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^otknagel's Practice



MALARIA, INFLUENZA
AND DENGUE

BY

DR. JULIUS MANNABERG DR. O. LEICHTENSTERN

Professor of Internal Medicine, University Formerly of the University of Cologne

of Vienna

EDITED, WITH ADDITIONS



MAJOR RONALD ROSS, RR.CS., F.R.S., CB.

Professor of Tropical Medicine, University of Liverpool

J. W. W. STEPHENS, M.D., D.P.H.

Walter Myers Lecturer in Tropical Medicine, University of Liverpool



ALBERT S. GRUNBAUM, M.D., F.R.C.P.

Professor of Experimental Medicine, University of Liverpool



AUTHORIZED TRANSLATION FROM THE GERMAN, UNDER THE
EDITORIAL SUPERVISION OF

ALFRED STENGEL, M.D.

Professor of Clinical Medicine in the University of Pennsylvania



PHILADELPHIA AND LONDON

W. B. SAUNDERS & COMPANY
1905



Copyright, 1905, by W. B. Saunders & Company.



PREFACE.



The excellence of the series of monographs issued under the editor-
ship of Professor Nothnagel has been recognized by all who are suffi-
ciently familiar with German to read these works, and the series has
found a not inconsiderable proportion of its distribution in this and
other Enghsh-speakiug countries. I have so often heard regret expressed
by those whose lack of familiarity with German kept these works beyond
their reach, that I was glad of the opportunity to assist in the brmging
out of an English edition. It was especially gratifying to find that the
prominent specialists who were invited to co-operate by editing separate
volumes were as interested as myself in the matter of publication of an
English edition. These editors have been requested to make such addi-
tions to the original articles as seem necessary to them to bring the
articles fully up to date and at the same time to adapt them thoroughly
to the American or English reader. The names of the editors alone
suffice to assure the profession that in the additions there Mill be pre-
served the same high standard of excellence that has been so conspicuous
a feature in the original German articles.

In all cases the German author has been consulted with regard to the
publication of this edition of his work, and has given specific consent.
In one case only it was unfortunately necessar}'- to substitute for the
translation of the German article an entirely new one by an American
author, on account of a previous arrangement of the German author to
issue a translation of his article separately from this series. With this
exception the Nothnagel series will be presented intact.

ALFRED STENGEL.



EDITOR'S PREFACE.



My duties as editor of this volume have been in one respect sUght,
in another more arduous. For, on the one hand, I have thought it
best to leave almost unchanged Prof. Mannaberg's very comprehen-
sive and learned treatment of the history, symptoms, and treatment
of malaria. The only changes I have made in his article have been
to correct the views and arguments based on the miasmatic theory
of the origin of malarial infection which the discovery of the part
played by certain mosquitos in transmitting infection has rendered
untenable. I have inserted a few details recently added to our knowl-
edge, of that still not fully understood exhibition of malarial infec-
tion, viz. : malarial hemoglobinuria, or blackwater fever. I would
insist here on the necessity of complete analyses of the urine in such
cases. To mention only one point : it is important to determine how
quinin is excreted, for if, as has been recently stated, quinin is not
eliminated in the urine during the actual hemoglobinuric attack, but
only subsequently, this would guide a physician in practice as to the
all-important question which he finds so difficult to answer, Shall I
give quinin or not?

Regarding ''malarial cachexia" we are in a transition period, for
w^hile many of these cases are due to a cUstinct parasite (Leishmania
donovani), yet in many, it appears from the most recent work, it is
impossible to find these.

I have further added a short note on the Romanow^sky-Ziemann
stain, the best of all stains for the malarial parasites, giving a prac-
tical and certain method of preparing it — leaving out of account the
numerous elaborate modifications which in my experience have no
advantage over the simple method given.

On the other hand, my duties have been more arduous in writing
an account of the mosquito-malaria question in all its manifold bear-
ings. I have endeavored to give a concise but brief account of all
the important facts now known to us. The task has been made
easier by the fact that since the discovery of the development of the
malaria parasites in the mosquito no fundamental change has been
made in our original knowledge. In one important respect this has

7



EDITOR >S PREFACE.

been extended by the discovery of the fJart played by the native pop-
ulations of tropical regions in disseminating the disease. The great
fact is now fully recognized that the native (children) population is
an ever-present and extremely dangerous source of infection, and the
origin of malaria among Europeans is completely explained.

Finally, the main methods of pro])hylaxis have been indicated.
Already progress has been made in the anti-malaria campaign, and

1 shall not have contributed this portion in vain if I have conveyed
to the physician the necessity, having regard to prophylaxis, for a
study not only of malaria but also of mosquitos and their habits.

J. W. W. Stephens, M.D. Cantab. D. P. H.

May, 1905.



CONTENTS.



MALARIAL DISEASES.

By Dr. Julii s Mannaberg. page

History 17

Geogr.\phic Distribution 22

Etiology 30

Climatic and Telluric Requisites 30

The Malarial Parasites 39

General and Special ^Morphology and Biology of Malarial

Parasites 45

The Unity or Multiplicity of the Parasites, Species of Para-
sites, and Types of Fever 54

Position of Malarial Parasites in Zoology 60

Special Characteristics of the Individual Species of Para

sites 62

Diagnosis of Malarial Parasites — Diagnostic Value of Posi-
tive and Negative Findings 87

Cultural Attempts 92

Toxin Production of the Human Parasite 93

Modes of Infection 94

Experimental Inoculation of Malaria 102

Incubation 103

Transference of Malaria in Utero 106

Relations of Malaria to Sex, Age, and Occupation 108

Debilitating Circumstances Predisposing to Malarial Infection. . 110

Influence of Race 110

Acclimatization — Acquired Immunity 112

Malarial Epidemics 114

Malaria in Its Relation to the Mosquito. (B}' J. W. W. Ste-

PHEXS-, M.D. Cantab., D. P. H.) 115

The Mosquito-Malarial Cycle 117

Developmental C^'cle in Mosquito 126

Mosquitos 130

Life-History of Culicida? 132

Distribution of Culicidse 140

Anatomy of the Mosquito 142

Classification of Culicidse 166

9



10 CONTENTS.

PAGE

Mosquitos (Continued).

Classification of Anophelinse 171

The Ova of Anoi^helina^ 181

Larvae 184

Pupa 198

Distribution of Anophelinse 199

Habits of Anophelinse 203

The Relation of Anophelinaj to ^lalarial Endemicity 206

Technic 215

General Symptomatology 221

Fever 221

Enlargement of the Spleen 227

Chloranemia and j\Ielanemia 228

Skin 233

Urine 234

Nervous System 237

Gastro-Intestinal Tract, Respiratory Tract, Circulatory Appa-
ratus 238

Classification of Malarial Diseases 241

Fevers Caused by Golgi's Common Tertian and Quartan Para-
sites 242

Quartan Fever, that is, Fever Caused by the Quartan Para-
sites 243

Tertian Fe^'er — Fever Caused Ijy the Common Tertian Para-
sites 247

Mixed Fevers 250

Fevers Caused by Crescent-Forming Parasites 252

Type of Fever 253

Quotidian Fever 256

Malignant Tertian 256

Ordinary Symptoms of the Fevers Caused by the Crescent -

Forming Parasites 261

Perniciousness 264

Typhoid Pernicious Malaria 272

Cerebral and Spinal Pernicious Fevers 282

Comatose Pernicious 283

Delirium 286

Motor Irritative Symptoms (Convulsions) 287

Paralysis 289

Pernicious Algid 291

Syncopal Pernicious 293

Diaphoretic Pernicious 293

Gastro-Intestinal Pernicious Fevers 294

Cardialgic Pernicious 295



CONTEXTS. 11



PAGE



Gastro-Intestinal Pernicious Fevers (Continued).

Choleraic Pernicious 296

Dysenteric Pernicious 300

Bilious Pernicious 301

Hemorrhagic Pernicious 306

Hemoglobinuric Bihous Fever 307

Pneumonic Subcontinued 328

Mixed Infections 329

Latent Fevers 330

Acute Malaria in Children and Old People 335

Relapses; Reinfections 340

Chronic Malarial Infection 344

Malarial Cachexia 349

Complications and Sequel.e 360

Respiratory Tract 360

Digestive Tract 367

Urogenital System 375

Heart and Blood-vessels 379

Nervous System 380

Functional Neuroses 388

Organs of Special Sense 389

Eyes 389

Ear 393

Smell and Taste 393

Diseases of the Skin 394

Muscles, Bones, Joints, and Lymph-Glands 395

Blood 396

Am3-loid Degeneration 400

Diabetes 401

The Relation of Malaria to Other Infectious Diseases 403

Malaria from a Surgical Aspect 407

Pathologic Anatomy 408

Acute Malaria 408

Chronic Malaria and Cachexia 416

Pathogenesis of Malaria: Its Position in Pathology 421

Diagnosis 436

Prognosis 442

Spontaneous Cure 446

Treatment 451

Preparations of Quinin. Methods of Administration 458

Time of Administration and Amount to be Administered 462

Special Treatment 464

Additional Effects of Quinin 470

Substitutes for Quinin 472



12 CONTENTS.



PAGE



Symptomatic Treatment of the Acute Infection 477

Treatment of Chronic Malaria and Cachexia 479

Prophylaxis 483

Remedial Prophylaxis 489

Literature 494



INFLUENZA.

By Prof. Dr. O. Leichtenstern.

History, Epidemiology, and Etiology of Influenza 523

Nomenclature of Influenza 525

Antiquity of Influenza 526

Retrospection of the Great Epidemics and their Distribution . . 526
Relation of Influenza Vera to the So-called " Catarrhal Fever,"

Vulgo " La Grippe" 529

Epidemiology of Pandemic Influenza 532

Origin of the Pandemic 532

The Geographic Distribution of the Disease in Regard to

Territory and Time 533

Manner and Rapidity of Spread of the Pestilence Formerly

and Now 537

Spread of the Pandemic of 1889 and 1890 Around the

World 541

Beginning, Acme, and End of the Epidemic 544

Epidemics Following the Pandemic 545

Influenza in Families, High Altitudes, and at Sea 554

Influenza in Institutions (Prisons, etc.) 560

Morbidity and Mortality 564

Influence of Age, Sex, and Occupation 570

Influence of Meteorologic and Telluric Conditions 573

Transmission of Disease through Merchandise 575

Immunit}^ 577

Duration of Period of Incubation 579

Bacteriology of Influenza 579

Influenza of Domestic Animals 586

Entrance and Exit of Influenza Organism 587

Relation of Influenza to Other Infectious Diseases 588

Pathology and Treatment of Influenza 590

The General Features of the Disease and Its Different Varieties 590

Onset and Duration. Convalescence. Relapses 593

Diagnosis 596



CONTEXTS. 13

PAGE

Differential Diagnosis 597

The Fever of Influenza 598

Symptoms Relating to the Respiratory Apparatus 601

Influenza Pneumonias 608

Affections of the Pleura 636

Tuberculosis of the Lungs and Influenza 637

Nervous Symptoms 638

Affections of the Sensory Xerves 639

Paralyses Due to Neuritis 640

The Influenza Encephalitis 642

Influenza Meningitis 647

The Comatose Variety of Influenza 651

Influenza Epilepsy and Other Manifestations of ]\Iotor Irri-
tation 653

Affections of the Spinal Cord from Influenza 656

The Influenza Psychoses 658

SymiDtoms Referable to the Digestive ApjDaratus (Including

Peritoneum, Spleen, and Parotid Gland) 662

Symptoms Referable to the Circulatory Apparatus (Including

Blood, Thyroid, and Lymph-Glands) 672

Symptoms Referable to the Genito-L'rinar}" Apparatus 681

Affections of the Skin and Locomotor Apparatus 684

Diseases of the Ear and Eye Follov;ing Influenza 688

Therapy of Influenza 691

Literature 701



DENGUE

By Prof. Dr. O. Leichtex.stern.

Nomenclature 720

Geographic Distribution and the ]\Iost Important Epidemics. . 721

Epidemiology and Etiology 723

Symptomatology 731

First Stage (Stadium Febrile) 732

Second Stage (Stadium Exanthematis) 735

Third Stage (Convalescence) 736

Complications and Sequel.e 736

Diagnosis, Prognosis, and Therapy 737

Epidemiologic and Clinical Differences Between Influenza

and Dengue 738

Literature 741

Index 743



MALARIAL DISEASES



DR. JULIUS MANNABERG



MALARIAL DISEASES.



GENERAL PART.

HISTORY.

The existence of malaria in the ancient times is proved from the
chronicles of contemporaneous writers. It appears, moreover, likely
that the disease extends to the infancy of the human race, for it
is in our day unquestionable that cultivation — especially cultivation
of the ground — and malaria are two factors that flourish counter to
each other, inasmuch as where husbandry does not exist, malaria
is luxuriant, and where the soil is tilled, malaria diminishes and even
disappears.

According to W. Groff, malaria was well known to the ancient
Egyptians. The word " Aat," occurring among others in the inscrip-
tions on the temple at Denderah, is said to indicate the annual re-
curring epidemic.

The history of our knowledge of malaria is divided into three
epochs by two principal discoveries: the first, the recognition of the
specific action of cinchona bark; the second, the demonstration of
the malarial parasites by Laveran.

Previous to the discovery of Peruvian bark and its introduction
into therapy, malaria was, with other fevers, thrown into a confused
conglomeration. Its separation from this confusion was brought
about by the effects of the bark, though it was only in our own cen-
tury that the classification was made absolute. This classification
was the result of clinical observation, and especially the study of
pathologic anatomy.

Though we may allow, without further discussion, that the an-
cients had no very clear ideas as to the differentiation of different
fevers, it is not true that such a differentiation was not anticipated
and earnestly sought. The writings of Hippocrates and Celsus show
that they had pretty correct notions as to whether or not a certain
fever would terminate favorably, as to the origin of the fever, and
as to the causal connection of the fever with its results.
2 17



18 MALARIAL DISEASES.

Hippocrates* classifies fevers "without evident pain" (therefore
without distinct localization of the symptoms) exactly as we do. He
writesf: "Omitting those arising with evident pain, there are four
types, the names of which are: continued fever, quotidian fever, ter-
tian fever, and quartan fever." That the distribution of fevers over
different seasons was remarked by Hippocrates is shown by the fol-
lowing quotations : " Of summer, certain of these (already mentioned),
and continued, ardent, and tertian fevers, " etc. ; further : " Of autumn,
most of the summer, quartan, and irregular fevers, enlarged spleen,
dropsy," etc. J

No one would fail to recognize that his irregular fevers refer to
relapsing fevers, his enlarged spleen and dropsy, to malarial cachexia.

That Hippocrates appreciated the causal connection between fever
and cachexia is evident from many expressions like the following:
"This disease is habitual to them both in summer and in winter, and
in addition they are very subject to dropsies of a most fatal char-
acter ; and in summer dysenteries, diarrheas, and protracted quartan
fevers seize them, and these diseases, when prolonged, dispose such
constitutions to dropsies, and thus prove fatal. § Or : "Convalescents
(therefrom) will pass into quartans, and from quartans into drop-
sies. "||

The favorable influence of humidity on fever is shown by: "But
if the winter be dry and northerly, and the spring showery and south-
erly, the summer will necessarily be of a febrile character."**

In relation to marsh land and the dwellers thereon he writes : "As
to the inhabitants of Phasis, their country is fenny, warm, humid,
and wooded; copious and severe rains occur there at all seasons;
and the life of the inhabitants is spent among the fens, for their dwell-
ings are constructed of wood and reeds and are erected amidst the
waters. For these reasons the Phasians have shapes different from
those of all other men ; for they are large in stature and of very gross
habit of body, so that not a joint or vein is visible. In color they
are sallow, as if affected with jaundice. Of all men, they have the
roughest voices, "ft

Hippocrates attributes the origin of the fever to the drinking of

* Hippocrates, " Sammtliche Werke," Uebersetzung von R. Fuchs, Miinchen,
by Dr. Liineberg, 1895. [The English translator has followed the translation of
Francis Adams, for the Sydenham Society, except in the first instance quoted from
the book on the " Nature of Man," which Adams considered spurious. — Ed.]

t " Nature of Man," chap. xvi. t " Aphorisms," sect, iii, 21 and 22.

§ " Airs, Waters, and Places," chap. viii. || Ihid., chap. x.

** Ihid., chap. x. tt i^id., chap. xx.



HISTORY. 19

contaminated water: "For water contributes much towards health.
Such waters then as are marshy, stagnant, and belong to lakes are
necessarily hot in summer, thick, and have a strong smell, since they
have no current; those who drink them have large and obstructed
spleens. . . " (chap, vii).*

Celsus has left us a finished clinical description of intermittent
fever and many of its accompanymg symptoms. He differentiates
a quotidian fever, composed of quartan attacks, and mentions as
an especially pernicious fever the malignant tertian (then called

rj/jLiTpiTacov).

That the Romans were very close to the trail in regard to the
etiology of malaria is proved from the writings of Varro, Columella,
Palladius, Vitruvius, and Avicenna, who made swamps, the emana-
tions from them, and the minute animals living in them, responsible
for the disease. This etiologic idea was lost in the middle ages on
account of the influence of Galen's teaching, and Morton, at the end
of the seventeenth century, was the first again to pick up the thread. f

Mercatus, the court physician to Philips II and III, gives a des-
cription of pernicious cases occurring in connection with intermittent
fever, and says that they were associated especially with the tertian
type. In general, this author is so deeply involved in the humoral
pathologic vagaries that pervaded medicine at his time as to be al-
most totally unintelligible to us.

The Arab physicians also, as Rhazes, Ebn Sina, were acquainted
with intermittent fever.

The second epoch began with the introduction of Peruvian bark
— the middle of the seventeenth century. Following its opening,
in quick succession, came the memorable treatises of Morton, Torti,
and Sydenham. The complete clinical pathology of malaria stands
out fully developed in the first two especially.

With cinchona in their hands, Torti and Morton divided the "es-
sential fevers" into two principal groups — namely, those that were

* Bellos (Athens) declares there is a complete identity between the fevers des-
cribed by Hippocrates and those occurring to-day in Greece.

t The goddess of fever (Mefitis) had a temple on the Capitol. She was repre-
sented as an emaciated, half-nude, bald-headed, horrid figure, with a huge belly
and swollen veins. That malaria played a role in public affairs at the time of the
empire is evident from Horace's letter to Maecenas ("Epistolarum," lib. i, ep. 7, vi
ad Maecenam). Horace begs Maecenas to extend his leave of absence, so as to
permit him to remain away during the intensest of the summer heat, for when
the first figs ripen and faces become pallid from fever, the chief of the funeral
pomps (designator), with his black assistants, is very active, and the reading of
wills becomes the order of the day (Jilek).



20 MALARIAL DISEASES.

curable by it, and those in which it had no effect. On the basis of
this differentiation Torti built up a description of malarial diseases
that must always remain classic. In a clinical way his work has
been surpassed by no subsequent writer, and will very probably
never be surpassed. Acuteness of observation, wealth of experience,
facility of exposition, are the factors that go to make its prominence.

We will often discuss Torti 's views in the following pages, and
will, therefore, refrain from repeating them now.

Morton's highly interesting book contains, besides a broad dis-
cussion of the action of quinin based on a large experience, the first
germ of an etiologic idea since Galen's time.

The notion of a connection, between the condition of the ground
and the meteorologic and climatic conditions and malaria was intro-
duced and popularized especially by Lancisi. He was, moreover,
the first who endeavored to demonstrate this question experiment-
ally; and, likewise, the first to remark the strikingly dark color of
the liver in fatal cases of malaria.

An acquisition to the subject in the eighteenth century that is
worthy of mention was de Haen's demonstration of the rise of tem-
perature during the chill.

It was owing to the progressive colonization, during the eigh-
teenth century, of the various parts of the world outside of Europe
that a knowledge of the wide geographic distribution of malarial dis-
eases was acquired (Lind, Pringle), though with it came new diffi-
culties in the differentiation of malaria from other endemic tropical
diseases, as yellow fever. The separation of these was the work of
pathologic investigation in the nineteenth century.

On one hand, the pigmentation of the organs and the blood of
malarial cases had become more and more striking (Bailly, Folchi) ;
on the other, the characteristic lesions of that disease most difficult
to differentiate from malaria, namely, typhoid fever, were found in
the small intestine by Prost, Bretonneau, Louis, Gerhard, and Pen-
nock.

An important epoch in the history of malaria was introduced by
Heinrich Meckel's discovery (1847) of the pigment and the pigmented
corpuscles. This discovery was made possible by the work of Vir-
chow, Heschl, Planer, and Frerichs. Yet we must not forget the
clinical work of Maillot, Haspel, Leon Colin, Griesinger, Le Roy de
Mericourt, Berenger-Feraud, Corre, Morehead, Fayrer, Baccelli, Tom-
aselli, Karamitsas, and Hertz in the rearrangement of the new mate-
rial, nor that of Kelsch and Kiener, based on recently discovered



HISTORY. 21

facts. All added a wealth of clinical and anatomic knowledge to
the subject.

Simultaneously, every effort was made to solve the etiology.
After many futile endeavors to find the disease excitant, the exist-
ence of which had long been surmised (Mitchell, Salisbury, Eklund,
Tommasi-Crudeli, and others), Laveran succeeded, in November,
1880. Several years of skepticism followed, but eventually Laveran 's
discovery, which opened up the third epoch of malarial investigation,
conquered the medical world. There is scarcely a known malarial
focus on the earth where this discovery has not been confirmed. A
large number of investigators at once took up the study of the develop-
ment of the disease from this point of view, though, remarkable to
say, the greatest number of these were found among the Italians and
the fewest among the compatriots of the discoverer. Some of the
names that must be mentioned in this regard are Golgi, Marchiafava,
Celli, Grassi, Feletti, Bignami, Bastianelli, Romanowsky, Di Mattel,
Osier, Thayer, Hewetson, Manson, Sakharoff, and Metschnikoff.

To this time also belongs the discovery of Gerhard t that malaria
could be transmitted by the inoculation of the blood of a patient.
Nor should we fail to mention the discovery of quinin by Pelletier
and Caventou (1820).



GEOGRAPHIC DISTRIBUTION.

Malaria is one of the most widely distributed infectious diseases;
yet its distribution is by no means uniform, for it is most prevalent
in the region of the equator and gradually diminishes toward the
north and south. The most northerly point at which malaria has
been observed is, as far as we have any knowledge, Brahestad (64°
41' N, L.), in Finland. Here, in 1861, Hjelt reported intermittent



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