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does not take place until blood is withdrawn. 5.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.