases the eruption did not appear until after five
months on the experimental diet. In the study of cases of pellagra
occurring among Armenian refugees, and in Turkish prisoners of
war, oedema was not infrequently noted and its occurrence usually
preceded the eruption.
=First Stage.=—In the first stage we note the alimentary tract
disturbances of sodden fissured conditions at the angles of the
mouth, a large indented tongue with central coating and bare
glistening sides and tips, often with a shiny mucus coating these
red borders and a red buccal mucosa. The fungiform papillae appear
as pinhead red elevations. Later on the tongue becomes bare, red and
fissured. There is often an increased flow of saliva. Aphthous ulcers
are less common than in sprue. The gums are often quite tender and in
cases where they are somewhat spongy and swollen, with a tendency to
bleed, we note the appropriateness of “Alpine scurvy” as a synonym
for pellagra.
In cases with very severe stomatitis there may be enlargement
of the salivary glands. The pharynx is congested and a similar
condition of the oesophagus gives rise to a burning sensation which
is often described by the patient as going up the gullet from the
stomach.
Gastric disturbances, especially gastralgia, pyrosis and
eructations, may be pronounced. Anacidity and deficiency of
pepsin are noted in gastric juice examinations. The intestinal
symptoms are those of recurring diarrhoea or occasionally of a mild
dysentery but in many cases there is a normal functioning of the
bowels. Although the skin manifestations usually follow those of
the alimentary tract they may precede them or occur simultaneously.
_The Eruption._—It is usual to designate the skin lesions of the
first stage as erythematous, in that they resemble a sunburn. These
pellagrous eruptions may follow some source of skin irritation as
well as that from exposure to the sun; thus the perianal, perineal,
vulvar, and even scrotal regions may show a marked erythema from
the slight irritation of the rubbing of clothes or opposite parts.
Chemical irritants may also be operative.
The pellagrous erythema shows itself most commonly during the late
spring or early summer. It may appear in the early spring or late
summer or early fall, but only exceptionally does it occur in the
winter. There are, however, alterations in the skin previously
involved which can at times be noted during the winter.
The typical eruption, however, is that which shows itself on the
backs of the hands or running up beyond the wrist to the lower third
of the forearm. The phalanges and especially the knuckles may also
show the eruption. On the face the eruption is most common over
the bridge of the nose, on the cheeks and forehead. There may be
spots back of the ears or on the nape of the neck. Occasionally the
butterfly outline of lupus erythematosus is seen. The face may show
the so-called pellagrous mask. On the neck we may have a band-like
eruption extending to the upper part of the sternum (Casal’s
necklace) or the erythema may extend down the sternum (cravat).
[Illustration: FIG. 85.—Dry dermatitis on face, hand, neck and upper
chest. Egyptian case. (From Lavinder and Babcock.)]
Very important were the observations of Goldberger that in his
six experimental cases the eruption first showed itself as a
symmetrical involvement of the sides of the scrotum.
On the feet the dorsal eruption does not usually go above the
malleoli and rarely involves the dorsal surfaces of the external
toes although rather commonly affecting the great toe. In the U. S.
the eruption may extend up the front and back of the leg (boot).
The soles of the feet and palms of the hands are not infrequently
involved in American cases as is also true of the tip of the elbow.
The eruption on the elbows rarely occurs until the patient takes
to his bed and is probably incident to irritation over olecranon.
Sandwith states that the skin lesions in Egypt are more widespread
than those seen in Italy.
These skin eruptions show striking symmetry, marked delimitation from
unaffected skin, with often more intense pigmentation at the border
line, and they burn rather than itch.
[Illustration: FIG. 86.—“Butterfly” eruption on face of child two
years old. (Deaderick and Thompson.)]
In 1679 cases of pellagra Merk found 77% with eruption solely on
backs of hands, 13% on backs of hands and neck, 8% on neck alone.
The eruptions on dorsal surfaces of feet and calves of legs are
chiefly seen in barefooted children. In the pellagra cases among
Turkish prisoners Bigland noted an eruption on the hands in all
but one of 232 cases. Rashes on the feet were noted in 111 cases
and rashes on the face with bilateral symmetry were observed in 47
cases. One case showed a scrotal eruption.
The more advanced skin lesions are those of a dermatitis rather
than an erythema. The affected skin is at first of a dull red
color like a sunburn and later becomes reddish-brown or livid
or chocolate-colored. Fox has likened the eruption to that of a
carbolic acid burn.
The normal elasticity is lost and the area appears as a dry, scaly,
atrophic patch—it is the skin of a very old man. The moist
oedematous skin lesions are far more common in the U. S. than
elsewhere and may show bullae and even gangrene. Such cases may
show the gauntlet desquamation.
_The nervous symptoms_ of this stage are chiefly vertigo, headaches,
which are usually occipital, and depression of spirits. Insomnia may
be a marked feature. Lack of mental concentration is often noted.
=Second Stage.=—In the second stage we have a continuation and
aggravation of the skin and alimentary tract symptoms with pronounced
neurological manifestations. Tremors of the tongue and hands appear.
There is great muscular weakness of the legs. Paraesthesias in great
variety are common. Pain on pressure in the dorsal and lumbar regions
of the back is common. The gait is more that of marked muscular
weakness.
Attacks of giddiness with tendency to fall forward or backward are
often reported. The deep reflexes may show variations from normal
and there may be variations in the reflexes of the two sides, thus
the patellar reflex on one side may be exaggerated and that on the
other normal or diminished. Ankle clonus is rare. Neurological
manifestations are slight in pellagrous children, the main symptoms
being the cutaneous ones.
The mental state is confused and the patient shows depression
and is often morose. The most common psychosis is that of simple
retardation. The patient answers questions in monosyllables and in a
low tone of voice after a more or less prolonged delay. Goldberger
states that mental disturbances sufficient to require institutional
care do not occur in more than 2 or 3% of cases.
In the second stage the urine shows rather marked indicanuria and
the faeces contain an excess of skatol. Loss of weight is as marked
a feature of pellagra as of tuberculosis. Well nourished pellagrins
are the exceptions.
=Third Stage.=—With the setting in of a confusional insanity and a
terminal cachexia we have the third and last stage of the disease.
On account of so many of the victims of pellagra becoming inmates of
insane asylums the disease is peculiarly dreaded.
[Illustration: FIG. 87.—Wet dermatitis. Localization usual. Hands
oedematous. Cachectic state. South Carolina case. (From Lavinder and
Babcock.)]
Pellagra often runs a rather acute course in the U. S., the patient
dying within two or three months. The usual course in Europe is one
prolonged over years, with at times intermissions covering one or
more years.
A form of pellagra known as typhoid pellagra often shows a high
fever with symptoms more or less resembling a very toxic case of
typhoid.
A mental state resembling the acute delirium of paresis may be
present. Such states are often terminal. The usual course of
pellagra is afebrile. Such terms as _pellagra sine pellagra_
are given to cases which may not show the skin lesions and the
designation _pseudopellagra_ has usually been used by those who
insist upon limiting the name pellagra to those cases which fit
in with their special etiological views so that cases clinically
pellagra but in which the special etiological factor does not
obtain are called pseudopellagra.
Symptoms in Detail
The cutaneous neurological and alimentary tract disturbances have
each already been separately described in detail.
_The Blood._—Hillman has made very careful blood examinations
of a series of cases and found a variable degree of chloranaemia
which however, was not a prominent feature. He notes the occasional
occurrence of a leucocytosis in the course of the disease. As a
rule there is a definite lymphocytosis, the average percentage
of lymphocytes being 33.99. The average percentage for the large
mononuclears was 2.59. The average percentage of eosinophiles was
2.73. The determinations of the coagulation time of the blood gave
normal figures.
In Ridlon’s series the average red count was 4,720,000, the
white count varied from 14,200 to 4200, average 8027. The
polymorphonuclear percentage averaged 68.2, that of lymphocytes 21,
of large mononuclears 8 and of eosinophiles 2.
Hb percentage averaged 77 and color index 0.81. The blood serum
failed to give positive Wassermann reactions.
_The Urine._—There is rarely any increase in albumin. The most
important urinary finding is in connection with indicanuria, 96.4%
of Ridlon’s cases showing this finding. As convalescence comes on
indicanuria tends to lessen.
_The Temperature Chart._—We expect a normal temperature in an
uncomplicated case of pellagra but in typhoid pellagra and in the
terminal stages of the disease a fever of from 101° to 103°F. is
generally noted. Fever makes for a bad prognosis. There is nothing
special about the circulatory system other than low blood pressure
and a tendency to vasomotor disturbances. With the genito-urinary
system other than the rather marked indicanuria, there is nothing
of note.
DIAGNOSIS
In the presence of the diagnostic triad of cutaneous, nervous and
alimentary tract manifestations there is little difficulty in
diagnosis but when the skin lesions are absent or only slightly
developed the difficulty is great. One of the most important points
in diagnosis is a history of preceding attacks.
There is no reliable laboratory test and the reports as to positive
reactions following injections of maize extracts seem unreliable.
Again there do not seem to be any antibodies in the serum of
pellagrins which can be utilized in serological diagnosis. A
primary requirement would be a suitable antigen. Competent workers
have been unable to find any bacterial organism in the blood of
pellagrins.
Erythema multiforme and dermatitis venenata seem to be the skin
diseases most liable to cause confusion.
In old people with arterio-sclerotic changes and consequent mental
symptoms there may be lesions of the hands or feet of more or less
gangrenous type, which may be a real source of confusion. The
lack of sharp delimitation of such lesions and the absence of the
pellagrous stomatitis should differentiate.
Poison ivy dermatitis, if bilateral, may be confusing, as may also
chapping of the hands.
In Italy a disease due to eating ergot-diseased rye meal and
called ergotism may be a source of confusion as this disease shows
gangrenous manifestations. The gangrene of ergotism is a dry one.
Sprue does not show the dermatitis, and the nervous manifestations
are solely those of irritability or possibly slight neurasthenia.
The sprue stool is not found in pellagra. See Diagnosis under Sprue.
Typhoid pellagra may be confused with severe typhoid fever or other
acute infectious diseases or with conditions associated with coma,
as diabetes or uraemia.
PROGNOSIS
It is a risk to venture a prognosis in pellagra because cases
that seem mild may suddenly become severe. The extent of the skin
lesions does not parallel the severity of the case although moist or
gangrenous dermatitis is usually seen only in severe cases.
When fever comes on the prognosis of the case is unfavorable and
when the mental manifestations are prominent the prognosis is bad.
The Italian physicians give a more hopeful prognosis than the
American ones, which is easily understood when it is considered that
American mortality from pellagra is given as from 25 to 39.10%. That
of Italy is certainly below 10% and recent statistics have shown a
mortality of only 3%. In the U. S. the mortality is now below 10%.
Of particular importance is the question of the liability to mental
trouble. Singer states that about 40% of all cases of pellagra
develop mental disturbances and that this incidence is much higher
in cases presenting recurrences. In Italy it is estimated that from
5 to 10% of pellagrins become permanently insane.
The earlier a case of pellagra comes under treatment the more
favorable the prognosis.
In the first stage the prognosis is very good but in the second,
when there is more or less involvement of the central nervous
system, it is much less favorable. In the third stage, or that
of the terminal cachexia with marked mental deterioration, the
prognosis is extremely bad. Each recurring attack makes the
condition more serious. The older the patient the more serious the
prognosis.
PROPHYLAXIS AND TREATMENT
=Prophylaxis.=—There does not seem to be any satisfactory evidence
as to the contagiousness of pellagra, so that any method involving
isolation is not indicated.
Even if the use of spoiled corn is not productive of pellagra it is
certainly advisable to prevent its sale by state regulation.
As a proper, well-balanced dietary is an important curative measure
it is therefore prophylactic.
=Treatment.=—In a disease which characteristically shows a marked
amelioration in the winter or a disappearance of symptoms for one or
more years we should be very conservative in attributing improvement
to any drug.
At the New York Post Graduate hospital, 17 cases were apparently
cured on rest in bed and full nutritious diet. Hospital treatment,
thereby removing the patients from the environment in which the
disease developed, is generally conceded of the greatest benefit.
It is always recommended by the advocates of some special drug
treatment that the patient be kept on a nutritious diet. Roussel in
1866 stated: “Without dietetic measures all remedies fail.”
Many authorities speak highly of arsenic in various forms as
Fowler’s solution, atoxyl, salvarsan, etc. Others are equally
pessimistic as to the value of arsenic in any form.
Niles is a strong advocate of hydrotherapeutic measures. He
recommends the drinking of two to six glasses of tepid water daily as
well as colon irrigations, cold abdominal compresses, hot packs and
saline baths.
Deeks prefers to eliminate sugar and starchy food from the dietary
of pellagrins for a few days at a time and to give fresh fruit
juices, with broths and milk. He highly recommends dilute nitric
acid, well diluted, before meals. As there is almost constantly
anacidity and pepsin deficiency in the gastric juice it would seem
that this condition should be treated.
It is advisable to keep the patient out of the sun and require him
to take his exercise after sunset.
Dyer recommends ½ to 1 ounce gelatin daily together with the juice of
two or more oranges or lemons. He prefers a diet of eggs, milk and
well-cooked vegetables. He also gives quinine hydrobromate in 3 grain
doses 3 times daily.
Psychotherapy seems to be of importance in the treatment of
pellagra.
Lavinder says that many people have pellagra because they have some
other condition and when this is cured the pellagra is also cured.
In truth, pellagra is very rarely a primary condition. We must then
give careful attention to the predisposing causes which may not only
be ancylostomiasis, alcoholism, or malaria, but, as well, various
gynaecological or alimentary tract disorders.
With the colloidal silica etiology in view Allesandrino has
recommended sodium citrate in treatment.
Goldberger has cited the following as showing the influence of diet:
In an orphan asylum with 211 orphans, 68, or 32%, had pellagra.
These children were divided into 3 groups and given different
rations, those under six years of age receiving milk and eggs,
while those over twelve years were given meat, as they assisted in
the work of the institution. The children between six and twelve
lived practically on a vegetarian diet in which corn products
and syrup preponderated with deficiency of legumes. Of 25 young
children only 2 showed pellagra, and there was but 1 case in the
66 children over twelve years of age while the 120 between six and
twelve gave 65 cases or 52%.
As the result of increasing the milk supply, so that every child
under twelve years got a pint daily, also at least one egg daily,
together with an increase in the use of beans and peas, as well as
fresh meat, the disease was entirely eradicated. The corn elements
of the diet were reduced but not excluded. There was increase in
proteins and a decrease of carbohydrates.
As to the diet in pellagra Niles recommends the exclusion of
all maize articles of diet. He recommends meat, eggs, milk or
buttermilk with peas and beans. When intestinal symptoms are
severe he gives barley gruel, rice-water, thick broths and dry
meat powders. As a drug treatment for diarrhoea he uses bismuth
beta-naphthol.
Babcock, recognizing the importance of the treatment of the
pellagrous neurasthenia, recommends the Weir-Mitchell plan of
prolonged rest in bed, nutrition, hydrotherapy and hygienic
measures. “Fat and blood” should be our aims and he notes the value
of cacodylate of soda in increasing fat. He also refers to the
susceptibility to suggestion of pellagrins and is an advocate of
psychotherapy.
Having in mind the vitamine deficiency view Voegtlin has treated
cases of pellagra with extracts of substances rich in vitamines.
Extracts prepared from fresh ox liver and fresh hog thymus caused
definite improvement in pellagrins so treated while extracts of
yeast and rice polishings seemed to be without value. It will be
remembered that the glands of animals are rich in fat soluble
A. For the burning of the erythema Niles recommends a lotion of
calamine (4 drams), powdered zinc oxide (3 drams), in 1 pint of
lime water. As regards climatic treatment the same authority
believes that a colder climate is indicated and that a patient with
pellagra should avoid hot weather for a year after all symptoms
have disappeared.
CHAPTER XX
SPRUE
DEFINITION AND SYNONYMS
=Definition.=—Under the designation sprue we have a form of chronic
diarrhoea characterized by periods of improvement alternating with
a return to the previous condition. The disease is afebrile, of
insidious onset and first manifests itself by soreness of the buccal
mucosa and vague digestive disturbances.
The soreness of mouth and gullet is soon followed by erosions,
especially at the site of the posterior molars, and a bare raw
tongue. Exceedingly characteristic are the voluminous, frothy
stools which are evacuated chiefly in the morning hours. The
patient becomes weak, emaciated, irritable and of an earthy pallor.
The disease chiefly affects Europeans who have lived in Southern
China, Cochin China and Java, and unless treated early tends to
progress to a fatal termination.
=Synonyms.=—The word sprue is a corruption of the Dutch term “spruw”
used to designate this tropical aphtha or aphthous stomatitis. The
name psilosis, meaning bare, was suggested by Thin and is the term
employed in many books instead of the better recognized designation,
sprue.
Other designations are: Chronic diarrhoea of the tropics, Ceylon sore
mouth and Cochin China diarrhoea.
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—The French (1868-1872) described this disease under
the name of chronic or endemic diarrhoea of Cochin China and noted
its resemblance to Moore’s “Hill Diarrhoea.” In 1876 Normand
incorrectly associated _Strongyloides_ with the disease.
The physicians of the Dutch East Indies described the disease under
the designation “spruw” and Manson in a very complete description
of the disease called it “sprue,” a corruption of the Dutch name.
It is interesting to note that Hillary in 1766, described a similar
disease of Barbadoes, W. I., which he called aphthoides chronica.
=Geographical Distribution.=—It is particularly prevalent in South
China and the East Indies. India and Ceylon are also regions of
the disease. In the West Indies it has been carefully studied, in
Porto Rico by Ashford, and of particular interest is the fact that
Wood has recently insisted on the presence of sprue in the Southern
States of the U. S. The Philippines and tropical Africa are also
sections from which the disease is reported.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—The cause is unknown. The disease makes its appearance
chiefly in Europeans who have lived many years in the tropics and may
not show itself until the patient has returned home. (In one case
reported by Thin seventeen years after the return home.)
It seems to select those who are weakened by dysentery or other
debilitating diseases, or who are compelled to subsist on
indigestible food or to lead a life of exposure to hardships.
Women in whom the menstrual flow is excessive or who are in the
period of lactation seem to be especially susceptible. Some think
alcoholics more susceptible. The idea has been advanced that the
abuse of calomel has been a factor and this view is one to be given
weight because it is well recognized that at the present there is
much less sprue than formerly and with this there has been a more
rational use of calomel. The excessive use of highly seasoned food,
so common with Europeans in the tropics, may have an influence.
Some have thought that sprue was the manifestation of a tropical
pancreas; at first congestion and later exhaustion of its function.
The character of the stools lends support to this view.
At one time it was thought that _Strongyloides stercoralis_ was the
cause; this idea had its origin in the finding of these larvae in
the stools of a patient with Cochin China diarrhoea.
Certain authors have considered bacteria giving a granulose
staining reaction as the cause while others have thought cocci to
be concerned.
Kohlbrugge found organisms resembling _Oidium albicans_ in the
intestines, oesophagus and tongue. He found similar organisms in
the stools and tongue scrapings of cases of sprue. Beneke found
bacilli in the tongue, oesophagus and intestines and considered
these as causative, regarding the thrush-like membranous deposit as
connected with the cachectic state and not causative.
Bahr is inclined to believe that _Monilia albicans_ (_Oidium
albicans_) is the cause, as he found these saccharomycetes in the
deep layers of the tongue, in the mucoid coating of the intestines
and in the deposit in the oesophagus. He thinks it the ordinary
thrush species which may take on greater virulence in the tropics.
Ashford states that he has found a species of _Monilia_, different
from that of thrush, almost constantly in tongue scrapings and
stools of sprue cases and he regards this species as the cause of
sprue. He states that this organism is common in Porto Rico bread
and thinks it possible that the disease is transmitted in this way.
It has been called _Parasaccharomyces ashfordi_. It is a round
yeast, 4 to 7 microns in diameter. Wood has recently expressed the
view that sprue is not infrequently mistaken for pellagra in the
Southern United States.
Castellani, in a study of moulds of the genus _Monilia_ in sprue
stools, holds them responsible for the excessive gas production,
although not the cause of the disease. Various protozoa, as amoebae
and spirochaetes, have been considered as possible causes.
While there does not seem to be any vitamine deficiency implicated
yet there is disordered assimilation, which may be due to
alimentary tract infection or to insufficiency of pancreatic
functioning. It has been suggested that secretin deficiency is the
essential disturbance.
=Epidemiology.=—The disease is rare in natives and is entirely
endemic. Some authorities have suggested a greater frequency of the
disease in those intimately exposed to a case, as in husband and wife
or the members of a family.
Sprue is usually a disease of mature life and affects women more
frequently than men. While climate cannot be considered as causing
sprue yet the effects of hot climates in producing exhaustion
states in Europeans must be borne in mind. The sprue patient should
always leave a tropical climate.
PATHOLOGY AND MORBID ANATOMY
The changes in the alimentary tract apparently originate in the
structures lying beneath the epithelial coverings, thus indicating
that the toxic material acts through the blood rather than as a
surface irritant to the mucosa. At first there is congestion of the
underlying connective tissue with a round cell infiltration. Later
on the epithelial covering of the alimentary tract suffers and
auto-intoxication, as evidenced by indicanuria, becomes operative.
At autopsy the subcutaneous fat is found to have almost
disappeared. The intestines, especially the ileum, show marked
thinning, this atrophy especially affecting the mucosa, the surface
of which is covered by a layer of dirty gray mucus. The submucosa
generally shows connective-tissue increase. The gut is pale and
diaphanous. The solitary follicles may show as small cysts filled
with a gelatinous material or as ulcers.
The liver is markedly atrophied. The mesenteric glands are usually
enlarged. The pancreas may show cirrhotic changes.
SYMPTOMATOLOGY
=A Typical Case.=—It is very difficult to obtain definite
information as to the onset which is characteristically insidious.
There is usually first noted a sensitiveness of the buccal mucosa
so that alcoholic drinks and acid or highly seasoned food cannot be
taken without marked discomfort. A sense of fulness or distention in
the epigastric region is often an early symptom. Frequently there
is a history of a rather intractable morning diarrhoea which may
alternate with periods of constipation.
The diarrhoeal movements are remarkably copious and soon change
from bile-colored, liquid evacuations to the characteristic
putty-colored, pultaceous, gas bubble permeated, offensive stool
of sprue. While the patient experiences a sense of relief from
the evacuation of the fermenting mass yet there is at times an
excoriation about the anus which may cause pain when at stool.
Neuralgic pains of the region of the anus may be present late in
the disease.
When examined microscopically the stools are found to show much
fat, yeasts and undigested food. The fats are chiefly in the form
of neutral fats and fatty acids rather than as soaps. The reaction
is acid. Nausea and vomiting, especially about noon, may be
complained of.
While the characteristic stools best show the full development of the
disease there are also changes noted in tongue and buccal mucosa.
Following the marked sensitiveness of the mouth above noted there
soon appears a redness of the sides and tip of the tongue with a
glistening coating of the surface. Small vesicles later becoming
superficial erosions develop along the tongue borders, frenum and
buccal mucosa.
There is also congestion and swelling of the fungiform papillae.
Very characteristic are ulcers at the site of the rear molars
(Crombie’s ulcers). Later on the tongue becomes bare, fissured and
even glazed, as if varnished.
The gullet may be raw and very sensitive. The appetite is apt to be
capricious and the patient may be very intractable, insisting upon
dietary indiscretions which he knows will aggravate his condition.
There is a progressive loss of strength, weight and energy. The
liver progressively diminishes in size but is difficult to map out
owing to the bulging, dough-like abdominal contents. The urine is
usually free of albumen but shows marked indicanuria. Sprue is
characteristically afebrile.
Anaemia becomes marked, the red cells going as low at times as
under 2,000,000, per cmm. and the Hb. percentage less markedly
reduced (color index above 1). The polymorphonuclears are reduced
in percentage.
There is a tendency to depression and irritability.
The period during which sprue runs its course is very variable.
Some cases drag on for ten or twelve years while others may be
subacute in type, death ensuing within a year or two.
In addition to the typical or complete sprue described above Bahr
would add: (1) _Incomplete sprue_, in which with typical stools there
is no abnormal appearance of the tongue, and (2) _Tongue sprue_, in
which with characteristic mouth involvement there is absence of the
sprue stool.
Symptoms in Detail
_The Stomatitis._—At first we have a disagreeable bitter taste
in an unusually sensitive mouth. Later there develop superficial
ulcers along the sides and frenum of the tongue, which subsequently
involve the buccal mucosa. The gums may be quite tender and saliva
dribble from the mouth.
In the later stages the tongue becomes bare, red, fissured and
glazed.
_The Stools._—Commencing as early morning diarrhoea, with at times
alternating constipation, there gradually sets in that which makes
for a diagnosis of sprue—putty-colored, fermenting, offensive
stools which are extraordinarily copious.
They are also very fatty and of acid reaction. They show a proteid
loss as well as lack of fat absorption.
_The Blood Findings._—There is a marked secondary anaemia with
great reduction in red cells and Hb. percentage.
The color index averages higher than normal and with the
poikilocytosis resembles the blood picture of an atypical
pernicious anaemia. Nucleated reds are rarely found. The
eosinophiles are reduced in percentage. The polymorphonuclears
often show a great number of nodes, as 7 or 8 instead of the
ordinary three.
There is a mononuclear increase with polymorphonuclear reduction.
The white count is somewhat below normal—4000 to 6000.
_Other Features of the Disease._—The liver is notably diminished
in size. The urine shows indicanuria. The patient has a dry earthy
skin and may show oedema about ankles.
Mentally there is lack of concentration with marked irritability
and moroseness. Tetany has been reported as occurring rarely in
very severe cases. The abdomen is doughy and the temperature in the
later stages tends to become subnormal.
DIAGNOSIS
_Thrush_ is characterized by the membranous coating which
microscopically shows the fungus. It also is chiefly a disease of
children and those who live under wretched hygienic conditions and
with insufficient food. The characteristic stools are absent.
_Pellagra._—The stomatitis, diarrhoea and mental irritability are
very similar in the two diseases. There is, however, absence of the
sprue stools in pellagra and the periodical recurrence and skin
manifestations of pellagra are absent in sprue.
Wood thinks that in the absence of any evidences of organic nervous
disease in sprue we have an important differentiation as he finds
that pellagra has as great a tendency to invade the nervous system
as has syphilis. Salivation is marked in pellagra, not in sprue.
The two diseases, however, are best differentiated by the darker,
more fluid, less copious stool of pellagra as contrasted with the
copious, light colored stool of sprue. Stools containing great
amounts of undigested fat are most characteristic of sprue; fat
absorption in pellagra is about normal (95%) while in sprue it is
only about 75%.
_Syphilis_ with its buccal mucous patches or geographical tongue
may be mistaken for tongue sprue.
=Hill Diarrhoea.=—Many authorities do not consider this as a disease
distinct from sprue. The English, however, note the features of
its occurrence only at high altitudes; thus persons going to Simla
suffer from hill diarrhoea but upon their return to the sea level the
disease disappears. The characteristic features of hill diarrhoea
or Simla trot, as it is often called, are the passage of from 2 to
6 watery, whitish stools in the early morning hours. The patient is
usually free from diarrhoea in the afternoon. The color may resemble
that of freshly made whitewash, hence diarrhoea alba.
At first it is only the annoyance that is complained of but later
on the appetite is lost and the patient becomes weak.
There is an absence of the sprue mouth. The laboratory diagnosis,
other than the finding of excess of fatty acids, soaps, undigested
food remnants and yeasts is unimportant.
PROGNOSIS
While the disease responds to treatment in those who are not too far
advanced yet it always should be considered a serious affection. The
chances of a complete restoration to health are better for those who
can leave the tropics and reside permanently elsewhere.
TREATMENT
It is essential that the patient possess the will power to carry out
the course of treatment; the clothing should be of wool to prevent
chilling and the patient should remain in bed until his condition has
decidedly improved.
_The Milk Treatment._—A preliminary dose of castor oil is given
and when this acts the patient should begin taking milk as the sole
food. At first about 4 pints of skimmed milk are given daily. The
milk should be given in two-hour feedings, well warmed and taken
through a glass tube or with a teaspoon—it should not be drunk. As
the stools become less frothy the amount of milk is increased so
that the patient takes from 6 to 7 pints daily. Milk should be the
sole food for six weeks from the time the stools become solid and
the mouth symptoms disappear. Rele prefers buttermilk to skimmed
milk. Eggs are usually well borne after the milk course. Stale
bread or toast is cautiously added and then some fish or chicken.
At times the patient seems benefited by giving a meat treatment day
once or twice a week during the course of the milk treatment.
_Meat Treatment._—If the patient is very ill it may be advisable,
after the preliminary dose of castor oil, to give meat juice
obtained by expressing the juice from slightly broiled meat, about
2 teaspoonfuls every half hour. If possible however one starts in
with the meat cure, which is about 4 ounces of a lightly broiled
chopped-up beefsteak, every four hours. Raw meat is usually given
in this treatment but there is danger of _T. saginata_ infection.
At least 4 pints of warm water should be taken daily but not at the
same time the patient eats the meat. Rest in bed and the avoidance
of chilling are important measures. In all food treatments we
should avoid forcing the patient to eat—it is better to give food
only when the patient desires it.
Some prefer to alternate the milk treatment with the meat one.
_Fruit Treatment._—The patient is allowed fruit in great
abundance. Strawberries, peaches, grapes, ripe gooseberries
and fully ripe bananas are usually recommended. Papayas are
particularly well suited. Pomegranates are also highly recommended.
Sour or fibrous fruits should be avoided. Strawberries and milk are
highly advocated. Cooked strawberries or other cooked fruits do
not benefit the patient, the curative principle being apparently
destroyed by heating. At all times alcoholic drinks and highly
spiced foods should be avoided.
The only drug that has been advocated to any extent is yellow
santonin, in doses of 5 grains, night and morning. It is very
doubtful if any drug treatment is of the least value.
LeDantec, with the elimination of the granulose bacteria in mind,
has recommended the cutting off of carbohydrates and the giving
of a strictly albuminous diet. Subsequently he gives lactic acid
producers as contained in _Bacillus bulgaricus_ preparations.
Schmitter has recommended emetine in the treatment of sprue, but
Ashford has found this drug, as well as santonin, of negative
value. Brown has had success in treating a case of sprue with
pancreatin, 30 grains daily. Since then he has had marked success
in three other cases. He now combines the pancreatic extract with
calcium carbonate.
In connection with Ashford’s work with a specific _Monilia, M.
psilosis_, cases of sprue have been treated with vaccines made from
this organism.
An autolysate of the cultures is sterilized at 56°C. for an hour
and then centrifugalized. A one per cent. suspension of the
sediment is used for injection increasing from about 0.1 cc. to 1
cc. at weekly intervals. Five or six injections are given.
It is stated that the symptoms at the start of the treatment are
aggravated.
SECTION IV
HELMINTHIC INFECTIONS
CHAPTER XXI
ANCYLOSTOMIASIS
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—It is very probable that hookworm disease existed in
Egypt in the remote past and it has been claimed that a disease
mentioned in the Ebers Papyrus was of that nature.
Goeze found a hookworm in a badger in 1782. He named the parasite
_Ascaris criniformis_. Froelich, in 1789, found hookworms in
the fox and named them hookworms from the hook-like ribs of the
copulatory bursa. He proposed the generic name _Uncinaria_.
Therefore _Uncinaria_ belongs to the hookworms of the fox and is
not valid for any human species.
In 1838, Dubini noted that these worms were generally found in
very anaemic cases and that the mucosa of the duodenum or jejunum
frequently showed punctate haemorrhages. On account of the four
ventral teeth projecting from the mouth he gave it the name
_Agchylostoma_ or correctly _Ancylostoma_.
In 1854 Griesinger, as a result of frequently noting the lesions
produced by the worms, stated that they were the cause of Egyptian
chlorosis. In 1866, Wucherer connected hookworms with a disease
of Brazil called opilacao. In 1878 Grassi noted that the disease
could be diagnosed by the finding of the characteristic eggs in the
stools of patients.
It was the prevalence of a severe anaemia among the workmen employed
in the construction of the St. Gothard tunnel, which Perroncito
proved to be due to hookworm infection, that established the great
importance of this parasitic disease as the cause of a severe and
fatal anaemia (1879). About the same time it became generally
considered that the anaemias which affected workmen in mines were of
a similar nature.
That the disease was very prevalent in the Southern States of the
U. S., as long ago as 1849, is shown by the writings of Duncan,
who noted the frequency of anaemia, often associated with dirt
eating, among the slaves. He described the oedematous legs, the
protuberant belly and cardiac palpitation. There were several
cases reported in the U. S. from 1893-1897 but they were mainly in
foreigners.
From 1895 to 1901, Stiles kept insisting that hookworm disease
should be of frequent occurrence in the U. S.
A. J. Smith found several cases in persons living in Texas and
recognized the fact that these hookworms were different from
those of Europe. It was from a study of material from Smith and
Claytor in the U. S. and, later on, from Ashford in Porto Rico,
that Stiles, in 1902, reported a new genus of hookworm as existing
in man. It was first named _Uncinaria americana_ but _Uncinaria_,
belonging to the hookworm of the fox, was not valid, so he changed
the name to _Necator americanus_.
[Illustration: FIG. 88.—Geographical distribution of
Ancylostomiasis. Stars show where disease is widely prevalent.
Triangles, where less so.]
=Geographical Distribution.=—The disease is rare outside the
tropical and subtropical countries except in mines or tunnels where
suitable conditions of warmth and moisture exist.
It is extremely prevalent in India and Egypt as well as in China
and other parts of the East. It is a very important infection
in Porto Rico and the Philippine Islands. It is extensively
distributed in South America, especially Brazil, as well as in
Central America, Mexico and the Southern States of the U. S. The
inhabitants of many of the islands of the Pacific are heavily
infested. Hookworm disease is common in southern Europe.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—The hookworm infections of man come almost entirely
from two parasites, _Ancylostoma duodenale_, the Old World species,
and _Necator americanus_, which is generally called the New World
species from its having first been reported from the U. S. by Stiles.
Hookworms belong to the class Nematoda and family Strongylidae.
Quite recently Lane has reported a new species, _A. ceylanicum_, as
having been obtained from 3 men in Bengal, after treatment. This
species is the one that infects the civet cat in Ceylon. So far as
we know the other human species belong solely to man.
The male hookworms are a little more than ⅓ of an inch (9 mm.) long
and the females a little more than ½ inch (13 mm.) in length. The
males can readily be distinguished by their posterior, umbrella-like
expansion or copulatory bursa. The tail of the female is pointed.
The vulva of _A. duodenale_ is located in lower half of the ventral
surface; that of _N. americanus_ in upper half. The large, oval mouth
of the Old World hookworm has four claw-like teeth on the ventral
side of the buccal cavity and two knob-like teeth on the dorsal
aspect. It also has a pair of ventral lancets below the four ventral
teeth. One cannot make out a dorso-median tooth. In _N. americanus_
the buccal capsule is round, smaller and the ventral teeth are
replaced by chitinous plates. Dorsally there are two similar but
only slightly developed lips or plates. A very prominent, conical
dorso-median tooth projects into the buccal cavity. Through it
passes the duct of the dorsal oesophageal gland. There are also 4
buccal lancets. The copulatory bursa of the _Necator americanus_ is
also different, being terminally bipartite and deeply cleft in the
division of the dorsal ray, rather than tripartite and shallow, as
with _A. duodenale_.
The anterior extremity of _Ancylostoma_ bends in the same direction
as the general body curve while that of _Necator_ hooks back in an
opposite direction to the body curve.
By dropping the worms, while still alive, into hot 70% alcohol they
readily assume the attitudes noted above.
In general, _Ancylostoma_ is larger and thicker than _Necator_.
The name hookworm was given to these nematodes from the hook-like
processes of the ribs of the rays of the copulatory bursa.
Dubini called the Old World parasite _Agchylostoma_, properly
_Ancylostoma_, on account of the 4 formidable hook- or claw-like
ventral teeth of the buccal capsule. (αγχὶλος, hook, and στομα,
mouth.)
_A. ceylanicum_ is somewhat smaller than _A. duodenale_ and in the
copulatory bursa of the male we have a deeper cleft in the dorsal
ray and 2 rather long tips to each branch instead of the shallow
cleft and 3 stumpy processes of the 2 branches as in _A. duodenale_.
=Life History.=—The delicate-shelled eggs pass out in the faeces,
and in one or two days a rhabditiform embryo (200 × 14 microns) is
produced. The mouth cavity of the embryo is about as deep as the
diameter of the embryo at the posterior end of the mouth cavity; that
of _Strongyloides_ is only about one-half as deep as the diameter.
[Illustration: FIG. 89.—1a, Copulatory bursa of _Necator
americanus_, showing the deep cleft dividing the branches of the
dorsal ray and the bipartite tips of the branches; also showing the
fusion of the spicules to terminate in a single barb. Scale 1/10
mm. 1b, Branches of dorsal ray magnified. 2a, The buccal capsule of
_N. americanus_. 2b, The same magnified. 3a, Copulatory bursa of
_Ancylostoma duodenale_, showing shallow clefts between branches of
the dorsal ray and the tridigitate termination. Spicules hair-like.
3b, The dorsal ray magnified. 4a, The buccal capsule of _A.
duodenale_, showing the much larger mouth opening and the prominent
hook-like ventral teeth. 4b, The same magnified. 5a, Egg of _N.
americanus_. 5b, Egg of _A. duodenale_. 6a, Rhabditiform larva of
_Strongyloides_ as seen in fresh faeces. 6b, Rhabditiform larva of
hookworm in faeces eight to twelve hours after passage of stool. From
Stitt.]
As a practical point, the anaerobic conditions in the intestines
seem to prevent development of the hookworm ova or at any rate
the absence of the oxygen, so necessary for the segmentations
preliminary to the formation of the embryo, prevents it. Therefore
hookworm ova in freshly passed faeces never show other than
commencing segmentation while development of the larvae of
_Strongyloides_ takes place in the intestines, so that in freshly
passed faeces we find, generally, actively moving larvae or at
least eggs containing fully developed embryos. Hookworm ova very
rarely show more than 4 segments or exceptionally 8 segments in the
freshly passed egg.
In the presence of oxygen these ova rapidly develop into larvae,
particularly at a temperature of about 27°C. Beyond 37°C. and below
14°C. development does not seem to take place.
The rhabditiform larvae grow rapidly and by the 3rd day are about
300 microns long and undergo a primary moulting. By the 5th day
the bulb-like swellings disappear and the larva becomes possessed
of a straight oesophagus, thereby becoming a strongyloid larva. It
then undergoes a 2nd ecdysis or moulting, but instead of casting
off this old covering, it retains it as a protecting sheath. The
full grown larva is about 550 by 24 microns. At this time it ceases
to take food but can move actively in its sheath so that it can
crawl up blades of grass or vertical sides of mines. They can live
in this state for months, when moisture and shade are present, but
are rapidly killed by drying. Before becoming encysted hookworm
larvae are readily destroyed by the action of the sun or chemicals
or even by dilution of the faeces, especially with urine. Cort and
others have found it a common occurrence for mature larvae to lose
their sheaths while living in the soil, and to continue their lives
in the unsheathed state. The proportion losing their sheaths varies
from 52 to 98%.
This is the _infecting stage_ in which the larvae bore their way into
the skin, which is the usual method of infection, or, occasionally,
by entering the mouth on vegetables or otherwise.
Looss thought that they entered the skin by way of the hair
follicles but the idea now is that they can bore into any part of
the skin. It only requires a few minutes for the larvae to enter
the skin. From the subcutaneous tissues they effect an entrance
into lymphatics or veins, go to the right heart, thence to lungs.
From the alveolar capillaries they pass into the pulmonary alveoli,
thence up the bronchi and trachea, to pass out of the larynx and
then down the oesophagus to the stomach. The larva loses its
protecting sheath in the stomach and in a few days develops a
provisional buccal capsule.
By the end of the 2nd week, after another ecdysis, the larvae
have grown to be about 2 mm. long and 130 microns broad and in
about 4 weeks become adults, usually in the jejunum, where, after
fertilization of the females by the males, the giving off of
eggs begins. The adults attach themselves to the mucosa of the
intestine, feeding on the deeper structures of the mucosa, or on
the tissues of the submucosa. Sambon believes that the larvae can
work their way into the jejunum without going there by way of the
trachea and oesophagus.
By providing an exit to the trachea, Fülleborn demonstrated that
in dogs, infected with the dog hookworm, great numbers of larvae
poured out of the trachea. In other dogs he stitched the oesophagus
to the skin and noted larvae coming out of these openings. In these
dogs, with the ordinary channel obstructed, infection did occur
with, however, only a few worms, thus showing the truth of Sambon’s
views but at the same time demonstrating the unimportance of such a
route of infection.
The mouth cavity of the embryo is about as deep as the diameter
of the embryo at the posterior end of the mouth cavity, that of
_Strongyloides_ is only about one-half as deep as the diameter.
The genital anlage of _Strongyloides_ is much larger than that of
_Ancylostoma_.
=Epidemiology.=—When faeces containing hookworm eggs are deposited
where conditions of moisture, warmth and shade exist, they develop
into the infecting stage, which is the nonfeeding but motile larva
inside the cuticle formed by the second moulting. While eggs and
younger larvae are killed rapidly, the encysted larvae withstand
drying for considerable periods.
[Illustration: FIG. 90.—_Ancylostoma duodenale_ (life size). Shows
some worms adherent to the intestinal mucosa and some free. (From
Jefferys and Maxwell.)]
Stiles notes that the more favorable conditions for development are
in a porous, sandy soil rather than in a clay one. Where a sewerage
system exists there is very little danger of the spread of hookworm
disease and the same is true where there is proper disposal of the
faeces by burning, boiling or treatment in a septic tank. In rural
districts, however, where the stool is often deposited in the shade
and retirement of a clump of trees, the soil becomes infested with
myriads of larvae, so that one standing with bare feet on such a
spot easily becomes infected. It is for this reason that shoes are
of protective value. In infected mines with temperatures below
22°C. infection is rare (6%); from 22°C. to 25°C. more common
(16.6%), and above 25°C., it may reach high figures (61%).
Those of the negro race do not suffer from the infection as do the
whites. They appear to have an immunity but serve as carriers of
the disease. There is difference of opinion as to the length of
time the parasites may live in man in the absence of reinfection.
Some consider this period one of a few months, others of two or
three years. We can certainly consider that a case leaving an
infested region will get rid of his parasites within seven years.
PATHOLOGY
The site of entrance of the larvae is characterized by a dermatitis
which is often called “ground itch” or “foot itch” by reason of
its frequent location in the foot which has come in contact with
the faeces-polluted soil. The dermatitis disappears in about two
weeks unless some secondary infection occurs. There are reports of
pulmonary irritation which may be explained by the wandering of the
larvae through the lungs.
[Illustration: FIG. 91.—Longitudinal section through a hookworm
attached to the intestinal mucosa, about 6 hours after the death of
the carrier. A portion of the submucous coat is drawn into the buccal
cavity and trails along cord-like into the oesophagus, in which 4
small tissue nuclei are still discernible. Section 0.01 mm. thick.
(From Mense.)]
Pronounced anaemia with yellow, wax-like skin is a feature of
severe cases but emaciation is rare, the subcutaneous fat still
remaining. There is frequently oedema about the ankles. In the
jejunum we find small haemorrhagic spots from the size of a pea
to that of a half dollar. A worm may be found in the center of
this spot. In sections from the tissues injured by the bite we
note an infiltration of eosinophiles. The heart often shows fatty
degeneration with dilatation. The liver and kidneys usually show
fatty change while the spleen is generally shrunken. Sandwith noted
splenic enlargement in many of his autopsies but such enlargement
must have been due to other causes.
There are many views as to the manner in which the damage due to the
hookworm is brought about. Some think it by bacterial infections
occurring through the wounds made by the worms, others that it is due
to a haemolytic toxic material excreted by the worms, while Stiles
considers the ingestion of the patient’s blood important. Looss
thinks it due to the gradual destruction of the intestinal mucosa
from the feeding on this, and especially of the submucosa, by the
worms. In their feeding the worms move from site to site. When they
leave a point bleeding continues and this may account for much of the
anaemia.
On the side of the blood we have at first a moderate leucocytosis
which disappears with the anaemia. Eosinophilia and Hb. percentage
reduction are often observed. In 3 cases I have known a fatal
pernicious anaemia to develop.
SYMPTOMATOLOGY
In a secondary anaemia, with early and marked cardiac palpitation
together with epigastric tenderness and a tendency to mental
retardation and physical deterioration, one should always examine the
stools for hookworm eggs.
The course of the disease is decidedly insidious and indefinite
and the clinical diagnosis notoriously uncertain, as shown by many
reports where physicians of experience, after examining a number
of persons in a mill or school and only diagnosing 2 or 3% as
infected, have been astonished, upon examination of the faeces of
the group, to obtain positive evidence of infection in 70 to 80% of
the number examined.
For convenience, it is well to divide hookworm cases into 3 groups;
1. Where the person infected fails to show any special evidence of
abnormality, the diagnosis resting almost entirely on the finding of
ova in the faeces.
Such cases may show very slight reduction in haemoglobin and
only admit of a certain lack of energy. The best indication that
hookworm infection is doing the host injury is that after treatment
they gain in weight and energy and show improvement in mental
concentration.
2. Mild cases with moderate degrees of anaemia, the Hb. percentage
ranging from 55 to 75. In these cases there is rather marked
epigastric tenderness with frequent attacks of acid eructations.
Cardiac palpitation and a tendency to shortness of breath may be
quite noticeable. Headache and vertigo may be present.
3. Severe cases. In such cases we may find extreme anaemia with Hb.
percentages around 35 or even as low as 15. I have always felt that
one was only approximating when recording percentages of 10 or lower.
These cases are very weak and show marked cardiac palpitation and
dyspnoea upon the slightest exertion. There is often dilatation of
the stomach and a protuberant abdomen. The red cells may fall below
1,000,000. There is also oedema, especially about the feet and
ankles. Tinnitus aurium is rather frequent.
Such cases often show depravity of appetite, the best-known craving
being that for earth. Other patients crave chalk, wood, cotton, etc.
[Illustration: FIG. 92.—Fatal case of ancylostomiasis. Red cells
810,000. Hb. 15%. White count 6400. Eosinophiles absent. Upper part
of small intestines lined with hookworms. (From U. S. Naval Medical
Bulletin.)]
It is in children that we have the most serious effects of
the disease, there being marked stunting of the growth with a
corresponding mental backwardness. Such children show marked
retardation and delay in answering the question asked them and
often repeat it in a drawling manner. Tested by the Binet-Simon
method we may find a sixteen year old child to have the mental
development of a ten year old one, but at the same time we would
note that from a standpoint of physical development the child only
seemed ten years old.
As the child approaches adult age we note a striking lack of sexual
development and the lack of pubic hair. In girls there is delay in
the onset of the menstrual periods or these may never appear.
In from 80 to 90% of cases there is a history of dermatitis,
particularly of toes or feet, which is commonly called “ground itch,”
“foot itch,” or “dew itch.” This is most frequent between the toes
or on the inner side of the sole of the foot. The irritation is
due to the penetration into the cutaneous tissues of the hookworm
larvae. The itching is intense and secondary infections often occur
as the result of scratching. Vesicles appear about the second day and
are often ruptured by the scratching with a resulting pustular or
impetiginous conditions. The skin and hair generally are dry.
As a rule the temperature is normal throughout the course of an
uncomplicated case of hookworm disease. During the first week or so
following a heavy infection there may be pulmonary manifestations
when the larvae are migrating by way of the lungs.
In the diagnosis of a case Stiles attaches much importance to a
tallow-yellow color of the alae of the nose and the forehead, as well
as to the eye characteristics which are like those seen in the eye of
a fish or that of an intoxicated person.
He also notes that the pupil tends to dilate instead of to contract
when the patient looks at a bright light. It has seemed to me that
the condition is rather one of hippus. In severe cases retinal
haemorrhages may occur. There may be night blindness. Ascites may
be present in advanced cases.
Symptoms in Detail
_Skin Manifestations._—The dermatitis following the penetration of
the larvae is most often about the toes or inner side of the sole
of the foot. The skin is very dry and often a pale earthy color.
A tallow-yellow tinting of the alae of the nose may be observed.
The hair is dry and scanty or absent in pubic and beard regions.
Oedema, especially of ankles or feet, is common.
_Circulatory and Respiratory Systems._—Palpitation of the heart is
early and marked. Functional murmurs are frequent in the advanced
stages. Pulsation of the neck veins is also common. The pulse
rate averages about 110 and the blood pressure is low. There is
frequently some right side dilatation of the heart. A high pulse
pressure is common in severe cases. Shortness of breath on slight
exertion is the most common respiratory symptom. There are at times
cough and bronchitis, probably induced by the irritation of the
larvae in the pulmonary alveoli.
_Digestive System._—Epigastric tenderness going to the right
is very characteristic. The stomach is often dilated and the
gastric juice hyperacid. As the anaemia increases the acidity
diminishes. It has been suggested that the desire to neutralize
this acidity with an alkali is the explanation of the desire for
alkali-containing earth on the part of “dirt eaters.”
Patients often are pot-bellied. Constipation is rather a common
feature and the stools very rarely show macroscopic blood.
_Nervous System._—Hookworm patients are not only physically
tired but, as well, mentally tired. The infection in children
leads to a backward mental state. Patients have very little
energy or initiative and are often considered stupid and lazy.
Hypochondriasis is at times noted and some severe cases become
melancholic.
_The Blood._—The red cell count averages in marked cases 2,500,000
to 3,000,000 red cells per cu. mm. The Hb. percentage is down in
such cases to between 30 and 50. The color index is well below
1, except in certain rare cases, when the color index is that of
pernicious anaemia, being above 1. These latter cases are very
resistant to treatment and often show very few infecting worms
notwithstanding the severity of the symptoms.
There is at times a moderate leucocytosis but as a rule the white
count is approximately normal.
Eosinophilia is quite characteristic and usually ranges from 15 to
35% of the leucocytes. Eosinophilia tends to disappear as the cases
become advanced.
The spleen and liver very rarely give rise to any symptoms and
while albuminuria is rather common in advanced cases with oedema
about the feet, yet casts are but rarely found.
DIAGNOSIS
=Clinical Diagnosis.=—The diseases with which it is most likely to
be confused are beriberi, chronic nephritis and malarial cachexia.
Stiles notes that heavy _Ascaris_ infections may give rather similar
symptoms.
The signs of a multiple neuritis should differentiate beriberi, and
the presence of casts or high blood pressure, chronic nephritis.
Recently, there has been a great deal written about the danger of
confusing hookworm disease and malarial cachexia, the statement
being often made that splenic enlargement is a feature of
ancylostomiasis. Most authorities, however, state that the spleen
of ancylostomiasis is not enlarged, this point being of diagnostic
value in differentiating it from malaria and kala-azar.
=Laboratory Diagnosis.=—As a matter of fact the diagnosis is almost
invariably made by finding hookworm ova in the faeces. The eggs are
oval and thin-shelled with a wide, clear, glassy zone separating the
more or less segmented, granular central portion from the shell.
Formed stools are more satisfactory for examination than the
liquid ones resulting from a dose of salts. Put about 2 drops of
water or 1% trikresol solution in the centre of a glass slide and
emulsify in it as much of the faeces as is held by the spatulate
end of a wooden toothpick. A small piece of wood or a match stick
will answer. These preparations can be readily examined without a
cover-glass, using a ⅔ inch objective, with a 1-inch ocular.
Cultural methods give a higher percentage of success than looking
for ova in the stools. Put a pile of 2 inch filter papers in the
center of a Petri dish. Fill the dish with water to the level of
the paper island. Smear a thick layer of faeces on the paper. The
larvae hatch out and can be found by centrifuging the water.
It is usually stated that about 500 worms must be present for
several months to produce symptoms. Grassi has thought that the
presence of 150 eggs in 0.01 gm. faeces indicates the presence of
1,000 worms, of which 25% would be males.
There may be as many as 4,000,000 eggs in a stool. Bass has
proposed the following method for the examination of faeces for
ova: The faeces, which have been made fluid, should be centrifuged
and the supernatant fluid containing vegetable débris poured off.
The sediment contains hookworm eggs. Then pour on sediment a
calcium chloride solution of sp. gr. 1.050. Again centrifuge and
decant. Next add calcium chloride solution of a sp. gr. of 1.250
and centrifuge. This brings to the surface the hookworm eggs which
may be pipetted off. As a rule, the finding of hookworm eggs is
very easy without such a technique.
[Illustration: FIG. 93.—Ovum of _Ancylostoma duodenale_. By J. A.
Thomson. (Jefferys and Maxwell.)]
Recently we have been using Barber’s technique. Emulsify the faeces
in equal parts of glycerine and saturated salt solution on a slide.
The eggs rise to the surface and are easily discovered with the
⅔-inch objective. As a centrifuge method, Barber emulsifies faeces
in this same mixture which brings the eggs to the surface. A wisp
of cotton is placed on the surface and 3 or 4 drops of melted
agar dropped on the cotton. The disc of agar is removed with the
cotton, deposited on a slide and examined for entangled eggs. With
operculated eggs this method does not seem to be satisfactory as
the salt solution loosens the operculum and floods the contents
of the shell,—thus altering the specific gravity of the egg and
preventing flotation.
_Lane Levitation Method._—Clayton Lane recommends a technique
which he designates as the levitation method. In this procedure the
concentrated sediment of a centrifuged specimen is transferred to a
glass slide, where it is mixed with one cc. of water. The slide is
allowed to stand for five minutes and is then immersed in water and
manipulated until all coarse matter has floated free. The hookworm
ova stick firmly to the slide and are not washed away. Lane reports
that on an average this method results in a ten-fold concentration
of ova.
In certain cases, where a microscope is not available, the
diagnosis may be made by finding the worms in the stool following a
thymol treatment.
Whyte has recommended the phenolphthalein test for occult blood as
of value in determining the cure of ancylostomiasis. This test is
so delicate that the least trace of blood from the mucosal lesion
will be detected.
The presence of eosinophilia is of great assistance in diagnosis but
it should be remembered that not rarely severe cases of the disease
fail to show any excess of eosinophiles.
Charcot-Leyden crystals are often present in hookworm stools.
PROGNOSIS
The disease is more serious in children than in adults, on account of
its interfering with physical and mental development. The dark races
do not seem to suffer as much as the white ones. Treatment is usually
most successful, but in those who are debilitated by other diseases
or, in those in whom the disease has assumed a pernicious anaemia
tendency, the outlook is not good.
The presence of eosinophilia is of good prognostic significance
as the absence of eosinophiles indicates an exhaustion of the
haemopoietic system.
The disease shortens the life of the people in an infected district
and makes them readily fall victims to intercurrent diseases.
Various statistics give the mortality as from less than one-half of
1% to figures approximating 7%.
PROPHYLAXIS AND TREATMENT
=Prophylaxis.=—The first measure is to diagnose infections in
carriers and to insist upon the treatment of such persons. The
proper disposal of the fecal material from hookworm patients is the
objective point in prophylaxis.
The use of some type of properly constructed privy is essential as
there is nothing more favorable to the development of the hookworm
larvae from eggs to infecting stage than the practice of defecating
on the ground where conditions of porous, sandy soil, shade and
moisture exist. Later on, such a spot teems with infecting larvae
and the person stepping there with bare feet is almost sure to
become infected. For this reason the wearing of shoes is an
important prophylactic measure. At the same time shoes are not a
sure protection, as Ashford has noted infections in soldiers who
wore good shoes. The fecal material, collected in a pail or tub,
should preferably be burned or boiled. Otherwise it should be
buried not less than 300 feet from the water supply and down hill
from the same.
The best method is to use some septic tank process as the anaerobic
processes of fermentation destroy the eggs.
The use of an amount of compound cresol solution equaling the fecal
mass, plus urine, is of value.
Hookworm disease tends to disappear in towns or cities where there
is an efficient sewerage system.
Hookworm disease is one of the most conspicuous examples of soil
pollution disease.
Some authors think _Ancylostoma_ more difficult to expel than
_Necator_.
=Treatment.=—The drugs best known in treatment are thymol and
chenopodium but carbon tetrachloride offers the greatest promise.
_The Thymol Treatment._—Bozzolo introduced this drug in the
treatment of hookworm disease in 1879. Thymol has an aromatic,
thyme-like odor and a pungent taste and, while soluble in about an
equal amount of alcohol, is only soluble in water in the proportion
of 1 to 1100.
It is usual to prescribe the drug in 5-grain capsules or preferably
in cachets, one part of thymol being triturated with an equal
amount of sugar of milk. If the cachet is moistened with a little
water it may be swallowed like a raw oyster.
Stiles prefers giving the treatment on Sunday so that the working
days of the patient may not be lessened. By giving the patient
bicarbonate of soda for a few days before the treatment it is
thought that the mucus lining of the jejunum is cleared away so
that the worms are more readily affected by the drug. At any rate
one should give about 1 or 2 ounces of a 50% solution of Epsom
salts on Saturday evening. Sodium sulphate is preferred by some.
The following morning at 6 A.M. the patient takes one-half the dose
of thymol proper for his age and at 8 A.M. he takes the remaining
half of the dose. At 10 A.M. he takes another dose of Epsom
salts. The reason for dividing the dose of thymol is that should
untoward symptoms occur after the first portion of the dose we do
not give the second. Stiles now prefers to divide his dose into
three portions, one to be given at 6 A.M., one at 7 A.M. and the
remaining third portion at 8 A.M., followed by salts at 10 A.M. The
patient should lie on the right side while taking the treatment to
facilitate the passage of the drug from the often dilated stomach.
The patient should remain in bed until 12 o’clock when he may take
some coffee, without milk, and crackers.
Patients must be warned to avoid anything containing fats or alcohol
while undergoing treatment as fats and alcohol dissolve the thymol
and tend to cause poisoning. Under no circumstances should castor oil
be used. People are apt to forget that butter, milk, etc., contain
the dangerous fats.
Seidell has shown that about one-third of the thymol dosage is
excreted in the urine and very little by faeces. This shows
absorption of the drug. It is thought some of the drug may be
excreted by the lungs. Congestion of the lungs has been reported in
fatal cases of thymol poisoning.
Mild symptoms of poisoning are burning in the pit of the stomach
and tingling sensations of the body. More severe symptoms are
those associated with cardiac weakness and respiratory distress.
Coffee and strychnine are the usual remedies for thymol poisoning.
Inhalation, but not swallowing, of aromatic spirits of ammonia is
often of value.
The thymol dosage recommended according to the age, or rather the
apparent age of the patient, is:
Under 5 years old 7½ grains.
From 5 to 9 years old 15 grains.
From 10 to 14 years old 30 grains.
From 15 to 19 years old 45 grains.
From 20 to 59 years old 60 grains.
Above 60 years old 30 to 45 grains.
Total dose to be divided into 2 or 3 portions. The patient is
allowed to eat only a light luncheon and supper the day of the
treatment but the next day he may resume his regular meals.
As a rule most of the worms expelled by the treatment will
have been passed by night of the day of treatment, although an
occasional one may be passed for four or five days.
In from 25 to 50% of cases all the worms may be expelled in
one treatment but it is usually necessary to give as many as 3
treatments, one on each of three Sundays.
_Thymol and Beta-naphthol._—Nicol in a comparison of the efficacy
of various drugs, noted that thymol in 90-grain doses, taken in
3 portions of 30 grains each, at 6, 8, and 10 A.M. expelled 98%
of the worms at the first treatment and the remaining worms at
the second treatment a week later. With this rather large dose he
frequently observed a tendency to syncope. He used Epsom salts as a
purgative.
On the other hand, while using 60 grains of beta-naphthol, given in
two portions at 6 and 8 A.M., followed by salts, 86% of the worms
were expelled at the first treatment and 14% with the second one.
He did not observe any bad effects from beta-naphthol.
The great objection to beta-naphthol is that it is a renal irritant
and may damage a kidney already diseased.
Nicol found the treatment with eucalyptus oil, 2 cc., chloroform,
3 cc. and castor oil, 30 cc. vastly inferior in anthelminthic
effect to the other two treatments and liable to cause severe
manifestations of nausea and syncope.
It is better to divide the dose as just stated into two portions,
the second half to be given about one-half hour after the first
portion. This reduces the danger from the chloroform.
Schüffner tried male fern and only obtained 7 hookworms while the
next day, using thymol, 1253 hookworms were expelled. He notes that
thymol is dangerous when administered to patients with acute or
subacute dysentery.
In Brazil a tabloid of 5 grains beta-naphthol combined with 1
grain of phenolphthalein has been generally employed. Using
phenolphthalein in this way enables them to dispense with purgation.
_Oil of Chenopodium Treatment._—As the result of comparing
the relative efficiency of thymol and oil of chenopodium the
International Health Board Commission reported in favor of oil of
chenopodium. In only 7.6% of the cases treated with chenopodium was
there failure to eradicate the parasites while there was noted 23.6%
of failures with thymol. The dose of oil of chenopodium recommended
was 1.5 cc. given in three divided doses of O.5 cc. at 7, 8, and 9
o’clock in the morning. Two such treatments will remove 99% of worms
present in a case. The Commission found the oil more efficient than
an emulsion of the oil.
The low diet and preliminary dose of salts, as noted under thymol
treatment, are to be recommended although the commission found
various purges to have little effect on the results of treatment.
At 11 o’clock give a purgative dose of magnesium sulphate.
The maximum dose of oil of chenopodium is usually given as 3 cc.
but a number of deaths have followed the administration of doses of
from 2 to 3 cc., so that it is better to keep within 1.5 cc.
After effects of treatment, such as dizziness, depression, unsteady
gait, partial loss of consciousness, tingling of hands and feet,
burning sensation in the epigastric region and nausea are more
frequent with chenopodium than following thymol. The toxic symptoms
may be greatly delayed and even be postponed for a day or so. A
large dose of castor oil seems to be the most important measure
in treating a case of chenopodium poisoning. The same methods of
stimulation as noted under thymol poisoning are also indicated.
Kantor has treated a large number of cases with oil of chenopodium
administered through the duodenal tube. After the bucket had passed
the pylorus he introduced into the duodenum about 2 cc. of oil of
chenopodium and followed this in six minutes with two (2) ounces
of a warm saturated solution of magnesium sulphate. The tube is
withdrawn after introducing the salts. Several copious watery
stools follow in a short time.
_Carbon tetrachloride_ in a dose of 3 cc. administered in hard
gelatine capsules, is recommended by Hall for the removal of
hookworms and ascarids. The drug is cheaper, more effective, and,
when chemically pure, safer than thymol or chenopodium. It does
not depress unstriated musculature or lessen peristalsis, thus
eliminating the use of purgatives, which is an item of expense in
extensive hookworm campaigns. The drug is of no value in treatment
of tapeworms and is as unreliable as other anthelminthics for the
removal of whip-worms.
There is a rapidly growing mass of reports concerning the clinical
use of carbon tetrachloride, all of which agree in confirming
experimental observations regarding its effectiveness, and indicate
that a standard dosage as high as 10 to 12 cc. may be safely employed.
After expelling the worms it is advisable to give the patient a
tonic containing iron or arsenic. In those cases with a tendency to
pernicious anaemia the arsenic treatment is better than that with
iron.
In the treatment of ground itch the usual application is a zinc
oxide ointment containing 10 grains of salicylic acid to the ounce.
Barlow recommends a 3% salicylic acid solution in alcohol.
CHAPTER XXII
FILARIAL INFECTIONS
GENERAL CONSIDERATIONS
The filarial worms are thread-like nematodes, with a thin cylindrical
oesophagus, which live in various parts of the body and may or may
not give rise to disease conditions. It is one of the most remarkable
facts in animal parasitology that a person may harbor numerous adult
filariae and myriads of embryos without in any way manifesting
symptoms of the infection. In most of the filarial worms the female
has a double uterus with the uterine opening near the anterior
extremity.
[Illustration: FIG. 94.—Geographical distribution of Filariasis.]
It has been proposed to designate the filarial embryo by the
term microfilaria, reserving the generic name _Filaria_ for the
adult parasite. This may be convenient for differentiation but
zoölogical nomenclature does not permit different names for adults
and embryos. While there have been almost 20 different filarial
species reported for man there is, in some instances, doubt as to
the correctness of the observation, and again, a well recognized
species has at times been considered as a new species and given a
new name.
From a practical standpoint we need only consider: (1) _Filaria
bancrofti_; the adult of which lives in the lymphatic glands and
vessels while the sheathed embryos (which from their appearance in
the blood only at night are called _Filaria nocturna_) obtain access
to the peripheral blood vessels.
[Illustration: FIG. 95.—1a, Adult female Guinea worm (_Dracunculus
medinensis_) showing anchoring hook at posterior extremity. 1b,
Cross section of female _Dracunculus_ showing uterus filled with
embryos. 1c, Striated embryos of the Guinea worm. 1d, _Cyclops
coronatus_, the minute crustacean which serves as the intermediate
host of _D. medinensis_. 2a-2d, Anterior and posterior extremities
of _L. loa_. 2c, Section showing tuberculated cuticle. 2b, Male
and female _L. loa_, natural size. 3a, Bulbous anterior extremity,
_Filaria bancrofti_. 3b, Tail of male. 3c, Tail of female. 3d, Male
and female, natural size of _F. bancrofti_. 4a, Tumor mass of _O.
volvulus_ laid open. 5, Mosquito showing filarial embryos in thoracic
muscles (a) and in labium (b). The labella which are separated from
the labium by Dutton’s membrane are seen at (c). 6(a) Embryo of _F.
bancrofti_. (b) Embryo of _L. loa_ showing filling of tail end with
cells. 7, Microfilaria of _F. bancrofti_ in blood. Dotted lines show
location of break in cell column and V spot.]
Various well-known conditions are caused by this parasite, such as
elephantiasis, varicose groin glands, chyluria, etc. This infection
was formerly stated to be caused by _Filaria sanguinis hominis_.
(2) _Loa loa_, the adult of which wanders about in the subcutaneous
tissues, characteristically in the region of the eyes, while the
sheathed embryo is found in the blood during the day, hence _Filaria
diurna_.
Calabar swellings, irregular febrile conditions and the
disagreeable sensations incident to the wanderings of the worm are
clinical features of this infection.
-----------+--------------------+--------------------+-------------------
| Adults | Embryos | Remarks
-----------+--------------------+--------------------+-------------------
|Male 40 by 0.1 mm. |Sheathed, 300 by 7.5|Transmitted by
| Female 90 by 0.28 | microns. Distance | mosquitoes, Culex
| mm. Smooth cuticle.| from head to V spot| fatigans and
Filaria | Bulbous anterior | 90 microns; to | Stegomyia pseudo-
bancrofti | extremity. | break in cells 50 | scutellaris.
| Occupy lymphatic | microns. Tail | Causes
| glands and vessels.| rather straight. | elephantiasis,
| | Terminal cells do | lymph scrotum,
| | not fill up tail | chyluria, etc.
| | end. Nocturnal |
| | periodicity in |
| | peripheral |
| | circulation. |
-----------+--------------------+--------------------+-------------------
|Male 27 by 0.3 mm. |Sheathed, 240 × 7 |Transmitted by
| Female 55 by 0.4 | microns. Distance |species of a biting
| mm. Cuticle tuber- | from head to V spot| fly—Chrysops.
| culated. Anterior | 65 microns; to | Causes calabar
Loa loa | extremity like | break in cells | swellings. Worms
| truncated cone. | 40 microns. Cork- | often visit ocular
| Wanders in | screw tail which is| region.
| subcutaneous | completely filled |
| tissues. | up with terminal |
| | cells. Diurnal |
| | periodicity in |
| | peripheral |
| | circulation. |
-----------+--------------------+--------------------+-------------------
|Male 40 by 0.07 mm. |Without sheaths, 200|Transmitting agent
| Female 75 by 0.1 | by 5 microns. Post-| not surely known.
| mm. Cuticle smooth.| erior two-thirds | Mosquitoes and
Acanthoch- | Tip of tail shows 2| tapers to blunt | ticks suggested.
eilonema | triangular | ending. Distance | No pathogenicity.
perstans | processes. Found | from head to V spot|
| about root of | 49 microns; to |
| mesentery. | break in cells 34 |
| | microns. Persists |
| | in circulation both|
| | day and night. |
-----------+--------------------+--------------------+-------------------
|Male 30 by 0.14 mm. |Without sheaths, 250|Method of trans-
| Female usually | by 7.5 microns. | mission unknown.
Onchocerca | fragmented. | Found in cyst-like | Causes small
volvulus | Possibly 75 by 0.36| spaces of tumors. | cystic tumors,
| mm. Cuticle | Not in peripheral | under skin of
| striated. Found | circulation. | thorax
| coiled up in | | especially.
| cyst-like tumors | |
| under skin. | |
-----------+--------------------+--------------------+-------------------
|Male from Leiper’s |Without sheaths. 600|Embryos swallowed
| monkey 22 mm. | × 20 microns. Long | by Cyclops. Man
| Female 80 to 90 cm.| slender tail. | drinks water
| long by 1.6 mm. | Cuticle striated. | containing
Dracunculus| wide. Smooth white | Extruded from break| Cyclops.
medinensis| body. Anchoring | in skin of patient.|
| hook at tail end. | |
| Female lives in | |
| subcutaneous | |
| tissue of lower | |
| extremity. | |
-----------+--------------------+--------------------+-------------------
(3) _Onchocerca volvulus._ The males and females of this parasite
are found coiled up in channeled connective tissue tumors of the
subcutaneous tissues.
The sheathless embryos have been surely found only within these
tumors and not in the blood.
(4) _Acanthocheilonema perstans._ This parasite does not seem to give
rise to clinical manifestations except possibly to cause an irregular
fever.
The adult is found in the retroperitoneal connective tissue or fat,
while the sheathless, blunt-tailed embryo is found in the blood,
both by day and night, hence _perstans_. The adult forms are found
in the tissues behind the abdominal aorta and at the attachment of
the mesentery.
(5) _Dracunculus medinensis._ The female of this parasite, about 36
inches long and 1/15 inch in diameter, travels to the subcutaneous
tissues of the extremities and boring through the skin causes a small
surface erosion.
An unimportant filarial worm which has been found only in the West
Indies and British Guiana is known as _Filaria demarquayi_ or _F.
ozzardi_. The embryos have sharp tails and are without a sheath.
The parasite is not known to produce symptoms.
HISTORY
_Filaria bancrofti._—While elephantiasis was frequently described by
ancient writers yet the confusion between Elephantiasis Graecorum, a
term applied to leprosy, and Elephantiasis Arabum, or the filarial
condition, made the question of the nature of the skin thickenings
very indefinite.
The thickenings due to leprosy and those connected with filariasis
were separated clinically by observers during the 17th and 18th
centuries, Hilary, in 1750, having accurately described the
progress of that form of elephantiasis connected with elephantoid
fever and lymphangitis. In 1863 Demarquay discovered filarial
embryos in the exudate of a chylous hydrocele and three years
later Wucherer, in Brazil, found similar nematode larvae in the
urine of a case of haematochyluria. Commencing with the year 1863
Lewis carried on a series of investigations in Calcutta in which
he found these embryos not only in the urine of patients with
chyluria but as well in the lymph and blood of those affected with
elephantiasis. He called the parasite _Filaria sanguinis hominis_,
a name still frequently employed by medical writers.
In 1876 Bancroft, in Australia, discovered the adult filarial worms
in a lymphatic abscess, hence the name _Filaria bancrofti_. In
1878 Manson, in China, demonstrated the mosquito transmission of
the disease as well as the phenomenon of nocturnal periodicity.
Manson’s idea, however, was that the fully developed embryo escaped
from the body of the infected mosquito at the time of the death of
the insect and that man contracted the infection in drinking water.
The investigations of Low and more recently those of Fülleborn and
Bahr and others have shown that the larvae escape by way of the
mosquito’s proboscis and enter the skin of man.
_Loa loa._—The knowledge of a filarial infection of the region of
the eye seems to date from the time of Magellan. Although the disease
is now confined to the west coast of Africa, cases were reported from
the West Indies by Mongin and Bajou during the 18th century. These
cases were in slaves who had contracted the infection in Africa.
[Illustration: FIG. 96.—Section of _Stegomyia pseudoscutellaris_,
showing filariae in thorax on tenth day of development, travelling
forwards into proboscis. By permission from Manson’s Tropical
Diseases.]
In 1891 Manson noted the presence of the larval forms which showed
a diurnal periodicity in the peripheral blood.
_Dracunculus medinensis._—Ancient Egyptian writings would indicate
that the disease was well known in those times. It is believed that
the fiery serpent of the wilderness, which afflicted the Children of
Israel, was an infection of this sort.
The prevalence of dracontiasis, as the infection is generally
termed, in Arabia, was well known to the Greeks and Romans.
Fedschenko, in 1870, noted the transmission of the disease by
species of _Cyclops_.
_Onchocerca volvulus_ was first discovered in 1893, in peculiar
tumors of the natives of the Gold Coast.
[Illustration: FIG. 97.—Female guinea worm (_Dracunculus
medinensis_) lying under the skin of the forearm. By permission from
Manson’s Tropical Diseases.]
_Acanthocheilonema perstans_ was first found by Manson, in 1891, in
the blood of natives of the Congo.
Daniels also found these embryos, along with those of _F.
demarquayi_, in the blood of natives of British Guiana.
FILARIA BANCROFTI
GEOGRAPHICAL DISTRIBUTION
This parasite has been found in almost all tropical and subtropical
countries. It is quite prevalent in the West Indies and has been
found in some of the Southern states of the U. S. It is very common
in some of the South American countries as well as in Central
America. The infection is widespread in Arabia, India and China.
Africa, especially the West Coast, and Australia, particularly in
Queensland, are parts of the world where the infection prevails.
It is especially in some of the Pacific islands, as Samoa and Fiji,
that it is extraordinarily prevalent. Bahr has stated that Fijians
in the proportion of 27% show filarial embryos in their blood. In
25% of these natives clinical manifestations of the disease exist
but the embryos are absent from the peripheral circulation. In
other words more than one-half of the population show absolute
evidence of infection.
LIFE HISTORY
It is a well-known fact that filarial embryos may be present at night
in the peripheral blood of persons not showing a single symptom of
filariasis and again, in those with marked elephantiasis, varicose
groin glands or chyluria there may be an entire and permanent absence
of embryos in the blood. When certain mosquitoes bite persons having
embryos in the blood they take into their stomachs the sheathed
embryos of _F. bancrofti_. Flu states he has succeeded in infecting
the following mosquitoes: _C. fatigans_, _S. scutellaris_, _M.
ludlowi_ and _M. rossii_. The most suitable carriers proved to be _C.
fatigans_ and _S. scutellaris_. Large numbers of larvae perish in
anopheline mosquitoes.
The following developmental cycle has been demonstrated for _Culex
fatigans_ and _Stegomyia pseudoscutellaris_. Bahr has found that
if there are too many embryos taken up by the mosquito the insect
is apt to die, as the result of too heavy an infection; so that
a person harboring many filarial embryos may be less dangerous
than one with a smaller number. Upon reaching the stomach of the
mosquito the sheath of the embryo becomes fixed in the viscid blood
contents and the embryo itself by active motions is able to force
itself from its sheath. This escape usually occurs within two hours
but may take longer. The free embryo then bores its way through the
stomach walls and within twenty-four hours has reached the thoracic
muscles of the mosquito. Within forty-eight hours the embryo begins
to broaden and the anterior and posterior V spots to become more
prominent. About the end of the first week there commences the
formation of an alimentary canal, by which time the developing
larva is about 0.5 mm. long. When the larva is about 0.6 mm. long
an ecdysis apparently takes place. Later on these larvae develop
3 or 4 terminal papillae and make their way to the fleshy labium
of the mosquito’s proboscis. An occasional larva may enter other
structures than the labium but in such case they would be unable to
effect an entrance to their definitive host, man. These larvae in
the proboscis are about 1.5 mm. long and about 20 microns broad.
The mosquitoes have two terminal processes, the labella, separated
from the labium by a thin membranous partition called Dutton’s
membrane. The larvae, having completed their developmental cycle
in the mosquito, which takes about three weeks, and moving down the
labium, break through this membrane when it is put upon a stretch
by the wide separation of the labella at the time of feeding on
the part of the mosquito. It was formerly supposed that the larvae
entered man through the puncture made by the biting parts of the
mosquito, but Bahr has shown by experiments that they effect
an entrance through the intact pores of the skin as does the
ancylostome larva.
These larvae upon entering the human host reach the lymphatic
vessels or glands and in this definitive host (man) the females are
fertilized by the males and give off sheathed larvae from the uterine
opening near the anterior end of the worm.
[Illustration: FIG. 98.—Male (a) and female (b) of _Filaria
bancrofti_. Natural size. (From Greene after Manson.)]
The sheath is simply the egg membrane which from being oval at
first becomes stretched by the developing embryo to finally become
a long, narrow sac encasing the fully developed embryo as it exists
in man. From the lymph stream they reach the general circulation.
In a case of a man with filarial embryos in his peripheral
circulation, who committed suicide one morning, Manson found the
embryos, in large part, contained in the vessels of the lungs.
There were 675 embryos per slide in blood from the lungs for one
from blood from the spleen or liver. It would thus appear that
during the day, when the embryos are absent from the peripheral
circulation, they retire to the lungs. In the case of the filarial
embryo of persons in the Pacific Islands there does not appear
to exist any periodicity. Bahr thinks this absence of nocturnal
periodicity to be connected with the habits of its principal
intermediary host, _Stegomyia pseudoscutellaris_, which feeds by
day. _Culex fatigans_ feeds at night.
With the filarial embryos found in patients in the Philippines
there is also a lack of nocturnal periodicity. In the opinion of
Ashburn and Craig the Philippine filarial worm is a new species,
_Filaria philippinensis_.
Walker, however, recently examined four adult filarial worms in
the Philippines and was unable to note any differences from _F.
bancrofti_.
PATHOLOGY AND MORBID ANATOMY
The adult worms may exist in numbers and over long periods of time
give off great numbers of embryos into the peripheral circulation
without there being any evidence of disease in the patient. There is
apt to be at such time a marked eosinophilia. The process by which
the fibrosis of lymph channels with obstruction to the flow of lymph
occurs is unknown. Some think that with the pouring out of embryos
inflammatory processes, bacterial or otherwise, may be set up. We
know that there is a tendency for these adults to die and become
calcified, in this way bringing about lymphatic obstruction.
Bahr notes the influence of adult filariae in producing an increase
in connective tissue in glands and considers such glands as less
resistant to bacterial infection.
Manson has an idea that some factor may cause the female to give off
immature embryos, which being oval, and of considerable width, may
block the lymphatics.
It has often been claimed that various cocci were the exciting
factors in the lymphangitis associated with filariasis. Recently
Dutcher has reported the isolation of an organism resembling
_B. subtilis_ as the cause of filarial lymphangitis (_Bacillus
lymphangiticus_).
As the result of the lymphangitis and blocking of the channels
the embryos cannot reach the peripheral circulation; hence when
obstruction does occur and symptoms of lymph stasis appear, there
may be an absence of embryos in the circulation.
It is now well established that patients with elephantiasis very
rarely show embryos in the peripheral circulation, and this fact
should be better understood because there is a tendency to negative
a filarial diagnosis when embryos are absent from the peripheral
circulation.
These lymph channel obstructions may at one time cause dilatations
or varices and at another bring about solid oedemas of the
tributary parts. The treatment will be considered under each
special form of the disease. It may be stated however that
salvarsan, arsenophenylglycin and other similar remedies have been
without special effect in destroying the filarial worms.
CLINICAL MANIFESTATIONS
Not only is it important to understand that elephantiasis and other
manifestations of filarial infection may and usually do exist
without there being embryos in the peripheral blood of the patient,
but also, that a high percentage of a population may show filarial
embryos in their blood and yet never or with extreme rarity show
any of the signs of filarial disease. These people, with abundant
embryos in their blood, usually show no disturbance of health. In the
Philippines one may rarely see a case of chylocele but usually there
is nothing clinical to note.
Johnson, in examining 400 people, in Charleston, S. C., found
19% with filarial embryos, yet only 5% showed any symptoms of
filariasis. Croll states that 11.5% of 4000 Europeans admitted
to the Brisbane Hospital (Australia) showed filarial infection
but practically none had symptoms. In South Queensland cases of
lymphangitis, chyluria and varicose groin glands are occasionally
seen and rather frequently hydrocele and filarial abscesses. There
is an absence of elephantiasis.
Elephantoid Fever
The febrile accessions that accompany the recurring attacks of
lymphangitis in elephantiasis, lymph scrotum and other filarial
manifestations, are very important because they may lead to errors in
diagnosis.
Thus in Barbadoes, where there is no malaria, a condition in
which there occurs a high fever of sudden onset with rigors and
associated erysipelatous redness of leg or scrotum, accompanied by
lymphangitis and painful lymphatic glands, has given a suggestion
of a malarial paroxysm. The tense inflamed area, after several
days, shows an exudation of lymph and the redness disappears,
but with some resulting thickening of the affected tissues. Such
attacks may terminate with profuse sweating.
The treatment of the condition is such as would be advisable for
ordinary lymphangitis—rest in bed, elevation of the part, laxatives
and local applications.
Lymph Scrotum
This condition is apt to set in with fever. The scrotal tissues are
somewhat tense and reddened and may show numerous lymphatic varices
which when pricked with a needle, give exit to lymph which may or may
not contain filarial embryos. The lymph continues to exude for a long
time. Erysipelatous manifestations are not uncommon. With recurring
attacks the scrotal tissues become more and more hypertrophied and
may go on to elephantiasis of the scrotum.
Ordinarily local applications with suspension of the scrotum is the
proper treatment. Should the thickening increase to a great extent
the blubbery tissues may be excised, care being exercised to avoid
the testicles and to bring together sound tissue for the enclosing
flaps. These wounds usually heal readily, although there may be
delay in healing from the outpouring of lymph in cases where the
flaps include diseased tissue.
Varicose Groin Glands
Swellings which come on rather slowly and insidiously may involve
the inguinal or femoral groups of glands of one or both sides.
The epitrochlear glands may also be involved. The skin over the
enlarged, rather doughy glands can be freely moved but the glands
themselves are bound down to the deeper tissues. Elephantoid fever
may set in associated with local manifestations of pain and redness.
If such glands are punctured with a hypodermic needle lymph,
which may contain embryos, exudes. This test together with their
slow disappearance on lying down and slow return on assuming the
upright position should differentiate hernia. When the contents of
a hernial sac are omental there is some difficulty in diagnosis. As
a rule it is not advisable to interfere surgically in this filarial
condition.
[Illustration: FIG. 99.—Varicose groin glands and elephantiasis of
scrotum and penis. (From Ruge and zur Verth.)]
Filarial Abscesses
As a rule injury to the adult filarial worms, which results in their
death, is not followed by abscess formation but such termination
may occur. These abscesses have been found deeply seated in the
extremities. Wise and Minett in a careful examination of 28 such
cases found evidences of adult filariae in 22 cases. In 21 of these
abscesses, infections with streptococci or staphylococci were
demonstrated. Very interesting also is the finding of filarial worms
in deep-seated abdominal abscesses.
As regards location, these filarial abscesses were found 31 times
in the pelvis of the kidney, 18 times in the epididymis, 12 times
in the retro-peritoneal tissues, 25 times in the inguinal glands,
4 times in the ilio-psoas muscles and 8 times in the lymphatic
vessels.
They regard the endemic funiculitis to which attention has been
directed by Castellani as simply a similar process involving
the tissues about the spermatic cord. The treatment of filarial
abscesses is similar to that of other abscesses.
Chyluria
As the result of obstruction of the lymphatic vessels varices may
form in the bladder lymphatics and, as the result of their rupture,
milky urine may be passed. If the thoracic duct be occluded the
urine will show an abundance of fat, while if the obstruction exists
only in other lymphatics, the milky fluid will be found to show but
little fat. Blood is usually present in chyluria so that the urine
will show an pinkish tinge.
Chylous urine coagulates rapidly and we have in such a specimen of
urine, upon standing, an upper fatty layer and pinkish sediment at
the bottom, with a clot between.
The sediment shows lymphocytes and at times filarial embryos. When
the exudate is lymph mixed with blood the term haematolymphuria
would be a better one.
Clots may form in the bladder and give rise to obstruction to the
flow of urine from the bladder.
The appearance of the chyluria is often preceded by heaviness about
the loins and pains in the region of the bladder.
The morning urine in such a case is apt to be clear while that
passed later in the day is milky in appearance.
A feature of chyluria is its tendency to disappear and reappear
so that when treating such a case one should be conservative in
considering the treatment as effecting a cure.
It is difficult to understand why chyluria should be common in
India and China while almost unknown in the filarial infections of
the Pacific islands.
In treating a case of chyluria one should enjoin rest in bed,
laxatives and a restriction of fluids and fats. Patients subject
to the condition should refrain from active exercise and other
conditions which might cause fatigue. Drugs are of little value.
Filarial Orchitis and Hydrocele
The condition rather resembles an attack of epididymitis. As a result
of recurring attacks hydrocele develops. The fluid may be lymphous
or chylous in appearance and upon microscopical examination may show
filarial embryos. These filarial hydroceles seemed to be the most
common manifestations of the disease as observed in the Philippines.
These hydroceles or chyloceles do not become very large but may
require tapping.
Elephantiasis
As the result of recurring attacks of lymphangitis the tissues of
the affected part show the effects of lymphatic obstruction by an
hypertrophy of the skin and subcutaneous tissues. It would seem that
the combination of lymphatic obstruction and bacterial infection is
necessary for the production of elephantiasis. The skin of a part
affected with elephantiasis is rough and the hair scanty. In addition
to the lymphoedema of the part there is a great increase in the
connective tissue.
On account of the lymphatic stasis incision into the blubbery
tissue causes the outpouring of much lymph.
Elephantiasis of the lower extremities is by far the most common
situation, giving us probably 90% of such affections. In Fiji
elephantiasis of the upper extremities is quite common.
Other favorite sites are the scrotum, vulva, breasts and penis.
Rarely the scalp or areas about neck or trunk may show involvement.
[Illustration: FIG. 100.—Elephantiasis of the legs. (From Ruge and
zur Verth.)]
Surgical treatment is the one usually followed. When an extremity
becomes too much of a burden, amputation may be indicated. The
employment of the method of lymphangioplasty, which consists in
the introduction of silk threads into the subcutaneous tissues,
to make a channel to the normal lymphatics, does not seem to have
been attended with any degree of success or at any rate permanent
results. These wounds tend to become infected and if this does not
occur the new channels are speedily obliterated.
Castellani recommends the use of Merck’s fibrolysin in injections of
from 2 to 4 cc. daily, for three to six months. After each injection
the part is tightly bandaged with flannel or rubber bandages. The
injections may either be made into the affected part or into the
gluteal region. Massage prior to the bandaging may give better
results. When the limb becomes smaller and the skin smoother, long
strips of skin and subcutaneous tissue may be dissected out and the
adjacent edges sutured.
In considering the advantages of operation in elephantiasis of the
scrotum it is usually stated that the only question involved is the
removal of a burdensome mass which in no way is a source of danger
to the life of the patient. At the same time such patients are
subject to attacks of elephantoid fever, a condition not without
its dangers. There is one factor not usually brought forward and
that is the remarkable effect of a successful operation on the
mental state of the patient. This is well shown in the accompanying
illustrations of the patient before and after operation. If
sexual deficiencies are of so powerful an influence on persons of
education how much greater must they weigh on an uneducated native
with but few of the higher interests of life.
Prior to operation the patient should be kept in bed for a day
or so to lessen the amount of fluid and to secure relaxation of
tissues. Thorough scrubbing with soap and water the day of and the
day before the operation and the use of alcohol as an antiseptic
are important. Some prefer iodine.
[Illustration: FIG. 101.—Elephantiasis of the scrotum. Before
operation. (Fauntleroy.)]
For the operation the lithotomy position is employed. An assistant
supports the scrotal tumor wrapped in a sterile towel. Fauntleroy,
whose method I give, does not recommend a tourniquet to the base of
the tumor as in his opinion it assists but little in controlling
haemorrhage and endangers asepsis. Haemostats answer better and as
the vessels which give most trouble are deeply situated the elastic
cord would not affect them. In some cases there is very little
bleeding. The upper part of the pear-shaped tumor usually affords
sufficient sound skin next the thighs for the flaps. As a rule
the elephantoid tissue does not involve the upper 2 or 3 inches
of the skin anteriorly, which is thus available to cover in the
base of the penis. In addition to this covering for the penis we
have a long prepuce which has been considerably stretched so that
after removing all elephantoid tissue there is enough sound prepuce
remaining to cover the distal 2 or 3 inches, so that usually there
is sufficient sound skin for a 5-inch penis.
[Illustration: FIG. 102.—Elephantiasis of the scrotum. After
operation. Note change in mental state. (Fauntleroy.)]
The flaps which are to cover the penis and testicles should be
mapped out with shallow incisions and care must be exercised that
only sound skin is included in these flaps. A horseshoe shaped
incision is made commencing at the left side of the base of the
tumor about 1 inch from the thigh and about at the level of the
penis in health. The incision is carried downward and passes just
below the opening of the penis on the tumor surface. A similar
incision on the right side completes the horseshoe curve. Next a
downward incision in the sound skin is made over the posterior
surface of the tumor, thus encircling the base of the scrotum. The
anterior horseshoe incision is now deepened to free the penis,
care being taken not to injure the spermatic cord. Next the
incisions are deepened laterally until the testicles are reached.
The testicles are usually in the center of the tumor imbedded in
a blubbery tissue from which they can be easily stripped. The
remains of the gubernacula are then hooked up and cut close to the
testicles. The tunicae vaginales are often thickened and contain
fluid which has to be drawn off.
In 60% of Fauntleroy’s cases it was necessary to remove one
testicle on account of extensive disease. One must also bear in
mind the possibility of hernial complications and undescended
testicle.
A sound is now introduced into the urethra and the septum of the
scrotum divided close to the sheath of the penis, then dissecting
away the blubbery tissue. At this stage there may be considerable
bleeding.
The testicles and spermatic cords are then dissected away from the
tunicae vaginales. The penis is now freed by a circular incision
around and above the opening in the anterior part of the mass.
The remainder of the horseshoe flap is now dissected up and the
penis freed. The proximal covering for the penis is made from this
horseshoe flap which is stitched to the distal one shaped from the
prepuce, carefully trimmed of elephantoid tissue.
The lateral flaps are brought together with linen or silk-worm gut
sutures leaving space for a drainage tube and we thus form a new
scrotum for the testicles.
The mortality is usually given as 5% but Fauntleroy did not lose a
case among 149 such operations, the tumors varying from 10 to 85
pounds in weight.
Chylous Hydrocele
Filarial affections of the tunica vaginalis or the testicle itself
are not rare. In the milky fluid obtained by tapping such a hydrocele
we may find filarial embryos.
Besides chylous hydrocele we may have a chylous ascites or a
chylous diarrhoea. Where there is no obstruction to the thoracic
duct there is less fat and the condition is more properly a
lymphocele rather than a chylocele. The same distinction is
applicable to the other conditions connected with lymphatic varices
due to lymphatic obstructions other than that of the thoracic duct.
LABORATORY DIAGNOSIS
The blood from a needle prick of the finger tip or the lobe of the
ear can be examined as a fresh preparation. It is advisable to make a
vaseline ring around the drop of blood on the slide and then apply a
cover-glass. Such a preparation will permit of the examination of the
living embryos for a day or more.
Smear preparations may be made by the Ehrlich method of drawing
cover glasses apart or by the Daniels method on slides. Some
prefer making a thick smear of a drop of blood and, after it
has dried, carefully to dehaemoglobinize it with water and then
staining with dilute haemotoxylin. Staining with Leishman’s or
Wright’s stain gives beautiful pictures. Fixation with methyl
alcohol or with heat, by burning off a film of alcohol, and then
staining with Giemsa’s stain or some haematoxylin preparation, is
to be recommended. On the whole I consider haematoxylin the most
desirable staining reagent, as such preparations hold their color
for a long time. The paper-like sheaths are seen as if twisted
about the larvae with their violet-stained cells. One should note a
break in the violet-stained cell column which is 50µ from the head
end of _F. bancrofti_ and 40µ for _L. loa_.
A V spot is seen posterior to the break in the cell column and
shows best with very light staining.
The break in the column of the cell nuclei marks the position of
the nerve ring, which is distant from the head one-fifth the total
length. The anterior spot, below the break in the cell column, is
distant about 30% of the total length. It is the location of the
excretory pore. In _F. bancrofti_ the cell nuclei extend to 95% of
length, thus differing from those of _L. loa_, which fill up the tail
end. At about 82% of the length from the head is located the anal
pore.
Ruge’s thick film method for malarial parasites gives excellent
results in staining filarial embryos. Either the Giemsa or
haemotoxylin staining may be employed.
Embryos may be found in the lymph from varicose groin glands or in
the exudate from a chylous hydrocele, as well as in the urinary
sediment from a case of chyluria.
The failure to find embryos in no way negatives the existence of a
filarial infection.
Adult filariae, either alive or dead and calcified, may be found in
the lymphatic glands or in the contents of filarial abscesses.
The blood shows an eosinophilia.
LOA LOA
This filarial infection is at present only known for the West Coast
of Africa. In the Cameroons and in Old Calabar the infection is quite
common.
As noted in the table previously given, the adults which are a
little more than an inch long have cuticular protuberances or
bosses, about 12 to 15 microns in height. The sheathed embryo is
very similar to that of _F. bancrofti_, but has a more twisted
tail and shows a complete filling up of the tail end with rather
elongated cells. The lines of the curves of the embryo show
irregularities and are not the smooth lines characteristic of _F.
bancrofti_ embryos.
The periodicity is diurnal, for which reason the parasite was
originally termed _F. diurna_.
Leiper has reported two species of _Chrysops_, one of the tabanid
biting flies, as transmitting agents and considers that the embryos
undergo development in the salivary glands of the fly.
The life history is not well understood but as a rule a period of
several years elapses after infection before adult filariae or
filarial embryos are found. Again, for some reason, adult filariae
may be noted and when extracted be found full of embryos and yet
embryos not be found in the peripheral circulation.
The adults are noted for their tendency to move about in the
subcutaneous connective tissues having been found in such tissues
in the region of scalp, trunk, penis and extremities.
Most frequently, however, they are noted in the tissues about the
region of the eyes and even under the conjunctivae, from which
location they have been frequently extracted. It is this which has
caused the name _Filaria oculi_ to be given the worm.
[Illustration: FIG. 103.—_L. loa_ above. _Acanthocheilonema
perstans_ below. (From Greene, after Fülleborn.)]
The course of the wandering worm is usually marked by an oedematous
track. In his own case, recently reported by a medical man, the
first symptoms were transient painless swellings about the joints,
associated with stiffness. Various diagnoses, such as rheumatism,
erythema nodosum and angioneurotic oedema were made in his case.
Although two adult filariae were removed at different times the blood
examinations were negative for embryos.
As a rule the appearance of the worms in the subcutaneous tissues
is characterized by itching sensations and a feeling of tension.
Warmth causes them to appear in the superficial tissues while
cold makes them confine themselves to the deeper structures.
Eosinophilia is rather pronounced.
=Calabar Swellings.=—Although we have no absolute proof that these
usually painless swellings, which occur rather suddenly on various
parts of the body having only a thin layer of connective tissue, as
forearms, face, ankles, hands, are connected with an infection with
_L. loa_, yet such is the general view. These swellings are about the
size of a hen’s egg, do not pit on pressure and last for about three
days. There is marked tension over the swellings and they may itch
greatly.
[Illustration: FIG. 104.—_L. loa_ in the subcutaneous tissues, twice
normal size. (From Greene, after Fülleborn.)]
Rarely does one note more than one swelling at a time. Eosinophilia
is quite marked during the attacks. Manson thinks the oedema
results from the extrusion of embryos from the female at the site
of the swelling. Ward considers the cause to be toxic material
excreted by the worm.
There is very little of importance in connection with treatment.
When the worms, which travel in the tissues about the eye, at the
rate of about ½ inch per minute, are noted, some local anaesthetic
may be used and the worm seized with forceps and extracted through
a small incision. Elliot recommends the application of hot
fomentations to the eye and upon the appearance of the worm under
the conjunctiva to instill cocaine solution, seize the worm with
forceps and then pass a silk ligature through the conjunctival
fold taking in the worm. The ligature is tied and an incision made
through which the worm is extracted. Cooling local applications, or
an ichthyol ointment, may be applied to the Calabar swellings.
ONCHOCERCA VOLVULUS
This name is given to a filarial worm, found principally on the
West Coast of Africa, which causes the formation of subcutaneous
tumors. In certain localities as many as 10% of the population may be
infected. More recently the parasite has been reported from Guatemala.
It is supposed that the adult worms cause an inflammation of the
lymphatic vessel in which they may lie and that a formation of
new connective tissue results, giving rise to a tumor-like mass,
which is most often found in the axilla or about the sides of the
thorax. This tissue stroma encompasses the worms except for the
anterior extremity of the female, with its uterine opening, and the
posterior extremity of the male carrying the spicules, which ends
lie loose in a sort of cyst-like dilatation, which is filled with
a viscid fluid swarming with unsheathed embryos. These tumor-like
masses cause very little discomfort, last indefinitely and do not
tend to ulcerate.
It was formerly thought that these larvae were absent from the
peripheral circulation but more recent investigations in cases of
onchocerciasis have shown sheathless larvae in the blood, which had
the characteristics of those in the contents of the tumors. Such
findings, however, are of extreme rarity, the blood examination being
almost invariably negative.
The cysts are usually found on the sides of the chest and are quite
superficial, with the skin freely movable over them. They may be as
large as a hen’s egg but usually are smaller. They are also found
over trochanters or along the crests of the ilium.
Dubois states that the embryos may be found in juice from puncture of
groin glands.
The tumors are easily enucleated.
In the American infections the tumours are more common in the
regions near the eye and it has been thought that certain cases of
keratitis may be due to onchocerciasis.
DRACUNCULUS MEDINENSIS
The disease caused by infection with this parasite is usually termed
dracontiasis and the parasite _Dracunculus medinensis_ or the Guinea
worm.
The geographical distribution includes India, Arabia, the West Coast
of Africa and Brazil.
_Life History._—The male has not surely been seen in man so that
the pathological condition is entirely connected with the female
worm. Almost invariably the female worm, which measures about
two feet long by 1/12 inch broad, tends to wander down to the
connective tissue structures of the lower extremity. In about 10%
of the cases the worm may present elsewhere, as scrotum, back or
arms. At the posterior extremity there is a sort of anchoring hook.
With the anterior extremity the worm presses against the overlying
skin and causes the formation of a blister-like lesion.
This vesicle later on bursts and, if water is applied to the
spot, a delicate tube, the uterus, is extruded and there exude a
few drops of a milky fluid, which swarms with the sharp-tailed,
striated, sheathless embryos. It is thought that the pouring forth
of embryos, when water touches the part, is in order that the
embryos may reach the water of a pool through which the infected
native may be wading. Once in the water of such a pool, the larvae
are swallowed by _Cyclops_ and gaining the body cavity of this
little crustacean, they continue to develop for about one month.
During this period there are two ecdyses, the first after about two
weeks, when the tail becomes blunt.
When one takes these infected cyclops into the stomach, by drinking
water containing them, the cyclops is killed by the gastric juice
and the Guinea worm larva breaks out of the dead intermediary host
and bores its way through the stomach wall and possibly goes to the
tissues about the retroperitoneal region. As a matter of fact we are
in ignorance of the exact cycle which goes on, until the fertilized
female, with her embryo-distended uterine tube, reaches the lower
extremity. A cross section of the female shows the body of the worm
to be almost entirely made up of uterus, with an insignificant
alimentary canal pressed to one side.
The period of incubation is from 8 to 12 months.
Usually there are no other symptoms than discomfort from the
blister and a feeling of heaviness about the affected extremity. At
times there may be pain and fever. The parasite may fail to gain
exit to the skin surface or die before reaching maturity. In such
cases she may become calcified or give rise to abscess formation.
The _x_-ray plate may show a convoluted cord-like structure with
frequent breaks in the line.
[Illustration: FIG. 105.—Guinea worm (_D. medinensis_). Rolled on a
stick for gradual extraction. (From Greene’s Medical Diagnosis.)]
_Treatment._—By douching the point of exit we may cause the uterus
to empty itself in about three weeks. At that time we may commence
extraction by intermittent traction by winding the worm around a
large toothpick or similar object. If undue force is exerted the worm
may break off and abscess formation or sloughing result.
Macfie has reported success in treating 23 cases of dracontiasis
with tartar emetic. He gave 1 grain intravenously every other day
and found that it was not necessary to give more than 6 grains in
the course of treatment. The inflammation quickly yielded and the
discharge from the sore ceased rapidly.
CHAPTER XXIII
THE SCHISTOSOMIASES
GENERAL CONSIDERATIONS
There is a group of diseases, caused by trematodes of the family
Schistosomidae, to which we apply the name schistosomiasis. The
Schistosomidae differ from other human flukes (Trematoda) by not
being hermaphroditic and by having nonoperculated eggs. From these
eggs a ciliated embryo (miracidium) emerges which gains entrance to
certain species of molluscs. In this intermediate host the miracidium
gives rise to a sporocyst, which latter forms daughter sporocysts.
These emerge from the mother cyst and enter the digestive gland of
the mollusc and produce cercariae.
These cercariae show an absence of a pharynx and upon the rupturing
of the sporocyst are discharged from the mollusc and furnish the
infecting stage for penetrating the skin of man or other animal.
There are those who think the entrance is effected through mucous
membranes, especially those of the mouth, genitalia and anus and even
the nasal mucosa.
It is generally admitted that infection by drinking water, containing
the ciliated embryos, is impossible, owing to the rapidity of their
destruction by solutions of HCl of similar strength to that of the
gastric juice.
Infecting mice with _S. japonicum_ cercariae from snails mashed on
the abdominal surface of the mouse, it was found by Suyeyasu that
after penetrating the skin the cercariae went to the right heart by
way of venous and lymphatic channels. From the pulmonary vessels they
penetrate the lungs and go by way of the mediastinum or pleura to the
diaphragm which they penetrate and make their way to the abdominal
cavity next penetrating the liver and entering the portal vein.
It is probable that the earlier stages of development take place
in the portal vein and that having reached maturity the female
attaches herself to the male and together they go, by way of
the inferior mesenteric vein, to the haemorrhoidal or vesical
terminals. The male is in the shape of a narrow leaf, about ½
inch long with a ventrally turned oral sucker and a closely
adjacent ventral sucker. The female is a somewhat longer and
cylindrical worm almost an inch in length and, like the male, has
two suckers. There is a dark brown zig-zag stripe which shows
prominently in the posterior part of the female and outlines the
blood-filled intestinal tract. When the female applies herself to
the ventral surface of the male there is an infolding of the sides
of the flattened surface giving the male a cylindrical outline
and resulting in the formation of a canal containing the female
(gynaecophoric canal).
[Illustration: FIG. 106.—_Schistosoma japonicum_ (male and female).
The sharp edges of the borders at the beginning of the gynaecophoric
canal formed by the male are an accidental appearance. (From Mense.)]
The males of the flukes which cause the vesical (_Schistosoma
haematobium_) and the rectal (_Schistosoma mansoni_) involvement are
covered externally with small tubercles and have a ventral sucker
only slightly larger than the oral one. The Japanese schistosome
(_Schistosoma japonicum_) is slightly smaller, has a smooth surface
and shows a prominent pedunculated ventral sucker of much larger size
than the oral one.
Both suckers are larger than those of the other species.
The eggs of _S. haematobium_ have a terminal spine and measure from
115 to 175 by 60 microns; those of _S. mansoni_ have a lateral
spine and measure from 110 to 125 by 50 microns while those of _S.
japonicum_ are devoid of spinous projections and measure about 100
by 70 microns.
Clinically, the three infections differ as will be noted further on.
Looss claims that the two tuberculated species are identical and
that the lateral spined egg is the product of an unfertilized
female. He has more recently regarded the egg as produced
parthenogenetically. Other helminthologists have noted slight
anatomical differences as to ovaries and testicles so that the
consensus of opinion is that vesical and rectal bilharziases are
caused by different species of the genus _Schistosoma_.
[Illustration: FIG. 107.—Ovum of _Schistosoma japonicum_. By J. A.
Thomson. (Jefferys and Maxwell.)]
Recently Leiper has found cercariae showing the absence of a pharynx
(characteristic of the genus) in a Japanese mollusc. Such molluscs
were teased out in water and laboratory bred mice immersed therein.
One of these mice was killed a month later and adult schistosomes
were found in the portal vessels. Leiper has also found cercariae
showing absence of pharynx in four different species of molluscs
in Egypt. With such molluscs he was able to infect white rats and
other animals. He states that infection with these cercariae from the
mollusc host can bring about infection either by way of the mouth or
through the skin. Sodium bisulphate in a strength of 1 to 1000 killed
these cercariae almost immediately.
It would therefore seem proven that all human schistosome
infections take place following cercarial and not miracidial
development. As proof that _S. haematobium_ and _S. mansoni_ are
different species, Leiper notes that mice infected by molluscs of
the genus _Bullinus_ showed schistosomes with terminal spined eggs,
the ovary lying in the lower half of the female. The male had four
or five large testes. In mice infected by molluscs of the genus
_Planorbis_, the eggs were lateral spined, the ovary was in the
anterior half of the body and the male had eight small testicles.
The mollusc host of _S. japonicum_ is _Blanfordia nosophora_. The
shell of this snail is of cornucopia shape.
As these flukes are found in the blood vessels they are often
referred to as the blood flukes.
HISTORY
Vesical schistosomiasis has undoubtedly existed in Egypt since
ancient periods as vesical calculi are frequent in the mummies of
various dynasties. Ruffer has found calcified schistosome ova in the
kidney of a mummy.
The French troops suffered greatly from the disease in 1800. It was
Bilharz in Cairo, in 1851, who first associated the haematuria with
the presence of the parasite and it is from his name that we get
the designation bilharziasis or bilharziosis for the disease.
In 1903, Manson found lateral spined eggs in a patient from the
West Indies who was suffering from rectal rather than bladder
symptoms. In 1907 Sambon, considering the points of difference
between the eggs and the involvement of rectum rather than bladder,
established a new species, _S. mansoni_.
In the West Indies, as shown by the reports of Surgeon Holcomb from
Porto Rico, rectal bilharziasis is rather common.
For a number of years Japanese physicians had noted the existence
of a disease characterized by splenic and hepatic enlargement,
ascites and cachexia. In August, 1904, Katsurada discovered ova
with a ciliated embryo in the stools of patients with this disease.
He found schistosomes in the portal vessels of dogs and cats
containing eggs similar to those seen in the human cases. He named
this trematode _S. japonicum_. In November, 1904, Catto discovered
the parasite at an autopsy on a Chinaman. In 1910 Lambert, in
China, described a disease, which he called urticarial fever,
and a short time afterward Houghton established the connection
between this disease and the more advanced stages of Japanese
schistosomiasis.
[Illustration: FIG. 108.—Ovum of _Schistosoma haematobium_. By
William Pepper. (Jefferys and Maxwell.)]
[Illustration: FIG. 109.—Ovum of _Schistosoma mansoni_. By William
Pepper. (Jefferys and Maxwell.)]
PATHOLOGY
The pathological lesions are almost entirely due to the irritation
of the eggs with resulting connective tissue increase or ulcerative
processes. For some reason these flukes select the inferior
mesenteric vein and make their way to the vesical plexus of veins in
the case of _S. haematobium_ and to the haemorrhoidal vessels for the
other species. At times the ova or worms may be carried over to the
systemic veins by way of the channels of anastomosis. In the terminal
vessels the female gives off the eggs which penetrate the adjacent
mucosa giving rise to inflammatory thickenings and the extrusion of
the irritating eggs into the lumen of the bladder or rectum.
In the bladder these terminal spined eggs cause haematuria and form
the nucleus for vesical calculi. The mucosa may also show wart-like
excrescences. If the eggs are swept back through the portal vessels
to the liver an interlobular cirrhosis results which would seem to
be due entirely to the irritation of these egg emboli and not to
toxic products of the worms themselves. Marked ureteral and kidney
lesions may result as complications of cystitis or primarily from
irritation by ova. In women the vagina, vulva and cervix uteri may
show papillomatous thickenings. Bilharzial lesions of the male
urethra are not uncommon and may lead to fibroid thickenings and
fistula.
In searching for the flukes at autopsy we should make a
longitudinal slit in the portal vein and with a spoon scoop out the
blood and search for the parasites in a glass dish.
In the intestinal form of schistosomiasis the rectum may be studded
with polypoid tumors which when projecting from the anus may ulcerate
and lead to a diagnosis of cancer of the rectum. In sections from
these masses great numbers of lateral spined eggs may be found.
The connective tissue increase is in the submucosa. The gut section
may also present small abscess-like areas.
Eggs have been found in the appendix as well as in the large
intestines and the small intestine has been found involved in one
case. In rare instances ova have been found in the lungs, spleen
and even in the brain and spinal cord.
By digesting selected tissues in 4% NaOH at 75°C. and centrifuging
one may find eggs which otherwise would be overlooked. Statistics
from Cairo usually note 30 to 40% of infection in natives but
Ferguson employing all methods found 61% infected at autopsies on
600 males. In all forms of schistosomiasis but particularly in the
Japanese infection, eosinophilia is pronounced.
In Japanese schistosomiasis the intestines may show thickenings at
the site of aggregations of eggs. In the liver a marked interlobular
cirrhosis occurs with numerous eggs in the connective tissue
increase. Rarely, eggs may lodge in the brain, giving granuloma-like
areas. The irritating eggs may also give rise to similar areas in the
lungs.
SYMPTOMATOLOGY
Vesical Schistosomiasis or Endemic Haematuria
This form of the disease is chiefly found in Egypt, Syria, Uganda
and South Africa. It is caused by _S. haematobium_ and the period of
incubation is approximately six months.
[Illustration: FIG. 110.—Vesical schistosomiasis showing fistulous
tracts opening from penis and scrotum. (From Ruge and zur Verth.)]
The first symptoms are pricking sensations about urethra and slight
haematuria which comes on at the end of the act of micturition.
Excesses or fatigue are apt to increase the haematuria. The diagnosis
is made by finding the ova in the sediment of the centrifuged urine.
Symptoms of cystitis and even pyelitis may follow the early
bladder and urethral manifestations. Pain in the back or symptoms
suggesting renal colic may be present. Anaemia and physical
weakness gradually develop. An important sequel is vesical
calculus. It is a question whether the eggs or some other product
of the infection form the nucleus of such a stone. Not only can
stone be recognized by cystoscopy but rather distinctive are
small, glazed yellowish nodules with areas of granulation tissue.
Papillomatous growths may also be seen upon cystoscopy.
Perineal fistulae in the male and vaginitis in the female may be
noted.
When reinfection does not occur the haematuria tends slowly to
disappear but recovery does not usually take place for several
years. The vesical schistosome (_S. haematobium_) often causes
pathological changes in the rectum so that a case may show both
vesical and rectal symptoms. The rectal schistosome (_S. mansoni_)
does not give rise to vesical trouble.
Rectal Schistosomiasis
While terminal spined eggs may be found in rectal lesions, but
usually combined with lateral spined eggs, in countries where the
vesical form of the disease exists, yet there are many parts of
the world where, with the exclusive existence of an intestinal
bilharziasis, only lateral spined eggs are found. The infection
resulting from _S. mansoni_ is the sole one in the West Indies, Congo
Free State and in North-eastern South America.
The symptoms are usually those of a chronic dysentery with more or
less tenesmus and straining. Prolapse is a common result and is the
cause of the ulcerations which may cause the disease to be diagnosed
as cancer. Cirrhosis of the liver is more apt to occur than in pure
vesical schistosomiasis.
Most writers fail to mention other than the later manifestations
of rectal bilharziasis, the earlier symptoms being overlooked
or attributed to other causes. The same was true of Japanese
schistosomiasis in which the initial “urticarial fever” was only
recognized as connected with the late manifestations of liver
cirrhosis and ascites a few years ago.
In 1916 Lawton noted in a number of Australian soldiers, encamped
in Egypt, a fever of about 7 to 10 days’ duration in which the
evening rise approximated 103°F. A diarrhoea and abdominal pain
accompanied the fever and along with this a cough and patchy
consolidation. Most of the cases showed urticaria which lasted from
one to seven days. All cases showed a well marked eosinophilia.
The diagnosis, but frequently only after prolonged and continued
search, was made by the finding of the lateral spined eggs of _S.
mansoni_. The period of incubation in these cases seemed to be from
one to three months.
Japanese Schistosomiasis
This is also called Katayama disease and in its early stages
urticarial fever or Yangtse fever. It is caused by the
nontuberculated species, _S. japonicum_, which is characterized by
the egg without a spine.
Laning, in a study of 7 well-controlled cases, has shown that the
disease sets in after two or three days from the time of exposure
to infection, by wading through paddy fields or still waters of
infected ponds or lakes. The disease occurs in China, Japan and
possibly in the Philippine Islands.
[Illustration: A B
FIG. 111.—A and B, Case of _Schistosoma japonicum_. Severe infection
of three years’ duration. Ova very abundant in stools. Liver dullness
diminished. Spleen not enlarged. (From Jefferys and Maxwell.)]
The course of the disease may be divided into 3 stages: the 1st, that
of urticarial, pulmonary and febrile manifestations, which lasts
about a month; the 2d, where ova begin to show in the small mass of
bloody mucus which may cap the stool, and finally the 3d stage with
cirrhosis of the liver, ascites, cachexia and death.
In the 1st stage we have headache and an evening rise of
temperature to about 101°F. or 102°F. Shortly after the onset
urticarial lesions, which may be 2 or 3 inches in diameter, may
appear and disappear on various parts of the body.
The pulse rate is usually low. Very characteristic and early
manifestations are those of the pulmonary involvement. Here
oedematous patches may give the signs of crepitation and
consolidation to rapidly disappear and reappear in another part of
the lungs.
These pulmonary manifestations and the associated fever frequently
cause a diagnosis of broncho-pneumonia to be made. A dry hacking
cough appears early and with the fever, etc., may make one think
of tuberculosis. The urticarial lesions often cause a diagnosis of
ptomaine poisoning to be made. The blood examination shows a marked
eosinophilia, of from 30 to 60%.
The 2d stage shows more or less intestinal disturbance with at times
bloody mucus containing ova. The ova may not be present for long
intervals or may never be found. Where reinfection does not take
place the patient tends to recover but if exposure to infection be
kept up then the 3d stage sets in with rather marked dysenteric
manifestations, emaciation, anaemia, ascites, dropsy and a terminal
cachexia.
The bladder never seems to be involved in Japanese schistosomiasis.
The eggs, however may be carried to the brain and produce symptoms
of Jacksonian epilepsy.
LABORATORY DIAGNOSIS
This consists in the search for ova in the centrifuged urine of
vesical bilharziasis or in the bloody mucus of the intestinal
manifestations of the disease. If one adds water to the urine the
ciliated embryo will be noticed to break out of the shell in a few
minutes and move about actively as if in search for some host.
The eosinophilia is of great diagnostic value and is usually
associated with an increase in the leucocyte count.
Fairley has introduced a complement fixation reaction in diagnosis,
using an extract of the livers of infected snails as antigen. The
reaction appears early in the infection but disappears in the later
stages. It is a group reaction as the livers of Bullinus answer for
the _S. mansoni_ serum as well as for the specific _S. haematobium_
serum.
PROPHYLAXIS
Bathing should be allowed only in filtered water, there being an
absence of the infecting cercariae in such a supply.
Then, too, if a water which does not contain fresh water snails is
stored for three or four days the cercariae which might have been
present in the freshly pumped up water will have died out, such
free cercariae only surviving for about this period. The gastric
juice will destroy cercariae so that it would seem impossible for
an infection to occur by the alimentary tract atrium with the
exception that cercariae might bore their way through the buccal
mucosa as well as through the skin. The sterilization of the urine
of cases of vesical bilharziasis and of the faeces in other forms
should be carried out where practicable. It is now considered
practicable to eradicate carriers of the infection with antimony
treatment.
TREATMENT
The most important matter is to avoid places where the infection is
known to exist. If one must wade through infected waters the body
should be protected by canvas or other closely woven garments.
Of various treatments, having in view the destruction of the worm,
such as salvarsan, etc., none seem to have been of any value except
antimony.
Robertson has reported relief of symptoms from the administration
of 2 grains of thymol dissolved in half a drachm of benzine. The
treatment is continued for a few weeks. Others have not had good
results from this treatment. Local treatment is necessary in
treating the cystitis and prolapse of rectum. Operative procedures
are indicated where calculi exist.
The results obtained by treatment with tartrate of antimony during
the past three years justify us in considering bilharziasis as a
disease which has a specific for its cure. Almost all cases will
yield to a course of intravenous injections of from one-half to two
grains of the drug, commencing with the smaller dose. The drug should
be well diluted (25 to 50 cc. sterile saline). Some use a 1% solution
but the higher dilutions are safer from a standpoint of avoiding
phlebitis. Intravenous injections are made twice weekly and the total
amount of drug given during the course should rarely exceed 25 to 30
grains. For details see under treatment of leishmaniasis.
CHAPTER XXIV
MINOR HELMINTHIC INFECTIONS
PARAGONIMIASIS
General Considerations
This is an infection with a trematode, _Paragonimus westermanni_ (_P.
ringeri_) (_Distoma pulmonale_). It is rather common in some parts of
Japan and Formosa.
[Illustration: FIG. 112.—_Paragonimus westermanni_: natural size; to
left showing ventral surface; to right showing dorsal surface. (Braun
after Katsuruda.) (From Tyson.)]
Arce has recently reported cases of paragonomiasis in three
Peruvians who had been in contact with Japanese immigrants.
In 1880, Baelz found the ova in the sputum of a case of haemoptysis
in a Japanese, as did also Manson in a Chinaman. Manson’s case
subsequently died and when autopsied showed in his lungs a fluke
which was responsible for the eggs seen by Manson. The fluke itself
is a little more than ⅓ of an inch (8 mm.) long and is almost round
on transverse section, there being, however, some flattening of
the ventral surface. The acetabulum is conspicuous and opens just
anterior to the middle of the ventral surface.
The branched testicles are posterior to the laterally placed uterus
and the genital pore opens below the acetabulum. The branched ovary
is opposite the uterus on the other side.
It is rather flesh-like in appearance and is covered with
scale-like spines. The flukes are usually found in tunnels in the
lungs, the walls of which are thickened connective tissue. These
tunnels result from hypertrophy of the bronchioles. There may be
also cysts formed from the breaking down of adjacent tunnel walls.
In addition to lung infection with this fluke, brain, liver and
intestinal infections may be found.
The life history and mode of infection of man, further than the
miracidium stage, has been unknown until recently. If the eggs in the
sputum are shaken up with water and the water renewed from time to
time a ciliated embryo or miracidium develops after a few weeks and,
at this time if one presses on a cover-glass covering some of these
more mature ova, the miracidium will break through the operculated
extremity of the egg and swim about actively in the surrounding
water.
[Illustration: FIG. 113.—Sputum of man containing eggs of the lung
fluke, greatly enlarged. (After Manson.)]
Nakagawa has found that the miracidia infest certain fresh water
molluscs and become cercariae in this first intermediate host. From
this host the cercariae go to certain fresh water crabs and encyst
in this second intermediate host, either in the liver or in the
gills. In Japan one of these crab hosts, _Potamon dehaanii_, is
eaten both raw and cooked.
[Illustration: FIG. 114.—_Paragonimus westermanni_; photograph from
a sexually immature specimen. (From Tyson.)]
Experimental feeding of puppies on infected crabs brought about
infection with the lung fluke. It is thought that the fluke, after
leaving the cyst, goes through the intestine to the abdominal
cavity. Thence it perforates the diaphragm and enters the pleural
cavity, finally penetrating the lung to become encysted there. The
lung is the favorite site but wandering flukes may invade other
tissues and organs even invading the central nervous system.
Besides man, dogs, cats and especially hogs may be infected.
Symptomatology, Diagnosis and Treatment
The case is usually considered as one of chronic bronchitis on
account of the occurrence of cough and morning expectoration of a
gelatinous sputum which is usually brownish. It is popularly known
as endemic haemoptysis for the reason that after violent exertion, or
at times without manifest reason, attacks of haemoptysis of varying
degrees of severity come on. The signs on percussion are usually
insignificant while those on auscultation at the time of haemoptysis
are often marked. The symptoms often disappear for months to again
reappear.
[Illustration: FIG. 115.—Anatomy of trematoda (flukes) of man. _O
S_, oesophageal sucker. _Ph_, pharynx. _Oes,_ oesophagus. _O P_,
genital pore. _V S_, ventral suckers or acetabulum. _Ut_, uterus.
_Int_, intestines. _Ov_, ovary. _Sh G_, shell gland. _T_, testicles.
_T G_, yolk glands or vitellaria. _Exc_, excretory pore.]
The course of the disease is very chronic, often lasting many
years. As a rule the patient is fairly well nourished although
recurring attacks of haemoptysis may bring on a rather marked
anaemia. Jacksonian epilepsy has been reported as occurring
in paragonomiasis, the ova being found in cysts of the brain.
There is some question as to whether some of the reports as to
paragonomiasis may not have been connected with infections with
Japanese schistosomiasis.
The diagnosis of endemic haemoptysis is readily made by finding the
operculated eggs in the more or less sanguinolent sputum. These eggs
are of a light yellow color and average 90 × 65 microns. One often
sees Charcot-Leyden crystals in the sputum.
As prophylactic measures we should forbid uncooked crabs or crayfish.
The sputum should be sterilized.
The treatment is entirely symptomatic.
[Illustration: FIG. 116.—Ova of _Clonorchis sinensis_. After Bell
and Sutton. (Jefferys and Maxwell.)]
CLONORCHIOSIS
This is an infection due to a trematode, _Clonorchis endemicus_
(_Opisthorchis sinensis_). It is also referred to as human liver
fluke disease. It is true that the common liver fluke of sheep,
_Fasciola hepatica_, may occur in man but such infections are rare,
only 23 cases having been reported. Another liver fluke of ruminants
is the lancet fluke, _Dicrocoelium lanceatum_, but it is also
unimportant for man, only 7 cases having been reported.
_Clonorchis_ infections are common in China and Japan, the fluke
being about ½ inch long by ⅛ inch wide. There is considerable
dispute as to whether we have a pathogenic and nonpathogenic
_Clonorchis_; the name _C. endemicus_ applying to the former and
_C. sinensis_ to the latter.
Looss considered the nonpathogenic _C. sinensis_ to be larger
(13-19 mm.), to show pigment in its parenchyma and to have breaks
in the vitelline glands. _C. endemicus_ was reported as smaller (10
to 13 mm.), and without pigment or breaks in the continuity of the
vitellaria.
The eggs of this fluke show slightly concave bending of the sides
at the operculated end and are about 30 × 16 microns. These flukes
are found within the thickened bile ducts and may be present in
great numbers. They may invade the pancreas as well as the liver.
These flukes are found in dogs and cats as well as man.
This fluke is supposed to produce most serious symptoms as
indigestion, swelling and tenderness of liver, bloody diarrhoea,
ascites, oedema and a fatal cachexia.
The course of the disease is insidious and chronic with periodic
improvement.
As a matter of fact, many physicians in China attribute very little
pathogenic importance to it. The disease is diagnosed by the presence
of the ova in the stools. The source of infection is probably through
the eating of uncooked fish.
[Illustration: FIG. 117.—_Clonorchis sinensis._ (Jefferys and
Maxwell.)]
Kobayashi has examined various molluscs and fish for trematode
larvae. He succeeded in infecting nine kittens and two cats by
feeding them with certain fresh water fishes whose flesh contained
trematode larvae. These fishes were found in districts where human
distomiasis was common.
Further experiments by Kobayashi have shown that the larval flukes
leave the cyst and start for the biliary passages. When the flukes
are very numerous the size is smaller. Maturity is reached in four
weeks. This investigator believes that the primary intermediate
host is a mollusc as cercariae found in these hosts are very
similar to the larval forms found in fish.
He does not consider that there are two species concerned in
_Clonorchis_ infections, as he has found variations in continuity
of vitellaria in small as well as large flukes. Number of parasites
present influences size. Age influences pigment production.
Another human fluke, _Opisthorchis felineus_, inhabits the gall
bladder and bile ducts of man and it is stated that the infection is
quite common in Siberia.
It is also a parasite of cats and dogs.
Both _Clonorchis_ and _Opisthorchis_ have the testicles in
the posterior end with the uterus anterior. The testicles of
_Clonorchis_ are branched (dendritic) while those of _Opisthorchis_
show as two lobes. In _Dicrocoelium_ the lobed testicles are
anterior to the uterus, which fills up the posterior end of the
fluke.
The mode of infection as well as the life history is not known but is
probably connected with the eating of raw fish.
The symptoms are similar to those caused by _C. endemicus_.
The fluke has two-lobed testicles as against the dendritic one of _C.
endemicus_.
INTESTINAL DISTOMIASIS
The most important intestinal fluke is undoubtedly _Fasciolopsis
buski_. It is now thought that this infection is more common than
was previously stated. Goddard states that more than 5% of stools
examined in Shaohing, China, show eggs of this parasite. It is a
very large fluke with an acetabulum 4 times the diameter of the oral
sucker. It is characterized by a very long and prominent cirrus.
_F. buski_ and _Fasciola hepatica_ are much alike in size and
outline. The acetabulum of the latter is only 1.6 times the
diameter of the oral sucker and the alimentary tract shows
branching which is best seen in the cone-shaped projection of its
anterior extremity. _F. hepatica_ is a liver fluke rarely found in
man.
_F. buski_ is found in China, Assam and India. It is a parasite of
hogs as well as man. The eggs measure from 80 to 120 microns, are
nearly colorless and have a thin shell with a very small operculum.
The symptoms are chiefly those of a chronic diarrhoea followed by
anaemia and wasting. The stool is light yellow in color, exceedingly
offensive and does not contain blood. Goddard thinks that they live
in the upper part of the small intestines.
The life history is unknown but Goddard states that fresh water
snails are much eaten by the people of Shaohing. Nakagawa notes that
the eggs of _Fasciolopsis_ hatch in two to three weeks. The miracidia
penetrate various species of snails in which the cercariae may encyst
and infect pigs eating such snails. The cercariae may also leave
the snail and encyst on blades of grass, to later infect an animal
feeding on the grass, this latter method of infection resembling that
of _Fasciola hepatica_.
Noc has reported success with treatment with thymol and Goddard with
beta-naphthol.
Other intestinal flukes such as _Cladorchis watsoni_, _Gastrodiscus
hominis_, _Heterophyes heterophyes_, and _Fascioletta ilocana_
are of less importance. _Heterophyes_ is probably a rather
common parasite but owing to its very small size (2 mm.) has been
generally overlooked at autopsy.
STRONGYLOIDES STERCORALIS
It was formerly supposed that a chronic form of diarrhoea in Cochin
China was due to an infection with the parthenogenetic female of
_Strongyloides stercoralis_. It is now known that the parasite is
widely distributed over the tropical and subtropical world and that
it rarely gives rise to manifest symptoms although some observers
regard it as capable of producing diarrhoea and more or less anaemia.
[Illustration: FIG. 118.—Ovum of _Fasciolopsis buski_. Bell and
Sutton. (Jefferys and Maxwell.)]
[Illustration: FIG. 119.—_Fasciolopsis buski._ Cleared in glycerin.
(From Jefferys and Maxwell.)]
It seems to be capable of setting up quite an eosinophilia at the
time the adult female is penetrating the crypts of Lieberkühn, so
that it is probably of pathogenic importance.
[Illustration: FIG. 120.—A, Egg of _Strongyloides intestinalis_
(parasitic mother worm) found in stools of case of chronic diarrhoea;
B, Rhabditiform larva of Strongyloides intestinalis from the stools.
(William Sydney Thayer, in Journal of Experimental Medicine.)]
The parasitic or intestinal form (also known as _Anguillula
intestinalis_) is represented only by females. These are about 1/12
of an inch (2 mm.) long and reproduce parthenogenetically. They have
a pointed, four-lipped mouth, and a filariform oesophagus which
extends along the anterior fourth of the body. The uterus contains
a row of 8 to 10 elliptical eggs which stand out prominently in the
posterior part of the body by reason of being almost as wide as the
parent worm.
They usually live deep in the mucosa and the embryos emerge from
the ova laid in the mucosa. The embryos escape from the eggs
while still in the intestines, so that in the faeces we only find
actively motile embryos. The eggs, which are strung out in a
chain, never appear in the faeces except during purgation. As they
greatly resemble hookworm eggs this is a point of great practical
importance.
In fresh faeces we find hookworm eggs and _Strongyloides_ embryos.
The embryos are rather common in stools in the tropics. These embryos
have pointed tails and are about 250 × 13 microns. They have a double
oesophageal bulb. They are about 250 microns when they first emerge
but may grow until they approximate 500 microns in the faeces. The
mouth cavity of the embryo of the hookworm is about as deep as the
diameter of the embryo at the posterior end of the mouth cavity; that
of _Strongyloides_ is only about one-half as deep as the diameter.
If the temperature is low, below 15°C., these rhabditiform embryos
develop into filariform embryos, which form the infecting stage.
It has been demonstrated by Fülleborn that infection of man takes
place through the skin. If the temperature is warm, 25° to 35°C.,
these embryos develop into the free-living form. In this we have
males and females, with double oesophageal bulbs, the male about
1/30 of an inch (¾ mm.) long with an incurved tail and 2 spicules
and the female about 1/25 inch (1 mm.) long with an attenuated
tail. These copulate and we have produced rhabditiform larvae,
which later change to filariform ones. At this time the length is
about 550 microns. These start up the parasitical generation.
For treatment thymol is usually recommended. Stiles speaks highly
of sulphur.
CHAPTER XXV
TABLE OF IMPORTANT ANIMAL PARASITE DISEASES
PROTOZOAL DISEASES
-----------------+--------+----------+-----------+-----------------------
Parasite | Defin. | Inter- | Important | Transmission and
| host | mediate | reservoir | pathogenicity
| | host | of virus |
-----------------+--------+----------+-----------+-----------------------
Entamoeba |Man. |Not |Man-carrier|Cysts in food or water.
histolytica. | | required.| stage | Flies may act as
| | | (feces). | carriers. Ingestive.
| | | | Amoebic dysentery.
-----------------+--------+----------+-----------+-----------------------
Balantidium coli.|Man |Not |Man-carrier|Transmission probably
| (hogs).| required.| stage | same as for E.
| | | (hogs). | histolytica. Found
| | | | in those having care
| | | | of hogs. Ingestive.
| | | | Balantidium dysentery.
| | | | Anaemia.
-----------------+--------+----------+-----------+-----------------------
Lamblia (Giardia)|Man |Not |Man-carrier|Transmission probably
intestinalis. | (mice | required.| stage | same as for E.
| and | | (mice and | histolytica. Rat
| rats). | | rats). | feces on human food
| | | | important. Ingestive.
| | | | Lamblia dysentery.
| | | | Giardiasis.
-----------------+--------+----------+-----------+-----------------------
Spiroschaudinnia |Louse |Man.(*) |Man |Cyclical development in
(Spironema) | (P. | | (blood). | louse. Bite puncture
recurrentis, | vesti- | | | contaminated by
carteri, etc. | menti).| | | crushed louse.
(louse group.) | | | | Relapsing fever.
-----------------+--------+----------+-----------+-----------------------
Spiroschaudinnia |Tick |Man.(*) |Man |Excretions of tick
(Spironema) |(species| | (blood). | contaminating
duttoni, novyi. |of | | | tick-bite. Tick
(Tick group.) |Ornith- | | | fevers. Relapsing
|dorus or| | | fever.
|Argas). | | |
-----------------+--------+----------+-----------+-----------------------
Treponema |Man. |Not |Man. |T. pallidum. Usually
(pallidum and | | required.| | venereal. Syphilis.
pertenue). | | | | T. pertenue. Flies or
| | | | contact. Yaws.
-----------------+--------+----------+-----------+-----------------------
Leptospira |Man |Not |Rat. |Common infection of
ictero- | (rat). | required.| | rats. Present in
haemorrhagiae. | | | | blood. Excreted in
| | | | urine. Ingestion.
| | | | Weil’s disease.
-----------------+--------+----------+-----------+-----------------------
Leptospira |Mosquito|Man. |Man |Cyclical development
icteroides. |(Stego- | | (blood). | in mosquito--12
|myia | | | days. Inoculative.
|calopus)| | | Yellow fever.
-----------------+--------+----------+-----------+-----------------------
PROTOZOAL DISEASES (Continued)
-----------------+--------+----------+-----------+-----------------------
Parasite | Defin. | Inter- |Important | Transmission and
| host | mediate |reservoir | pathogenicity
| | host |of virus |
-----------------+--------+----------+-----------+-----------------------
Leptospira |Man |Not |Rat. |Man inoculated by
morsus-muris. | (rat). | required.| | bite of infected rat.
| | | | Rat bite fever.
-----------------+--------+----------+-----------+-----------------------
Trypanosoma |Fly |Man. |Man--game |Cyclical development
gambiense |(Glossina| | animals? | in tsetse fly.
and rhodesiense.|species)| | (blood). | Inoculative. Sleeping
| | | | sickness.
-----------------+--------+----------+-----------+-----------------------
Schizotrypanum |Lamus |Man. |Man. |Cyclical development
cruzi. |megistus| | | in bug. Inoculative.
| | | | Brazilian
| | | | trypanosomiasis.
-----------------+--------+----------+-----------+-----------------------
Leishmania |Not |Man. |Man. |L. donovani—Bed bug?
(donovani, | surely | | | kala-azar. L. infantum
infantum, and | known. | | | —dog flea? infantile
tropica). | | | | leishmaniasis. L.
| | | | tropicum--biting
| | | | insects? Oriental
| | | | sore; American
| | | | leishmaniasis.
-----------------+--------+----------+-----------+-----------------------
Plasmodium |Mosquito|Man (with |Man (blood)|Cyclical development
malariae, |(Anoph- | schiz- | (with | in mosquito—12
vivax and | eline | onts). | gametes). | days. Inoculative.
falciparum. |species)| | | Malaria.
-----------------+--------+----------+-----------+-----------------------
Rickettsia |Man. |Louse (P. |Man (blood)|Cyclical development in
prowazeki. | | vesti- | | louse. Bite puncture
| | menti). | | inoculated by
| | | | louse feces. Typhus
| | | | fever.
-----------------+--------+----------+-----------+-----------------------
Dermacentroxenus |Man |Tick |Goats and |Excretions of tick
rickettsi. |(goats, |(Dermacen-| rodents. | contaminating
|rodents,|tor ander-| | tick-bite. Rocky
| etc.). |soni). D. | | Mountain fever.
| | venustus.| |
-----------------+--------+----------+-----------+-----------------------
Bartonella |Man. |Unknown. |Man (blood)|Transmission unknown.
bacilliformis. | | | | Species of
| | | | Phlebotomus suggested.
| | | | Oroya fever.
-----------------+--------+----------+-----------+-----------------------
NOTE.—(*) Some authorities give man as definitive host of
Spiroschaudinnia (Spironema). Diseases often classified as filterable
virus ones of protozoal affinity are (1) Dengue. Cause unknown.
Transmitted by Stegomyia species. (2) Pappataci fever. Cause unknown.
Transmitted by Phlebotomus species. Other protozoal diseases are (1)
Tsutsugamushi. Probably a protozoan. Transmitted by Kedani mite. (2)
Trench fever. Probably Rickettsia. Transmitted by louse.
HELMINTHIC DISEASES—TREMATODES
-------------+--------+-------------+-----------+-----------------------
Parasite | Defin. |Intermediate |Important | Transmission and
| host | host |reservoir | pathogenicity
| | |of virus |
-------------+--------+-------------+-----------+-----------------------
Clonorchis |Man |1st, snail |Man. |Not definitely known.
sinensis. | (cats, | (Melania | | Eating raw fish.
|dogs and| libertina)? | | Ingestive. Human liver
| hogs). | and 2d, fish| | fluke disease.
-------------+--------+-------------+-----------+-----------------------
Opisthorchis |Man |1st, mollusc.|Cats and |Man infected by eating
felineus. | (cats | 2d, fish. | dogs. | raw fish. Ingestive.
| and | | | Liver fluke
| dogs). | | | disease.
-------------+--------+-------------+-----------+-----------------------
Fasciolopsis |Man |Possibly 1st,|Hog. |Not definitely known.
buski. | (pig). | mollusc. | | Intestinal
| | Cercariae | | Distomiasis.
| | encyst on | |
| | grass. | |
-------------+--------+-------------+-----------+-----------------------
Heterophyes |Man |1st, probably|Dogs and |Not definitely known.
heterophyes.| (dogs | mollusc. | cats. | Intestinal Distomiasis.
| and | 2d, probably| |
| cats). | fish. | |
-------------+--------+-------------+-----------+-----------------------
Paragonimus |Man |1st, snail. |Cats, dogs |Eating raw crabs
ringeri. | (dogs, | 2d, crab. | and hogs. | containing cercariae.
|cats and| | | Ingestive. Lung fluke
| hogs). | | | disease.
-------------+--------+-------------+-----------+-----------------------
Schistosoma |Man. |Snail |Man |Bathing or drinking
haematobium.| | (Bullinus). | (urine). | water containing
| | | | cercariae. Penetrative.
| | | | Vesical bilharziasis.
-------------+--------+-------------+-----------+-----------------------
Schistosoma |Man. |Snail |Man (feces)|Bathing or drinking
mansoni. | | (Planorbis).| | water containing
| | | | cercariae. Penetrative.
| | | | Rectal bilharziasis.
-------------+--------+-------------+-----------+-----------------------
Schistosoma |Man. |Snail |Man (feces)|Bathing or drinking
japonicum. | |(Blanifordia)| domesticated | water containing
| | | animals). | cercariae. Penetrative.
| | | | Katayama disease.
-------------+--------+-------------+-----------+-----------------------
NOTE.—Rare trematodes of man are (1) Fasciola hepatica. Chiefly
disease of sheep. Cercariae from snail (Limnea) encyst on grass.
(2) Dicrocoelium lanceatum. Chiefly disease of cattle. (3)
Heterophyes nocens. A very small intestinal fluke of man. (4)
Metagonimus yokogawai. Another very small intestinal fluke of man.
Intermediate hosts: mollusc and gold fish. (5) Echinostoma ilocanum.
A rare intestinal fluke of the Philippines. (6) Two genera of
Paramphistomidae—Cladorchis and Gastrodiscus. Intestinal flukes.
HELMINTHIC DISEASES (Continued). NEMATODES
-------------+--------+-------------+-----------+------------------------
Parasite | Defin. |Intermediate |Important | Transmission and
| host | host |reservoir | pathogenicity
| | |of virus |
-------------+--------+-------------+-----------+------------------------
Filaria |Man. |Mosquito |Man |Indirect in mosquito.
bancrofti. | | (various | infected | Mature larva
| | species). | (blood). | penetrates skin.
| | | | Elephantiasis, etc.
-------------+--------+-------------+-----------+------------------------
Loa loa |Man. |Fly. Species |Man |Probably indirect
(F. loa). | | of Chrysops | infected | (cyclical) in Chrysops.
| | (mangrove | (blood). | Probably inoculative.
| | flies). | | Ocular filariasis, etc.
-------------+--------+-------------+-----------+------------------------
Acantho- |Man. |Not |Man |Transmission by
cheilonema | | definitely | infected | mosquitoes and ticks
perstans (F.| | known. | (blood). | suggested. No
perstans). | | | | pathogenicity.
-------------+--------+-------------+-----------+------------------------
Dracunculus |Man. |Species of |Man |Larvae enter cyclops.
medinensis. | | cyclops. | infected | Infected cyclops in
| | | (subcuta- | drinking water.
| | | neous | Ingestive. Guinea
| | | tissue). | worm infection.
-------------+--------+-------------+-----------+------------------------
Onchocerca |Man. |Not |Man |Possibly Glossina.
volvulus (F.| | definitely | (blood?). | Subcutaneous tumor
volvulus). | | known. | | and lymphangitis.
-------------+--------+-------------+-----------+------------------------
Strongyloides|Man. |Not required.|Man (feces)|Parasitic filariform
stercoralis.| | | | larva penetrates skin.
| | | | Pathogenicity doubtful.
-------------+--------+-------------+-----------+------------------------
Necator |Man. |Not required.|Man (feces)|Encysted strongyloid
americanus | | | | larvae penetrate skin.
and | | | | Ancylostomiasis.
Ancylostoma | | | |
duodenale. | | | |
-------------+--------+-------------+-----------+------------------------
Trichinella |Man (rat|Hog (man and |Hog |Encysted larva in raw
spiralis. | and | rat). | (muscle). | or insufficiently
| hog). | | | cooked pork. Ingestive.
| | | | Trichinosis.
-------------+--------+-------------+-----------+------------------------
NOTE.—Ascaris, Trichuris and Oxyuris do not require intermediate
host. With Ascaris and Trichuris, larva gradually develops in egg
passed in faeces. Infection by ingestion of embryo-containing eggs.
Embryo-containing eggs contaminate fingers from crushing female
Oxyuris in perineal region.
HELMINTHIC DISEASES. CESTODES
-------------+--------+-------------+-----------+-----------------------
Parasite | Defin. |Intermediate |Important | Transmission and
| host | host |reservoir | pathogenicity
| | |of virus |
-------------+--------+-------------+-----------+-----------------------
Dibothrio- |Man. |1st, cyclops?|Man |Eating raw fish
cephalus | | 2d, fish. | (feces), | containing pleocercoid
latus. | | | dog and | larvae. Broad Russian
| | | cats. | tapeworm disease.
-------------+--------+-------------+-----------+-----------------------
Hymenolepis |Man. |Not required.|Children |Man intermediate and
nana. | | | (feces). | definitive host.
| | | | Ingestive. Dwarf
| | | | tapeworm disease.
-------------+--------+-------------+-----------+-----------------------
Taenia |Man. |Cattle (ox). |Man (feces)|Eating insufficiently
saginata. | | | | cooked beef containing
| | | | cysticerci. Ingestive.
| | | | Beef tapeworm
| | | | disease.
-------------+--------+-------------+-----------+-----------------------
Taenia |Man. |Hog. |Man (feces)|Eating insufficiently
solium. | | | | cooked pork containing
| | | | cysticerci. Ingestion.
| | | | Pork tapeworm
| | | | disease.
-------------+--------+-------------+-----------+-----------------------
Taenia |Dog. |Man, sheep |Dog (feces)|Dogs infected at
echinococcus.| | and hogs. | | abattoir. Hydatid
| | | | disease.
-------------+--------+-------------+-----------+-----------------------
NOTE.—Rare cestodes of man are (1) Dipylidium caninum. A parasite
of the dog with louse or flea as intermediate host. (2) Hymenolepis
diminuta. A parasite of rats. Intermediate host in insects. (3)
Species of Davainea. Intermediate host possibly cockroach. These
cestodes are probably accidental parasites of man.
ARTHROPODAN DISEASES
--------------+---------------------------+------------------------------
Parasite | Life history | Disease and manifestations
| | and remarks
--------------+---------------------------+------------------------------
Linguatula |Adult in nasal cavity of |Porocephaliasis. Man may
serrata | dogs, etc. Eggs in nasal | harbor adult or larva. Larvae
(Lingua- | mucus contaminate grass. | usually in lungs or liver
tulidae). | Rabbits, cattle infected. | and do not seem to cause
| Larvae in liver, lungs. | symptoms.
--------------+---------------------------+------------------------------
Porocephalus |Adults in lungs of snakes. |Porocephaliasis. Larvae wander
armillatus | Eggs contaminate water | in abdominal cavity or lungs
(Lingua- | or food. Larvae in liver, | in which latter they produce
tulidae). | lungs, etc., of lions, | a chronic bronchitis which
| monkeys, man, etc. | may resemble phthisis.
--------------+---------------------------+------------------------------
Demodex |All stages passed within |Demodectic acariasis. Causes a
folliculorum | hair follicles or | resistant itch in dogs. In
(Demodicidae).| sebaceous cysts especially| man, may invade eyelids or
| about nose. Adult may | meibomian glands, and has
| wander. | been reported as causing
| | various forms of dermatitis.
--------------+---------------------------+------------------------------
Sarcoptes |Female lives in burrow of |Scabies. Burrows show as
scabei | skin giving off eggs which| blackish lines, especially
(Sarcoptidae).| hatch into larvae. | between fingers, flexor
| | surfaces of arms and penis.
| | Itching worse at night.
--------------+---------------------------+------------------------------
Pediculoides |Female lives on wheat straw|Grain itch. The mites leave
ventricosus | worm or grain moth. Larval| wheat straw or grain and
(Tarson- | mites develop inside | attack harvesters or those
emidae). | mother. | sleeping on straw mattresses.
| | Attack upper trunk, neck and
| | arms. Erythematous or
| | vesicular eruption with
| | constitutional symptoms.
---------------+--------------------------+------------------------------
Microtrombidium|Adults live in fields or |Autumnal erythema. The larval
pusillum | woods. The larval mite | mites known as red bug or
(Trombidoidae).| lives on grasshoppers or | jigger attack man causing a
| small rodents. | severe itch.
---------------+--------------------------+------------------------------
Dermanyssus |Mites live in chicken |Poultryman’s itch. The mites
gallinae | houses and feed on fowls. | attack man producing
(Gamasidae). | | eczematous dermatitis on
| | backs of hands and forearms.
--------------+---------------------------+------------------------------
Dermacentor |Adults live on cattle, |Tick paralysis. The bite of
venustus | sheep, etc. May bite man. |this tick or Ixodes holocyclus
(Ixodidae). | | may produce paralysis in
| | sheep. An ascending type of
| | paralysis due to tick bites
| | has been several times noted
| | in man, chiefly in children.
--------------+---------------------------+------------------------------
Pediculus |Adults live on clothing or |Pediculosis—Phthiriasis.
humanus | hair and feed on man. | Produce skin irritation with
(Insecta, | | later on pigmentation
Pediculidae).| | (Vagabondismus).
--------------+---------------------------+------------------------------
Dermatophilus |Impregnated female |Sandflea or chigoe
penetrans. | penetrates skin of man or | infestation. Site of penetr-
(Sarco- | animals, especially toes | ation shows as black spot
psyllidae). | and feet. | with whitish induration
| | surrounding it. Apt to form
| | ulcers.
--------------+---------------------------+------------------------------
ARTHROPODAN DISEASES (Continued)
--------------+---------------------------+------------------------------
Parasite | Life history | Disease and manifestations
| | and remarks
--------------+---------------------------+------------------------------
Dermatobia |Eggs of fly become attached|A cutaneous myiasis. Larva at
cyaniventris | to mosquitoes or ticks. | first club shaped (ver
(Oestridae: | These latter bite man and | macaque), later worm shaped
Bot Flies). | larva penetrates skin. | (torcel). Larva causes a
| | swelling with black opening.
| | May invade eye.
--------------+---------------------------+------------------------------
Hypoderma |Larvae of this or other |Creeping eruption. Larva
lineata | flies burrow under skin. | migrans. The burrows make
(Oestridae). | | zig-zag lines on face or
| | soles of feet. Causes
| | itching.
--------------+---------------------------+------------------------------
Chrysomyia |Fly deposits eggs in |Screw worm infection. Nasal
macellaria, | nostrils. Larvae wander to| myiasis. Larvae in their
and C. dux | nasal sinuses. May invade | wandering destroy tissues of
Muscidae). | aural canal. | nasal cavities, or of ear,
Oestrus ovis | | and may cause death. May
(Oestridae). | | infest wounds or vagina. C.
| | macellaria causes American
| | nasal myiasis, C. dux causes
| | Indian nasal myiasis and O.
| | ovis causes African nasal
| | myiasis.
--------------+---------------------------+------------------------------
Ochromyia |An African fly, which |Larvae bore under skin,
(Cordylobia) | deposits eggs on children | causing boil-like lesions
anthropophaga| and animals. | with central opening. Larvae
(Muscidae). | | mature in two weeks.
--------------+---------------------------+------------------------------
Auchmeromyia |An African fly deposits |Congo floor maggot. The bite
luteola | eggs on floors of native | is not painful.
(Muscidae). | huts. Larvae bite man. |
--------------+---------------------------+------------------------------
Calliphora |Blow and bluebottle flies, |Larvae may be cause of obscure
vomitoria | depositing eggs on tainted| abdominal conditions; may be
and Lucilia | meats. Larvae may be found| found in nasal cavities,
caesar and L.| in feces. | causing serious symptoms, or
serricata | | in ear.
(Muscidae). | |
--------------+---------------------------+------------------------------
Musca |Eggs presumably deposited |Larvae have been found in male
domestica | near genitalia or ear. | urethra and in the ear.
(Muscidae). | |
--------------+---------------------------+------------------------------
Sarcophaga |Viviparous. Larvae are |Larvae gain access to wounds,
carnaria | deposited on decaying | nasal cavities, etc., at
(Sarcoph- | flesh (wounds, orifices | times causing death. Commonly
agidae). | of body). | found in intestinal myiases.
| | May occur in vagina.
--------------+---------------------------+------------------------------
Anthomyia |Larvae deposited in body |Occasionally reported as found
pluvialis | orifices. | in ear.
(Anthomyidae).| |
--------------+---------------------------+------------------------------
Fannia |Eggs deposited near |Symptoms of urinary irritation
canicularis | external genitalia and | or obstruction. Has been
(Anthomyidae).| larva penetrates urethra. | found in gastro-intestinal
| | tract.
--------------+---------------------------+------------------------------
SECTION V
INFECTIOUS GRANULOMATA OF THE TROPICS
CHAPTER XXVI
YAWS OR FRAMBOESIA
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—Some authorities think that a disease described by the
Arabian physicians of the 10th century was yaws, but the first
description of what was undoubtedly yaws was that of Oviedo, who in
the 16th century described such an affection as existing in the West
Indies. Bontius, later on, noted the existence of the disease in the
East Indies as well as in the West Indies.
It is known that yaws often occurred in epidemic form on board the
slave ships and it is thought that this disease may have been an
African importation into the new world.
=Geographical Distribution.=—Yaws is essentially a disease of
tropical regions.
In Africa it is very prevalent in the equatorial region, especially
in the Congo Free State. It is also found more rarely in Tripoli
and Algiers and to a less extent in the Sudan region. It is common
in the West Indies and tropical America.
In Asia it is very prevalent in the Malay Peninsula, Siam, the East
Indian Islands and in the Philippines. It does not exist in Japan.
In many of the islands of the Pacific it is exceedingly prevalent,
particularly in Samoa. It is also present in Northern Australia.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—In view of the fact that many great authorities,
especially J. Hutchinson, insisted upon the syphilitic nature of
yaws it was a matter of great interest when Castellani, in 1905,
discovered the causative organism which is characterized by the same
sharp-cut, corkscrew spirals that are noted with the syphilitic
spirochaete discovered by Schaudinn in the same year. _Treponema
pertenue_ is found in the epidermis of the yaws granuloma and has
been demonstrated in lymphatic glands and spleen. Although it has not
been demonstrated in the blood, through microscopical examination, it
must exist there as monkeys infected with the blood of yaws patients
develop the lesions of yaws in which the spirochaetes are present.
Another name for the organism is _Spirochaeta pallidula_; this
however is only a synonym.
Inoculation experiments as well as clinical manifestations show
yaws and syphilis to be distinct. Thus Charlouis, in 1881,
inoculated a native suffering from typical yaws wistations
of syphilis followed. There have been many instances of the
development of yaws, naturally and by inoculation, in those
affected with syphilis. Nichols has shown that a rabbit which had
been infected intratesticularly with _T. pallidum_ and then cured
by salvarsan did not show immunity to _T. pertenue_ when the latter
was used to infect the testicle.
In the monkey inoculation over the eyebrow gives a flat dry and
scaly lesion with syphilitic material while yaws inoculation gives
a softer, more oedematous one.
Levaditi and Nattan Larrier have noted that monkeys which had been
inoculated with syphilis were immune to yaws inoculation but yaws
monkeys could be infected with syphilis, thus indicating that yaws
was a mild form of syphilis. In Guam, it has recently been shown
that 68% of cases of gangosa, a disease supposed to be a tertiary
form of yaws, give a positive luetin reaction. This would indicate
a close relationship between yaws and syphilis.
Salvarsan is more specific for yaws than it is for syphilis and the
percentage of positive Wassermann tests is as great in yaws as in
syphilis.
Notwithstanding the above points, which would indicate a close
relationship, all authorities are now agreed that clinical and
pathological evidence show the two diseases to be separate entities.
=Epidemiology.=—Charlouis inoculated 32 Chinese prisoners with
scrapings from yaws lesions. The disease developed in 28 of them,
first showing itself at the site of inoculation.
Paulet inoculated 14 negroes with yaws material and after a period
of incubation of from twelve to twenty days a primary lesion
appeared, to be followed by the generalized eruption. In naturally
acquired yaws the period of incubation is from three to six
weeks. These experiments are in line with the known fact that any
skin abrasion which comes in contact with a yaws lesion becomes
infected, as when the mother nurses an infant with lesions on its
face and develops a yaws lesion at the site of some fissure about
the nipple.
Yaws shows a striking limitation to the tropics and in a disease so
communicable by direct contact it seems remarkable that it does not
spread from the occasional case introduced into temperate regions.
In the tropical world it seems limited to low level areas. Another
feature of yaws epidemiology is the vastly greater susceptibility
of colored races, even those of mixed white blood showing a certain
degree of immunity.
All evidence is against a congenital form of yaws.
In particular are flies important factors in the transmission of the
disease, transferring the secretions from yaws lesions to abrasions
or ulcers on the skin of healthy persons.
The greater the attention to personal hygiene the less probable is
the spread of yaws, so that Europeans are rarely infected while the
disease may be prevalent in the native population.
In countries where it is prevalent it is chiefly a disease of
children, the adults possessing immunity as the result of attacks
in childhood.
PATHOLOGY
The primary yaws lesion is histologically the same as the lesions of
the generalized eruption of the second stage. In these lesions we
fail to find the endothelial proliferations and perivascular round
cell infiltrations so characteristic of syphilis. There is great
thickening of the interpapillary pegs of the epidermis which dip down
deeply into the corium. Areas are noted in the epithelium containing
swollen degenerated epithelial cells, polymorphonuclears and granular
débris. There is marked oedema in the corium with dilatation of the
blood vessels and lymphatics.
There is less oedema of the corium in yaws than in a syphilitic
condyloma thus accounting for the greater dryness of the former. The
main point in the pathology of a yaws lesion is the predominating
involvement of the epidermis and the comparatively slight change in
the corium.
In a Levaditi-stained specimen the spirochaetes are found in the
epidermal layers instead of in the corium as with syphilis.
The visceral organs and central nervous system are not affected
although Harper has reported cases of tabes and general paresis in
Fijians following yaws. He excludes syphilis.
SYMPTOMATOLOGY
It is usual to consider the clinical course of yaws as exhibiting
two stages, the primary one, which comes on from 2 to 5 weeks after
introduction of the virus and is characterized by a papular initial
lesion, which later shows the fungoid appearance of a typical yaws
tubercle, and the secondary stage in which yaws lesions similar to
the initial one develop as a generalized eruption.
Some authorities recognize a tertiary stage in which gumma-like
nodules, with subsequent ulceration, appear. There is much evidence
to indicate that a destructive ulceration of the nasopharyngeal
region, in natives of Guam, is a tertiary manifestation of yaws.
[Illustration: FIG. 121.—Yaws. This case shows an abundance of
yaws tubercles on face. Distribution on trunk and extremities less
extensive. (From Ruge and zur Verth.)]
_The Primary Stage_.—During a period of incubation, averaging three
weeks, vague digestive troubles, nocturnal headache, joint pains
and an irregular fever may be noted which often abate upon the
appearance of the initial papule at the site of inoculation. There
may be enlargement and tenderness of the lymphatic glands about the
time of the appearance of the eruption. This initial lesion may be
single or there may be several papules grouped together. In some
cases it may be impossible to get any history of a primary lesion or
it may have been overlooked. The primary lesion is almost invariably
extra-genital and it has the same appearance as the lesions of the
secondary stage, thus differing from syphilis.
[Illustration: FIG. 122.—Child with yaws. (From U. S. Naval Medical
Bulletin.)]
The yaws lesion, whether primary or secondary, starts as a papule
which in a few days enlarges to the size of a small pea. It is
conical and surrounded by an inflammatory areola. At this time the
thickened epidermis begins to crack and a yellowish sero-purulent
fluid exudes from the underlying fungoid base. They bleed easily
but are not painful. It is this fungoid yellowish or yellowish-red
tubercle which has been thought to resemble a raspberry, hence
the name framboesia. French authors liken it to a fig which has
been turned inside out. The moist or crusting surface soon shows
an underlying ulcer, which may dry up leaving a pigmented spot or
become exuberant and appear as a mass of fungating granulations, 1
to 2 inches in diameter. Such lesions are given the name “mother
yaw.”
_The Secondary Stage_.—In from six weeks to three months after the
appearance of the initial lesion, which may have dried up and left
only a scar, or which more commonly is still present, there again set
in malaise, headache and joint pains with an irregular inconstant
fever.
The secondary eruption is made up of lesions having the same
character and course as the primary yaws tubercle. In the general
eruption, the papules appear frequently in the region of the
junction of skin and mucous membrane as about mouth, nose and anus.
In such regions they may become very moist and resemble the mucous
patches of syphilis.
Besides their location on face and about the perineal region they
are numerous on neck, arms, legs, and buttocks. They are rare on
the trunk and scalp.
In their ordinary locations the yaws tubercles are not painful
unless pressed firmly but when located on the palms of the hands or
soles of the feet the thick skin of these regions exerts pressure
so that in such situations the lesions are painful.
In this stage yaws does not involve mucous membranes or affect the
viscera.
The secondary stage lasts from 3 or 4 months to 2 or 3 years, the
yaws tubercles coming out in successive crops in long standing
cases.
_The Tertiary Stage_.—Daniels noted in the Fiji Islands destructive
lesions of the naso-pharyngeal region which he thought might be
associated with a preceding yaws attack. He noted cutaneous lesions
which resembled lupus vulgaris. Boissiere has noted not only the
nasopharyngeal lesions and lupus-vulgaris-like ones but also tibial
involvement, joint swellings and dactylitis.
Numa Rat describes various tertiary manifestations. There may
be subcutaneous nodules about ankle or leg which soften and may
produce bone lesions and deformities. He notes destructive lesions
of nares, pharynx and palate which may set in years after an
attack of yaws. His description of the process starting as an
ozoena or sore throat followed by destruction of the uvula, velum
palati and septum nasi is much like gangosa. Howard has noted the
greater frequency of destructive lesions of the nasopharynx in
those parts of Africa where yaws is prevalent than in parts where
syphilis prevails.
[Illustration: FIG. 123.—Tertiary jaws, “Gomma”. (Johns Hopkins
Bull., Moss and Bigelow.)]
According to Castellani the characteristic lesions of tertiary yaws
are gummatous nodules and deep ulcerations. Such ulcerations may
give rise to contractures.
In Guam the view now prevails that the condition known as gangosa
is a form of tertiary yaws.
Other than a moderate anaemia there is very little in the blood of
yaws which differs from the normal.
_Peculiar Types of Yaws_.—When yaws tubercles develop in the
palms of the hands or soles of the feet we have a very painful
and incapacitating condition resulting. The pressure of the thick
unyielding epidermis on the tubercles beneath gives rise to marked
pain, thus differing from tubercles on other parts of the body.
Eventually these tubercles break through and the affected sole may
have a worm-eaten appearance. The name “crab yaws” is a common
one for such a condition involving the soles of the feet and is
so-called from the difficulty in walking which has a resemblance
to the locomotion of a crab. In some cases the yaws tubercles
adjoin one another to form a circle enclosing unaffected skin. Such
an arrangement of lesions is often described under the name of
“ringworm yaws.”
[Illustration: FIG. 124.—Tertiary yaws. Clavus or Crab-yaws. (Johns
Hopkins Bull., Moss and Bigelow.)]
DIAGNOSIS
=Clinical Diagnosis.=—Bromide eruptions may greatly resemble yaws
but the history of the taking of the drug and the effect upon
withdrawal should differentiate.
_Syphilis and Yaws._—Degorce gives a very complete table of the
points of difference between syphilis and yaws, some of the more
important of which are the following:
YAWS
1. Primary lesion of soft consistency, or very little infiltrated,
with granulating or pimply surface, situated almost invariably
extragenitally, resembling the secondary lesions. Lymphadenitis not
marked.
2. Roseola resembling that of syphilis but rarer.
3. Secondary cutaneous lesions at first in the form of conical
elevations of a light red color, not infiltrated at base, appearing
in close groups. The lesions are similar to those of syphilis,
namely, on the scalp in the form of encrusted papules; on
thin-skinned regions in the form of ulcerating papules, and in the
case of the palm of the hands and plantar surface of the feet, in
the form of simple papules.
4. Circinate lesions with the edges more raised than in syphilis,
covered with yellow crusts.
5. On the face lesions of the same type, but more striking and with
irregular projections.
6. Cutaneous lesions do not itch.
7. Perionychia similar to that of syphilis, but occasionally giving
rise to pimply lesions.
8. Alopecia has not been described.
9. Lesions in the buccal and pharyngeal mucosa often absent. No
erythema. No typical mucous patches. Sometimes fissures at the
angles of the mouth. The typical lesions are raised, pure white and
occasionally covered with intact epithelium.
10. Lesions with prominent edges or even pustular with yellowish
crusts, occasionally also ulcerations resembling mucous patches.
11. Similar condylomata, but larger and more raised.
SYPHILIS
1. Primary lesion infiltrated and indurated, with flat and
smooth surface, ordinarily situated on the genital organs; often
accompanied by abundant lymphadenitis. Phagedenic processes
frequent.
2. Roseola present.
3. Secondary cutaneous lesions papular from the first, dark red,
infiltrated and fairly regularly scattered.
4. Circinate lesions with pink edges, slightly raised, with fine
scales.
5. Seborrheic syphilides on the face.
6. Cutaneous lesions do not itch.
7. Perionychia present.
8. In syphilis, alopecia rather the exception.
9. Lesions in the buccal and pharyngeal mucosa are not numerous
and are slight in degree. Erythema of the soft palate and pharynx
occurs. Mucous patches. Ulcers of the lips and at the angles of the
mouth.
10. In the glans, prepuce or vulva, the lesions are more or less
typical mucous patches.
11. Moist condylomata at the margin of the anus.
The authorities generally discuss extensively the points of
distinction between yaws and syphilis. This is probably more
connected with possible relationship than practical importance in
diagnosis.
=Laboratory Diagnosis.=—The staining of the juice from yaws
tubercles by the India ink method or with Giemsa’s stain is the usual
procedure.
Baermann gives the percentage of positive Wassermann reactions in
untreated, clinically positive cases, as 80 to 100%; in treated
cases, 50%, and in the latent ones as from 35 to 40%. In an
examination of the serum of 281 cases of gangosa, Halton obtained
37.3% positive Wassermann reactions. Kerr found that 73.8% of 2,429
natives of Guam had had yaws, usually in childhood.
Among other diseases which may be confused with yaws, particularly
as regards the nasopharyngeal ulcerations of tertiary yaws, may be
mentioned American cutaneous leishmaniasis. The differentiation
rests in finding _Leishmania tropica_ in such lesions.
Sections from a yaws tubercle treated and sectioned according
to Levaditi’s method show the treponemata in the region of the
thickened interpapillary pegs of the epidermis.
PROGNOSIS
This is almost entirely favorable as regards danger to life. The
death rate is approximately ½ of 1% and such fatalities generally
occur in young children in whom secondary infections develop on the
site of the ulcerating yaws lesions.
PROPHYLAXIS AND TREATMENT
=Prophylaxis.=—Daniels thinks the frequency of infection about the
angles of the mouth, which frequently show fissures, is explained by
the exchange of particles of food or other substances by children,
thus transferring the infection.
Of course care should be taken to prevent articles of clothing
contaminated with yaws discharges from acting as infecting agents.
The main point in prophylaxis is to prevent flies from having
access to abrasions on the skin, so that all cuts or sores should
be protected by dressings. The sound skin is a barrier to infection.
=Treatment.=—It can certainly be stated that in salvarsan we have an
absolute specific for yaws, the results which obtain in a few days
being almost miraculous when one considers the protracted normal
course of the disease.
The drug is given intravenously although neosalvarsan
intramuscularly is more convenient for those not prepared to give
intravenous injections.
The methods of administration are exactly as for the treatment of
syphilis. The drug gives best results when used early in the course
of the disease.
Doses of 0.4 gram of salvarsan usually suffice and frequently
one dose effects a cure. The dose for women, children and thin
individuals should be less than for strong adult men. Atoxyl does
not seem to be effective in yaws. In other words the methods of
treatment are the same for the two treponemata, except that the
effect of salvarsan may be termed specific for yaws and less so
for syphilis. Bergen found that about 4% of cases treated with
salvarsan or neosalvarsan relapsed. The average time to effect a
cure was eleven days.
Many of the older writers have reported the value of mercury in the
treatment of yaws but the present view is that this drug has very
little if any place in the therapy of the disease. Potassium iodide
does seem to be a very useful drug in the absence of opportunity
for obtaining some arsphenamine product. Where the specific remedy
cannot be secured the next best treatment is Castellani’s yaws
mixture. The formula for the preparation is the following:
Tartar emetic one grain (0.06 gm.)
Potassium iodide twenty grains (1.3 gms.)
Sodium salicylate ten grains (0.6 gm.)
Sodium bicarbonate fifteen grains (1 gm.)
Chloroform water and syrup one ounce (30 cc.)
The above is a single dose and it is given well diluted about three
times daily. This treatment is continued for about a week and after
an interval of another week is resumed according to the response
to such treatment. In children between seven and fifteen years the
dose is reduced one-half and for younger children correspondingly.
It would seem well to start treatment with a smaller dosage than
the standard one, being guided by the ability of the patient to
stand an increase in the dose of the drugs.
For local treatment use antiseptic dusting powders as iodoform or
boric acid.
CHAPTER XXVII
GANGOSA
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—It is known that in 1828 a Spanish Commission,
investigating the diseases of the Ladrone Islands, reported the
existence, in those islands, of a disease which was called gangosa,
by reason of the muffled character of the voice, the Spanish word
_gangosa_ meaning muffled voice. The Commission recommended that
cases of this disease, as well as those with leprosy, be isolated,
thus showing that the disease was differentiated from leprosy at that
time.
Daniels, who studied similar naso-pharyngeal lesions in Fiji,
considered the disease as a sequel of yaws and stated that if it
were not a stage of yaws it was probably a separate and distinct
disease. Leys, who studied gangosa in Guam, in 1904, gave it the
name rhino-pharyngitis mutilans and described it as a disease _sui
generis_.
=Geographical Distribution.=—The disease is very prevalent in
Guam, and is also present in other islands of the Caroline group.
It exists in Fiji and many cases have been reported by Numa Rat
from the island of Dominica, in the West Indies. Cases have also
been reported from the Philippines and Ceylon.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—The two most prominent views as to its etiology are that
it is a sequel of either yaws or syphilis. The fact that gangosa
responds to antisyphilitic treatment is no proof as to its luetic
origin because yaws yields equally well to such remedies.
Gangosa cases also give a considerable percentage of positive
Wassermann reactions, 105 positives in 281 cases. Halton who made
these tests found 100% positive reactions in cases of yaws and 46%
of positives in those who had had yaws several years previously.
The main points against the syphilitic nature of the disease are
absence of either congenital or acquired syphilis among the natives
of Guam. There is an absence of Hutchinson’s teeth and interstitial
keratitis. Leys states that neither primary nor secondary syphilis
had been seen in a native of Guam during a year in which a very
large number, including several prostitutes, had been treated.
Recently a positive luetin reaction has been obtained in 253 out of
369 cases of gangosa, of which 143 were papular type reactions,
65 pustular and 45 torpid reactions (taking ten days or more for
the reaction to manifest itself). The syphilitic and yaws antigens
seem to be reciprocal so that these tests do not throw out yaws.
The great stumbling block of the advocates of the luetic etiology
has been to show the presence of syphilis among the people of Guam.
Under tropical ulcer it will be noted that Jeanselme failed to find
the eye or teeth signs of congenital syphilis among natives of
Indo-China with the disease.
[Illustration: FIG. 125.—Cases of Gangosa from Guam. (U. S. Naval
Medical Bulletin.)]
Kerr, who has been an advocate of the yaws etiology, has shown that
of 315 cases of gangosa, 205 could show yaws scars and knew where the
mother yaw had been and of the entire 315 only 18 claimed never to
have had yaws and failed to show scars.
Rossiter, who observed active ulcerations of the nasal septum and
hard palate in the case of a two-year old Samoan child, following
yaws, states that he found yaws treponemata in smears from the
ulcerated areas.
=Epidemiology.=—If gangosa is a sequel of yaws then the same factors
which are operative for yaws apply to gangosa.
PATHOLOGY
Sections made from the ulcerating margins of the nasopharyngeal
lesions have failed to show treponemata when stained by Levaditi’s
method. In sections of such tissue stained by Giemsa’s method I noted
a rather marked infiltration with lymphocytes and a great number of
mast cells. Fordyce has noted the presence of giant cells.
From the histological study one can only state that the lesions
present the characteristics of the granulomata.
A remarkable feature of the disease is the rapidity with which
ulceration destroys cartilage and bone. The nasal duct seems to be
prone to attack and it is through this channel that the process
reaches the eye to bring about its destructive tendency in that
organ.
Of 81 cases studied by McLean and Mink the eye was involved in 21.
The larynx was involved in 33 of these cases. It is the frequent
perforation of the hard palate that gives these patients the nasal
voice, whence the name of the disease is derived.
SYMPTOMATOLOGY
Patients with the disease have rarely been observed prior to the full
development of the mutilating ulcerations. In a few cases, however,
it was noted that a patch of membrane first appeared in the region
of the soft palate. This membrane rapidly became honeycombed and an
examination three or four days later showed underneath a deep ulcer,
surrounded by an area of marked congestion.
The ulcerating process advances rapidly, destroying bone as well as
soft parts. The process seems to extend from within outward, giving
a funnel-shaped loss of tissue. The ulceration advances upward and
forward, destroying the nasal septum and structures forming the
tip of the nose, leaving the upper lip as the lower border of this
external opening.
The active process tends to become quiescent in one or two years,
the cases then showing extensive loss of tissue with cicatricial
borders. Occasionally active ulceration may again set in after a
period of quiescence.
The voice character is that of any case where there is a
perforation of the hard palate and is not distinctive of the
victims of this disease.
During active ulceration there is a malodorous sero-purulent
discharge which makes the patients very objectionable. These cases
seem to suffer very little impairment of the general health even
when the process is active.
Although the destructive lesions about the nasopharynx and the region
of the face are the most striking ones it would appear that similar
ulcers on the extremities are of the same nature as those more
prominently situated.
In an examination of the blood of 10 of these cases in Guam I did
not observe any abnormal findings, other than an eosinophilia,
which was present to an equal degree in those unaffected. Musgrave
and Marshall reported a slight leucocytosis in their case.
DIAGNOSIS
Gangosa is chiefly to be differentiated from leprosy, syphilis and
lupus vulgaris. Its more rapid course should distinguish it from
leprosy and lupus and the history from syphilis.
TREATMENT
Odell found that a thorough antisyphilitic treatment cured these
ulcerations. He used mercurial injections. Recently salvarsan has
been used with striking curative results. It has been thought that
local application of tincture of iodine was effective in stopping the
progress of the early ulcerations but this would seem doubtful, it
being advisable immediately to give salvarsan.
On account of the offensive odor of the discharge solutions of
permanganate of potash have generally been used.
CHAPTER XXVIII
MYCETOMA
GENERAL REMARKS
Various destructive processes of different parts of the body, but
more commonly of the foot, which are caused by invasion and growth
of fungi are generally designated mycetomas. Chalmers and Archibald
have studied these conditions most carefully and have grouped most
of them under maduro-mycoses and actinomycoses. The mycetomas are
characterized by the presence of fungi in the form of grains composed
of hyphae, and at times chlamydospores, imbedded in a matrix. These
grains may be imbedded in the tissues or present in the discharge
from the sinuses. Eosinophile bodies are usually present. The
maduro-mycoses have grains with large segmented mycelial filaments,
possessing well defined walls and usually chlamydospores. We have
white or yellow, black and red ones according to the colour of the
grains. The actinomycoses have very fine nonsegmented mycelial
filaments with ill-defined walls and no chlamydospores. We have
black, yellow and red grain actinomycoses. In addition to the
mycetomas we recognize paramycetomas and pseudomycetomas, the former
of which show fungi which do not show any grain formation and the
latter failing to have present either fungi or eosinophile bodies.
The pseudomycetomas are associated only by reason of clinical
resemblance.
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—The disease was first described by Kaempfer about 200
years ago, but at that time was often confused with elephantiasis.
The first exact clinical description of the disease, with its
pathology, in which was noted the fungus nature of the granules given
off in the discharges from the sinuses, was that of Vandyke Carter,
whose studies were carried on from forty to fifty years ago.
=Geographical Distribution.=—The name Madura foot takes its origin
from the great prevalence of the affection about Madura, in the
Madras Presidency of India. It is less frequent in other parts of
India. It also occurs in Ceylon. The disease is rather widespread
in Africa, having been reported from Algiers, Tripoli, Tunis, Egypt
and the Sudan as well as from Madagascar. Cases have also been
reported from Italy and Greece in Europe and from the West Indies
and some of the South American countries. Several cases have been
reported from North America and Sutton, in 1913, reported two cases
from Kansas, one in a Mexican and one in a native of Texas.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—The disease is caused by the penetration of certain
species of fungi into the tissues of the foot, although rarely the
hand or some other part of the body may be affected. These species
of fungus develop in granulomatous areas from which sinuses lead to
the surface of the foot, in the discharges from which are found small
granules resembling those found in the discharges from actinomycosis
lesions.
As a rule only one kind of fungus is found in a single case.
The most common infection is that due to _Discomyces madurae_
(_Nocardia madurae_) which is the fungus of the fish-roe-like
granules of the pale or white variety of mycetoma. These, like the
fungus of actinomycosis, _Discomyces bovis_, show a felted mycelium
in the center and peripheral club-like structures. These granules
are yellowish-white and vary in size from a pin’s head to a small
pea. The mycelial threads are very narrow, 1 to 1½ microns. It
grows aerobically and the cultures show slender mycelial threads
which are Gram-positive. This is the organism of Carter’s white
mycetoma.
Other species of the pale, white or ochroid group of mycetoma
fungi are _Indiella mansoni_ (Brumpt’s white mycetoma),
_Nocardia asteroides_ (Musgrave and Clegg’s white mycetoma),
_Sterigmatocystis nidulans_ (Nicolle’s white mycetoma) and several
others.
The cases caused by the black varieties are more rare and are
characterized by the presence in the discharges from the sinuses of
black gunpowder-like grains.
These hard, brittle, irregular grains are caused by various species
of fungi of which the best known is Carter’s black mycetoma
(_Madurella mycetomi_). This species was cultured by Wright and
first shows a grayish growth, later becoming black. Other black
varieties of mycetoma are due to various other fungi. Bouffard’s
black variety is caused by _Aspergillus bouffardi_. DeBeurmann’s
black mycetoma has as cause _Sporotrichum beurmanni_.
Besides the white and black varieties we also have a red variety of
mycetoma. The fungus grains are quite small and reddish in color.
It is not an uncommon infection in certain parts of Africa, as
Senegal. The cause is _Nocardia pelletieri_.
Boyd and Crutchfield have noted an ascomycete in an American case,
with white granules, to which has been given the name _Alleschiria
boydii_.
=Epidemiology.=—We know very little about the occurrence of these
mycetoma fungi, other than in man. It is thought that such fungi lead
a saprophytic existence on thorns or blades of grass or spine-like
grains of various cereals. Thus Nicolle’s case in Tunis started from
a puncture wound by a grain of barley.
As the vast majority of such cases are noted in the feet, and as
such cases are chiefly in those who work barefooted, it seems
reasonable to consider that the fungi are introduced on some
puncturing object and the external wound having healed development
goes on in the deeper structures.
PATHOLOGY
In more than 75% of cases of mycetoma the foot is the only part
infected. More rarely there is involvement of hands, knees and
buttocks.
The affected part shows nodules on the external surface which
connect with the granulomatous lesions of the interior of the foot
by sinuses. In advanced cases there may be a network of sinuses
and cyst-like dilatations which are filled with a viscid fluid
packed with the small fish-roe granules in the white variety or the
gunpowder grains of the black mycetoma. The bony structures of the
foot may undergo disintegration as well as muscular and areolar
tissue so that on cutting into such a foot there is nothing normal
remaining—simply a cheesy mass.
In the early granulomatous areas are found the actinomyces-like
granules surrounded by an area of mononuclear and polymorphonuclear
infiltration. Giant cells are occasionally found. There is an
inflammatory oedema. Externally we have connective tissue cells and
a fibrous wall. The blood vessels show endothelial proliferation
and thrombosis.
SYMPTOMATOLOGY
The disease usually begins in the sole of the foot with the formation
of firm swellings about ½ inch in diameter. The cases are rarely seen
at this stage, the natives waiting before seeking medical advice
until the nodule has softened and begun to discharge the viscid fluid
with the various-colored granules floating in it. As stated before,
the soft, yellowish-white, fish-roe-like granules are most commonly
observed, the more friable, hard, gunpowder-like grains less so. The
nodules continue to form and to break down until the foot has become
greatly enlarged, the under surface bulging out in a convex mass with
the toes and heels appearing as if raised up. The dorsal surface is
also puffed up and studded with broken down nodules, and the sides
well rounded. There is no increase in the length of the foot. This
swollen distorted foot is borne on a thin peg-like leg which makes
the size of the foot more striking. Very rarely cases have been
reported where the hand or thigh have been involved.
If one probes the discharging sinuses bone may or may not be felt
according to the advancement of the degenerative changes. There is
rarely pain or bleeding following the probing.
It is more from the onerous burden of carrying around this fungoid
mass of a foot, 3 or 4 times the normal size, than pain, that the
patient complains of.
[Illustration: FIG. 126.—Mycetoma. (From Greene.)]
Uncomplicated cases do not show fever and the occasional
enlargement of lymphatic glands is probably connected with
bacterial infections.
There are never visceral metastases in mycetoma as is true of the
nearly related actinomycosis.
The process shows no tendency to heal naturally or under treatment
but fortunately does not extend, the process being confined to
a foot or a hand. The joints are rarely if ever invaded. Unless
the sinus-riddled member is amputated the drain on the patient
gradually exhausts him and death ensues in ten or fifteen years.
DIAGNOSIS
The distorted appearance of the foot or hand, riddled with sinuses
discharging a viscid fluid containing the variously colored granules,
which upon microscopical examination are found to be sclerotia of
fungi, is absolutely diagnostic. As regards recognition of the
causative fungus one should culture the discharge or grains on
maltose agar, potato or rather dry blood serum. The recognition of
species of fungi is a very difficult matter, even for an expert.
PROGNOSIS
This is absolutely unfavorable as regards the relief of the condition
but as regards life it is not unfavorable provided the drain on the
system is gotten rid of by amputation of the part.
PROPHYLAXIS AND TREATMENT
=Prophylaxis.=—The wearing of shoes in the fields or forests would
seem to be the best means of protection against small wounds from
thorns, splinters and the like.
Then, too, any such wound which might occur should be treated with
tincture of iodine.
[Illustration: FIG. 127.—Important tropical fungi.]
=Treatment.=—It is usual to try the effects of curetting the lesions
and if taken early enough this may have effect. As a rule the process
goes on but is limited to the member attacked so that amputation of
the diseased part brings about a cure. Iodide of potash is of no
value. X-ray treatment seems to be of value in relieving the pain and
in lessening the discharge from the sinuses but is of questionable
curative effect. It might be of greater value if tried early in the
disease.
CHAPTER XXIX
GRANULOMA VENEREUM
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—It is generally stated that Daniels first noted the
disease in British Guiana, in 1896, but Daniels regards the disease
previously described by Macleod from India under the designation
“serpiginous ulceration of the genitals,” as referring to granuloma
venereum.
=Geographical Distribution.=—Cases of the disease have been
chiefly reported from British Guiana and the West Indies. It is now
recognized, however, that it occurs in India, China and Northern
Australia as well as in some of the islands of the Pacific. It also
occurs in Northern and Central Africa.
Grindon has reported 3 cases from the United States.
ETIOLOGY
Various spirochaetes have been reported as present in the lesions.
The finding by Wise of spirochaetes resembling _Treponema pallidum_
has not been generally accepted.
Donovan has reported the presence, in scrapings from the
ulcerations, of an oval bacillus (1½ × 2 microns) which was
contained in large phagocytic cells. There were sometimes several
such bodies in a single cell.
Flu has recently reported the presence in plasma cells as well
as occasionally in other cells of a capsulated organism which he
believes related to the Friedlander group. His cultural work has
not been conclusive. It is probable that this capsulated organism
is merely a secondary invader.
There is also a suggestion of the cellular reaction characteristic
of the chlamydozoa.
The disease is rather more common in women than in men and is
rarely seen before the period of puberty. It is thought that it is
transmitted by sexual intercourse.
PATHOLOGY
The pathological process manifests itself as a small round cell
infiltration of the superficial portion of the corium. The growth
is well supplied with blood vessels. Giant cell formation and
caseation have not been noted. There is an abundance of plasma
cells.
There is a marked tendency to the formation of fibrous tissue.
SYMPTOMATOLOGY
The disease usually first shows itself as a papule or vesicle on the
penis or labia minora. The process extends and the thin epidermal
layer rubs off leaving a surface of granulations which bleed easily
and give off a creamy discharge which is frequently very offensive.
[Illustration: FIG. 128.—Venereal granuloma. (After Martini; from
Mense.)]
The process usually extends from the penis to the groins by
continuity and thence down the inner surfaces of the thigh. When
the glans penis is involved there may be a fungating growth
suggestive of epithelioma. In the female the process extends from
the labia minora into the vagina and also to the labia majora and
thence to the perineum and perianal region. Recto-vaginal fistulae
often result. The process extends more rapidly and markedly when
invading mucous membranes.
While the granulomatous process is advancing there is frequently
cicatrization of the areas previously invaded forming a scar tissue
which breaks down easily. There is little pain or itching and the
general health is not impaired.
There is no enlargement of the lymphatic glands. Although the
process extends by continuity yet it may also pass to parts in
contact with the diseased area. While healing of affected skin
tends to occur that of mucous membrane does not.
There is really very little tendency to ulceration.
DIAGNOSIS
It is usual to suspect a syphilitic process but the absence of gland
involvement and secondary manifestations of syphilis negatives this.
It may be suggestive of tuberculous or epitheliomatous processes.
The marked chronicity and tendency to scarring are striking.
TREATMENT
Excision of the entire granulomatous area going well into the normal
skin has been thought by some to be the only cure.
Ordinary antisyphilitic treatment does not seem to have any effect
and the good reports that have been made as to therapeutic success
with salvarsan may have been due to diagnosing a syphilitic process
as granuloma venereum. Radiotherapy has been recommended.
Local treatment with antiseptic or deodorant washes or ointments is
necessary in these cases.
_Antimony Treatment._—Breinl reports success in treatment by using
tartar emetic injections. This treatment is now the standard one
and the drug is given intravenously as described under treatment of
leishmaniasis. It is also recommended to apply locally compresses
soaked with a ½% solution of tartar emetic.
SECTION VI
TROPICAL SKIN DISEASES
CHAPTER XXX
TROPICAL ULCER
GENERAL CONSIDERATIONS
Under the names tropical phagedaena or tropical ulcer various skin
lesions have been described, from all parts of the tropics, which
vary greatly in etiology and symptomatology.
These skin ulcers are most frequently observed on the dorsum of the
foot or front of the leg but may appear on the hands or forearms and
have rarely been reported from other parts of the body.
There is no doubt but that many of the cases reported as tropical
ulcer are really manifestations of tertiary syphilis.
Jeanselme has noted the insignificant manifestations of the
secondary stage of syphilis in natives of Indo-China and the
malignancy of the tertiary ones as regards the skin lesions. In
fact a striking feature of the late stages of syphilis in the
natives of the tropical world is the frequency and severity of skin
lesions and the rarity or absence of involvement of the central
nervous system to produce tabes or general paresis.
Again congenital syphilis is common in most tropical countries
which have been visited by white men for long periods and Jeanselme
has noted the rarity in natives so affected of interstitial
keratitis and Hutchinson’s teeth, signs upon which medical men are
apt to base a diagnosis of such a condition.
Again, Butler, studying the serological side of 27 ulcerations
which clinically could be diagnosed as tropical ulcer, obtained
strongly positive Wassermann tests in 26, or 96 per cent. of the
cases. Shattuck found that about 94% of the chronic ulcerations of
the Philippines could be ascribed to syphilis.
Besides syphilis one must bear in mind the possibility of the ulcers
being a manifestation of tertiary yaws, a condition which also gives
a high percentage of positive Wassermann tests.
In Guam, the natives separate the ulcerations about the lower
extremities from the naso-pharyngeal ones by designating the
former cases llagosos and the latter gangosas. It is probable
that the leg ulcers are manifestations of the same disease as the
naso-pharyngeal ones whether it be syphilis or yaws. These ulcers
of the leg in Guam as well as those studied by Butler in the
Philippines would certainly be classed as tropical ulcers.
There are undoubtedly many cases which can be explained by
infections with ordinary pyogenic organisms of the skin which are
enabled to get a foothold in an abrasion or other minor wound, in a
person whose resistance has been reduced by such cachexia-producing
diseases as malaria, dysentery or ancylostomiasis.
Indeed some authorities attach special importance to the tibial
ulcers found in advanced cases of hookworm disease. Some of the
sores are due to irritating applications used by the natives of
many countries as setons. In many instances the sores are from
neglected wounds.
Vincent has called attention to the association of the fusiform
bacillus and delicate spirillum, better known in connection with
Vincent’s angina, in smears from tropical ulcers.
Such findings have also caused many to consider tropical ulcer as
related to hospital gangrene. There is no doubt but that smears
from the dirty membranous deposit on these ulcers do frequently
show the fusiform bacillus and at times the spirillum, but we also
frequently find various fungi in such smears. Very few hold that
these have anything to do with the production of the ulcer.
Inoculation experiments have as a rule been indefinite in result.
LeDantec has incriminated a very large Gram-negative bacillus which
was noncultivable.
Prowazek believes that he has found the cause in a spirochaete which
possesses fewer turns and these more widely separated than those
of the spirochaete of syphilis. The association with the fusiform
bacillus has also been noted.
Wolbach and Todd note the frequent finding of spirochaetes in
tropical ulcers and attach considerable importance to a spirochaete
with abruptly tapering ends. The name of Spirochaeta schaudinni has
been given to the organism. They also generally found associated
micrococci and bacilli as well as the fusiform bacillus.
Other than the noting of granulation tissue and the presence of
plasma and small round cells there does not seem to be anything
definite in the histopathology of tropical ulcer. This is what
one might expect in view of the lack of definite knowledge of the
condition.
_Veld sore._—Under the name of Veld sore we have a form of tropical
ulcer which is common in various desert regions.
These ulcerations may appear on the face as well as on the dorsal
surfaces of the hands or forearms or on the lower extremities. They
seem to arise from infections of abrasions of the exposed parts.
In the early stages of the lesion the diphtheria bacillus has been
frequently isolated and some of the cases have been followed by
diphtheritic palsies. It would appear that these lesions have at
times been those of cutaneous diphtheria. Such cases were reported
by Craig in cases in the Sinai desert. The simultaneous existence
of cases of ordinary faucial diphtheria should make one suspicious
of the real nature of such ulcerations. Skin diphtheria is more
frequent than is generally considered.
SYMPTOMATOLOGY
These ulcers are most frequently found on the dorsum of the foot,
over the shin and about the external malleolus. More rarely they
involve the dorsum of the hand or back of the wrist.
In the multiplicity of clinical descriptions from various parts of
the tropics we obtain two types of ulceration.
One is that of a rather chronic ulcer, which slowly develops from
a painless swelling, which is not unlike a gummatous process.
Surrounding the swelling there is a circumscribed, reddened, glazed
area of skin. After two or three weeks the swelling begins to soften
and a serous fluid exudes from its summit.
Ulceration, with the frequent formation of a membrane-like deposit,
now sets in and later on we have a more or less punched-out ulcer
showing indurated margins. There may be no impairment in the health
of those with this type of ulcer.
The other type is generally seen in persons who are much debilitated
or suffering from some cachectic state. In the earliest stages
these sores seem to resemble an area which has been excoriated
and inoculated with vaccine virus, there being a rather dry,
angry-looking spot of erythema. This within a few hours may be
surrounded by a circle of vesicles beyond which is an encircling
inflammatory areola.
There is marked subjective pain and tenderness. The serum from
the vesicles fails to show any bacteria and the cellular contents
are made up almost entirely of polymorphonuclear leucocytes.
Within a few hours to one or two days the area within the ring
of vesicles is converted into a dark gray to black pultaceous
diphtheroid membrane which when detached shows underlying fungating
granulations, covered with greenish-yellow pus. This membrane, if
stripped off, tends to reform with great rapidity (twenty-four to
forty-eight hours), and in many respects resembles the membrane of
diphtheria except for its dark color.
These ulcerations extend with great rapidity and even when showing
a tendency to heal may suddenly, from a point along the margin,
proceed to form a new area of ulceration, extending somewhat as
would a ringworm. When the original site of ulceration fails
to heal during a period of several weeks, the edges become
rather indurated but do not show the punched-out or undermined
characteristics of the first type.
These cases last for months and are far more tantalizing than
the former type of ulceration for the reason that from time to
time they show a strong tendency to heal, the process clearing up
almost entirely, when suddenly the former area of the ulceration is
equalled or exceeded.
TREATMENT
Many of these ulcerations yield readily to salvarsan and in such
cases we naturally think of a syphilitic or framboesial etiology.
Castellani has recommended a protargol ointment, 5 to 10%, which is
applied to the ulcer after previous flushing with hydrogen peroxide
or other antiseptic lotion.
At times thorough cauterization with pure carbolic acid followed by
neutralization with alcohol may shorten the process.
Iodide of potash benefits some cases but has no effect on others
and the same is true of mercurial treatment.
An 8% ointment of scarlet red should be tried on these sores when
treatment with ordinary applications fails.
CHAPTER XXXI
TINEA IMBRICATA
GENERAL CONSIDERATIONS
This form of tropical ringworm is chiefly found in the islands of
the South Pacific and in the Malay Archipelago. It is also found in
Southern China and quite recently has extended to Southern India and
Ceylon. Recently it has been reported from Brazil.
On account of the disease having been carried from the Tokelau Group
to Samoa it is often designated _tokelau_.
Manson was the first to recognize the affection as due to a fungus
which he demonstrated microscopically in the scales.
He was also able to transmit the disease by inoculation experiments
and found that after about ten days a raised, brownish spot appeared
at the site of inoculation. This spot increased in size until when
about ¼ inch in diameter its central portion became detached, thus
giving rise to several thin, rosette-like scales, free at the center
but still attached peripherally. The fungus advances peripherally,
leaving a smooth surface within. Again there is a similar process
developing in the original central spot to again form a circle of
scales within the older and more peripheral circle. The process is
repeated until several rings of scales are formed each originating
from the central focus as concentric ripples form on water from the
fall of a pebble.
These scale circles are from ⅛ to ½ inch apart and give a festooned
appearance to the affected skin. It was formerly supposed that the
causative fungus was _Aspergillus concentricus_ but Castellani has
demonstrated that fungi of this genus, when present, are merely
accidental. He has isolated in cultures what he considers the
causative fungus, _Endodermophyton concentricum_. He treated scales
for ten minutes with absolute alcohol and then placed single scales
in a series of tubes of maltose bouillon.
The fungus grows between the rete malpighii and the external
epidermal layers forming a network of mycelial threads, about 3
microns broad.
Another fungus cultured from tinea imbricata scales is
_Endodermophyton indicum._ Inoculation of this organism in pure
culture produced the disease.
The characteristics of the genus _Endodermophyton_ are: The
growth of a mycelial network between the rete malpighii and the
superficial epidermal layers; in cultures only mycelial filaments
are found; there are no conidia-bearing hyphae.
The fungus is also called _Trichophyton concentricum_.
When this skin disease is introduced into a country with high
relative humidity and fairly uniform temperature, between 80° and
90°F. it spreads with great rapidity.
A dry climate or one showing considerable variations in temperature
is not favorable for its spread.
SYMPTOMATOLOGY
[Illustration: FIG. 129.—Tinea imbricata from the South Seas. (After
Kramen; from Mense.)]
The clinical characteristic of this form of ringworm is the
presence of rosette-like lesions of several concentric circles of
shingle-like, papery scales which are fixed peripherally and free
toward the center, thus, from its imbrications, suggesting the name
given it by Manson.
If one passes the finger over the affected surface from without
inward there is no sensation of roughness but if passed from the
center outward the free borders of scales cause a sensation of
roughness.
As these circles extend peripherally they meet the peripheral rings
of other circles so that various curves appear which give the general
appearance of watered silk.
The flaky scales are of tissue paper thinness and are of a dirty,
brownish-gray color.
The general health of the patient is not affected but the itching
is very severe.
There is an entire absence of inflammation about this ringworm thus
differentiating it from the more common tropical ringworms. Again
the axillae and crotch are much more rarely affected than in other
ringworms as is also true of the face, palms of hands and soles of
feet. The scalp is never affected.
Some claim that the fungus never invades the nails but Manson
states that this frequently occurs. The presence of the fungus in
a scale treated with 10% solution of sodium hydrate differentiates
the scales from those of ichthyosis.
Tinea intersecta is somewhat similar to tinea imbricata when
first appearing, showing dark brown patches but it never shows
the concentric rings. The ordinary ringworms present inflammatory
characteristics.
TREATMENT
A thorough preliminary scrubbing with soap and water in order better
to expose the fungus to curative applications is important.
For treatment Manson recommends iodine liniment. This contains 12½%
of iodine as against 7% for the tincture. The liniment has also
3½% of glycerine which is not an ingredient of the tincture. Both
tincture and liniment have 5% of potassium iodide. The application of
the tincture does not seem to be as satisfactory as the liniment, the
stronger preparation being more effective.
Chrysarobin is very effective but very irritant and has to be
used with care. An application of a 5% solution of chrysarobin in
chloroform to the affected area, then painting it over with a 50%
aqueous solution of ichthyol, often gives good results.
Some prefer a 2% to 5% ointment of chrysarobin. Chrysarobin
produces a conjunctivitis if used near the eyes. Again if absorbed
it may act as a renal irritant.
Castellani strongly recommends the use of resorcin in tincture
of benzoin (60 to 120 grains of resorcin in 1 ounce of tincture
of benzoin). Either remedy alone has very little effect, the
combination being necessary. The application is made once or twice
daily. In addition to this treatment the patient should be scrubbed
with sand-soap and hot water twice a week.
As regards prophylaxis the clothing should be boiled. The natives
attach value in preventing the disease to anointing the body with
cocoanut oil.
CHAPTER XXXII
TINEA CRURIS
GENERAL CONSIDERATIONS
Under the name “dhobie itch” this fungus affection is probably better
known to Europeans than any other tropical skin disease. This name
dhobie or washerman’s itch has been given on account of associating
it with the infection of the underclothing while being washed in the
pools or streams along with the garments of those who have this skin
disease. This, like every other widespread view, has probably some
foundation but cannot be verified. It is the eczema marginatum of
Hebra.
This affection is caused by various species of _Epidermophyton_.
This genus differs from _Trichophyton_ in that it never invades the
hair or hair follicles.
The species which have been more frequently reported are
_Epidermophyton cruris_, _E. perneti_ and _E. rubrum_. The mycelium
is about 4 microns broad and the spores about 5 or 6 microns. All
of these fungi can be cultured on Sabouraud’s maltose agar, growth
appearing in about a week, except _E. perneti_, which grows more
rapidly.
SYMPTOMATOLOGY
The favorite site is the crotch although the axillary region is also
frequently involved. The process starts as a papule but these rapidly
develop and give rise to an angry red, swollen patch with sharply
delimited margins. These red, festooned patches are usually limited
to the perineum, scrotum and inner surfaces of the thighs.
The itching is unbearable and many secondary infections or eczematous
lesions result from the fierce scratching of the parts.
If the patient goes to a cooler place the process subsides to
return when he comes back to the hot moist climate where the
infection was originally contracted.
In some cases the fungus invades the region between the toes and
gives rise to intolerable itching and from secondary bacterial
infections to a condition known as “Mango toe.”
It has seemed to me that when one has a coccal infection engrafted
upon the fungus one the condition becomes what might be termed
fulminating, so rapidly does the itch extend.
TREATMENT
When the process is markedly inflammatory mild applications are
indicated, such as calamine lotion (30 grains each of calamine
and zinc oxide with 5 or 10 drops of carbolic acid in 1 ounce of
saturated solution of boric acid).
A 10% to 15% solution of sodium hyposulphite can, however, be used on
the area even when markedly inflammatory.
Iodine applications are too irritating for the region of the scrotum.
An ointment of resorcin, 20 to 30 grains with 1 dram of sulphur
to the ounce, may be tried. If chrysarobin be used it should be
applied with greatest care as noted under tinea imbricata. Many
advocate applications of solutions of salicylic acid in alcohol, 2%
to 5%.
Manson’s dusting powder of equal parts of boric acid, zinc oxide
and starch should be freely used.
CHAPTER XXXIII
PINTA
GENERAL CONSIDERATIONS
This is a parasitic skin affection due to various species of fungi.
It is only found in the tropical portion of the new world, and is
especially prevalent in Colombia, where it has been estimated 4% of
the population have the disease. It is also found in Mexico, Central
America and some of the other countries of South America as well as
Colombia.
Other names for the disease are caraate and mal de los pintos.
At first it was thought that the different colors shown by the
eruption were due to varying depths of the proliferating fungi in
the skin layers but it is now known that the explanation is in a
variety of species in the different types of pinta.
The pure violet pinta is caused by _Aspergillus pictor_ while the
grayish-violet one is due to _Penicillium montoyai_. A species
of _Monilia_ causes the white variety and different species of
_Montoyella_ a black and a red variety respectively. The genus
_Montoyella_ is stated by Castellani to have both slender and thick
mycelial threads, from the thicker of which spring delicate hyphae
terminating in pear-shaped conidia.
Material scraped from the lesions and mounted in liquor
potassae shows the fructification terminations characteristic
of _Aspergillus_ or _Penicillium_ in the violet or gray-violet
varieties while the white, black and red ones only show mycelial
threads and scattered spores. These pinta species of fungi can be
cultivated on Sabouraud’s medium.
Montoya thinks that the pinta fungi lead a saprophytic existence
in the waters of mines or other places with a constant high
temperature, and states that he has obtained pure cultures from
such sources.
SYMPTOMATOLOGY
The spots of the eruption are generally first noted on the hands or
face and are rather rough, dry and only slightly raised. Itching is
quite marked and the scratching probably is largely responsible for
the gradual spread of the affection over the body generally.
The palms of the hands, soles of the feet and nails are never
involved. The course is essentially chronic and shows no tendency to
spontaneous cure.
The red pinta is that most often found in white people, the patches
being of brick-red color.
The white pinta may not only be caused by a species of _Monilia_
but it may represent an area formerly invaded by a species
producing some other color and then dying out leaving a
vitiligo-like area.
The violet pinta is quite common among miners, while the black one
is the type which more often appears in the black population. The
black varieties may show either a pure black or a violet-black
color.
TREATMENT
Local applications of iodine preparations or of chrysarobin seem most
effective. The resorcin sulphur ointment noted under tinea cruris is
best for the face.
CHAPTER XXXIV
MINOR TROPICAL AFFECTIONS OF THE SKIN
DERMATOPHILIASIS
This is a skin infection due to the penetration of the region about
the feet and especially the toes by the female sand flea or chigoe.
It is also sometimes called the jigger. This flea is a member of
the subfamily Sarcopsyllinae which differs from the ordinary flea
subfamily in that the impregnated female becomes fixed in the tissues
of the host instead of developing her eggs in a free state. The
proper name for this flea is _Dermatophilus penetrans_, synonym
_Sarcopsylla penetrans_. It is found abundantly in Central America
and Northern South America as well as in the West Indies. It is also
found in East and West Africa as well as India and is apparently
rapidly spreading over the tropical world.
[Illustration: FIG. 130.—Sandflea female; much enlarged. (From
Mense.)
FIG. 131.—Sandflea male; much enlarged. (From Mense.)]
This flea attacks not only man but many wild and domesticated
animals as well, and in particular the pig. The males and females
live in dry sandy soil and feed on the blood of various mammals.
The importance of the parasite is that upon impregnation the
female ceases to lead a free existence but burrows into the tissues
of man or other host and becomes enormously distended with eggs.
There is some question as to whether these eggs are extruded by the
female or whether they are set free in the ulceration process which
tends to occur around the imbedded flea. The eggs develop into
13-segment larvae, which form a cocoon from which the insect comes
out in about ten days.
[Illustration: FIG. 132.—Sandflea female. Shortly after penetrating
the skin. The anterior part of the abdomen is much more distended
than the posterior; the enlarged part is disk-shaped, not globular.
(From Mense.)]
The female flea tends to burrow into the skin about the sides of
the toe nails, although more rarely boring into other parts of
the body as penis, scrotum, thighs or hands. Finally only the tip
of the abdomen projects. This marks the black spot which is noted
in the tense itching area which is quite white unless bacterial
infection starts up inflammation.
The swelling is about the size of a small pea by the end of five or
six days. Ulceration is the usual termination of the infection if
untreated and such ulcers may be very intractable or form a favorable
soil for infection with the tetanus bacillus. Quiros has estimated
that 250 deaths from tetanus occurred in Costa Rica in 4 years from
infection of nigua (sand flea) ulcerations.
Well-made shoes are most important in prophylaxis and the best
treatment is to enucleate the egg-distended flea with a needle
and then touch the cavity with pure carbolic acid followed by
neutralization with alcohol. It is astonishing how expert the
natives become in dissecting out these insects.
TROPICAL IMPETIGO
Under the designation pemphigus contagiosus Manson describes a very
common skin disease of the tropics. The condition, however, is not
pemphigus. A bacteriological examination shows in the smear great
numbers of pus cells containing phagocytized diplococci. Wherry has
named the organism _Diplococcus pemphigi contagiosi_. As a matter
of fact, culturally, this organism is the common _Staphylococcus
pyogenes aureus_.
It is also a matter of common observation that this organism when
in pus cells of active inflammatory processes shows a diplococcus
morphology rather than a staphylococcal one.
These staphylococcal lesions which do not start in the hair
follicles are often designated as “pyoses.”
The disease is markedly contagious in children and is strikingly
autoinoculable so that unless the first lesion is taken in hand
immediately the eruption may become generalized. A small spot of
erythema first appears which rapidly becomes vesicular, the bleb
covering the entire spot, so that there is practically no surrounding
inflammatory areola.
The diaphanous covering rubs off with the slightest touch and
leaves underneath a raw-looking surface which extends peripherally
to form an angry-looking red patch an inch or more in diameter. In
adults it rarely affects parts other than the axilla or crotch.
The general health of the child is practically unaffected.
The usual treatment is with bichloride lotions followed by a
dusting powder of equal parts of boric acid, starch and zinc oxide.
I have found, however, that an ointment of ammoniated mercury, 2%
to 5% according to age, is the most satisfactory treatment.
_Tropical Boils._—It is interesting that the same organism
responsible for this more fulminating lesion should be the one
responsible for the common cosmopolitan boil and in fact boils are
exceedingly common in the tropics. These boils may be larger and
with a greater tendency to widespread distribution and in some
regions they are so common as to have a regional designation (Nile
boils). The staphylococcus of tropical impetigo seems to have
greater virulence than that of the boils. Autogenous vaccines are
often most successful in the treatment of boils.
PIEDRA
This is a fungus disease of the hairs in which small nodules form
along the shaft. They are about the size of the nits of head lice but
more or less surround the hair instead of projecting off at an angle
as do the ovoid lice nits. These little masses are black in color
and very hard, hence the name piedra—stone. The disease is chiefly
found in Colombia and is thought to be due to the application, by the
women, of a mucilaginous preparation to their hair. If an infected
hair be examined in liquor potassae the nodule will be found to
be made up of faceted bodies matted to the side of or, at times,
encircling the hair. These bodies are the spores of _Trichosporum
giganteum_.
Besides piedra there are also other nodular affections of the
hairs due to species of _Nocardia_. Chalmers has recently reported
several cases of trichonocardiasis where the axillary hairs were
matted together and the skin of the region inflamed. Castellani
called attention to this condition in 1911 and reported a narrow,
bacillus-like fungus as the cause, _Nocardia tenuis_. The nodules
are rather soft and may be yellow, black or red in color.
Microscopical examination shows the fungus.
Chalmers had excellent results by treating the affected hairs with a
2% formalin solution in alcohol. At night a 2% ointment of sulphur
was applied. A 5% alcoholic solution of salicylic acid has also been
recommended.
[Illustration: FIG. 133.—Insects in which the larval stage is
important. (1) _Chrysomyia macellaria_; (2) larva; (3) _Dermatobia
cyaniventris_ larva, early stage (ver macaque); (4) _D. cyaniventris_
larva, later stage (torcel or berne); (5) _D. cyaniventris_; (6)
_Auchmeromyia luteola_; (7) _A. luteola_, larva; (8) _Sarcophaga
magnifica_; (9) _S. magnifica_ larva; (10) _Anthomyia pluvialis_;
(11) _A. pluvialis_ larva.]
CUTANEOUS MYIASES
=Ver Macaque.=—The best known of these myiases is that due to the
larva of a botfly (Oestridae), _Dermatobia cyaniventris_.
The larva is at first club shaped and in this stage is called ver
macaque. Later on it becomes worm shaped and is then called torcel in
Venezuela or berne in Brazil. The natives of most of the countries
where the infection is found have called the larvae “mosquito
worms” or “gusano de zancudo” and they have even incriminated large
mosquitoes belonging to the genus _Psorophora_ as being responsible
for the infections.
Surcouf has noted that these fly larvae have been found cemented to
mosquitoes of the genus _Janthinosoma_ by a glue-like substance.
These mosquitoes are vicious biters and evidently the young larvae
escape from the eggs attached to the mosquito and enter the wound
made by the biting parts of the mosquito. Some have thought that
_D. cyaniventris_ deposits its eggs in a glue-like material on the
leaves of plants and that they stick to mosquitoes flying about
such plants. From the facts that these eggs apparently only become
attached to this particular mosquito, and further in that the eggs
are attached in a constant manner with the hatching end outward, it
would seem that the mother fly must in some way seize the mosquito
and deposit her eggs on it. As the larva grows in the subcutaneous
tissues of man or other animals a tumor-like swelling develops with
a central orifice, toward which the posterior extremity of the
larva points and through which it takes air into its spiracles.
It has been stated that the eggs of _D. cyaniventris_ may be
conveyed by ticks.
The swelling somewhat resembles a blind boil and may be as large as a
pigeon’s egg.
These botfly boils tend to break down and discharge a sero-purulent
fluid and it is supposed that the larva, when mature, escapes as a
result of the disintegration of the tumor.
In Brazil they make tobacco juice applications which cause the
larva to protrude and then squeeze it out. The injection of a
little chloroform into the larva with a hypodermic syringe, prior
to its extraction with a forceps, makes the process less painful.
=The Screw Worm.=—This is the larva of a bluebottle fly, _Chrysomyia
macellaria_, which differs from the common bluebottle fly, _Lucilia_,
by having 3 black lines on scutum. This muscid fly lays 200 to 300
eggs in wounds or orifices having offensive discharges, as from nose,
ears, etc. The larvae burrow into the adjacent tissues and cause
frightful destruction of all soft parts. The mature larvae are a
little more than ⅔ inch long and have circlets of spines around each
of the 12 segments.
This infection is especially common in tropical and subtropical
America and is important in animals as well as man.
In Yount’s 23 cases 18 were of nasal myiasis; the mortality for
the 23 cases was 15% and for the nasal ones 22%. Irrigation with
chloroform water or a 5% carbolic acid or compound cresol solution
gives the best results in treatment. If the larvae reach the
sinuses it may be necessary to open them to get at the parasites.
CREEPING ERUPTION
This is a skin affection which is also called larva migrans
on account of its being due to the burrowing of more or less
undetermined fly larvae in the subcutaneous tissues. In their
advance, which is at the rate of from one to several inches daily,
they leave a raised pinkish line. The burrow is approximately ⅙ inch
in diameter. The disease is most common in Southern Russia but is
also found in Africa, Asia and South America. Looss considers that
hookworm larvae, when penetrating the skin, may produce similar
lesions.
[Illustration: FIG. 134.—Wing venation of Diptera. _A_, first
posterior cell; _B_, discal mid cross-vein; a, auxiliary vein;
_C_, marginal cell; _D_, submarginal cell. In the illustration of
the Chrysops wing, the letter “B,” indicating the discal cell, is
misplaced. It should be in the same relative position as in the
Tabanus wing.]
TUMBU FLY DISEASE
This African myiasis is due to the penetration of thighs or buttocks
by the larvae of _Cordylobia anthropophaga_. The appearance of the
tumefied area is quite similar to that of the tumor of _Dermatobia
cyaniventris_ and the treatment is similar.
CRAW-CRAW
This is a rather chronic papular skin disease which is reported from
the west coast of Africa. These papules may be as large as a small
pea and are quite hard. They are found chiefly on legs and arms. The
proximal lymphatic glands may be enlarged.
[Illustration: FIG. 135.—Markings of breathing slits on posterior
stigmata of various larvae. 1. _Musca domestica_, showing both
stigmata; 2. _Calliphora vomitoria_; 3. _Stomoxys calcitrans_; 4.
_Auchmeromyia luteola_; 5. _Cordylobia anthropophaga_; 6. _Sarcophaga
magnifica_.]
Undoubtedly many of the cases called craw-craw are scabies. In fact
the Africans give the name to a host of different skin affections.
O’Niel thought he had found a filarial larva in one of his cases
and Nielly incriminated a nematode larva of the Anguillulidae
family. The cause is unknown and the disease very intractable to
treatment.
SECTION VII
TROPICAL DISEASES OF DISPUTED NATURE OR MINOR IMPORTANCE
CHAPTER XXXV
VERRUGA PERUVIANA AND OROYA FEVER
It is thought that Oroya fever was the disease which proved so
fatal to Pizarro’s army in the 16th century. In 1870, great
interest was aroused in these diseases on account of their
prevalence in the workmen constructing the railroad from Lima to
Oroya, a town in the Andes. At this time there was much conflict
of opinion as to whether the two diseases were identical. In 1885,
Carrion, a medical student of Lima, inoculated himself with the
blood from a verruga lesion and died from Oroya fever about one
month later. As the result of this it seemed to be established
that infection with verruga material would produce the serious
first-stage fever and many call the fever Carrion’s disease.
Consequently these two diseases have, until recently, been
considered as two stages of the same disease, the usual idea being
that Oroya fever is the first stage, following which, provided
the patient does not die from this very fatal fever, there sets
in an eruption which is the second or verruga stage. In order to
reconcile the observations of the development of the eruptive stage
without a severe, febrile, preliminary one of three or four weeks,
it was considered that the first stage might be exceedingly mild.
Strong and his colleagues, however, inoculated a volunteer with
material from verruga lesions and sixteen days later the eruption
appeared without the preliminary fever and anaemia that are so
characteristic of Oroya fever, and it is now recognized that they are
two distinct entities.
OROYA FEVER
GENERAL CONSIDERATIONS
Oroya fever is an acute, infectious disease, often terminating
fatally, caused by the _Bartonella bacilliformis_, and characterized
by an insidious onset, irregular fever, pains in the bones and a
rapidly developing anaemia of the pernicious anaemia type.
The disease is chiefly found in towns situated in narrow,
wind-protected valleys of the west side of the Andes, at elevations
of from 3000 to 9000 feet. Townsend has suggested that a species of
_Phlebotomus_, _P. verrucarum_, which is very prevalent, may be the
transmitting agent. This investigator believes that verruga and Oroya
fever are the same disease. It may be stated that malaria and enteric
fevers, as well as verruga, are common in the localities where Oroya
fever prevails and much of the confusion in the literature of Oroya
fever is due to failure to differentiate the better known conditions.
Strong noted that Oroya fever was common from January to April,
particularly towards the close of the warm, rainy season. Cases were
rare in April and May and did not occur in the months of June, July
and August. He notes that verruga was not uncommon at the time when
Oroya fever was not occurring. Concomitant infection with Oroya fever
and verruga may occur but this is also true of malaria or malaria and
verruga may exist at the same time.
Barton isolated a paratyphoid bacillus from the blood of a patient,
besides which other bacteria have also been isolated. In 1909,
Barton noted certain rod-like organisms in the red cells of Oroya
fever patients which he considered protozoal in nature.
Strong and his colleagues found in the blood of Oroya fever cases
rod-shaped forms in the red cells, varying from 1 to 2 microns in
length, the red cells containing from 1 to 30 of these elements.
A study of sections of lymphatic glands of severe fatal cases showed
great numbers of these bodies packed in the endothelial cells. These
cells rupture and set free the organisms.
Intravenous inoculation of blood containing these elements
into monkeys and rabbits was negative in result. Strong failed
to cultivate the organism. These organisms were considered as
intermediate between bacteria and protozoa. They are closely
related to _Grahamella_ and the Harvard commission has proposed
the name _Bartonella bacilliformis_. In many ways they resemble
piroplasms, especially _Theileria_.
PATHOLOGY
At autopsy the skin shows the pale yellowish waxy hue of pernicious
anaemia. The lymphatic glands are somewhat enlarged and may be
oedematous. The heart is flabby and ecchymoses may be present in
the pericardium. The spleen is enlarged, shows numerous infarctions
and contains large amounts of pigment in the form of yellowish
masses or granules deposited between the splenic cells and in the
endothelial leucocytes. This pigment is like melanin in not giving
the iron reaction. The liver likewise is enlarged, shows areas of
toxic degeneration and contains moderate amounts of pigment. The
femoral marrow is soft and dark red. Microscopically, the endothelial
cells of the lymphatics distended with the causative organisms were
particularly noted by Strong.
SYMPTOMATOLOGY
The incubation period is about three weeks and the onset of the
disease is marked by malaise and apathy, to be followed by a
rapidly developing anaemia, of the pernicious anaemia type, with an
irregular fever of a remittent character fluctuating between 100°
and 102°F. and only exceptionally going up to 104°F., and pains in
head, joints and bones. The tenderness over the bones is undoubtedly
associated with the marked changes going on in the bone marrow and is
particularly marked over the sternum.
The patient rapidly develops a very severe anaemia and death
results in 20 to 40% of cases in two or three weeks. Delirium is
often noted.
The spleen and the lymphatic glands are somewhat enlarged.
Associated with the profound anaemia there may be oedema of legs
and about joints and functional cardiac murmurs. The kidneys do not
seem to be affected. There may be a diarrhoea in the later stages
of the disease. There is no eruption in uncomplicated cases.
The most important findings in the disease are those in connection
with the blood examination. The rod-shaped organisms, which are
thought to be the cause of the disease, are somewhat difficult to
observe in fresh blood preparations. They show definite motility
within the red cells, particularly after warming the blood slide. The
motion is a rather gliding one. In Romanowsky-stained preparations
the 1 to 2 micron-long rods within the red cells may occur singly or
in numbers of 4 or 5. V-shapes are frequently seen. The rod shows a
bluish staining with a deep purplish-red chromatin-stained granule at
one extremity. Rounded, oval or pear-shaped forms may also be seen.
While the parasites are present in great numbers in severe cases they
may be very scarce in mild forms of the disease.
Very striking is the rapidly developing anaemia which frequently
shows a red cell count of less than a million within a few days.
Normoblasts are quite numerous and fulminating cases show numerous
megaloblasts.
Polychromatophilia and poikilocytosis are noted.
In the red cells we have the picture of a rapidly developing
pernicious anaemia The color index is above 1.
The leucocytes number about 20,000 of which 60 to 70% are
neutrophiles. Immature neutrophiles, as the metamyelocyte, are very
common.
PROPHYLAXIS AND TREATMENT
The transmitting agent not being known we are in the dark as to
prevention. Evidence points to some arthropod biting at night as the
incidence of the disease decreased when those working in the Oroya
fever zone were compelled to leave the valleys before sundown. The
treatment is largely one of nursing although some have reported
favorably from the intravenous administration of salvarsan.
VERRUGA PERUVIANA
GENERAL CONSIDERATIONS
Verruga peruviana is an infectious eruptive disease, caused by an
unidentified virus, lasting two or three months, and characterized by
successive eruptions exhibiting two types of lesion,—the miliary and
the nodular,—both of which show a pronounced tendency to ulceration
and haemorrhage. The eruption of verruga somewhat resembles that of
yaws and it was at one time suggested that verruga was simply yaws
as influenced by high altitude. Strong and his colleagues found
that they could infect rabbits intratesticularly and that lesions
resembling those of man could be produced in dogs and monkeys
by cutaneous and subcutaneous inoculations. The virus has been
transmitted from monkey to monkey. The monkey is not as susceptible
to the virus as man and the rabbit and dog less so. Inoculation of
the monkey is not followed by a generalized eruption. The Wassermann
reaction was negative. In extracts from the granulomatous lesions
they found a very active haemolysin. It will be remembered that
animals are not susceptible to Oroya fever blood inoculations.
From the fact that it is possible to inoculate a person by rubbing
verruga material on a scarified surface it would seem that the
infection might be transmitted by insects.
As regards the pathology of verruga, Cole has noted involvement
of the lymphatic channels, which become obstructed by a cellular
exudate, around which lymphatics are found plasma cells and
fibroblasts. There is marked dilatation of the capillary blood
vessels. The structure of these granulomatous tumors is very
vascular, almost cavernous, hence the tendency to haemorrhage. The
haemolysin may also be operative in the liability to haemorrhage.
Strong and his colleagues found the early lesions to consist of
newly formed blood vessels lying in an oedematous connective
tissue. The endothelial cells lining them may be in more than
one layer. Around these blood vessels we have aggregations of
cells which are considered as angioblasts. These angioblasts show
frequent mitotic figures. There is a resemblance to a fibrosarcoma.
SYMPTOMATOLOGY AND TREATMENT
The period of incubation is about two weeks as shown by experimental
inoculation but may be as long from the standpoint of clinical
observation as forty days. At the onset we have rather severe pains
of joints, especially the knees, ankles and wrists, together with
a fever sometimes reaching 104°F. but usually not above 100°F.
Following the eruption, the temperature usually subsides to normal
in a few days. The eruption shows two types, the one with numerous,
small, wart-like lesions, not exceeding the size of a small pea (2
to 5 mm.)—the miliary type, and the other, with less numerous but
much larger nodular masses—the nodular type. The latter type is more
rarely seen than the former.
[Illustration: FIG. 136.—Verruga Peruviana. (From Ruge and zur
Verth.)]
_The Miliary Type._—The eruption is most abundant on the face
and extensor surfaces of the extremities and less common on the
trunk. In this type a pink macule appears which rapidly takes on a
bright red color and becomes nodular. These nodules may be flat or
somewhat pedunculated and bleed easily. At first smooth and shiny,
it later on shrivels up without leaving a scar. This form of the
eruption may involve the mucous membranes, as of conjunctivae,
nose, pharynx, etc. In children the disease is usually of a mild
type.
_The Nodular Type._—The _nodular eruption_ develops slowly and the
lesions may become as large as a pigeon’s egg. They tend to become
strangulated and then show as ulcerating, fungating masses which
are a source of danger from haemorrhage. The nodular eruption does
not invade mucous membranes and is usually confined to the regions
of joints, as flexures of elbows, knees, etc.
The eruptions tend to come out in crops and the duration of the
disease extends over two or three months.
_Treatment._—The ordinary principles of cleanliness apply to the
care of the lesions to prevent secondary infections. When the large
tumor-like masses begin to ulcerate or become gangrenous they
should be excised. It must be remembered that dangerous bleeding
may occur at unexpected times, for which reason the patients should
be provided with styptics or compresses to prevent serious loss of
blood.
CHAPTER XXXVI
DENGUE AND DENGUE-LIKE FEVERS
DEFINITION AND SYNONYMS
=Definition.=—Dengue is an epidemic disease due to an
ultramicroscopic, filterable virus which has been stated to be
transmitted by _Culex fatigans_. More recent work points to
_Stegomyia_.
It is characterized by an initial three or four-day febrile paroxysm
of very sudden onset, a remission, which comes on about the fourth
day and a terminal rise of temperature for two or three days—_the
saddle-back temperature course_.
Backache and pains about the muscular attachments at the joints and
especially a marked postorbital soreness are important features.
An eruption appears about the third or fourth day. Leucopenia and
polymorphonuclear reduction are constantly noted. Apathy and a mild
neurasthenic state may continue into convalescence.
=Synonyms.=—Dandy Fever (the word dengue is supposed to be derived
from the Spanish equivalent of dandy or denguero), Break-bone Fever,
Bouquet. German. Dengue-fieber.
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—While Hirsch gives the credit for the first mention
of the disease to the chronicler Gaberti, who described a disease
with certain resemblances to dengue as existing in Cairo in 1779,
yet, for the reason that certain clinical features of this epidemic
would hardly appear to belong to dengue, as we now know it, there
would seem to be good ground upon which to give the credit of
priority to Benjamin Rush, who, under the designation break-bone
fever, gave us a true picture of dengue as it manifested itself in
Philadelphia in 1780.
Gaberti was particularly impressed with the knee involvement so
that from his description the disease was known as the disease of
the knees. He further noted swelling of the fingers and that the
pains continued for more than a month. The sudden onset and the
sweating would seem to belong to relapsing fever as well as to
dengue and in support of the view that the disease described by
Gaberti might have been relapsing fever we have the statement of
Sandwith that bone pain, chiefly of the knee, is the symptom most
complained of by the Egyptian native with relapsing fever.
Boylon, who reported an outbreak of an epidemic disease in Batavia
in 1780 stated that everybody was attacked and that the symptoms
were almost the same as those ushering in plague—headache,
lassitude and pains in the joints. He noted, however, that this
epidemic had no bad consequences, patients getting rid of it in
three days under moderate diet and copious beverages.
Ashburn and Craig, in 1907, proved that the disease could be
transmitted by injections of blood, unfiltered as well as filtered.
=Geographical Distribution.=—The disease may occur in epidemic
form in almost any part of the tropical or subtropical world. It is
very common in the countries about the China Sea and in the West
Indies.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—One can only state that the disease is caused by a
filterable virus which is present in the patient’s blood from the
second to the fifth day. Graham reported a piroplasm-like organism as
the cause but other workers have failed to confirm this. Reports as
to bacterial causative organisms have not been verified. Cleland and
his colleagues inoculated guinea pigs and rabbits without result and
were unable to find spirochaetes. Couvy has reported the presence of
short spirochaetes in the blood 2 or 3 hours before the onset of the
fever,—never later. They had two or three turns and fine extremities.
=Epidemiology.=—As regards the epidemiology of dengue there seems
to be a general acceptance of the idea that dengue is transmitted
by the common culicine mosquito of the tropics, _Culex fatigans_.
There is not, however, that definiteness which attaches to the
transmission of yellow fever by _Stegomyia calopus_ or to pappataci
fever by _Phlebotomus papatasii_, in both of which a certain period
of development of the unknown filterable virus in the arthropod host
is necessary before the insects become capable of transmitting the
infections.
It will be remembered that in the nine experiments as to dengue
transmission, conducted by Ashburn and Craig, the authors threw out
five of the cases for such reasons as previous immunity or refusal
of the experimental mosquitoes to bite. Of the four remaining
volunteers only one developed dengue. This man, however, had been
on duty at the Division Hospital in Manila and the statement is
made that he had not been exposed to the disease so far as could
be determined. This of course rather militates against the value
of this isolated experiment and furthermore the mosquitoes which
bit him had fed on the blood of a dengue patient only two nights
previously. If this is to be considered as a valid experiment, we
must believe that only a short sojourn of the virus in the mosquito
is requisite, which is rather at variance with the twelve days for
the yellow fever virus and eight days for that of pappataci fever.
In the recent Australian epidemic (1916) experiments failed to show
_C. fatigans_ capable of transmitting the disease. _Stegomyia_,
however, gave success in 4 out of 7 cases, the volunteers
developing dengue in from six to nine days after being bitten.
_Stegomyia_ mosquitoes are often termed the domesticated ones,
since they are observed to breed and pass their lives in the
immediate environment of man and further to be distinctly urban,
rather than rural, in their distribution. For their breeding places
they choose artificial collections of water, such as cisterns,
barrels, pails, bottles and cans, in or near dwellings.
These mosquitoes are small in size, silver-striped, vicious feeders
and very alert. The female alone bites, blood apparently being
necessary for ovulation. It feeds especially during the morning
and afternoon hours,—much less commonly at night unless there is
a light. The life history of _Stegomyia_ is discussed more fully
under yellow fever.
As regards the transmission of the disease by blood filtered through
a diatomaceous filter it will be remembered that Ashburn and Craig,
by proving this fact, placed the dengue virus in the same category
with the filterable viruses of the two diseases just considered.
Cleveland found the virus in the washed cells as well as in the
serum. The virus maintains its potency for several days outside the
body it being present in the blood at periods of from 18 to 90 hours.
Lavinder injected dengue blood from cases in the second to fifth
day into rhesus monkeys without noting any variation in their
temperature or blood findings.
Graham in Beirut carried out some experiments, one of which would
seem almost positively to demonstrate mosquito transmission. He
took mosquitoes which had fed on dengue patients, to a village in
the mountains where no case of dengue existed. He caused these
mosquitoes to feed on two natives of the village and both men
became sick with dengue four and five days respectively after
being bitten by the mosquitoes. Graham’s claims to have noted
piroplasma-like organisms in dengue blood have not been verified
and do not receive credence.
The most convincing evidence as to mosquito transmission of dengue
is that afforded by the absence of dengue in Port Said during the
years 1906 and 1907 notwithstanding the prevalence of the disease
in adjacent parts of Egypt. This was attributed to the absence of
mosquitoes, these having been destroyed in the fight to make Port
Said malaria-free. This campaign was commenced in May, 1906.
Other species of culicine mosquitoes, among which may be noted
_Stegomyia_, have been incriminated. In the Philippines I was
convinced that _Culex microannulatus_ might transmit the disease
as well as _C. fatigans_. In one of his experiments Graham claimed
to have produced dengue by injecting an emulsion of the salivary
glands of a mosquito which had fed on a dengue patient one or two
days previously.
PATHOLOGY
As death almost never occurs from the disease there is nothing to
note other than the marked leucopenia.
SYMPTOMATOLOGY
After a period of incubation of from four to fifteen days the disease
manifests itself with striking suddenness, in fact the patient can
generally recall almost the hour of the onset.
The temperature rapidly rises and in a few hours reaches a maximum
of from 102° to 105°F. Associated with this primary fever we have
frequently a blotchy congestion of the face—the so-called initial
rash.
We also have intense headaches, principally supraorbital and
postorbital. The pulse rate is slightly accelerated at first but
soon becomes slow and may fall to 50 from the fourth to fifth day.
There is no involvement of the joints, and the so-called joint pains
are really pains of the muscular insertions about the joints.
The backache of dengue is usually a well marked feature. Pain on
motion of the eyeballs is a prominent symptom—it is a deep soreness.
Insomnia, characterized by frequent dropping off to sleep to be
awakened immediately by disturbing dreams, is often noted.
The depression, mental and physical, is altogether out of
proportion to the lack of seriousness of the disease.
Malaise and anorexia are marked. Constipation is the rule at first.
About the third or fourth day the temperature drops to normal or
about that and remains so lowered for from twelve hours to three
days. At this time the patient feels much better and views his
affection in a less serious light. After this variable intermission
the temperature rises to possibly a greater height than primarily,
although as a rule it is less marked. This interval, or intermission,
separating two periods of fever gives us a chart designated
“saddle-back.” There may be only one rise of fever.
This second febrile attack is attended with pains and possibly
greater depression than the first accession. It is usually,
however, of shorter duration and during this period the terminal
rash appears. This is the most characteristic feature of the
disease. It generally manifests itself about the dorsal surface
of hands and feet advancing up forearms and legs. Later on it may
involve all extremities, face and trunk. The eruption is much like
that of measles but lacks the dusky red appearance of the measles
rash. It may however be punctiform and thus resemble the rash of
scarlet fever.
With the appearance of the terminal rash we may have crises such as
profuse sweating or marked diarrhoea or epistaxis.
The desquamation is furfuraceous in character and may be attended by
marked itching.
In some patients (European) there is a rosy carmine flush of palms
of hands and soles of feet. Some authorities have reported glandular
enlargements in dengue.
[Illustration: FIG. 137.—Temperature charts of dengue and
dengue-like fevers.]
Convalescence is apt to be protracted, being especially
characterized by malaise and nervous depression, practically
neurasthenia.
Leucopenia and polymorphonuclear percentage reduction appear by the
second day.
_Clinical Types._—In different epidemics it is noted that some one
clinical feature may seem outstanding. Of these we may note:—
(1) The pulse rate is slow for the temperature rise, thus reproducing
a phenomenon common in yellow fever (Faget’s law). It is in recent
epidemics particularly that clinical descriptions have recorded the
frequency of a very slow pulse, most of the older authorities having
noted a pulse rate which corresponded to the elevation of temperature.
(2) In some epidemics the feature of glandular swelling is prominent,
while in others the swelling is so slight as to be overlooked.
(3) The characteristic “saddle-back” temperature chart seems lacking
in the general run of cases in certain outbreaks. It is possible that
such epidemics, showing atypical temperature curves, may have been
due to phlebotomus fever, or seven-day fever, instead of dengue.
(4) In some epidemics, the rash is insignificant or very slight in
most cases. This observation is possibly dependent on the ephemeral
character of the eruption in certain groups of cases.
(5) From the chart Fig. 138, analyzing the symptoms in one epidemic,
it will be noted that Lane observed cold, clammy, dusky extremities
in 17 per cent of his cases. This is an unusual finding.
Symptoms in Detail
_Onset and the Temperature Chart._—Dengue probably sets in more
abruptly than any other disease. The temperature chart is typically
saddle-back.
_The Pains._—Very marked soreness deeply seated about the place of
origin of the ocular muscles so that every movement of the eyeballs
is at once complained of as giving pain.
General pains all over the body, more especially of the back and
about tendinous insertions of the muscles which cause the pains to
be referred to the joints. The knee-joint pains are probably the
most frequent. The rachialgia may be as great as that in variola or
yellow fever.
_The Eruption._—The characteristic eruption does not appear until
about the time of the intermission or with the accession of the
terminal fever.
The fall of fever about the third or fourth day is often attended
by a critical epistaxis, sweat or diarrhoea, to be succeeded by an
intermission of from one to three days of a feeling of well-being.
About this time or with the secondary rise of fever the true dengue
rash appears. It is at first noted about the bases of the thumbs
and extending over the dorsal surfaces of the wrists. Almost
simultaneously a measles-like rash appears over the dorsal and
internal surfaces of the big toe extending to the ankle, especially
over the internal malleolus. Later on the elbows and knees may be
involved or the rash may cover thickly the entire body. A carmine
flush of the palms of the hands and soles of the feet is not
uncommon. A furfuraceous desquamation with much itching at times
follows the eruption. The so-called primary eruption is nothing
more than an initial flushing of the face, it is ephemeral. The
true dengue rash may also be quite ephemeral but usually it lasts
for two or three days, or possibly four or five days.
_The Nervous System._—Besides the headaches we have insomnia and
depression which extends through convalescence. Apathy is marked.
_The Blood._—This shows a leucopenia of about 4000 from shortly
after the onset together with a reduction of the percentage of
polymorphonuclears to about 45%. During the attack the eosinophiles
are decreased but there is an increase during convalescence.
DIAGNOSIS
The two diseases with which dengue can be most easily confused are
influenza and yellow fever. In fact when the great pandemic of
influenza (1890) first made its appearance in France, many regarded
it as an atypical form of dengue.
[Illustration: CLINICAL CHART ONE HUNDRED CASES OF DENGUE FEVER
FIG. 138.—Dengue. Analysis of Symptoms, from 100 cases occurring in
epidemic at St. Thomas, V. I. (After Lane, from U. S. Naval Medical
Bulletin.)]
The respiratory involvement of influenza and the eruption and
comparatively slow pulse of dengue are the principal points of
difference. It must be remembered that affections in the tropics,
diagnosed as influenza, have shown but slight respiratory symptoms,
the cases being more of a nervous or intestinal type. The eruption
of dengue may fail to appear or be missed in the study of the case.
The blood findings should aid in differentiation from influenza as
is also true of yellow fever, a disease which likewise has blood
findings of practically a normal character. Other than the blood
picture we have in yellow fever (1) albuminuria, coming on about
the second day, and (2) jaundice appearing about the third day.
In dengue the eruption appears from the third to the fifth day.
Albuminuria is absent in dengue.
Dengue may be mistaken for measles, but the early coryza, Koplik
spots and marked rash, first appearing about the face, should
differentiate.
In scarlet fever the rapid pulse, angina and leucocytosis should be
sufficiently differentiating.
Confusion with articular rheumatism may arise when the pain
about wrists, knees and ankles has been mistaken for true joint
involvement.
The headache and backache of smallpox may be confusing until the
eruption about the forehead appears. The leucopenia of dengue is
the main differential point in these first three days of doubt.
PROPHYLAXIS AND TREATMENT
=Prophylaxis.=—This would seem to rest entirely upon the question of
destruction of mosquitoes and prevention of the mosquito from biting
a patient. In dengue the virus is apparently in the blood for four or
five days so that screening of patients is necessitated for a longer
period than for yellow fever or phlebotomus fever.
=Treatment.=—The malaise and depression are generally so great that
the patient keeps his bed voluntarily. A light diet is indicated
although the anorexia is so marked that it is difficult to persuade a
patient to take food.
Cold spongings, provided the patient is not disturbed by being
moved, are of value for the insomnia. Phenacetine may be given for
the relief of the headache and backache. It is rarely necessary to
give morphine.
During convalescence tonics are indicated and if there is any
condition where a good wine is of value, it is in this, to
counteract the terrible depression. It has been suggested that
adrenal insufficiency may account for the asthenic, protracted
convalescence and from this standpoint adrenalin has been
recommended.
DENGUE-LIKE FEVERS
PHLEBOTOMUS OR PAPPATACI FEVER
=Etiology and Epidemiology.=—This fever, which is often called
three-day fever, on account of its running its course in this period,
is caused by a filterable virus. This virus only seems to be in the
blood of the patient’s peripheral circulation during the first
twenty-four hours of the illness, blood abstracted toward the end of
the second day and injected into a well person failing to reproduce
the disease.
If the blood is filtered through a Pasteur candle F, the filtrate
will set up an attack just as well as the unfiltered blood, in this
respect being like dengue and yellow fever. Couvy reports having
found spirochaetes in the blood 3 hours and 24 hours after the
onset.
The transmitting agent is a moth midge, _Phlebotomus papatassii_.
This midge, as is true of the psychodid family, to which it belongs,
is very hairy. It has long slender legs and narrow wings. The
proboscis is as long as the head and the lancets project beyond the
labium.
The female alone bites, which act takes place chiefly at night;
cool, moist, shady places, away from sleeping rooms, being
preferred in the day time. The insect is a persistent, vicious
feeder, difficult to escape from, as mosquito nets offer no
protection. It takes from six to eight days after feeding on a
patient in the first day of the fever before the midge is capable
of transmitting the disease, this being in accordance with the
twelve-day developmental period in the mosquito, that holds
for yellow fever. Doerr thinks that the pappataci virus may be
transmitted hereditarily by the insect to the egg.
At present, of the genera of the three families of midges, only
_Phlebotomus_ is known to transmit disease. _P. papatasii_
transmits phlebotomus fever in the Balkans. _P. minutus_ is the
host at Aden. Another species, _P. perniciosus_, can transmit the
disease. These moth midges are 2 mm. in length and have the body
densely covered with long yellow hairs. The second longitudinal
vein has three distinct branches. The antennae have 16 restricted
joints and the proboscis is as long as the head. The species of
_Phlebotomus_ are separated by slight variations in wing venation,
palpal lengths, etc., thus the second segment of palpi of _P.
papatasii_ is a little longer than the third one, while with _P.
perniciosus_ these segments are of equal lengths. In _P. minutus_
the second segment is only half the length of the third. The insect
lays about 40 eggs in damp dark places. The period of metamorphosis
from egg to insect is about one or two months, according to
temperature.
_Phlebotomus_ larvae die out in dry soil and very wet earth is
unfavorable. Moderate moisture and protection from light seem
necessary for their development. The remains of dead insects also
seem to make good breeding places. It is in cracks of old damp brick
or stone walls that the female most often deposits her eggs. Caves
are also selected.
Blood seems necessary for the fertilization of the eggs but lizard
blood seems more common in the stomach of _P. minutus_ than human
blood. They have also been observed to feed on other reptilian
bloods. The female insect has been kept alive in captivity up to
forty-six days.
Cases first appear in the late Spring and the disease becomes
epidemic during the Summer.
An attack produces quite an immunity.
The disease has chiefly been studied in the Balkan States but
undoubtedly it is widespread.
The disease is almost never fatal so that we know nothing of its
pathology.
=Symptomatology.=—The symptoms will answer perfectly for cases
of dengue one sees in a dengue epidemic in which, instead of the
saddle-back course of fever, we have a three-day primary rise and
then a fall to normal without any secondary fever rise. Cases of
phlebotomus fever are occasionally reported where the fever continues
seven or eight days.
The symptoms as usually given are as follows: After a period of
incubation of from three to six days there is an abrupt onset with
congested face and injected conjunctivae. There is pain in head,
eyes and back. There is marked malaise with great depression of
spirits. There is anorexia with coated tongue and rarely vomiting
and diarrhoea. There may be some congestion of the pharynx and
even a slight bronchitis. So much in common with influenza has it
clinically that a synonym is summer influenza. The liver and spleen
are normal. Mental depression is frequently noted. Epistaxis is
rather common.
There is a leucopenia and polymorphonuclear percentage decrease. The
two points which are chiefly advanced in its clinical differentiation
from dengue are (1) slow pulse, a bradycardia, and (2) only three
days of fever and absence of eruption.
SEVEN-DAY FEVER
Rogers first described a dengue-like fever which occurred in India
during the summer months as seven-day fever. The fever course was at
times typically saddle-back and again would be of continuous type.
A pulse relatively slow for the temperature is generally recorded,
together with sudden onset and general malaise. The spleen is at
times enlarged and there is a definite leucopenia and polynuclear
percentage reduction. The eruption is only occasionally present
(about 10%) and is an erythema which makes its appearance on the
extensor surfaces of the forearm about the fourth day after the onset.
=Etiology.=—In cases similar clinically to the seven-day fever of
Rogers, Ido, Ito and Wani have found a spirochaete resembling that
of infectious jaundice and designated _Leptospira hebdomadalis_.
It can be differentiated from _L. icterohaemorrhagiae_ by immunity
reactions. It is found in the blood during the fever period and young
guinea pigs can be infected by such blood either subcutaneously
or by mouth. The organism can be cultured by Noguchi’s method. The
spirochaete is to be found in the urine towards the end of the
disease and the urine is probably the source of infection. In Japan
field mice seem to be the carriers of this spirochaete. In about 3%
of such rodents the spirochaete can be found in the urine and the
disease is limited to the sections in which the field mice are found.
There is practically no mortality and the treatment is symptomatic.
SAND-FLY FEVER, AND THREE-DAY FEVER
These dengue-like fevers of India are practically identical
clinically with phlebotomus fever. The usual idea is that dengue
epidemics are far more explosive in character than is true of
epidemics transmitted by the sand-fly.
The strongest point in differentiation of sand-fly fever and dengue
is that neither confers any immunity for the other disease.
The distinctions of enlarged glands and break-bone pains are often
advanced as characteristic of dengue and not of sand-fly fever. I
have never observed other than slight glandular enlargement in dengue
cases.
SIX-DAY FEVER
Deeks has described a disease from Panama with a dengue-like clinical
course.
There were but slight changes from normal in the pulse rate or blood
findings. Some of the cases showed a late scarlatiniform eruption.
It was considered that the continuous fever for six days and
the enlargement of the spleen, which accompanied the disease,
differentiated it from dengue.
CHAPTER XXXVII
TSUTSUGAMUSHI
DEFINITION AND SYNONYMS
=Definition.=—This is an acute febrile disease caused by the bite of
the larval Kedani mite of the region where the infection prevails.
The onset is characterized by headache and giddiness, a rather
rapidly rising temperature and swelling of the lymphatic glands
draining the region in which is situated a small necrotic ulcer
marking the site of the bite. With injected conjunctivae, continuous
fever and hyperaesthesia, the disease goes on for about a week when
a macular eruption appears about face, then chest, extremities and
trunk. About ten days after the appearance of the eruption there is a
fall of fever by lysis.
[Illustration: FIG. 139.—The Kedani mite. _Trombidium akamushi._
(From Ruge and zur Verth.)]
=Synonyms.=—Flood fever, Japanese River fever, Kedani mite disease.
Shimamushi.
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—There are records which would indicate that the disease
has been known for more than 1000 years.
=Geographical Distribution.=—It is only in the western part of the
island of Nippon, when the banks of the Shinanogawa are inundated
each spring, that we find the disease. The disease is supposed
to be confined to Japan although Ashburn and Craig have thought a
disease observed by them in the Philippines as possibly identical.
ETIOLOGY AND EPIDEMIOLOGY
The cause is unknown, but has been attributed by some to various
bacteria and by others to a protozoon.
Nagayo attaches importance to piroplasm-like forms found in the
spleen and lymphatic glands.
Kawamuro and his colleagues could not demonstrate any organism by
any method of examination. The virus is in the blood and even as
small an amount as 0.001 cc. may infect a monkey although 0.1 cc.
is usually required. The virus is present also in the enlarged
lymph glands. Heating the blood at 50°C. for 10 minutes destroys
the virus. Recently Hayashi has reported as cause minute rod,
ring-shaped or spheroid bodies which when stained with Giemsa’s
stain are brought out in the lymphocytes and endothelial phagocytes
of lymph nodes and spleen. They also occur in the blood plasma
and in severe cases in red blood cells. He has transmitted the
disease to monkeys, guinea pigs and rabbits. These bodies resemble
bacteria, in this respect resembling the organisms of typhus and
spotted fever of the Rocky Mountains. Hayashi regards the organism
as resembling _Theileria parva_ and _Bartonella bacilliformis_,
and believes he has shown the field mouse to be a reservoir of the
virus.
The disease is not communicable from person to person and
only follows the bite of a larval mite, _Trombidium akamushi
(Leptotrombidium akamushi)_. This is a minute orange-red arachnoid
which can scarcely be seen with the naked eye. This mite is only a
source of danger in the region of the inundated river banks, its
bite not producing the disease elsewhere.
Persons harvesting hemp during August are liable to contract the
disease if bitten by the larval mite.
The mite is found in large numbers on the ears of field mice, these
hosts, however, not appearing to be suffering from any particular
disease.
PATHOLOGY
Other than the local ulcer and the swollen regional glands, there is
little that is definite. The spleen shows enlargement and there is
also swelling of the mesenteric glands. The lower part of the ileum
may show injection.
SYMPTOMATOLOGY
=A Typical Case.=—About one week after receiving the bite of
the larval mite, which may not have been noticed by the patient,
there develop chilliness, giddiness and headache, with a rising
temperature. In two or three days from the onset, painful glands are
noticed in certain regions as of groin, axilla or neck. From these
glands we can often by following inflamed lymphatics find the small
necrotic ulcer which is often located in the armpit or in the region
of the genitals. There is a dark red areola about the ulcer which is
only slightly tender. The glands are not very much enlarged and are
not excessively tender. There may be general glandular enlargement
following that of the primary swellings. The pulse rate is only from
80-100, notwithstanding the rise of the fever to 104°F. or even 105°F.
The body is decidedly hyperaesthetic and the conjunctivae are
injected. There is frequently deafness. About the seventh day a
macular eruption appears first on the face and then spreads to
chest, extremities and trunk. The eruption never becomes petechial.
The tongue becomes dry and cracked. There is often a cough. The
blood shows a leucopenia. The eruption disappears in from seven to
ten days and the fever becomes remittent or intermittent and, after
a few days, reaches normal. Parotitis may occur as a complication.
Schüffner has described a similar disease from Sumatra. The mortality
is, however, only 3% as against the 30% in Japan. He thinks it is
transmitted by a tick. In his cases the necrotic ulcer and glandular
enlargements were followed by a roseola which reached its maximum
on the eighth to tenth day and was most marked on the trunk and
flanks. The nervous symptoms resembled typhoid fever and there was a
lymphocytosis.
Symptoms in Detail
_The Nervous System._—There is marked giddiness and headache at
the onset. Hyperaesthesia of the body is quite characteristic.
There is often delirium at night. Deafness is frequently noted.
_The Cutaneous System._—A small necrotic ulcer about ⅙ inch in
diameter, with a dusky red areola, is noted at the site of the bite
of the larval mite. The healing of the ulcer is delayed well on
into convalescence.
About one week after the onset a dusky macular eruption appears
first on the face (cheeks), then going to the chest, legs, forearms
and trunk. It is not marked on neck, arms or thighs. It never
becomes petechial.
_Fever Course._—The temperature, which on the first day or
two reaches only 101° to 103°F., becomes later on higher and
continuous. About the tenth day from the appearance of the eruption
it begins to fall, becoming remittent and then intermittent.
_The Lymphatic System._—Very characteristic is the swelling of the
glands proximal to the initial ulcer. The connecting lymphatics may
be inflamed. Later on other glands may show slight swelling and
tenderness.
The spleen is usually enlarged.
_The Blood._—There is no change in the red cells but there is a
leucopenia.
DIAGNOSIS
In the differential diagnosis the limited geographical distribution
should prevent error and, in particular, where one has the initial
necrotic ulcer, with enlargement of the glands draining the region
in which it is located, there should be little confusion. Of course
plague may have a primary vesicle or ulcer with enlargement of
neighboring glands; these glands however are matted together and are
exquisitely tender.
Then too the eruption of tsutsugamushi and the early and more
stuporous state of plague should differentiate, even without the
aid of the laboratory.
It is usual to consider tsutsugamushi, typhus fever and spotted
fever of the Rocky Mountains as having many characteristics in
common. These diseases may best be differentiated by the fever
course and eruption as shown in the following table:
------------------+-------------------------+---------------------------
| Fever course | Eruption
------------------+-------------------------+---------------------------
_Tsutsugamushi_ |Fever increases each day |Begins on face, then chest,
| until reaching maximum | legs, forearms and trunk.
| about 4th or 5th day. | Does not become petechial.
| Fall by lysis after | First appears about 7th
| fading of eruption. | day.
------------------+-------------------------+---------------------------
_Tabardillo._ |Onset and termination |Begins on abdomen, sides of
_Typhus fever._ | of fever characterized | chest, thence going to
_Brill’s | by considerable | extremities. Petechial
disease._ | abruptness. | tendency. First appears
| | about 5th day.
------------------+-------------------------+---------------------------
_Spotted fever |Gradual rise during a |Begins on forearms and leg.
of the Rocky | week with lysis. | Petechial tendency. May
Mountains._ | | have gangrene of prepuce
| | and scrotum. First appears
| | on 2d to 5th day.
------------------+-------------------------+---------------------------
TREATMENT
There is no specific treatment. It may be necessary to use drugs to
combat the insomnia.
The serum of monkeys which have recovered from the disease seems to
have some value.
CHAPTER XXXVIII
SPOTTED FEVER OF THE ROCKY MOUNTAINS
DEFINITION AND SYNONYMS
=Definition.=—The disease is chiefly reported from certain sections
of the states of Montana and Idaho. The virus is not filterable
and is probably bacterial in nature and is transmitted solely by
the tick, _Dermacentor andersoni_, which arthropod host gets its
infection from certain rodents of the section serving as virus
reservoirs.
Maxey described the disease as follows: “An acute endemic,
noncontagious, but probably infectious febrile disease,
characterized clinically by a continuous moderately high fever,
severe arthritic and muscular pains and a profuse, petechial
eruption in the skin, appearing first on the ankles, wrists and
forehead but rapidly spreading to all parts of the body.”
=Synonyms.=—Rocky Mountain fever. Tick fever of the Rocky Mountains.
Black fever. Blue disease.
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—The disease was first noted in the Snake River Valley
of Idaho, about 1893, and in the Bitter Root Valley of Montana,
about 1890. There is some evidence that the disease may have
existed among the Indians prior to the advent of white settlers in
the Bitter Root Valley. The disease was first described by Doctor
M. W. Wood, U. S. A., in 1896. It is interesting to note that the
first white settlers of the Bitter Root Valley suffered from what
was considered a very fatal form of “black measles.”
In 1902 Wilson and Chowning reported that the disease was due to a
piroplasm of the squirrel and that it was transmitted to man by the
bite of a tick (_Dermacentor venustus_). Later Ashburn and others,
while accepting the tick transmission, failed to corroborate the
piroplasm etiology.
It is chiefly to Ricketts that we owe much of our detailed
knowledge of the epidemiology of the disease.
The work of McClintic and Frick along lines of prophylaxis has
given us practical measures for the control of the disease.
The views of Ricketts, Wolbach and Frick as to etiology are
discussed under that heading.
=Geographical Distribution.=—The two best known regions of
prevalence of the disease are the Bitter Root Valley of Montana and
the Snake River Valley of Idaho. It is also reported from limited
sections of Washington, Oregon and California, as also from Nevada
and Utah.
In Wyoming it is rather widely distributed.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—Wolbach states that he has noted certain bacterial forms
in the endothelial cells of the blood vessels of guinea pigs infected
with the virus, as well as a very general distribution in infected
ticks.
There are two morphological types—one, a chromatic-staining
lanceolate diplococcoid organism, found in the circulating blood as
well as in the endothelial cells, the other type—a blue-staining
rod-shaped form.
Ricketts noted certain chromatin-staining bacteria, in man and
in eggs of infected ticks, which were about 1 micron long by ⅓
micron broad, showed chromatin staining, were about the size of
_B. influenzae_, and appeared as two lanceolate-shaped bodies.
These bodies are now considered as belonging to the _Rickettsia_
group of organisms. Wolbach has named the organism of spotted fever
of the Rocky Mountains _Dermacentroxenus rickettsi_. In infected
guinea pigs Wolbach found these bodies particularly abundant in the
endothelial cells.
Frick has also found bodies within the red cells of human cases
and infected guinea pigs, as well as extracellularly, which showed
chromatin-staining characteristics, there often being an elongated
reddish body joined on to a larger blue-staining protoplasm.
In 1902 Wilson and Chowning reported the finding of piroplasm-like
bodies in the blood of human cases of Rocky Mountain Spotted
Fever. Ricketts proved that the virus was not filterable. A tick,
_Dermacentor andersoni_ transmits the disease.
=Epidemiology.=—The transmitting tick, _D. andersoni_ (_D.
venustus_) lives on the domesticated animals of the region of
geographical distribution of the disease. Ricketts showed that
the reservoir of the virus was to be found in ground squirrels,
chipmunks, mountain rats, etc., and that ticks feeding on these
rodents become infected and transmit the disease to man. The guinea
pig, white rat and monkey are also susceptible.
The virus can be propagated indefinitely in guinea pigs without
loss of virulence by weekly blood inoculations in another animal.
The virus seems to be transmitted by the salivary secretion of the
tick and a tick once infected remains infective for the remainder
of life.
Frick succeeded in obtaining anaerobic cultures from infected blood
of a bacillus, somewhat resembling the _B. typhi exanthematici_ of
Plotz. These bacteria, however, did not show complement fixation
with immune serum and were nonpathogenic to guinea pigs.
Spotted fever is a disease of rural districts and tends to give
only one case to a house, thus indicating the negative rôle
of bedbugs, lice, etc. It is at the time when ticks are most
abundant, in the months of the spring, that the disease makes its
appearance. The virus is in the blood during the entire febrile
course.
PATHOLOGY
The cadaver shows marked jaundice with petechial spots on extremities
and trunk.
There is marked venous engorgement and the blood is very dark and
fluid.
In the blood vessels we have proliferation of the endothelial cells
leading to thrombosis.
Ricketts noted enlargement of the lymph glands. The spleen is three
or four times the normal size and is quite firm. Microscopically
it shows extensive endothelial cell proliferation. The kidneys are
enlarged and congested. Gangrene of the prepuce and scrotum are
often noted.
SYMPTOMATOLOGY
The period of incubation is from five to ten days when the disease
sets in with considerable abruptness, with more or less marked
rigors, headache, malaise and severe pains of the larger joints, but
without inflammatory changes.
Some cases present a prodromal period lasting a day or so with
malaise and chilly sensations followed by the symptoms noted above.
Hyperaesthesia and photophobia are apt to be present during the
course of the disease.
The eruption first appears from the second to the fifth day as
macules about the wrists and ankles, thence spreading over the
extremities and extending to the trunk. These macules tend to
become petechial.
_The Pulse._—The pulse is not very rapid (90-110) and the fever
steadily rises day by day from the initial 102°F to reach a maximum
of about 105°F. by the end of a week or so. A toxaemic condition
appears early.
A stuporous state is fairly common but in many cases the mind is
clear throughout the course.
The spleen is palpable early in the disease and is quite firm, not
soft like the spleen of typhoid fever.
The kidney involvement shows itself early as an albuminuria.
Constipation is rather a constant feature.
Icterus and vomiting tend to come on later in severe cases.
_Gangrene._—Gangrene of the tonsils, scrotum and prepuce are more
common in the milder type of the disease, as seen in Idaho, than in
the more severe one of Montana.
There is leucocytosis early in the disease, falling to about 10,000
after a few days. There is an increase in the large mononuclears.
The eosinophiles are decreased in percentage.
DIAGNOSIS
The association of a tick bite and proper geographical distribution
is of prime importance. The more sudden onset, joint pains and
negative Widal differentiate it from typhoid fever.
Typhus fever shows more marked abruptness of onset and decline
of fever than does Rocky Mountain fever. The guinea pig, while
susceptible to both infections, is more easily infected with this
disease than with typhus fever.
As a matter of fact there are marked clinical resemblances between
typhus fever and Rocky Mountain fever. Tsutsugamushi and trench
fever also have points of resemblance.
[Illustration: FIG. 140.—Generalized eruption of spotted fever of
the Rocky Mountains. (Kindness of Doctor Frick.)]
PROGNOSIS
It is very remarkable that the disease should rather constantly
give a mortality approximating 75 to 90% in western Montana and
only about 5% for Idaho.
Where the nervous manifestations are marked the prognosis is more
unfavorable. Death tends to occur in the second week and patients
living through this week have a good chance for recovery. The death
rate is greatest in old people and least in young children.
PROPHYLAXIS AND TREATMENT
=Prophylaxis.=—_Dermacentor andersoni_ requires a long time to
become attached and feed on the human host—at least one or more
hours—hence inspection of one’s person for ticks after returning
from exposure and removing those found would tend to prevent
infection.
When these ticks attach themselves to the wool of grazing sheep,
87% seem to die, possibly from the effect of the fat in the wool.
Again such sheep can be dipped for further destruction of the ticks.
[Illustration: FIG. 141.—Female D. andersoni. 2. Head showing (a)
hypostome, (b) chelicerae, (c) palps. 3. Male.]
=Treatment.=—Just as with typhus fever the most important point
in the care of the patient is good nursing. The room should be
darkened and quiet maintained. Cool sponging lowers the temperature
and is a tonic for the nervous disorders. An ice cap is good for
the headache. The diet should be liquid and water should be given
freely on account of the tendency to renal involvement.
There is a tendency to heart failure so that the recumbent position
is demanded and cardiac stimulants indicated.
Michie and Parsons found sodium citrate of greatest benefit in
treating infected guinea pigs and recommended it for human cases.
It is to be used intravenously and about 60 cc. of a 5% solution
given twice daily. Immune sera were tried out by Ricketts, but
without result.
CHAPTER XXXIX
TYPHUS FEVER
DEFINITION AND SYNONYMS
=Definition.=—Typhus fever is an acute infectious disease, possibly
caused by _Rickettsia prowazeki_. There is a fairly abrupt onset,
with a continued fever lasting about two weeks, followed by a
critical fall or rather rapid lysis of temperature. About the fifth
day a rose spot eruption, similar to that of typhoid, first appears
about the loins and abdomen later on extending over the trunk and
extremities. The rash tends to become petechial and stands out rather
prominently on a general cutaneous mottling. The stuporous state is a
marked feature of the disease. It is transmitted by lice.
=Synonyms.=—Jail fever; Ship fever; Putrid fever; Petechial fever;
Typhus exanthematicus. Ger. Fleckfieber; Fr. Typhus exanthématique;
Sp. El tabardillo; Ital. Typho-esantematico.
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—Hirsch notes that the history of typhus fever belongs
to the dark pages of the world’s story, at times when war, famine,
and misery of every kind are present. It is reasonable to suppose,
according to this author, that many of the pestilences of ancient
times and the Middle Ages were typhus fever. This disease was
prevalent among the Spanish soldiers at the time of the conquest of
Grenada and the designation of the disease then used (Tabardillo)
is the one now given typhus fever in Mexico.
The disease was first described with sufficient accuracy by
Frascatorius, in the 16th century, to enable us distinctly to
differentiate it from plague; the stuporous states of the two
diseases having previously caused them to be confounded. In
England, in the 16th century, the disease was very prevalent in
the jails and court officials attending the trials of prisoners
often contracted the disease and died; hence the designation “black
assizes.”
During the Thirty Years War, in the 17th century, typhus fever
spread over central Europe.
Typhus fever was very prevalent at the time of the epidemic of
plague known as the great plague of London and it is a matter of
practical interest that the two diseases were not infrequently
confounded by medical men. There were some very severe epidemics of
the disease in Ireland in the 19th century.
Typhoid fever and typhus fever were only separated as distinct
diseases by Gerhard, 1837. Huxham, however, had previously noted
the marked difference between putrid malignant fever and slow
nervous fever.
Until very recent times it was declared that typhus fever was among
the most contagious diseases of man and innumerable instances were
cited of frequent contagion of those attending or visiting typhus
patients. In 1909, Nicolle, in North Africa, demonstrated that the
disease was transmitted by lice and the recent experiences in the
Balkan war and in the Servian epidemic of 1915 show that in the
absence of such vermin the disease does not appear to be contagious.
=Geographical Distribution.=—The disease has largely been
eradicated from European and other countries where hygienic
measures leading to the destruction of vermin have existed.
During the recent war the disease became one of importance, owing
to the difficulty of preventing the spread of body lice to the
soldiers.
In the tropics the disease, when present, is usually found in
regions of high altitude. In Mexico tabardillo, as typhus is there
designated, is a disease of the elevated regions. This is also true
of India.
Sporadic cases of typhus, known as Brill’s disease, have appeared
from time to time in New York.
During the great war typhus first appeared in Servia, thence
extending to Austria, Germany and Russia. Its nonappearance on the
Western battle line must be attributed to the active measures of
the Germans in attacking the lice problem. It is now widespread in
Russia and Poland.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—Recent work by Anderson and Ricketts has shown that the
blood of human cases is infective for monkeys. The virus does not
seem to pass through a Berkefeld filter and the epidemiology points
to the body louse as the sole transmitting agent. Nicolle reported
the filterability of the virus. More recently he has considered this
filterability as doubtful.
The guinea pig is susceptible to the virus as well as the monkey
but only shows temperature rise. Nicolle has shown that lice do not
become infective until about the tenth day after feeding on typhus
blood. The virus is found in the blood of man and in the spleen and
blood of monkeys and guinea pigs.
Plotz has isolated a Gram-positive pleomorphic bacillus from
the blood of typhus patients which has been named _B. typhi
exanthematici_. This organism is of historical interest only and
apparently has nothing to do with the causation of typhus fever.
Hort states that only blood recently taken from typhus patients
will cause the disease in monkeys while the same blood which
has been incubated several hours or days fails to produce the
disease. Others, as well as Hort, doubt the etiological relation
of the organism of Plotz to typhus fever or to the mild form of
the disease as seen in New York City and there known as Brill’s
disease. Tabardillo or Mexican typhus is the same as typhus.
Rocha-Lima insists upon the etiological importance of short oval
bodies, often showing polar staining with Giemsa preparations, and
found in the epithelial cells of the alimentary tract of lice which
have fed on the blood of typhus patients.
Ricketts noted similar bodies in such lice. They differ from the
Plotz organism in that they are Gram-negative and apparently cannot
be cultivated. Lice feeding on blood other than that of typhus
patients fail to show these bodies and furthermore the blood of
typhus cases during the period of convalescence fails to infect
lice. When guinea pigs are inoculated with emulsions of lice
containing such bodies they show the temperature reaction of typhus
fever. Plotz states that his organism may be Gram-negative at first
and believes these organisms to be the same. Wolbach and Todd
take the view that the bodies described by Rocha-Lima and called
_Rickettsia prowazeki_ are the cause of typhus fever. Similar
bodies have been found in trench fever and even in certain normal
lice. These bodies, however, are extracellular and are more oval
and stain more intensely than the typhus bodies. These Rocha-Lima
bodies require a Romanowsky stain to bring them out. In man these
bodies are found in the endothelial cells of the small blood
vessels, occurring singly or in clumps. In the louse the epithelial
cells of the intestine may be found distended with masses of these
organisms.
It is not certain whether the virus is transmitted by the bite of
the louse or by inoculation of faeces. Monkeys and guinea pigs can
be infected by injection of emulsions made from infected lice.
Loewe and others have succeeded in cultivating the virus of typhus,
using deep tubes containing 10 cc. of a rich ascitic fluid and a
piece of sterile rabbit kidney. The medium was inoculated with 2
cc. of typhus blood, after which 0.3 cc. of a 20% dextrose solution
was added and the culture sealed with liquid petrolatum. Its
reaction was pH 7 to 7.4. Cultures were incubated at both room and
body temperature.
As proving the culturing of the virus, it was noted that 1 cc. of
a fourth-generation culture would infect a guinea pig. This would
represent 0.00000016 cc. of the original typhus blood. The bodies
cultivated differ in morphology from the bacillus of Plotz in
that they are even more minute, of slight hazy outline and do not
assume polymorphous involution forms. They vary also in cultural
characteristics. Concerning the question as to the identity of the
bodies with _Rickettsia prowazeki_, no definite decision is as yet
permissible, nor were the authors able to decide whether the bodies
are of bacterial or of protozoan nature.
=Epidemiology.=—Until recently authorities stated that typhus fever
was the most contagious of all diseases. We now know that in the
absence of body or possibly head lice the disease is only slightly,
if at all contagious.
At the same time recent experience has shown that it requires
the greatest care on the part of those having charge of louse
destruction to avoid being infected while attending to this duty.
The same is true of those examining patients with the disease prior
to the eradication of the body lice of the sick.
A knowledge of the life history of the body louse is necessary. The
body louse, _Pediculus vestimenti_, is slightly larger than the head
louse, _P. capitis_, and is the species concerned in the transmission
of Indian and North African relapsing fevers as well as typhus fever,
although it is probable that the head louse can also transmit these
infections.
While the head lice live among the hairs of the head and show
their presence chiefly by the appearance of their pear-shaped
eggs (nits) projecting from the hair shaft, the body lice attach
themselves to the under surface of the garments worn next the skin,
and holding fast to the undershirt, feed about twice daily on the
human host. They are but rarely found on the skin. The female body
louse is about ⅐ inch long and about 1/15 inch broad (3.5 mm. ×
1.5 mm.). The antennae are somewhat longer than those of the head
louse. Warburton found that the egg stage, in experiments, lasted
from eight to forty days, the larval stage about eleven days, and
that the male louse lived three weeks and the female four weeks.
Of course, under natural conditions these periods may not hold.
Development of the eggs takes place best at a temperature of 30°C.
Lice feed at once after being hatched and a young louse will die
unless it feeds within 24 hours.
Lice will leave their host only when he has fever or when he dies
but they may drop off a host or be brushed off. They are not apt to
be found in bedding.
PATHOLOGY
Fraenkel, in 1914, first called attention to proliferative changes
in the endothelium of the arterioles and arterial capillaries,
followed by necrotic changes. These changes are chiefly manifest in
the vessels of the skin, central nervous system and myocardium. In
addition to the proliferation of the endothelial cells we have a
perivascular infiltration of small round cells. Kurt Nicol notes that
there is a combination of proliferative and inflammatory changes.
These are microscopical and there is absence of characteristic
macroscopic findings.
The petechiae are due to thrombosis of the smaller vessels
and subsequent haemorrhagic manifestations. Bronchitis and
broncho-pneumonia are extremely frequent and form the most common
fatal complication. The brain lesions are most common in the basal
ganglia, the cerebral cortex and the medulla.
The blood is dark-colored and the liver and kidneys show cloudy
swelling. The spleen is somewhat enlarged during the early stages of
the disease but tends to be normal in size later on. It is very soft
and may rupture while being handled at autopsy. There are no changes
in the Peyer’s patches and the mesenteric glands are not enlarged,
thus differentiating from typhoid fever. The heart muscle tends to
show degenerative changes.
SYMPTOMATOLOGY
The period of incubation varies from five to fifteen days, usually,
however, about twelve days. The period of onset may cover about
two days, during which time the patient has headache, giddiness,
backache, anorexia, perhaps nausea, and general malaise. There may be
rigors or chilly sensations.
[Illustration: FIG. 142.—Female _Pediculus corporis._—(Schamberg
_After Kuechenmeister_.)]
About the end of the second day the temperature rises fairly
rapidly to become 103° or 104°F. by the third or fourth day. With
the rise of fever the face becomes flushed, the eyes injected and
the expression apathetic. The headache is usually quite severe and
may be frontal, occipital or generalized. The temperature remains
elevated with slight morning remissions for from twelve to fourteen
days when it may fall by crisis or more gradually by rapid lysis.
Well-marked prostration and cardiac weakness are early noted. There
is a tendency to constipation and the mouth becomes foul and the
teeth rapidly covered with sordes, unless the greatest precautions in
oral cleanliness are observed.
There is a marked tendency to clouding of the consciousness. At
times the disease shows an abrupt onset rather than that described
above.
The eruption first appears about the fifth day and shows as slightly
elevated rose spots, which at first disappear on pressure, but
quickly tend to become permanent and later purpuric. The eruption
first appears in the flanks and then extends to the abdomen, chest
and later to the extremities.
The term mulberry rash is sometimes used to describe the rash of
typhus. In addition to the above there is a subcuticular mottling.
Along with the appearance of the rash the symptoms become aggravated,
the effect on the heart is more marked and the pulse becomes feeble.
The face is often dusky. There may be a bronchial catarrh with an
annoying cough.
By the end of the first week the delirious or stuporous condition
becomes more marked with a tendency to muttering delirium, tremors
and subsultus, the coma-vigil of the older writers. Terrifying
hallucinations may cause the patient to jump from the window and
kill himself. There is a tendency to parotitis and otitis media
connected with the mouth condition. On account of the circulatory
weakness there is a tendency to gangrene of the extremities,
especially the toes, rarely the fingers.
[Illustration: FIG. 143.—Temperature chart of typhus fever. (Pepper,
American Text-book of Medicine.)]
In cases which recover there is a critical change in the apparently
desperate condition of the patient about the end of the second week,
the sudden striking change for the better being more marked in typhus
fever than in any other disease. At this time the urine changes from
a high-colored, often albuminous one, to an abundant secretion of
more or less normal character.
The sporadic mild cases of typhus, which occurred from time to
time over a period of years in New York, were known as _Brill’s
disease_. According to Brill these cases showed intense headache,
apathy and prostration, with a continuous fever, maculo-papular
eruption and a rapid lysis or critical fall of temperature at the
end of about fourteen days. The spots only rarely became purpuric.
There was almost never marked delirium and the mortality was less
than 2%.
Symptoms in Detail
_The Eruption._—This first appears about the fourth day as macules
about loins, then spreading over abdomen, chest and back. It is
often more pronounced on the back than elsewhere. It almost never
appears on the face but may occur on the palms and soles. It has
a resemblance to the rash of measles. At first disappearing on
pressure it soon becomes permanent and then petechial. The livid
color of the rash has brought about the designation “mulberry
rash.” The rash lasts from a few days to two weeks.
_The Fever._—The fever rise following a chill is much more rapid
than in typhoid fever, reaching its fastigium in about three days.
A more or less continuous range of fever (103° to 104°F.) follows
until about the fourteenth day, when there is often a rapid lysis
or possibly crisis, at which time the patient tends to fall into a
refreshing sleep and to show a rather marked diuresis.
_The Alimentary Tract._—Constipation is usually noted. Very marked
is the tendency of the mouth and tongue to become dry and sordes
to collect on the teeth. The dry black tongue has led to the
designation “parrot tongue.” It is difficult to get the patient to
protrude his tongue when told to do so.
_The Circulatory System._—Very outspoken is cardiac weakness due
to myocardial degeneration. The heart sounds are very weak and
the pulse feeble. The blood pressure is very low, especially the
diastolic. Bradycardia may be marked during convalescence.
_The Respiratory System._—Cough may appear in the first days, but
usually is first troublesome about the time of the eruption. By the
end of a week the cough becomes loose and râles of various types
may be noted. Death often occurs from a terminal broncho-pneumonia.
_The Nervous System._—Clouding of the consciousness is as marked
in this disease as in plague. Dull aching frontal headache is
marked and a dull stuporous state soon comes on. Delirium is marked
in some cases. As in plague there are often the facies and mental
state of alcoholic intoxication.
_The Blood._—There does not seem to be anything very
characteristic in the blood examination. Prowazek noted that the
polymorphonuclears showed early fragmentation of the nucleus
and that the cytoplasm stained very red with Giemsa’s stain.
Robinowitsch noted that the leucocyte count fell in the first
day or two, then gradually rose until the crisis and then again
fell. The leucocytosis is only moderate, about 10,000, and the
polymorphonuclears make up about 80 to 85%. Eosinophiles are
decreased. Other observers have noted an increase in the large
mononuclears.
_Complications._—A bronchitis is very common and later on there
may be such a profuse expectoration that the patient cannot get rid
of it and may become cyanotic. Broncho-pneumonia is a very frequent
cause of death. Otitis media and parotitis are not infrequent
complications. Deafness is often marked.
Thrombosis of various vessels may be noted.
Gangrene of the extremities, especially the toes, is frequently
present. Gangrene of areas subjected to pressure, as over the
sacrum, is not infrequent. There does not seem to be the same
tendency to gangrene of the genitalia as in spotted fever of the
Rocky Mountains.
DIAGNOSIS
The more gradual course of the fever and the less marked stuporous
condition, together with positive blood cultures, should
differentiate typhoid fever.
Plague has the same picture of alcoholic intoxication as typhus,
but is without the rash. Influenza, with its acute onset, is
confusing but does not show any increase in leucocytes.
Other than a moderate leucocytosis and marked acid staining of
the polymorphonuclears there is not much that is of help from the
laboratory. When guinea pigs are inoculated with typhus virus the
period of incubation is from 7 to 10 days.
_Weil-Felix Reaction._—In the diagnosis of typhus fever we attach
great importance to an agglutination reaction (Weil-Felix reaction)
which the serum of typhus patients has upon certain organisms
designated as X_{2} and X_{19}. These correspond in characteristics
to certain strains of _Proteus vulgaris_, producing indol in peptone
solution, and acid and gas in glucose, maltose and saccharose, but
not in lactose or mannite. They digest gelatine and blood serum
somewhat more slowly than typical cultures of _Proteus vulgaris_.
Although these organisms have been isolated from the urine of several
typhus cases, it seems certain that these X bacilli are neither
causative organisms nor secondary invaders. The reaction is therefore
heterologous and not specific.
The reaction appears during the first week of the disease but becomes
quite marked in the second week and during convalescence. Thus a
titre of 1 to 25 on the fifth day usually rises to 1 to 200 or higher
by the end of the second week. The test is made either with living
or dead cultures and is carried out as for typhoid agglutinations,
preferably by the macroscopic method.
PROGNOSIS
Old people are apt to succumb, as do also those who show marked
delirium. In childhood it is a very mild disease.
An increase of eosinophiles is favorable while an absence of these
cells makes for a grave prognosis.
The death rate runs from 15 to 60% in many epidemics while Brill’s
disease only gives 1 or 2% of deaths.
PROPHYLAXIS AND TREATMENT
PROPHYLAXIS.—This consists almost exclusively in the destruction of
body lice, or preventing their access to the person.
Those attending cases should wear gowns, closely fitting at
neck and wrists, and rubber gloves. Better than a gown would be
“unionalls,” with stocking extremities to go over the shoes. The
typhus case should be deloused with the greatest thoroughness, and
his clothing sterilized.
For ridding the body of lice, the following steps are essential:
1. The hair of the body and head should be clipped.
2. The subject should be bathed, there being used freely
kerosene-emulsion soap, prepared by boiling 1 part of soap in
4 parts of water, and then adding 2 parts of kerosene oil. The
resultant jelly, when mixed with 4 parts of water, makes a liquid
soap that is convenient to use and which may be applied effectively.
3. Following the bath, the body may be anointed with kerosene,
special care being devoted to the hairy parts. Skin irritation may,
however, require early removal of the oil.
4. It has been found that lice on clothing removed from the
body may remain alive nine days and their eggs as long as forty
days. The clothing therefore should be disinfected by one of the
following methods:
(_a_) Steam; (_b_) boiling for five minutes; (_c_) 5% compound
cresol solution for 30 minutes; (_d_) chemicals such as cyanide or
chlorpicrin.
5. In the absence of facilities for carrying out the steps
described, or to prevent infestation subsequently, dusting powders
are sometimes used. Of these the N.C.I. powder, containing
commercial naphthalene, 96 Gms., creosote, 2 cc., and iodoform, 2
Gms., is the most widely known; but Moore’s powder—creosote, 1
cc.; sulphur, 0.5 Gm., and talc, 20 Gms.—is less irritating and
is said to be six times as effective. It has also been recommended
to wring out the underclothes in 5% compound cresol solution, then
drying thoroughly, or to impregnate them with substances such as
the halogenated phenols.
TREATMENT.—There is no disease in which careful nursing is so
important. This applies especially to the care of the mouth. It is
very necessary to maintain the recumbent position.
A mouth wash of equal parts of boric acid solution, glycerine and
lemon juice should be used to swab out the mouth several times
daily. Constipation should be controlled by enemata.
It is best to give the patient abundance of fresh air so that tent
treatment is to be recommended. Cool sponging lessens the nervous
manifestations as well as lowering temperature. Ice bags to the
head relieve the headache. Cardiac stimulants are indicated, as
caffein and camphor. Thyroid extract has been recommended. Lumbar
puncture has given amelioration of symptoms. Abundance of water
should be given and the diet should be milk and broths.
The virus of typhus is present in all the organs of an infected
guinea pig and Nicolle has prepared a serum by injecting horses
with emulsions of spleen and adrenals of such animals. The serum
has apparently given good results in human beings when employed
early in the disease, the temperature falling with each injection.
The dosage was about 20 cc. daily.
CHAPTER XL
TRENCH FEVER
DEFINITION AND SYNONYMS
=Definition.=—Trench fever is a specific, acute infectious disease,
probably caused by _Rickettsia quintana_, acquired usually through
the agency of the body louse, characterized by an abrupt onset, a
febrile period of about five days often followed by one or more
relapses, and ending in complete recovery.
Trench fever was one of the most widespread diseases occurring in
the forces of the World War. It is transmitted by contamination of a
skin abrasion or of a louse-bite wound with the faeces of an infected
louse, although Strong and his colleagues reported the bite of an
infected louse as a demonstrated method of infection.
Clinically, it shows an abrupt onset, with fever, headache, pain
on moving the eyeballs, soreness of the muscles of the legs and
frequently hyperaesthesia of the shins. As a rule the initial fever
is followed after a few days by a single short rise but there may be
a fever course of many relapses with apyretic intervals. Recovery is
complete, death practically never occurring; but convalescence may be
protracted, and incapacitating after-effects, such as neurasthenia,
cardiac disturbances and myalgia, may be noted.
=Synonyms.=—Pyrexia of Unknown Origin (P. U. O.), Meuse fever,
Volhynian fever, Shin fever, Quintan or five-day fever.
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—It is remarkable that so striking and communicable a
disease as trench fever should have been an unrecognized entity
prior to the recent war. While resembling dengue in some respects,
and relapsing fever in others, as well as various well-recognized
exotic fevers, there is no satisfactory account of the prior
existence of such a type of fever. Werner was of the opinion that a
quintan fever of the Middle Ages might have been trench fever, and
it has been suggested that a quintan fever described by Hippocrates
may have been of this nature, but the evidence is not convincing.
Some have thought that the miliary fever reported in France from
1821 to 1855 might have been a type of trench fever since it had no
mortality.
=Geographical Distribution.=—During the war, trench fever was
reported not only in Flanders, but also among the troops fighting
in Macedonia and Mesopotamia, and in the forces of the Central
Powers on the German and Austrian fronts. It is remarkable that
since the war this louse-borne disease seems to have disappeared,
although other diseases transmitted by lice, as typhus fever and
relapsing fever, continue to occur widely in Poland, Russia and the
Balkans.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—It now seems rather definitely settled that trench
fever belongs to the group of diseases caused by Rickettsia bodies,
and this species has been named _Rickettsia quintana_. Like the
other organisms of the group, these bodies are very small (0.3 to
0.5 by 1.5 to 2 microns), Gram-negative, nonmotile and stain best
by Giemsa’s method. As these bodies with their coccal or bipolar
staining characteristics, when observed in the eggs of ticks
infected with the virus of spotted fever of the Rocky Mountains,
showed the so-called chromatin staining, Ricketts regarded them as
chromatin-staining bacteria. Since, however, they are transmitted by
an arthropodan host, we believe now that they are probably protozoal
in nature.
Bradford and his colleagues stated that they were able to culture
these organisms by Noguchi’s method for culturing the organism of
syphilis, but Strong failed to obtain growth. As the organism of
typhus fever has recently been cultured by the same method, it
would appear that the trench fever organism also is cultivable.
The virus is present in the whole blood, in the plasma and in
the washed erythrocytes; it is nonfilterable, and withstands a
temperature of 56°C. for 20 minutes but not one of 80°C. for 10
minutes. These organisms in the alimentary tract of the louse are
extracellular, and not contained within the cells of the epithelium
of the gut of the louse. The trench fever bodies differ from those
of typhus in that they are plumper and stain more deeply with
ordinary aniline dyes.
=Epidemiology.=—The ordinary method of transmission is by the agency
of infected lice, but the disease can be produced artificially by
the injection of the blood of an infected person. It is probable
that urine also may be a factor in transmission, as Strong brought
about infection by smearing skin abrasions with urinary sediment from
trench fever cases.
It is now considered that the bite of the louse is noninfectious,
although Strong succeeded in transmitting the disease by this
means in five cases. The accepted explanation of the mechanism
of infection is that it takes place through contamination of an
abrasion or wound of the skin with louse faeces or with the juices
from the crushed bodies of infected lice. In this connection,
excoriations of the skin resulting from the scratching of
scabies-infested areas makes a scabies patient peculiarly liable
to trench fever infection. The louse faeces become infective only
after seven days from the time of feeding on trench fever cases,
this fact indicating a developmental cycle in the louse.
PATHOLOGY
As the disease of itself is never fatal, there have been no
opportunities for studying the pathological changes.
SYMPTOMATOLOGY
The period of incubation is usually given as from two to three
weeks. In the experimentally produced cases of the American Red
Cross Commission, the incubation period varied from five to thirty
days; thus with intravenous injection of blood it varied from five
to twenty days, and with inoculation of scarified areas with louse
faeces the period was between seven and eleven days.
The onset is quite abrupt with headache, dizziness and pain on motion
of the eyeballs. There is pain also in the back and limbs. The
conjunctivae are injected. The fever rises rapidly to 102°-104°F. and
falls rather abruptly to normal at about the fourth day. In most of
the cases a secondary rise occurs so that we may have a saddle-back
type of temperature chart.
The temperature charts tend to be grouped in three classes: (1)
Those with a short febrile course of a few days, followed by a
fall to normal, with or without a subsequent rise; (2) those with
a more or less sustained type of fever, extending over five or six
weeks without distinct relapses, and (3) those more typically of a
relapsing type, with five or six distinct febrile periods.
In more than one-half of the cases there occurs an eruption
of small (2 to 4 mm.) erythematous spots, which disappear on
pressure. They are usually located on chest, back or abdomen,
appear on the second day of the fever, and fade out by the fourth
day. Constipation and anorexia are usually noted. The spleen is
often somewhat enlarged. There is frequently a trace of albumin
in the urine, but it is not accompanied by casts. The cutaneous
hyperaesthesia over the shins is a prominent feature, but the same
disturbance of sensation may be complained of over the ulna or
fibula. Usually we find a leucocytosis but many cases show a normal
white count or even a slight leukopenia. During the apyrexia there
is an increase in mononuclear percentage. The pulse is rather slow
for the temperature.
DIAGNOSIS
Notwithstanding the intensive study given this disease during the
war, we do not seem to have any constant or reliable laboratory test.
In some of the cases where muscle pains of the neck are marked there
may be a stiffness of the neck that is suggestive of cerebro-spinal
fever. Similarly, pain of the abdominal muscles may cause a suspicion
of appendicitis and lead to an unnecessary operation.
The onset of trench fever is very like that of dengue or influenza.
In epidemic jaundice, the occurrence of the jaundice and marked
albuminuria should differentiate.
PROGNOSIS
This is most favorable as to ultimate complete recovery, but some
cases show a prolonged convalescence with manifestations of irritable
heart or neurasthenia.
PROPHYLAXIS AND TREATMENT
Prophylaxis consists in attacking the louse problem, although
attention should be given to the disinfection of the urine.
Acetylsalicylic acid may be given to relieve the headache and the
muscle pains; and some laxative for the usual constipation. There is
no specific treatment.
CHAPTER XLI
HEAT STROKE AND HEAT PROSTRATION
GENERAL CONSIDERATIONS
It has been customary to differentiate etiologically, as well as
clinically, the two most common manifestations of the effects of
high temperature. Clinically we note cases (1) with a rapidly rising
temperature, which often reaches a very high point, together with a
hot, dry, reddened skin, heat stroke; and again we note cases (2)
with pale clammy skin, marked evidences of cardiac weakness and a
normal or subnormal temperature, heat prostration.
Brooks in a most excellent discussion of the subject applies the
designation diathermasia to the former group of cases and regards
them as connected with an undue retention of heat within the body.
To the latter group, which he considers to be connected with
exposure to the actinic rays of the sun, he applies the designation
phoebism.
In diathermasia he considers that we have so great a strain on
the thermotaxic mechanism that there is loss of balance between
the heat discharge and heat producing centers, while in phoebism
there is primarily an acute cerebral or cerebro-spinal congestion
followed by a chronic inflammatory condition of the meninges and
due to damage from the actinic or ultra-violet rays of the sun.
While admitting that there may be cases where the effects of
certain rays of the sun are responsible for clinical manifestations
varying from death of striking suddenness to vague complaints of
irritability, headache and defective memory, yet the generally
accepted views are that high temperature, high relative humidity and
lack of evaporation from the skin, whether from excessive humidity or
from lack of circulation of the surrounding air, can and do produce
at one time heat stroke and at another heat prostration. Such factors
as muscular exertion, disease conditions, alcoholism and dietary
indiscretions undoubtedly play a part in the production of and
variance in the clinical manifestations brought about by the effects
of heat.
Sambon has suggested that there is a possibility that heat stroke
or, as it is also designated thermic fever or siriasis, is due to
a germ infection, but without advancing any particular evidence in
favor of such an hypothesis.
There is undoubtedly, however, much in favor of the views of
those who regard heat stroke and heat prostration as due to an
auto-intoxication from the accumulation of toxic substances resulting
from increased metabolic activity due to excessive heat retention and
having a selective action on the nerve cells.
Others think that as the result of more active metabolism there
is a retention of carbonic and lactic acid with a demand on the
alkali content of the blood resulting in an acidosis. As a matter
of fact treatment of heat stroke cases with intravenous or rectal
injections of sodium bicarbonate seems to be of marked value.
It would seem advisable to take the ground that heat retention
resulting from lack of heat radiation and insufficient skin
evaporation causes various manifestations of discomfort or bodily
injury. Aron in Manila showed that monkeys exposed to the sun died
in about one hour but that a control monkey, similarly placed, but
kept in a current of air from an electric fan, suffered little or no
injury. The reason that monkey and man react differently to exposure
to the sun is on account of the more numerous and more active sweat
glands possessed by man which give rise to increased evaporation and
resulting loss of heat of the body.
High relative humidity is a potent factor in checking evaporation.
The rectal temperature in Haldane’s experiments showed a rise of a
little over 1°F. when the wet bulb was at 90°F., 2°F. when at 94°F.
while at 98°F. it was about 4°F. per hour. Leonard Hill has noted
that the air surrounding the victims of the Black Hole of Calcutta
became saturated with water vapour and heated to the temperature
of the body so that it was heat stroke and not suffocation that
caused death. The power of air to hold water vapour and its
evaporative power increase rapidly with rising temperature; thus
at 50°F. a cubic foot of air holds 4.08 grains water, at 80°F.
10.9 and at 100°F. 19.7 grains. Hill states that the limit of an
Englishman’s power to keep cool is passed when the wet bulb exceeds
88°F. in the still air of a room even when stripped to the waist
and resting. If muscular work is performed the limit may be 80°F.
Walking in a tropical climate, wet bulb 75° to 80°F., dry bulb
80° to 90°F. may raise the temperature 2° to 3°F. and send the
pulse up to 140 to 160. All the students of ventilation stress
the importance of circulation of the air in promoting evaporation
and comfort. According to Hill with the air saturated and the wet
bulb reading 89°F. the wet ‘Kata’ readings would be 3.3 with still
air, 8.0 with the wind moving 1 meter a second and 15.1 with a
velocity of 9 meters per second. In tropical parts of the world
when the wet bulb not infrequently reaches 90°F. the circulation
of air by punkahs or electric fans becomes a necessity. There
is great variation in capacity for sweating which, according to
Hearne, is the basis of heat stroke. He notes that sweating is
suppressed from 1 to 48 hours before the attack. With sweating
suppressed the body temperature rises until, when 108°F. or more
is reached, unconsciousness and convulsions develop. Hearne thinks
that the inhibition of sweating is local in the sweat glands, and
not central, as diaphoretics fail to cause sweating once it has
stopped. As a practical point Hearne watched subjects for dryness
of the skin and when discovered they were stripped, covered with
a wet sheet and evaporation promoted by a current of air from an
electric fan. Doctor Leonard Hill has noted the inefficiency of the
application of pieces of ice to the hyperpyrexial body as compared
with evaporation. Thus water evaporation at body temperature
abstracts 0.59 calories per gram while melting ice only takes away
0.08 calories. Furthermore the application of ice constricts the
capillaries and interferes with evaporation. He also notes that 70
grams of water evaporated from the skin takes away as much heat as
1000 grams of ice water used as an enema.
PATHOLOGY
Pathologically, there is usually congestion of the
brain and meninges, that of the brain being particularly marked about
the region of the medulla. There may even be punctate haemorrhages
and the nerve cells show chromatolysis. These changes are much more
evident in heat stroke than in heat prostration.
McKenzie and LeCount have noted the following autopsy findings:
Generalized passive hyperaemia of brain and lungs, oedema of brain
and lungs as well as petechial haemorrhages of various mucous
membranes and the skin.
_Susceptibility to Heat Stroke._—As a matter of fact in a body of
men exposed to identical conditions of heat of sun and relative
humidity we note certain cases exhibiting typical heat stroke while
other men will only show evidences of heat prostration.
Alcoholism, obesity, diseases of heart and lungs, overcrowding,
muscular fatigue, insufficient circulation of air, with the wet
bulb about 90°F., and not drinking a sufficient amount of water,
predispose to heat injury.
It must always be kept in mind that the hyperpyrexial type of
malignant tertian malaria may give a clinical picture of heat
stroke.
Fiske has noted that in oil-burning firerooms, even with a
temperature of 140°F., 10° higher than on similar ships burning
coal, there were no cases of heat prostration. He attributes this
to the less fatiguing work in tending oil-burning furnaces and the
smaller number of men required, this reducing overcrowding.
SYMPTOMATOLOGY
_In heat stroke_ there are usually prodromata of dizziness, dry
skin, headache, and somnolence, following which the body temperature
shoots up to 105°F. or even above 110°F. There is a desire for
frequent micturition, which may be considered as a prodromal warning
of embarrassment of the sweating function. The skin is hot and dry
and the pupils may be contracted. The pulse which is at first full
and rapid, soon becomes irregular. There may be delirium or coma or
convulsive seizures. The patient is unconscious with irregular or
Cheyne-Stokes respiration.
Hiller divides these cases into (1) those showing an asphyxia
syndrome, as characterized by cyanosis and collapse, with cessation
of respiration and enfeebled circulation. Prolonged artificial
respiration is required in such cases. (2) A paralytic type
with deep coma, recurring convulsions and extreme hyperpyrexia.
These cases exhibit oedema of lungs and brain and necessitate
venesection. (3) A psychopathic type in which there is delirium
often of a violent type with delusions of persecution. Such cases
often commit suicide.
In _heat prostration_ we have giddiness and possibly nausea with pale
face, often bathed in cold perspiration and dilated pupils. The pulse
is very weak and syncope may ensue. The temperature is not elevated
and may be subnormal. Rarely the temperature is slightly elevated.
The respiration is shallow and sighing. Headache is often complained
of after recovery. Following this or the more dangerous heat stroke
we may have lack of mental concentration or loss of memory with
recurring headache upon even moderate exposure to the sun.
_Heat Cramps._—Among those working in firerooms on board ships
cruising in tropical waters, there is met frequently a condition
characterized by cramps of the voluntary muscles, chiefly those of
the extremities and abdomen.
Ill health and individual susceptibility appear to predispose
toward attacks, but apparently hard physical labor, in conjunction
with the environmental conditions, is the factor that determines
the occurrence of the cramps. Their causation is usually attributed
to dehydration of the tissues, or to accumulation of metabolic
products, but some believe that they represent a condition
differing from all other conditions recognized as being due to
heat. Cases, probably identical in nature and having the same
causative factors, have been noted as occurring among workers in
steel-mills.
The cramps are usually preceded by fibrillation of the muscles
later to be affected. When frankly spastic attacks are developed,
they recur at intervals of from 2 to 10 minutes, and may be severe
and very painful. The pupil is dilated, but so far as known, no
other organs are involved. The cramps are commonly accompanied by
signs of heat prostration. This, however, is not necessarily so,
there often being absolutely no thermal disturbance.
The treatment is in general that of heat prostration. Immediate
relief may be obtained by sudden slapping of an affected muscle.
For mild cases, immersion in a warm bath is recommended.
Apomorphine in sub-emetic doses is said to confer immediate
relaxation.
TREATMENT
With heat stroke we have a condition in which every moment lost
before the institution of proper treatment reduces the chances of
recovery. The two important measures are reduction of temperature
and elimination of toxic material. For the former ice packs or ice
baths are the most efficient. When the temperature starts down it
may fall with great rapidity and collapse result. Consequently when
giving these ice packs or baths the treatment should be discontinued
when the temperature by rectum reaches about 103°F., the patient
then being removed from the bath and covered with a blanket. If the
temperature again shoots up the ice bath can be repeated. Many have
reported great benefit from the use of enemata cooled with ice. Some
prefer to apply ice to the head and rub the body with pieces of ice.
This can be carried out on a rubber sheet placed on a cot. If there
is no ice available a sheet wet in dilute alcohol, plus the effects
of a current of air from the electric fan or otherwise, may be tried.
In a case with marked cyanosis venesection may be necessary. In
asphyxial types of sun stroke prolonged artificial respiration is
indicated.
Above has been noted the inefficiency of ice in reducing temperature
and the far greater effect from evaporation, brought about by
directing the current from a fan on the body covered with a wet sheet.
To promote elimination of toxic products venesection plus the use
of intravenous injections of normal saline is the best treatment.
In those terrible paralytic type cases which show a mortality of
more than 50% it is well to think of acidosis and give slowly about
a liter of a 1 or 2% solution of sodium bicarbonate. (See under
treatment of cholera.) The use of alkaline enemata often gives
good results, about a liter of a solution containing 2% of sodium
chloride and 2% of sodium carbonate or bicarbonate.
As soon as possible after the more urgent hydrotherapeutic
methods have controlled the case we should give calomel followed
by salines. The coal tar products should be avoided as far as
possible, from the danger of cardiac depression.
In the nonfebrile heat prostration the treatment is entirely
eliminative and stimulant. The patient should be placed on his back
in a cool shady place and tight clothing released, particularly about
the neck. Rubbing the limbs as for any syncope-type affection, with
hot water bottles if the collapse is marked, should be one line of
treatment. Many give a little aromatic spirits of ammonia or whiskey
but a hypodermic of strychnine would be better in a severe case.
Calomel and salines should be given after cardiac weakness
disappears. To avoid these dangers of the tropical heat one should
keep the body clean to promote good action of the sweat glands. The
clothing should be light and loosely fitting and should permit a
free circulation of air to assist evaporation. There does not seem
to be any indication for the wearing of orange-colored clothes as
the actinic rays are apparently unimportant. Puntoni recommends
green-colored clothing for neck and spine. The green cloth should
be covered with white material.
The head and nape of the neck should be protected by a light
well-ventilated helmet. Alcohol should be avoided, or at any rate
absolutely so, until evening. Water or lemonade should be taken
freely and a siesta in the middle of the day is an important
conserver of one’s resisting powers.
CHAPTER XLII
CLIMATIC BUBO, AINHUM, GOUNDOU, JUXTA-ARTICULAR NODULES AND VISCERAL
MYCOSES
CLIMATIC BUBO
General Considerations
The naval surgeons of various countries have for many years been
interested in a condition where inguinal buboes develop which have no
relation to venereal infection.
All attempts to find any organism in these lesions have so far
failed. Cultures from excised glands or from the necrotic centers of
such glands fail to show any growth.
Stained smears and India ink preparations alike fail to show any
causative organism. The Wassermann test is also negative. The
disease seems much more common in the West Indies than elsewhere,
statistics showing it to be about 10 times as often contracted by
sailors in those waters as by crews in the seaports of China. In
a recent article Rost states that he thinks there is evidence to
show that the disease is contracted by sexual intercourse with
prostitutes of the colored races. Of his 17 cases all had exposed
themselves in this way.
Children never show climatic bubo and it seems peculiarly to
affect the young adults composing the crews of ships. Even among
the native prostitutes such a condition does not seem to exist and
climatic bubo does not affect the male natives.
There may or may not be a periadenitis but there is thickening of
the capsule and fibrous septa of the glands. At times an apparently
healthy gland may show a necrotic centre, the contents of which,
however, will be found to be sterile. One often notes in sections
haemorrhagic infiltrations and oedema in the region of the peripheral
lymph sinuses. A point of differentiation from ambulant plague
buboes is the great increase in plasma cells in climatic bubo. It
will be remembered that Cantlie suggested that climatic bubo was an
attenuated plague but this idea has never been accepted. It has been
suggested that malaria might cause climatic bubo.
Symptomatology
The period of incubation is a rather long one, Rost in a
well-controlled case noting a period of at least five weeks. The
onset is very gradual, so the first intimation of a swelling in the
groins may be when a sense of heaviness is noted in that region after
prolonged work. For this reason they have been called “fatigue”
glands.
The glands of one side of the groin are usually involved although
the swellings may affect both sides. The deep iliac glands also
often show marked increase in size but the glands of the other
parts of the body, as axillary or cervical, are practically never
involved.
The swollen glands are only slightly tender and at first are discrete
and not attached to skin or underlying tissues. Later on with the
development of a periadenitis they may be firmly attached. In size
they are usually as large as a hen’s egg but may become much larger.
The overlying skin is as a rule normal and one may at times palpate
a soft center in an otherwise hard gland. Fever tends to come
on as an irregular remittent type and I have seen cases showing
temperature curves covering periods of two or three months which
were not unlike those of Malta fever. With increase in size of the
buboes there would be a two or three weeks’ rise to be followed,
with the subsidence of the swelling, by lysis and later on to be
renewed with reappearance of the bubo.
Climatic bubo runs a protracted course and does not respond at all
well to treatment. The cases often develop a moderate secondary
anaemia, which is most often noted in the relapse cases.
Diagnosis and Treatment
The history aids in differentiating gonorrhoeal, chancroidal and
syphilitic buboes. There is not the hardness and marked absence of
tenderness we get in syphilitic inguinal glands, and the reddened
overlying skin of the other veneral buboes should differentiate.
Plague buboes are exquisitely tender and the patient usually
manifests signs of extreme illness. In climatic bubo the patients
rarely seem sick.
Surgical treatment is usually recommended and some advocate a
radical enucleation of all glands in the region involved as we
find at times apparently normal glands to show necrotic centers.
My objection to enucleation is that the deep iliac glands are also
often involved and it is not only impossible to remove all affected
glands in such an inaccessible region but the surgical risks of
wounding the deep veins are great. I have seen this accident
occur more than once. Again the radical removal of all glandular
structures in the groins, with subsequent scar tissue formation,
obstructs lymph return so that elephantoid conditions result.
Rest in bed and hot compresses are of value when periadenitis
sets in. When softening occurs the aspiration of the pus with an
aspirating syringe and the subsequent injection of glycerite of
boroglycerine containing 10% of iodoform are to be recommended.
Some apply ointment of ichthyol, others pressure by shot bags.
X-ray treatment has been recommended.
Emily strongly recommends the injection of 3 or 4 drops of iodoform
ether (5%) into the center of the enlarged gland. This effects a
rapid cure. The author also employs other measures such as rest in
bed, wet compresses, and light mercurial ointment inunctions over
the bubo at night.
AINHUM
General Considerations
This disease, equivalent clinically to a spontaneous amputation of
the little toe, has been chiefly noted in the natives of the West
Coast of Africa, especially among the Kroomen and in Brazil. Cases
have been reported from the West Indies and rarely from the Southern
States of the United States. It does not attack white people and
the susceptibility of black races is probably connected with their
tendency to keloid development.
There have been all sorts of suggestions as to etiology: (_a_) that
it is related to leprosy, (_b_) that it is a tropho-neurosis, (_c_)
that it results from wearing constricting bands or rings on the
toe, (_d_) that it is connected with frequent injuries to the under
surface of the little toe.
Pathologically we find a fibrous cord which has replaced the bony
structures normally attaching the toe to the foot. We have, according
to Unna, a ring-form sclerodermia with thickening of the epidermis
causing an endarteritis with the production of a rarefying osteitis.
The disease is chiefly found in male adults between twenty-five and
thirty years of age.
=Symptomatology and Treatment=
In 90% of cases the little toe is the one affected, more rarely the
fourth toe or very rarely both the fourth and little toe. The little
toes may be attacked at the same time but the condition usually first
starts in one toe. At first we have a crack in the digito-plantar
fold of the little toe. This extends laterally and finally appears
on the dorsum. The distal portion of the toe enlarges and becomes
bulbous so that it looks like a small potato. The connection between
the foot and the bloated-looking toe is a limp fibrous cord which
permits the toe to wabble in various directions and to interfere
greatly with walking.
The course of the disease extends over several years if the toe
is not amputated by cutting through the fibrous pedicle or as the
result of ulceration from injury to the pedicle.
GOUNDOU
General Considerations
This is a disease which almost exclusively affects the black race
and is chiefly found in the West Coast of Africa, where it is called
big-nose or dog-nose. It is also found occasionally in China and the
Malay Peninsula.
The prominent root of the nose is due to exostoses from the nasal
processes of the superior maxillary bones.
Nothing definite is known as to etiology. Suggestions have been made
that it is connected with yaws, syphilis or leprosy. Again that it is
due to rhinoscleroma. Maclaud thought the hypertrophied tissues to
be incident to irritation from dipterous larvae in the nasal fossae.
Pathologically we have spongy bone covered by a thin layer of compact
bone.
Symptomatology and Treatment
At first there is complaint of headache and an associated nasal
discharge. At times the nasal passages may be obstructed by the
developing growth, which however usually projects externally on both
sides of the root of the nose just below the inner angle of the eyes.
Breathing through the nose is not as a rule interfered with.
The bony exostoses develop in a downward and outward direction.
The shape is generally oval. The disease commences in childhood
and the bony outgrowths slowly increase in size so that by adult
life they attain the size of a walnut. The overlying skin is normal
and not attached to the bony tumor. As the tumors grow they tend
to interfere with the vision of the patient. This is purely from
obstructing the lines of vision as the growth does not usually
invade the orbits. The treatment is entirely surgical and consists
in chiselling away the bony outgrowth.
JUXTA-ARTICULAR NODULES
General Considerations
These nodular masses were first noted by Macgregor from cases in New
Guinea but since then have been described from various parts of the
tropical world.
These tumor masses were given the name juxta-articular nodules by
Jeanselme, who studied the affection in natives of Siam. It may
be stated that at present we know nothing definite as to etiology
although several authors have reported fungi as the cause. This
fungus has been stated to be a species of _Nocardia_. Some of the
cases which have been reported would seem to be late manifestations
of yaws.
Symptomatology and Treatment
These tumor masses vary in size up to that of a golf ball and are
very hard in consistence. The skin over them is at first freely
movable, but later on may become attached. They are located
subcutaneously, especially about the external surfaces of the
extremities and particularly in relation to the joints. They are
not sensitive and rarely or never suppurate. The course is most
chronic and but rarely do they become absorbed.
[Illustration: FIG. 144.—Juxta-articular nodules. (After Steiner;
from Mense.)]
In those parts of Africa where the tumors due to _Onchocerca
volvulus_ are found there may be confusion in diagnosis but
these filarial nodes are elastic. By aspirating the swelling
microfilariae should be found in onchocerciasis.
The treatment of juxta-articular nodules is by excision should they
give trouble.
VISCERAL MYCOSES
The majority of cases of visceral mycoses reported from tropical
regions have been considered as caused by species of _Monilia_,
but not infrequently fungi of the genus _Cryptococcus_ have been
incriminated. As a rule the mycosis is reported as occurring in
cases which had been regarded as pulmonary tuberculosis. In some of
the cases there were cutaneous lesions, enlarged glands and even
generalized conditions as well as lung involvement.
Among the fungi reported for the lungs we have: _Rhizomucor
parasiticum_, _Nocardia pseudotuberculosis_, _Aspergillus
fumigatus_, _Penicillium crustaceum_, _Monilia tropicalis_,
_Monilia candida_, _Cryptococcus gilchristi_, _Coccidioides
immitis_ and various other species. A satisfactory study of the
true nature of the causative fungi has been made in only certain
instances and a scientific investigation of this phase of tropical
pathology is desirable.
_Bronchomoniliasis._—Castellani has used this designation for two
types of cases in which various species of _Monilia_ have been
reported as causative. In one type the symptoms are mild with
but slight impairment of health, there being only a cough with
expectoration of muco-purulent sputum. No fever is present. In the
severe type we have the symptomatology of pulmonary tuberculosis
with abundant reddish-gray sputum. In both types the diagnosis is
made by finding the fungi in perfectly fresh sputum. This should
be cultured in a hanging-block culture using Sabouraud’s medium.
The mycelium and budding forms can best be studied in such a
preparation. Negative findings for tubercle bacilli are important
in diagnosis. Potassium iodide is recommended in treatment.
_Sporotrichosis._—The infection with various species of
_Sporotrichum_ usually gives rise to gummatous lesions along the
lines of the lymphatics of the extremities. These tumor masses
break down and discharge a yellowish-brown pus. Rarely the process
generalizes, then often invading the lungs. Culturing of the pus or
sputum is necessary for diagnosis. In cultures the sporothrix shows
a narrow (2µ) mycelium with grape-like clusters of oval spores
at the end of a filament. The treatment recommended is iodide of
potash.
_Blastomycosis._—The causative organism, _Cryptococcus
gilchristi_, is found in the purulent discharge as oval to round,
doubly contoured, budding yeast-like cells 10 to 16µ. In cultures
we have formation of a mycelium resembling that of an oidium. The
lesions may be solely cutaneous or generalized in which latter case
the lungs are apt to be involved giving a condition resembling
pulmonary tuberculosis.
_Coccidioidal granuloma._—This is a very rare and fatal infection
caused by _Coccidioides immitis_, a fungus somewhat similar in
cultures to _C. gilchristi_ but differing in tissues in that it
gives rise to endogenous spore formation in the cells found in
the granulomatous material. The spores are about 3µ in diameter
and contained in a large cell (30-60µ) which does not bud. We may
have skin lesions accompanying visceral involvement or the latter
alone. When involving the lung the infection closely resembles
pulmonary tuberculosis. The spores metastasize readily by way of
the lymphatics involved and we may have a picture of pyaemia. Skin
lesions, when present, are ragged and punched out. About 40 cases
have been reported, chiefly from California.
PART II
DIAGNOSTICS OF TROPICAL DISEASES
CHAPTER XLIII
DIAGNOSTIC PROBLEMS AND PROCEDURES TOGETHER WITH COSMOPOLITAN
DISEASES IN THE TROPICS
In temperate climates we always keep in mind syphilis, tuberculosis
and the pyogenic infections when a diagnosis is in question. In the
tropics these conditions are just as common, if not more so, and
added to them we have many other diseases with protean manifestations
such as malaria, beriberi, leprosy, ancylostomiasis and other
helminthic infections, pellagra and amoebiasis.
The common mistake made by the physician when he first arrives
in a tropical country is to expect to deal chiefly with diseases
designated tropical. Before going to any tropical country the most
important preparation is the study of the statistical reports
from that section, covering a number of years. Everyone taking up
the study of tropical disease should first study the geographical
distribution of such diseases and those practising in temperate
climates should remember that the first question to be asked a man
suspected of having a tropical disease is “Where have you been
during the past months and years?” Then too the same question
should be applied as to intimate associates of the patient.
We all know how rare it is in temperate climates to find definite
pathological conditions in people who are apparently well. In such
people a definite finding of a cause sufficient to account for
an illness is usually the key to the diagnosis. With those from
the tropics, however, it is different. A single individual may be
found upon examination to have amoebiasis, malaria, filariasis and
syphilis, yet none of these infections prevent him from following his
usual occupation. When such a patient comes to a ward it requires a
correlating mind to eliminate four or five definite diagnoses, and
fix upon some disease which is common to both tropics and temperate
climates, as for example, typhoid fever.
In diagnosis in the tropics it is necessary to have at one’s
fingers’ ends the various physical signs and subjective symptoms
more or less characteristic of every disease of man as well as the
laboratory findings. It is only when one has at hand all obtainable
information that the solution of the medical problem becomes
possible.
Furthermore, it is necessary to be familiar with the fact that
certain infections, which at times give rise to marked alterations
in the health of a patient, may at other times, and in particular
when different races of man are concerned, give rise to no
recognizable interference with health. This is particularly true
of certain helminthological diseases, as for instance the slight
effects often noted in hookworm infection in the African races as
against the marked damage to those of the white race harboring such
parasites.
While the medical man is apt to have superabundant energy during
the first few months of his tropical service this later gives way
to the opposite state and in particular to a lack of initiative. It
is possible to do that which is absolutely demanded in the daily
work, but this is along the lines of routine requirements and to the
exclusion of new and difficult methods of diagnosis.
Consequently, while in possession of full energy and zeal one should
cultivate thorough and modern methods of study of his cases and make
these matters of routine, to use in the listless period to follow.
We do not usually fully appreciate the assistance the history of
the present illness as well as personal and family history of a
patient gives us, although it is generally recognized as the first
line of approach in diagnosis. In the tropics, when dealing with
natives, we have the difficulty of language to contend with as
well as with native superstition and popular ideas as to nature
and causation of disease. When employing a native interpreter
it is always well to keep in mind the fact that such assistants
will rarely admit of ignorance of the language of the medical man
and, furthermore, they try to twist the answers of the patients
to make them agree with what they may think is in accordance with
the desire of the examiner. Again in carrying out the physical
examination it is difficult to be certain that the findings as to
location or degree of pain, sensations, or time of appearance of
lesions, as well as data as to pulmonary, renal and alimentary
tract disorders, are correct.
For these reasons it would seem advisable to reverse the ordinary
methods of diagnosis when employed in the tropics. Instead of making
a tentative diagnosis following the physical examination, and then
confirming or adding to evidence with laboratory data, it is better
to first secure the findings as to blood, faeces, urine, sputum,
etc., and then check up such indications as to the diagnosis by a
final and thorough physical examination.
This method of procedure has been criticised by some of my
friends and in fact is a source of criticism on my part when,
as a laboratory worker, I have been asked by a purely clinical
colleague to make a routine laboratory examination of one of his
patients without any previous study of the case on his part. Every
laboratory man recognizes the assistance a tentative diagnosis
on the part of the clinician gives him in that it suggests the
examinations which should be gone into with particular care.
The present trend, even in temperate climate practice and always
with the tropical internist, is to have familiarity with laboratory
technique and interpretation as well as with the methods of
physical diagnosis; consequently the tropical practitioner makes no
dividing line between the diagnostic information obtained in the
laboratory and that gotten at the bedside.
It is not difficult to train a native helper to make and stain
good blood smears as well as to examine such preparations, and the
same holds for the urine and faeces preparations. The skill in
making preparations, the familiarity with pathological findings
and the patience in studying a preparation on the part of these
assistants is at times a matter of surprise. Thus in a few minutes
the physician can check up these findings or the lack of findings
and have them at hand to assist him in his study of his case.
=Laboratory Examination.=—In the laboratory the routine examination
should embrace, first, a study of a _stained blood smear_. It is
essential that the smear be well made and the Romanowsky stain used a
good one.
While more difficult to make than a smear on a slide the
cover-glass smear method of Ehrlich has the advantage that the
white cells are more evenly distributed and consequently the
differential count more reliable. Furthermore, after a little
practice, one can approximate the white count of a patient by
examining the stained smear with a low power objective (16 mm).
In my experience I get a better general impression of a large
mononuclear increase with the low power than I do with the
oil-immersion. As a matter of fact one can make his differential
count with a low power objective after some practice. Next, using a
high dry or immersion objective, we search for malarial parasites.
It must be remembered that even when there is nothing diagnostic
in a stained blood smear there is much information to be obtained
in the way of diagnostic exclusion. Furthermore, while looking
over the preparation some diagnosis may suggest itself and there
is nothing more important in diagnosis than to have possibilities
of diagnosis in mind. It is often stated in connection with the
diagnosis of liver abscess that one should always suspect liver
abscess in a tropical patient and this will hold for other diseases
and thus the careful examination of a blood smear may be suggestive
if not diagnostic.
Next the _faeces_ should be examined both in an ordinary preparation
and in one mounted in Gram’s iodine solution.
In the preparation made from a particle of faeces, emulsified
in salt solution, we can note any excess of fatty acids or soap
crystals and lack of normal digestion of meat fibres as well as
presence of ova of intestinal parasites. Again such a preparation
is necessary for noting amoeboid activity of amoebae as well as for
the motility of flagellates and _Strongyloides_ embryos. In the
preparation mounted in Gram’s iodine solution we have distinctly
brought out the nuclear division of encysted amoebae, our most
practical means of differentiating between the pathogenic and
nonpathogenic amoebae. This method also brings out flagellate
characteristics. Again, any undigested starch grains show up
distinctly by reason of their blue color. Blood cells and yeast
cells stain a golden yellow.
In the examination of the _urine_ it is well to take up with a
pipette the entire sediment from a centrifuged tube of urine and
deposit it on a slide.
Examination with diminished illumination and using the two-thirds
objective quickly enables us to ascertain presence and character
of casts. This same sediment is then treated with Gram’s iodine
solution and a cover-glass applied. Such a preparation, using the
one-sixth objective, brings out distinctly the differentiation
of pus cells from renal epithelium as well as showing clearly
golden-yellow red blood cells. While centrifuging one can test for
albumin. A qualitative test for sugar takes only a few moments to
make.
These simple quick tests of blood, faeces and urine suffice for
the preliminary laboratory work in a case. Following the physical
examination we can carry out more elaborate laboratory tests as
indicated by the tentative diagnosis obtained from the physical
examination and preliminary laboratory investigations.
=Physical Examination.=—As regards the physical examination it must
be remembered that in the tropics glandular enlargements and skin
eruptions are so essential in diagnosis that the rule generally
adopted in skin clinics should be adhered to, that is an inspection
of the entire body surface, either by stripping the patient or
removing clothing from one part at a time.
The sphygmomanometer is of value in the diagnosis of tropical
affections as well as those of temperate regions. Similarly,
functional tests of the heart and kidneys, basal metabolism
determinations, chemical examination of the blood, and tests for
acid-base equilibrium may give definite information—in one climate
as in another.
Palpation is peculiarly important in the diagnosis of the enlarged
spleen, liver and glands of many tropical affections as well as for
mapping out intestinal thickenings. Again in going over the patient
for outlining heart, liver, etc., palpatory percussion is more
satisfactory than the usual mediate percussion.
I find the use of the entire palmar surface of the middle finger,
gently tapped over the surface, to give better results than any
other method. In this way the percussion note is well elicited
and the sense of resistance most satisfactorily obtained. The use
of the tips of the index, middle and ring fingers, with a piano
playing stroke, also should be employed.
One should always determine the character of the reflexes. Of these
the most important are the patellar and biceps ones. This latter
reflex is normally rarely obtained.
The pupillary reactions also require little time for eliciting and
are of much value in differentiating a peripheral neuritis from a
cord lesion.
COSMOPOLITAN DISEASES IN THE TROPICS
In considering the matter of the general prevalence of disease in
the tropics it has seemed advisable to present statistics from
the standpoint of deaths rather than admissions for disease, the
probability of accuracy in diagnosis being greater where there may be
the assistance of an autopsy.
In the following table I have selected three tropical places under
American sanitary control, the city of Manila, the city of Panama
and the Island of St. Thomas, Virgin Islands. The statistics
embrace the calendar years of 1918, 1919 and 1920 The statistics of
Manila relate solely to the Filipino population resident in Manila,
it does not include Americans or other nationalities. The Filipino
population of Manila in 1920 was 263,386. The three years covered
had respectively a death rate of 49.97, 28.66 and 27.48 per 1000.
-----------------+------------------+-----------------+-----------------
| City of Manila | | St. Thomas, Vir-
Place | (Filipinos only) | City of Panama | gin Islands of
| | | United States
-----------------+------------------+-----------------+-----------------
Population | | 263,386| | 60,500| | 10,191
No. of deaths |11,840|7,378|7,238|1,314|1,211|1,297| 248| 176| 185
Rate per 1000 | 49.97|28.66|27.48|21.41|19.73|21.44|24.33|17.27|18.15
Calendar year | 1918| 1919| 1920| 1918| 1919| 1920| 1918| 1919| 1920
-----------------+------+-----+-----+-----+-----+-----+-----+-----+-----
Typhoid fever | 180| 171| 226| 0| 3| 2| 4| 0| 0
Malaria | 64| 46| 75| 14| 10| 4| 1| 1| 0
Smallpox | 837| 31| 1| 0| 0| 0| 0| 0| 0
Measles | 16| 3| 12| 2| 0| 1| 0| 0| 0
Whooping-cough | 7| 0| 5| 1| 7| 2| 0| 1| 1
Diphtheria | 14| 16| 9| 4| 10| 5| 0| 0| 0
Influenza | 424| 42| 31| 7| 1| 29| 8| 1| 0
Asiatic cholera | 108| 328| 2| 0| 0| 0| 0| 0| 0
Dysentery | 678| 390| 253| 3| 9| 5| 2| 1| 0
Leprosy | 2| 2| 3| 3| 1| 2| 0| 0| 0
Purulent | | | | | | | | |
infection and | | | | | | | | |
septicaemia | 26| 23| 28| 9| 9| 7| 0| 1| 0
Tetanus | 82| 83| 84| 3| 2| 1| 1| 1| 0
Pellagra | 0| 0| 0| 6| 5| 5| 15| 4| 0
Beriberi | 551| 324| 548| 1| 2| 1| 0| 0| 0
Tuberculosis of | | | | | | | | |
the lungs | 1,605|1,334|1,340| 223| 206| 169| 20| 20| 27
Cancer and other | | | | | | | | |
malignant tumors| 80| 73| 65| 26| 34| 44| 6| 11| 6
Alcoholism | 3| 3| 2| 2| 1| 2| 0| 1| 0
Diabetes | 6| 6| 11| 3| 3| 0| 0| 0| 0
Simple meningitis| 448| 292| 300| 12| 11| 14| 1| 2| 0
Cerebral | | | | | | | | |
hemorrhage | 109| 99| 93| 27| 39| 40| 10| 9| 4
Convulsions | | | | | | | | |
(infants) | 224| 148| 91| 3| 4| 5| 4| 1| 1
Acute | | | | | | | | |
endocarditis | 46| 29| 28| 17| 14| 7| 0| 1| 2
Organic diseases | | | | | | | | |
of the heart | 118| 95| 93| 63| 37| 45| 9| 17| 27
Diseases of the | | | | | | | | |
arteries | 18| 23| 15| 15| 27| 34| 9| 7| 9
Acute bronchitis | 975| 335| 630| 34| 14| 17| 0| 0| 0
Chronic | | | | | | | | |
bronchitis | 286| 331| 235| 4| 1| 3| 0| 0| 0
Broncho-pneumonia| 872| 293| 372| 86| 109| 108| 15| 10| 6
Pneumonia | 220| 86| 101| 60| 62| 59| 5| 8| 8
Diarrhoea and | | | | | | | | |
enteritis (under| | | | | | | | |
two years) | 642| 365| 365| 156| 136| 162| 13| 4| 11
Diarrhoea and | | | | | | | | |
enteritis (over | | | | | | | | |
two years) | 429| 253| 164| 9| 16| 13| 9| 4| 5
Acute nephritis | 159| 88| 102| 18| 21| 14| 0| 1| 1
Chronic nephritis| 265| 248| 156| 72| 63| 63| 15| 16| 21
Intestinal | | | | | | | | |
parasites | 16| 12| 5| 0| 2| 0| 1| 0| 0
Congenital | | | | | | | | |
debility | 614| 460| 611| 32| 13| 21| 13| 14| 6
Senility | 531| 451| 357| 17| 7| 9| 13| 0| 1
+------+-----+-----+-----+-----+-----+-----+-----+-----
|10,655|6,483|6,413| 932| 879| 893| 174| 136| 136
-----------------+------+-----+-----+-----+-----+-----+-----+-----+-----
The population of the city of Panama during the year 1920 was
60,500. The death rate during the years covered was 21.41, 19.73,
and 21.44 per 1000, respectively.
It may be stated that the average population of the Canal Zone
during 1920 was 27,459, with 242 deaths, giving a death rate of
8.81 per 1000.
The population of St. Thomas during 1920 is estimated at 10,191.
The death rate during 1918 was 24.33, during 1919, 17.27 and during
1920, 18.15 per 1000.
The diseases in the table of deaths do not account for all the
deaths, the others having been from other diseases, accidents, etc.
In studying the Manila statistical reports more in detail we note
that during 1920 there were reported 64 cases of diphtheria, 387 of
measles and 577 of typhoid fever. The reasons for the high death
rate in 1918 are clearly seen, namely, the epidemics of influenza
and smallpox. As is the case in nearly every epidemic of influenza,
the increase in deaths from this disease was accompanied with a
large increase in deaths from acute bronchitis and the various
pneumonias, conditions that in many cases should have been ascribed
to influenza. The smallpox epidemic during 1918 was brought under
control by a very extensive vaccination campaign. Only one death
from this disease occurred in 1920.
During 1920, there were reported in Panama 95 cases of diphtheria,
313 of influenza, 154 of measles, 9 of typhoid fever, 4 of scarlet
fever, 14 of smallpox and 311 of tuberculosis.
During the same period there were reported in St. Thomas 6 cases
of chickenpox and 40 cases of tuberculosis. No cases of influenza,
smallpox, measles or typhoid fever occurred. From reports for the
year of 1921, it is noted that an extensive although not severe
epidemic of measles has been present in the Virgin Islands during
said year.
From the above tables we note that as far as actual causes of
deaths are concerned the cosmopolitan diseases play a more
important rôle than those we designate tropical diseases.
Tuberculosis ranks first, other respiratory infections come a
close second. Organic diseases of the heart and other degenerative
diseases, such as chronic nephritis, are also noted for their
frequency. The gastro-intestinal infections, typhoid fever,
dysentery, diarrhoea, probably serve as a barometer of the sanitary
conditions of a city.
But there are many other diseases whose importance from an economic
standpoint may not be fully appreciated from mortality tables.
Notable among these are venereal diseases, malaria, filariasis,
yaws and hookworm diseases. Further it may be noted that many
diseases without being the direct cause of death have a distinct
bearing on the mortality. Amongst these we note particularly the
various worm-infestations. The experience in Bilibid prison is an
illustrating example. The mortality amongst the prisoners dropped
markedly after the inmates had been cured of their various worm
conditions.
=Rheumatic Fever and Scarlet Fever.=—From a study of the statistical
reports and from the writings of various authorities there would
seem to be two cosmopolitan diseases, which are of extreme rarity in
the tropics, rheumatic fever and scarlet fever.
It is true that in the Gold Coast report for 1911 there are noted
614 cases of rheumatic fever with one death.
There does not, however, appear to be any striking increase in
admissions for valvular disease of the heart as would naturally be
expected.
In Calcutta, in 1911, there were 74 deaths from rheumatic fever.
As regards scarlet fever, statistical reports from various parts of
the tropical world fail to show cases.
In a report from Shanghai, which can hardly be considered as a
tropical city, there is a statement that this disease first made
its appearance in 1900, since which time it has spread among the
Chinese, exhibiting marked virulence. Again in a Basutoland report
there were quite a number of cases reported (67), but as this
colony is in the extreme south of Africa it could hardly be called
tropical.
=Typhoid Fever.=—When reliance for diagnosis rested almost solely on
clinical manifestations, it was held that typhoid fever was rare or
unknown in the tropics.
Since the advent of laboratory methods of diagnosis it has become
known that typhoid and the paratyphoid fevers are quite common. The
paratyphoid infections are more common in the tropics than in the
temperate regions. The fever course and clinical picture of typhoid
in the tropics are distinctly atypical. It was formerly common to
consider cases of typhoid as malaria and in the southern states of
the United States it was a common thing to diagnose typho-malarial
fever.
Of course, latent malaria is apt to flare up in a person sick with
typhoid, but the idea that there was a symptom-complex partaking
of the characteristics of typhoid fever and malaria is now classed
with historical data.
It is a remarkable fact that in many of the cities of the Orient
conditions favoring infection with typhoid fever, such as neglect
of the most elementary measures of disposal of faeces and lack of
safeguarding of water supplies, exist and yet the natives seem to
have an immunity to organisms causing alimentary tract diseases. It
must be that such immunity is acquired by attacks of the disease
in childhood. Certainly, Europeans in such communities have no
protection unless they are vaccinated. It must be remembered that
the protection from vaccination against the enteric group of
bacteria can be relied on for not longer than a period of two years.
It would seem that typhoid fever in tropical countries is more
serious than in temperate climates—thus the death rate in India is
about twice as great.
In the absence of laboratory tests the chief reliance in the
clinical diagnosis of typhoid should rest in the rather gradual
onset of a continued fever, with a rather apathetic toxaemia. Of
course atypical cases may have a fairly abrupt onset. An important
point in the diagnosis is the rather slow pulse rate for the
temperature elevation.
_Marris Atropine Test._—Manson-Bahr regards the Marris atropine
test as of the utmost value in the diagnosis of the enteric
group of fevers. In this test one gives a hypodermic injection
of grain 1/50 of atropine sulphate. Should the case be typhoid
or paratyphoid the pulse rate is practically uninfluenced during
the period from 25 to 50 minutes after the injection. In other
infections or in normal individuals, the pulse rate drops at first
but after 10 or 15 minutes rises to exceed the pulse rate before
the injection by 30 or 40 beats during the period of 25 to 50
minutes following the injection.
In the laboratory tests the prime reliance must be placed in blood
culture, which of course should be made during the first ten
days of the illness. Blood cultures give positive results in the
inoculated as well as in those not protected by vaccination.
Agglutination tests are the ones of choice after such a period, but
one must discount agglutination in those who have been vaccinated
previously. Of course the rising agglutination titre during the
course of the disease gives valuable information, and the Dreyer
technique, where simultaneous tests are made on emulsions of
typhoid, paratyphoid A and paratyphoid B at intervals of 4 days,
noting a distinct rise for one of these organisms, is based on this
factor. At the same time this technique is exacting and does not
seem to have given the results that were at first expected.
Culturing the urine is of more value in diagnosis than that of the
faeces. Bacilluria may be expected in about one-fifth of cases
after the second week. Faeces culturing gives positive results in a
smaller proportion of cases and is attended with much difficulty.
_The Paratyphoid Fevers._—The paratyphoids would seem to be
more prevalent, in proportion to typhoid, in the tropics than
in temperate climates, thus in India, of 1886 British soldiers,
convalescent from enteric fevers, 791 were diagnosed as typhoid,
633 as paratyphoid A, 136 as paratyphoid B and 326 as enteric cases
of uncertain etiology. Paratyphoid B cases seem more frequent in
temperate climates than paratyphoid A ones, as noted during the
war in France. Cruickshank, and Lafrenais, in a study of carriers,
among the 1886 cases noted above observed that 49 became carriers
and of these 34 were from paratyphoid A cases, 9 from typhoid
convalescents and 6 from paratyphoid B convalescents. Of 13 chronic
carriers (those carriers excreting organisms after a period of six
months) 8 were carriers of paratyphoid A, 4 of typhoid and 1 of
paratyphoid B.
This evidence would indicate that paratyphoid A, once introduced,
would spread more widely than the other enteric affections.
Clinically, paratyphoid A cases resemble typhoid ones rather
closely, although as a rule less severe in course. With paratyphoid
B the course is less severe than with the other enteric organisms
but it often shows an abrupt onset and is frequently similar to
cases of meat poisoning. This organism and the Gärtner bacillus
are common excitants of the so-called ptomaine poisoning cases.
Paratyphoid B cases show a tendency to localize in the pelvis of
the kidney or elsewhere and may cause a broncho-pneumonia.
_Colon Infections._—Such infections seem to be rare in temperate
climates other than as localized conditions especially of the
urinary bladder. Cholecystitis is not infrequently due to a colon
bacillus infection. In the tropics, however, especially following
bacillary dysentery, we may have a generalized infection which may
result in a fatal septicaemia. In such cases abscess formation in
the kidneys is usually found.
Cases diagnosed as mild typhoid fever have as a result of blood
cultures been found to occasionally be due to a colon bacteriaemia.
In temperate climates as well as in the tropics pyelitis is often
due to a colon infection and probably 10% of cases of appendicitis
are caused by the colon bacillus alone, although it is extremely
frequent in association with streptococci or staphylococci.
_Bacillus alkaligines faecalis_ infections. Cases similar to
typhoid fever have been found to be due to infections with this
member of the typhoid-colon group of organisms.
=Tuberculosis.=—The negro race seems to possess a greater
susceptibility to tuberculosis than the white one, a fact well
recognized in the United States, where the colored population suffers
far more severely than their white neighbors. The yellow races also
show marked susceptibility to the scourge and in the Philippines it
is easily the greatest cause of death.
In tropical regions the natives of the sea-level regions suffer
more than those of the mountain plateaus and where the humidity is
high rather than in arid sections. Thus tuberculosis is very rare
or almost unknown in the dry desert-like regions of upper Egypt and
the Sahara desert.
The disease gains headway in the rainy season and diminishes in
prevalence during the dry season.
One factor in the great spread of the disease is the intimate
contact of natives living together in a small room.
It is generally recognized that susceptibility is greater in
childhood and that infection by way of the alimentary tract is common
in children.
When one notes the habit of expectorating anywhere and everywhere
on the part of people untrained in hygienic rules, it is easy
to recognize the opportunity babies and young children have of
ingesting tuberculous material taken up on their hands while they
are crawling about.
During the war there was a great deal of tuberculosis among the
native African troops serving in France, and a study of the disease
in these men has furnished us information as to the existence
of two clinical types among them. In the soldiers from Morocco
and Algiers, the type observed was similar to that occurring in
Europeans, and this was explained on the basis of the opportunity
that had been given the people of the areas from which the troops
came to acquire tuberculosis from contact with white colonists and
during a period of many years to have acquired a certain degree of
resistance to the invasion of the tubercle bacillus.
In connection with the Senegalese troops and some others coming
from sections of Africa where tuberculosis was rare or nonexistent
another type was observed which corresponded with the tuberculosis
one sees in a young child or a guinea pig.
In these cases the disease starts with enlargement of the glands
at the roots of the lungs. This finding of course would require
an X-ray plate but it was found that the enlargement of the
supraclavicular glands at a point near the insertion of the
sternocleidomastoid was one of the best early signs. The glandular
stage lasted about five to ten weeks during which time the general
health did not seem to be materially impaired. Following this stage
and lasting only about two weeks or up to two months a stage of
generalized tuberculosis sets in with fever, emaciation, caseous
pneumonia or manifestations of miliary tuberculosis. There was
no tendency to fibrosis or cure of the process, death almost
invariably occurring. Borrel, who studied the disease in these
natives, states that if put at rest and placed on a generous diet,
while the case is in the glandular stage, one-half of them may
recover. It was noted that sputum examinations of these cases were
almost invariably negative.
=Smallpox.=—This disease may justly be considered the greatest
scourge of the natives of tropical countries. It is responsible for
much of the blindness noted in natives of sections where vaccination
has not been employed.
In some of the countries of the Orient smallpox kills more people
than cholera, plague and dysentery together. Many reports have
shown that as many as 80 to 90% of a native population may be
attacked in an outbreak and of these practically one-half die. In
such communities the disease is more one of young children, the
adults possessing a certain degree of immunity from attacks in
childhood during previous epidemics. It has frequently been noted
that the native colored races do not seem to acquire as marked an
immunity as is observed among the white races of temperate climates
following an attack of the disease. Again it has been insisted
that the immunity following vaccination is not as marked as that
obtaining in European countries. This point would seem not well
founded because efficient and universal vaccination has apparently
caused smallpox in the Philippines to be of no more importance
than it is among any other well vaccinated people. It is striking
to note the great number of pitted faces among adult Filipinos,
whereas this condition is practically absent in the generation
following the general vaccination introduced by the Americans.
In tropical natives the most severe forms of smallpox are
observed—confluent and haemorrhagic.
Opportunities for the spread of the disease are most favorable in
many parts of the tropical world by reason of intimate association,
religious festivals and pilgrimages.
Under the name _alastrim_ or Kaffir milk-pox, a disease similar
to a mild form of smallpox has been reported from Africa and the
West Indies. Various points were raised to differentiate it from
smallpox, but in a recent epidemic in Jamaica and Haiti proof was
adduced to demonstrate its identity with smallpox. In Haiti the
epidemic was controlled by vaccination with smallpox vaccine, and
those individuals exposed to the infection but properly vaccinated,
uniformly escaped. Among the soldiers of the Marine Corps in Haiti
there were only two cases and these occurred in men who gave no
evidences, of successful vaccination.
=Varicella.=—This disease is of common occurrence in the tropics
and does not seem to give rise to greater mortality than it does in
temperate climates.
In the Philippines I have been struck by the resemblance it bears
to cases of varioloid, inasmuch as we frequently note as numerous
lesions on the face as on the body. In fact I have been sure that
the pustular lesions of the face of such cases were those of
smallpox, until I noted typical varicella lesions on the body.
=Mumps.=—This disease is found in many parts of the tropics and
presents similar features to the epidemic parotitis of temperate
climates.
In the Philippines there seem to be cases similar to mumps but
without the contagious feature so characteristic of the disease in
Europe.
=Glanders.=—This rare disease of Europe and the United States seems
to be much more common in many tropical countries. In the Philippines
it generally shows itself in the acute form and is much dreaded by
reason of its great infectiousness.
=Diphtheria.=—Formerly there was an idea that diphtheria, like
scarlet fever, was extremely rare or unknown in the tropics.
The assistance of the laboratory has shown that this old idea is
incorrect and that the disease is fairly prevalent in many tropical
regions.
=Vincent’s Angina.=—While not rare in temperate climates, various
affections of the oral mucous membrane due to the fusiform bacillus
in symbiosis with various species of spirilla are fairly common in
the tropics. The best known condition is one in which the tonsils
show somewhat the appearance of a follicular tonsillitis but
ulceration is more common and severe, with however, less evidence of
toxaemia.
The temperature in a case of pure Vincent’s Angina rarely exceeds
101°F. but if there is a mixed infection with other pyogenic
organisms the temperature and other signs of a severe infection
may be more marked. There is usually more or less swelling of
tributary glands. Associated with the angina or alone we may
have a gingivitis in which the spongy gums more or less resemble
those of scurvy or of pyorrheoa alveolaris. In fact these Vincent
organisms have been considered as factors in the development of
pyorrhoea alveolaris. In the tropics there have been many reports
of organisms of the type of those described by Vincent occurring in
skin ulceration or affection of the mucous membranes other than the
oral ones, more particularly the pudendal mucous membranes.
The infections are readily and easily diagnosed by a smear stained
with any simple aniline dye. Care must be taken not to accept such
a finding as the sole cause, as an underlying diphtheria, syphilis
or other dyscrasia may be more important.
=Malignant Tumors.=—It is usually stated that malignant tumors
are very rare among tropical natives. The proper solution of this
question, however, is complicated by the frequent lack of careful
autopsies.
=Pneumonia.=—Just as with the tubercle bacillus so does the black
race seem to have less resistance to the _Pneumococcus_ than does the
white one.
Great engineering works employing tropical natives are frequently
associated with very fatal epidemics of pneumonia, especially
broncho-pneumonia. Again in the black races the infection tends to
become generalized rather than localized in the lungs. It is more
toxic and insidious in its course than is true of the infection in
the white man; it has the fatal trend of pneumonia of the aged.
Another tendency is to invasion of the meninges.
=Influenza.=—In temperate climates we associate this disease with
bronchial and coryzal manifestations. In the tropics types almost
unrecognized in Europe are noted, especially the gastro-intestinal
and nervous ones. The similarity in the clinical picture of dengue
with slight eruption and tropical influenza is striking.
During the recent pandemic of influenza there was a frequent
complication of influenza pneumonia; many of these influenza
bronchopneumonias resembled plague pneumonia.
=Tetanus.=—This infection is far more prevalent in tropical than
in temperate climates. It is particularly fatal to infants, the
infection occurring from errors in the dressing of the cord at the
time of childbirth.
=Syphilis and Other Venereal Diseases.=—Syphilis is rampant in many
parts of the tropical world. Jeanselme has noted that syphilis among
tropical natives often starts with an extra-genital lesion which
tends to become phagedenic and that the secondaries are but slightly
marked. It is in the tertiary stage that the disease shows itself in
its malignancy.
All tropical workers have noted the absence of tabetic and paretic
manifestations in the native syphilitics. LeDantec notes that he
has not observed parasyphilis in any European who had contracted
syphilis from a native woman and brings up the question of a
difference in strains of syphilis.
The American Naval Surgeons at Guam and Samoa have been struck
with the absence of primary lesions of syphilis among the natives
of these islands and Butler has suggested that this is due to an
immunity received as result of contracting yaws in childhood. There
certainly are many reasons for considering syphilis and yaws as
closely related.
_Soft chancre_ is common in many tropical seaports and shows itself
in a rather virulent form. In particular it is apt to be complicated
by suppurating buboes.
In _tropical gonorrhoea_ it would seem that involvement of the
testicles is more common than in temperate climates.
=Endocrine Disturbances.=—Internists in all parts of the world
are beginning to appreciate that many of the puzzling complaints
of ill-health are connected with abnormal functioning of the
ductless glands. The conditions resulting from excessive or
diminished functioning of the thyroid gland are well understood and
the determination of the basal metabolism rate is now a standard
laboratory procedure. There are many types of apparatus on the market
and the determination is within the reach of any hospital staff.
Hyperthyroidism is now rarely unrecognized as is also true of
myxoedema but sub-states of thyroid functioning are less frequently
recognized.
McCarrison has stressed the importance of endocrine disturbances
in dietetic deficiencies and notes atrophy of all the glands
of internal secretion in such conditions with the exception of
the adrenal which tends to hypertrophy. There is possibly some
hypertrophy of the pituitary in males. The oedema which accompanies
most of the food deficiency diseases he associates with the adrenal
enlargement and hyperactivity of function, although oedema does
not invariably result from such hypertrophy. In pellagra there is
a low blood pressure, possibly due to adrenal hypofunction. Goitre
is found in many parts of the tropical world and Castellani states
that this disease is met with frequently in Ceylon and various
regions of Africa. Disturbances of the internal secretion of the
pancreas, resulting in diabetes, are common in parts of Asia.
_Determination of Basal Metabolism_.—In the study of cases where
abnormal thyroid functioning is suspected the most accurate method of
such determination is by estimating the percentage of the patient’s
metabolism as above or below the normal average.
Basal metabolism is that caloric value which an individual produces
while resting in bed and prior to taking breakfast—in other words
when the effects of food and exercise on caloric output are least
operative. Basal metabolism is expressed in terms of calories per
hour per square meter of body surface. It varies with different
ages. It is proportionate to body surface which is calculated
from the height and weight of the individual. Normally this
metabolism should not vary more than 15% above or below accepted
normal figures. The use of the respiration calorimeter is the most
accurate method for determination of heat production but it has
now been found that the oxygen consumption during short periods
gives data for calculation of such heat production (indirect
calorimetry). In the Benedict portable respiration apparatus
the patient breathes into and out of a confined volume of air
circulating through a series of purifiers which remove the carbon
dioxide. A determination of the volume of oxygen consumed is made
from the decrease in the total air volume. The heat production
resulting from the absorption of one litre of oxygen is relatively
constant whether used to burn fat or carbohydrate and gives an
accurate index of total heat production. The Benedict apparatus
can also be employed for determining carbon dioxide excretion and
thereby giving data for the respiratory quotient. The determination
of the heat produced in the excretion of carbon dioxide is less
accurate although easier of determination. In marked cases of
hyperthyroidism the basal metabolism ranges 75% above the normal
figures, between 50 and 75% for severe cases and less than 50% for
mild cases. In hypothyroidism the figures are usually 20 to 40%
below the normal averages. The average respiratory quotient is
taken as O.82 and the calorific value of oxygen at this respiratory
quotient is 4.825 per litre. We multiply the litres of oxygen
by 4.825 to compute the heat output. It must be remembered that
patients with high fever give 30 to 40% heat production over normal
figures. Severe cardiac and renal conditions as well as leukaemias
also give high values. The average calorie output per square meter
of body surface per hour based on the Du Bois “height-weight”
formula, is 39.7 for man and 36.9 for women between the ages of 20
and 40, being greater in youth and less beyond forty.
=Focal Infections.=—In recent years our attention has been directed
to the importance of certain localized bacterial foci which may
extend through blood or lymph channels and give rise to various
systemic or localized diseases. Most important of these diseases are
various types of arthritis together with endocarditis, myocarditis
and pericarditis. Next in importance are renal infections, chiefly of
the glomerulonephritis type.
Cholecystitis, appendicitis, pancreatitis and various skin lesions
may also have origin in a focal infection. The primary foci may be
localized in any part of the body but those seated in the tonsilar,
peridental membrane, nasal and accessory sinus tissues are the
most common and important. Focal infections of the genito-urinary
tract may also give rise to generalized conditions as is also
true of such foci in the alimentary tract. In the tonsils we
should particularly examine the material of crypts for various
streptococci and likewise the bacterial flora of tooth abscesses or
pyorrhoea alveolaris.
TABLE SHOWING NUMBER OF TIMES EACH FOCUS WAS CONSIDERED A PROBABLE
SOURCE OF INFECTION IN A SERIES STUDIED BY BILLINGS AND ASSOCIATES
No.
Tonsil 336
Teeth 136
Sinus 12
Bronchi 5
Uterus and tubes 12
Prostate and genito-urinary tract 24
Gallbladder 3
Enterocolitis 2
Appendix 1
Middle ear 1
CHAPTER XLIV
ONSET AND THE TEMPERATURE CHART IN THE DIAGNOSIS OF TROPICAL DISEASES
While a knowledge of the variations in type and course of the body
temperature in the various tropical diseases is of great value in
diagnosis, yet such information is liable to lead one astray, unless
such data are controlled by a careful consideration of the other
and, in my opinion, more important factors of physical diagnosis and
laboratory examinations.
The idea that there is a scientific exactness in the employment of
the clinical thermometer tends to make one overestimate its value
in diagnosis.
It must be remembered that the high air temperature one encounters
in the tropics affects the clinical thermometer, which is of the
maximum type. This is particularly true when the sun may be shining
on the container in which the thermometer may be kept. Even if one
shakes down the column of mercury before putting it in the mouth,
the glass of the instrument will quickly cause the mercury column
again to rise. It should be a practice to place the instrument in
cool water before inserting it in the mouth and we must not forget
that a sufficient retention in the mouth, from two to five minutes,
should be insisted upon before accepting the temperature reading.
For practical purposes we may divide tropical diseases, from a
standpoint of body temperature, into two classes. (1) _Those diseases
in which the absence of fever in the general course of the illness is
the rule, and_ (2) _those diseases in which the presence of fever in
the general course of the illness is the rule_.
=Nonfebrile Diseases.=—Among the nonfebrile diseases we may note
the following: Beriberi, sprue, pellagra, cholera, leprosy, amoebic
dysentery, hookworm disease, filariasis, bilharziosis, endemic
haemoptysis or paragonomiasis, liver fluke disease, malarial
cachexia, yaws, verruga, oriental sore and ulcerating granuloma of
the pudenda, as well as the various tropical skin diseases.
One should always keep in mind the fact that a latent malaria often
gives way to frank malarial manifestations when some intercurrent
disease still further reduces the body resistance. This is not
infrequently the explanation of a febrile onset in the course of
a disease typically afebrile. In the tropics if a fever chart
does not show a characteristic periodicity one can often obtain
indications of periodicity even in a continued or remittent fever
course by the greater elevation of temperature every third day
(tertian periodicity).
Another disease which often flares up following conditions which
lower vitality and giving rise to fever and manifestations of
toxemia is tuberculosis, a disease as common in the tropics
as elsewhere. Then too, one must always keep in mind febrile
manifestations not unrarely marking syphilis. This triad of
diseases, malaria, tuberculosis and syphilis, must always be
thought of, as well as septic conditions, when fever is present in
a disease typically afebrile.
There are certain exceptions in the above list which may be here
noted.
_Beriberi._—There has been considerable discussion as to whether
a disease with fever and a rash, but otherwise resembling wet
beriberi, is the same disease or a distinct disease entity. The
fever in _epidemic dropsy_; as it is called, is rarely over 102°F.,
usually ranging from 99° to 101° and accompanying the dropsy.
_Pellagra._—While there may be slight variations from the normal
yet the ordinary case of pellagra fails to show a distinct febrile
course, so much so that the appearance of fever in a case of
pellagra makes for an unfavorable prognosis. In the so-called
typhoid pellagra, an acute, rapidly fatal form of the disease,
a high temperature curve may be obtained. At the same time this
condition has been noted by Italian and German writers as being
present in patients not showing any rise in temperature. It is
possible that the development of enteric fever in a pellagrin may
at times be the explanation of the fever.
_Cholera._—Instead of a favorable stage of reaction there may set
in a condition with low muttering delirium, dry brown tongue and
with an elevated temperature, the so-called typhoid state, which is
speedily fatal.
Rarely a rise of 3 or 4 degrees which does not last more than
forty-eight hours may be present in a stage of reaction going on to
a favorable convalescence.
It must be remembered that the rectal temperature in the majority
of cases of cholera may show elevation of temperature approximating
100°F., while the axillary temperature may be as low as 95°F.
When there is a great difference between the rectal and axillary
temperatures, instead of the more common 4 or 5 degrees of a
typical case of cholera, the prognosis is bad. The temperature
taken by mouth may be as low as 86°F.
_Leprosy._—Among the prodromata of leprosy, along with epistaxis,
feeling of great weakness, somnolence and occasional sweats, there
may be recurring attacks of fever. These are at times diagnosed as
malarial manifestations. With the appearance of typical lesions
the course is apt to be nonfebrile with the exception that febrile
accessions often accompany the early macular manifestations.
_Amoebic Dysentery._—Unless complicated by hepatitis or some
bacterial infection of the amoebic lesions the disease progresses
without fever.
_Sprue._—While sprue is certainly one of the most typical of
afebrile diseases yet a form of sprue is recognized which begins as
an acute entero-colitis with fever. This must be most exceptional,
or only a coincidence, as sprue is characterized by a very
insidious onset.
_Ancylostomiasis._—The occasional reports of fever being present
are probably connected with bacterial infection at the site of
attachment of the hookworm.
_Filariasis._—There is a febrile manifestation of filarial disease
which is attended by rigors and high fever. This is a lymphangitis
which causes an erysipelatous appearance about the region involved.
It is these recurring attacks of lymphangitis which gradually
lead to the enormous thickening of the skin characteristic of
elephantiasis. Such attacks are designated _elephantoid fever_.
They are often diagnosed as malarial chills and in Barbadoes, where
there is no malaria, such attacks are called “ague.”
Lymph scrotum is the filarial condition in which elephantoid fever
is most frequently noted.
_Schistosomiasis._—In the vesical type of the disease we may have
as a complication a pyelitis which could give rise to febrile
manifestations. In Japanese schistosomiasis the disease sets in
with fever and urticaria. Before this combination of symptoms
was recognized as belonging to schistosomiasis we designated it
_urticarial fever_.
[Illustration: FIG. 145.—General type of fever onset in the
various tropical diseases.]
_Malarial Cachexia._—Attacks of an irregular type of fever are
frequently noted in the malarial cachectic, especially setting in
upon some exposure to dampness or chilling, to alcoholic excesses
or to excessive fatigue. Cases are also met with in the tropics,
particularly among natives, where fever plays no apparent part in
the profound anaemia of these ague-cake victims. It is this absence
of fever which many consider the evidence of immunity to malaria in
the native with his anaemia and large spleen.
Such cases often show crescents in their blood and act as
reservoirs of virus for mosquito infection.
_Latent Malaria._—Following treatment, or even when quinine has
not been exhibited, cases of malaria often cease to show clinical
symptoms or even laboratory findings until a relapse develops
in case a cure has not been effected. As noted elsewhere, these
relapses, in which the febrile manifestations are prominent, often
follow exposure to tropical sunlight, wetting, etc. Besides such
frank manifestations, we may have numerous symptoms, that exhibit
periodicity, arising in the course of nonfebrile latent malaria.
_Yaws._—While fever of a more or less irregular type frequently
occurs at the onset of both primary and secondary stages,
especially just before the secondary general eruption, yet the
course of yaws as it runs over months or years is afebrile.
_Verruga._—The recent views as to verruga being a separate
condition, and not the secondary stage of a typhoid-like fever,
Carrion’s disease, removes from its clinical features the fever
characteristics generally noted.
=Diseases with Subnormal Temperatures.=—_There are certain
diseases in which marked lowering of the temperature may be a
feature of some stage._
The algid stage of _cholera_ is that which gives to cholera the
picture of a living death with the cadaveric features and icy
breath. Again in the choleraic type of _algid pernicious malaria_
we may have a subnormal temperature.
[Illustration: FIG. 146.—General type of termination of the febrile
course in the various tropical diseases.]
In infections with Shiga’s bacillus of _bacillary dysentery_ we may
have cases showing extreme toxaemia with algid manifestations and a
subnormal temperature.
During the last stages of _sleeping sickness_ a lowering of the
temperature is fairly constant.
In _heat prostration_ the temperature tends to be subnormal.
Clinically this condition with its pale clammy skin is just
the opposite of heat stroke with its turgid countenance and
hyperpyrexia.
In the _Indian type of relapsing fever_ we may have a fall to
subnormal temperatures at the time of the crisis of the first
paroxysm, often attended with manifestations of collapse.
_Sprue_ cases tend to run a subnormal temperature during the
terminal period.
=Febrile Diseases.=—The diseases in which the presence of fever, in
the general course of the illness, is the rule, may be considered in
two groups:
1. Those in which the temperature chart is of prime importance in
diagnosis.
2. Those in which the character of the fever gives but little
assistance in diagnosis.
DISEASES IN WHICH THE TEMPERATURE CHART IS OF PRIME IMPORTANCE IN
DIAGNOSIS
_Benign Tertian and Quartan Malaria._—The presence of a fever of
tertian or quartan periodicity is absolutely characteristic of
malaria. In rare cases however of meningococcus sepsis, without
cerebral localization, we may have a tertian or even quartan
periodicity. Such cases are apt to show petechial spots and
blood cultures give the diagnosis. There is also a polynuclear
leukocytosis. As the result of the introduction by infected
mosquitoes, on successive days, of two generations of malarial
parasites in benign tertian or of three generations in quartan
malaria, a quotidian periodicity may obtain.
Such a type of fever is observed in tuberculosis, liver abscess
and various pyogenic infections. The rise of temperature in
benign tertian and quartan malaria takes place in about one-half
the cases somewhat early in the day, while the daily rise in
tuberculosis, septic conditions and liver abscess, is more apt
to occur in the evening, the evening rise being almost the rule
in such diseases. Hectic fevers generally show a less distinct
cycle of chill, hot stage and sweating than do the benign malarial
paroxysms. At the same time the enlarged spleen, presence of
parasites in the peripheral circulation and response to quinine are
diagnostic points in malaria which must always be thought of. When
quinine administration has caused the parasites to be temporarily
absent from the blood the increase of large mononuclears is very
suggestive.
_Dengue._—In this disease the extremely sudden onset with a fever
rising rapidly to 104°F. or more and remaining elevated for three or
five days, to fall by crisis to normal and, after an apyrexial period
of one or two days, to be succeeded by a second febrile accession,
gives a fever chart which is quite characteristic—_the saddle-back
chart_.
The typical dengue eruption does not appear until towards the end
of the primary fever or about the commencement of the secondary
one. Intense postorbital soreness is a striking feature in dengue.
The comparative slowness of the pulse may be noted in dengue
as well as in yellow fever. Leucopenia and polymorphonuclear
percentage reduction are rather characteristic.
_Relapsing Fevers._—These fevers, when there are three or more
relapses, can perhaps be more easily diagnosed from the temperature
chart alone than is the case with any other disease, excepting
malarial fevers showing tertian or quartan periodicity. With an
abrupt rise of temperature, which remains elevated for from three
to seven days and drops by crisis to normal, to be followed by
approximately a week of normal temperature, with two or three
repetitions of the fever and apyretic intervals we have an extremely
characteristic temperature chart.
Unlike malaria and yellow fever the onset is apt to be towards
evening rather than in the morning hours.
The spleen is apt to be enlarged during the pyrexia and less so
when the temperature is normal. The spirochaetes are to be searched
for while fever is present as they disappear from the peripheral
circulation during the apyretic intervals. In tick fever numerous
relapses are frequent in the European and less common in the native.
_Malignant Tertian Malaria._—While benign malarial infections are
more common in temperate climates malignant tertian is the one which
usually prevails in the tropics.
While the Italian designation of this type of fever as
aestivo-autumnal has more general acceptance yet Koch’s term,
tropical malaria, is eminently appropriate. The onset in malignant
tertian is rather insidious so that the case may be suspected
as one of typhoid fever. At the same time the first paroxysm is
apt to show a tertian periodicity while subsequent ones, by only
remitting, and not showing an intermission, give the temperature
picture of a continued fever in which periodicity is not easily
noted. At the same time a study of such a chart will probably
show that the curve tends to approach normal every other day.
The suggestion of periodicity is almost of as great value as the
actual drop to normal in the intermission. The remittent or even
continuous type of fever in malignant tertian tends to yield to an
intermittent one after a week or more of such fever.
Very characteristic of malignant tertian paroxysms is that they set
in with chilly sensations rather than a frank chill. It is for this
reason that the so-called “dumb chill” is recognized as more serious
than the frank unmistakable chill.
The main feature of malignant tertian paroxysms is the pronounced and
prolonged hot stage, which frequently lasts from twenty to thirty-six
hours and may run over into the rising temperature connected with the
development of the succeeding generation of parasites.
The terms anticipation and postponement are frequently used to
explain the drawn-out fever of this type of malaria.
There is great irregularity in time of development so that we get
the impression of completed cycle before the accepted forty-eight
hours as shown by a rising temperature within thirty-six
hours—anticipation; or, instead of showing indications of a
completion of cycle in forty-eight hours the fever still keeps
up—retardation.
The descent of the fever curve is much more gradual than the rise
at the onset of the paroxysm. The fine hair-like rings of the
tropical parasite are the only schizont stages usually found in the
peripheral blood. As the rings enlarge they fail to appear in the
peripheral blood so that blood examination at such times will be
negative. The finding of crescents is proof of a malignant tertian
infection.
In view of the fact that one is likely to fail to find parasites just
before or just after a paroxysm search should particularly be made
for the pigment-carrying phagocyte—_the melaniferous leucocyte_.
In certain of the pernicious manifestations of malignant tertian,
especially the hyperpyrexial type of cerebral malaria, the
temperature may reach a very high degree, 107°F. to 110°F., and it
is often mistaken for sun stroke by one not familiar with the fact
that so-called sun stroke is often only this fatal form of malaria.
In algid pernicious malaria the axillary and, in particular, the
rectal temperature remain elevated even with a subnormal surface
temperature.
The infection in _latent malaria_ is most often a malignant
tertian one. Such cases often develop paroxysms following surgical
operations or at time of pregnancy or childbirth. Clark has
noted the abundance of parasites in smears from the placenta
taken at time of delivery when the peripheral blood showed few
or no parasites. Such an examination is of enormous value in
differentiating a malarial paroxysm from puerperal sepsis.
_Malta Fever._—In this disease, in which the wave-like febrile
periods during every three or four weeks are so characteristic
as to give it the name of “febris undulans,” there is a very
insidious onset. For a week or ten days the temperature climbs up
step-ladder-like and then descends in like manner to be followed by a
few days of apyrexia with succeeding similar relapses. The case would
suggest an attack of typhoid with relapses.
The course of the disease is attended by rather marked anaemia
and physical and mental depression. Very characteristic are
the fleeting joint pains which involve chiefly the knees, hip,
ankle and shoulder joints. There are pain and some swelling but
without redness. Neuralgic pains are also common. There is often
a bronchitis which, when associated with the rather common night
sweats of the disease, is suggestive of phthisis.
The cardiac muscle seems to be especially liable to the toxic
effects of the disease so that a weak heart and intermittent
pulse are often noted. It has a very protracted course of, on the
average, about four months.
An astonishing fact is that so severe and a prolonged fever should
give such a slight mortality (2%).
Occasionally, a case shows a high continued or remittent fever
and aggravated symptoms, going into a typhoid state. Such cases
are often fatal. There is an increase in the lymphocytes but no
increase in total leucocytes.
The wave course of the fever, with afebrile intervals and increasing
anaemia, is suggestive of kala-azar, particularly when there is a
greater enlargement of the spleen than is usual in the disease.
Ordinarily the splenic enlargement about corresponds to that of
typhoid fever but at times it may be so much enlarged as to suggest
the splenic tumor of kala-azar.
DISEASES IN WHICH FEVER IS AN IMPORTANT FEATURE BUT GIVES LITTLE
ASSISTANCE IN DIAGNOSIS
_Kala-azar._—This disease has a peculiarly insidious onset because,
with a fairly high remittent fever, it may cause but slight feeling
of illness in the patient.
Rogers insists upon the importance of taking the temperature every
four hours so that one may note the fact of there being _two distinct
rises_ in the twenty-four hours instead of the single evening rise of
typhoid fever.
At first it is confused with malaria as well as typhoid. The spleen
becomes greatly enlarged by the third or fourth month and later
on we also have enlargement of the liver. Periods of fever and
apyrexia occur irregularly and over a period of months or even
longer than a year.
There is a marked leucopenia and the presence of the
leishman-donovan bodies, often in huge numbers, in the juice from
spleen or liver puncture, makes for a certain diagnosis.
_Yellow Fever._—With a sudden onset and rapidly rising fever, which
often occurs in the early morning hours, in a patient who has gone
to bed feeling well, we have a markedly congested face and neck
with injected conjunctivae and intense headache and backache. The
fever tends to remain elevated for about three days after which
there may be noted a fall in temperature or even an intermission.
This, which has been termed the period of calm, is often slight and
of short duration. About this time the jaundice and haemorrhages
show themselves and the temperature tends again to rise although
less marked than with the sthenic fever of the first two or three
days. Of great importance is the fact that the pulse rate falls
with a maintained temperature or does not increase in rate as the
temperature rises (_Faget’s law_). A very slow pulse is quite
characteristic of yellow fever after the third day.
Important in the diagnosis of yellow fever from bilous remittent
fever and blackwater fever is the absence of splenic enlargement
in the former. In particular must it be remembered that jaundice
does not show itself in yellow fever until about the third day,
following which we may have bleeding from the gums and black vomit.
Melaena and haematuria may also be noted. The presence of a marked
albuminuria is one of the leading characteristics of yellow fever.
_Blackwater Fever._—The onset is usually quite sudden with a rather
severe chill and marked lumbar pain.
The temperature rises rapidly to about 104°F. and may fall in a few
hours to a point but little above normal accompanied by profuse
sweating. The fall in temperature is not followed by a feeling
of improvement. On the other hand there may be a fever course of
remittent or even continuous type. That which is most characteristic
and which in the majority of cases enables the patient to make his
own diagnosis is the passage of dark or porter-colored urine.
The urinary sediment is simply granular débris, there are no intact
red cells. It is a haemoglobinuria and not a haematuria. If there
is any blood in the urine in yellow fever it is in the form of a
haematuria. The urine in both blackwater fever and yellow fever
is highly albuminous. In some cases the haemoglobinuria seems to
result from quinine administration alone, in which case there is
not the high fever of typical blackwater fever. As distinguishing
it from yellow fever we have a marked jaundice which comes on in
a few hours or even with the first appearance of haemoglobinuria
instead of being delayed until the third day, as in yellow fever.
Again, the blackwater paroxysm is intensely prostrating, it is
markedly asthenic, while the onset of yellow fever is quite sthenic
in character. The enlarged tender spleen of blackwater fever is
also a prominent feature, which is absent in yellow fever. Bilious
vomiting is an early and severe feature of blackwater fever but not
the black vomit of yellow fever which does not come on until after
the third day.
The jaundice of bilious remittent fever does not appear before the
second day and the urine shows bile pigments instead of haemoglobin.
_Plague._—The fever rapidly rises, so that the maximum temperature
of 104°F. or more may be attained on the first day of the disease.
In general the type of fever is continuous with a rather marked
remission about the third day, following which, the fever again goes
up with the appearance of the glandular involvement (bubonic plague).
In fatal cases the temperature may shoot up just prior to death.
The drawn anxious countenance, the mental state and speech as of
one suffering from alcoholic intoxication, and the early cardiac
involvement, with very weak and irregular pulse, give one a clue to
plague even before the buboes appear. Smears and cultures from the
buboes make the diagnosis.
In _plague pneumonia_ there is nothing characteristic about the
rather continuous fever which sets in suddenly and continues elevated
until death, which generally occurs about the third or fourth day.
The marked mental involvement, the extreme illness of the patient,
with but slight physical signs of the involvement of the lungs,
should make one suspect a plague pneumonia during an epidemic. The
abundant, rather watery sputum, which later becomes sanguineous,
gives us a diagnosis by reason of its being loaded with bipolarly
stained plague bacilli. This material should be rubbed on the shaven
abdomen of a guinea pig to make the diagnosis absolutely sure.
In _septicaemic plague_, if such be considered a distinct
type, there is very little that is manifest except a fever in
a profoundly ill person. The powers of resistance may be so
overwhelmed that the temperature response is slight and the chart
not show temperature records above 100°F. or 101°F. Blood cultures
make for the diagnosis in septicaemic plague.
_Typhus Fever._—While the classical temperature chart is usually
described as one with a rapid rise, reaching the maximum of 103° or
104° by the second day, with a fastigium of twelve to fourteen days,
followed by a critical fall, yet many cases recently observed in the
Balkans show a fairly gradual onset with a fall by lysis.
A stuporous condition with, about the fifth day, a rash first
appearing about abdomen and flanks, to soon become petechial, are
important in diagnosis. There is a leucocytosis with marked acid
staining of the granules of the polymorphonuclears.
_Trypanosomiasis._—The fever of trypanosomiasis is markedly
irregular and may exist in natives without preventing them from
carrying on their duties as porters. The onset is on the whole
insidious.
In this first stage of trypanosomiasis or _trypanosome fever_,
when trypanosomes are found only in the glands and peripheral
circulation, what may probably be considered as leading
peculiarities of the fever are the great daily oscillations, a
normal morning temperature being succeeded by an evening rise up to
102°F. or 104°F.
While the febrile course is usual in Europeans it is often absent
in natives. With them the febrile manifestations are noted in the
sleeping sickness stage.
Again a very rapid, low tension pulse is present, whether the
temperature be low or high. These febrile accessions are followed
by apyrexial intervals.
Extremely important in diagnosis are the glandular enlargements
of which those of the upper posterior cervical triangle are the
most characteristic (Winterbottom’s sign). Gland juice is more
apt to contain trypanosomes than the smear from the blood. Deep
hyperaesthesia is also a very characteristic symptom (Kérandel’s
sign).
When the trypanosomes are found in the cerebro-spinal fluid we have
the second stage of trypanosomiasis or that of _sleeping sickness_.
This is ushered in by a tremor of the tongue and mental symptoms
of great apathy and listlessness. An irregular fever is present
at times during the course of this stage of sleeping sickness
but toward the end of the disease the temperature tends to be
subnormal.
Progressive weakness and emaciation with finally a comatose state
are features of the terminal weeks.
_Brazilian Trypanosomiasis._—The disease begins acutely in young
children with an irregular remittent fever. The parasites are not
apt to be found except during the fever. The lymphatic glands become
swollen. With repeated accessions of fever, followed by apyrexial
intervals, the child becomes weaker and more anaemic. The spleen is
enlarged. This infection is very fatal for children.
In adults the disease tends to assume a chronic type and often,
from involvement of the thyroid, gives symptoms of myxoedema.
_Bacillary Dysentery._—The onset may be quite sudden and the
temperature rise to 102°F. or 103°F. There is apt to be some evidence
of toxaemia as shown by headache, slight flightiness and gastric
upset. The dysenteric stool is of a whitish, mucopurulent appearance
and flecked or streaked with blood rather than showing the uniformly
brownish or greenish gelatinous material of amoebic dysentery.
In very severe bacillary dysentery algidity may come on with a
cold clammy skin, reminding one of cholera. At such times the
temperature is subnormal.
_Liver Abscess._—In the so-called pre-suppurative stage of amoebic
hepatitis the only symptom may be an irregular remittent fever of
moderate degree. This and a leucocytosis may be the only points noted.
In fully developed liver abscess we have a painful liver which is
enlarged upward often with pain referred to the right shoulder
and a crepitation at the base of the right lung. The fever is
distinctly hectic in type with an evening rise and associated with
profuse sweatings. The evening rise of temperature does not usually
tend to exceed 102°F. and apyrexial intervals are frequently
observed in the fever chart.
It must be remembered that liver abscess has been found at autopsy
where fever had not been noted. A sensation of chilliness often
accompanies the evening rise of temperature.
_Heat stroke._—The onset may be as sudden as in apoplexy, although
there are usually prodromata of dizziness and headache. The patient
is unconscious with dry burning skin, labored or stertorous
breathing, and a temperature of from 107° to 111°F.
The hyperpyrexial malarial paroxysm presents much in common with
heat stroke.
_Climatic Fevers._—From many parts of the tropical world there
have been reported cases of fever supposed to be due to exposure to
prolonged action of tropical heat. They are often designated as
climatic or inflammatory fevers.
A careful study of the clinical manifestations tends to show that
many of them are much like dengue. Some may be due to infection
with the Gärtner group of bacteria.
_Rat Bite Disease._—Following a rather long incubation period of
from six to eight weeks, during which time the bite has healed,
we have a rather sudden invasion with high fever, 103° to 104°F.,
chill and at the same time inflammation of the site of the bite with
lymphangitis and some swelling of tributary glands.
After two or three days of high fever we have a fall by crisis
with profuse perspiration. The temperature remains normal for a
few days during which time the local swelling and inflammation
subside. The fever again comes on, frequently with an eruption, to
later on disappear and reappear. At such times the fever course is
irregular. There may be as many as 12 of these febrile accessions.
_Tsutsugamushi._—The disease sets in about a week after the bite
of the Kedani mite with headache, chills and fever of about 101°F.
There is also pain in certain lymphatic gland groups which will be
found to drain the area in which is located a small necrotic ulcer,
the site of the bite of the mite. The temperature continues to rise
during the next two or three days to 104°-105°F. and remains as a
high continuous fever for about a week, when an eruption of irregular
dusky macules appears, first on the face and later on chest,
extremities and trunk. About the tenth day the fever begins to go
down by lysis and the eruption fades. Injection of the conjunctivae
is marked.
Certain authorities have considered that there is a striking
clinical similarity and possible relation attaching to
tsutsugamushi, Rocky Mountain spotted fever, trench fever and
typhus fever. At present we believe that tabardillo or Mexican
typhus is the same as the well-known typhus of temperate climates,
hence that which describes typhus fever obtains for tabardillo.
_Spotted Fever of the Rocky Mountains._—In tabardillo the onset
and termination of the fever is rather abrupt while in spotted
fever of the Rocky Mountains it climbs up gradually for a week to
reach its maximum and falls by lysis.
All these diseases are characterized by a more or less stuporous
state.
_Oroya Fever._—It was formerly supposed that this fever was the
first stage of verruga, but it is now considered as a distinct
disease entity, caused by a protozoon of bacillary form which invades
the red cells. With pains of various joints and bones we have a
gradual rise of temperature which after a few days reaches 103° to
104°F. and tends to become remittent or continuous.
There is a remarkable and excessive destruction of the red cells
which may fall to a million or less per c.mm. The fever after about
three weeks begins to fall by lysis. Enlargement of liver, spleen
and lymphatic glands are common. Pain over the bones, especially
the sternum, is often excruciating.
_Epidemic jaundice_ shows an irregular pyrexia of from 102° to 103°F.
with jaundice about the second or third day.
_Trench Fever._—Cases of varying types of fever, some charts more or
less resembling the dengue ones, while others show repeated relapses
of short duration, have been designated _trench fever_.
In _tularaemia_ we have an irregular fever course of rather rapid
onset, extending over two or three weeks. There is very little
evidence of toxaemia. Convalescence is tedious.
_Typhoid fever_ and the _paratyphoid infections_ are far from
uncommon in the tropics and present clinical courses at variance with
those observed in temperate climates. The temperature charts in such
cases are irregular and atypical.
It must be remembered that paratyphoid infections may show marked
gastro-intestinal symptoms and that the rose rash of such cases
tends to be far more profuse than that of typhoid.
_Intestinal Parasites._—There are many conditions which seem to
be productive of febrile attacks as evidenced by the disappearance
of the fever upon removing such cause. Thus patients presenting
abdominal distress and a fever of varying type may be completely
relieved of all symptoms upon evacuating the larvae of various flies
following purgation. This condition is designated intestinal myiasis.
Abdominal pains and fever may also be caused by various helminths
usually considered nonsymptom-producing as has been noted in heavy
_Ascaris_ infections.
CHAPTER XLV
BLOOD EXAMINATIONS IN THE DIAGNOSIS OF TROPICAL DISEASES
In a short chapter on such a large subject only the more important
methods and findings can be considered. As regards interpretation
of blood findings in various tropical diseases one may note in
the recent work of Schilling-Torgau the difficulties which at
present beset the subject. Until some universal agreement as to
standard methods of technique and in particular complete accord as
to the characteristics of the diagnostic cells can be arrived at,
conflicting reports as to findings must of necessity be obtained.
In taking up this subject it has seemed convenient to divide it into
4 heads: (1) The microscopical examination of fresh preparations or
stained blood smears; (2) blood culture methods; (3) serological
examinations, and (4) other practical methods of haematological study.
In the companion volume on laboratory work I have endeavored to
take up rather in detail the various methods and techniques but in
this chapter I shall only give single methods or point out short
cuts in well-recognized ones or make suggestions as to new methods
of blood study which may eventually aid us in diagnosis.
Those who work in temperate climates cannot realize the
difficulties which beset the tropical laboratory worker from the
lack of proper assistance, damaging effects of heat and moisture on
stains and media and, of greater importance, the impairment of that
driving energy so necessary for the carrying out of complicated
methods. A short and simple method has a far greater value in the
tropics than at home.
BLOOD PREPARATIONS
To obtain blood, except for blood cultures, use either a
platino-iridium hypodermic needle which can be sterilized in the
flame, a small tenotome, or a surgical needle with cutting edge.
Needles should be sterilized by boiling since flaming dulls the
edge. A steel pen with one nib broken off or the glass needle of
Wright may also be used. To make a glass needle, pull straight
apart a piece of capillary tubing in a very small flame. Tap the
fine point to break off the very delicate extremity. Scarcely any
pain attends the use of such a needle. In puncturing either the tip
of the finger or lobe of the ear a quick piano-touch-like stroke
should be used. The ear is preferable, as it is less sensitive
and there is less danger of infection. Before puncturing, the
skin should be cleaned with 70% alcohol and allowed to dry. It is
advisable to sterilize the needle before using it.
Note that in order to secure in the specimen a cell count that
corresponds to that obtaining in the circulation as a whole it
is necessary to massage the ear vigorously prior to making the
puncture. Subsequently there should be no manipulation of the part,
the blood examined being that which exudes freely. This procedure
renders more likely the finding of blood parasites.
The first drop of blood which exudes should be taken up on the
paper of the Tallquist haemoglobinometer, using subsequent ones
for the blood pipettes and smears. If it is necessary to make a
complete examination, it is rather difficult to draw up the blood
in the pipettes, dilute it, and then get material for fresh blood
preparations and films without undue squeezing, which is to be
avoided. Of course, fresh punctures can be made. Ordinarily, complete
blood examinations are not called for. It is only a white count or a
differential count or an examination for malaria that is required.
As a practical point it is very rare that a red count is indicated.
There is one point not sufficiently recognized by physicians and
that is that a routine blood examination is not apt to be as
carefully conducted as one calling for a specific feature. Without
disparaging the necessity of routine examination of urine as well
as blood it is a fact that the internist who knows what he wants
gets better results from the laboratory man.
THE MICROSCOPICAL EXAMINATION OF FRESH PREPARATIONS OR STAINED BLOOD
SMEARS
As regards haemocytometry it may be stated that in the tropics the
counting of red cells is required more frequently in comparison to
white ones than is the case in temperate climates where probably 100
white counts are necessitated as against 1 red count. This is on
account of the frequency of secondary anaemias in the tropics.
The idea that time may be saved by making a white and red count
from the same preparation is not borne out practically so that it
is better to make white and red counts separately.
As a diluting fluid for red counts a normal salt solution,
preferably about 0.9%, answers perfectly and if desired may be
tinged with neutral red, methyl green or gentian violet to bring
out white cells. When available, however, I prefer a 2½% aqueous
solution of potassium bichromate for red cell counts.
=Rulings.=—The most desirable rulings are those of Türck, Zappert
and Neubauer.
[Illustration: FIG. 147.—Neubauer’s ruling.]
In these the entire ruled surface consists of nine large squares,
each 1 mm. square. These are subdivided, and in the central large
square are to be found the small squares used for averaging the
red cells. These small squares are 1/20 mm. square and are arranged
in nine groups of 16 small squares by bordering triple-ruled lines.
As the unit in blood counting is the cubic millimeter, if one
counted all the white cells lying within one of the large squares
(1 mm. square), he would have only counted the cells in a layer
one-tenth of the required depth, so that it would be necessary to
multiply the number obtained by 10. This product, multiplied by
the dilution of the blood, would give the number of white cells in
a cubic millimeter of undiluted blood. The Neubauer ruling is the
most satisfactory.
[Illustration: FIG. 148.—Thoma-Levy counting chamber, Bürker double
type with two Neubauer rulings.]
=Bürker Haemacytometer.=—Some workers prefer the _Bürker
haemacytometer_. In this there are two ruled wedge-shaped pieces of
glass, separated at their bases, which take the place of the ruled
disc of the Thoma apparatus. Two oblong pieces of glass are on
either side of the ruled wedges and are 0.1 mm. higher, thus taking
the place of the shelf. Clamps fix a cover-glass on these shelves
giving a space 1/10 mm. over the ruled surfaces. The blood is run
in by capillarity from the mixing pipette. I gave up this type of
counter because the clamps made manipulation awkward.
=Thoma-Levy Chamber.=—In the Thoma-Levy modification of the Bürker
apparatus the central portion of the slide is cut away and in this
depression is cemented a rectangular strip of glass, divided by a
central channel. Each half of this strip of glass has a Neubauer
ruling on it so that one can make a white count on one side and a
red one on the other, simply touching the tip of the red pipette
to the space separating the under surface of the cover-glass from
the ruled rectangular slips on one side and then with the white
pipette repeating the same on the other side. An advantage of the
Thoma-Levy is that the original thickness of the slide makes the
shelf on which the cover-glass rests instead of the support being
strips on either side of the ruled surfaces and cemented to the
slide. The Neubauer ruling is undoubtedly the most satisfactory of
the haemacytometer rulings, its rulings being simpler than those of
the Türck system. The unit square in all these haemacytometers is
the small square for counting red blood cells, 1/20 mm. square.
[Illustration: FIG. 149.—The Türck ruling. Thoma-Zeiss
Haemacytometer.]
=To Make a Red Count.=—Having a fairly large drop of blood,
apply the tip of the 101 pipette to it and, holding the pipette
horizontal, carefully and slowly draw up with suction on the rubber
tube a column of blood to exactly 0.5. The variation of 1/25 of an
inch from the mark would make a difference of almost 3%. If the
column goes above 0.5, it can be gently tapped down on a piece of
filter-paper until the 0.5 line is cut. Now insert the tip of the
pipette into some diluting fluid, and revolving the pipette on its
long axis while filling it by suction, you continue until the mark
101 is reached.
A variation of 1/25 of an inch at this mark would only give an
error of about 1/30 of 1%. This gives a 1-200 dilution. After
mixing thoroughly by shaking for one or two minutes, the fluid
in the pipette below the bulb is expelled (this of course is
only diluting fluid). A drop of the diluted blood of a size just
sufficient to cover the disc when the cover-glass is adjusted, is
then deposited on the disc and the cover-glass applied by a sort
of sliding movement, best obtained by using forceps in one hand
assisted by the thumb and index-finger of the other.
In red counts we use exclusively the small 1/20 mm. squares which
are in groups of 16 bounded by triple-ruled lines.
The depth of fluid over the ruled surface is 1/10 mm., hence each
of these small squares is 1/10 × 1/20 × 1/20 = 1/4000 of a c.mm.,
so that it takes 4000 such spaces to equal the unit for blood
counting (1 c.mm.). My practice in making red counts is to count
the red cells in five of the groups of 16 small squares. This in
normal blood is about 100 for the 16 squares. After counting 5
groups of 16 we have counted the red cells of 80 small squares
which is 1/50 of 4000 (the number in the 1 c.mm. unit). For this
reason 50 × 200 (the blood dilution) = 10,000, so that it is only
necessary to multiply the number of red cells found in 5 groups of
16 small squares by 10,000 in order to obtain the number of red
cells per c.mm. For more accurate determination the process can be
repeated with a second or third drop of the diluted blood, which
would give an average from 160 or from 240 small squares.
=To Count White Cells.=—Draw up the blood in the white pipette
to the 0.5 line. Then, still holding the pipette as near the
horizontal as possible, because the column of blood tends to fall
down in the larger bore, draw up by suction a diluting fluid which
will disintegrate the red cells without injuring the whites. The
best fluid is 0.5% of glacial acetic acid in water. This makes the
white cells stand out as highly refractile bodies. Some prefer to
tinge the fluid with neutral red or gentian violet. The 0.5 mark is
preferred because it takes a very large drop of blood to fill the
tube up to the 1 mark and if there is much of a leucocytosis a 1 to
10 dilution is not sufficient.
The blood having been drawn up to 0.5, we have a dilution of 1 to
20.
Making a preparation, exactly as was done in the case of the red
count, we count all of the white cells in one of the large squares
(1 sq. mm.). The cross ruling greatly facilitates this. Note the
number. Then count a second and a third square. Strike an average
of the large squares counted and multiply this by 10, as the depth
of the fluid gives a content equal to only 1/10 of a c.mm. Then
multiply by the dilution.
EXAMPLE.—First large square 50; second large square 70; third
large square 60. Average 60. Then 60 × 10 × 20 = 12,000, the number
of leucocytes in 1 c.mm. of blood. In order to save time the count
is preferably made with a low power (⅔-inch objective) as the
leucocytes stand out like pearls. It is more accurate, however,
to use a higher power, so that pieces of foreign material may be
recognized and not enumerated as white cells.
If one will accustom himself to comparing the distribution of
the leucocytes in a well-made stained dried-blood film, prepared
according to Ehrlich’s cover-glass method, with that in a
haemacytometer preparation, he can readily acquire an experience
which will enable him to determine with considerable accuracy the
degree of leucocytosis by the examination of a stained, cover-glass
preparation alone.
After making a blood count, the haemacytometer slide should be
cleaned with soap and water and then rubbed dry, preferably with
an old piece of linen. As the accuracy of the counting chamber
depends upon the integrity of the cement, any reagent such as
alcohol, xylol, etc., and in particular, heat, will ruin the
instrument. The pipettes should be cleaned by inserting the ends
into the tube from a vacuum pump, as a Chapman pump. First draw
water or 1% sod. carbonate solution through the pipette, then
alcohol, then ether, and finally allow air to pass through to dry
the interior. If the interior is stained, used 1% HCL in alcohol.
If a vacuum pump is not at hand, a bicycle pump or suction by mouth
will answer.
PREPARATIONS FOR THE STUDY OF FRESH BLOOD
Many authorities prefer a fresh blood specimen to a stained dried
smear in the study of parasites of the blood. In malaria in
particular there is so much information as to species to be obtained
from a fresh specimen that the employment of this method should never
be neglected. While waiting for the film to stain one has five or six
minutes which could not be better spent than in examining the fresh
specimen which only requires a moment to make.
=Manson’s Method.=—Have a perfectly clean cover-glass and slide.
Touch the apex of the exuding drop of blood with the cover-glass
and drop it on the center of the slide. The blood flows out in a
film which exhibits an “empty zone” in the center. Surrounding this
we have the “zone of scattered corpuscles,” next the “single layer
zone” and the “zone of rouleaux” at the periphery. It is well to
ring the preparation with vaseline. When desiring to demonstrate
the flagellated bodies in malaria, it is well to breathe on the
cover-glass just prior to touching the drop of blood.
=The Method of Ross= is very easy of application and gives most
satisfactory preparations. Take a perfectly clean slide, and make
a vaseline ring or square of the size of the cover-glass. Then,
having taken up the blood on the cover-glass, drop it so that
its margin rests on the vaseline ring. Gently pressing down the
cover-glass on the vaseline makes beautiful preparations which
keep for a very long time. If it is desired to study the action
of stains on living cells, this method is also applicable. A very
practical way to do this is to tinge 0.85% salt solution containing
1% sodium citrate (the same as is used in opsonic work) with
methylene azur, gentian violet, or methyl green. With a capillary
bulb pipette, take up one part of blood, then one part of tinted
salt solution. Mix them quickly on a slide and then deposit a
small drop of the mixture in the center of the vaseline ring and
immediately apply a cover-glass and press down the margins as
before. This method will be found of great practical value.
PREPARATION AND STAINING OF DRIED FILMS
When preparations are desired for a differential count, Ehrlich’s
method of making films is to be preferred, as the different types
of leukocytes are more evenly distributed. In making smears by
spreading, there is a tendency for the polymorphonuclears to be
concentrated at the margin while lymphocytes remain in the central
part of the film.
=Cover-slip Films.=—In _Ehrlich’s method_ we have perfectly clean
dry cover-slips. Take up a small drop of blood without touching the
surface of the ear or finger. Drop this cover-glass immediately on
a second one and as soon as the blood runs out in a film, draw the
two cover-slips apart in a plane parallel to the cover-glasses.
Ehrlich uses forceps to hold the cover-glasses to avoid moisture
from the fingers, but I find I can work more quickly and
satisfactorily with the fingers alone. The method shown in Fig. 150
is a very convenient one. In making malarial smears it is better to
wash the finger or ear with soap and water to get rid of all grease
and dirt. Then dry thoroughly before puncturing. Alcohol is not so
efficient.
[Illustration: FIG. 150.—1, 2, 3, 4, Making blood smears on slide.
5. Smear ready for staining—grease marks prevent Wright stain
from running over slide. 6. U-shaped glass tubing to hold slide in
staining. 7. Right hand holding two cover-glasses. One cover-glass is
being touched to drop of blood from ear. 8. Cover-glasses transferred
to left hand in preparing to place one cover-glass on another and
spread film. 9. Separating cover-glasses by sliding one from the
other.]
Slides and spreaders should be absolutely clean and grease-free.
Scrubbing with soap and water, thorough rinsing and drying, then
subjecting the slide to the flame to make it grease-free is
satisfactory.
For removing dirt and grease from skin, a mixture of acetone, 40;
alcohol, 60; is the best and quickest means. A bottle is kept on
hand, with the puncturing needle embedded in the stopper.
For cleaning a slide, nothing equals Bon Ami. Rub up some with the
wet finger, rub the slide with the lather until there is a friction
squeak; let dry; polish with a clean, dry cloth. This is far
better than soap and water, alcohol, ether and flaming combined.
Note how a drop of water spreads on a glass so treated.
=Smears on Slides.=—Of the various methods of spreading films on
slides, that described by Daniels is quite satisfactory. In this the
drop of blood is drawn along and not pushed along. The films are
even, can be made of any desired thickness by changing the angle
of the drawing slide, and there is little liability of crushing
pathological cells. Take a small drop of blood on the end of a clean
slide. Touch a second slide, about ½ inch from end, with the drop and
as soon as the blood runs out along the line of the slide end, slide
it at an angle of 45° to the other end of the horizontal slide. The
blood is pulled or drawn behind the advancing edge of the advancing
slide. An angle less than 45° makes a thinner film; one greater, a
thicker film.
Instead of a slide a square cover-glass may be used and if the edge
be smooth it makes a more satisfactory spreader than the slide.
Instead of the Daniels method I prefer to take up the drop of blood
on the slide on which the smear is to be made, about ½ inch from
the end. Then apply the spreader slide and so soon as the drop runs
along the end of the spreader slide proceed as above described.
This method is shown in Fig. 150.
=Spreaders.=—Of the various methods of making smears by means of
cigarette paper, rubber tissue, needles, etc., the best seems to be
to take a piece of capillary glass tubing and use this instead of a
needle in making the film. There is one advantage about the strip
of cigarette paper touched to the drop of blood and drawn out along
the slide or cover-glass, and that is that it is almost impossible
not to make a working preparation by this method.
THICK-FILM METHODS
Such methods are of the greatest practical value in searching
for malarial parasites when they are in very small numbers in
the peripheral circulation, in finding trypanosomes, relapsing
fever spirochaetes and filarial embryos. Ruge’s method so brings
out the polymorphonuclears that such a technic can be used for
opsonic index. Many workers prefer the _Ross thick-film method_ in
examining for malaria. In this about one-half of a drop of blood
is smeared out over a surface about equal to that of a square
cover-glass and allowed to dry. It is then flooded with 1/10
of 1% aqueous solution of eosin for about fifteen minutes. The
preparation is then gently washed with water and then treated with
a polychrome methylene-blue solution. After a few seconds this is
carefully washed off and the preparation dried and examined.
James smears out an ordinary drop of blood so that it makes a
circular smear about ¾ inch in diameter. This may be easily
accomplished with a spatulate toothpick. When dry, treat the blood
smear with alcohol containing HCl (Alcohol 50 cc., HCl 10 drops)
until the haemoglobin is dissolved out. Then wash thoroughly in
water for five or ten minutes. Allow to dry and then stain as
ordinarily with the Wright or Giemsa stain.
=Ruge’s Method.=—The best thick-film method is that of Ruge. After
the blood has dried well gently move the slide about in a glass
containing a 2% solution of formalin to which has been added 1%
of glacial acetic acid. After laking is completed, as shown by
disappearance of brown color, treat the slide in the same way in a
glass of tap water to remove all traces of acid. Next wash gently
in distilled water and stain with dilute Giemsa (1 drop to 1 cc. of
water) for twenty to thirty minutes. Wash in water and allow to dry
without heat or blotting paper. Some workers prefer to stain the
dried thick smear for one hour in a jar containing dilute Giemsa
stain (1 to 40) without previous fixation or dehaemoglobinization. At
present, I make my thick films by taking up a large loopful from the
exuding drop of the puncture wound.
This is deposited at one end of the slide and from it three or four
more daubs are made in succession toward the other end of the slide.
These daubs are quickly smeared out before coagulation takes place in
the first daub.
With all thick-film methods it is extremely important to have
thorough drying of the smear before dehaemoglobinizing or staining.
This ordinarily requires one or two hours in the air or twenty to
thirty minutes in the incubator. It is particularly important in
working with such smears, although holding for ordinary smears, to
protect them from flies, ants, etc., as such insects will eat up
the smear in a few minutes if left exposed.
=Fixation of Film.=—In Wright’s, Leishman’s, and other similar
stains the methyl-alcohol solvent causes the fixation. In staining
with Giemsa’s stain, or haematoxylin and eosin, separate fixation
is necessary. For Giemsa either absolute alcohol (ten to fifteen
minutes) or methyl alcohol (two to five minutes) answers well.
For haematoxylin and eosin, heat gives the best results. The
best method is to place the films in an oven provided with a
thermometer. Raise the temperature of the oven to 135°C. and then
remove the burner. After the oven has cooled, take out the fixed
slides or slips.
One of the handiest methods is to drop a few drops of 95% alcohol
on the slide or cover-glass. Allow this to flow over the entire
surface; then get rid of the excess of alcohol by touching the edge
to a piece of filter-paper for a second or two. Then light the
remaining alcohol film from the flame and allow the burning alcohol
to burn itself out.
=Staining Blood-films.=—As separate staining with eosin and
methylene blue rarely gives good preparations and as the
modifications of the Romanowsky stain recommended are easy to make
and employ, and give much greater information, the separate method of
staining is not recommended.
_Wright’s Method._—The stain is made by adding 1 gram of methylene
blue (Grubler) to 100 cc. of a ½% solution of sodium bicarbonate in
water. This mixture is heated for one hour in an Arnold sterilizer.
The flask, containing the alkaline methylene-blue solution should
be of such size and shape that the depth of the fluid does not
exceed 2½ inches. When cool, filter the methylene blue solution,
and add 500 cc. of a 1 to 1000 eosin solution (yellow eosin, water
soluble). Add the eosin solution slowly, stirring constantly
until the blue color is lost and the mixture becomes purple with
a yellow metallic lustre on the surface, and there is formed a
finely granular black precipitate. Collect this precipitate on
a filter-paper and when thoroughly dry (dry in the incubator
at 38°C.) dissolve 0.3 gram in 100 cc. of pure methyl alcohol
(acetone-free). Wright lately has recommended using 0.1 in 60 cc.
methyl alcohol. This constitutes the stock solution. For use filter
off 20 cc. and add to the filtrate 5 cc. of methyl alcohol.
A _modification by Balch_ is very satisfactory. In this method
instead of polychroming the methylene blue with sodium bicarbonate
and heat, the method of Borrel is used. Dissolve 1 gram of
methylene blue in 100 cc. of distilled water. Next dissolve 0.5
gram of silver nitrate in 50 cc. of distilled water. To the silver
solution add a 2 to 5% caustic soda solution until the silver oxide
is completely precipitated. Wash the precipitated silver oxide
several times with distilled water. This is best accomplished
by pouring the wash-water on the heavy black precipitate in the
flask, agitating, then decanting and again pouring on water.
After removing all excess of alkali by repeated washings, add the
methylene-blue solution to the precipitated silver oxide in the
flask. Allow to stand about ten days, occasionally shaking until
a purplish color develops. The process may be hastened in an
incubator. When polychroming is complete, filter off and add to the
filtrate the 1 to 1000 eosin solution and proceed exactly as with
Wright’s stain.
In _Leishman’s method_ the polychroming is accomplished by adding
1 gram of methylene blue to 100 cc. of a ½% solution of sodium
carbonate. This is kept at 65°C. for twelve hours and allowed to
stand at room temperature for ten days before the eosin solution is
added. The succeeding steps are as for Wright’s stain.
_In all Romanowsky methods_ distilled water should be used. If not
obtainable, the best substitute is rain-water collected in the open
and not from a roof.
_Method of staining:_
1. Make films and air dry.
2. Cover dry film preparation with the methyl-alcohol stain for one
minute (to fix).
3. Add water to the stain on the cover-glass or slide, drop
by drop, until a yellow metallic scum begins to form. It is
advisable to add the drops of water rapidly in order to eliminate
precipitates on the stained film. Practically, we may add 1 drop of
water for every drop of stain used.
4. Wash thoroughly in water until the film has a pinkish tint.
5. Dry with filter-paper and mount.
Red cells are stained orange to pink; nuclei, shades of violet;
eosinophile granules, red; neutrophile granules, yellow to lilac;
blood platelets, purplish; malarial parasites, blue; chromatin,
metallic-red to rose-pink.
_Giemsa’s Modification of the Romanowsky Method._—This is one of the
most perfect of the modifications. The objection is that greater time
in staining films is required than with the Wright or Leishman method
and the stain is very expensive.
Take of Azur II eosin 0.3 gram. Azur II 0.08 gram.
Dissolve this amount of dry powder in 25 cc. of glycerine at 60°C.
Then add 25 cc. of methyl alcohol at the same temperature. Allow
the glycerine-methyl alcohol solution to stand overnight and then
filter. This is the stock stain. To use: Dilute 1 cc. with 10 to 15
cc. of distilled water. If 1 to 1000 potassium carbonate solution
is used instead of water it stains more deeply. These same dyes,
mixed with methylene violet, are now obtainable commercially as a
powder ready for solution in methyl alcohol.
The alkaline diluent is used to obtain the coarse stippling in
malignant tertian (Maurer’s clefts). Having fixed the smear with
methyl alcohol for one to five minutes, pour on the diluted stain,
and after fifteen to thirty minutes wash off and continue washing
with distilled water until the film has a slight pink tinge. For
_Treponema pertenue_ stain from one to twelve hours.
=Haematoxylin Staining.=—While the Romanowsky methods are more
satisfactory for differential counts and for the demonstration of
the malarial parasites, and especially for differentiating species,
yet by reason of the liability to deterioration in the tropics of
methylene blue the haematoxylin methods may be preferable. Many
workers in blood-work and cytodiagnosis prefer the haematoxylin.
1. Fix the film either by heat, with methyl alcohol for two minutes
or with Whitney’s fixative. Heat is to be preferred.
2. Stain with Meyer’s hemalum or Delafield’s haematoxylin for from
five to fifteen minutes according to the stain. Frequently three
minutes will be found sufficient. To make the hemalum, dissolve
0.5 gram of haematin in 25 cc. of 95% alcohol. Next dissolve 25
grams of ammonia alum in 500 cc. of distilled water. Mix the two
solutions and allow to ripen for a few days. The stain should be
satisfactory in two or three days.
3. Wash for two to five minutes in tap water to develop the
haematoxylin color.
4. Stain either with a 1 to 1000 aqueous solution of eosin or with
a one-half of 1% eosin solution in 70% alcohol. The eosin staining
only requires fifteen to thirty seconds.
5. Wash and examine.
DIFFERENTIAL COUNT
In making a differential count I would recommend the following from
the directions of Schilling-Torgau. It will be remembered that
considerable interest was raised a few years ago in what was termed
the Arneth index. In this the more normal, more mature, better
resisting polymorphonuclears were considered to have 3 or 4 lobes
to the nuclear structure, even occasionally 5. The immature cells
had only one or at most two lobes to the nucleus. The index was
obtained by adding the percentages of cells showing 1 and 2 lobes
to ½ the percentage of those with 3 lobes. As will be understood a
high percentage of these immature cells was unfavorable in prognosis.
These cells are graded from left to right, I, II, III, IV, V, as to
separate masses in the nucleus, so that when the percentage is shoved
or displaced to the left it indicates an increase in the immature
cells.
Schilling-Torgau divides his polymorphonuclears into: (1) The
myelocyte which is always of course a pathological cell. (2)
The immature form polymorphonuclear. In this there is a close
resemblance to the neutrophile myelocyte but there is a nuclear
indentation instead of the round nucleus of the myelocyte. It is
this cell which often puzzles us as to whether to regard it as a
true myelocyte. It is the meta-myelocyte of many authorities. (3)
Between the mature or segmented polymorphonuclear and the immature
one or metamyelocyte we have what may be designated the band-form
nucleated one. These show the type of nucleus which one is familiar
with in the nucleus of the transitional. (4) The mature, multilobed
or segmented nucleus of the typical polymorphonuclear.
It would seem that if all tropical workers would agree upon
some single method of recording differential counts it would be
advantageous.
Under the blood findings in liver abscess, in a paragraph to follow
in this chapter, I give suggestive counts indicating the value of
Schilling-Torgau’s method.
In the differential count he not only divided up the
polymorphonuclears but makes no separation of small from large
lymphocytes. Although I have always divided lymphocytes into large
and small ones I believe it unnecessary and unpractical and shall
henceforth group all such cells in one grouping. The statement that
large mononuclears and transitionals are cells of a similar origin,
type and significance has always been my view.
SCHEME OF SCHILLING-TORGAU
-------------------------------------------------+-------+---------------
| Normal| Percentage
Type of Cell |Percen-|Moderate Sepsis
| tage |(W. C. 14,000)
-------------------------------------------------+-------+---------------
1. Mast cells | 1 | 1.0
2. Eosinophiles | 3 | 1.5
{ a. myelocytes | 0 | 0.5
3. Neutro- { b. immature forms (metamyelocytes) | 0 | 5.0
philes { c. band-form (Stabkernige) | 4 | 13.5
{ d. multilobed (Segmentkernige) | 63 | 64.0
4. Lymphocytes | 23 | 10.5
5. Large mononuclears and transitionals | 6 | 4.0
-------------------------------------------------+-------+---------------
BLOOD CULTURING
Among tropical diseases, only malta fever, kala-azar and plague
demand this method of diagnosis, although there are met commonly in
the tropics many cosmopolitan diseases in which blood culturing is a
principal diagnostic procedure. There are many ways of carrying out
the cultivation of organisms from the blood but the one which may be
strongly recommended is the following. The blood is obtained from a
vein, the overlying skin of which has been painted with tincture of
iodine to insure a sterile skin surface.
A stout hypodermic needle is attached to about 6 inches of rubber
tubing which in turn is pushed over a downward bent glass tube
which passes through a doubly perforated rubber stopper. A second
glass tube, which also passes through the stopper, is bent upward
to be attached to a second piece of rubber tubing for use in
suction by the mouth. The glass tubes project about ½ inch below
the under surface of the rubber stopper and above are about 2½
inches including the bent arm. This system of tubing and stopper is
readily sterilized by boiling in a pan or instrument sterilizer.
As a receptacle for the blood we employ Erlenmeyer flasks of 100
cc. capacity, containing 25 cc. of salt solution with 1% of sodium
citrate, for prevention of coagulation. Blood that contains 0.2%
of sodium citrate will not coagulate so that a 0.5% solution could
be used instead of the usual 1% one. These citrated salt solution
flasks are plugged with cotton, sterilized and kept on hand ready
for immediate use, so that we only have to sterilize the stopper
and tubing by boiling and flame the neck of the flask when removing
the cotton plug to insert the stopper of the system. By suction we
can take any amount of blood desired. I usually count the drops
of blood as they fall into the citrated salt solution allowing
16 drops to the cc. In this way we may take from 10 to 25 cc. of
blood at the bedside and then later on in the laboratory, when it
is convenient, inoculate various media from the flask. For plates
add 2 or 3 cc. of this citrated blood to 6 or 8 cc. of melted
agar at 45°C. The blood mixture can also be added to various
sugar bouillons for fermentation reactions. Finally we place the
receiving flask in the incubator and culture it as well as the
other media.
=Clot Cultures.=—A very simple method is to take blood with a Wright
U-tube. Then centrifuge and use the serum for agglutination tests and
the clot, emulsified in some liquid medium, for the blood culturing.
For paratyphoid culturing _bile media_ are preferable, just as for
typhoid.
=Lyon Blood Tube.=—Quite recently I have been using the blood
tube recommended by Lyon. To make it, heat a 5- or 6-inch section
of ¼ inch tubing in the centre and draw out as for making 2
bacteriological pipettes. Divide and seal off the large end in the
flame. Next seal off the capillary end. Then apply a very small
flame to a point on the large end just before it begins to taper
to the capillary part. The heat causes the heated sealed-off air
inside to force out a blow hole. To use: Break off the sealed
capillary end and allow the capillary end to suck up blood from a
drop just as with the Wright tube. I consider this tube superior to
the Wright one.
=N. N. N. Medium.=—In culturing blood for protozoa the N. N. N.
medium is usually employed. Novy and MacNeal originally used a 12½%
meat infusion containing 2½% agar, 2% peptone, 1% normal sodium
carbonate solution and ½% salt. To one part of this agar, melted
and cooled to 60°C., they added twice the amount of defibrinated
rabbit’s blood. In the N. N. N. medium, as modified by Nicolle,
there is beside the blood only salt and agar—no peptone or meat
extractives.
Citrated salt solution was the medium used by Rogers in the
cultivation of splenic juice from kala-azar patients.
THE TAKING OF BLOOD FOR SEROLOGICAL TESTS
This can be done with the Wright tube, pipetting off the clear serum
after centrifuging. We usually draw blood from a vein by use of the
system of stopper and tubing described under blood culturing but
employing an empty, sterile centrifuge tube.
Agglutination Tests
There are two methods of testing the agglutinating powers of a
serum—the microscopical and the macroscopical or sedimentation
method.
=For the microscopical method= draw up serum to the mark 0.5 of
the white pipette. Then draw up salt solution to the mark 11. This
when mixed gives a dilution of 1 to 20. One loopful of the diluted
serum and one loopful of a bouillon culture or salt solution
suspension of the organism to be tested gives a dilution of 1 to
40. One loopful of the 1-20 diluted serum and 3 loopfuls of the
bacterial suspension give a dilution of 1-80. These two dilutions
answer in ordinary diagnostic tests. The red pipette with a 1-100
or 1-200 dilution may be used where dilutions approaching 1-1000
are desired. Having mixed the diluted serum and the bacterial
suspension on a cover-glass, we invert it over a vaselined concave
slide and examine with a high power dry objective (⅙ inch). It
is simpler to make a ring of vaseline to fit the cover-glass and
make the mixture of diluted serum and culture in the centre of
this ring or square. Then apply the cover-glass, press it down on
the vaseline ring and examine as with the ordinary hanging drop.
In making dilutions it is preferable to use salt solution, as
the phenomenon of agglutination requires the presence of salts.
Ordinarily, thirty minutes is a sufficient time to wait before
reporting the absence of agglutination. Agglutination is more
rapid at body temperature than at room temperature. In reporting
agglutination, always give time and dilution. It is absolutely
necessary that a control preparation be prepared in every instance;
that is, one with the bacterial culture alone or with a normal
serum of the same dilution as the lowest used. Some normal sera
will agglutinate in 1 to 10 dilution, and group agglutinations (as
paratyphoid with typhoid serum) may occur in 1 to 40 or possibly
higher. It is very unusual for sera to agglutinate any other
bacteria then the specific one in dilutions as high as 1-80.
=Macroscopic Agglutination.=—For the macroscopical or
sedimentation test, take a series of small tubes (⅜ × 3 inches) and
deposit 1 cc. of salt solution in each of the series. Now, having
taken an empty test-tube, drop 4 drops of serum in it and then
add 12 drops of salt solution. This approximately gives 1 cc. of
a 1 to 4 dilution of the serum. It is more exact to make the 1 to
4 dilution with a graduated pipette. With a rubber-bulb capillary
pipette, which has been graduated to hold 16 drops or 1 cc., draw
up the contents of the tube containing the 1 to 4 serum and add it
to the next tube containing 1 cc. of salt solution. This gives 2
cc. of a dilution of 1 to 8. Now mix thoroughly by drawing up and
forcing out with the bulb pipette, and then withdraw 1 cc. and add
to the next tube containing 1 cc. of salt solution. This gives a
dilution of 1 to 16. Having mixed as before, again withdraw 1 cc.
of the mixture and add it to the 1 cc. in the next tube. We now
have a dilution of 1 to 32. Again withdrawing 1 cc. and adding it
to the fourth tube containing 1 cc. of salt solution we have a
dilution of 1 to 64. In tube 1 there is now 1 cc. of a dilution of
the serum of 1 to 8; in tube 2, there is 1 cc. of a dilution of 1
to 16; in tube 3 of 1 to 32. Tube 4 contains 2 cc. of 1 to 64. The
dilutions can be carried on in the same manner to any extent that
may be desirable. In cholera agglutinations we may run up to 1 to
5000 or thereabouts. Of course, where such dilutions are employed,
we generally start with 2 cc. of 1 to 50 in the first tube. When
we have completed the series, each tube having 1 cc. of diluted
serum, and the last 2 cc., we remove with the pipette 1 cc. from
the last tube and discard it by ejection from the pipette leaving
1 cc. in the last tube. Now adding 1 cc. of a culture of typhoid
or any other organism, we have the dilution of the serum in each
tube doubled. Tube 1 now contains a serum in dilution of 1 to 16,
acting on the bacteria; tube 2 of a 1 to 32; tube 3 of a 1 to 64.
Now place these tubes in the incubator and, after two to five hours
or overnight, we examine for the clearing up of the supernatant
fluid. If the serum in a certain dilution agglutinates, the clumps
gravitate to the bottom and the upper part becomes clear. If so
desired, these dilutions may be carried on to 1 to several hundred
in the same way. It is safer to work with dead cultures instead of
living ones. To prepare, take a twenty-four-hour agar slant culture
of typhoid or paratyphoid and emulsify in salt solution (about 6
cc. to a slant).
By adding 0.1 of 1% of formalin to the typhoid emulsion and placing
in the ice-box the cultures will be found sterile in about three
days. The emulsion should be shaken twice daily while undergoing
sterilization in the ice-box. Such cultures are not easily
contaminated and appear to retain their agglutinable qualities
for several months. The macroscopic methods are preferable with
such dead cultures. For our Dreyer emulsions we use a two-billion
suspension of typhoid or para-typhoid organisms in 1 cc. of the
formalinized culture.
_Combination of Microscopical and Macroscopical
Methods._—Microscopic: Prepare dilutions of serum as above
described and take from each or several of the series, a loopful
of the diluted serum. For control use a loopful of salt solution.
Place on a cover-glass and add loopful of bouillon culture of the
living organisms. Make hanging drop preparation, report after one
hour at room temperature. Use ⅔ inch lens for examination.
Macroscopic: Add to each of the series, including the control, an
equal amount of an emulsion of killed organisms.
The method of using a slide with two vaselined rings, one
containing an emulsion in the specific serum and the other in salt
solution, is of great practical value. This method is described
under cholera.
_Complement Fixation._—Complement fixation tests have been
employed in the diagnosis of several tropical diseases but do not
seem to be at present sufficiently reliable or practical with the
exception of that for yaws and tularaemia. The chief difficulty
with complement fixation tests for suspected sera is to obtain a
reliable antigen. Should we later on be able to prepare bacterial
antigens as satisfactory as Noguchi’s acetone-insoluble antigen
is for the Wassermann test there may be a field for such tests in
tropical pathology.
OTHER PRACTICAL METHODS OF HAEMATOLOGICAL STUDY
Haemoglobin Estimation
The standard method now is the estimation of the oxygen capacity of
the blood, using some gas apparatus, such as Van Slyke’s. Otherwise,
the most accurate instrument for this purpose is the Miescher
modification of the v. Fleischl haemoglobinometer.
[Illustration: FIG. 151.—Sahli’s Haemoglobinometer. (Greene.)]
The apparatus is expensive, requires considerable time and care in
the making of estimations, and is exclusively an instrument for a
well-equipped laboratory.
=Sahli’s Haemometer.=—A simple and apparently very scientific
instrument which has been recently introduced is the Sahli
modification of the Gower haemoglobinometer. Instead of the tinted
glass, or gelatin colored with picrocarmine to resemble a definite
blood dilution, Sahli uses as a standard the same coloring matter
as is present in the tube containing the blood. By acting on blood
with 10 times its volume of N/10 HCl, haematin hydrochlorate is
produced, which gives a brownish yellow color. In the standard
tube, which is sealed, a dilution representing 1% of normal blood
is used. To apply this test, pour in N/10 HCl to the mark 10 on
the scale of the graduated tube. Add to this 20 cubic millimeters
of the blood to be examined, drawn up by the capillary pipette
provided. So soon as the mixture assumes a clear bright dark-brown
color, which requires about ten minutes, add water drop by drop
until the color of the tubes matches. The reading of the height of
the aqueous dilution on the scale gives the Hb. reading. The tubes
are encased in a vulcanite frame with rectangular apertures. This
gives the same optical impression as would planoparallel glass
sides.
The most accurate readings are obtained with artificial light in a
dark room but almost as satisfactory comparisons can be obtained
with natural light from a window. It is advisable to turn the ruled
side around so that one may match colors without being influenced
in his determination by the scale.
The apparatus must be kept in a dark place as strong light will
change the color of the standard tube. It is recommended that the
N/10 HCl be preserved with chloroform.
The Dare instrument is excellent.
Pappenheim has recently proposed an instrument in which the
blood is converted into haematin hydrochloride as for the Sahli
apparatus. Instead of matching a standard tube, with a dilution
made drop by drop in the second tube, the new method employs a
wedge-shaped glass vessel showing graduations of the brown colored
blood, the treated blood being matched against the wedge-shaped
container (Autenreith-Koenigsberger Haemocolorimeter).
=Tallquist’s Haemoglobin Scale.=—This is a small book of specially
prepared filter-paper with a color-scale plate of ten shades of
blood colors. These are so tinted as to match blood taken up on
a piece of the filter-paper and are graded from 10 to 100. So
soon as the blood on the filter-paper has lost its humid gloss,
the comparison should be made. This is best done by shifting the
blood-stained piece of filter-paper suddenly from one to the other
of the holes cut in each shade—the piece of filter-paper being
underneath the color plate. At least a square centimeter of the
filter-paper should be stained by the blood. Daylight coming from
a window to the rear or at the side should be used in making the
comparison. The error with this method is probably not over 10%
after a little experience. If the colored plate is not kept in the
dark, the tints tend to fade.
NORMAL BLOOD
In considering what may be termed normal blood, it must be borne in
mind that the normal varies for men, women, and children:
Hb. Red Cells Leucocytes
Men, 90 to 110%, 5 to 5½ million, 7500.
Women, 80 to 100%, 4½ to 5 million, 7500.
Children, 70 to 80%, 4½ to 5 million, 9000.
COLOR INDEX
This is obtained by dividing the percentage of the haemoglobin by the
percentage of red cells, 5,000,000 red cells being considered as 100%.
To obtain the percentage of red cells it is only necessary to
multiply the two extreme figures to the left by two. Thus if a
count showed the presence of 1,700,000 red cells the percentage
would be 34 (17 × 2 = 34). If the Hb. percentage in this case were
50, then the color index would be 50 ÷ 34, or 1.4.
In normal blood the color index is, approximately, 1.
In anaemias we have three types of color index: 1. The pernicious
anaemia type which is above 1. Here we have a greater reduction in
red cells than we have of the haemoglobin content of each cell.
For example, in a case of pernicious anaemia we have 2,000,000 red
cells (40%) and 60% of haemoglobin, 60 ÷ 40 = 1.5. 2. The normal
type, when both red cells and haemoglobin are proportionally
decreased, as in anaemia fallowing haemorrhage. 3. The chlorotic
type. Here there is a great decrease in haemoglobin percentage,
but only a moderate decrease in the number of red cells. Hence the
color index is only a fraction of 1. For example, in a case of
chlorosis we have 40% of haemoglobin and 4,000,000 red cells, 40 ÷
80 = 0.5.
One can judge fairly well the approximate color index by noting the
character of the staining of the red cells. This is faint in bloods
of low color index and deeper than normal in cells in a case with
high color index.
TESTS FOR AGGLUTINATION AND HAEMOLYSIS OF THE RED CELLS (TRANSFUSION)
Transfusion of blood has become a method of greatest value in many
types of anaemia.
In the selection of a donor for blood for transfusion it is always
necessary to try his red cells against the serum of the recipient as
well as the patient’s red cells against the serum of the donor, in
order to prove the absence of haemolyzing or agglutinating bodies.
Certain persons have isohaemolysins in their blood which dissolve
the red cells of other persons and in paroxysmal haemoglobinuria
autohaemolysins may be present which can destroy the patient’s
own red cells. This autohaemolysin seems operative only when a
low temperature is followed by a high one. When haemoglobinaemia
exists the liver converts it into bile pigment, causing bilious
stools and jaundice. If one-sixth of the red cells are destroyed
haemoglobinuria results.
In the following tables, two groupings of blood are given. Both are
quoted in text-books, and both are in common use. Although that of
Moss is more generally followed in France, England and the United
States, the obvious desirability of having one classification
universally employed, in order to avoid confusion and the possibility
of serious accidents, has led to the recommendation that, on the
basis of priority the grouping of Jansky be adopted.
In 1907, Jansky described the following four groups.
Group 1, the serum of which agglutinates the corpuscles of Groups
2, 3 and 4, while the cells are not agglutinated by any serum.
Group 2, the serum of which agglutinates the corpuscles of Groups
3 and 4, but not those of Groups 1 and 2, while the corpuscles are
agglutinated by the serum of Groups 1 and 3, but not by those of
Groups 2 and 4.
Group 3, the serum of which agglutinates the cells of Groups 2
and 4, but not those of Groups 1 and 3, while the corpuscles are
agglutinated by the serum of Groups 1 and 2, but not by those of
Groups 3 and 4.
Group 4, the serum of which does not agglutinate any corpuscles,
while the corpuscles are agglutinated by the serum of all other
groups.
In 1910, Moss made the following classification:
Group 1, the serum of which does not agglutinate any corpuscles,
while the corpuscles are agglutinated by the serum of Groups 2, 3
and 4.
Group 2, the serum of which agglutinates the corpuscles of Groups 1
and 3, while the corpuscles are agglutinated by the serum of Groups
3 and 4.
Group 3, the serum of which agglutinates the corpuscles of Groups 1
and 2, while the corpuscles are agglutinated by the serum of Groups
2 and 4.
Group 4, the serum of which agglutinates the corpuscles of Groups
1, 2 and 3 while the corpuscles are not agglutinated by any serum.
At the present time it is accepted that the four groups considered
include all adult persons; i.e., that the classification is
complete.
=Before transfusing= carry out the following tests:
From a vein take about 1 cc. of blood in a centrifuge tube
containing 1% of sod. citrate salt solution; then shift the stopper
of the blood system to a dry centrifuge tube and draw into it about
3 or 4 cc. of blood. Throw down the citrated blood, pipette off the
supernatant fluid and wash the sediment with normal saline.
Again pipette off the saline after centrifuging and make a 10%
emulsion of the red-cell sediment in normal saline.
Centrifuge the coagulated blood in the other tube and collect the
serum which separates from the clot.
Carry out these procedures for both donor and recipient.
Tests: 1. In a small test-tube deposit 1 drop of the donor’s 10%
red-cell emulsion and then add 4 drops of the recipient’s serum.
2. Treat similarly 1 drop of the recipient’s red-cell emulsion with
4 drops of the donor’s serum.
3. Treat 1 drop of donor’s red-cell emulsion with 4 drops of his
serum.
4. Treat 1 drop of recipient’s red-cell emulsion with 4 drops of
his serum. Finally add 1 cc. of salt solution to each of the four
tubes, shake gently and place in incubator for two hours.
5. Treat one drop of donor’s red-cell emulsion with four drops of
salt solution.
6. Treat one drop of recipient’s red-cell emulsion with four drops
of salt solution.
Tubes 5 and 6 are controls of saline.
Tests 3 and 4 should fail to show either agglutination or
haemolysis. If agglutination or haemolysis appears in tubes 1 or 2,
the donor is not satisfactory; but if agglutination appears in tube
2 only, he may be used in an emergency.
Some prefer to keep the tubes overnight in ice-box after the
preliminary examination following incubation.
_Lee’s Technique._—For the regular carrying out of this method one
should keep on hand the sera of individuals belonging to groups 2
and 3 (Moss). To carry out the tests prepare a suspension of the
donor’s red cells by dropping 2 or 3 drops of his blood into 1 cc.
of citrated salt solution. Deposit a platinum loopful of standard
serum 2 on a slide and emulsify in it a loopful of the donor’s
red-cell suspension. A concave slide with two concavities is
convenient, the serum-cell emulsion being made on the cover-glasses
which are to be inverted over the vaseline ringed concavities. The
agglutination can be observed with a high power magnifying glass or
the ⅔-inch objective. Agglutination, when it occurs, is usually
complete in five to fifteen minutes. Repeat test with serum 3. If
both test sera agglutinate the donor’s cells he belongs to group
one. If neither agglutinate, to group four.
Agglutination by group two serum but not by three puts the donor in
group three. Agglutination by group three serum but not by group
two shows a group two donor. It would seem safe to use the cells
of any donor of group 4, as such cells are not agglutinated by
the sera of any group. It is, however, advisable to try to obtain
a donor whose blood belongs to the same group as the donee. When
standard sera 2 and 3 are not on hand one may use the following
_emergency method_ of Lee:
“A small amount of blood is collected from a patient (1 cc. from
the ear or finger is sufficient), and allowed to clot. The serum
is then obtained. One drop of this serum is placed on a slide
and mixed with a drop of suspension of blood of the donor taken
into 1.5% citrate solution. (A few drops of blood are taken into
approximately 10 times the amount of 1.5 citrate solution and
shaken. It is very important that the blood be dropped directly
into the citrate, and should not be partially coagulated.) The
test will appear in a few moments, and is best examined under
the microscope, where, in the event of a positive test, marked
agglutination will be evident. The test will also be evident
macroscopically. In the event of a negative test it is a wise
precaution to raise the cover-glass, and after making sure that the
serum and cells are well mixed, to examine the preparation again.
The only possible source of confusion is the appearance of rouleaux
of the red corpuscle, indicating a too thick emulsion. If the test
is negative, transfusion may be regarded as entirely safe.”
In the absence of agglutination haemolysis never occurs. Only about
one-fifth of agglutinating sera prove also haemolytic. Rarely a
pernicious anaemia patient’s serum may agglutinate his own red
cells. This auto-agglutination is regarded as an important test in
acquired haemolytic jaundice.
OCCULT BLOOD
When the presence of blood in the faeces, gastric contents, urine or
body fluids, is suspected but cannot be recognized by macroscopic
or microscopic methods, it is necessary to resort to spectroscopic
or chemical tests. These tests are, however, individually
unsatisfactory. The spectroscopic method is not delicate, the
haemin-crystal method does not give uniform results and the various
color tests, although very sensitive, are given by many substances
other than blood. Consequently, it may be said that, with the color
tests, it is negative results that are significant, and with other
than the color tests it is positive findings that are informative.
Serological tests are the most satisfactory medicolegally.
_Haemin Crystal Test (Teichmann)._—Prepare a solution (stable) of
0.1 gm. each of KI, KBr, and KCl in 100 cc. acetic acid. Mix a few
drops with some of the material on a slide, apply a cover-glass,
and _gently_ warm until bubbles begin to appear. Then cool
_slowly_, and examine for the characteristic dark-brown crystals.
_Haemochromogen Crystals (Donogány)._—Mix one drop each of
suspected fluid, pyridin, and 20% NaOH on slide, and let dry. If
positive, radiating needles will form after several hours.
_Spectroscopic Tests._—These depend upon the recognition of the
characteristic absorption spectra of haemoglobin or its derivatives
(Fig. 24). The degree of concentration influences their appearance,
and one should start with a relatively concentrated solution,
diluting cautiously until the bands are typical.
The small, direct-vision (hand) spectroscope suffices. A wavelength
scale is a convenient attachment. Daylight or strong artificial
light (such as the “daylite” lamp) is used. Have solution in a
small test tube or, preferably, a flat cell with a thickness of
about 1 cm. Before use, focus Frauenhofer’s lines sharply.
Reducing agents are employed, such as ammonium sulphide, or Stokes’
solution made up as follows: Dissolve 3 gm. FeSO_{4} in cold
H_{2}O; add cold, aqueous solution of 2 gm. tartaric acid; make
up to 100 cc.; immediately before use, add strong NH_{4}OH until
precipitate first formed is dissolved. Both solutions must be
freshly prepared, and the sulphide must be warmed to about 50°C.
Material that is uncontaminated, relatively fresh and in relatively
concentrated aqueous solution may give any or all of the upper
three spectra, a few drops of reducer changing the first to the
second.
If the material is older, dissolve the suspected stain in 1-2 cc.
of 10% NaOH, heat almost to boiling, cool, and add a few drops of
reducer. Examination shows Spectrum 5.
It is better, however, especially with much contamination, to
prepare an ethereal, acid extract. After having ground the material
thoroughly with water, if it is not already in liquid form, shake
it with an equal volume of neutral ether. Reject ether extract,
and, to 10 cc. of residue, add 3 to 5 cc. of glacial acetic acid.
Shake thoroughly with an equal volume of ether. If the ether does
not separate readily, mix gently with a few drops of alcohol.
Remove ethereal extract, and evaporate it to a small bulk for use
in tests. Examination will show spectrum of acid haematin, which,
however, in ethereal solution, resembles Spectrum 3 more than 4.
_Donogány’s Method_ increases the delicacy of the spectroscopic
test, and is also a color test. Dissolve the pigment with 20% NaOH,
add fresh pyridin and, if necessary, fresh ammonium sulphide.
Filter. The filtrate will be more or less orange-red according to
blood content, and will show Spectrum 5.
_Color Tests._—The reliability of these may be enhanced by the use
of methods which involve the removal or destruction of interfering
substances. In such a method, the original aqueous solution is
boiled for 15 to 20 seconds, and the acid ethereal extract is
prepared as previously described. This extract is dropped on
filter-paper, the reagents being applied to the moistened spot. The
delicacy of these several tests is variable, being greater with
blood in aqueous solution than in biological fluids, but it may
be given as approximately 1-25,000 for the guaiac and aloin, and
1-250,000 for the benzidine test.
(_a_) Treat moist spot with a few drops of freshly prepared 2%
alcoholic solution of _guaiac_ resin, and then a few drops of
hydrogen peroxide. A blue color is “positive.”
(_b_) Treat moist spot with a few drops of 3% _aloin_ in 70%
alcohol, and then with ozonized turpentine (turpentine that has
stood for a few days in an open vessel in sunlight). A purplish-red
color within 10 minutes is “positive.”
(_c_) Treat moist spot with 2 drops of glacial acetic acid, a few
crystals of _benzidine_ (preferably white), and finally 2 drops of
hydrogen peroxide. A greenish-blue color is “positive.”
ACIDOSIS
Everyone is familiar with that form of respiratory disturbance
associated with diabetic coma that is known as Kussmaul’s air hunger.
Here we have hyperpnoea, a form of dyspnoea typically without
cyanosis, and furnishing the best clinical evidence of acidosis.
Acidosis, however, is now recognized to be but a particular phase of
disturbance of the _acid-base equilibrium_ of the body, and recent
work has radically changed our conceptions of its features and its
intricate relationships.
Van Slyke restricts the use of the term “acidosis” to describe
a condition caused by acid retention sufficient to lower either
the bicarbonate or the pH of the blood below normal limits. The
pH of the blood may be considered the danger sentinel; as long as
it is normal, the acid-base equilibrium is normal or compensated;
otherwise, it is uncompensated, and life is seriously threatened.
The normal pH of the blood may be given as 7.3 to 7.5 (a slightly
alkaline reaction), each individual, however, probably having
normally narrower limits of variation. That of the blood serum is
about 0.2 pH higher, and that of the other body fluids (not the
excretions) probably closely approximates and promptly follows any
change in that of the blood plasma. Variations to the acid side
may, for a short time at least, be as low as 7.0, although not much
lower without fatal results; 7.0 is considered the point where
coma occurs. Variations to the alkaline side (Alkalosis) beyond
7.8 are accompanied by symptoms of tetany, although one is not at
present justified in assuming that all tetany is either caused,
or accompanied, by alkalosis. So, the extreme range of reaction
compatible with life probably lies approximately between pH of 7.0
and 7.8.
Recent, but as yet unconfirmed, work suggests that the severe
reactions following intravenous medication or infusions may be due,
at least in part, to the fact that the pH of the fluid introduced
is decidedly more acid or alkaline than that of the blood. This
applies to solutions of glucose, the salines, and possibly also to
sodium citrate, arsphenamine, sera, antitoxins, etc. The question
of suitably buffering such solutions, _e.g._, with suitable
phosphate mixtures, in order to avoid disturbance of the acid-base
equilibrium, is being studied, and the preliminary results are
promising.
The hydrogen-ion concentration (or its derivative, pH) of
the blood varies as the ratio between the concentrations of
dissolved carbonic acid and bicarbonate (generally indicated by
(H_{2}CO_{3})/(NaHCO_{3})), i.e., a relative increase in the
H_{2}CO_{3} increases the hydrogen-ion concentration and lowers
the pH, and vice versa. The stability of this ratio is preserved
by body mechanisms operative in controlling its two factors,—the
H_{2}CO_{3} being under respiratory control, and the NaHCO_{3},
considered as representing the alkali reserve, being normally
maintained by food.
The erythrocytes control the concentration of bicarbonate by virtue
of their haemoglobin and the reversible reaction.
H_{2}CO_{3} + NaCl ⮂ HCl + NaHCO_{3}
The HCl passes into the cell, and is probably held by the
haemoglobin. In the lungs, the CO_{2} is excreted and NaCl
reformed. This ability of haemoglobin to form bicarbonate is
important inasmuch as the corpuscles can conceal 5 to 10 times as
much acid as the plasma bicarbonate can ordinarily neutralize.
A full appreciation of the significance of this ratio being the
basis of an intelligent comprehension of acid-base equilibrium, a
detailed analysis of factors that tend to influence the ratio is
given.
Factors Operating:
_A. To increase or protect bicarbonates:_
1. Administration of bicarbonate.
2. Loss of gastric HCl induced by obstructing the pylorus,
and regularly washing out the stomach for some
days.
3. Processes indicated by increased excretion in the urine of
ammonia compounds, the ammonia being probably
diverted from urea formation, and of substances
producing a titrable acidity, they including buffer
acids such as acid phosphates.
4. Possibly a shift of HCl to the tissue cells from the plasma
like that from the plasma to blood cells.
_B. To decrease bicarbonate:_
5. Acid substances, by their
(_a_) Increased production.
(_b_) Decreased elimination or
(_c_) Ingestion.
6. Diuresis, with elimination via the urine.
7. Lack of Factor A (3).
8. The hyperpnoea associated with deficient oxygen.
_C. To increase carbonic acid:_
9. Administration of carbonic acid.
10. Impaired diffusion in the alveoli of the lungs.
11. Slowing of respiration.
_D. To decrease carbonic acid:_
12. Hyperpnoea.
(_a_) Voluntary.
(_b_) Due to disease processes.
(_c_) Due to low oxygen content of air.
(_d_) Emergence from warm water.
13. Low atmospheric content of CO_{2}.
[Illustration: FIG. 152.—Carbon dioxide absorption curves. (Modified
from Peters, Barr, and Rule, and Van Slyke).]
Figure 152 is a graphic representation of essential facts in
acid-base equilibrium. Ordinates represent total CO_{2} content,
which comprises that in simple solution and that as bicarbonate
of whole blood in volumes per cent, and abscissae the mm. CO_{2}
tension in the blood as drawn. The line OT gives the proportion
of total CO_{2} present in simple solution. pH values are shown
by the lines OL, OM, etc. The extreme normals for carbon dioxide
absorption curves are OP and OR. The CO_{2} tension of alveolar
air may be the same or vary as much as 20 mm. below, while that of
venous blood will be about 6 (0.8-10.0) mm. higher than that of
arterial blood. The “CO_{2} capacity” (or “CO_{2} combining power”)
of plasma may be as much as 15 vol. % more than the total CO_{2} of
whole blood.
The actual state of acid-base balance, then, can only be determined
by the use of any two of a number of interdependent variables, such
as total CO_{2}, CO_{2} tension, pH, H_{2}CO_{3} concentration,
other buffers than bicarbonate, plasma chloride, ratio of
oxyhaemoglobin to haemoglobin, etc. Findings that fall within ABCD
and at about 40 mm. tension indicate a normal equilibrium for the
resting individual at ordinary altitudes. Or, such a normal would
be a total CO_{2} of about 49 (43-56) vol. % for whole blood, and
50-65 vol. % for plasma. The normal for the individual falls within
narrower limits.
If either H_{2}CO_{3} or bicarbonate varies from normal values,
there is apparently an effort on the part of the body to compensate
by adjusting the other so as at least to maintain a normal pH.
This is accomplished by respiration, or by diverting alkali from
or recalling it to the blood stream. Naturally, treatment of any
such abnormal condition will do well to imitate Nature’s efforts.
Haggard and Henderson have demonstrated that blood alkali may be
decreased in two ways—by acids (the _acidotic process_) or by
acapnia (the _acapnial process_). By the forced breathing of the
acapnial process the lungs are over-ventilated and an excessive
amount of carbon dioxide is washed out of the blood, thus bringing
on a temporary alkalosis. In case of prolonged forced breathing,
nature prevents an extreme alkalosis by causing the alkali to
leave the blood, it being stored in the tissues or excreted in the
urine. Blood relatively poor in carbonic acid or relatively rich in
alkali acts to depress respiration, and the slowing of respiration
produces an acidosis by the resultant retention of H_{2}CO_{3},
this causing alkali to be recalled from the tissues. Thus acidosis,
in calling more alkali into the blood from the tissues, represents
what may be regarded as a restorative effort. Hence, administration
of bicarbonate is indicated in acidotic processes, and of CO_{2} in
acapnial; the use of the wrong one is dangerous.
The numbered regions of the chart are associated with various
clinical conditions, e.g., tetany from 1, 2, and 3; the acidosis of
diabetes mellitus, nephritis, or infantile marasmus with 6 or 9;
pneumonia, morphine narcosis, and breathing of air containing 3-5%
CO_{2} with 7 or 8; emphysema with 4; some cardiac cases with 9;
overdose of bicarbonate with 1 or 4; fever with 2; as the result of
high altitudes, 2 or 3, or, when acclimated, 6; shock (handling of
intestines), deep ether anesthesia, and carbon monoxide asphyxia
with lowered bicarbonate. The disturbances of acid-base equilibrium
in the last two are the result of acapnial processes.
Normal metabolism results in the constant formation of acids,
especially H_{2}CO_{3}, and disease processes may occasion the
presence of still more. A constant loss of alkali results, the
neutralization products being eliminated mostly in the urine, and
the H_{2}CO_{3} via the lungs; the body fluids are excellently
buffered, the most important buffers being bicarbonate, proteins
(especially haemoglobin), and phosphates. In the maintainance
of the normal pH, the CO_{2} (or H_{2}CO_{3}) is the easily
variable factor. The onslaught of invading acids is first met
by the bicarbonates (acidotic process); hyperpnoea lowers the
H_{2}CO_{3} and a normal pH is maintained until the bicarbonates
are reduced to one-fourth (perhaps even to one-eighth) of their
normal concentration. If, nevertheless, the pH falls (and only
then), the other buffers are used, and, if it reaches 7.0, most of
the remaining bicarbonate becomes available. The blood handles the
situation, but buffers from the tissues or other body fluids also
become available in extreme cases.
As noted above, measurement of one variable will be inadequate
exactly to determine the state of acid-base equilibrium. As long,
however, as the pH is normal, which is the usual finding in most
pathological conditions, including mild acidosis, one determination
will suffice. Clinical methods comprise tests for whole blood or
plasma CO_{2} or bicarbonate, alveolar CO_{2} tension, bicarbonate
tolerance, pH of blood or urine, Sellard’s test, NH_{3} quotient of
urine, or presence of abnormal acids (particularly acetone bodies)
in blood or urine. The first two methods are the ones of choice,
particularly the first, as, by it, one can estimate the reserve
of the very important blood buffer, bicarbonate, and its result
closely indicates the total buffers.
The _tolerance for bicarbonate_ is a very convenient and practical
measure of acidosis, and means the dose of NaHCO_{3} required to
produce a urine alkaline or amphoteric to litmus. A normal finding
is 5-10 grams; 20 is required with a mild, 30-40 with a more severe,
and more than 40 gm. with extreme degrees of acidosis. In coma, it is
usually impossible to produce an alkaline urine.
Certain changes in the urine are recognized and acceptable as
indirect evidence of acidosis, but these changes are not synonymous
with acidosis, being dependent in part upon renal integrity and
other factors. The NH_{3} quotient of urine (ammonia nitrogen;
total nitrogen), as usually determined with patient on a mixed
diet, is normally about 5%. Values of 10-40% occur in acidosis.
It may be increased by diet, disturbances of protein metabolism,
ammoniacal fermentation, etc., and there may be no increase in
certain diseases with acidosis. The ammonia probably does protect
the blood alkali, but its efficacy is intimately associated with
renal function, inasmuch as Nash and Benedict have presented strong
evidence to the effect that urinary and blood NH_{3} is the product
of an active synthetic function of the kidneys themselves. Acetone
bodies in the urine (_ketonuria_), in the blood (_ketosis_), or in
the breath, have diagnostic value but are poor indices of severity
of acidosis and may be absent in acidosis. Acetone and diacetic
acid have the same significance: a progressive increase gives a
grave prognosis, and it is generally considered that the presence
of β-hydroxybutyric acid indicates greater severity.
Acidotic acidosis is due either to the abnormal formation or
ingestion of acid substances, or to decreased elimination of
normal metabolic products. Ketosis is the important example of the
former, and retention of acid phosphates of the latter. In either
case, the body is robbed of its bases. The acidosis of diabetes
mellitus is characterized by ketosis and increased NH_{3} quotient
of urine, while that of nephritis is a phosphate retention without
ketosis, and, as one would expect, the NH_{3} quotient is usually
not increased. Infantile diarrhoea with ileocolitis shows a marked
ketosis, but, lacking the ileocolitis, the ketosis is only moderate
and the acidosis is due to phosphate retention.
The appearance of an acidosis in disease constitutes a serious
development demanding immediate attention. It is usually present at
time of death and may be the immediate cause. We must be prepared for
the appearance of acidosis in the course of numerous cosmopolitan
diseases, and its presence has been recognized in a few tropical
conditions. Before we generally recognized the great importance of
the acidosis factor in pathology, there were two standard treatments
for _yellow fever_ and _blackwater fever_, the Sternberg one in the
former and the Hearsey one for the latter, both of which had as a
basis the administration of alkalis, which is our best means for
neutralizing the deleterious action of increased acid production
in the body or defective elimination of the same. It was a very
important contribution to the therapeutics of _cholera_ when
Sellards, recognizing the tendency of the nephritis to produce an
acidosis in this disease, made use of intravenous injections of
NaHCO_{3} to combat the condition, thus counteracting the anuria,
one of the chief complications leading to death. More recently, the
Egyptian workers noted an acidosis in _kala-azar_, a finding verified
and emphasized by Rogers. There is also an acidosis in _heat stroke_,
so that intravenous or rectal injections of NaHCO_{3} are of value.
It will thus be seen that acidosis is a most important condition to
keep in mind in tropical conditions, and it will be well to be on the
watch for other varieties of disturbance of acid-base equilibrium.
Relative to the _administration of bicarbonate_ in treatment, there
is now a decided reaction against the use of amounts that may prove
injurious by reason of the danger of alkalosis. There is a tendency
to employ it only in decompensated acidosis, and control it by
estimations of plasma CO_{2} capacity, 0.5 gm. NaHCO_{3} per 19
kg. body weight will raise the plasma CO_{2} capacity by 1 vol %.
It is distinctly contraindicated in cases whose low plasma CO_{2}
is due to acapnial processes. Early administration is desirable in
children, and good results are obtained, especially with the older
ones. An acidosis, however, once established in infants may cause
death despite alkali. In order to avoid over-dosage of bicarbonate,
methyl red, which is more sensitive than litmus to early changes in
the reaction of the urine, should be employed as an indicator. The
appearance of a yellow color upon its addition to the urine is the
sign to suspend further administration of alkali.
Glucose is indicated in conditions with ketosis due to carbohydrate
deficiency, providing the organism can assimilate it.
CHEMICAL ANALYSIS OF BLOOD
The chemical analysis of the blood has attained a clinical simplicity
and significance that demands recognition. It provides points of
value in diagnosis, prognosis, and treatment, being especially useful
in nephritis, diabetes, acidosis, comatose conditions, gout, and in
questions of renal function and treatment, especially dietetic. Urine
findings are always dependent upon kidney function, and, by blood
chemistry, we can pass behind this barrier.
Few diseases have been as yet studied thoroughly in this respect,
but our fund of knowledge is receiving constant additions. The
field of tropical medicine is practically untouched, and it is
quite possible that an investigation along this line might there
yield facts of interest and value.
The following table (amplified from Myers), is a concise summary of
normal findings and those encountered in various clinical conditions.
The diagnostic significance is evident. Some of the results are
based upon the analysis of many cases; others upon but few. One
might include the findings mentioned elsewhere regarding acidosis
in certain tropical diseases, but, except for such, we have no
other data relative to them, unless one mentions that blood sugar
is increased in the tropics. The values are given in milligrams per
100 cc. whole blood (the usual system), except those for diastatic
activity (recorded in Winslow’s empirical units) and acidosis
(expressed in terms of plasma carbon dioxide combining power—volumes
%). “Inc.” and “Dec.” signify increased and decreased respectively.
RESULT OF CHEMICAL EXAMINATION OF BLOOD
CONDITION
--+-------+-------+------+-------+--------+-------+-------+-------+------
| Non | | | | | | | |Plasma
|protein| Urea | Uric |Creati-| Sugar |Choles-|Chlor- | Dias- |CO_{2}
| nitro-|nitro- | acid | nine | | terin | ides | tase |capa-
| gen | gen | | | | | | | city
--+-------+-------+------+-------+--------+-------+-------+-------+------
NORMAL
| 25-300| 10-15 | 2-3 | 1-2 | 90-120 |170-250|450-500| 8-64 | 53-77
| | | | | | | | |
DIABETES
MELLITUS,
MILD
| | | | |150-300 | | | Inc. |
| | | | | | | | |
DIABETES
MELLITUS,
SEVERE
| | 20 | 4-10 | 2-4 |300-1200| Inc. | Dec. | Inc. | 10-50
| | | | | | | | |
NEPHRITIS,
ACUTE
| | 40-100| 5-15 | 2-6 |120-180 | | Inc. | 20-45 |
| | | | | | | | |
NEPHRITIS,
INTERSTITIAL,
EARLY
| | 15-25 | 5-12 | 2-3.5 |120-150 | | | Inc. |
| | | | | | | | |
NEPHRITIS,
INTERSTITIAL,
TERMINAL
|100-300| 60-300| 5-27 | 5-28 |120-240 | Inc. | Vari- | Inc. | 12-40
| | | | | | | able | |
NEPHRITIS,
PARENCHYMATOUS
(NEPHROSIS)
| 20-50 | 2-5 | 2-4 |120-200| Inc. | Inc. | | |
| | | | | | | | |
NEPHRITIS,
CHRONIC
DIFFUSE,
SEVERE
| | to 230| to 10| to 16 | to 250 | | | |
| | | | | | | | |
URAEMIA
| 90-350| 70-300| | | | | | |
| | | | | | | | |
KIDNEY
POLYCYSTIC,
DOUBLE
| | to 75| to 5 | to 8 | to 200 | | | |
| | | | | | | | |
PROSTATIC
OBSTRUCTION
| Inc. | 12-40 | 3-9 |1.5-3.5|110-160 | | | |
| | | | | | | | |
GOUT
| | | 4-10 | | | | | |
| | | | | | | | |
HYPERTHY-
ROIDISM
| | Inc. | | | Inc. | | | Inc. |
| | | | | | | | |
HYPOENDOCRINE
CONDITIONS
| | Dec. | | | 60-90 | | Dec. | Dec. |
| | | | | | | | |
ECLAMPSIA
| 25-45 | 10-25 | 4-8 | | | | | | 43-58
| | | | | | | | |
INTESTINAL
OBSTRUCTION,
ACUTE
| 75-170| 45-120| Inc. | Inc. | | | | |
| | | | | | | | |
FEVER,
ACUTE
| Inc. | Inc. | to 4 | | Dec. | Dec. | | |
| | | | | | | | |
PNEUMONIA,
SEVERE
AND LATE
| | to 53 | to 18| to 3.5| to 180 | Inc. | Dec. | | Dec.
| | | | | | | | |
ANAEMIA,
PERNICIOUS
| to 108| to 75 | to 10| to 3.1| to 300 | Dec. | Inc. | | Dec.
| | | | | | | | |
MALIGNANCY,
LATE
| Inc. | Inc. | Inc. | Inc. | | Dec. | Inc. | | Dec.
| | | | | | | | |
DEMENTIA
PRAECOX,
CATATONIC
| | 6-10 | Dec. | | Inc. | | | |
| | | | | | | | |
SHOCK
| Inc. | Inc. | | Inc. | Inc. | | | | Dec.
| | | | | | | | |
BICHLORIDE
OF MERCURY
POISONING
|to 370 | to 300| to 15| to 33 |120-200 | Inc. | | |
| | | | | | | | |
PLUMBISM
| Inc. | Inc. | Inc. | | | | | |
--+-------+-------+------+-------+--------+-------+-------+-------+------
_Interstitial nephritis_ is characterized by a nitrogen retention,
while _parenchymatous nephritis_ has relatively little nitrogen
retention but does have a decided tendency towards chloride
retention. _Essential hypertonia_ with its normal blood chemistry
is differentiated from _arteriosclerosis_ with its frequent
nitrogen retention. The imminence of _uraemia_ may be judged
by the extent of the nitrogen retention. We have an aid in
the differentiation of the uraemia of nephritis accompanied
by a flagging heart from the passive congestion of cardiac
decompensation, especially as to which is the secondary condition,
and thus therapeutic indications relative to mooted questions
of treatment (hot packs, morphine, renal stimulants, etc.).
Unsuspected cases of nephritis showing only gastric symptoms
clinically have been detected by blood chemistry. The significance
of albumin in traces and occasional casts in urine has been more
definitely established by examination for increase of uric acid
in the blood—an increase arguing for an organic lesion. Values
of over 4 for creatinine do not occur without great impairment
of renal function, and findings of more than 5 have practically
uniformly foretold a fatal termination in less than six months,
except in acute nephritis and mild bichloride of mercury poisoning.
The creatinine is also the best guide to the status of renal
function in terminal cases. The chloride and nitrogen content
afford guides to diet.
The blood may indicate a prediabetic state, and place the
practitioner upon his guard. There is a condition but recently
recognized in which there is a normal blood sugar, a persistent
glycuresis of usually less than 1% and independent of carbohydrate
intake, occasionally polyuria, but with no other symptoms of
diabetes mellitus. It is known as _renal diabetes_, is apparently
harmless, probably not uncommon, and may represent the condition
affecting most of those “diabetics” who can disregard diet with
impunity. The blood sugar and plasma CO_{2} are usually considered
the only safe guides in the treatment of _diabetes mellitus_ and
no extended medical treatment or surgical interference should ever
be attempted without their estimation. Glycosuria is a poor guide,
especially in advanced cases.
In _comatose conditions_, nitrogen retention will indicate the
uraemic, and hyperglycaemia the diabetic cases. But _acute
nephritis_ should always be borne in mind, as it may have a
pronounced acidosis but no nitrogen retention.
A high uric acid finding alone is characteristic of gout, and
aids in differential diagnosis from simple rheumatic fever and
other arthritides, any uric acid retention in them being usually
accompanied by retention of other nitrogenous elements. It is
especially useful in the diagnosis of gouty arthritis without tophi.
The efficacy of treatment will, in general, be shown by the degree
of approach to normal blood findings.
LEUCOPENIA
This is a term used to designate a reduction in the normal number
of leucocytes. A leucocyte count of 5000 would represent a slight
leucopenia; one of 2000, a marked leucopenia. In the later stages
of typhoid, and in acute miliary tuberculosis, we expect a moderate
leucopenia. Glandular tuberculosis may give a very marked leucopenia.
Tuberculous peritonitis will show moderate leucopenia or a normal
count.
The leucopenia of typhoid is moderate and is often preceded in the
first few days by a moderate neutrophile leucocytosis. Later on we
have a decided increase in the lymphocytes. A marked diminution or
absence of eosinophiles is so characteristic that any increase in
eosinophilic percentage negatives a diagnosis of typhoid.
Paratyphoid gives a similar blood picture.
Chronic alcoholism and chronic arsenic poisoning cause a reduction
in the number of the white cells. Pernicious anaemia, especially
the aplastic type, shows a marked leucopenia, as is also the case
with Banti’s disease. Two tropical diseases, kala-azar and dengue,
show a marked leucopenia, the counts often being below 2500. During
the apyrexial period of malaria we may have a white count of 5000.
It has recently been claimed that a leucopenia with a coincident
marked reduction in the lymphocytes is characteristic of measles and
that this occurs several days before the Koplik spots appear.
Kocher notes that in exophthalmic goiter the leucocyte count is
considerably diminished and that the polymorphonuclears are not
much more than one-half the usual percentage while the percentage
of the lymphocytes is almost double the normal.
X-ray treatment tends to destroy leucocytes in the exposed region,
especially polymorphonuclears. The small lymphocytes are least
affected.
EOSINOPHILIA
Where the eosinophiles are increased to 5%, we have a moderate
eosinophilia. In some cases of infection with intestinal parasites,
especially hookworms, but also from other parasites, as round and
whip-worms, we may have an eosinophilia of 30 to 50%. In Guam, among
the natives, it is difficult to find an eosinophile count under 15%.
The eosinophilia tends to disappear when the anaemia becomes very
severe.
_Echinococcus_ infection has an eosinophilia which disappears when
the cyst is removed. Continuance of the eosinophilia indicates that
all cysts were not gotten rid of.
The eosinophilia of trichinosis is best known, and a combination of
this blood finding with fever and marked pains of muscles, would
justify the excision of a piece of muscle for examination for
encysted embryos.
In true asthma eosinophilia is marked, and its absence is of
value in indicating other causes for the condition. Certain skin
diseases, especially pemphigus, show eosinophilia. Blastomycoses
are usually found to show eosinophile increase.
An increase of eosinophiles always attracts attention to the
possibility of intestinal parasite infections or to skin affections.
The explanation of eosinophilia is obscure although Neisser regards
the increased production of eosinophiles as an expression of
sympathetic system irritation.
Eczema and psoriasis are not apt to give more than 3 or 4%
eosinophiles. A rather high degree of eosinophilia is found in
mycosis fungoides.
Scabies also gives an eosinophilia.
The proportion of eosinophiles in the blood of children is greater
than in that of adults.
Increase of both eosinophiles and mast cells is found in
myelogenous leucaemia.
An eosinophilia tends to appear following splenectomy.
With a Wright stain showing acid tendencies one may count
polymorphonuclears as eosinophiles unless noting smaller size of
granules.
LEUCOCYTOSIS
It is to an increase in the polymorphonuclears that this term is
usually applied, the term lymphocytosis or eosinophilia being
employed where white cells of eosinophile or lymphocyte nature are
increased. We have physiological leucocytosis in the latter weeks of
pregnancy, also in the new-born, and in connection with digestion.
=Pathological Leucocytosis.=—Pneumonia. In this disease we have
a leucocytosis of 20,000 to 30,000 or higher. The eosinophiles
are almost absent. A normal leucocyte count in pneumonia makes a
prognosis unfavorable.
The leucocyte count drops about the time of the crisis, and with
the reappearance of eosinophiles is a favorable sign.
Toxaemic conditions as uraemia, diabetic coma and poisoning by
CO_{2} tend to show a leucocytosis.
Septic processes. The leucocyte count is of great value, especially
when we obtain a leucocytosis with 80 to 90% of polymorphonuclears,
as in appendicitis, cholecystitis, or other suppurative conditions.
A marked leucocytosis is of diagnostic importance in acute ulcerative
endocarditis provided it is not fulminant in type.
According to Cabot, leucocytosis varies in infections as follows:
1. Severe infection—good resistance; early, marked and persistent
leucocytosis.
2. Slight infection—slight resistance; leucocytosis present, but
not marked.
3. In fulminating infections we may have no increase in whites, but
a higher percentage of polymorphonuclears.
4. Slight infection and good resistance may not be productive of
leucocytosis.
It is in connection with the question of operation in appendicitis
or similar conditions that the matter of a leucocyte count is of
prime importance. If there be a leucocytosis but with less than
75% of polymorphonuclears it indicates an infection of little
virulence or a walled-off process with an exacerbation. It is
difficult to form an opinion when the polymorphonuclears are
under 80%. Leucocytosis with polymorphonuclear percentage of 85
to 90 indicates immediate operation; percentages over 90 point to
peritonitis and if with such percentages of polymorphonuclears
there is absence of leucocytosis the prognosis is grave.
The blood of cases with malignant tumors tends to show a moderate
leucocytosis except in epithelioma of the skin. When a cancer is
ulcerating quite a high white count may be obtained.
Spirochaete fevers, as relapsing fever, may give a leucocytosis of
from 25,000 to 50,000.
Smallpox, especially at time of pustulation, plague, scarlet fever,
and liver abscess give a leucocytosis of from 12,000 to 15,000.
Smallpox often shows a very large percentage of very characteristic
large mononuclears.
The leucopenia and lymphocyte increase in measles are important
points in differentiating it from scarlatina.
Influenza shows a leucopenia at first, then a leucocytosis and,
following the fall in fever, a second lowering. The very fatal
pneumonias of the 1918 epidemic of influenza showed a marked
leucopenia.
With meningitis counts of 25,000 are not unusual, in abscess of the
brain the white count rarely exceeds 15,000.
Poliomyelitis and polioencephalitis give a slight leucocytosis during
the febrile accession.
Erysipelas and epidemic cerebro-spinal meningitis also give a
leucocytosis of from 15,000 to 20,000. In malignant diseases we
sometimes have a moderate leucocytosis. Rogers states that in liver
abscess, with a leucocytosis of 15,000 to 20,000 we have only
about 75 to 77% of polymorphonuclears—there being also a moderate
increase in the percentage of large mononuclears.
Drugs such as antipyrin may give a leucocytosis. The leucocyte
increase of pilocarpine is rather a lymphocytosis. Cinnamate of
soda, sodium nucleate, bacterin injections and turpentine have been
used in kala-azar to increase leucocytes.
LYMPHOCYTOSIS
Of course, the disease in which we have the most marked lymphocytosis
is lymphatic leucaemia.
The lymphocytosis of typhoid fever has been taken up under
leucopenia.
Whooping-cough may give a lymphocytosis of 20,000 to 30,000.
Young children have normally an excessive proportion of lymphocytes
even to a reversal of the polymorphonuclear-lymphocyte relation
of adults. This is apt to be particularly marked in hereditary
syphilis. Enlarged tonsils may give rise to lymphocytosis of
10,000 to 15,000 when more than 50% of the white cells will be
lymphocytes. Rickets and scurvy give a lymphocytosis.
In pellagra there is a moderate lymphocytosis, averaging 34% in
about a normal count.
Varicella and mumps may also give an increase in the percentage of
lymphocytes.
Malta fever is a disease which may show quite a lymphocyte
increase, this going with a reduction in polymorphonuclears.
_Glandular fever_ (Pfeiffer, 1889) is a mild acute febrile disease,
the fever coming on after a short incubation period and lasting
about one week. Its main characteristics,—soft enlargement of
the lymphatic glands, splenomegaly, and a leucocytosis of about
20,000 with 80% lymphocytes of the lymphoblastic type and many
with bilobed Rieder nuclei,—lead often to its being mistaken for
lymphatic leucaemia. Throat infections, particularly Vincent’s
spirillosis, are thought by some to be concerned in its genesis.
INCREASED LARGE MONONUCLEARS
In tropical work we combine the large mononuclears and transitionals
in a differential count. They are the phagocytes of animal cells or
parasites. The disease in which their increase is best recognized
is malaria and an increase to 15% where the blood shows moderate
leucopenia is very significant. The melaniferous leucocytes of
malaria are cells of this type.
Other protozoal infections, as kala-azar, trypanosomiasis and
amoebiasis cause it. Filterable-virus diseases may show a
mononuclear increase, thus yellow fever and dengue both give an
increase about the fifth or sixth day.
In Banti’s disease there is an increase in cells of this type and a
transitional increase is reported for Hodgkin’s disease.
DISEASES IN WHICH THERE IS A NORMAL LEUCOCYTE COUNT
Uncomplicated tuberculosis, influenza, Malta fever, measles,
trypanosomiasis, malaria, syphilis, and chlorosis.
In malaria we have a leucocytosis at the time of the rigor, while
during the apyrexial period there is a moderate leucopenia. In
malaria we have a marked increase in the percentage of the large
mononuclears and transitionals. These may form from 20% to 30%
of the leucocytes. When bearing particles of pigment they are
known as melaniferous leucocytes—macrophages which have ingested
malarial material. In dengue, at the time of the terminal rash,
we may have as great a percentage of large mononuclears. In this
disease, however, we have a great diminution of polymorphonuclears
from the start (25 to 40%). Instead of a large mononuclear we have
at the onset a lymphocytic increase. There is an increase of large
mononuclears in trypanosomiasis.
The white count is about normal in uncinariasis (Ashford’s average
was 7800). Some have reported a leucopenia in severe cases.
While eosinophilia is the most marked feature in hookworm disease
yet in very severe cases it may be absent.
Coagulation Rate of Blood
This determination is of value in connection with operations on
jaundiced patients.
Wright’s coagulometer is a standard instrument but is cumbersome.
A simple method of determining the rate is to take a piece of
capillary glass tubing and hold it downward from the puncture to
let it fill for 3 or 4 inches. Then at intervals of thirty seconds
scratch with a file the capillary tubing at short distances and
break off between the fingers. When coagulation has taken place a
long worm-like coagulum is obtained. Normally coagulation occurs in
about three to four minutes, when the temperature is that of the
hand in which the tubes are conveniently held. Rudolf recommends
placing the tubes in metal tube-containers in a Thermos bottle at
20°C. He gives the normal coagulation rate for this temperature
as eight minutes, while at a temperature below this the period is
lengthened. Age and sex do not influence the rate. Sabrazes, the
originator of this method found no appreciable variation in tubes
from 0.8 to 1.2 mm diameter.
In Burker’s test you mix a drop of blood in a drop of distilled
water on a slide and with a capillary tube sealed off at the end
stir the mixture every half minute. So soon as fibrin threads
appear you have coagulation.
For the proper testing for coagulation rate the blood should be taken
from vein and not from that exuding from a needle stab of ear or
finger. Our experience shows that it is not necessary to use venous
blood.
Specific Gravity of the Blood
Hammerschlag has a method for the determination of the Hb. percentage
based upon the specific gravity of the blood.
In this method a mixture of benzol and chloroform is made of a
specific gravity of about 1050. A medium size drop of blood is then
taken up with a pipette and dropped into the mixture. If it sinks
add more chloroform from a dropping bottle, if it tends to rise,
more benzol. The mixture in which the drop of blood tends to remain
stationary, near the top of the mixed benzol and chloroform, has
the same specific gravity as that of the blood. This is determined
by an accurately graduated hydrometer. The normal average specific
gravity for men is 1059, for women 1056. A table, giving the Hb.
percentage corresponding to the specific gravity, accompanies the
outfit.
To determine the necessity for intravenous infusion in cholera
Rogers has recently recommended the employment of small bottles
containing aqueous solution of glycerine with specific gravities
varying from 1048 to 1070, increasing the specific gravity in each
successive bottle by 2°.
An accurate hydrometer will suffice to determine the specific
gravity. Drops of blood from the cholera patient are deposited
at the center of the surface of the fluid in the bottles from a
capillary pipette. If the specific gravity of the blood is 1062 at
least a liter of saline or sodium bicarbonate solution is needed.
If 1066 at least two liters. Formerly he estimated the indications
by blood pressure considering a pressure of 80 in Europeans or of
70 in natives as indicating intravenous injections.
PRACTICAL APPLICATION OF METHODS OF BLOOD EXAMINATIONS TO THE VARIOUS
TROPICAL DISEASES
In considering the value of blood examinations in the various
tropical diseases we may _first_ note those in which such
examinations are of little or no value and _second_ those in which
such examinations are crucial or at any rate of prime importance.
1. IN THE FIRST GROUP WE MAY INCLUDE THE FOLLOWING:
_Beriberi._—The leucocytes are about normal in number with
possibly a slight increase in lymphocytes. Of course there may be
anaemia present with the progress of the disease. Some think there
is a slight diminution from the normal percentage of eosinophiles.
Noc found the percentage of lymphocytes in beriberi patients to be
about 35 as against 32 for those unaffected.
_Sprue._—There is considerable reduction in red cells which
may fall below 2,000,000 in advanced cases. The whites may show
a slight tendency to leucopenia with a relative increase in
lymphocytes. The haemoglobin is not as much reduced as the red
cells so that we obtain a color index of from 1.1 to 1.3.
Poikilocytosis and punctate basophilia are often noted, but rarely
does one find nucleated reds. In a severe case the blood picture
is rather that of an aplastic anaemia than a typical pernicious
anaemia. The eosinophiles are rare or absent as the case advances.
One often finds many (7-9) nodes in the polymorphonuclears.
_Pellagra._—This disease may show a chloranaemia. Some authorities
have stated that we have an increase in the percentage of large
mononuclears but Hillman found a rather definite increase in the
lymphocytes (34%) and a normal large mononuclear percentage.
_Yaws._—This disease may show a moderate anaemia with a low color
index. The leucocytes are about normal in number with a moderate
increase in the percentage of large mononuclears.
_Leprosy._—There is, as would be expected, with the progress of
the disease, an anaemia which is of the chlorotic type. Leprosy
bacilli may be found in the blood, especially during the time of
the febrile accessions, but such examinations are of very little
value in practical diagnosis and there are so many liabilities to
error, as shown in the work with tubercle bacilli in blood, that we
should be very conservative in this direction.
There is probably an increase in the percentage of lymphocytes.
_Yellow Fever._—The blood findings are usually given as normal
although Noc states that at first we have an increase in
polymorphonuclear percentage to be followed by an increase in the
large mononuclears about the fifth day. He also noted an absence or
diminution of eosinophiles.
Intraperitoneal inoculation of animals with blood from patient
should be practised. Should the diagnostic reliability of the
procedure be established, yellow fever should then be placed in
Group 2, among those diseases in which examinations of the blood
are of prime importance.
_Cholera._—As cyanosis develops the red count goes up even to
8,000,000 with a corresponding or greater increase in the leucocyte
count. The estimation of the low blood pressure is important
as indicating the necessity for intravenous injections. The
determination of the degree of serum acidosis is also indicated
with reference to alkaline treatment. In a convalescent from a
disease suspected as cholera an agglutination test would be of
value, and in the absence of the serum of immunized animals one
could use that of a cholera convalescent against a spirillum
isolated from the stool of a suspected case of cholera.
2. OF THE DISEASES IN WHICH AN EXAMINATION OF THE BLOOD SHOULD ALWAYS
PLAY A PART IN DIAGNOSIS MAY BE NOTED THE FOLLOWING:
_Malaria._—The examination of the blood is necessary not only
to prove the existence of a malarial infection but, as well, to
determine the species of parasite present, this latter a matter of
much importance as to prognosis and intensity of treatment according
as one has to deal with a benign or malignant parasite. More exact
information (and with the expenditure of much less time) can be
obtained from a smear stained with some Romanowsky modification than
by examining a fresh preparation.
At the same time it is advisable to make a wet preparation and
study it for amoeboid activity of the parasites and character of
the pigment while awaiting the completion of the staining process.
In the blood of a malarial anaemia the central vacuolation of many of
the red cells may give an appearance of young nonpigmented parasites.
Malarial parasites tend to move about to take peripheral locations
and furthermore they do not change in size upon focussing up and down
as do the vacuoles.
Melaniferous leucocytes can be made out better in a fresh specimen
than in a dried, stained one.
One can better differentiate species by an even thin film than by a
thick-film method. There is often great doubt with a thick film as
to whether the object noted is an artifact or a parasite. The Ruge
thick-film method has given very good results.
There is only a moderate variation from a normal white count but
in cases when the parasites are very scanty or when they have been
driven from the peripheral circulation by quinine treatment we may
make a tentative diagnosis of malaria on a leucocytosis during the
paroxysm with a leucopenia during the afebrile interval with, at
this time, an increase in the percentage of large mononuclears to
10 to 15%.
Melaniferous leucocytes are rarely noted in the benign tertian
infections but in some of the very puzzling aestivo-autumnal fevers
they may give the diagnostic clue.
Schüffner’s dots are yellowish dots in the infected red cells
and are characteristic of benign tertian. The Maurer clefts of
malignant tertian are less commonly noted. Always carefully note
the pale, swollen, infected red cells of benign tertian, the
shrunken degenerated cell of malignant tertian and the normal one
of quartan. The fine hair-like ring of malignant tertian is often
noted on the periphery of the red cell as a narrow line while the
half-grown schizont of quartan is often seen as an equatorial band.
In the anaemia following malaria we may have very low red counts and
haemoglobin percentages. They usually run parallel, so that the color
index approximates 1.
Punctate basophilia is quite common in malarial anaemias. Up
to the present time the culturing of the parasite can scarcely
be considered an aid to diagnosis as it is difficult to carry
the development beyond one generation so that we do not get
multiplication of parasites. In cases where confusion exists as to
the nature of the species of parasite present culturing would help
as regards the possibility of noting the developmental stages of
_Plasmodium falciparum_.
_Blackwater Fever._—The same points which hold for malaria hold for
blackwater fever.
The striking feature of blackwater, from the side of the blood, is
the rapid and great reduction in red cells and haemoglobin. As a
result of the pathognomonic haemoglobinuria we may have in a few
days a fall of red cells from 4 or 5 million to approximately 1
million with haemoglobin down to 20%. The color index is usually
about 1. The blood is thin and the serum tinged. Probably from
the excessive haemolysis one does not see degenerated cells
as frequently as would be expected. Tests for acidosis and
coagulability of the blood are indicated as there is a reduction in
titrable alkalinity of the serum and coagulation rate.
_Oroya Fever._—This disease, within two or three weeks, gives
the blood picture of a marked pernicious anaemia. The rod-shaped
protozoon may be seen lying in the red cells singly or in V-shapes.
These rods show a chromatin granule at one extremity. Normoblasts
are very numerous and megaloblasts appear later. There is both
polychromatophilia and poikilocytosis. The color index is that of
pernicious anaemia, above 1. The leucocytes are increased to about
20,000 with 75% of neutrophiles, among which are many immature
forms or metamyelocytes. The pathological process shows its
greatest activity in the bone marrow.
_Malta Fever._—In this disease blood cultures offer the surest and
most practical way of making the diagnosis. The blood should be taken
from a vein at the time of the height of the fever rise. To prevent
coagulation the blood should be forced from the syringe into about
an equal amount of citrated salt solution and subsequently added to
melted agar to then be poured into Petri dishes. Cultures can also be
made by smearing the citrated blood over poured plates of agar.
It must be remembered that the colonies are quite small and do not
develop for four or five days.
The citrated blood can also be added to bouillon. The blood culturing
has rather replaced the culturing from spleen juice. As the coccus is
in the blood it is eliminated in the urine and plates should be made
from the urine as well as the blood.
Malta fever is one of the diseases which can be diagnosed quite
early by agglutination tests, the reaction often appearing before
the end of the first week and often continuing for months after
recovery. There is a liability to error when low dilutions are
employed so that the former use of dilutions of 1 to 20 and 1 to
40 is no longer advised. Probably a dilution of 1 to 100 would be
sufficiently specific but dilutions of 1 to 500 and even higher are
frequently obtained. It is now thought best to heat the patient’s
serum to 56°C. for twenty minutes before applying the test so as
to destroy nonspecific agglutinins. Opsonic index and complement
fixation tests have been employed in diagnosis.
As the disease progresses a secondary anaemia develops. The white
count is about normal but with the polymorphonuclears somewhat
reduced in percentage and the mononuclears increased.
Some observers have reported a leucopenia as of some diagnostic
value but others find the leucocyte count normal and Rogers
considers the absence of leucopenia as differentiating kala-azar
from Malta fever.
_Plague._—In septicaemic plague blood cultures offer the surest
method of diagnosis as clinically there may be very little to suggest
plague. This is about the only disease in which one may find the
causative bacterium in a blood smear. For this examination the
thick-film method has been recommended. Just as with the material
from a puncture of a bubo or the sputum from plague pneumonia we
should employ animal inoculation as well as cultural procedures with
the blood.
We usually have a marked leucocytosis due to a great increase in
the polymorphonuclears. The white count may exceed 50,000. Just as
septicaemic plague may so overwhelm the organism that it does not
respond with fever so may the leucocytosis be absent. Bubonic and
pneumonic plague tend to become septicaemic, so that in such types
of the disease we may obtain results with blood cultures.
_Liver Abscess._—Schilling-Torgau brings out the point that even
with an absence of the usual blood findings it is possible to
diagnose the disease and make a just prognosis with his method of
differential counting. Ordinarily we have a leucocytosis of from
twelve to twenty thousand with only about 70% of polymorphonuclears
and about 12 to 15% of large mononuclears. When a bacterial
infection accompanies the amoebic one of course the leucocytosis and
polymorphonuclear percentage reach higher figures. The eosinophiles
may entirely disappear in an uncomplicated case of amoebic abscess.
In comparing his method with the ordinary one Schilling-Torgau
notes a case with a differential count showing 72% of
polymorphonuclears, 17% of lymphocytes and 8% of large mononuclears
with a white count of 6000—apparently a normal blood. By his
method 33% of these neutrophiles were found to be of the band-form
or less mature cells, thus showing that the blood really did
deviate from the normal.
In other examinations he noted very unfavorable indications from
the high percentage of metamyelocytes and even myelocytes when the
ordinary count did not suggest the serious condition.
As stated previously this method would seem to offer many
advantages over the ordinary one.
_Trypanosomiasis._—While the blood, when examined in ordinary
smears or with thick-film methods, does not give as good results
as by examining the gland juice for trypanosomes, yet, by taking
5 or 10 cc. of blood in citrated salt solution with 2 or 3
centrifugalizations, we may obtain greater success in finding the
parasites in this way than when using gland juice.
In wet preparations we may note the clumping of the red cells.
This is the phenomenon of auto-agglutination thought by some to be
rather characteristic of trypanosomiasis.
We may carry out the leucocyte attachment test using the inactivated
serum of the suspected patient.
As the disease progresses we get a secondary anaemia. The leucocyte
count is usually normal but the differential count shows an
increase in the large mononuclears. Bacterial infections often
supervene when a leucocytosis will be noted.
_Kala-azar._—Quite recently there has been success in the diagnosis
of kala-azar by culturing the blood of the suspect on N. N. N.
medium. The key to success when culturing from the blood is to
wait for two or three weeks before giving up the examination
of the cultures. It will be remembered that almost invariably
leishman bodies are present in the blood only in extremely small
numbers so that there is not time by the end of a few days for
sufficient development to have taken place. In probably 80% of
cases the parasite of kala-azar may be found in stained smears
from the peripheral blood but only after prolonged and patient
search. They may be found phagocytized by large mononuclears or
polymorphonuclears. Of course splenic puncture examinations show
far greater abundance of parasites than blood smears but it is not
without danger.
The marked anaemia of kala-azar does not appear until the earlier
symptoms of fever and splenic enlargement have gone on for some
time. Very characteristic and important in diagnosis, however, is
the marked leucopenia of kala-azar, approximating 2000 leucocytes
on the average. Again the white cells are only about in the
proportion of 1 to 1000 red cells. There is an increase in the
percentage of large mononuclears. Some authorities have reported an
acidosis of the blood serum. Coagulation rate is delayed.
In kala-azar the coagulability of the serum is altered as shown by
the formol-gel test. In this test, a drop of clear serum from the
patient is placed on a slide which is then inverted over a watch
glass containing a few drops of liquor formaldehyde. In cases of
kala-azar the serum will solidify, appearing as an opaque, stiff
jelly which adheres to the slide; while other sera will remain
fluid, running off the slide when it is tilted. The reaction
appears not to be specific since it has been reported for syphilis
and other diseases.
_Relapsing Fever._—The spirochaetes are not so numerous in the blood
of the peripheral circulation in tropical relapsing fevers as in
those of Europe.
The spirochaetes can best be seen in stained smears but the
agitation of the red cells in a wet preparation by the motile
spiral organisms is of assistance in their recognition. Dark-field
illumination, India ink smears and Fontana’s silver method are used
as well as Giemsa staining.
During the afebrile period the parasites disappear from the
peripheral circulation.
If the disease is first seen during the afebrile stage we may try
Lowenthal’s reaction, which consists in taking a drop of the blood
of the suspected patient, mixing it on a vaseline ringed slide with
the blood of a patient showing spirochaetes, then covering with a
cover-glass and incubating for thirty minutes at 37°C. A positive
reaction shows clumping and loss of motility of the spirochaetes.
Reports vary as to the white count but on the whole there would
seem to be more evidence in favor of a moderate leucocytosis
although some observers have noted a fall from the normal. The
usual statements give a leucocytosis of from 12 to 15 thousand with
a polymorphonuclear increase to between 75 and 80%. The statement
is usually made that the normal percentage of large mononuclears
helps in the differentiation of malaria. Kieseritzky has reported
leucopenia and slight increase in lymphocytes.
The leucocyte count tends to be higher about the time of crisis.
_Weil’s Disease._—This spirochaete infection is due to _Leptospira
icterohaemorrhagiae_. The spirochaete has been found in the blood
and has possibly been cultured anaerobically from the blood. The
practical method is by inoculating guinea pigs with blood or
urine sediment. Spirochaetes are found in the liver smears of the
sick guinea pigs. In the first week of Weil’s disease we have a
leucocytosis—later on a leucopenia.
_Filariasis._—The sheathed embryos of _Filaria bancrofti_ are found
in the peripheral circulation at night only, hence _F. nocturna_,
while those of _F. loa_ are only to be found in the daytime, hence
_F. diurna_. In the islands of the South Pacific the filarial
infection is considered as of _F. bancrofti_ but the embryos are
present in the peripheral circulation both by day and by night.
Instead of being uncommon it seems rather to be the rule to fail
to find embryos in the blood preparations in cases showing marked
evidences of filarial disease, as in elephantiasis, calabar
swellings, etc. The positive blood findings are most frequent in
those who do not as yet show symptoms. There has not yet been
sufficient obstruction in the lymphatics to keep the embryos from
reaching the blood stream.
In some countries where a large percentage of the population may show
embryos in the peripheral circulation, manifestations of the disease
are very rare.
We may examine the blood either with fresh preparations, when the
movements of the embryos assist in their detection, or by staining
dried smears. Haematoxylin staining is better than the Romanowsky
one as the break in cells and other points are better brought out.
An eosinophilia is usually considered as constantly present but
this is not invariable. The leucocyte count is about normal.
_Dengue and Phlebotomus Fever._—In these diseases a leucopenia,
which begins to show itself by the second day, is very characteristic.
The average leucocyte count is about 3500 and along with this we
have a reduction in the percentage of polymorphonuclears to about
50%. Towards the end of the terminal fever we have an increase in
the percentage of large mononuclears.
_Bacillary Dysentery._—The agglutination tests are of little value
in diagnosing the presence of or type of an infection with dysentery
bacilli, as the agglutinating power does not appear until during
convalescence.
It is now customary to use a polyvalent antidysenteric serum
in treatment so that it is not very essential to ascertain the
strain involved in an infection. As a practical matter we make our
diagnosis of the presence as well as type of dysentery bacillus
involved in an infection by isolating the organism from the
dysenteric stool.
During the fever we may have a moderate polymorphonuclear
leucocytosis.
_Enteric Group of Fevers._—In fevers of atypical course in the
tropics one must always remember that _typhoid_ and the _paratyphoid
fevers_ are anything but uncommon and blood cultures should always be
made when such suspicion arises. In some tropical regions paratyphoid
A infections seem most common although the usual experience is to
encounter the paratyphoid B infection more frequently. In temperate
climates the noting of a moderate leucopenia with an absence of
eosinophiles is important in the diagnosis of typhoid, but in the
tropics there are so many intestinal parasites and skin infections
productive of eosinophilia that we cannot attach any importance to
such a finding.
_Typhus Fever._—Plotz attaches importance to the culturing of
_B. typhi exanthematici_ from the blood of typhus cases, but the
relationship is now regarded as not causal. _Rickettsia_ bodies,
which can be demonstrated in the louse or in capillaries at autopsy,
are now considered to be the exciting organism.
A mononuclear leucocytosis has at times been reported.
_Spotted Fever of the Rocky Mountains._—Injection of the blood of
the patient into guinea pigs produces the disease in the animal.
Frick has reported the finding of chromatin-staining bodies in the
red cells of such pigs and Wolbach has found chromatin-staining
bacteria in the endothelial cells of such animals. These bodies are
now classed as _Rickettsia_.
These findings cannot as yet be considered of diagnostic value.
_Various Helminthological Infections._—In the earlier stages of
ancylostomiasis and schistosomiasis we have a rather notable increase
in the percentage of eosinophiles but with the advanced stages of
these infections, with severe anaemia, the eosinophiles may even be
absent.
One should always keep in mind the very characteristic and marked
eosinophilia of _trichinosis_ when such a blood finding is
encountered. There is often a leucocytosis of 15,000 to 20,000 in
this disease.
In the _urticarial fever_ stage of _Japanese schistosomiasis_
the marked eosinophilia is of great assistance in diagnosis. One
trouble about attaching importance to eosinophilia in the tropics
is the confusion which is difficult to eliminate and which arises
from infections with the more common but less important group of
intestinal parasites such as _Ascaris_, _Trichuris_, etc.
The eosinophilia-producing characteristics of many skin diseases
must also be kept in mind.
CHAPTER XLVI
THE CIRCULATORY, RESPIRATORY AND LYMPHATIC SYSTEMS TOGETHER WITH
ANAEMIA, HAEMORRHAGES AND OEDEMA IN TROPICAL DISEASES
THE CIRCULATORY SYSTEM
_Beriberi._—Almost as important in diagnosis as the weakness of
the legs, with anaesthetic and oedematous areas, is the early
palpitation of the heart upon the slightest exertion. Later on as
the vagal degeneration becomes more prominent we have a loss of the
normal cardiac rhythm, to even become embryocardial, together with
dilatation of the right heart, pulsating jugulars and various blowing
murmurs, which are propagated into the vessels of the neck. The pulse
is weak and rapid and this combination of a tumultuous heart action
and weak pulse is striking. Blood pressure is below normal.
Cardiac involvement is also a feature of _ship beriberi_ as well
as _infantile beriberi_. In the latter a marked hypertrophy of the
right heart is characteristic.
In _yellow fever_ we have at first a high blood pressure. The pulse
rate, which at first corresponds with the rise of temperature, soon
shows Faget’s law—a falling pulse with a constant temperature or a
constant pulse with a rising temperature. It is a markedly slow pulse
after the third day. The blood pressure is low in the asthenic stage.
In _dengue_ we do not have the rise in blood pressure but the slow
pulse is quite a feature of many of the dengue-like fevers.
In _blackwater fever_ the pulse is rapid and soon becomes weak and
of low tension.
_Plague_ shows a striking toxic action on the heart muscle so that
we soon get a soft, dicrotic pulse, rapid from the first and soon
becoming thready. Patients with plague may die from cardiac failure
upon getting up from bed.
A rapid pulse, especially in the morning, is thought to be a
feature of _active leprosy_.
In _cholera_ the pulse is rapid and feeble during the stage of
evacuation and with the onset of the algid stage we practically have
a cessation of the circulation. The systolic pressure may fall as low
as 65 or 70 mm.
_Hookworm anaemia_ shows early and marked cardiac palpitation. The
pulse rate averages about 110 and the blood pressure is low. There is
often some right-side dilatation of the heart.
_Malaria_ generally gives a small, rapid, high tension pulse in the
cold stage to become full and bounding in the hot stage. A cardiac
type of pernicious malarial fever has been described, particularly
by the French.
Both _Malta fever_ and _bacillary dysentery_ tend to have a toxic
effect on the heart.
_Typhus fever_ is a disease which tends markedly to affect the heart.
Along with faint heart sounds we have a rapid, low tension pulse. In
_bacillary dysentery_ the tendency to an increase in pulse rate is of
some value in differentiating it from amoebic dysentery.
_African trypanosomiasis_ shows a rapid pulse rate whether the
case shows temperature or not. In _Brazilian trypanosomiasis_
the parasites may tend to invade the cells of the heart muscle
thus producing manifestations of myocardial disease. The parasite
(_Schizotrypanum cruzi_) may also affect the adrenals, causing a
low blood pressure along with other signs of Addison’s disease.
THE RESPIRATORY SYSTEM
_Sputum Examination._—We should make a routine of examining a
fresh specimen of sputum as well as stained smears. It is in such a
specimen we search for the ova of the lung fluke.
Frequently the material submitted for examination as sputum is
simply buccal or pharyngeal secretion, or more probably secretion
from the nasopharynx, which has been secured by hawking. It should
always be insisted upon that the sputum be raised by a true
pulmonary coughing act, and not expelled with the hacking cough
so frequently associated with an elongated uvula. When there is
an effort to deceive, some information may be obtained from the
watery, stringy mucoid character of the buccopharyngeal material
and also from the presence of mosaic-like groups of flat epithelial
cells (often packed with bacteria).
The pulmonary secretion is either frothy mucus or mucopurulent
material, and if the cells are alveolar they greatly resemble the
plasma cells. At times these cells may contain blood-pigment granules
(heart-disease cells).
In the microscopic examination a small, cheesy particle, the size
of a pin head, should be selected. This should be flattened out
in a thin layer between the slide and cover-glass and should be
examined for elastic tissue, heart-disease cells, eggs of animal
parasites, amoebae, and fungi. _Echinococcus_ hooklets, Curschman
spirals besprinkled with Charcot-Leyden crystals, and haematoidin
and fatty acid crystals may also be observed.
Curschman spirals indicate bronchial as against cardiac or uraemic
asthma. Charcot-Leyden crystals have no special significance,
except in certain tropical diseases when these crystals often are
present in paragonomiasis sputum and in the pus of amoebic liver
abscesses discharging by way of the lungs.
It may facilitate the examination of the sputum for elastic tissue
and actinomycosis and other fungi to add 10% sodium hydrate to the
preparation.
To make smears for staining, the sputum should be poured on a
flat surface, preferably a Petri dish, and a bit of mucopurulent
material selected with forceps. A dark background facilitates
picking out the particle. A toothpick is well adapted to smearing
out such material on a slide. After using the toothpick it can be
burned. When dry, the smear is best fixed by pouring a few drops
of alcohol on the slide, allowing this to run over the surface,
and then, after dashing off the excess of alcohol, to ignite that
remaining on the film in the flame and allow to burn out.
In _beriberi_ we have shortness of breath with the early cardiac
palpitation. In acute pernicious beriberi the pulmonary congestion
and oedema divide with the heart the terrible manifestations of such
an attack. The diaphragm may become paralyzed in beriberi. Some
authors refer to the dyspnoea of beriberi as the beriberic corset.
_Paragonomiasis_ gives rise to a chronic cough attended with
the expectoration of more or less bloody sputum containing ova.
Haemoptysis is not infrequent. The physical signs on percussion are
slight but may be more marked on auscultation.
_Hirudiniasis._—In Northern Africa, as well as in many islands of
the Orient, the drinking water of ponds may contain leeches and
these water-leeches tend to attach themselves to the pharyngeal
mucosa. They may also attach themselves to the tissues about the
larynx. In these cases we not only have cough and haemoptysis
but dyspnoea from laryngeal oedema. It is probable that cases of
dyspnoea called _halzoun_, and due to the attachment in the region
of the larynx of flukes (_Fasciola hepatica_), as the result
of eating raw liver, may often be due to leeches, as the two
affections occur in the same regions.
_Plague pneumonia_ is characterized by profound prostration in a
patient whose physical signs do not seem to justify such extreme
illness. The rather abundant and watery sputum soon becomes
sanguinolent. Herpes labialis is absent. Besides primary plague
pneumonia which develops directly from contact with a former case we
have a secondary pneumonia which develops in the course of a typical
case of bubonic plague.
In _malaria_ we have a slight bronchitis in the ordinary types and
many recognize a pulmonary type of pernicious malaria.
_Malta fever_ tends to show a bronchial involvement about the twelfth
day of the disease. Crepitant râles, a moderate cough and slight
dyspnoea may be noted. It was the presence of pulmonary signs along
with the profuse sweating and anaemia of the disease that justified
the designation Mediterranean phthisis.
In _liver abscess_ the crepitation at the base of the right lung,
following congestion incident to the abscess of the right lobe of
the liver, is of value in diagnosis. Rupture of a liver abscess
into the lung occurs in about 10% of cases.
In _heat stroke_ we may have Cheyne-Stokes respiration and
pulmonary oedema.
_Japanese river fever_ often shows bronchial involvement and cough
at the time of the height of the fever.
In _ancylostomiasis_ cases with cough and bronchitis have been
reported and it seems probable that such manifestations may be
connected with the course of the larvae through the pulmonary
passages to reach the intestinal tract.
The filarial embryos of _F. bancrofti_ remain in the lung capillaries
during the day and recently such embryos have been found in blood
coughed up from the lungs.
_Katayama disease_ may show a localized bronchitis early in the
attack and from its rapid appearance and disappearance would seem
to be a sort of patchy pulmonary oedema. This is connected with the
passage of the larvae through the lungs.
Broncho-pneumonia is probably the most common complication of
_typhus fever_.
An affection known as _gangosa_ or _rhino-pharyngitis mutilans_
causes great tissue loss about nasal and buccal cavity. The voice has
a peculiar nasal quality. It is possibly a manifestation of tertiary
yaws.
_Kala-azar_ patients are often carried off by a terminal pneumonia
probably connected with the leucopenia and marked diminution of
polymorphonuclears.
In _leprosy_, also, the victims are frequently carried off by
pulmonary tuberculosis.
_Relapsing Fever._—In relapsing fever there is frequently a moderate
bronchitis at the time of the first febrile accession.
_Bronchial Spirochaetosis._—There is a condition which more or
less resembles lobar pneumonia, even to rusty sputum, but without
signs of consolidation, and with negative Roentgenograms, when
we find spirochaetes in the sputum. Another type of _bronchial
spirochaetosis_ is when the clinical picture is more that
of pulmonary tuberculosis. There is question whether these
spirochaetes are causative or only accidental.
Cases have been reported where a phthisis-like condition was due
to a mould infection (_Monilia_). While such a condition may be
primary it is more often secondary in cachexias as may be the
case with buccal _Monilia_ infections (thrush) which occur in the
victims of cachectic states.
_Guha._—In Guam there is also a rather fatal capillary bronchitis
affecting young children which goes under the name of epidemic
asthma or, as termed by the natives, guha. This affection comes on
during the rainy season and is attended with marked dyspnoea and
slight elevation of temperature.
_Nasal Myiasis._—In the tropical and subtropical parts of North and
South America a fly, _Chrysomyia macellaria_, is apt to deposit its
eggs about the nasal orifices of persons with an offensive discharge
from the nose. The fly seems to be attracted by foul odors. The
larvae which develop are called “screw-worms” on account of the
segmental bands of bristles and tend to invade the various sinuses,
causing great destruction of tissue.
The case sets in with signs of a very severe coryza, together with
fever and marked frontal headache. The face becomes swollen, red,
and tender in the region of the nose. As the larvae reach maturity
they come out of the nose. A nasal douche of 15 parts chloroform in
100 parts milk is often efficacious in bringing away the larvae. At
times _Sacrophaga_ larvae may be found.
THE LYMPHATIC SYSTEM
_Plague._—The buboes are the most characteristic feature of the
more common form of plague, bubonic plague. There may also be slight
enlargement and tenderness of the glands in septicaemic and pneumonic
plague but many such cases fail to show any evidence of superficial
glandular enlargement. In pestis minor the only feature suggestive of
plague is the glandular enlargement.
Very characteristic of the glandular involvement in plague is
the marked tenderness of such glands. The slight pressure of
palpation causes some pain and a sharp punch over an affected
gland, excruciating pain. So exquisitely painful are these buboes
that the patient with groin or axillary buboes will flex the leg or
extend the arm to relieve pressure. In about 70% of cases the bubo
is located in the groin, with 15% to 20% for axillary involvement
and 5% to 10% for the submaxillary or cervical region. There may
be involvement of both deep and superficial glands of a region,
such buboes giving a large area of induration. As a rule there is
a single bubo. The bubo is formed not only by the glands but by a
periglandular oedema which fuses the glands into a solid mass. The
buboes tend to suppurate about the commencement of the second week,
so that gland puncture with subsequent culturing for plague bacilli
and animal inoculation should be carried out before this time as
pyogenic organisms replace the plague bacilli upon suppuration
taking place.
_Trypanosomiasis._—One of the characteristics of the disease
recognized as diagnostic more than 100 years ago is enlargement of
the glands of the posterior cervical triangle (Winterbottom’s sign).
There may be general enlargement of the lymphatic glands which
are rather hard, discrete and not bound down to the overlying
skin. These glands may be somewhat tender or entirely painless.
One of the most valuable methods of diagnosis of trypanosomiasis
is by gland puncture, the juice obtained therefrom being examined
in smear or inoculated into a monkey or guinea pig. Brazilian
trypanosomiasis also shows glandular involvement.
_Filariasis._—Varicose groin glands are frequently associated with
lymph scrotum, chylocele or chyluria. The glandular masses are soft
and doughy. The consistency is often that of a lipoma.
The overlying skin slips over the glandular mass. These glands are
often mistaken for inguinal hernia. They do not give a tympanitic
note and disappear slowly upon firm pressure with the patient lying
down but return even with the pressure maintained upon assuming the
upright position. There is no impulse on coughing. If a sterile
hypodermic needle be inserted into the mass a chylous fluid slowly
and persistently comes out of the needle drop by drop and this
material may show filarial embryos.
The filarial worms _Onchocerca volvulus_ obstruct the lymphatics and
may give rise to swellings of considerable size along the course of
the lymphatics.
_Climatic Bubo._—The onset is gradual often accompanied by a low
remittent type of fever. There is an absence of venereal sore.
These glands are only slightly tender and are often called fatigue
glands as they produce a feeling of weariness after even moderate
exercise. The inguinal glands of one or both sides are the ones
involved but the overlying skin does not show the redness of a
chancroidal or gonorrhoeal bubo. There is often a softening in the
center of the affected glands.
_Tsutsugamushi._—The glands which drain the area in which is located
the ulcer at the site of the bite of the Kedani mite show swelling
and tenderness.
_Rat bite fever_ also shows glandular enlargement in the glands
tributary to the healed infecting bite of the rat.
In _tularaemia_ the lymph glands draining the site of the infecting
bite become inflamed and swollen, often suppurating.
In _leprosy_ the glands draining involved regions become enlarged
but do not show a tendency to suppuration. The glands most
frequently involved are the cervical and groin glands.
In _kala-azar_ the recommendation has lately been made to excise the
somewhat enlarged glands and make smears from a piece of such gland
and then examine the smear for leishman bodies. Gland puncture has
not given as satisfactory results.
It is often stated that the superficial cervical glands are
enlarged in _dengue_ but not in dengue-like fevers. I have not
observed in the cases I have seen either constant or well marked
glandular enlargements.
In _yaws_ there may be glandular enlargement. According to Finucane
the cervical glands are often involved in Fiji children. These glands
do not tend to break down.
In _pediculosis_ of the hairy scalp the scratching back of the
neck may result in pus infection with enlargement of the tributary
cervical glands.
_American leishmaniasis._—Not only is there often enlargement of
the lymphatic glands but likewise we may have lymphangitis lines
leading from the ulcer to the glands. The glands may be large and
painful and may remain enlarged after the recovery of the patient.
ANAEMIA
The old idea that tropical life produced an anaemia is no longer
held, the view now being that such anaemic conditions are almost
invariably due to some well recognized cause, the most important of
which is malaria. Natives of the tropics may appear bleached out but
show a normal red count and haemoglobin percentage. Chamberlain’s
observations have shown that a residence in the tropics of
approximately two years has no appreciable influence on the red cell
count or haemoglobin content of the blood of white men and that the
actinic rays do not seem to be operative in producing anaemia.
_Malarial Cachexia._—Although the malignant tertian infection
has the greatest tendency to produce anaemia yet any type may,
when untreated, bring about the more or less profound anaemia with
earthy skin, enlarged spleen, dyspnoea on slight exertion, and
oedema of the ankles characteristic of malarial cachexia.
_Oroya Fever._—In this disease we have what might well be termed
a fulminating pernicious anaemia. The rod-shaped protozoon which
attacks the red cells seems to be peculiarly active in the bone
marrow, excruciating bone pains being quite a feature of the disease.
There may be a reduction in red cells to one million per c.mm.
within a few days. Normoblasts are abundant and megaloblasts may be
observed in the more severe cases. The anaemia is intense and 20%
to 40% of cases die within two or three weeks. A severe anaemia in
which the blood picture is that of pernicious anaemia may accompany
infections with the _Balantidium coli_.
_Blackwater fever_ may produce a fall in red cells almost as marked
as in Oroya fever.
_Sprue_ shows a slowly progressive anaemia which in the later
stages of the disease may become extreme, going down to one
million, with a fairly high color index.
_Ancylostomiasis_ is along with malaria the disease to be first
thought of in connection with anaemia. The splenic enlargement of
malaria should be thought of, although the view has recently been
advanced that the spleen may be enlarged in hookworm disease.
In advanced cases of hookworm disease, showing a picture of
profound anaemia, there may be so few worms present that the
method of making diagnosis by finding ova may be unsuccessful. I
have seen a case of typical aplastic pernicious anaemia, confirmed
by autopsy, undoubtedly following a vicious cycle set up by the
hookworm infection, in which scarcely a worm was to be found in
searching the intestines.
_Kala-azar_ gives a marked anaemia with an earthy color of the skin.
The leucopenia and splenic enlargement are characteristic and the
finding of parasites confirmatory.
_Malta fever_ is usually followed by a moderate anaemia.
The _helminthic infections_, besides hookworm disease, are always
to be thought of in the presence of anaemia. Very important among
these are rectal and vesical schistosomiasis as well as that from
the Japanese schistosome, together with liver and lung fluke
disease. Even the ordinary round-worm, _Ascaris lumbricoides_, is
to be thought of in a tropical anaemia.
Cases of anaemia, in which no other demonstrable cause has been
noted, have been thought to be due to _trichocephaliasis_.
_Tropical dysenteries_ are often responsible for anaemia and in
liver abscess the patient becomes quite earthy in color, provided no
operation is performed. In chyluria there is a marked drain on the
patient.
The anaemia in _liver abscess_ is not so great as the muddy
complexion would indicate. The emaciation is greater than the
anaemia.
HAEMORRHAGES
The loss of blood through haemoglobinuria and haematuria has been
taken up under the urine. The haemoglobinuria is the pathognomonic
symptom of blackwater fever. There is also recognized a haemorrhagic
form of pernicious malaria with epistaxis and alimentary tract
haemorrhages. Moderate haemoglobinuria may be found in severe cases
of malignant tertian infections.
_Yellow Fever._—During the asthenic period of the disease, which
sets in about the fourth day, we have, as a result of the damage to
the endothelial lining of the capillaries, various haemorrhages.
Of these the best known and most dreaded is that from the stomach,
black vomit. The bleeding from the gums is apt to appear before
that from the stomach. Not only may bleeding occur from the
intestines but from any mucosa, as that of the nose, conjunctiva or
vagina.
In _vesical and rectal bilharziasis_ the perforation of the terminal
branches of the portal vein by the terminal or lateral spined eggs
gives rise to haemorrhages.
In _dengue_ we may have an epistaxis at the time of the crisis of
the first febrile paroxysm.
In _dysentery_ the blood-admixed mucous stools are of diagnostic
importance.
In _endemic haemoptysis_ the operculated eggs of _Paragonimus
westermanni_ are to be sought for in the sputum.
In _leprosy_ epistaxis may be an early sign.
The damage to the endothelial lining of capillaries in _plague_ gives
rise to frequent haemorrhages into the skin.
There is a question whether the hookworms abstract blood from the
intestines, although tests for occult blood are deemed important by
some authorities in the diagnosis of this disease.
The granulomatous lesions of _verruga_ are markedly haemorrhagic.
Some consider _ship beriberi_ to be of the nature of _scurvy_ in
which case one should have in mind spongy, bleeding gums and the
intramuscular haemorrhages of scurvy.
_Typhus Fever._—The petechial rash of this disease (mulberry rash)
is a distinctive feature.
OEDEMA
Oedema, especially about the ankles, is to be looked for in all
the secondary anaemias of the tropics, particularly malaria and
ancylostomiasis.
_Beriberi._—The oedema begins at first about the feet, especially
about the dorsal junction of phalanges and metatarsus. It is
characteristically pretibial. It may remain confined to the shin or
go up to knees, scrotum, sternal region or trunk. It is generally
symmetrical but may be unilateral. It may become a general anasarca,
even in forty-eight hours.
The swelling of the face is at times enormous, the eyelids being so
oedematous that the patient can see only by separating them with
the fingers. The oedema is more solid than that of nephritis. It
not only rapidly appears but disappears as rapidly.
The oedema of beriberi may involve the glottis (oedema of glottis).
Oedema of genital regions is less marked than in nephritis or
cardiac disease. We may also have localized areas of oedema 3 or 4
inches in diameter.
_Ship beriberi_, which has points in common with both beriberi and
scurvy, shows oedema which may be limited to the lower extremities
or generalized. _Epidemic dropsy_ is a type of beriberi in which
there are fever and an erythema over the dropsical areas.
_Calabar Swellings._—These seem connected with infections with
_Filaria loa_. The swellings originate suddenly and disappear in
three or four days. They are hard and do not pit on pressure. These
smooth swellings, often 2 to 4 inches in extent, are most often seen
on arms, face or ankles.
In _trypanosomiasis_ oedema of the face and especially of the
eyelids may be striking. There may also be patches of oedema
elsewhere.
In _Katayama disease_ the urticarial areas of oedema have given it
the name of urticarial fever.
A peculiar disease of North China, known as _atriplicism_, is
caused by the eating by the very poor of a weed, _Atriplex_, common
around Pekin. There is itching of the fingers, quickly followed by
swelling. This tends to extend to the back of the hands and up the
outer surface of the forearm. The face becomes so swollen that the
eyelids may be closed.
CHAPTER XLVII
JAUNDICE AND THE LIVER AND SPLEEN IN TROPICAL DISEASES
JAUNDICE
Although the appearance of jaundice immediately suggests a disease of
the liver yet as a matter of fact those diseases of the tropics in
which the liver involvement is the sole or chief feature rarely show
marked jaundice.
In _tropical hepatitis_ or congestion of the liver or, as it is
often termed, tropical liver, there is rarely a distinct jaundice
and if such occur it is only temporary. Such terms as earthy,
muddy, sallow, sub-icteric or pale lemon tint are more often
applied than jaundice.
_Liver abscess_ rarely gives rise to a definite jaundice unless the
abscess be so situated as to cause pressure on the bile ducts.
In _clonorchiosis_, or the liver fluke disease of man, jaundice is
not a feature of the disease except in the very late stages.
In those liver cirrhoses associated with _Katayama disease_,
_malaria_ or _kala-azar_ there is no typical jaundice.
The tropical diseases in which jaundice is an important diagnostic
feature are yellow fever, blackwater fever, bilious remittent fever
and relapsing fever.
_Yellow Fever._—There are cases which succumb without having shown
jaundice but immediately following death the yellowish discoloration
has been noted. At autopsy the yellow fever cadaver is almost
invariably deeply jaundiced.
Very important is the fact that the jaundice of yellow fever does
not appear until late, about the third or fourth day. When jaundice
appears earlier, as by the second day, the prognosis is almost
surely a fatal one.
According to Dutroulau the designation red fever would be more
appropriate for the deeply congested facies of a yellow fever case
in its first days.
The icterus is more marked about the face, neck and upper parts of
the trunk. The albuminuria precedes the jaundice.
_Blackwater Fever._—In a typical case of this disease we have within
a few hours a marked jaundice which tends to deepen. It is usually
more or less marked according as the haemoglobinuria may be. It does
not show the tendency to persist as does the jaundice of yellow fever.
_Bilious Remittent Fever._—The jaundice appears rather earlier than
that of yellow fever but is rarely seen on the first day of the
paroxysm as with blackwater fever.
Of great diagnostic value is the early appearance of bile-colored
urine as different from the haemoglobin-tinged urine of blackwater.
The albuminous urine of yellow fever is not apt to show any bile
coloring in the first three or four days of the disease.
_Relapsing Fever._—There is a clinical type of relapsing fever
associated with jaundice and a high death rate which was first
described by Griesinger from Egypt. This icteric type is not
infrequent in Asia. This jaundice is late and the disease much
resembles yellow fever. The enlarged painful spleen and the finding
of spirochaetes in the peripheral circulation are essential to
differentiation.
_Weil’s disease._—Much interest has been recently aroused in
_Weil’s disease_, or epidemic jaundice, on account of the frequency
of the disease in soldiers in the Balkan campaign. While a
spirochaete has been shown by Inada and others to be the cause, yet
many workers have isolated paratyphoid B organisms from the blood
of such cases. Frugoni obtained cultures of this organism from the
duodenal fluid of 11 cases from 48 cases investigated. The accepted
cause of true Weil’s disease is _Leptospira icterohaemorrhagiae_.
The jaundice begins about the third day of an irregular fever.
Like yellow fever these cases showed injection of the conjunctivae
and albuminuria. There were, however, usually a leucocytosis and
enlarged spleen.
In severe cases of _spotted fever of the Rocky Mountains_ we may
have a generalized jaundice. Rarely cases of _typhus fever_ may show
jaundice.
ALTERATIONS IN SIZE OF THE LIVER
There is only a slight enlargement in the ordinary case of tropical
liver but in some cases it may extend 3 or 4 fingers’ breadth below
the costal cartilages or rarely to the umbilicus.
In _liver abscess_ the enlargement is a rather late feature, and
the condition should be diagnosed before we have the assistance of
protruding ribs and distention of the intercostal spaces. As the
abscess is usually located in the upper portion of the right lobe
the enlargement is usually upwards and is best made out with the
X-ray, showing the cupola-like projection.
In _kala-azar_ the liver does not begin to enlarge until after about
three months from the time of onset at which time the spleen will
be quite large. Decided enlargement is generally noted by the sixth
month.
The liver cirrhoses due to _schistosomiasis_ or _malaria_ may show
slight enlargement or no particular change.
_Sprue_ is a disease which gives a decided atrophy of the liver.
Some authorities have noted a decrease of the size of the liver in
cholera. The liver of _yellow fever_ is of normal size and is not
associated with splenic enlargement.
In the tropics one must always keep in mind the possibility of a
liver enlargement being due to _syphilis_.
PAINS OF THE LIVER
In _tropical liver_ there is more a sensation of weight than one
of pain. In _liver abscess_, however, there are painful dragging
sensations and, at times, with abscess of the upper right lobe, pain
referred to the right shoulder. There is a marked tendency to splint
the liver as shown by the costal breathing and moderate rigidity of
the right rectus. The patient tends to lie on his back as shifting
to either side, especially the left, causes pain. The legs are drawn
up to relieve tension. Any jolting of the liver in palpation is
exquisitely painful.
When active suppuration is going on in the liver the pain may be
of an acute throbbing character. With abscess of the left lobe the
pains may suggest gastric disease while with an abscess of the
concave surface of the liver there may be referred pain in the
appendix region.
In _blackwater fever_ and _bilious remittent fever_ there may be
tenderness of the liver as well as the more prominent pain in the
spleen.
_Epidemic jaundice_ shows tenderness of the liver.
In _plague_ there is a marked congestion of the liver as of other
viscera and there may be some tenderness.
The liver becomes tender as well as showing enlargement in
infections with _Clonorchis_.
SPLENIC ENLARGEMENTS AND PAINS
Splenic puncture has been carried out for diagnosis chiefly in
kala-azar, malaria and Malta fever. Some authorities have reported
fatalities from spleen puncture in kala-azar approximating 1% so that
many advise the safer liver puncture to that of the spleen.
Spleen puncture would only exceptionally be called for in malaria
as there is usually no difficulty in making the diagnosis from a
blood smear. Malta fever can usually best be diagnosed by blood
culture taken at the height of fever and recent work by Wenyon and
others would indicate that blood cultures on N. N. N. medium might
take the place of spleen puncture in kala-azar.
_Kala-azar._—The splenic enlargement is the most conspicuous change
in the disease, the spleen often reaching the umbilicus by the third
month and later possibly filling up the entire left side of the
abdomen. The coincident emaciation of the patient makes the splenic
tumor more apparent. When first enlarging the spleen may be the
source of considerable pain and tenderness.
Fluctuations in the size of the spleen have been noted in the
course of the disease, diminution in size often attending severe
diarrhoeal attacks. In spleen or liver puncture the needle must be
dry so that the parasites shall not suffer distortion.
_Malaria._—Splenic enlargement and tenderness are important points
in diagnosis of malaria.
In acute malignant tertian infections the spleen is often diffluent
so that it is liable to rupture upon slight injury. One should
even exercise care not to palpate the spleen too violently and the
possibility of accident should be thought of in making a spleen
puncture.
The typical malaria spleen is the _ague cake_ of malarial cachexia.
Here we have a greatly enlarged spleen with a thickened capsule and
firm consistence. This spleen may fill up one side of the abdomen.
_Malta Fever._—The splenic enlargement in this disease usually
corresponds about to that of typhoid fever. At times, however, the
size may be so great as even to suggest kala-azar.
_Relapsing Fever._—Splenic enlargement and tenderness are marked
features in this disease, often being noted early in the course.
_Blackwater Fever._—The spleen is painful and enlarged. The
splenic enlargement in this disease and relapsing fever is
important in differential diagnosis from yellow fever, a disease in
which the spleen is unaffected.
The spleen may be enlarged in _Japanese schistosomiasis_ as well as
in rectal schistosomiasis.
Darling has recently noted that it may be difficult to
differentiate the anaemia of malarial cachexia from that due to
hookworm disease. As a matter of fact most authorities note a
diminution in the size of the spleen in _ancylostomiasis_ rather
than an increase and splenic enlargement would certainly favor a
diagnosis of malarial anaemia.
One point of distinction between spotted fever of the Rocky Mountains
and typhus fever is that the spleen of the former disease is enlarged
three or four times the normal, while that of _typhus fever_ shows no
increase in size. The palpable spleen of _Rocky Mountain fever_ is
firm instead of soft as with typhus fever.
CHAPTER XLVIII
THE CUTANEOUS SYSTEM AND THE ORGANS OF THE SPECIAL SENSES
THE SKIN
_Ringworm infections_ of the skin are so common in the tropics
that one should always make an examination for the causative fungi
when doubt as to the nature of the lesion exists. Another point is
that many hyperaemias, incident to other diseases, seem to furnish
a favorable soil for fungi; thus, not infrequently I have found
abundant spores and mycelial structures in scrapings from the
erythema of the early syphilitic secondaries. Again pruritic lesions
may become infected with fungi as the result of scratching, which
scratching may not only have this result but furthermore may obscure
the dermatological characteristics of the primary disease.
The most expeditious way to examine for fungi is to treat the
scales or hairs with a 10% solution of caustic potash or soda.
Then crush between two slides; heat moderately over the flame and
examine after from 10 to 30 minutes.
A very satisfactory method is to scrape the scales with a small
scalpel, and smear out the material so obtained in a loopful
of white of egg or blood serum on a glass slide. By scraping
vigorously the serum may be obtained from the patient. After the
smear has dried, treat it with alcohol and ether to get rid of
the fat. It may then be stained with Wright’s stain or by Gram’s
method. The ordinary Gram method may be used or the decolorizing
may be done with aniline oil, observing the decolorization under
the low power of the microscope.
_Hanging-block cultures._—To make these, pour melted agar in a
Petri dish and cut from the film so formed sections 1 cm. square.
Place a section on a slide, inoculate and drop on a cover-slip.
Another method is to allow a drop of melted agar, previously
inoculated, to spread over a cover-slip which is then inverted on a
concave slide.
_Prickly heat_ is another condition extremely common in the tropics
and the scratching to relieve the itching often leads to infection
with fungi or pyogenic cocci.
_Pellagra._—In no other general disease is the skin eruption of such
importance in diagnosis and it is practically impossible to make
a sure diagnosis of pellagra in the absence of an eruption or the
history of an eruption.
The eruption tends to show itself in the spring but may first
appear in the early fall. The lesions resemble a sunburn and burn
instead of itch. The characteristics of the eruption are bilateral
symmetry and sharp delimitation from the sound skin.
As a rule the lesions are dry and atrophic but more rarely, and
usually in severe cases, the eruption may be moist and oedematous.
The backs of the hands are the most common sites for the eruption
but frequently there is an extension up the forearm. The neck,
the bridge and alae of the nose, the region back of the ears and
the front of the chest are often involved. In children the feet
and legs are frequently involved. Scrotal eruptions are early
manifestations.
_Leprosy._—In _nodular leprosy_ we have the appearance of macules
of greatly varying size and shape with a tendency sooner or later to
symmetry. They tend to appear and recur in association with febrile
accessions and, even when they have become permanent spots, they show
increased redness, infiltration and tension when there is fever.
The color is rather that of a sunburn and may be uniform or the
center may be pale with copper-colored periphery. These spots
appear by preference on face, backs of hands, buttocks, extensor
surfaces of extremities and back. They may mark the location of
later developing nodules. At first they are oily rather than scaly.
We soon note a disappearance of hair within the spot. These spots
soon tend to become anaesthetic. The tubercles of leprosy are
usually of a reddish-brown color.
In _nerve leprosy_ the spots tend to appear on parts of the body
usually covered by clothing, as scapular region, shoulders, arms,
thighs or buttocks. The outline is ovoid rather than round and the
spots may at first be hyperaesthetic rather than anaesthetic, as they
later tend to become.
In circinate eruptions we often note a pale center with
brownish-red borders. These borders may be hyperaesthetic while the
centers show anesthesia. Bilateral symmetry is more common in this
than in nodular leprosy.
Besides the spots nerve leprosy may show blister-like lesions on
backs of hands and feet especially in the region of the knuckles.
Ulceration may follow.
_Malaria._—The most common cutaneous manifestation of malaria
is herpes labialis. This is more common in benign types than in
malignant ones. Urticaria is next in frequency. Malaria has seemed to
be the cause of certain cases of purpura simplex.
In attributing skin manifestations to malaria one must always have
in mind the scarlatiniform, urticarial and erythematous rashes due
to quinine used in treatment.
_Urticarial Fever._—In Japanese schistosomiasis the earliest
symptoms are the urticarial rash and fever.
_Plague._—Rarely cases of bubonic plague may show a small vesicle
marking the site of the flea bite. Areas of necrosis of the skin,
which are really sloughing patches, and incorrectly designated
“carbuncles,” may be noted, especially over the site of the buboes.
In the later stages haemorrhages into the skin (petechiae) are
common.
_Trypanosomiasis._—Patchy areas of erythema are often noted in
Europeans affected with this disease. These are frequently circinate
with fading in the center and tend to appear on the trunk.
In natives a dry skin is more often noted.
_Rat Bite Disease._—An eruption of purplish spots may accompany the
fever. There is a resemblance to erythema multiforme.
_Dengue._—The true eruption of dengue is the one that appears about
the fourth or fifth day as a measles-like eruption, starting about
wrists or ankles.
_Kala-azar._—There is a darkening of the colored skin of the natives
suffering from this disease and it is to this feature that the
disease owes its name.
In Europeans the appearance is more that one sees in old malarial
cachectics, an earthy gray color. The characteristics of cutaneous
leishmaniasis are discussed under that heading.
_Typhus Fever._—Gangrene is particularly a feature of _spotted fever
of the Rocky Mountains_ and _typhus fever_, chiefly of the scrotum
and prepuce with the former and of the extremities in the latter.
The distinctions of the eruptions of these two diseases and of
_tsutsugamushi_ are given on page 445.
_Tsutsugamushi._—A small necrotic ulcer with a dusky red areola,
often located in the armpits or region of the genitals, marks the
site of the bite of the infecting mite. From it a lymphangitis leads
to the swollen glands. About the seventh day a macular eruption,
which never becomes petechial, appears on face, then on trunk and
extremities.
_Tularaemia._—There is often a local lesion at the site of the bite
of the infecting _Chrysops_. The tributary glands are swollen.
In _ancylostomiasis_ the site of entrance of the infecting stage of
the larvae is marked by a dermatitis—ground itch.
Tibial ulcers are also features of this disease.
In _filariasis_ we not only have the bleb-like lesion of guinea
worm infection but also the calabar swellings of _Filaria
loa_. Elephantiasis and lymph scrotum are the best known skin
manifestations of _F. bancrofti_, but there may also be present
filarial abscesses. The tumors of _O. volvulus_ are most often on
sides of chest, are quite superficial with the skin freely movable
over them.
_Epidemic Dropsy._—It is a question, whether such a disease as
epidemic dropsy is distinct from beriberi. An erythematous eruption
about the face and a macular one of the trunk and extremities are
usually stated to be features of this disease.
_Juxta-articular Nodes._—This is a condition in which small tumors
form under the skin especially in the region of the elbows. These
bean to walnut-sized tumors of the subcutaneous tissues may also be
noted about the knees. A fungus has been reported as cause but the
present view is that the cause is unknown.
_Oriental Sore._—This form of cutaneous leishmaniasis is especially
common in Asiatic Turkey and Northern Africa. It begins as a small
papule which eventually ulcerates, the sore scabbing over from time
to time and again breaking down. Indolent granulations and a very
protracted course are rather characteristic features.
_American Leishmaniasis._—The most important point of
differentiation of this form of leishmaniasis from oriental sore
is the occurrence of ulcerating lesions of the mucous membranes of
mouth or nose subsequent to the appearance of the oriental sore-like
lesions on forearm, legs, trunk, or rarely the face. In Peru the term
_uta_ more properly belongs to the skin affections while _espundia_
is the designation applied to the lesions of the mucous membranes.
It may be stated that a form of oriental sore has been reported from
Greece where mucous membrane ulcerations have been associated with
the ordinary skin-type lesion.
_Dermal Leishmanoid._—Brahmachari has described a form of
generalized cutaneous leishmaniasis, bearing a superficial
resemblance to leprosy, which may develop a variable number of
months after apparent cure of kala-azar by antimony. Having found
leishmania bodies in the lesions, he conjectured that some of the
parasites survive the action of the drug, but with their virulence
so attenuated that they can give rise only to a milder disease,
a variant of cutaneous leishmaniasis, to which he gives the name
“dermal leishmanoid.”
NOTE.—The special tropical diseases of the skin are discussed
under their respective headings.
THE EYE
_Glaucoma._—According to Elliott glaucoma is very much more
common in the East than in Europe. He states that simple chronic
glaucoma is extraordinarily common in India. Often the only
symptoms are retraction of the field, cupping of the disc and at
a later stage impairment of the central visual acuity. He notes
that the advancement of the disease is often as unobtrusive as it
is relentless. These patients often only present themselves at the
clinic in the late stages of the disease; thus at the Madras hospital
the vision was only that of hand perception, or less, in 40% of cases.
_Cataract._—The general impression is that cataract is more frequent
in the tropical regions than in Europe and as bearing out this view
Elliott notes that cataract among those Europeans who have served
in India seems more frequent than among those who have remained in
England. Cataract is also more common in the southern part of China
than in the northern portion.
_Lachrymal Obstruction._—Elliott notes the extreme frequency of this
condition in India, and states that in the Madras Ophthalmic Hospital
125 operations for excision of one or both lachrymal sacs were
performed in 1907.
_Trachoma._—There are certain tropical countries where trachoma is a
disease of the greatest importance. Thus in China its prevalence is
great, as is also true of India, Egypt and Japan.
Outside of imported cases it is very prevalent in many parts of the
United States.
In this disease there is hypertrophy of the conjunctiva, granule
formation and subsequent cicatricial changes. Pannus and corneal
ulcerations are frequent complications.
The disease is contagious through transfer of the secretion by
hands or flies. It is usually considered as caused by the so-called
trachoma bodies or cell inclusions, which are best brought out by
Giemsa staining. The trachoma granules are yellowish, translucent
bodies set in the reddened conjunctiva.
_Leprosy._—The eye is more frequently involved in nodular than in
nerve leprosy. In the former we have infiltration of the conjunctiva
which may extend to the cornea.
The leprous nodules invading the palpebral conjunctiva tend to
ulcerate and bring about various distortions of the eyelids,
producing ectropion. Iritis, irido-cyclitis and irido-choroiditis
are less frequent than conjunctivitis and keratitis. The optic
nerve and the retina are only rarely involved.
In nerve leprosy the eye changes are chiefly connected with the
lesions of the fifth and facial nerves. Ptosis and paralytic
ectropion occur with frequency.
Ophthalmia and corneal ulcerations may lead to total destruction of
the eye. The cornea may be anaesthetic. Paralysis of one or more
ocular muscles may cause squint or diplopia.
_Malaria._—It is questionable whether the forms of conjunctivitis
and keratitis at times reported as due to malarial infection are not
rather of other origin.
Iritis is rarely a complication of malaria.
Retinal haemorrhages may occur in malarial cachexia and cerebral
types of pernicious malaria.
Another rare malarial complication is amblyopia. In this there is
an optic neuritis with grayish-red disc and the loss of vision is
not complete, while in quinine amblyopia the disc is white and the
vision completely lost for a time.
_Filariasis._—In that filarial infection caused by _Loa loa_,
at one time designated _Filaria oculi_, there seems a special
tendency for the adult worms to wander to the subcutaneous tissues
in the neighborhood of the eyes or under the palpebral or ocular
conjunctivae. When moving under the conjunctiva the worms cause
marked irritation and at times pain.
There may be considerable swelling so that the patient cannot for a
time see out of the invaded eye. It has been stated that the worms
may enter the anterior chamber of the eye but this is questionable.
It is believed that lesions of the cornea and iris may result from
the migrations through the body of the _Onchocerca volvulus_.
_Trypanosomiasis._—Eye lesions are quite frequent in this disease
these being keratitis, irido-cyclitis or conjunctivitis.
Oedema about the eyes is of importance in diagnosis. Eye lesions
seem more common in Rhodesian trypanosomiasis. The atoxyl treatment
of the disease may cause optic neuritis and blindness.
_Tick Fever._—In the relapsing fever of South Africa iritis has been
noted as occasionally occurring.
_Yellow Fever._—In the period of onset a feature of the so-called
“facies” of the disease is marked injection of the conjunctivae with
sensitiveness to the light.
Rush likened it to the eye of a wild animal as contrasted with
the less ferocious eye of bilious remittent fever which more
resembled that of a domesticated animal. About the third day the
earliest manifestation of jaundice presents itself in the ocular
conjunctivae.
_Ancylostomiasis._—Retinal haemorrhages may occur with marked
hookworm anaemia. Stiles notes a fixed stare in hookworm cases, the
eye itself somewhat resembling the eye of a fish.
Among other diseases showing ocular manifestations may be mentioned
one associated with fibrous nodules in the upper lid due to a
larval dibothriocephalid, _Sparganum mansoni_.
_Bacillary Dysentery._—Quite a number of cases have recently been
reported where along with an arthritic complication there has been
conjunctivitis. In 6 cases of dysenteric conjunctivitis, Maxwell
noted that 4 cases had arthritis and 3 of the latter showed anterior
uveitis. The conjunctivitis lasted about a week. Relapses seem liable
to occur. In none of the cases has there been recovered from the
conjunctival secretion the organism of dysentery.
_Cholera._—As a result of the loss of all body fluids the lachrymal
secretion is scanty or absent and we have various conjunctival and
corneal troubles unless the eye is frequently irrigated with normal
saline. Vitreous opacities and cataract may follow cholera.
_Beriberi._—In this disease there have been reported the following
eye complications: (1) retrobulbar neuritis; (2) paralyses of the
muscles of the eye and (3) decreased sensibility of the cornea and
conjunctiva.
_Night Blindness and Xerophthalmia._—Both of these conditions are
quite common in certain parts of the tropics and the view that the
heat of the tropics and the tropical sunlight were potent factors
had precedence until our study of vitamine requirements showed the
etiology to rest in deficiency of fat soluble A. It is now known that
cod-liver oil is particularly rich in this vitamine and that in this
agent we have our best preventive and curative agent for these eye
conditions. It is well known that rats fed on a diet deficient in fat
soluble A develop xerophthalmia.
Night blindness (nyctalopia) is best known among the crews of
sailing ships, especially when becalmed in tropical waters, and
some influence of sunlight was considered the cause, but we now
know that it is among such personnel that ship beriberi and scurvy
are prone to occur by reason of deficiencies in water soluble B and
the antiscorbutic vitamines. In such a dietary fat soluble A would
also probably be lacking.
In those parts of the tropics where famine conditions are common
both night blindness and xerophthalmia are frequent in young
children, not necessarily associated but frequently combined.
In a mild case of xerophthalmia there is a dry area of triangular
shape extending from either side of the cornea and covered with a
fine, whitish foam. In bad cases the whole eye may be dry, wrinkled
and opaque and eventually the cornea may slough away and bring
about destruction of the eye. There is very little pain attending
this frightful condition.
Elliot notes that from earliest times it was the custom in China
to treat these conditions with extracts of liver. We now know
that liver and kidneys are glandular organs rich in fat soluble A
although not so rich in this vitamine as cod-liver oil.
_Typhus fever._—There may be a rapid development of cataract of
the soft variety, particularly in young patients. Ocular palsies,
especially of the third and sixth nerves may occur during the febrile
period. Corneal ulcers are not uncommon during convalescence and may
be severe and very painful, often accompanied by conjunctivitis and
iritis.
THE EAR
_Aural Myiasis._—While the larva of _Chrysomyia macellaria_, known
as the “screw worm,” is the one most frequently reported from the
external auditory canal, yet many such cases have been connected
with the larvae of _Sarcophaga carnaria_, _Calliphora vomitoria_ and
_Anthomyia pluvialis_. These larvae are usually deposited in the
auditory canals of those with otorrhoea.
The symptoms are intense earache, giddiness and possibly
convulsions. The larvae tend to perforate the tympanic membrane.
Instillations of 10% chloroform in milk or the use of oils kill the
larvae.
In the stuporous states of _plague_ and _typhus fever_ there often
appears to be a state of deafness.
One must always keep in mind the ringing of the ears indicative
of the physiological action of quinine. Permanent deafness may be
produced by the long continued use of quinine.
In leprosy the lobes of the ears are special sites of preference for
the nodules and I always palpate the lobes where the nodules are not
distinctly visible.
THE NOSE
_Nasal Myiasis._—In cases of ozaena certain flies appear to be
attracted and to deposit their eggs at the nasal orifices. The larvae
developing from the eggs of _Chrysomyia macellaria_, a fly common
in tropical America, are known as “screw-worms” and cause frightful
destruction of the nasal structures.
They may bore into the adjacent sinuses. Marked frontal headache
and a purulent or bloody discharge are symptoms. Great swelling of
the nasal structures precedes the destruction of the cartilaginous
and bony tissues.
_Leprosy._—The nasal mucosa is apt to be the seat of leprous
nodules. Those located on the septum may ulcerate and material from
these ulcers show abundant leprosy bacilli. Alternations of dryness
and hypersecretion of the Schneiderian membrane are among the early
manifestations of the disease.
=Epistaxis.=—This is a feature of the early stages of _leprosy_
often associated with rhinitis, in particular the alternation of
coryza-like conditions with others characterized by dryness of the
nasal mucosa.
There is also a peculiar nasal tone to the voice of lepers.
In _yellow fever_ and _plague_ epistaxis is often the first sign of
the degeneration of the endothelial linings of the capillaries.
_Gangosa._—A disease of certain islands of the Pacific, especially
Guam, characterized by naso-pharyngeal lesions and a nasal voice,
is known as _gangosa_.
In _goundou_ we have exostoses from the nasal processes of the
superior maxillary bones.
CHAPTER XLIX
THE URINE AND THE GENITO-URINARY APPARATUS IN THE DIAGNOSIS OF
TROPICAL DISEASE
THE URINE
Of the chemical tests employed in the examination of urine that for
the presence of sugar is rarely of value, as there is no tropical
disease in which the presence or absence of sugar is of diagnostic
importance.
The determination not only of the presence of albumin in the urine
but, as well, of the variations quantitatively from day to day
is, however, most necessary in many of the tropical diseases and
particularly in yellow fever and blackwater fever.
=Tests for Albumin.=—The simplest and most reliable test for
albumin is the heat test with the subsequent addition of a
sufficient number of drops of 5% acetic acid to make the boiled
urine acid and incidentally to dissolve any phosphates which may
have separated out on boiling.
Ulrich’s test is a very simple one and only calls for reagents
which are usually at hand. Heat a saturated solution of common
salt, containing 2% of glacial acetic acid, and superimpose the
urine to be tested upon the hot reagent. A ring shows the presence
of albumin.
For Heller’s test, pour a small amount of nitric acid into a narrow
test tube and, while holding the tube at an angle of about 45°,
superimpose a layer of the urine to be tested, which is delivered
drop by drop from a pipette and allowed to flow down the side of
the tube.
This test can be converted into a quantitative one which is
sufficiently accurate for clinical purposes. It is based on the
fact that a specimen of urine containing 0.003% of albumin will
give a perceptible ring at the layering of the urine and acid in
two minutes. If the ring appears at once or in a few seconds the
albumin content is greater. From the qualitative test an idea can
be formed as to the amount of albumin which the urine contains,
a heavy ring forming immediately showing a considerable albumin
content. Probably the highest elimination of albumin is found in
chronic parenchymatous nephritis where it may run from 1 to 3%.
In an ordinary case of acute nephritis O.5% would be an average
content.
Recently I have been using for both qualitative and quantitative
albumin tests the following apparatus. This is simply a 5-inch
piece of ¼-inch soft glass tubing heated at a point 2 inches from
one end, drawn out for about 2 inches and bent to form a U-tube
with one end shorter than the other. This form of tube enables
one to perform two tests with the same column of nitric acid and
is easily cleaned and dried. They may be kept suspended around a
glass tumbler’s rim. Taking up a small amount of nitric acid with
a capillary bulb pipette it is deposited in the capillary curve
of the bent tube. This acid pipette should be kept attached to
the acid bottle. With a second pipette the urine is deposited in
the short arm of the U-tube and the presence of albumin shows by
a distinct ring at the junction of urine and acid in the clear
capillary tubing. The long arm will serve for the introduction of a
second specimen of urine for the albumin test.
For quantitative test we dilute the filtered urine with one or
more parts of normal salt solution according to the intensity of
the albumin ring. A very convenient way of making the dilution is
with a graduated centrifuge tube. Make a one to ten dilution of the
urine, mix and draw up with a bulb pipette and deposit in the short
arm of the U-tube. A distinct ring forms in two or three seconds.
Pour off one-half of the diluted urine and make up with an equal
amount of saline. Deposit this one to twenty dilution in the long
arm. The ring forms in about a minute. With further testing it is
found that a one to forty dilution shows a perceptible ring in
just two minutes. This final and successful dilution multiplied by
0.0033 gives the percentage of albumin in the urine (40 × 0.0033 =
0.13%).
Should it be desired to determine the nature of the proteids
present either in urine or in exudates or transudates the following
method is applicable. Determine the percentage of total proteid by
the method employed above. Then throw down the globulins by the
addition of an equal amount of a saturated solution of ammonium
sulphate, filter and estimate the proteid content of the filtrate.
The difference between that and the total gives the percentage of
globulin. The filtrate is now treated with 5% acetic acid until a
precipitate of nucleo-proteid ceases to form; the fluid is filtered
and the clear filtrate (which should not show any turbidity with a
drop of 5% acetic acid) is tested for its proteid content, which
represents the serum albumin. When the combined percentage of
globulins and serum albumin is subtracted from the total proteid
percentage we have the percentage of nucleo-proteid.
=Tests for Blood.=—Very important in tests of the urine are those
for blood. With an unaided eye a smoky colored urine, more or less
reddish-brown in color, is suggestive in cases of haematuria, while
in haemoglobinuria we usually have a more or less porter-colored,
turbid fluid which, however, shows a clear haemoglobin-tinged fluid
when centrifuged to throw down the haemoglobin casts and granular
débris of the disintegrated red cells. Upon shaking such urine we get
a pinkish foam instead of the yellowish one of icteric urine.
A strip of white filter-paper when partially dipped into urine
shows pinkish-colored waves which are more deeply colored at the
summit of the waves while the paper which absorbs bile-containing
urine shows the yellowish color and waves less yellow at the
summits of the colored waves.
For haematuria we may use either the microscopic method for the
recognition of red cells or chemical ones. The red cell is best
recognized by the double contour of the 7.5 micron disk. Spores of
moulds, which greatly resemble red cells, are smaller, usually not
more than 5 microns.
The following technic is of the greatest value not only because
it makes the red cells more distinct but because by staining the
various epithelial elements it gives us more exact information as
to distinction between the segmented nucleus of pus cells and the
single one of renal cells. Make a streak of vaseline across a slide
one inch from one end. Then deposit a drop of urinary sediment,
taken up from the centrifuge tube with a pipette, about ¼ inch from
the grease line. Then drop a large drop of Gram’s iodine solution
on this sediment and then apply one side of a square cover-glass
to the vaseline line and allow it to fall gently on the drop of
sediment and stain. There is no current motion, and casts and other
urinary elements remain under the cover-glass instead of floating
out beyond the margins. It is well to examine the unstained
sediment with a ⅔ inch objective before adding the iodine and
applying the cover-glass, as one gets a better idea of casts with a
low power and unstained than in any other way.
With haemoglobinuria we necessarily turn to chemical or spectroscopic
tests which are also applicable to microscopically doubtful cases of
haematuria.
For the detection of occult blood, the technique described on page
524 should be observed, and alkaline urines faintly acidified with
acetic acid before examination.
=Indicanuria.=—In _sprue_ and _pellagra_ we have a rather marked
increase in indican. It is probable that many cases of vague
manifestations of neurasthenia with loss of physical and mental
energy are connected with auto-intoxication rather than tropical heat
or intestinal parasites.
=Urobilinuria.=—In conditions where there is a great destruction
of red cells tests for urobilin are important. Plehn considers the
presence of urobilin as of importance in the diagnosis of _latent
malaria_, which is true, provided other causes for red blood cell
destruction are excluded. _Blackwater fever_ cases usually show
an intense urobilinuria. Urobilinuria is also a sign of deficient
functioning of the liver.
=Bile Pigment Tests.=—In conditions associated with the presence
of bile pigments in the urine we may conveniently employ the Gmelin
test in the following manner. Filter the urine several times through
the filter and then touch the moist inner surface of the paper with
a glass rod dipped in commercial nitric acid. A ring-like play of
colors, green, blue, violet and red circle out from the spot touched.
A green color must be noted for positive diagnosis.
Tests for bile acids seem to have but slight value in differential
diagnosis.
A very simple and apparently quite reliable test for deficiencies in
liver functioning is that known as Ehrlich’s aldehyde reaction. The
reagent is a 2% solution of p. dimethylaminobenzaldehyde in equal
parts of water and concentrated hydrochloric acid.
For the test treat 5 cc. urine with 5 to 10 drops of the reagent.
Agitate a few minutes and a positive reaction is shown by a fine
cherry-red color, thought to be due to urobilinogen.
The urine sample should be perfectly fresh and not long exposed to
light.
AMOUNT OF URINE IN 24 HOURS
Normally a man passes about 1200 cc. of urine in twenty-four hours,
a woman somewhat less. When the amount is under 750 cc. we have an
oliguria. To consider a polyuria as present the patient should pass
more than 3000 cc., as this amount may be considered the upper normal
limit. In anuria we have a cessation of renal activity.
The disease in which anuria is most characteristic is _cholera_.
During the stage of evacuation the urinary secretion becomes less and
less along with the progressive failure of circulation and, during
the algid stage, we have a suppression of urine.
The anuria seems to run parallel with an acidosis and intravenous
injections of bicarbonate of soda solutions tend to prevent anuria.
In the stage of reaction the favorable outcome is the reappearance
of urine, which increases in amount to become a polyuria. In
unfavorable cases the anuria continues.
In _blackwater fever_ anuria may result from the blocking up of the
renal tubules by haemoglobin casts.
Blackwater fever also shows an acidosis and alkaline treatment is
here indicated. Blackwater urine is irritating so that there is
vesical tenesmus with frequent urination.
The degree of renal involvement is of great prognostic value in
_yellow fever_, and those cases where the oliguria goes on to
suppression are apt to terminate fatally.
In _heat stroke_ there is an oliguria or anuria which may be
followed, during convalescence, by a polyuria. Marked irritation
of the bladder, associated with suppression of sweating, may be
indicative of oncoming heat stroke.
In _dropsical beriberi_ there is an oliguria or, rarely, an anuria
which with the rapid disappearance of the general body oedema may
become an excessive polyuria.
Rarely one may observe a critical flow of urine in _dengue_ at the
time of the fall of the primary febrile accession.
ALBUMINURIA
The disease in which this is of peculiar diagnostic and prognostic
value is _yellow fever_. We expect albumin about the second day with
a steady increase in amount during succeeding days of the fever.
The degree of oliguria or rather anuria is of greater prognostic
value than the degree of albuminuria. The albuminuria is of great
diagnostic value in differentiating yellow fever from dengue.
_Blackwater fever_ shows a great abundance of albumin with the
appearance of the haemoglobinuria and diminishes as the color of
the urine clears up.
In _malaria_ albumin was present in 38% of benign tertian
infections and 58% of malignant ones at Johns Hopkins Hospital.
The absence of albumin in _beriberic urine_ is important in
differential diagnosis from acute nephritis.
HAEMOGLOBINURIA
Paroxysmal haemoglobinuria or haemoglobinuria resulting from
potassium chlorate poisoning, severe burns, intravenous injections
of foreign sera, or—most commonly—syphilis, may be noted in the
tropics.
The vast majority of cases of true tropical haemoglobinuria, however,
are due either to blackwater fever or to the administration of the
acid salts of quinine to one predisposed to quinine haemoglobinuria.
While it must be admitted that haemoglobinuria may result from
quinine it is certainly so rare in subtropical countries, where great
amounts of quinine are administered in treatment of malaria, as to
be unimportant. It is only where the malignant tertian parasite
flourishes that we have the question of the importance of quinine in
producing haemoglobinuria brought up.
Certain persons have isohaemolysins in their blood which dissolve
the red cells of other persons and in paroxysmal haemoglobinuria
autohaemolysins may be present which can destroy the patient’s
own red cells. This auto-haemolysis seems operative only when a
low temperature is followed by a high one. When haemoglobinaemia
exists the liver converts it into bile pigment causing bilious
stools and jaundice. If one-sixth of the red cells are destroyed
haemoglobinuria results.
The dark, porter-colored urine of blackwater is diagnostic even to
the patient. The urinary sediment consists of granular débris with
occasional haematoidin crystals. Albuminuria runs parallel with the
haemoglobinuria. Pain in the loins, probably, from the plugging
of the renal tubules by the detritus of red cell destruction, is
a feature of blackwater fever. In blackwater fever we have the
early appearance, even in a few hours, in a patient who is markedly
asthenic and miserable, of jaundice, porter-colored urine and
albuminuria.
HAEMATURIA
Among tropical diseases that which immediately suggests haematuria
is vesical bilharziasis. The blood in the urine is in the form
of red cells; it is a haematuria and not a haemoglobinuria. The
passage of blood usually occurs at the end of micturition and it is
either in the last few drops of urine or in the sediment obtained
after centrifuging that we note the terminal spined eggs of _S.
haematobium_ which prove the diagnosis.
Red blood cells in the urine may also be noted in the
haematochyluria of filarial disease.
When we have blood in the urine in yellow fever it is a haematuria
and comes on about the same time as the black vomit and other
haemorrhages resulting from degeneration of the endothelial linings
of the blood capillaries, which only takes place about the third or
fourth day of the disease.
Haematuria may also be noted in plague at the time when the
haemorrhages into the skin occur.
CHYLURIA
Vesical varices from lymphatic obstruction, due to filarial disease,
are the most frequent cause of the milky urine of chyluria. The
urine usually has a pinkish tinge from blood admixture so that the
condition is really a haematochyluria. The thoracic duct may not be
the seat of obstruction which has taken place elsewhere when the
condition is lymphuria instead of chyluria. Lymph and chyle differ
in fat content, the former having from very little to about 3% while
the latter has 5% or more of emulsified fat. Chyle has also more than
twice as much proteid as does lymph.
In chyluria the morning urine is often clear while that at
night is milky. On standing, chylous urine separates into an
upper cream-like layer with a pinkish sediment and, between, a
pinkish-white fluid in which floats a clot. Filarial embryos may or
may not be found.
KIDNEY FUNCTION AND ITS DETERMINATION
The ability of the kidney to excrete substances from the blood stream
is frequently affected by disease, especially such as disturbs the
kidney, and is usually diminished after the age of 50 years. Disease
of the kidney, however, does not necessarily imply an inability to
eliminate substances—the functional need not parallel the anatomical
lesion. Function may be normal especially when the changes are of
focal type.
Impairment of renal function does not affect the excretion of
different compounds to the same extent. It is well established
that functions for chlorides and for urea are independent of each
other. In any urinary examination, then, one should bear in mind
the possible effect of an impaired excretory power relative only to
the substance under consideration. In this connection, we speak of
the _kidney threshhold_ for a substance, i.e., the concentration
required in the blood stream before the kidney will excrete it, at
least in abnormal amounts. For chlorides, this is quite definite at
562 for blood plasma; for sugar, it is about 160-180 for whole blood.
The threshold is not necessarily absolute, but simply indicates
that with less sugar, for instance, only the normal traces will be
passed. Chloride excretion begins only when their concentration
passes the threshold value, and the rate of elimination depends upon
their excess. Other compounds, such as urea, for example, may have
no definite threshold value. Disease may affect the value, either
by raising it and causing abnormal retention, or by lowering it and
giving rise to depletion.
We can establish the status of the renal function in any given
case, and are then in a position to intelligently prescribe
dietetic and other treatment. Chemical analysis of the blood
indicates the metabolic products affected and guides us in the
adjustment of the diet, etc., to the excretory powers of the
kidneys. One must, however, not overlook the nutritive needs of the
body.
Many methods are employed for the determination of kidney function,
and their relative values are still debatable. Probably those
least open to criticism are chemical analysis of the blood, the
phenolsulphonephthalein test, and Mosenthal’s method. Ambard,
McLean, Van Slyke, and others have devised formulae to this
end, based upon chloride, urea, or sugar excretion, which have
many warm advocates as well as severe critics. A rough clinical
comparison of the two kidneys may be obtained by determining the
urea in specimens of urine simultaneously collected by the ureteral
catheter.
_Blood Chemistry_, now that its value has been established, is
generally given preference and allowed greater weight in case of
disagreement with other tests. It measures excretory function for
normal metabolic products, and has the additional value of an aid
in diagnosis and prognosis and a guide to treatment, especially
dietetic. It has the disadvantage of a possibly unfamiliar technique,
and does not afford a comparison of the two kidneys.
The substances usually considered are the nitrogenous compounds
(nonprotein nitrogen, urea nitrogen, uric acid, etc.), but
retention of others (sugar, chlorides, cholesterin, etc.) are
also of significance in this connection. Of the nitrogenous
constituents, the kidney excretes creatinine most readily, urea
next, and uric acid with the most difficulty. As a consequence, an
impairment of function results first in the retention of uric acid,
then urea, and, finally, creatinine is also retained. Owing to the
relatively small amounts of uric acid and creatinine present, the
nonprotein nitrogen, which includes the nitrogen in them as well
as in other compounds, is not appreciably affected except by the
urea increase. This is the basis of an intelligent interpretation
of the findings. The urea and nonprotein nitrogen are so markedly
affected by diet, especially among nephritics, that judgment must
be exercised when they are employed as indices of renal function.
This fact was not properly appreciated until recently, and probably
accounts for much of the discredit cast upon blood chemistry in
this connection. The uric acid, being less exogenous in origin,
is perhaps the most delicate and the safest index; the increase
appears early, and 3.5 may be considered the high normal value.
On the usual restricted hospital diet, over 20 for urea nitrogen
should be considered suggestive of impaired kidney function; over
75 speaks decisively for renal involvement and probably uraemia.
_Phenolsulphonephthalein (Phthalein, or Red) Test._—This was
developed by Rowntree and Geraghty, and its simplicity makes
it very useful, especially to the isolated practitioner with
limited laboratory facilities. It estimates only function for a
foreign substance, is not considered quite as reliable as chemical
analysis of the blood, and, of course, does not give the additional
information that the latter supplies. It is, however, of much
value, has no contraindications, and does compare the kidneys when
combined with ureteral catheterization or use of a separator.
Positive results are of more significance than negative, and it is
less affected by glomerular than tubular changes. Values of more
than 75% for 2 hours may be accompanied by diuresis, and Frank
considers such a finding suggestive of renal disturbance with
irritation if there is any corroborative evidence.
The technique comprises administration of the dye, determination of
the interval before it appears in the urine, and the amount then
excreted during definite periods. The dye is employed in solution,
and is conveniently purchased already sterilized in ampules, each
containing slightly more than 1 cc. of a solution of its monosodium
salt of the strength of 6 mg. per cc. The patient drinks 200-400
cc. water, and 6 mg. of the dye are injected intramuscularly
(lumbar muscles), or intravenously, 20 minutes later. The bladder
is immediately emptied, and the urine discarded. The succeeding
portions of urine may be collected by voiding, but it is more
accurate to catheterize the bladder or ureters, and catheterization
is practically a necessity for determination of the “appearance
time.”
The appearance time is the interval of time elapsing between
injection of dye and its appearance in the urine. It is determined
by allowing the urine to drip from the catheter into a receiver
containing a drop of 10% NaOH. The first traces of the dye will
cause a pink color.
The time interval chosen for calculating excretion is then computed
from the instant of this appearance. There is considerable
diversity in practice as regards this time interval, and it would
seem that shorter intervals and quicker results are gaining in
preference, as well as being considered equal in value to longer
periods.
The percentage excretion of the dye is now measured in each sample
of urine. To do this, prepare a standard solution, made by diluting
0.5 cc. of the phenolsulphonephthalein solution mentioned above
to about 200 cc. with water, adding 5-10% NaOH until no further
intensification of the red color is produced (requires a few cc.),
diluting to one liter, and mixing. This standard then represents
50% (3 mg.) of the amount of the dye injected. The color of the
urine sample is similarly developed with alkali, and the mixture
diluted to 1 liter, mixed, and compared with the standard in a
colorimeter. The per cent excretion in the specimen equals the
reading of the standard solution multiplied by 50 and divided by
the reading of the urine mixture, when the colors are matched in
the instrument.
For accurate work, it is desirable to balance in the standard the
urine color of the unknown, and this is accomplished by including
in the standard a volume of urine (dye-free) _proportional_ to that
in the unknown. Also, with a low excretion, it is better not to
dilute the unknown to 1 liter, but to some lesser volume that will
give a tint closer to that of the standard, and then allow for the
variation in the calculation.
[Illustration: FIG. 153.—Fibres, starch granules, etc., which may
be found in urine sediment. No. 12 gives appearance under microscope
of scratches on old used glass slides. No. 15 (_a_), _Tyroglyphus
longior_ a mite. No. 15 (_b_), _Trichomonas vaginalis_. No. 16
(_a_), Egg of _Eustrongylus_; (_b_), _Echinococcus hooklets_; (_c_)
_Schistosoma_ egg; and (_d_), _Filaria bancrofti_ embryo.]
Dunning has devised a simple, inexpensive colorimetric outfit with
permanent standards in ampules for this test. It is satisfactory
unless the colors of the standards fade.
After intravenous injection, the normal appearance time is 4-6
minutes, and the normal elimination is 35-40% in 15 minutes, and
totals of 50-65% for 30 minutes and 65-80% for 60 minutes; or, for
the first 30 minutes, it may be stated as about 1% per minute from
each kidney.
After intramuscular injection, the normal appearance time is nearer
10 minutes, and the normal elimination is 30-40% in 30 minutes, and
totals of about 50% (40-60) for 60 minutes, and about 80% (60-85)
for 2 hours, or 20-25% during the second hour. If the appearance
time is not determined, it is customary to allow for it, collecting
the first hour’s specimen at 70 minutes after injection of dye and
the second hour’s 60 minutes later.
Impairment of kidney function, of course, increases appearance time
and lessens excretion, serious cases not unusually excreting less
than 1% during two hours.
When the question of the kidney involved arises, the urine must be
taken by ureteral catheterization or by a separator.
=Starches and Fibres.=—In examining urinary sediments it is
important to be familiar with the various textile fibres and starch
grains which are so frequently present, the fibres coming from the
clothing and the starch grains from dusting powders. Wool fibre
fragments show bark or scale-like imbrications and are round.
Cotton fibres are flattened and twisted, while linen ones show a
striated flattened fibre with frayed segments as of a cane stalk.
Silk shows a glass-like tube with mashed-in ends.
Corn and rice grains are the most common of the starch grains and
their nature is immediately disclosed by their blue color when
mounted in iodine.
AFFECTIONS OF THE GENITO-URINARY ORGANS
In _blackwater fever_ we have marked pain in the region of the
kidneys due to the plugging of the tubules with haemoglobin casts.
Vesical tenesmus and pain along the ureters may also be present.
In _malaria_ Thayer states that nephritis occurs in about 2% of
malignant tertian cases.
In _bilharziasis_ the kidneys are involved secondarily—the change
being brought about by stone in the bladder and cystitis leading to
hydronephrosis and pyelonephritis.
Cases of cystitis occurring in dysentery have been reported which
showed amoebae in the sediment of the urine. Such cases probably were
connected with recto-vesical fistulae caused by amoebic ulceration.
In _cholera_ the kidneys are markedly affected, especially the
epithelial lining of the tubules.
_Malta fever_ may rarely be attended by an orchitis.
One of the manifestations of filarial disease is _lymph scrotum_ in
which the scrotum is covered with small blebs containing a chylous
fluid which may possibly contain microfilariae. It is associated with
recurring attacks of lymphangitis. There is also a filarial orchitis
and we may have a lymphangitis of the lymphatics of the cord. Again
filarial disease may show a chylocele in which the tunica vaginalis
contains a fluid similar to that seen in the varices of lymph
scrotum. This fluid may also show filarial embryos.
In _endemic funiculitis_ there is a sudden onset with high
temperature and pain in spermatic cord and epididymis. The general
condition rapidly becomes grave with a hard, tender, cylindrical
swelling along the cord and also pain and swelling of epididymis.
It is a streptococcus infection usually engrafted on a filarial or
bilharzial process and demands immediate surgical measures.
_Kala-azar_ may be accompanied by sloughing of the scrotum at the
time manifestations of cancrum oris are noted.
Cases of gangrene of the scrotum have been reported as connected with
_malaria_.
Gangrene of the scrotum and penis is not infrequently noted in
_Rocky Mountain fever_.
In puzzling febrile cases in the tropics one should always think of a
possible _pyelitis_. Then too keep in mind _renal tuberculosis_.
If _leprosy_ comes on before puberty the sexual organs remain in
an undeveloped condition. Leprous infiltrations are noted in the
testicles and ovaries. In nerve leprosy, which does not usually
come on until after puberty, the women may bear healthy children
and it is now thought that the view that leprosy markedly tends to
produce sterility is lacking in confirmation.
In _ancylostomiasis_ menstruation is markedly interfered with and
amenorrhoea is often a prominent symptom. Young men who have been
affected before puberty show lack of development of pubic hair
along with infantile genital organs. The girls do not show normal
breast development.
_Granuloma of the pudenda_ is a disease which is rather frequent in
British Guiana.
_Dhobie itch_ is characteristically located in the crotch region.
BACTERIOLOGICAL EXAMINATION OF URINE
About the only tropical disease in which a bacteriological
examination of the urine is of particular value is that in connection
with _Malta fever_. It is advisable to cleanse the meatus with
alcohol and then having discarded the first ounce or so of the urine
to receive the remainder in a sterile salt mouth bottle. A drop of
this urine can be deposited on a poured agar plate and smeared out
over the surface.
As dysentery bacilli and cholera spirilla are practically absent
from the blood, urine examination for the causative organisms in
these diseases is fruitless.
The culturing of the urine to find paratyphoid or typhoid organisms
should be carried out, as well as blood cultures, where we are
dealing with puzzling fevers in the tropics. The Teague plating
medium described under the chapter on Faeces is a very satisfactory
one.
In culturing urine from a case of pyelitis blood agar is a most
excellent differentiating medium for streptococci.
CHAPTER L
THE FAECES AND THE ALIMENTARY TRACT IN TROPICAL DISEASES
THE FAECES
It is advisable to examine a stool macroscopically before taking up
the microscopical examination. Pus or blood in stools may often be
noted without the aid of the microscope.
The normal stool is sausage-shaped and soft.
The mucus of bacillary dysentery is opaque and grayish from the
great number of pus and phagocytic cells. It is well to remember
that Charcot-Leyden crystals, which are practically always absent
from bacillary dysentery stools, are not infrequent findings in
the amoebae-containing stools; of course, these crystals appear in
other intestinal parasite infections.
In obstruction of the common bile duct we have acholic, whitish,
foul-smelling stools. If the putty color be due to bacterial change
exposure to the air will restore the brownish tinge.
Sprue stools are whitewash to putty-colored, pultaceous, and filled
with air bubbles. The amount is excessive.
A very practical way of obtaining amoebae is to pass a rectal tube
or a piece of drainage tube with fenestrations into the bowel, and
amoebae may be found in the mucus filling the perforations in the
tube.
Ordinarily the stool is best collected in quart fruit jars
and examined as soon after evacuation as possible. The wooden
spatula-like tongue depressors are well adapted for handling the
specimen.
In examining a stool, it is well to color the drop of faeces, which
is to be covered with the cover-glass, with a small loopful of ½%
solution of neutral red. If diluting fluid is used, it should be
salt solution, and not water. The neutral red tinges the granules
of the endoplasm of amoebae and flagellates a very striking
brown-red color, thus differentiating them from vegetable cells or
body cells.
Encysted protozoa are difficult to diagnose, unless one possesses
considerable experience. In examining for encysted amoebae as well
as for bringing out the number of flagella of flagellates I now use
the following method: Take a clean slide and make a vaseline line
across it about 1 inch from the end. A drop of the iodine solution
is placed on the slide about ½ inch from the vaselined line and a
suitable portion of the faeces to be examined is emulsified in it.
The edge of a square cover-glass is then applied to the vaselined
line and allowed to drop on the preparation. By pressure suitable
thicknesses of fluid can be examined. There is an absence of
current motion.
Epithelial cells are generally more or less disintegrated. In
the mucus of bacillary dysenteric stools, however, large intact
phagocytic cells are frequent, which may be mistaken for encysted
amoebae, and the polynuclear cell count averages 90% as contrasted
with the average polynuclear count of 7.5% in amoebic dysentery.
When a smear preparation is desired, we may smear out a fragment
of mucus and stain by Romanowsky’s or Gram’s method. Beautiful
preparations may be made by mixing the faeces with water, then
centrifuging for one minute. This throws down vegetable débris
and crystals. Now decant the supernatant fluid, which holds the
bacteria in suspension, and add an equal amount of alcohol. Again
centrifuge, decant, and smear out and examine the bacterial
sediment.
Simply taking a small mass of faeces and emulsifying it with a wooden
toothpick on a concave slide in 70% alcohol—then, after the sediment
settles, taking up a loopful with platinum loop from the surface and
smearing out, gives a very satisfactory smear. Gram’s method, with
dilute carbol fuchsin counterstaining, gives the best picture.
To culture for typhoid, dysentery, cholera, or other bacteria,
take up the material in a tube of sterile bouillon and smear it
out with a swab over a lactose litmus agar plate or an Endo or
Conradi-Drigalski plate. Before streaking the plates they should
be very dry on the surface. This can be best done by pouring the
melted agar into a plate with a circular piece of filter-paper in
the lid and placing in the incubator for one-half hour to dry. The
filter-paper absorbs the moisture. Then inoculate the surface of
the plate with the faecal material.
=Teague Medium.=—We have formerly preferred the Endo plate for
typhoid work and the lactose litmus agar when culturing for dysentery
bacilli. More recently we have obtained most satisfactory results
with the Teague medium. The colon colonies, after eighteen hours,
are deep black and opaque while the typhoid-dysentery group show
colorless, transparent colonies.
The medium is prepared as follows: Nutrient agar is made in the
usual way, containing 1.5% agar, 1% Witte’s peptone, 0.5% sodium
chloride, and 0.5% Liebig’s meat extract, to the liter of distilled
water. It is cleared with egg-white, placed in flasks, and
sterilized in the Arnold sterilizer on three successive days. The
reaction is brought to plus 0.8. The agar is melted and saccharose
0.5% and lactose 0.5% are added. The medium is then heated for ten
minutes in the Arnold. To every 50 cc. of the medium are added 1
cc. of 2% yellowish eosin and 1 cc. of 0.5% methylene blue. The
mixture is shaken and plates poured. Eosin solution should be added
first.
=Occult Blood.=—In performing the test for occult blood, one
should exclude the possibility of blood reaching the bowels from an
extraneous source, such as ingested foods, mouth, nose, lungs and
vagina, and the absence of interfering substances should be ensured.
An absolute milk diet, or, at least, a diet containing neither meat
nor green vegetables, is indicated for two or three days prior to
the test, and all medication should be suspended. The technique noted
on page 524 should be followed scrupulously when dealing with faeces.
It has been suggested that the absence of occult blood from the
faeces may be accepted as an indication of cure in ancylostomiasis.
[Illustration: FIG. 154.—Cestodes and cestode ova.]
=Ova in Faeces.=—It is in the faeces we examine either for the
parasites or for their ova in connection with practically all the
flukes, except the lung fluke and the bladder fluke; for intestinal
taeniases and for practically all the round-worms, except the
filarial ones.
In the tropics, the examination of the faeces exceeds in value that
of urine and is possibly more important than blood examinations.
=Helminthiasis Statistics.=—There is one point in connection with
the statistical reports as to the presence of intestinal parasites in
a given section of the tropics that I desire to emphasize.
Because a limited district shows a certain prevalence of intestinal
parasites we should not conclude that the entire country from which
such findings emanate shows a similar extent and type of infection.
Take for instance the Philippine Islands.
[Illustration: FIG. 155.—Trematode ova.]
In 1910, there were made in Cavite Province 932 stool examinations
upon specimens from cases of sick people and of these only such
patients as it was thought required such an examination for
diagnostic reasons were made to bring such a specimen of faeces.
Of the 932 examinations, 135 or 14.4% failed to show the presence
of intestinal parasites or their ova. The remaining positive
examinations gave findings as follows:
-------------------+----------------------+---------------
Organism | Number of infections | Per cent.
-------------------+----------------------+---------------
_Ascaris_ | 627 | 67.2
_Trichocephalus_ | 607 | 65.1
Flagellates | 135 | 14.4
Amoebae | 111 | 10.9
Hookworm | 23 | 2.4
_Taenia saginata_ | 3 | 0.3
_Balantidium_ | 1 | 0.1
_Strongyloides_ | 1 | 0.1
-------------------+----------------------+---------------
At Bilibid Prison, Garrison encountered amoebic infection in 23% of
the cases. In the medical survey of Taytay, his findings were 2.7%.
Rissler and Gomez report only 0.39% of amoebic infection in their
examinations in Las Piñas and no cases showing such infections in
Tuguegarao and Santa Isabel. Such numbers are in striking contrast
with those of former investigators, some of whom have reported as
high a percentage of infection as 70.
[Illustration: FIG. 156.—Nematode ova.]
Our findings as regards flagellates (14.4%) corresponded fairly
closely with those of Garrison, namely, 21% at Bilibid and 5.5% at
Taytay.
Garrison, for _Trichocephalus_ infection, obtained 59% at Bilibid
and 77% at Taytay; Rissler and Gomez give 53% at Las Piñas; 25.9%
at Tuguegarao, and 6.23 at Santa Isabel. Our findings were 65.1%.
As regards _Ascaris_ we found a higher rate of infection than for
any other parasite (67.2%). Garrison encountered 26% at Bilibid and
82.9% at Taytay. The percentages of Rissler and Gomez are 77, 73,
and 60 respectively for Las Piñas, Tuguegaroa, and Santa Isabel.
Garrison noted at Bilibid an incidence second only to
_Trichocephalus_ for hookworm infection, namely 52%. His percentage
of infection at Taytay was 11.6. Rissler and Gomez found 11.14% of
all cases examined infected with hookworms at Las Piñas, 8.01%
in Tuguegarao, and 45.38% in Santa Isabel. We noted only 2.4% for
Cavite, San Roque, and Caridad.
Our findings as regards _Strongyloides_ (0.1%) were far below
those reported by Garrison at Bilibid (3%) and at Taytay (0.7%).
Rissler and Gomez found 2.24% infected in Las Piñas, but no cases
were encountered in Tuguegarao and Santa Isabel. The same factors
influencing hookworm infection in this locality may be operative
for _Strongyloides_. Garrison found 0.2% of the individuals
examined at Taytay to be infected with ciliates, while Gomez and
Rissler failed to find such infections at Tuguegarao or Santa
Isabel. We found a single case in the 932 examinations.
[Illustration: FIG. 157.—Microscopical constituents of faeces.
(_v. Jaksch._) _a_, Muscle fibres; _b_, connective tissue; _c_,
epithelium; _d_, leucocytes; _e_, spiral cells; _f_, _g_, _h_, _i_,
various vegetable cells; _k_, “triple phosphate” crystals; _l_,
woody vegetable cells; the whole interspersed with innumerable
microorganisms of various kinds.]
THE ALIMENTARY TRACT
The Mouth
In _pellagra_ we have moist fissuring at the angles of the mouth with
a large indented tongue with central coating and bare tip and sides.
There is often a glairy mucus covering these red borders on the side.
The fungiform papillae are prominent. Later on the tongue may become
fissured and uniformly red. The buccal mucosa shows a carmine flush.
The gums are tender but there is not the tendency to aphthous ulcers
one sees in sprue. The flow of saliva is frequently increased.
In _sprue_ there is at first great sensitiveness of the buccal mucosa
so that articles of moderate pungency give rise to painful burning
sensations. The tongue becomes quite sore with vesicle formation
along borders and tip which soon turn into ulcers. Ulcerations also
occur on the buccal mucosa, particularly at the site of the posterior
upper and lower molar teeth (Crombie’s ulcer).
The congestion causes a great increase in mucus especially about
the faucial pillars and pharynx. Ulcers are common about the
fraenum of the tongue. While the tongue is coated at first with
red ulcerated tip and sides it later becomes bare of any coating,
red and finally even glazed as though varnished. It is at times
fissured.
_Onyalai._—A very peculiar disease of Portuguese West Africa and
possibly the Soudan region, known as _onyalai_ is characterized by
the appearance of blood-distended vesicles of the mucosa of the
cheeks and hard palate. The tongue is often swollen. The skin may
show haemorrhages and haematuria is not infrequent. The mouth blebs
vary in size from that of a split pea to a diameter of ½ inch or
more. The cause is unknown.
_Herpes labialis_ is not so common in tropical as in temperate
climate malarias. It is absent in plague pneumonia.
In _leprosy_ the nodules which form on the inside of the cheeks and
fauces tend to show ulceration and thickenings. The discharges from
the ulcerations in the nose, especially that on the vomer, reach
the pharynx and such leprosy bacilli-containing discharges may be
expectorated and cause one to consider the material as coming from
the lungs.
In _yellow fever_ the bleeding from the gums usually precedes the
black vomit.
In _kala-azar_ and possibly in _malaria_ we may have gangrenous
conditions of the cheek, as cancrum oris.
In the miliary type of _verruga_ we may have the granulomatous
lesions appearing on the mucous membranes of the mouth.
In _typhus_ fever the mouth is strikingly foul with marked sordes
covering the teeth. The dry brown tongue in this disease is known
as the “parrot tongue.”
We may rarely have parotid gland enlargement in _Malta fever_,
_malaria_ and _tsutsugamushi_.
Parotitis is not uncommon in typhus fever. A type of parotitis
which differs from mumps in not being contagious has been reported
from the Philippines.
Stomach and Oesophagus
Very important in diagnosis is a tenderness in the pyloric end of the
stomach, which is brought out by attempting to palpate the epigastric
region. It is marked in yellow fever and acute pernicious beriberi
as well as in blackwater fever and bilious remittent fever. We also
frequently have epigastric tenderness, extending to the right, in
ancylostomiasis.
Hookworms patients are often “pot-bellied” and the craving for
eating unusual articles, as earth, may be connected with the
gastric hyperacidity which the patient desired to neutralize with
alkaline earth.
_Sprue_ gives a flatulent dyspepsia with gaseous eructations.
_Pellagra_ gives eructations and pyrosis and very common is a burning
sensation going up from the stomach along the line of the oesophagus.
The esophagus is raw in _sprue_ so that swallowing is painful.
Nausea and Vomiting
So many diseases are attended with nausea, besides those in which
nausea is accompanied by rather constant vomiting, that it would
hardly seem advisable to consider it alone. At the same time the
slight nausea which often accompanies _bacillary dysentery_, as one
of the manifestations of toxaemia, is of value in differentiating
this type of dysentery from the amoebic one.
In _yellow fever_ there may be early vomiting of whitish or
bile-stained mucus but the well-known black vomit is a later
feature, only occurring after the fourth day when the other
haemorrhagic manifestations set in.
Bilious vomiting is the feature in _bilious remittent fever_ which
causes the patient the greatest distress.
In _blackwater fever_ the frequent retching and bilious vomiting tend
to exhaust the patient and the persistent vomiting of green bile
often precedes death.
Bilious vomiting may be quite a feature of the icteric type of
_relapsing fever_.
_Vomiting sickness._—There is a disease known as _vomiting sickness_
which has been noted in Jamaica. It occurs chiefly in children
and has a sudden onset with marked vomiting followed by cerebral
symptoms and great mortality. Some have thought the disease to be
yellow fever but the fever and jaundice of that disease are absent.
Scott has thought it to be epidemic cerebro-spinal meningitis, but
more recently has suggested that it is possibly due to the eating of
some poisonous substance, plant or otherwise, and that it is not an
infectious disease. It is now recognized as due to ackee poisoning.
Vomiting is often a sign of dangerous vagal involvement in _acute
pernicious beriberi_. Some consider that the extreme dilatation of
the right heart, pressing on the stomach, may be the excitant of
this vomiting.
The vomiting of _cholera_ follows the diarrhoea. The material vomited
may be of the same character as the rice-water stools.
In _ptomaine poisoning_ vomiting precedes the diarrhoea.
Rarely a _liver abscess_ may burst into the stomach, in which case
we would have the vomiting of pus. Of course the more common route
is by the lungs in which case the chocolate-colored liver abscess
pus would be coughed up instead of vomited up.
The Intestinal Tract
It is usual to consider constipation as a clinical feature of
such diseases as plague, yellow fever, Malta fever, beriberi and
tsutsugamushi, as well as typhus fever.
Abdominal pains are most often connected with _dysenteric_
conditions and it is customary to state that the greater the
tormina, or intestinal griping, the nearer is the dysenteric
process to the caecum.
In _cholera_ the cramping of the abdominal muscles may follow that of
the calf muscles.
In _sprue_ we may have a doughy sensation on palpating the abdomen
due to the fermenting contents of the intestine.
In the algid type of _pernicious malaria_ the abdominal griping may
be severe.
Tenesmus is the condition which along with tormina gives a diagnosis
of some form of dysentery.
In rectal _schistosomiasis_ the thickenings and blood
extravasations, resulting from the eggs extruded by the fluke,
may give rise to prolapse of the rectum. This may also occur in
severe bacillary dysentery and in a disease of British Guiana
and Venezuela, known as _epidemic gangrenous rectitis_, prolapse
and gangrene of the rectum may occur. The symptoms are those of
gangrenous dysentery.
Diarrhoea
The chronic diarrhoeas of the tropics are often associated with
amoebic dysentery and in such cases we generally get a history of
recurring attacks of diarrhoea separated by periods of constipation.
In _sprue_ the condition generally sets in as a morning diarrhoea,
very profuse and painless. _Hill diarrhoea_ also shows frequent
stools of whitish color from early morning until about noon.
The typical stool of _sprue_ is a gas-permeated, putty-colored,
offensive mass, extraordinarily copious.
In _cholera_ the rice-water stool, which is not attended by pain,
causes an unusual sense of prostration even at the onset of the
stage of evacuation.
In _pellagra_ we often have a recurring diarrhoea or mild
manifestations of dysentery.
The stool of pellagra is darker and less copious than that of sprue
and shows only a normal fat content while that of sprue is very
fatty—as much as 30% of ingested fat appearing in the sprue stool
as against the 5% for the normal one.
In _Japanese schistosomiasis_, following the stage of urticarial
fever, we have our best diagnostic means in examining the
blood-tinged bit of mucus capping the stool for the spineless ova of
the fluke.
The _fluke diseases_ of the liver and intestines give rise to
various disturbances. The diagnosis is by the finding of the
specific ova.
In infections with _Strongyloides stercoralis_ there may be vague
manifestations of neurasthenia and diarrhoeal disturbances. Cochin
China diarrhoea was once thought to be a _Strongyloides_ infection.
Infections with amoebae, intestinal flagellates and ciliates are
discussed under dysentery.
Intestinal flagellates are so common in the stools of well people
in the tropics that one should be very careful in assigning a
pathogenic rôle to them.
It is now generally accepted that _Lamblia (Giardia)_ can bring
about exhausting diarrhoeas.
Intestinal Myiases
In the tropics vague intestinal disturbances or violent abdominal
cramping may be brought about by dipterous larvae in the intestinal
canal. The symptoms may be those of a dysentery and may be attended
with fever and malaise. The biliary tract also may be invaded. For a
more detailed statement of the several myiases, see Chapter XXV.
[Illustration: FIG. 158.—Larva of _Musca vomitoria_ (_Calliphora
vomitoria_); below: of natural size; above, enlarged. (Leuckart.)
(From Tyson.)
FIG. 159.—Larva of _Anthomyia canicularis_, enlarged. Rarely found
in the stool. (Gould.) (From Tyson.)]
The larvae usually obtain access to the alimentary tract in food
taken in by the mouth. Flies of the genus _Sarcophaga_ are prone
to deposit their larvae on food, especially meat that is somewhat
tainted. Other flies, as _Musca_ or _Anthomyia_, may lay their eggs
on food. Flies of the genus _Anthomyia_ tend to lay their eggs on
plants.
It is possible for a fly to deposit its eggs or larvae about the anus
while the man is at stool.
Great care must always be observed to assure one’s self that fly
larvae, which may be present in the stool, have not originated from
larvae deposited on the stool subsequent to its passage.
DETERMINATION OF DIPTEROUS LARVAE
There are certain points in the anatomy of dipterous larvae which
must be considered in recognition of the genus or family of the
flies concerned in the various myiases. The broad extremity is the
posterior one and the tapering one the anterior. The dark hook-like
processes, which may be in pairs or fused, project from the anterior
or head end and above them is a pair of projecting papillae. The
second segment from the head has on either side projecting hand or
fan-like structures with varying numbers of terminal divisions, 4 to
40 or more. These are the anterior spiracles.
The large terminal segment has on its posterior surface two
chitinized plates with 3 slits of various architecture in each.
These are the posterior stigmal plates and are the structures we
pay particular attention to in identification. In the early larval
stages there is only one slit; in the second stage there are two.
It is only in the fully developed larval stage that we note the
characteristic 3 slit stigmal plates. The presence or absence of a
rounded protuberance or button at the base of each stigmal plate
should be looked for. The area carrying the stigmal plates may be
sunken to form a pit. (See Fig. 135.)
KEY TO LARVAE OF THE MYIASES. (BANKS.)
1. Body with lateral and dorsal spinose processes Homalomyia.
Body without such processes 2
2. Body ending in two fleshy processes; rather small
species 3
Body truncate or broadly rounded at end 4
3. Processes bearing the stigmal plates; body about
5 mm. long Drosophila.
Processes not bearing the stigmal plates; body 10
mm. or longer Piophila.
4. But one great hook; posterior stigmal plates with
winding slits; no distinct lateral fusiform areas;
tip of body with few if any conical processes Muscinae.
With two great hooks; slits in the stigmal plate
not sinuous 5
5. No tubercles about anal area; no distinct processes
around stigmal field 6
Distinct tubercles above anal area; often processes
around stigmal field; lateral fusiform areas
usually distinct 7
6. Stigmal plates on black tubercles; lateral fusiform
areas distinct Ortalidae.
Stigmal plates barely if at all elevated; lateral
fusiform areas indistinct; stigmal plates often
contiguous or nearly so; slits long and
subparallel Trypetidae.
7. Slits in stigmal plates rather short, and arranged
radiately 8
Slits slender and subparallel to each other 9
8. Two tubercles above anal area; stigmal field with
distinct processes around it Anthomviidae.
Four or more tubercles above anal area; slits of
stigmal plates usually pointed at one end Muscinae.
9. A button to each stigmal plate; slits rather
transverse to body Calliphorinae.
No button to stigmal plates, slits of one plate
subparallel to those in opposite plate; plates
at bottom of a pit Sarcophagidae.
A specimen of stool containing fly larvae may be incubated in a moist
chamber in order to obtain the imago for species determination.
CHAPTER LI
THE JOINTS, BONES AND MUSCLES IN TROPICAL DIAGNOSIS
In considering the diagnostic significance of bone and joint
manifestations of tropical diseases, it is essential that the
practitioner in the tropics bear in mind the cosmopolitan
arthropathies.
It should be remembered that lesions of joints may accompany
or follow almost all infectious diseases, and that it is often
impossible to ascertain if the lesions be due to the actual
presence of organisms within the joint or to the action of toxic
substances elaborated elsewhere; so that infectious arthritis
is broadly defined as arising from the presence within the body
of a focus of infection. This definition is further expanded to
include joint affections of intestinal origin, and also those
in which neither the causal organism nor its focus of origin is
discoverable, but which by analogy we unhesitatingly recognize as
being due to an infective agent.
It is to be noted that the lesions of arthritis may develop either
in the intra-articular membranes or in the bony parts adjacent to a
joint, and that they may remain confined to their primary site or
eventually extend to involve other tissues.
INFECTIOUS ARTHRITIS
A. Of known etiology.
May be acute or chronic. Examples are: Gonorrhoea, typhoid,
tuberculosis, bacillary dysentery, pneumococcus infections,
pyogenic cocci, filariasis, Malta fever, secondary to any
recognized focus.
B. Of unknown etiology.
May be acute or chronic: Examples are: Acute articular rheumatism,
rheumatoid arthritis, four types beginning with acute symptoms, one
type having insidious onset. These are often due to unidentified
foci.
NONINFECTIOUS ARTHRITIS
A. Traumatic.
1. Acute, due to known traumatism.
2. Chronic, generally static in origin, or due to chronic strain
or irritation. Possibly includes villous arthritis of the knee and
hypertrophic arthritis in the young.
B. Trophic.
1. Metabolic. Examples are gout, psoriasis and probably
hypertrophic arthritis.
2. Senile.
3. Neuropathic. Examples are tabes, leprosy, syringomyelia,
Raynaud’s disease, and scleroderma.
4. Arteriosclerotic.
C. Blood dyscrasias, as haemophilia, anaemias and scurvy.
D. Toxic, as lead poisoning.
The diseases of more peculiar importance for the tropics in which
joint involvement must be considered in the diagnosis are the
following:
_Malta Fever._—This infection offers a good example of a disease
in which joint symptomatology is of diagnostic and therapeutic
importance. A prolonged typhoid-like course with sudden and painful
swelling of various joints, hip, shoulder, ankle or costo-vertebral
articulations, if occurring in the endemic area of Malta fever,
would at once make one suspect this disease. Typhoid does not give
painful joints, dengue is not accompanied by joint swelling, while
gonorrhoeal polyarthritis will be accompanied by other evidence of
gonorrhoeal infection.
The neuralgias, sciaticas and painful joints, together with the
sweats which exhaust the sufferer from Malta fever, often tempt
both patient and physician to resort to narcotics. Acute or
subacute effusion into one or more joints is present in at least
40 per cent of cases of Malta fever according to Rogers. The Malta
fever joint is not red, which fact, taken with its evanescent
character, differentiates it from the arthritis of acute rheumatic
fever.
_Dengue._—Sporadic dengue is difficult to diagnose. In an epidemic
the characteristic pains referable to tendinous insertions about
joints are present in at least 50 per cent of cases and is of great
diagnostic value. There is no swelling of the joints although the
turgescence of the skin over them may give the impression of an
arthritis. The intensity of pain varies from a feeling of muscular
soreness to excruciating pain when muscles or joints are actively
moved. Passive movement is not usually painful. In addition to
the rachialgia, bone and joint pains, some writers have described
swelling of the joints. This in my experience is unusual. Joint pains
are so characteristic that they distinguish dengue from all other
eruptive fevers.
Joint pains during convalescence may produce stiffness and
crippling continuing for many weeks after the cessation of fever.
_Relapsing Fever._—Bone, muscle and joint pains are practically
always present in this disease. In addition rachialgia and headache
are prominent symptoms and the aching gnawing pains in loins or nape
of neck may make one think of beginning smallpox, dengue or yellow
fever. There is no swelling of the joints in relapsing fever. As
in dengue the pains in the neighborhood of the joints may be quite
persistent.
_Yaws._—This disease gives us bone, joint and muscle lesions
similar to those of syphilis. From the mother lesion to the tertiary
framboesioma the course and symptoms of the two diseases are
similar. Thus we may have the flying pains and osteocopic pains of
the early days of infection and, as later events, chronic synovitis,
frambroesial infiltration of perisynovial membranes, frambroesial
infiltration of synovial membranes, chondro-arthritis, epiphysitis
and chronic frambroesial periostitis. These pathological processes
cause such conditions as we know under the names dactylitis, saber
shin, mutilating oro-rhino-palato-pharyngeal ulcerations, Parrot’s
nodes and cranio-tabes.
The uncomplicated framboesioma must be pathologically similar
to the gumma. Certainly the later effects of bone and joint
destruction and scarring are wonderfully like some of the
middle-age European descriptions “when lues was in flower.” In
framboesial disease the damage from bone destruction or from
contracture following cicatrization may be so complete as to render
useless a finger, a hand, one of the large joints or even a whole
extremity.
_Bacillary Dysentery._—As far back as the 17th century (Sydenham)
it was noted that joint pains or actual arthritides were occasional
complications of dysentery. We now know that the bacterial types
of dysentery are those most likely to show joint complications.
Because the joint fluid in these lesions is usually sterile, it is
assumed that they are the effect of toxins (or a toxin) produced by
_B. dysenteriae_. Of the two hypothetical toxins of the dysentery
bacillus one is supposed to produce neuritis and joint complications.
Arthritides are more common in some epidemics than in others and
with certain strains of bacilli than with others. The Shiga strain
is the worst offender in this regard. Manson reports 27% of joint
involvement in one epidemic.
Clinically, dysenteric arthritis is more apt to affect one of the
larger joints, the knee, ankle and hip, being most affected. The
elbow, wrist or shoulder joint may be affected, though this is
unusual. The pain and swelling may be an incident of the early part
of the attack. Usually it comes on when the acute symptoms are
abating or as a sequela. The joint is distended with effusion and
this involves the ligaments around the joint. Given an arthritis
in the course of a frank dysentery there is nothing it could
ordinarily be confused with. It is well to remember, however, that
patients with dysentery may have also a concurrent gonorrhoea or
arthritis from some focal infection. The dysenteric rheumatism
ordinarily completely subsides with the cure of the colitis.
In hepatic abscess following _amoebic_ colitis pain of some type is
a frequent symptom. Rheumatic-like pains and swelling of the hands
occur rarely, rapidly disappearing when the abscess is evacuated.
_Filariasis._—Maitland and Bahr have noted a synovitis which is
apparently a complication of filariasis. Bahr has found a fibrotic
ankylosis often to follow such a joint condition. The synovitis may
be followed by pus formation with serious or fatal outcome.
_Guinea Worm Disease._—Very rarely the female _Dracunculus_ may
penetrate a joint and cause synovitis or arthritis.
_Leprosy._—Occasionally there is joint involvement, especially of
the wrist and ankle joints, in which erosion of the cartilage and
bone dislocation occur giving us a condition similar to the Charcot
joint.
It will be remembered that the Charcot joint is most often seen
in tabes and may give one of the greatest joint swellings. As a
rule only one joint, usually knee or hip, is involved in tabes and
the affection is generally painless. The progress may be acute,
subacute or chronic. Syringomyelia, a disease which may be confused
with leprosy, may also show joint involvement, usually of the upper
extremity.
BONE AFFECTIONS
_Mycetoma._—As the result of the invasion of an extremity—usually
the foot—with the causative fungi, disorganization of the tissues
involved takes place. The granulomatous process invades muscles
and bones and as a result of the sinus formation we have the bones
converted into a softened, cheesy mass. This disintegration of bone
and other tissues is attended with little or no pain. The granules
discharging through the sinuses make for a proper diagnosis.
_Goundou._—In goundou the nasal bones and the nasal processes of the
superior maxilla are the seat of symmetrical swellings of the nature
of an hypertrophic osteitis. These exostoses may be quite large so
that there is interference with vision. There is little or no pain
connected with the bony growths and there is no invasive tendency.
_Big Heel._—There has been observed in natives of the Gold Coast
an affection of the os calcis somewhat like that involving the
superior maxillary bones in goundou. The disease begins with pain and
tenderness of one or both heels. The enlargement may involve only one
os calcis or affect both bones. There is no joint involvement but
locomotion is interfered with. There are periods of improvement which
are followed by return of the pains.
_Ainhum._—In this disease there is thinning or absorption of the
bones of the toe. A fibrous cord replaces the bony structures.
_Oroya Fever._—In this very serious disease of certain areas of Peru
the bone pains may be excruciating. These bone pains are especially
marked in the sternum but also involve the long bones.
_Trench Fever._—Pain over the shin bone is a prominent complaint in
this affection so that the term “trench shin” has been employed.
_Relapsing Fever._—Bone pains, especially referred to the knees, are
complained of by patients with the bilious typhoid of Griesinger.
This is a type of relapsing fever occurring in Egypt.
_Leprosy._—The bone affections of leprosy are considered under the
muscles.
MUSCLE INVOLVEMENT
_Leprosy._—In this ancient disease the course of which is marked
by anaesthesia, atrophy, absorption and accidents (cigarette burns,
etc.), the lesions of bones, joints, muscles and indeed of all other
tissues are, in great part, due to infiltration of nerves by the
organism of leprosy. The effects are secondary and trophic on the
one hand, and on the other partly due to secondary infection of
the leproma by various bacterial agents. Leprosy was for centuries
confused with other diseases in which ulceration and mutilation
are features. The value of mercury in differentiating syphilis,
the recognition of the importance of anaesthesia in this disease,
together with the discovery of the bacillus of leprosy and of the
etiological factors of several other confusing diseases, have made of
leprosy one of the easiest of all diseases to diagnose correctly. It
is, however, essentially a laboratory diagnosis.
In nerve leprosy we often get atrophy of the small muscles of the
hand and of the muscles of the forearm. The contracture which
takes place under these circumstances gives the “claw hand.” In
tubercular and mixed forms of leprosy we may get in addition
trophic disturbances of the fingers and toes and also extraneous
infections which may ultimately result in amputation of fingers
or toes. This process, going on over a considerable time or being
repeated, results often in stumping of fingers or hands or toes and
feet.
In addition to these openly destructive processes there is often
seen in leprosy a condition of subcutaneous absorption of all the
tissues. In this way the distorted finger nail may come to occupy a
seat over the knuckle or even (though rarely) further up the back
of the hand or arm. Briefly in leprosy we have, as representing the
pathology, muscular atrophy from nerve involvement, periostitis
and arthritis, interstitial absorption of bone and contractures
resulting in mutilation of fingers, toes, hands and feet from
trophic disturbance and intercurrent bacterial infection.
_Beriberi._—In this disease we have muscular atrophies, especially
of the muscles innervated by the peroneal and ulnar nerves, similar
to those following other forms of peripheral neuritis.
_Amoebiasis._—There have been reported very rarely disintegrating
lesions of muscles and cutaneous tissues in which amoebae have been
found.
_Heat Cramps._—In those working in firerooms or steel-mills,
the excessive heat to which they are subjected may cause various
manifestations of heat prostration, among which the painful muscle
cramps are prominent. These cramps are similar to those which are
such a feature of Asiatic cholera and in each instance are supposed
to be the result of dehydration of muscle tissue.
_Trichinosis._—Acute muscle pain is a feature of the stage of muscle
penetration by the larval _Trichinella spiralis_. In the disease we
have a fever suggestive of typhoid fever and oedema about the face.
A marked eosinophilia is characteristic. Another helminthic parasite
which may invade the muscles of man is the larval _Taenia solium_.
This must be of extreme rarity because infection with the adult _T.
solium_ is most rare and it is only accidental that the embryonic
stage would occur in man. It is a fact that the common tapeworm of
man, _Taenia saginata_, is found in the human host only as a sexually
mature parasite in the intestines; there is never a cysticercus stage
in the muscles.
_Myositis purulenta tropica._—We may have a suppurative myositis
with a single abscess formation or with disseminated foci or a
diffuse purulent infiltration. The attending fever and toxaemia
are similar to those attending any deep abscess formation. Abscess
formation in the muscles has been reported from various parts of
the tropics, especially the Gold Coast. It is possible that _F.
bancrofti_ infections are concerned in some of these conditions.
_Filariasis._—Filarial abscesses were found in the ilio-psoas
muscles in four cases. Wise and Minett found evidences of adult
filarial worms (_F. bancrofti_) in 22 out of 28 deep-seated
abscesses, which were examined by them.
CHAPTER LII
NEUROLOGICAL CONSIDERATIONS IN TROPICAL DISEASES
There is a great tendency in the tropics to ascribe neurological
manifestations to beriberi or malaria. It must be acknowledged,
however, that various sensory and motor phenomena, which may show
themselves from time to time, in those who have suffered from
beriberi, are common and prove sources of confusion in diagnosis.
Tropical sunlight with its ultra-violet rays had a vogue which held
sway for a brief period as explaining most nervous conditions in
Europeans in the tropics. At present we are inclined to believe
that excesses in eating and drinking and late hours may be more
potent in the production of nervous breakdowns than are factors less
cosmopolitan.
While syphilis is rampant in many parts of the tropical world the
usual views are that the luetic neurological manifestations, so
common in temperate climates, are more or less nonexistent. At the
same time it would seem advisable with this point in view to study
the cases attributed to other causes along the line of laboratory
investigations of the cerebro-spinal fluid.
Clinically there are many points of difference between syphilis
as seen in the native races of tropical regions and as observed
in Europeans at home, and it would seem advisable to do more work
along the line of spinal fluid examinations. The examination of the
spinal fluid for syphilis should include a Wassermann test using
several concentrations ranging from 0.2 to 1.0 cc., a globulin
estimation, cell count and Langes colloidal gold reaction,—the
last not being necessary however, unless positive findings are
obtained in one or more of the other tests. Of course the most
important test is the Wassermann of the spinal fluid and every one
should bear in mind the marked complement fixation power of the
spinal fluid of paretics. In such a fluid we almost always obtain a
positive reaction where quantities of 0.2 cc. or less are employed,
while with locomotor ataxia or cerebro-spinal lues amounts of 0.5
to 1 cc. are generally required to give a positive test. It is not
necessary to inactivate spinal fluid.
These tests can only be carried out in a well equipped laboratory
and the same is true of the colloidal gold one. The tests for cell
increase and globulin increase, however, can be made by anyone
prepared to do ordinary clinical laboratory work.
_The normal spinal fluid_ is as clear as water, has a specific
gravity of about 1.010 and is under a pressure of about 5 to 7 mm.
of mercury or 60 to 100 mm. of water. The sugar content is about
0.07% and the proteid content about 0.03 to 0.04%.
CEREBRO-SPINAL FLUID EXAMINATIONS
To withdraw spinal fluid for bacteriological examination or
cytodiagnosis we use a sterile needle about 4 inches long for an
adult, preparing the skin as described for blood cultures from
a vein (see page 516). The patient is placed on the left side
with knees drawn up and head and shoulders carried forward to
give the greatest possible space between the spinous processes by
arching the spine. A line at the level of the iliac crests passes
between the third and fourth lumbar vertebrae. Select a point
midway between the spinous processes of these lumbar vertebrae
and enter the needle two-fifths of an inch to the right of this
point, pushing the needle inward and upward. Collect the material
in two or three sterile test tubes, to avoid contamination of the
entire sample by a drop of blood which may come out in the first
portion. The presence of blood in very slight amount interferes
with cytodiagnosis and globulin tests and, if present in more than
a trace, it makes the colloidal gold test practically worthless.
Make cultures on blood serum at the earliest possible moment.
Centrifugalize a portion of the fluid at high speed and examine
the sediment for bacterial content. After the puncture the patient
should drink a glass or so of water and remain in bed for a day,
preferably with the head lower than the feet.
In general terms, excluding syphilis, it may be stated that:
1. A lymphocytosis indicates a tuberculous or poliomyelitis process.
With these diseases, the fluid will probably be clear.
2. An abundance of polymorphonuclear and eosinophilic leucocytes
indicates an infection with pyogenic organisms, in which cloudy fluid
is the rule.
Meningism shows very few cells.
Trypanosomiasis gives a cellular increase very similar to syphilis.
In the work of the French Sleeping Sickness Commission five cells per
cubic millimeter was taken as normal.
Not only may trypanosomes be found in the spinal fluid, when
they mark the setting in of the “sleeping sickness” stage of
trypanosomiasis, but a case has been reported of the presence of
_Trichinella_ embryos in the spinal fluid. Recently a few cases
have been reported of anthrax meningitis, in which anthrax bacilli
have been found in the spinal fluid.
=Cell Count.=—A method of examination considered by neurologists as
of differential diagnostic value is to count the number of cells in a
cubic millimeter of the cerebro-spinal fluid. The technic is to use a
gentian-violet-tinged 3% solution of acetic acid. This is drawn up to
the mark 0.5, and the cerebro-spinal fluid is then sucked up to 11.
After mixing, the cell count is made with the haemacytometer.
Count all the cells appearing in the entire ruled area (9 large
squares) and add one-sixth of this number to find the approximate
total number of cells per cubic millimeter of spinal fluid
examined as above. It is advisable to make the cell count of the
fluid as soon after obtaining it as possible, the cells tending
to degenerate or adhere to the glass of the tube. The latter can
be minimized by vigorous shaking before withdrawal of the fluid
for counting. Normally we have only two to ten cells per cubic
millimeter, but in tabes and general paresis this is increased to
50 or 100 cells, greatest at onset of disease.
_Pleocytosis._—Miller gives the following table as to pleocytosis:—
AVERAGE INCIDENCE OF LYMPHOCYTOSIS IN THE SPINAL FLUID
(Plaut, Relim and Schottmuller)
--------------------+-----------+-------------------------------------
Clinical diagnosis | Frequency,| Remarks
| per cent. |
--------------------+-----------+-------------------------------------
Cerebro-spinal lues | 85-90 | Counts often over 100—may reach
| | 1000 per c.mm.
--------------------+-----------+-------------------------------------
Tabes dorsalis | 90 | Counts usually under 100.
--------------------+-----------+-------------------------------------
General paresis | 98 | Counts average 30-60 cells per c.mm.
--------------------+-----------+-------------------------------------
Secondary lues | 30-40 | Moderate increase as a rule.
--------------------+-----------+-------------------------------------
Multiple sclerosis | 25 | Border-line counts.
--------------------+-----------+-------------------------------------
Cerebral haemorrhage| {Frequency|
Cerebral tumors | { is | Cellular increase is apt to be a
Sinus thrombosis | { variable| very moderate one.
--------------------+-----------+-------------------------------------
_Globulin Increase Tests._—Noguchi’s butyric acid test is very
satisfactory, but because of the objectionable odor of the butyric
acid, we use the Ross-Jones and Pandy tests routinely in our
laboratory.
For the Ross-Jones method, one cc. of saturated solution of
ammonium sulphate is placed in a small test tube and one cc. of
spinal fluid placed on top of this column. If globulin increase
is present a turbid ring appears within a few seconds at the
junction. Normally there is no sign of a ring. This test is a
modification of Nonne’s Phase 1 reaction. For Pandy’s test, prepare
a saturated solution of carbolic acid crystals in distilled water.
Place 1 cc. of this reagent in a small test-tube and add 1 drop of
spinal fluid. In a normal fluid, only the faintest opalescence is
observed; but in a fluid with globulin increase a smoke-like white
cloud develops instantly where the drop comes in contact with the
reagent.
=Colloidal Gold Test (Lange’s).=—It is now generally accepted that
this test is more diagnostic of general paresis than any other single
test. The color changes in the first five tubes (1-10 : 1-160)
are so constant that the term “paretic curve” is applied to such
findings. Of less diagnostic value are the so-called cerebro-spinal
lues curves where the color changes, though of less intensity than
the paretic ones, are most marked in the third, fourth, fifth and
sixth tubes (1-40 to 1-320). In various types of meningitis, other
than luetic, the color changes are at times more marked in the tubes
with the higher dilutions of spinal fluids (from 1-320 to 1-2560).
The paretic curve of the colloidal gold test generally runs
parallel with a spinal fluid Wassermann and globulin increase. This
agreement does not exist at all constantly for positive blood serum
Wassermann tests and increased cell counts.
It may be stated that this test is of more importance in paresis
than any single one of the four reactions of Nonne, viz.: (_a_)
blood serum Wassermann; (_b_) spinal fluid Wasserman; (_c_)
globulin increase, and (_d_) increased cell count of spinal fluid
(pleocytosis). Of course, all of these tests should be carried out.
_Test._—The test is carried out by preparing a series of ten
test tubes containing dilutions of spinal fluid in 1 cc. of
normal saline, ranging from 1-10 to 1-5120, and adding 5 cc. of
the colloidal gold reagent to each tube and to a control tube
containing salt solution alone. The successful application of
the test is dependent upon (_a_) care in the preparation of the
reagent; (_b_) absolute cleanliness of all glassware used, and,
(_c_) on the entire absence of blood from the spinal fluid. Before
using a new colloidal gold solution, it should be tested with
spinal fluid of known reaction, so that it may be discarded if
too sensitive or not sufficiently so. The color changes usually
start almost immediately and if there is no change evident in half
an hour, there will probably be none later. The maximum change
occurs after several hours, so that readings are made after the
tubes have stood overnight at room temperature. The proper color
of the control in tube 11 should be salmon-red or old rose and the
fluid should be perfectly transparent. When the color is changed
in tubes containing dilutions of the spinal fluid we record one
showing a bluish tint as 1. When the change is to a lilac we record
it as 2. A distinct blue is marked as 3 and a pale blue as 4. When
decolorization is complete there is the highest color change, which
is noted as 5.
_Mastic Test._—The mastic test as devised by Cutting is apparently
of value as an aid in the diagnosis of syphilis of the nervous
system. The test is made by treating six dilutions of spinal fluid
in test tubes with an alcoholic extract of pure gum mastic, diluted
with distilled water before using. Its great value lies in the ease
of preparation from an effective gum mastic, and in the keeping
qualities of the stock alcoholic extract. After standing at room
temperature for twelve to eighteen hours or at 37°C., for six to
twelve hours, readings are made. In positive cases (paresis) the
mastic will be precipitated in the first one, two, three or four
tubes (higher in strongly positive cases) leaving the supernatant
fluid clear, with the mastic as a white flocculent precipitate at
the bottom of the tube. In some positive reactions the opalescence
of the fluid persists with a fine white precipitate at the bottom.
The control tube must remain unchanged.
SHOWING THE AVERAGE FREQUENCY OF THE VARIOUS REACTIONS IN SYPHILIS OF
THE CENTRAL NERVOUS SYSTEM (MILLER)
-----------------------+---------------+----------------+---------------
| Paresis | Tabes dorsalis | Cerebro-spinal
| per cent. | per cent. | syphilis
-----------------------+---------------+----------------+---------------
Blood Wassermann | 98-100 | 70 | 70-80
Spinal fluid Wassermann| 97 | 60-80 | 85-90
Pleocytosis | 98 | 85-90 | 85-90
Positive globulin test | 100 | 90-95 | 90-95
Colloidal gold test | 98-100 | 85-90 | 75-80
| Paretic curves| Luetic type of | Luetic curve
| | curve |
-----------------------+---------------+----------------+---------------
_Other Chemical Constituents._—Normally the fluid reduces Fehling’s
or Benedict’s qualitative copper solutions. It is well for one to
gain experience with the degree of reduction to be normally expected
as the test is but slightly marked. Quantitatively, the reducing
substance is equivalent to 60-70 mg. glucose per 100 cc.
The urea is practically the same as in the blood, parallels any
change in the latter, and has the same significance. Creatinine
is about half that of the blood, and has apparently no clinical
significance. Uric acid is present in still smaller proportion.
DELIRIUM AND COMA
It is difficult to make a sharp distinction between a disease showing
delirium and one showing coma as delirious states tend to be followed
by coma or such conditions may alternate.
In _yellow fever_ the alert, suspicious mental state may give way
to one of marked delirium requiring close watching to prevent the
patient throwing himself from his bed.
In _plague_ there is more of a mild delirious state in which the
patient has a great tendency to wander about. The mental state is
rather that of an intoxicated person with the thickness of speech
and retardation of mental processes.
_Typhus fever_ and _spotted fever of the Rocky Mountains_ tend to
produce stuporous states.
A delirious state, especially at night, is often noted in
_tsutsugamushi_.
_Rat bite fever_ also tends to show delirium.
In the ordinary paroxysm of _malignant tertian_ there is quite a
tendency to flightiness during the prolonged hot stage. In the
cerebral types of pernicious malaria there may be violent delirium
followed by coma or the patient may be comatose from the onset of
the paroxysm. Such conditions are often mistaken for sun stroke. In
the comatose form of malaria we have a high temperature with sighing
or stertorous breathing and at times Cheyne-Stokes respiration.
Following upon the algid stage of _cholera_ we may have a stage of
reaction without the disappearance of anuria, in which a typhoid
state, with low muttering delirium or even with an acute delirious
state, supervenes.
Toward the end of the sleeping sickness stage of _trypanosomiasis_
we have a subnormal temperature with a comatose state.
Comatose states following upon the acute confusional psychoses of
_pellagra_ are not uncommon. Pellagra may show an acute collapse
delirium.
In _heat stroke_ we may have either delirium or coma. There is no
more difficult problem encountered in the tropics than the one of
differentiating cerebral malaria from heat stroke.
_Oroya fever_ is frequently accompanied by delirium.
In _typhus fever_ (tabardillo) delirious or stuporous states are to
be expected about the end of the first week or even earlier. This
is a disease in which the clouding of the consciousness is almost
as marked as in plague. Delirium is more apt to occur at night.
In very toxic cases of _bacillary dysentery_ there may be a mild
delirium.
=Insomnia.=—Sleeplessness or, at any rate, a condition where the
patient only dozes is often seen in _dengue_. This mental alertness
and wakefulness may also be noted in _yellow fever_. In malaria,
possibly connected with quinine administration, we may have marked
insomnia although cases have been reported of insomnia due to malaria
which has been relieved by quinine.
Just as cardiac decompensation from any cause will be attended by a
distressing insomnia so is this also a feature of _beriberi_ where
cardiac involvement is marked.
_Liver abscess_ may be attended with insomnia.
_Malta fever_ is often attended with a weariness from suffering with
the various joint and nerve pains so that insomnia is often marked.
Even in _trypanosomiasis_ insomnia may be present at first.
Insomnia is also one of the early neurasthenic manifestations of
_pellagra_.
=Somnolence.=—The disease in which this symptom is best known is
_sleeping sickness_. The patient may go to sleep lying in the bright
sunlight or in the midst of eating a morsel of food. These cases can
be easily aroused but quickly drop off to sleep afterwards. They
often deny that they were asleep. Later on in sleeping sickness the
patient may sleep from 24 to 36 hours continuously and a more marked
tendency to somnolence may be present by day than by night.
In the prodromal stage of _leprosy_ somnolence is often marked and
accompanied by a sensation of unaccountable weakness. Sweatings and
accessions of fever may also be noted at this time.
In _plague_ the rather stuporous state of the patient may give the
impression of somnolence.
CEPHALALGIA, RACHIALGIA AND OTHER PAINS
_Yellow fever_ is marked by pains in the lumbar region, the _coup de
barre_ of the French. It is as if the patient had been beaten over
the small of the back with a bar of iron. The headache is rather
orbital and is often excruciating. There are also frequently heavy,
dull pains of the extremities.
_Blackwater fever_ also has marked pains in the lumbar region giving
expression to the kidney damage done by the haemoglobin detritus
plugging the tubules.
In all forms of _malaria_, but especially in the paroxysms of
malignant malaria, there are severe headaches and pains in the
extremities. Intermittent neuralgia is often regarded as malarial.
_Dengue_ gives rise to a marked post-orbital soreness rather than
pain. There is also a marked rachialgia with pains in the limbs
often referred to the regions of the joints, which, however, are not
swollen.
In _Malta fever_ the neuralgias, especially sciatica, often
associated with suddenly appearing, painful joint swellings, are
prominent features.
In _trypanosomiasis_ headache is often marked, together with a
characteristic deep hyperaesthesia, so that the striking of a limb
against a hard object gives rise to excruciating pain, there being,
however, a delay in the experiencing of the painful sensation.
In _relapsing fever_ the headache is often intense with pains in the
back and bones.
In _cholera_ one of the most striking phenomena of the disease
is the terrible cramping of the muscles, especially those of the
calves and feet. These pains actually torture the patient. Cramps
of abdominal muscles as well as those of extremities are often
noted in _heat stroke_ in men in firerooms.
In _beriberi_ there is often pain in the epigastric region so that
the slightest touch causes great distress. This epigastric tenderness
is also a feature of yellow fever. The calf muscles are also
markedly hyperaesthetic in beriberi.
In _leprosy_ the neuralgic pains may be very severe while the nerves
are being pressed upon by the connective tissue increase of the
endoneurium and perineurium. Mention has been made of excruciating
pains of toes, especially the big toe, even suggesting gout.
The excruciating pains of _Oroya fever_ are connected with the
changes taking place in the bone marrow. There is probably more
rapid alteration in the blood picture in this disease than in any
other. It might be designated a fulminating pernicious anaemia.
Pain on pressure on dorsal or lumbar spine is common in _pellagra_.
_Plague_ may be associated, during the first day or two, with an
excruciating headache. This may even be prodromal but tends to
disappear with the rapidly developing stuporous state of the patient.
In _typhus fever_ boring headache, oppressive rather than
lancinating, is a feature of the first days. It is usually frontal
or temporal.
In _malignant tertian_ the headache is often quite intense during the
prolonged hot stage. The headache of malaria is usually frontal or
suboccipital.
In _trench fever_ we may have a cutaneous hyperaesthesia over the
shins. _Rocky Mountain fever_ shows joint pains.
TREMORS AND CONVULSIONS
It is in _trypanosomiasis_ that we have the most important tremor.
It is the fine tremors, which first are noticeable in the tongue
and later in hands and even legs, that mark the onset of the stage
of sleeping sickness with the trypanosomes in the cerebro-spinal
fluid. At times an intention tremor may be noted in advanced cases
of sleeping sickness. In addition we have epileptiform seizures in
sleeping sickness.
In cerebral manifestations of _pernicious malaria_ there is a type
characterized by epileptiform convulsions.
In the acute stage of _Brazilian trypanosomiasis_ we may have
almost any type of cerebral or cord lesion.
Tremors of tongue and hands may be present in the second stage of
_pellagra_.
Fibrillary tremors have been noted in the main-en-griffe of
_beriberi_ but tremors of the tongue and hands, so common in
alcoholic neuritis, are rare in beriberi.
Convulsive seizures are not uncommon in the hyperpyrexial type of
_heat stroke_.
In infantile beriberi the child often becomes rigid. There is not
a true convulsion but such cases are at times thought to have
meningitis.
In _schistosomiasis_ and _paragonomiasis_ as well as in infections
with the larval stage of _Taenia solium_ we may have brain
involvement and manifestations of Jacksonian epilepsy.
ALTERED REFLEXES INCLUDING SENSORY AND MOTOR DISTURBANCES
_Beriberi._—It is usually stated that the tendon reflexes of the
lower extremity, especially the patellar reflex, are absent. While
this is generally true they may at first show an exaggeration and
some cases do not seem to show any decided change. There may be
striking variation from day to day in the reflexes. The superficial
reflexes, especially the cremasteric, are as a rule more active than
normally.
The sensory changes in beriberi are less marked than those of the
motor side. There is rarely complete anaesthesia but rather a
blunting of sensation. Hyperaesthesia, particularly of the muscles of
the calf of the leg, is well marked when the muscles are grasped with
the hand.
The anaesthesia is earliest noted over the shin bone and dorsum of
the foot. A loss of tactile sense is often noted about finger tips
making it difficult for the patient to button his coat.
The most striking motor phenomena are the foot and wrist-drop,
especially the former. The extensor muscles are more markedly
involved than the flexors. There is marked muscular weakness of
foot as well as hands. The weakness of the muscles of the leg is
often the first symptom to be complained of. The type of palsy in
beriberi is mainly paraplegic although hemiplegic and monoplegic
types have been reported. The paralysis of the diaphragm is the
most serious of the muscle palsies.
Contractures of the muscles of the foot or calf of the leg may occur.
Contractures of the muscles of the upper extremity are more rare.
Muscular atrophy of the leg muscles is often marked. In the upper
extremity the muscles of the hand are most frequently atrophied.
_Pellagra._—There is considerable variation from time to time in the
reflexes. Some authorities attach diagnostic value to the appearance
of an exaggerated reflex on one side and a diminution or absence
of the corresponding reflex on the other side. Ankle clonus may be
present.
Paraesthesias and in particular a burning sensation of the
erythematous areas are often noted. Hyperaesthesia of the dorsal
and lumbar regions is often noted. Pruritus is at times complained
of in the region of the perineum. We have muscular weakness.
_Sleeping Sickness._—The deep reflexes are usually exaggerated and
the superficial ones diminished or absent.
There is no distinct alteration of motor or sensory function except
that of deep hyperaesthesia (Kérandel’s sign). There is usually
marked weakness of muscles of locomotion.
_Leprosy._—The usual statement is that there is an exaggeration of
the deep reflexes. Ankle clonus has been rarely reported.
Anaesthesia is the most important symptom in the diagnosis of
leprosy. This loss of sensation is often for pain and temperature
with retention of tactile sense (dissociation of sensation—a
prominent symptom of syringomyelia). The anaesthesia is not only
found in the spots but associated with the leprous neuritis which
chiefly involves the ulnar, facial and peroneal nerves. Muscle
palsies and atrophies are common and the main-en-griffe appearance
of the hand is seen.
In _lathryism_ we have spasticity and an exaggeration of the
reflexes.
A very remarkable disease called _kubisagari_ or _paralytic
vertigo_ has been observed in Japan. This disease is thought to
affect those living in stables. The attacks only last a few minutes
and at other times the patient seems normal. An attack shows ptosis
and diplopia, speech disturbances and palsy of muscles of back of
neck, causing the head to fall forward. There may also be some
paresis of muscles of extremities. The disease is not fatal. Cases
have been observed in Switzerland.
THE GAIT
There are no gaits in tropical diseases which can strictly speaking
be regarded as special types of gait. In beriberi we often note the
designation _tripod gait_ of _beriberi_. This simply refers to the
manner in which a case of the paraplegic type of beriberi uses a
stick held by his hands to assist him in dragging along his atrophied
and enfeebled legs. The legs are widely separated and the stick
placed in front makes the two legs and stick resemble a tripod.
It is true that beriberics show the steppage gait of multiple
neuritis as, owing to more or less foot-drop and lack of power to
extend the toes, the patient lifts his foot high from the ground to
avoid scraping the toes, and bends to the other side. It is as if a
man were walking through a mire.
When other groups of muscles than the foot extensor ones become
involved the gait is that of extreme weakness—a shuffling one.
In _sleeping sickness_ it is a shuffling gait. It is as if one were
dragging the feet along from pure muscular weakness.
In _pellagra_ we may see a gait in which the patient separates his
legs rather widely and uses a stick in front, shuffling his feet
along with knees slightly bent and soles of the feet scarcely raised
from the ground.
Some cases show a typical spastic paralytic gait.
We often note under _dengue_ the designation dandyfied gait. This
refers to the stilted, mincing gait of a dandy and is probably the
explanation of the derivation of the word dengue. The pains about
the site of the insertions of muscles with the slightest movement
make these patients walk in a stiff, self-conscious manner.
PSYCHIC AND NEURASTHENIC STATES
A very remarkable fact is that in many tropical and subtropical
regions where syphilis is rampant among the natives there is slight
or absent incidence of general paresis and locomotor ataxia.
Jefferys and Maxwell state that the parasyphilitic manifestations
were absent in thousands of cases observed by them in Formosa.
In the Philippines one sees occasionally typical cases of these
parasyphilitic diseases but of course standard methods of treatment
of syphilis have been employed there for many years.
In China, where there is practically no treatment for syphilis,
luetic ulcerations are exceedingly common and it has been suggested
that insufficient treatment cures the skin lesions but adds to
the effects on the nervous system. It will be remembered that
skin and nerve tissue arise from similar embryological layers
(epiblast) hence a suppression of toxic effect on one tissue may
add to the burden on the other. It has been suggested that if the
surface lesions are allowed to develop to maturity, the skin,
which is the great elaborating center for antibodies, will produce
enough adequately to protect the whole body; whereas, if the
surface lesions are aborted, there is a diminished stimulus with
consequent diminished elaboration of protective bodies. The brain
is then liable to parenchymal invasion, since chemicals, owing to
difference in their physical properties, cannot replace natural
antibodies in controlling the disease in this location. This theory
takes no reckoning of differences exhibited by variant strains of
treponema in their tendencies toward selective localization. It has
been noted that the form of syphilis endemic in certain regions is
much less virulent than is the cosmopolitan form.
_Pellagra._—Very important in diagnosis is a more or less
prolonged prodromal period of neurasthenia which is apt to be more
marked in the winter at a time when the skin and alimentary tract
manifestations are in abeyance. Along with the anxiety and unrest of
this neurasthenia we have lack of mental concentration and depression
of spirits.
A melancholic state is almost always present in the psychosis
of pellagra. There is not the indifferent, satisfied, more or
less happy mental state of the case of general paresis. Some
consider the pellagrous psychosis to belong to the toxic group,
as from alcohol or cocaine, while others place it in the group of
infective psychoses, as the post-influenzal one. Gregor regards it
as belonging to the infective-exhaustive group. The insanity of
pellagra is that of an acute confusional one.
In the final cachexia there is a dementia.
_Sleeping Sickness._—It may be many months or even years before the
mental changes follow the trypanosome fever stage. At first a change
in disposition is noted, the patient becoming listless and apathetic.
There is great impairment of mental concentration and memory. There
may be later on catatonic manifestations as echolalia, mutism or
flexibilitas cerea. There may at times be paranoid manifestations
to be succeeded by states of profound melancholia. In the terminal
stage a comatose state overshadows the psychical manifestations.
_Malaria._—Leaving out of account the acute delirious states which
accompany cerebral malaria there have been reported cases showing
various manifestations of psychic disturbances even to maniacal or
melancholic forms of insanity.
It is a common practice to attribute the irritability and lack of
mental concentration of those who have lived for a long time in
the tropics to the damage done the cerebral cortex by the malarial
parasite. It is certainly more reasonable to attribute these minor
psychic disturbances to malaria rather than to actinic rays of the
sun.
There is no doubt but that quinine, given either for treatment or
prophylaxis of malaria, is a cause as potent as alcohol and tobacco
in tropical neurasthenia.
_Insolation._—It is popular to assign neurasthenic manifestations to
the actinic rays of the sun or the tropical heat, as these influences
operate on every resident of the tropics. It is very necessary to
exclude derangements of the digestion due to errors in diet with
resulting exhaustion of the pancreatic and hepatic functions.
Alcohol is a potent factor for tropical neurasthenia as the
tendency is for excess in this direction in those who in temperate
climates are only moderate drinkers.
_Hookworm Disease._—The patients with this disease are apt to become
hypochondriacal and even melancholic.
There is a correspondence between the physical and mental
backwardness of children with this disease, a child of twelve, who
by the Binet-Simon test will only be rated at 7 will also not seem
larger or better developed physically than a child of seven years
would be.
_Malta Fever._—Owing to the neuralgic pains and insomnia patients
with this disease are apt to become neurasthenic. They are peculiarly
liable to form the morphine habit if this drug be placed in their
hands for the relief of pain.
The victims of _leprosy_ not only may show an indifference to their
condition but may also exhibit a moral apathy.
_Dengue_ often shows a rather marked neurasthenia during
convalescence and this may be protracted if the patient tries to
resume his active duties before his complete recovery.
In _latah_ there is echolalia and echopraxia, the patient repeating
words he hears and mimicking movements he sees. The mind is usually
clear. As a matter of fact the symptoms show similarity to those of
the catatonic form of dementia praecox. The disease is more common in
that part of the world centering in the Malay peninsula. Suggestion
is an important factor in this neurosis.
In _amok_, a sort of epileptiform seizure in which the patient is
obsessed with a desire to kill, there may be no recollection of the
running amok. After the attack the patient may be stuporous.
LUNACY IN THE TROPICS
Van Loon, having examined over 200 cases from among 1100 insane
patients in Java, found the most common types of mental disease to be
dementia praecox, general paresis, various manifestations of cerebral
syphilis and acute maniacal or confusional states. Not only were all
forms of mental disorder known in European countries represented,
but their comparative frequency and the types of conduct exhibited
were, on the whole, what might be expected in the study of a group of
similar cases encountered in any other part of the world.
Overbeck-Wright in his book—“Lunacy in India”—notes that 44% of
cases were under treatment for various types of mania, 15.9% for
melancholia, 4.8% for delusional insanity, 5.2% for idiocy, 5.7%
for dementia and 6.6% for insanity following the use of _Cannabis
indica_. It is noted that dementia praecox is not included in the
statistical returns, but the author states that in his experience
hebephrenia and katatonia account for a much larger proportion of
cases than melancholia.
Overbeck-Wright is of the opinion that general paresis is quite
common in India notwithstanding the fact that for many years the
opinion has obtained that syphilis of the central nervous system
and the parasyphilitic diseases were exceedingly rare among
tropical natives. He regards the incidence of cerebral disease
in syphilitic natives as less than with Europeans, attributing
this fact to the existence of an immunity acquired through the
prevalence of syphilis among these people during a period of
several centuries. Cases of general paresis are generally reported
under the diagnosis of chronic mania.
Van Loon also notes the mistake made in most books on tropical
medicine as to the rarity of general paresis. General paresis
being a disease in which we have such characteristic laboratory
diagnostic tests, especially the colloidal gold test, there should
be little difficulty in settling this question of its absence or
relative infrequency among natives of tropical regions.
INDEX
Acanthocheilonema perstans, 339
Acidosis, 525
in blackwater, 58
in cholera, 236
in heat stroke, 468
in kala-azar, 131
Aedes calopus, 105, 433
Agglutination tests, 517
in blood transfusion, 521
in cholera, 230
in dysentery, 184
in Malta fever, 244
Ainhum, 471, 595
Alastrim, 486
Albumin tests, 570
Albuminuria, 574
in blackwater, 61
in malaria, 39
in yellow fever, 110, 574
Alcohol, and neuritis, 270, 287
and liver abscess, 167
Alimentary tract, 586
American leishmaniasis, 138
Amoebae, 148, 158, 159
Amoebic dysentery, 147
Amok, 610
Anaemia, 553
Ancylostomiasis, 319, 493, 546, 548, 554, 563, 567, 609
ancylostoma in, 320
diagnosis in, 329
epidemiology of, 323
geographical distribution of, 320
ground itch in, 328
history of, 319
life history of hookworm, 321
pathology of, 324
prognosis in, 331
prophylaxis in, 331
symptomatology of, 326
Ancylostomiasis, symptoms in detail of, 328
treatment of, 332
Anopheline mosquitoes, 18, 20, 24
Antimony, administration of, 134
Arsenic and beriberi, 270
Arsphenamine, administration of, 96
Arthritis, infectious, 592
noninfectious, 592
Aspergillus fumigatus, 474
Atriplicism, 556
Aural myiasis, 568
Bacillus alkaligines faecalis, infection with, 485
dysenteriae, 175
icteroides, 101
leprae, 248
pestis, 190
Bacterium tularense, 214
Balch’s staining method, 513
Basal metabolism, 489
Benign malaria, 29
Beriberi, 268, 492, 547, 555, 596
acute pernicious, 282
and scurvy, 286
asylum, 279
atrophic, 280
definition of, 268
diagnosis in, 285
endocrine gland disturbances and, 274
epidemic dropsy, 278
epidemiology of, 276
etiology of, 269
food deficiency, 270
geographical distribution of, 269
history of, 268
infantile, 279, 287, 547
paraplegic, 282
pathology of, 277
Beriberi, polyneuritis gallinarum and, 275
prognosis in, 288
prophylaxis in, 288
rice in, 272
rudimentary, 280, 282
ship, 285, 547
symptomatology of, 278
symptoms in detail of, 284
synonyms for, 268
treatment of, 290
types of, 280
vitamines in, 271, 275
wet, 280
Berne, 421
Big heel, 595
Bilharziasis, 357, 360
Bilious remittent malaria, 34
Bilious typhoid of Egypt, 92, 111
Black death, 188
Blackwater fever, 55, 498, 541, 547, 553, 557, 560, 572, 574, 579
complications in, 60
definition of, 55
diagnosis in, 61
epidemiology of, 58
etiology of, 57
geographical distribution of, 56
history of, 55
pathology of, 59
prognosis in, 64
prophylaxis in, 64
symptomatology of, 59
symptoms in detail of, 61
synonyms for, 55
treatment of, 64
Blastomycosis, 474
Blood, chemical analysis of, 530, 576
groups of, 521
specific gravity of, 538
transfusion of, 521
Blood examinations, 504
acidosis in, 525
coagulation rate in, 537
counting cells in, 507, 508
culturing in, 516
differential count in, 514
Blood examinations, dried smears, 509
fresh preparations in, 509
haemoglobin in, 519
in blackwater, 541
in malaria, 39, 539
in kala-azar, 131, 543
staining films, 509, 512
thick films in, 511
wet preparations in, 509
Blood in tropical diseases, 504, 538
blackwater fever, 541
filariasis, 544
kala-azar, 543
liver abscess, 542
malaria, 539
Malta fever, 541
plague, 542
relapsing fever, 544
trypanosomiasis, 543
typhus fever, 546
Weil’s disease, 544
Boils, tropical, 420
Bone affections, 595
Brazilian trypanosomiasis, 80, 501, 548
diagnosis of, 84
epidemiology of, 81
etiology of, 80
prophylaxis in, 84
symptomatology of, 83
transmission of, 81
treatment of, 84
types of, 83
Bronchial spirochaetosis, 550
Bronchomoniliasis, 474
pulmonary tuberculosis and, 474
Bubas, 138, 564
Calabar swellings, 354, 556
Carriers, in cholera, 225
in dysentery, 153, 178
in malaria, 24, 47
Cephalalgia, 604
Cerebro-spinal fluid, 598
Chaulmoogra oil, 266
Chenopodium, 163, 334
Cholera, 218, 492, 547, 579, 597
agglutination in, 230
Cholera, autopsy findings in, 227
blood transfusion, 235
carriers in, 225
definition of, 218
diagnosis in, 230
disinfection in, 233
epidemiology of, 222
etiology of, 220
geographical distribution of, 219
history of, 218
pathology of, 226
prognosis in, 232
prophylaxis in, 233
sequelae in, 229
serum in, 236
symptomatology of, 227
symptoms in detail of, 229
treatment of, 235
vaccination in, 234
water transmission, 223
Cholera red reaction, 232
Cholerine, 229
Chrysomyia macellaria, 422, 551, 568
Chyluria, 346, 575
Circulatory system, 547
Climatic bubo, 469, 552
diagnosis in, 470
symptomatology of, 470
Climatic fevers, 501
Clonorchiosis, 371
symptomatology of, 372
Clonorchis endemicus, 372
Coagulation rate, 537
Coccidioidal granuloma, 474
pulmonary tuberculosis and, 474
Coccidioides immitis, 474
Cochin China diarrhoea, 312, 374
Colloidal gold test, 600
Colon bacillus infection, 484
Color index, 520
Coma, 602
Conorhinus rubrifasciatus, 123
megistus, 80
Convulsions, 605
Cosmopolitan diseases, 480
Craw-craw, 424
Creeping eruption, 422
Cryptococcus gilchristi, 474
Culex fatigans, 432, 342
Culicine mosquitoes, 20
Culturing blood, 516
Cutaneous system, 561
Cyclops, 356
Danysz’s virus, 210
Delirium, 602
Dengue, 431, 495, 545, 563, 593, 608, 609
clinical types, 435
definition of, 431
diagnosis in, 436
epidemiology of, 432
etiology of, 432
geographical distribution of, 432
history of, 431
mosquitoes in, 432
pathology of, 434
prophylaxis in, 438
spirochaetes in, 432
symptomatology of, 434
symptoms in detail of, 436
synonyms for, 431
treatment of, 438
Dengue-like fevers, 438
Dermatobia cyaniventris, 421
Dermatophiliasis, 418
Dhobie itch, 414
Diagnosis in tropics, 477
Diarrhoea, 589
Diphtheria, 487
Dracunculus medinensis, 339, 355
Dysentery, 141
bacterial, 145, 174
ciliate, 143
definition of, 141
etiology of, 142, 148, 175
flagellate, 142
from animal parasites, 142
from poisons, 146
helminthic, 145
protozoal, 142
Dysentery, (amoebic), 147, 492, 554, 596
Charcot-Leyden crystals in, 157
complications in, 155
diagnosis in, 156
epidemiology of, 153
etiology of, 148
geographical distribution of, 148
history of, 147
pathology of, 154
prophylaxis in, 160
symptomatology of, 154
transmission of, 153
treatment of, 160
Dysentery (bacillary), 145, 174, 501, 545, 548, 567, 594, 603
chronic, 182
collapse types, 181
complications in, 181
diagnosis in, 182
epidemiology of, 177
etiology of, 175
gangrenous, 181
geographical distribution of, 174
history of, 174
pathology of, 179
prophylaxis in, 185
symptomatology of, 180
treatment in, 186
vaccination against, 185
Ear diseases, 568
Ekiri, 145
Elephantiasis, 347
of scrotum, 348
Emetine, 160, 171, 318
Endemic haematuria, 363
Endocrine disturbances, 489
Entamoeba coli, 149, 150
histolytica, 142, 148, 164
tetragena, 149
Eosinophilia, 533
Epidemic dropsy, 278
gangrenous rectitis, 589
Epistaxis, 569
Espundia, 138, 564
Eye diseases, 565
Faeces, 581
intestinal parasites, 583
occult blood in, 582
ova in, 583
Fasciolopsis buski, 373
Fever-free diseases, 491
Filaria bancrofti, 337, 341
Filariasis, 336, 493, 544, 550, 552, 564, 566, 575, 594, 597
abscesses in, 346
and chylous hydrocele, 351
chyluria, 346, 575
clinical types, 344
diagnosis in, 351
elephantiasis, 347
elephantoid fever, 345, 493
etiology of, 337
history of, 339
life history of F. bancrofti, 342
mosquitoes in, 342
orchitis in, 347
pathology of, 343
scrotum in, 345
varicose groin glands in, 345
Flagellate dysentery, 142
Flagellated body, 8
Fleas in leishmaniasis, 124
in plague, 192
Focal infections, 490
Framboesia, 384
Funiculitis, endemic, 346, 580
Gaits, 607
Gametes in malaria, 8
Gangosa, 395, 550, 569
and yaws, 395
diagnosis in, 398
epidemiology of, 397
etiology of, 395
geographical distribution of, 395
history of, 395
pathology of, 397
symptomatology of, 397
treatment of, 398
Genito-urinary system, 570, 579
Giardia, 142
Giemsa’s stain, 514
Glanders, 487
Glandular fever, 536
involvements, 551
Globulin increase, 600
Glossina morsitans, 67, 71
palpalis, 66, 69
Goundou, 472, 569, 595
Granuloma venereum, 404
diagnosis in, 406
etiology of, 404
history of, 404
pathology of, 404
symptomatology of, 405
Guha, 551
Guinea worm, 339, 340, 355, 595
Haemacytometry, 505
Haematoxylin staining, 514
Haematuria, 575
Haemoglobin estimations, 519
Haemoglobinuria, 574
haemoglobinuric fever, 55
paroxysmal, 61, 574
Haemolysis, test for, 521
Haemorrhages, 554
Haemosporidia, 4
Haffkine’s plague prophylactic, 211
cholera vaccine, 234
Heat prostration, 464, 467, 494
cramps, 467, 597
stroke, 464, 501, 550, 573, 603
etiology of, 464
susceptibility to, 466
symptomatology of, 466
treatment of, 467
Hill diarrhoea, 316
Hirudiniasis, 559
Hosts, 9
Impetigo, 419
Index of malaria, 9
Infantile beriberi, 279
scurvy, 287
Influenza, 488
Insolation, 464, 609
Insomnia, 603
Intestinal bacteria, 177
parasites, 503, 583
tract, 589
Jansky’s blood grouping, 515
Jaundice, 557
epidemic, 114
Jaundice, infectious, 114, 503, 544, 558
cultivation of Leptospira icterohaemorrhagiae, 115
definition of, 114
diagnosis in, 117
epidemiology of, 116
etiology of, 115
geographical distribution of, 114
history of, 114
pathology of, 116
prophylaxis in, 117
symptomatology of, 116
synonyms for, 114
treatment of, 117
Joint involvement in tropical diseases, 592
Juxta-articular nodules, 472, 564
Kaffir milk-pox, 486
Kala-azar, 121, 127, 498, 543, 552, 554, 558, 560, 563
diagnosis in, 131
epidemiology of, 127
etiology of, 123
history of, 121
pathology of, 128
prognosis in, 133
prophylaxis in, 133
symptomatology of, 128
symptoms in detail of, 130
synonyms for, 121
treatment of, 133
Katayama disease, 364, 550, 556
Kidney function and its determination, 575
Kubisagari, 607
Lamblia, 142
Lamus megistus, 81
Large mononuclear increase, 536
Latah, 610
Latent malaria, 35
Lathyrism, 288, 607
Laverania, 5
Leishmania donovani, 123, 127
infantum, 123, 127
tropica, 123
Leishmaniases, 121
American, 138, 553, 564
canine, 123
cutaneous, 135, 564
infantile, 130
post-antimonial, 564
relationship, 126
visceral, 127
Leishmanoid, dermal, 564
Leishman’s staining method, 513
Leprosy, 246, 492, 539, 555, 562, 565, 569, 580, 595, 596, 605,
607, 609
bible and, 247
cultivation of bacillus, 249
definition of, 246
diagnosis in, 261
epidemiology of, 249
etiology of, 248
geographical distribution of, 247
history of, 246
lepra cells in, 253
nerve, 257
nodular, 255
of rats, 252
pathology of, 252
prognosis in, 264
prophylaxis in, 264
symptomatology of, 254
symptoms in detail of, 260
synonyms for, 246
transmission of, 251
treatment of, 265
Wasserman reaction in, 262
Leptospira icteroides, 98
icterohaemorrhagiae, 115
morsus-muris, 118
Leucocytosis, 534
Leukopenia, 533
Liver, alterations in size of, 558
pains of, 559
tropical, 166
Liver abscess, 164, 501, 542, 550, 557, 558, 559
Liver abscess, complications in, 166, 168
diagnosis of, 169
emetine in, 171
etiology of, 164
geographical distribution of, 164
history of, 164
operation for, 172
pathology of, 165
prophylaxis in, 171
rupture of, 166
symptomatology of, 166
symptoms in detail of, 168
treatment of, 171
Liver fluke disease, 371
Loa loa, 337, 352, 566
Lunacy in the tropics, 610
Lymphatic glands, in trypanosomiasis 76, 551
system, 551
Lymphocytosis, 536
Lymph scrotum, 345
Lyon blood tube, 516
Maize in pellagra, 296
Malaria, 1, 493, 494, 495, 496, 539, 548, 553, 560, 562, 566, 574,
579, 602, 605, 609
algid, 34
anaphylaxis and the paroxysm in, 18
cachexia, 36
cerebral, 33
cultivation of parasite, 16
definition of, 1
diagnosis in, 40
discovery of parasite, 2
epidemiology of, 24
etiology of, 4
geographical distribution of, 4
heredity in, 16
history of, 1
immunity in, 17
in animals, 5
index of, 9
latent, 35, 493
life history of parasite, 7
malignant tertian, 28, 30
masked, 36
mosquitoes in, 6, 18
pathology of, 25
perniciousness in, 31
prognosis in, 42
prophylaxis in, 42
provocative measures in, 41
quinine-affected parasites, 16, 17
relapses in, 35
sequelae of, 37
symptomatology of, 27
symptoms in detail of, 37
synonyms for, 1
toxin in, 7, 16
transmission of, 7
treatment of, 47
variations in cycle, 27
Malignant tumors, 488
Malta fever, 237, 497, 541, 550, 554, 560, 579, 580, 593, 603,
604, 609
clinical types of, 242
complications in, 242
definition of, 237
diagnosis in, 243
epidemiology of, 239
etiology of, 238
geographical distribution of, 238
goat milk in, 239
history of, 237
pathology of, 240
prognosis in, 244
prophylaxis in, 245
sequelae in, 242
symptomatology of, 241
symptoms in detail of, 242
synonyms for, 237
treatment of, 245
Marris atropin test for fevers, 484
Mastic test, 601
Media, Aronson’s, 232
Teague, 582
Methylene blue, in malaria, 53
Mexican typhus, 452
Micrococcus melitensis, 238
Monilia Candida, 474
tropicalis, 474
Mosquito, anatomy of, 20
Anopheline, 18
destruction, 43
hibernation of, 21
in dengue, 432
in filariasis, 342
in yellow fever, 105
malaria transmitters, 6
Moss’ blood grouping, 521
Mouth, 586
Mumps, 487
Muscle involvement in tropical diseases, 592, 596
Mycetoma, 399, 595
diagnosis in, 402
epidemiology of, 400
etiology of, 400
geographical distribution of, 399
history of, 399
pathology of, 401
prognosis in, 403
symptomatology of, 401
treatment of, 403
Mycoses, visceral, 473
Myiasis, cutaneous, 421
intestinal, 590
larval characteristics, 590
Myositis purulenta tropica, 597
Nasal myiasis, 551, 568
Nausea, 588
Necator americanus, 320
Neo-arsphenamine, administration of, 95
Neurasthenia, 608
Neurological manifestations, 598
Night blindness, 567
N. N. N. medium, 517
Nocardia pseudotuberculosis, 474
Nose, diseases of, 568
Occult blood, 523, 571, 582
Oedema, 555
Oesophagus, 587
Onchocerca volvulus, 339, 341, 354, 552
Onyalai, 587
Opisthorchis felineus, 372
Oriental sore, 137, 564
diagnosis in, 139
epidemiology of, 136
etiology of, 123
geographical distribution of, 136
history of, 135
pathology of, 137
prophylaxis in, 140
symptomatology of, 137
synonyms for, 121
treatment, 140
Ornithodorus moubata, 89
talaje, 91
Oroya fever, 425, 541, 553, 595, 603
etiology of, 426
pathology of, 426
prophylaxis in, 428
symptomatology of, 427
treatment of, 428
Pappataci fever, 438, 545
Paragonimiasis, 368, 549, 555
diagnosis in, 371
etiology of, 368
history of, 368
symptomatology of, 369
Paragonimus westermanni, 368
life history, 368
Paralytic vertigo, 607
Paratyphoid fever, 484, 503, 545
Pediculi, 454
Pellagra, 291, 492, 539, 561, 572, 586, 588, 589, 603, 605, 606, 608
amino-acid deficiency in, 294
animal experimentation in, 298
blood in, 308
corn in, 296
definition of, 291
diagnosis in, 308
diagnostic triad in, 302
epidemiology of, 298
eruption of, 300, 303
etiology of, 292
experimental, 295
geographical distribution of, 292
history of, 291
moulds and, 296
Pellagra, mouth in, 586
pathology of, 299
periodic recurrences of, 302
prognosis in, 309
prophylaxis in, 309
protein deficiency in, 294
Simulium in, 298
stages in, 302
symptomatology of, 300
symptoms in detail of, 308
synonyms for, 291
treatment of, 310
urine in, 308, 572
Penicillium crustaceum, 474
Pernicious malaria, 31
Phenolsulphonephthalein test, 577
Phlebotomus fever, 438, 545
pappatassii, 439
Piedra, 420
Pinta, 416
Piroplasms, 58
Plague, 188, 499, 542, 547, 549, 551, 559, 575, 602, 604, 605
bubonic, 199
confusing organisms in suspected, 191
cutaneous, 200
definition of, 188
diagnosis in, 205
epidemiology of, 192
etiology of, 190
Flugges droplet method, 197
geographical distribution of, 189
guinea pig test, 207
Haffkine’s prophylactic, 211
history of, 188
pathology of, 198
pneumonic, 197, 201, 549
prognosis in, 208
prophylaxis in, 208
rat and, 191, 196
septicaemic, 203
symptomatology of, 199
symptoms in detail of, 203
synonyms for, 188
tokens in, 200
treatment of, 211
Yersin’s serum, 211
Plasmodium falciparum, 12
malariae, 11
vivax, 10
Pneumonia, 488
Polyneuritis gallinarum, 275, 277
Prickly heat, 561
Proteosoma, 4
Psychoses, 608
Quinine, 45, 47
administration of, 49
in blackwater, 64
idiosyncrasy to, 47
prophylaxis, 45
toxic effects, 47
Rachialgia, 604
Rand scurvy, 286
Rat bite fever, 118, 502, 552, 563, 602
definition of, 118
epidemiology of, 118
etiology of, 118
pathology of, 119
symptomatology of, 120
treatment of, 120
Rats and leprosy, 252
and plague, 191, 196
Reflexes, 606
Relapsing fever, 86, 494, 495, 544, 550, 558, 560, 596, 604
definition of, 86
diagnosis in, 93
epidemiology of, 89
etiology of, 87
geographical distribution of, 87
history of, 86
Panama and, 91
pathology of, 91
prognosis in, 94
prophylaxis in, 94
symptomatology of, 91
symptoms in detail of, 92
synonyms for, 86
transmission of, 87
by the louse, 88
by the tick, 87
treatment of, 94
Remittent fever, 28
Respiratory system, 548
Rheumatic fever, 482
Rhino-pharyngitis mutilans, 395
Rhizomucor parasiticum, 474
Rice and beriberi, 272
Ringworm infections, 561
Rocky Mountain spotted fever, 446, 502, 546, 558, 560, 563, 580,
602, 605
definition of, 446
diagnosis in, 449
epidemiology of, 447
etiology of, 447
history of, 446
pathology of, 448
prophylaxis in, 449
symptomatology of, 448
synonyms for, 446
treatment of, 450
Romanowsky stains, 513
Saline enemata, 65
infusions in blackwater, 65
in cholera, 235
in heat stroke, 468
Sand-fly fever, 441
Sarcopsylla penetrans, 418
Scarlet fever, 482
Schilling-Torgau’s differential count, 514
Schistosoma haematobium, 363
japonicum, 364
mansoni, 364
Schistosomiasis, 357, 493, 546, 555, 560, 563, 575, 579, 589, 590, 606
diagnosis in, 366
etiology of, 357
geographical distribution of, 363, 364
history of, 360
infection in, 357
Japanese type, 364
pathology of, 362
prophylaxis in, 367
rectal type, 364
symptomatology of, 363
treatment of, 367
urticarial fever in, 366
vesical type, 363
Schizogony, 7
Schizotrypanum cruzi, 81
Screw worm, 422, 568
Scurvy, 286
Seven-day fever, 440
Ship beriberi, 285
Simulium reptans, 292
Six-day fever, 441
Skin diseases, 561
eruptions, 561
Sleeping sickness, 66
Smallpox, 486
Somnolence, 603
Spinal fluid, 598
Spirillum cholerae asiaticae, 220
Spironema duttoni, 87
recurrentis, 86
Spleen, enlargements of, 559
pains of, 559
puncture in kala-azar, 132, 559
Sporogony, 8
Sporotrichosis, 474
Sporozoites, 8
Spotted fever of the Rocky Mountains, 446
Sprue, 312, 492, 538, 553, 559, 572, 586, 588, 589
and hill diarrhoea, 316
and pellagra, 316
diagnosis in, 316
etiology of, 313
history of, 312
pathology of, 314
stools in, 316, 589
symptomatology of, 314
symptoms in detail of, 315
tongue, 315, 586
treatment of, 317
Sputum examination, 548
Statistics of cosmopolitan diseases, 481
of intestinal parasites, 584
Stegomyia calopus, 105, 433
Stomach, 587
Strongyloides stercoralis, 374
Strongyloides stercoralis, life history of, 375
symptoms of infestation, 374, 590
treatment of infestation, 376
Syphilis and liver abscess, 170
and yaws, 392
and tropical ulcer, 407
in tropics, 488, 598
Tabardillo, 451
Table of arthropodan diseases, 382
cosmopolitan diseases, 481
filarial worms, 338
helminthic diseases, 379
intestinal bacteria, 177
malarial parasites, 14
protozoal diseases, 377
Tartar emetic, 53, 80, 134, 140
Temperature chart in blackwater fever, 498
dengue, 495
kala-azar, 498
liver abscess, 501
malaria, 493, 494, 495
Malta fever, 497
Oroya fever, 502
plague, 499
relapsing fever, 495
trypanosomiasis, 500
typhus fever, 500
yellow fever, 498
Tetanus, 488
Thick film smears, 511
Three-day fever, 441
Thymol treatment, 332
Ticks, 89, 447
Tinea cruris, 414
etiology of, 414
symptomatology of, 414
treatment of, 415
Tinea imbricata, 411
etiology of, 411
symptomatology of, 412
treatment of, 413
Trachoma, 565
Transfusion of blood, 521
Trematode diseases, 357, 368, 379
Tremors, 605
Trench fever, 460, 503, 596, 605
definition of, 460
diagnosis in, 462
epidemiology of, 461
etiology of, 461
geographical distribution of, 461
history of, 460
pathology of, 462
prognosis in, 463
prophylaxis in, 463
symptomatology of, 462
synonyms for, 460
treatment of, 463
Treponema pertenue, 384
Trichinosis, 534, 597
Tropical liver, 166
and syphilis, 170
etiology of, 166
symptomatology of, 166
treatment of, 167
ulcer, 407
Trypanosoma brucei, 68, 84
gambiense, 66, 68, 69
nigeriense, 68
rhodesiense, 67, 69
Trypanosomes in animals, 84
Trypanosomiasis, 66, 500, 543, 548, 551, 556, 563, 566, 603, 604,
605, 607, 608
Brazilian, 80
definition of, 66
diagnosis in, 77
epidemiology of, 70
etiology of, 67
geographical distribution of, 67
history of, 66
Kérandel’s sign in, 74
pathology of, 72
prognosis in, 78
prophylaxis in, 78
symptomatology of, 72
symptoms in detail of, 76
synonyms for, 66
treatment of, 79
Tsetse flies, 70
Tsutsugamushi, 442
diagnosis in, 445
epidemiology of, 443
etiology of, 443
symptomatology of, 443
Tuberculosis, 485
Tularaemia, 213, 503, 552, 563
definition of, 213
diagnosis in, 217
epidemiology of, 214
etiology of, 214
geographical distribution of, 213
history of, 213
pathology of, 215
prognosis in, 217
prophylaxis in, 217
symptomatology of, 216
synonyms for, 213
treatment of, 217
Tumbu fly disease, 423
Typhoid fever, 483, 545
Marris atropin test in, 484
Typhus fever, 451, 500, 546, 548, 555, 558, 560, 565, 568, 587, 602
definition of, 451
diagnosis of, 457
epidemiology of, 453
etiology of, 452
history of, 451
louse in, 454
pathology of, 454
prophylaxis in, 458
symptomatology of, 455
synonyms of, 451
treatment of, 459
Urine, 570
amount of, 573
bacteriology of, 580
bile pigment in, 572
blood in, 571
Erlich’s aldehyde test, 573
Urobilinuria, 572
in blackwater, 572
Urticarial fever, 364, 493, 546, 563
Uta, 138, 564
Varicella, 487
Veld sore, 408
Venereal diseases, 488
Ver macaque, 421
Verruga, 425, 428, 494
pathology of, 428
symptomatology of, 429
treatment of, 430
Viscerel mycoses, 474
Vincent’s angina, 487
Virus, filterable, in dengue, 432
Vitamines, 271, 275, 288, 290, 293, 567
Vomiting, 588
sickness, 588
Weil’s disease, 114, 544, 558, 559
Wright’s staining method, 513
Xerophthalmia, 567
Yaws, 384, 494, 539, 553, 593
and syphilis, 392
diagnosis in, 391
epidemiology of, 385
etiology of, 384
geographical distribution of, 384
history of, 384
inoculation experiments, 385
pathology of, 386
prognosis in, 393
prophylaxis in, 393
symptomatology of, 387
Yaws, tertiary, 389
treatment of, 393
Yellow fever, 97, 498, 539, 547, 554, 557, 560, 566, 569, 573, 574,
575, 602, 604
Bacillus icteroides, 101
black vomit in, 109, 110
Commission reports, 103
definition of, 97
diagnosis in, 111
epidemiology of, 105
etiology of, 98
experimental work, 99, 103
Faget’s law, 108
geographical distribution of, 98
history of, 97
immune sera, use of, 113
immunity in, 105
Leptospira icteroides, 98
pathology of, 107
prognosis in, 112
prophylaxis in, 112
Stegomyia in, 101, 105
symptomatology of, 108
symptoms in detail of, 109
synonyms for, 97
treatment of, 112
vaccination against, 112
Yersin’s plague serum, 211
Zygote, 9
TRANSCRIBER’S NOTE
Obvious typographical errors and punctuation errors have been
corrected after careful comparison with other occurrences within
the text and consultation of external sources.
For consistency four occurrences of P^2O^5 (superscripts) have been
changed to P_{2}O_{5} (subscripts).
For consistency a few occurrences of the ligatures æ and œ have
been replaced by ae and oe.
Some hyphens in words have been silently removed, some added,
when a predominant preference was found in the original book.
The wide table on page 159 has been split into two parts; the first
column has been duplicated in the second part. The wide table on
page 532 has been slightly restructured with no loss of text; the
first column has been put into CAPS for readability.
Except for those changes noted below, all misspellings in the text,
and inconsistent or archaic usage, have been retained.
Pg xii: ‘CHAPTER LI ... 392.’ replaced by ‘CHAPTER LI ... 592.’.
Frontispiece: ‘MALARIAL PARASITIES’ replaced by ‘MALARIAL PARASITES’.
Pg 17: ‘become chilled’ replaced by ‘becomes chilled’.
Pg 21: ‘completely convered’ replaced by ‘completely covered’.
Pg 26: ‘matter fo fact’ replaced by ‘matter of fact’.
Pg 44: ‘part salcohol)’ replaced by ‘parts alcohol),’.
Pg 50: ‘must be sterlie’ replaced by ‘must be sterile’.
Pg 58: ‘apearances may not’ replaced by ‘appearances may not’.
Pg 100: ‘about the infecton’ replaced by ‘about the infection’.
Pg 102: ‘it would negative’ replaced by ‘it would negate’.
Pg 102: ‘could t have been’ replaced by ‘could not have been’.
Pg 122: ‘bodies, Lavaran’ replaced by ‘bodies, Laveran’.
Pg 128: ‘spleen, parcicularly’ replaced by ‘spleen, particularly’.
Pg 128: ‘pulp tords’ replaced by ‘pulp cords’.
Pg 128: For consistency the heading ‘Symptomatology’ has been changed
from =bold= to an ALLCAPS heading.
Pg 133: ‘place in diaganosis’ replaced by ‘place in diagnosis’.
Pg 137: For consistency the heading ‘Symptomatology’ has been changed
from =bold= to an ALLCAPS heading.
Pg 152: ‘magnesium oxdie’ replaced by ‘magnesium oxide’.
Pg 172: ‘dressing froceps’ replaced by ‘dressing forceps’.
Pg 177: ‘B. enteritidis’ replaced by ‘B. enteriditis’.
Pg 185: ‘than prophylatic’ replaced by ‘than prophylactic’.
Pg 187: ‘praise yaghurt’ replaced by ‘praise yoghurt’.
Pg 223: ‘district and among’ replaced by ‘districts and among’.
Pg 233: ‘The most scrupuous’ replaced by ‘The most scrupulous’.
Pg 235: ‘was striken by’ replaced by ‘was stricken by’.
Pg 249: ‘that of Kedrowski’ replaced by ‘that of Kedrowsky’.
Pg 256: ‘cernea and iris’ replaced by ‘cornea and iris’.
Pg 262: ‘nodular ases’ replaced by ‘nodular cases’.
Pg 262: ‘of mixed lepcosy’ replaced by ‘of mixed leprosy’.
Pg 265: ‘and very rarley’ replaced by ‘and very rarely’.
Pg 269: ‘of Berberi’ replaced by ‘of Beriberi’.
Pg 279: ‘formicaton of the’ replaced by ‘formication of the’.
Pg 291: ‘exacerabtions but’ replaced by ‘exacerbations but’.
Pg 309: ‘do not parallel’ replaced by ‘does not parallel’.
Pg 314: ‘mind. sprue patient’ replaced by ‘mind. The sprue patient’.
Pg 316: ‘Hill Diarrhea’ replaced by ‘Hill Diarrhoea’.
Pg 331: ‘phenolphthalin test’ replaced by ‘phenolphthalein test’.
Pg 332: ‘and chenopodiun’ replaced by ‘and chenopodium’.
Pg 334: ‘Carbon tetrachlorid’ replaced by ‘Carbon tetrachloride’.
Pg 350: ‘dose not involve’ replaced by ‘does not involve’.
Pg 381: ‘Broad Rusian’ replaced by ‘Broad Russian’.
Pg 393: ‘or with Giemas’ replaced by ‘or with Giemsa’.
Pg 436: ‘cases occuring in’ replaced by ‘cases occurring in’.
Pg 452: ‘eradicted from’ replaced by ‘eradicated from’.
Pg 466: For consistency the heading ‘Pathology’ has been changed
from _italic_ to a separate ALLCAPS heading.
Pg 469: ‘peculiarly o affect’ replaced by ‘peculiarly to affect’.
Pg 481: ‘Diarrhea and’ replaced by ‘Diarrhoea and’ (twice).
Pg 484: ‘a broncho-penumonia’ replaced by ‘a broncho-pneumonia’.
Pg 486: ‘is responsibile for’ replaced by ‘is responsible for’.
Pg 494: ‘with manifestaitons’ replaced by ‘with manifestations’.
Pg 501: ‘amoebic dystentery’ replaced by ‘amoebic dysentery’.
Pg 501: ‘that liver abcess’ replaced by ‘that liver abscess’.
Pg 507: ‘mixing throughly’ replaced by ‘mixing thoroughly’.
Pg 510: ‘Erhlich’s method’ replaced by ‘Ehrlich’s method’.
Pg 517: ‘ring of vsaeline’ replaced by ‘ring of vaseline’.
Pg 522: ‘pippette off the’ replaced by ‘pipette off the’.
Pg 527: ‘ension of alveolar’ replaced by ‘tension of alveolar’.
Pg 529: ‘are not synonomous’ replaced by ‘are not synonymous’.
Pg 530: ‘by bl d chemistry’ replaced by ‘by blood chemistry’.
Pg 532: ‘the ura ic, and’ replaced by ‘the uraemic, and’.
Pg 539: ‘febrile accesssions’ replaced by ‘febrile accessions’.
Pg 557: ‘liquor formaldehydi’ replaced by ‘liquor formaldehyde’.
Pg 573: ‘aldehyd reaction’ replaced by ‘aldehyde reaction’.
Pg 574: ‘adminstration of’ replaced by ‘administration of’.
Pg 590: ‘For more detailed’ replaced by ‘For a more detailed’.
Pg 596: ‘and multilation are’ replaced by ‘and mutilation are’.
Pg 598: ‘howevert, unless’ replaced by ‘however, unless’.
Pg 605: ‘endo- and perineurium’ replaced by ‘endoneurium and
perineurium’.
*** END OF THE PROJECT GUTENBERG EBOOK THE DIAGNOSTICS AND TREATMENT
OF TROPICAL DISEASES ***
Updated editions will replace the previous one--the old editions will
be renamed.
Creating the works from print editions not protected by U.S. copyright
law means that no one owns a United States copyright in these works,
so the Foundation (and you!) can copy and distribute it in the
United States without permission and without paying copyright
royalties. Special rules, set forth in the General Terms of Use part
of this license, apply to copying and distributing Project
Gutenberg™ electronic works to protect the PROJECT GUTENBERG™
concept and trademark. Project Gutenberg is a registered trademark,
and may not be used if you charge for an eBook, except by following
the terms of the trademark license, including paying royalties for use
of the Project Gutenberg trademark. If you do not charge anything for
copies of this eBook, complying with the trademark license is very
easy. You may use this eBook for nearly any purpose such as creation
of derivative works, reports, performances and research. Project
Gutenberg eBooks may be modified and printed and given away--you may
do practically ANYTHING in the United States with eBooks not protected
by U.S. copyright law. Redistribution is subject to the trademark
license, especially commercial redistribution.
START: FULL LICENSE
THE FULL PROJECT GUTENBERG LICENSE
PLEASE READ THIS BEFORE YOU DISTRIBUTE OR USE THIS WORK
To protect the Project Gutenberg™ mission of promoting the free
distribution of electronic works, by using or distributing this work
(or any other work associated in any way with the phrase “Project
Gutenberg”), you agree to comply with all the terms of the Full
Project Gutenberg™ License available with this file or online at
www.gutenberg.org/license.
Section 1. General Terms of Use and Redistributing Project
Gutenberg™ electronic works
1.A. By reading or using any part of this Project Gutenberg™
electronic work, you indicate that you have read, understand, agree to
and accept all the terms of this license and intellectual property
(trademark/copyright) agreement. If you do not agree to abide by all
the terms of this agreement, you must cease using and return or
destroy all copies of Project Gutenberg™ electronic works in your
possession. If you paid a fee for obtaining a copy of or access to a
Project Gutenberg™ electronic work and you do not agree to be bound
by the terms of this agreement, you may obtain a refund from the
person or entity to whom you paid the fee as set forth in paragraph
1.E.8.
1.B. “Project Gutenberg” is a registered trademark. It may only be
used on or associated in any way with an electronic work by people who
agree to be bound by the terms of this agreement. There are a few
things that you can do with most Project Gutenberg™ electronic works
even without complying with the full terms of this agreement. See
paragraph 1.C below. There are a lot of things you can do with Project
Gutenberg™ electronic works if you follow the terms of this
agreement and help preserve free future access to Project Gutenberg™
electronic works. See paragraph 1.E below.
1.C. The Project Gutenberg Literary Archive Foundation (“the
Foundation” or PGLAF), owns a compilation copyright in the collection
of Project Gutenberg™ electronic works. Nearly all the individual
works in the collection are in the public domain in the United
States. If an individual work is unprotected by copyright law in the
United States and you are located in the United States, we do not
claim a right to prevent you from copying, distributing, performing,
displaying or creating derivative works based on the work as long as
all references to Project Gutenberg are removed. Of course, we hope
that you will support the Project Gutenberg™ mission of promoting
free access to electronic works by freely sharing Project Gutenberg™
works in compliance with the terms of this agreement for keeping the
Project Gutenberg™ name associated with the work. You can easily
comply with the terms of this agreement by keeping this work in the
same format with its attached full Project Gutenberg™ License when
you share it without charge with others.
1.D. The copyright laws of the place where you are located also govern
what you can do with this work. Copyright laws in most countries are
in a constant state of change. If you are outside the United States,
check the laws of your country in addition to the terms of this
agreement before downloading, copying, displaying, performing,
distributing or creating derivative works based on this work or any
other Project Gutenberg™ work. The Foundation makes no
representations concerning the copyright status of any work in any
country other than the United States.
1.E. Unless you have removed all references to Project Gutenberg:
1.E.1. The following sentence, with active links to, or other
immediate access to, the full Project Gutenberg™ License must appear
prominently whenever any copy of a Project Gutenberg™ work (any work
on which the phrase “Project Gutenberg” appears, or with which the
phrase “Project Gutenberg” is associated) is accessed, displayed,
performed, viewed, copied or distributed:
This eBook is for the use of anyone anywhere in the United States and
most other parts of the world at no cost and with almost no
restrictions whatsoever. You may copy it, give it away or re-use it
under the terms of the Project Gutenberg License included with this
eBook or online at www.gutenberg.org. If you are not located in the
United States, you will have to check the laws of the country where
you are located before using this eBook.
1.E.2. If an individual Project Gutenberg™ electronic work is
derived from texts not protected by U.S. copyright law (does not
contain a notice indicating that it is posted with permission of the
copyright holder), the work can be copied and distributed to anyone in
the United States without paying any fees or charges. If you are
redistributing or providing access to a work with the phrase “Project
Gutenberg” associated with or appearing on the work, you must comply
either with the requirements of paragraphs 1.E.1 through 1.E.7 or
obtain permission for the use of the work and the Project Gutenberg™
trademark as set forth in paragraphs 1.E.8 or 1.E.9.
1.E.3. If an individual Project Gutenberg™ electronic work is posted
with the permission of the copyright holder, your use and distribution
must comply with both paragraphs 1.E.1 through 1.E.7 and any
additional terms imposed by the copyright holder. Additional terms
will be linked to the Project Gutenberg™ License for all works
posted with the permission of the copyright holder found at the
beginning of this work.
1.E.4. Do not unlink or detach or remove the full Project Gutenberg™
License terms from this work, or any files containing a part of this
work or any other work associated with Project Gutenberg™.
1.E.5. Do not copy, display, perform, distribute or redistribute this
electronic work, or any part of this electronic work, without
prominently displaying the sentence set forth in paragraph 1.E.1 with
active links or immediate access to the full terms of the Project
Gutenberg™ License.
1.E.6. You may convert to and distribute this work in any binary,
compressed, marked up, nonproprietary or proprietary form, including
any word processing or hypertext form. However, if you provide access
to or distribute copies of a Project Gutenberg™ work in a format
other than “Plain Vanilla ASCII” or other format used in the official
version posted on the official Project Gutenberg™ website
(www.gutenberg.org), you must, at no additional cost, fee or expense
to the user, provide a copy, a means of exporting a copy, or a means
of obtaining a copy upon request, of the work in its original “Plain
Vanilla ASCII” or other form. Any alternate format must include the
full Project Gutenberg™ License as specified in paragraph 1.E.1.
1.E.7. Do not charge a fee for access to, viewing, displaying,
performing, copying or distributing any Project Gutenberg™ works
unless you comply with paragraph 1.E.8 or 1.E.9.
1.E.8. You may charge a reasonable fee for copies of or providing
access to or distributing Project Gutenberg™ electronic works
provided that:
• You pay a royalty fee of 20% of the gross profits you derive from
the use of Project Gutenberg™ works calculated using the method
you already use to calculate your applicable taxes. The fee is owed
to the owner of the Project Gutenberg™ trademark, but he has
agreed to donate royalties under this paragraph to the Project
Gutenberg Literary Archive Foundation. Royalty payments must be paid
within 60 days following each date on which you prepare (or are
legally required to prepare) your periodic tax returns. Royalty
payments should be clearly marked as such and sent to the Project
Gutenberg Literary Archive Foundation at the address specified in
Section 4, “Information about donations to the Project Gutenberg
Literary Archive Foundation.”
• You provide a full refund of any money paid by a user who notifies
you in writing (or by e-mail) within 30 days of receipt that s/he
does not agree to the terms of the full Project Gutenberg™
License. You must require such a user to return or destroy all
copies of the works possessed in a physical medium and discontinue
all use of and all access to other copies of Project Gutenberg™
works.
• You provide, in accordance with paragraph 1.F.3, a full refund of
any money paid for a work or a replacement copy, if a defect in the
electronic work is discovered and reported to you within 90 days of
receipt of the work.
• You comply with all other terms of this agreement for free
distribution of Project Gutenberg™ works.
1.E.9. If you wish to charge a fee or distribute a Project
Gutenberg™ electronic work or group of works on different terms than
are set forth in this agreement, you must obtain permission in writing
from the Project Gutenberg Literary Archive Foundation, the manager of
the Project Gutenberg™ trademark. Contact the Foundation as set
forth in Section 3 below.
1.F.
1.F.1. Project Gutenberg volunteers and employees expend considerable
effort to identify, do copyright research on, transcribe and proofread
works not protected by U.S. copyright law in creating the Project
Gutenberg™ collection. Despite these efforts, Project Gutenberg™
electronic works, and the medium on which they may be stored, may
contain “Defects,” such as, but not limited to, incomplete, inaccurate
or corrupt data, transcription errors, a copyright or other
intellectual property infringement, a defective or damaged disk or
other medium, a computer virus, or computer codes that damage or
cannot be read by your equipment.
1.F.2. LIMITED WARRANTY, DISCLAIMER OF DAMAGES - Except for the “Right
of Replacement or Refund” described in paragraph 1.F.3, the Project
Gutenberg Literary Archive Foundation, the owner of the Project
Gutenberg™ trademark, and any other party distributing a Project
Gutenberg™ electronic work under this agreement, disclaim all
liability to you for damages, costs and expenses, including legal
fees. YOU AGREE THAT YOU HAVE NO REMEDIES FOR NEGLIGENCE, STRICT
LIABILITY, BREACH OF WARRANTY OR BREACH OF CONTRACT EXCEPT THOSE
PROVIDED IN PARAGRAPH 1.F.3. YOU AGREE THAT THE FOUNDATION, THE
TRADEMARK OWNER, AND ANY DISTRIBUTOR UNDER THIS AGREEMENT WILL NOT BE
LIABLE TO YOU FOR ACTUAL, DIRECT, INDIRECT, CONSEQUENTIAL, PUNITIVE OR
INCIDENTAL DAMAGES EVEN IF YOU GIVE NOTICE OF THE POSSIBILITY OF SUCH
DAMAGE.
1.F.3. LIMITED RIGHT OF REPLACEMENT OR REFUND - If you discover a
defect in this electronic work within 90 days of receiving it, you can
receive a refund of the money (if any) you paid for it by sending a
written explanation to the person you received the work from. If you
received the work on a physical medium, you must return the medium
with your written explanation. The person or entity that provided you
with the defective work may elect to provide a replacement copy in
lieu of a refund. If you received the work electronically, the person
or entity providing it to you may choose to give you a second
opportunity to receive the work electronically in lieu of a refund. If
the second copy is also defective, you may demand a refund in writing
without further opportunities to fix the problem.
1.F.4. Except for the limited right of replacement or refund set forth
in paragraph 1.F.3, this work is provided to you “AS-IS”, WITH NO
OTHER WARRANTIES OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING BUT NOT
LIMITED TO WARRANTIES OF MERCHANTABILITY OR FITNESS FOR ANY PURPOSE.
1.F.5. Some states do not allow disclaimers of certain implied
warranties or the exclusion or limitation of certain types of
damages. If any disclaimer or limitation set forth in this agreement
violates the law of the state applicable to this agreement, the
agreement shall be interpreted to make the maximum disclaimer or
limitation permitted by the applicable state law. The invalidity or
unenforceability of any provision of this agreement shall not void the
remaining provisions.
1.F.6. INDEMNITY - You agree to indemnify and hold the Foundation, the
trademark owner, any agent or employee of the Foundation, anyone
providing copies of Project Gutenberg™ electronic works in
accordance with this agreement, and any volunteers associated with the
production, promotion and distribution of Project Gutenberg™
electronic works, harmless from all liability, costs and expenses,
including legal fees, that arise directly or indirectly from any of
the following which you do or cause to occur: (a) distribution of this
or any Project Gutenberg™ work, (b) alteration, modification, or
additions or deletions to any Project Gutenberg™ work, and (c) any
Defect you cause.
Section 2. Information about the Mission of Project Gutenberg™
Project Gutenberg™ is synonymous with the free distribution of
electronic works in formats readable by the widest variety of
computers including obsolete, old, middle-aged and new computers. It
exists because of the efforts of hundreds of volunteers and donations
from people in all walks of life.
Volunteers and financial support to provide volunteers with the
assistance they need are critical to reaching Project Gutenberg™'s
goals and ensuring that the Project Gutenberg™ collection will
remain freely available for generations to come. In 2001, the Project
Gutenberg Literary Archive Foundation was created to provide a secure
and permanent future for Project Gutenberg™ and future
generations. To learn more about the Project Gutenberg Literary
Archive Foundation and how your efforts and donations can help, see
Sections 3 and 4 and the Foundation information page at
www.gutenberg.org
Section 3. Information about the Project Gutenberg Literary
Archive Foundation
The Project Gutenberg Literary Archive Foundation is a non-profit
501(c)(3) educational corporation organized under the laws of the
state of Mississippi and granted tax exempt status by the Internal
Revenue Service. The Foundation's EIN or federal tax identification
number is 64-6221541. Contributions to the Project Gutenberg Literary
Archive Foundation are tax deductible to the full extent permitted by
U.S. federal laws and your state's laws.
The Foundation's business office is located at 809 North 1500 West,
Salt Lake City, UT 84116, (801) 596-1887. Email contact links and up
to date contact information can be found at the Foundation's website
and official page at www.gutenberg.org/contact
Section 4. Information about Donations to the Project Gutenberg
Literary Archive Foundation
Project Gutenberg™ depends upon and cannot survive without
widespread public support and donations to carry out its mission of
increasing the number of public domain and licensed works that can be
freely distributed in machine-readable form accessible by the widest
array of equipment including outdated equipment. Many small donations
($1 to $5,000) are particularly important to maintaining tax exempt
status with the IRS.
The Foundation is committed to complying with the laws regulating
charities and charitable donations in all 50 states of the United
States. Compliance requirements are not uniform and it takes a
considerable effort, much paperwork and many fees to meet and keep up
with these requirements. We do not solicit donations in locations
where we have not received written confirmation of compliance. To SEND
DONATIONS or determine the status of compliance for any particular
state visit www.gutenberg.org/donate
While we cannot and do not solicit contributions from states where we
have not met the solicitation requirements, we know of no prohibition
against accepting unsolicited donations from donors in such states who
approach us with offers to donate.
International donations are gratefully accepted, but we cannot make
any statements concerning tax treatment of donations received from
outside the United States. U.S. laws alone swamp our small staff.
Please check the Project Gutenberg web pages for current donation
methods and addresses. Donations are accepted in a number of other
ways including checks, online payments and credit card donations. To
donate, please visit: www.gutenberg.org/donate
Section 5. General Information About Project Gutenberg™ electronic works
Professor Michael S. Hart was the originator of the Project
Gutenberg™ concept of a library of electronic works that could be
freely shared with anyone. For forty years, he produced and
distributed Project Gutenberg™ eBooks with only a loose network of
volunteer support.
Project Gutenberg™ eBooks are often created from several printed
editions, all of which are confirmed as not protected by copyright in
the U.S. unless a copyright notice is included. Thus, we do not
necessarily keep eBooks in compliance with any particular paper
edition.
Most people start at our website which has the main PG search
facility: www.gutenberg.org
This website includes information about Project Gutenberg™,
including how to make donations to the Project Gutenberg Literary
Archive Foundation, how to help produce our new eBooks, and how to
subscribe to our email newsletter to hear about new eBooks.
