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MALARIAL FEVERS.
CHAPTER I.
Definition, cause, and mode of spread.
M ALARIAL fevers are the class of fevers caused by the specific Definition.
organisms named the plasmodia of malaria; their chief clinical
character is the regular recurrence of paroxysms of fever at definite intervals*
of 24, 48 or 72 hours ; if recognised at a sufficiently early stage they always
yield to proper treatment by quinine ; they are carried from person to
person by mosquitoes of a particular kind.
The cause of malarial fevers,
In the year 1880 Laveran, a French army surgeon, discovered that Cause.
malarial fevers are caused by a special organism which is present in the blood
of patients suffering from the disease. This organism is called the plasmodium
of malaria. It is an animal of a primitive type classified by zoologists
in the division of the animal kingdom known as the PROTOZOA. The
essential character of an animal belonging to this division is that it is formed
of only one cell. Thus the first fact to be learned about the plasmodium of
malaria is that it is an animal composed of a single undivided cell of proto-
plasm. Such an animal is sharply separated from those in the other great
division of the animal kingdom, the METAZOA, even the simplest of which
is formed of many cells. The second important fact to be learned about the
organism is that it is a parasite, which means that it passes its life in and at
the expense of other animals, which, for this reason, are called its hosts ;
to indicate this mode of life and for the sake of simplicity the plasmodium
is often referred to as "the malaria parasite."
The malaria
parasite lives
in two hosts.
Now it frequently happens that the environment in which a protozoal
parasite is situated in one kind of host is not suitable for all stages of its life,
* The interval is the period that elapses between the beginning of one paroxysm and
the beginning of the next. The intermission i the fever-free period between the end of
one paroxysm and the beginning of the next.
B
( 2 )
Structure of
(he parasite.
Mode of
reproduction.
The sexual
mode of
reproduction
is essential
for continued
life.
and in order to prevent the parasite from becoming extinct it is needful
for some stages to be passed in a host of a different kind ; it is needful also
that there should be some means by which, when necessary, the parasite
can be transferred from one host to the other. As regards such protozoal
parasites as require two hosts, it is usual for one of the hosts to be a
vertebrate animal and the other an invertebrate. This is the case with the
malaria parasite, for part of its life is passed in man and the remainder in
a particular kind of mosquito : in man it is parasitic in the red blood
corpuscles ; in the mosquito it is parasitic in the tissues of the stomach wall
and in the salivary glands. This wonderful arrangement for the preservation
of so minute an animal adds great interest to the subject of malaria, but it
makes the life history of the parasite difficult to follow in all its details, and
before tracing it out it will be well to deal briefly with some other characters
which the malaria parasite possesses in common with other protozoa. These
have to do with its structure and mode of reproduction. As regards struc-
ture it is necessary only to note that the malaria parasite, like all protozoa.
is provided with a nucleus and that the substance of which its body is com-
posed has the same general properties as the protoplasm of the cells which
build up the tissues of the higher animals ; it is "irritable," it moves, it
assimilates food, it grows and divides, and it produces, by chemical processes,
a variety of chemical compounds. As regards reproduction it must be men-
tioned first that in the malaria parasite, as in the vast majority of protozoa,
reproduction takes place by two methods—asexual and sexual. The asexual
method consists simply in the division of a fully grown parasite into a num-
ber of smaller ones, each of which is exactly similar, excepting in size, to the
original one. The sexual method consists essentially in the union of two
individuals which have acquired different properties (male and female) follow-
ed by growth of the fertilized cell and its division into a number of smaller
cells, each of which becomes a parasite exactly similar to the original one. It
may be said that, as a general rule, all protozoa, at the commencement of
their life, multiply by the asexual method only, and that after a certain
number of generations have been produced by this method, sexual forms
appear, which are capable, under suitable conditions, of carrying on multi-
plication by the sexual method. Without sexual reproduction the organism
would, after a certain number of asexual generations, become worn out and
( 3 )
die. It is impossible here to give the reasons why, when the energy with
which a protozoon started life is almost all used up in multiplying by simple
division, sexual forms appear. The answer to such a question would involve
a consideration of the whole problem of the origin of the sexes. 1t is
sufficient with regard to the malaria parasite to say that after a certain num-
ber of asexual generations have been formed, sexual forms appear, which, if
transferred to the body of another host (the mosquito), can, by a process of fertili-
zation and subsequent growth and division, produce forms which, when
retransferred to the original host, develop into entirely rejuvenated young
parasites with as much energy for asexual reproduction as was possessed by
the original organism.
Parthenojene-
sis.
It is held by some very able observers that the malaria parasite has yet
a third method of reproduction, the process being known as parthenogenesis.
This word is derived from two Greek words, parthenos, a virgin, and genesis,
birth or production, and means in this instance the production of a number
of small parasites from a fully mature female parasite which has not been
fertilized by the male element. It is said that the female forms of the para-
site are capable of continuing to live in the blood long after all other forms
have died off, and that, perhaps months or even years after a patient has
apparently recovered, a special stimulus such as a chill or shock to the
system may rouse these forms to renewed activity, when they reproduce
themselves parthenogenetically and cause the appearance of a fresh crop of
young parasites in the blood, thus occasioning a " : relapse."
The parasite's
life history.
The a sexual
cycle in man.
With this preliminary explanation we are in a position to describe the
complete life history of the malaria parasite.* It has been stated already
that part of its life is passed in man and the remainder in a particular kind
of mosquito, and for the sake of simplicity we may commence with the
young form of the parasite [schizont]+ as it is found inside one of the red
corpuscles of a man's blood. It will be seen under the microscope as a small
unicellular mass of protoplasm, undergoing amoeboid movement and occupy-
ing but a small portion of the whole corpuscle (Pl. I, 2). It gradually grows
larger, feeding upon the substance of the red blood corpuscle and converting
* A careful study of Plate I will render the following description easily understood.
†The correct names of the different stages of the parasite are inserted between
square brackets. It is not necessary for the beginner to remember these names.
B 2
PLATE I
PLATE I.
1. Normal red blood corpuscle. 2. Bed corpuscle containing Malignant Tertian
parasite. 3. Larger form of the same parasite containing pigment in short rods.
4, 5, Segmentation of the parasite. 6. The small parasites have escaped from the red cell
and are free in the plasma. 7. A young sexual form (crescent) developed from a similar
parasite to 3. 8. Male sexual form. 9. Female sexual form. 10, 11. .Further develop-
ment of these forms. The remains of the red blood corpuscle still surround them.
12. Free male form which has developed microgametes. 13. Free female form.
14. Fertilization of the female by a microgamete. 15. Travelling vermicule.
16, 17. Zygotes in the stomach wall of the mosquito. 18. The sporozoites fully deve-
loped have burst from the zygote.
The mode of reproduction by parthenogenesis is not shown in this plate.
( 5 )
the haemoglobin into dark granules of pigment (melanin), which can be
plainly seen in the parasite (Pl. I, 3). When it has grown to its full size,
so that it nearly or quite fills the corpuscle, the grains of pigment collect
together into a mass, and the parasite begins to divide up into a number of
small parts (PL I, 4, 5), each of which is capable of becoming a new para-
site identical in all respects with the original one. These parts or segments
(" spores ") [merozoites] remain in contact with each other for a short time
and then burst through the red blood corpuscle—which forms at this time
little more than a thin shell round the parasite—and become free in the blood
(Pl I, 6). Each of them now seeks out and enters a red blood corpuscle,
in which it begins to grow in the same way as the original one did,
ultimately reaching its full size and dividing up into a number of embryo
parasites which again enter other corpuscles and go through the same cycle.
This is the asexual method of multiplication [schizogony] by simple division of
a full grown parasite into a number of small ones, and it is clear that even if
originally only one corpuscle contained a parasite, a very large number of
corpuscles will, by this method, soon become infected.
The sexual
cycle in the
mosquito.
After this method of multiplication has gone on for a number of
days, some of the parasites in the red blood cells instead of going on
to their full size and dividing up into a number of small parasites, proceed
to the formation of sexual forms [gametocytes]. These sexual forms are,
as a rule, readily distinguished from the full grown asexual forms. Two
kinds are present, viz., male forms [microgametocytes'] and female forms [mac-
rogametocytes]. Having attained to their full size, they appear as coarsely
pigmented round or crescent shaped bodies enclosed within the thin shell or
envelope of the red blood corpuscle (PL I, 8, 9). In the blood of man they
undergo, as a rule, no further development, and if they remain in this host they
gradually die off.* It is at this stage of the life history therefore that a
second kind of host in which these forms can continue to live and develop
becomes necessary. Such a host is found to be a mosquito of a particular
kind, namely, an Anopheline. When a mosquito of this kind bites a person
with these sexual forms in his blood, some of them are carried into the
mosquito's stomach with the blood which the insect extracts, and undergo the
* See, however, the remarks regarding parthenogenesis on page 3.
( 6 )
The sexual
cycle in the.
mosquito- -
contd.
following development there. As a result of the mixture of the blood with
the fluids in the mosquito's stomach, aided by the digestive action of the
stomach juices, the thin envelope of red blood corpuscle which protected the
parasite while it was in the blood of man, becomes disintegrated, and the
parasite escapes and is free in the fluid of the mosquito's stomach. Imme-
diately following its escape from the corpuscle great changes are seen to take
place in the character of the parasite. The female sexual form becomes
a granular spherical body (Pl. I, 13). The pigment of the male sexual
form is seen to be agitated violently, and then, from the periphery
of the parasite, three or four long filaments [microgametes] are suddenly pro-
truded (Pl. T, 12). After lashing about for a few moments the filaments
break off from the main body of the parasite and swim about in the fluid in
the mosquito's stomach. They are the true male element in the sexual pro-
cess. When one of them meets a female sexual form it enters it and fertilizes
the true female element [ macrogamete ] contained in it (Pl. I, 14). After this
act of fertilization has occurred, the female parasite acquires new characters.
Changing from the shape of a sphere to that of an ovoid with a pointed end
[ ookinet] (Pl. I, 15), it begins to move about, and making for the inner wall
of the stomach of the mosquito it passes through the internal coats and comes
to rest between the epithelial and muscular layers. Here a thin capsule is
formed round it, and it begins to absorb nourishment from the host and to grow,
until in a, low days it has attained a comparatively large size (PL I, 16). At
this stage it is usually called a zygote [öocyst]. By a process of division
(called sporogony, which distinguishes it from the process already described
under the term schizogony) an enormous number of embryo parasites called
sporozoiles, elongated in shape and provided with a nucleus, are formed in the
full grown zygote (Pl. I, 17, 18). After a time the capsule of the zygote
bursts, and the sporozoites are liberated into the lymph sinuses which surround
the outer surface of the stomach. Thence they are conveyed by the circula-
tion to the salivary glands, and penetrating the outer wall of the gland cells
they come to rest in them and in the salivary duct, which has its external
opening at the point of one of the piercing stylets of the proboscis which enter
the skin in the act of biting. This completes the history of the life of the
parasite in its second host, and if this host dies before the parasite can be
( 7 )
transferred again to the first host the parasite dies also. But a mosquito
which has lived through the ten or twelve days required for the development
just described is not likely to die very soon, and before it dies it will, in all
probability, have many opportunities of biting human beings. Its salivary
gland cells and duct are crowded with innumerable sporozoites, and each time
it bites a person it injects some of these into his blood with the salivary or
poison fluid. * Having got into the blood of man again the sporozoites, after
a certain time, are found in the red blood corpuscles as young parasites identi-
cal in all respects with those from which the description of the life history
was commenced.
The malaria
parasite exists
in nature
nowhere
except in one
or other of its
two hosts.
It will be seen from this description that the whole life of the malaria
parasite is passed in one or other of its two hosts and that no part of its life
is passed in air or water or soil. This is very important because it is obvious
that if the organism does not exist in these media malarial fevers cannot be
contracted from them.
The method by which malarial fevers are contracted.
How malaria
is contracted.
From what has been said above it will readily be seen how malarial fevers
are contracted. An Anopheline mosquito bites a man who has been suffering
for some days from malarial fever, and has sexual forms of the parasite in his
blood. These sexual forms are taken into the mosquito's stomach with the
blood which it sucks in, and there they undergo the development that I have
just described, resulting after some days in the formation of numerous sporo-
zoites which lodge themselves in the salivary or poison gland of the mosquito.
When this mosquito next bites a healthy man, it injects some of these sporo-
zoites into his blood with the salivary fluid, and so produces a malarial infec-
tion in him similar to that of the man from whom it originally sucked blood.
Fortunately every kind of mosquito cannot act as a suitable host for the
human malaria parasite, and in all probability only mosquitoes of one kind,
namely, Anopheline mosquitoes, can do so. Malarial fevers can therefore be con-
tracted by the bite of an Anopheline mosquito only. It must be remembered
also that malarial fever cannot be contracted even by the bite of an Anopheline
* It should be particularly noted that the tube down which the salivary fluid and
sporozoites pass when injected into man, is quite separate from that through which
blood is sucked up by the mosquito.
( 8 )
mosquito, unless that mosquito has sporozoites in its salivary glands. This
means that it must have bitten a man with malarial fever a week or more
previously, and that the temperature and other factors necessary for the
development of the parasites in the mosquito's body, were favourable.
Again it is not sufficient for an Anopheline mosquito to have bitten a man
with malarial fever unless sexual forms of the parasite (which alone can
develop in the mosquito) were present in the man's blood at the time he was
bitten, and in addition the sexual forms must have been fully developed, for,
as a general rule, sexual forms cannot proceed to further development even
in an Anopheline unless they have reached a certain stage of maturity. Thus
in order that an Anopheline mosquito may be able to carry infection it must
have previously bitten a malarial fever patient at a particular period of his
case.
In malarious places, however, cases of malarial fever are so frequent, and
the number of Anopheline mosquitoes is so great, that many opportunities
occur for all the required conditions to be fulfilled, so that it is always
possible in malarious places to find a number of Anopheline mosquitoes with
sporozoites in their salivary glands.
Recapitula
tion of the
chief facts.
The most important facts which we have learnt so far may be summed
up as follows :—
(1) Malarial fevers are caused by the presence in the blood of the
patients of a small parasitic animal belonging to the lowest grade
of the animal kingdom, the PROTOZOA.
(2) This parasite passes its life in two hosts, viz., man and Anopheline
mosquitoes.
(3) In man it multiplies itself by a process of simple division for some
time, and then produces sexual forms, which for their further
development require to be taken into the body of the second
host which is an Anopheline mosquito.
(4) This is effected when such a mosquito bites a man with those forms
in his blood.
(5) In the mosquito's body the female sexual form is fertilized by the
male, the cell which results being called a zygote. By the growth
and division of the zygote an enormous number of new forms of
( 9 )
the parasite, called sporozoites, are produced, which, become
lodged in the salivary or poison gland and duct of the mosquito.
(6) When this mosquito next bites another man, some of the sporozoites
are injected into him with the salivary fluid.
(7) In his body they develop into the young parasitic animals in the red
blood cells exactly identical with the original ones.
(8) As the malarial parasite does not pass any part of its life in any
other environment than men and mosquitoes, it follows that men
and mosquitoes are the only sources of infection of malarial
fevers.
(9) It has been proved almost beyond any possible doubt that there is
no other method by which malarial fevers are contracted in
nature than by the bite of a properly infected Anopheline mos-
quito.
(10) We cannot contract malarial fevers from drinking impure water, or
from the soil, or by breathing impure air ; and water and air
are only indirectly connected with malarial infection in the sense
that they are the homes of the malaria-carrying mosquitoes.
( 10 )
CHAPTER II.
Subjects regarding which every student of the malarial fevers must have
a practical knowledge.
BEFORE
continuing our account of the malarial fevers we must discuss
some subjects of which every student who desires to study these
fevers seriously should have a practical knowledge.
1.—The examination of the blood,
Any one who wishes to understand fully the life history of the malaria
parasite or desires to be able to diagnose and treat cases of malarial fever
successfully, must be thoroughly familiar with the appearances assumed by
the parasite in human blood. In order to acquire this knowledge, it is
necessary to be able to make preparations of blood for examination, and to be
able to recognise the parasite in such preparations. The matter is not really
difficult if one sets about it in the way I shall endeavour to describe, but it
should be noted that no directions given in a book are of any value in com-
parison with the practical demonstration of parasites by one who is familiar
with the subject, and no student should leave college without having made it
his duty to obtain such a demonstration from one of his professors.
The first thing to be learned is how to take specimens of blood and how to
prepare them for examination. It is almost unnecessary to say that the blood
can be examined microscopically either in the fluid state or in dried, stained
preparations, and that whenever possible both methods should be used and
results compared.
How to take
specimens for
the examina-
tion of liquid
blood.
The articles required for preparing fluid specimens of blood are :—(1) Thin
cover glasses, (2) glass slides, (3) a pair of forceps for holding the cover
glasses, (4) alcohol, (5) a surgical needle. The thinnest and best cover
glasses and slides only should be used, and they should be perfectly clean and
well polished. Immediately before being used the slides and cover glasses
should be rewashed in alcohol, thoroughly dried and polished with a silk
cloth, and placed on a sheet of white paper under a glass tumbler in order
to keep them free from dust. The palmar surface of the patient's finger
tip where the prick is to be made is then thoroughly cleaned with alcohol.
( 11 )
The prick is best made with an ordinary surgical needle. If it is made
without hesitation, sharply and not too deeply, no pain will be felt by the
patient ; but even this simple operation requires practice. The first drop of
blood which appears should be wiped off, and before the second drop is
squeezed out a cover glass should be taken up in the forceps and held ready
over the finger. As soon as the second drop of blood—which should not be
larger than a pin's head—appears, the centre of the cover glass is made to
touch it. The drop of blood comes away on the cover glass which is then
quickly laid on to one of the glass slides. If the operation has been done
successfully the blood immediately spreads out in a thin film between the
cover glass and the slide. A slight tap with the end of the forceps on the
upper surface of the cover glass sometimes assists the blood to spread out
more easily, but if the slides and cover glasses are perfectly clean this
should not be necessary. After waiting a few seconds, the edge of the
cover glass may be ringed with vaseline in order to prevent evaporation.
The specimen will then keep good for several hours.
How to take
•specimens for
the examina-
tion of dried
blood.
For making stained preparations dried blood films must be used. A
straight surgical needle, the eye of which has been removed with a pair of
forceps, and glass slides are all the articles necessary for taking these films.
Cover glasses are not required.
The finger is pricked and a clean glass slide is lowered on to the drop of
blood that exudes so that it touches the drop about half-an-inch from one
end of the slide. The slide is then held between the finger and thumb of the
left hand, and the shaft of the needle (which is held by the point) is placed
crosswise on the slide over the drop of blood.
The blood will run along the under surface of the needle which is then
drawn evenly along the slide to the end, thus making a broad thin film of blood.