malaria. This may very well be an exaggeration, but there can be little
doubt that, of all the ills that flesh is heir to, malaria is the most
deadly, and exercises the most profound influence on the distribution
and activities of man. It will be seen later that the disease is most
rife where the densest populations are found, and the mortality of such
a closely crowded area as India gives some idea of the enormous loss of
life and the widespread suffering caused by this disease. In 1892, out
of a total population in India of 217,255,655, the deaths from all
causes reached the figure of 6,980,785. Of these, 4,921,583 were
ascribed to ‘fever.’ All these fevers were not, of course, malarial, but
comparison with other statistics leads to the belief that a high
percentage of them was caused by malaria. Major Ross states that in 1897
over 5,000,000 deaths in the same country were recorded as due to
‘fever,’ and that out of a total strength of 178,197 men in the British
army in India, 75,821 were treated in the hospitals for malaria. Fifty
years ago the loss from malaria amongst the European population of India
was 13 per thousand. With improved methods of living and more skilful
treatment this has been reduced to 7 per thousand; but the native, who
is slow to change his ways, and usually averse to modern methods of
treatment, still retains a very high fever death-rate--over 18 per
thousand. During the years 1887-1897 the average mortality in Italy
attributed to malaria was 15,000 a year, and 2,000,000 patients annually
suffered from ‘fever.’
Apart from the mortality due to this disease, the amount of suffering
and the decline in human power and activity which it entails deserve
careful attention. Compared with the number of patients, the number of
deaths is by no means large. In round numbers, out of every thousand
soldiers in the British army in India in 1897, 420 men were attacked by
malaria, but only one in a thousand died; even in the ‘most malarious’
districts the death-rate only amounted to 6 per thousand. In Sierra
Leone, a district much more fatal than any in India, the average
death-rate of the white troops, based on hospital records extending from
1892 to 1898, is estimated by Major L. M. Wilson at 42·9 per thousand,
whilst that of the coloured troops is 5·9 per thousand. On the other
hand, the European troops show an annual number of cases of 2,134 per
thousand, and the non-European troops one of 1,056 per thousand. These
figures probably under-estimate the amount of fever amongst the troops.
It must be remembered that many soldiers who have slight attacks of
fever do not present themselves at the hospital, whilst of those who do
a considerable number are only detained for slight treatment, and are
never entered on the hospital books, and so are not recorded on the
returns.
From the statistics quoted above, it appears that of our soldiers in
India three out of every seven suffer from an annual attack of malaria
sufficiently pronounced to be recorded on the medical books, whilst our
soldiers on the west coast of Africa have an average of at least two
attacks a year, and a considerable number of them die. There is no
reason to believe that the civil population of India or West Africa is
in any degree more exempt from the disease than the military, but the
statistics in the latter case are more readily accessible.
Malarial fever, when it does not kill, leaves great weakness behind; and
all who have watched malaria patients, or patients who are already
recovering from an attack, cannot fail to have noticed the listlessness
and want of interest in their surroundings and the lack of inclination
to work that they all show. Apart from the mortality, the disease
probably levies a heavier tribute on the capacity of the officers and
officials who administer the British Empire than does any other single
agency.
Before describing the organism which causes all this misery a word or
two must be said about the distribution of the disease. Roughly
speaking, malaria is confined to a broad irregular belt running round
the world between the 4th isothermal line north of the Equator and the
16th line south. It is, however, said to occur occasionally outside
these limits--for instance, in Southern Greenland and at Irkutsk in
Siberia; but until recently the accurate diagnosis of the disease has
been difficult, and too much reliance must not be placed on these
statements. The chief endemic foci of the disease are along the banks
and deltas of large rivers, on low coasts, and around inland lakes and
marshes. Malaria is common all round the Mediterranean region: it was
well known to, and its symptoms were clearly noted by, the early
physicians since the time of Hippocrates. They even recognized the
difference between the mild spring and summer attacks and the more
pernicious effects of the autumnal fever. In France there are several
prominent malarial districts: the valley of the Loire and its tributary
the Indre, and the valley of the Rhone; also the sea-coast stretching
from the mouth of the Loire to the Pyrenees, and again the Mediterranean
sea-board. It occurs in Switzerland, and is found in Germany along the
Baltic coasts, and on the banks of the Rhine, the Elbe, and other
rivers, and in many other parts. Scarcely a province in Holland is quite
free from it, and it is found in Belgium and around Lake Wener, in
Sweden. It extends along the Lower Danube and around the Black Sea, and
spreads across Russia, being especially prevalent along the course of
the Volga and around the Caspian. From Europe it spreads over Asia
Minor, and affects all Southern Asia as far as the East Indies, but in
Japan it is curiously rare. It is also infrequent in Australia--where it
is confined to the northern half of the continent--and in many of the
Pacific Islands; and it is unknown in the Sandwich Islands, New Zealand,
Tasmania, and Samoa. In America it is more common, and of a more severe
type an the Atlantic sea-board than on the Pacific; in the last hundred
years its northern limit is said to have retreated in the centre of the
continent, though some observers think it is creeping further north in
the Eastern States. In a mild form it is known around the Great Lakes,
and in Canada and in New England; but it reaches a high degree of
intensity in the Southern States, Mexico, Cuba, and Central America,
where it probably played a greater part in ruining the projected Panama
Canal than all the corrupt financing of the speculators in Paris. It
extends throughout the warmer parts of South America, and is known in a
virulent form all over Africa except the extreme south.
In Great Britain it used to flourish. The following extract from
Graham’s ‘Social Life of Scotland in the Eighteenth Century’ shows what
a part it played in the life of the Scottish peasant:
‘The one ailment to which they were most liable, and in which dirt
had no share, was ague. This was due to the undrained land, which
retained wet like a sponge, and was full of swamps and bogs and
morasses in which “green grew the rushes.” Terribly prevalent and
harassing this malady proved to the rural classes, for every year a
vast proportion of the people were prostrated by it, so that it was
often extremely difficult to get the necessary work of the fields
performed in many districts. In localities like the Carse of
Gowrie, which in those days abounded in morasses and deep pools,
amongst whose rushes the lapwings had their haunt, the whole
population was every year stricken more or less with the trouble,
until the days came when drainage dried the soil, and ague and
lapwings disappeared.’
In England it was once very prevalent. James I. died of ‘a tertian ague’
at Theobalds, near London, and Cromwell succumbed at Whitehall to a
‘bastard tertian ague’ in 1658, a year in which malaria was very widely
spread and very malignant; and it is only within recent memory that the
fen districts in Cambridgeshire and Lincolnshire, Romney Marsh in Kent,
and the marshy districts of Somerset, have lost their evil reputation
for ague. The older chemists in the towns in the fen districts still
recall the lucrative trade their fathers carried on in opium and
preparations of quinine with the fenmen during the first half of last
century; but with the improved drainage of the fens this has all
disappeared, and at present cases of endemic malaria appear to be
unknown in England, though sporadic cases turn up at rare intervals. It
was also very prevalent along the estuary of the Thames, both on the
Essex and Kentish marshes. Pip in ‘Great Expectations’ says to his
convict:
’“I think you have got the ague.” “I’m much of your opinion, boy,”
said he. “It’s bad about here,” I told him. “You’ve been lying out
on the meshes, and they’re dreadful aguish.”’
Ireland, which appears at first sight peculiarly adapted for the
disease, seems to have been remarkably free from it. It may be that the
strong antiseptic quality of the peaty bog-water hinders the development
of the larval mosquito.
Turning now to the cause of the disease, it is interesting to note that
the discovery of the organism which produces all this misery and death
took place just about the time when Koch was making his far-reaching
investigations into the cause of tuberculosis. In 1880 Koch was at work
on the tubercle bacillus; and in the same year a French army surgeon,
named Laveran, looking down a microscope in a remote military station in
Algiers at a preparation of blood taken from a malarious soldier,
recognized for the first time the small organism which has played a
larger part in human affairs than the greatest politician or general
that ever lived. This small organism is an animal, not a plant. It
belongs to the great group of single-celled organisms, mostly
microscopic in size, called Protozoa, and it lives as a parasite inside
the body of other animals, from which it abstracts what nutriment it
needs. Before describing its structure and life-history, a word or two
must be said about its surroundings in the body of man.
That blood consists of a fluid in which enormous numbers of cells called
blood-corpuscles float is now a matter of common knowledge. These
corpuscles are of two main kinds, the red and the white, but the red
surpass the white in number, in proportions ranging from 300 up to 700
to 1. A cubic millimetre of blood contains about 5,000,000 red
corpuscles; and since these act as the carriers of oxygen from the lungs
to the tissues all over the body, and on their return journey carry away
the carbon dioxide from the tissues to the lungs, where it is given off,
it is obvious that the presence of a parasite in the red corpuscle will
have a most serious effect upon the welfare of the body.
Before Laveran’s discovery, Lankester had described a parasitic organism
living in the blood-cells of a frog, and within the last twenty years
numerous other organisms have been discovered and described by various
investigators living in the blood-corpuscles of reptiles, birds,
monkeys, and bats. There are at least three species of Hæmatozoa, as
they are called, which live in the blood of man, and these three
correspond to the three kinds of malaria--the tertian, the quartan, and
the æstivo-autumnal, or, as it is often termed, the irregular type of
malarial fever, which occurs so frequently in the late summer and autumn
in Italy and elsewhere. The hæmatozoön causing the last-named fever has
been especially studied by the Italian observers, and it differs more
markedly from those causing the tertian and quartan fevers than the
latter do _inter se_. It is not universally conceded that the
differences between these three forms of organism are such as to
establish a difference of species, but the weight of opinion is in
favour of this view. Ross even places the parasite of the
æstivo-autumnal fever in a separate genus, and we have throughout this
article adopted his nomenclature. Zoologically he groups all the three
species infesting man in Wassielevski’s family Hæmamœbidæ, which,
besides the human parasites, includes a species found in monkeys, three
species in bats, and two in birds. The species causing tertian and
quartan fevers are grouped by Ross in the genus _Hæmamœba_, the
former being called _Hæmamœba vivax_, the latter _Hæmamœba
malariæ_. The parasite causing the æstivo-autumnal fever is called
_Hæmomenas præcox_.
With the exception of a few details the life-history of all these forms
is practically identical, although the time which is occupied by
different phases of their life-cycle varies in the different species.
The account given here applies in the main to them all.
The organism which Laveran saw living in the blood-corpuscles of his
malarious patient was a minute cell of irregular shape whose nucleus can
be demonstrated by the use of appropriate reagents. The cell constantly
but slowly changes its outline, pushing out and withdrawing blunt
rounded processes; in fact, the cell resembles the lobate forms of one
of the simplest microscopic animals we know, the Amœba (Fig. 1). The
movements and change of shape consequent on them are termed amœboid,
and the organism in this stage is known as an amœbula. These
amœbulæ whilst in the blood-cell grow rapidly, and in some way they
collect the hæmoglobin, or colouring matter of the red corpuscle, within
their own bodies, and convert it into a number of dark brown or black
pigment granules, which crowd around the nucleus of the parasite. This
pigment, the so-called malarial pigment or melanin, had been recognized
by Virchow and others about the middle of the nineteenth century as a
characteristic product in the blood of malarial patients. The amœbulæ
continue to grow rapidly, at the expense of their cell-host, until,
after a definite period, which varies from one to several days, they
become mature, and by this time they have completely filled up the red
corpuscle, whose scanty remains form a tight skin round the fully-grown
parasite (Fig. 1, 1-8). When mature, one of two things happens--either
they become (1) gametocytes, whose meaning and fate we will consider
later, or they become (2) sporocytes. In the latter case the nucleus of
the amœbula breaks up into a number of small nuclei, and each
surrounds itself by a small mass of protoplasm and forms a spore (Fig.
1, 5-8). The result of this process of division may be roughly realized
if we imagine an orange with
[Illustration: FIG. 1.--THE PARASITE OF TERTIAN FEVER, HÆMAMŒBA VIVAX
(ROSS). HIGHLY MAGNIFIED.
Nos. 1, 2, 3, 4, show the growth and the changing shape of the
parasite within the blood-corpuscle; Nos. 3, 4, etc., show the
aggregation of the pigment, melanin, in the parasite; No. 5 is a
sporocyte, which in Nos. 6, 7, and 8, shows the several stages of
sporulation; No. 9 shows the spores derived from a single
sporocyte, escaped from the blood-corpuscle and free in the
blood-plasm, ready to infect new corpuscles; No. 10 is a male
gametocyte, removed from the body of man, and either in the stomach
of _Anopheles_ or on a microscope-slide, forming there flagella or
spermatozoa, _a_, Parasite; _b_, red blood-corpuscle; _c_, spore;
_d_, granules of pigment, melanin; _e_, flagellum or spermatozoön.
(From Thayer.)
]
[Illustration:
FIG. 2.--VARIOUS STAGES WHICH THE PARASITE OF THE ÆSTIVO-AUTUMNAL
FEVER, HÆMOMENAS PRÆCOX (ROSS), PASSES THROUGH IN THE BODY OF THE
MOSQUITO ANOPHELES. MAGNIFIED 2,000 TIMES. AFTER ROSS AND
FIELDING-OULD.
No. 1, Flagella or spermatozoa from male gametocyte (see Fig. 1
above); No. 2, flagellum or spermatozoön entering and fertilizing
the female gametocyte; No. 3, the fertilized cell or zygote; Nos.
1, 2, 3, are found in the blood in the stomach of the _Anopheles_;
No. 4, the fertilized cell piercing the wall of the stomach of the
mosquito to come to rest at No. 5, between the epithelial lining of
the stomach and the muscular sheath.
_To face page 136._]
but one pip in each quarter. Then the skin of the orange will represent
what is left of the red blood-corpuscle, the flesh will represent the
divided sporocyte, each quarter will represent a spore, and the pip will
represent its nucleus.
At this stage the skin to which the red corpuscle has been reduced
breaks, and the spores fall into the liquid part of the blood (Fig. 1,
9). The pigment granules which escape at the same time also pass into
the liquid of the blood, and are eaten up and removed by those
scavengers of the vascular system, the white corpuscles. Each of the
spores, after remaining a short time in the fluid of the blood, attaches
itself to a new red corpuscle, penetrates its body, and becomes a small
amœbula, which repeats the life-history described above. In this way
a few organisms will soon produce enough spores to infect a very large
number of blood-corpuscles; as many as 60 per cent. are in some cases
infected. The severity of the attack naturally depends in a great degree
on the number of corpuscles infected. Laveran not only first recognized
and described the organism[4] we are dealing with, but he definitely
connected its presence with malaria; but it was not until some time
later, in 1885, that Golgi described the sporulation of the sporocyte
and pointed out that the moment of the escape of the spores from the red
corpuscle coincides with the paroxysm of the fever. Since all the
amœbulæ of one crop are at about the same stage of growth in any one
host, millions of spores in a well-infected patient are thrown into the
liquid of the blood at about the same time; and it is clear that this
must be accompanied by a profound disturbance of the system. This
disturbance manifests itself in a feverish attack. The period when the
spores have left the corpuscles and are free in the liquid of the blood
is also the time at which the administration of quinine is said to be
most effective. Further, it is only at this stage that the disease can
be artificially transferred from one man to another. All efforts to
transmit the gametocytes have ended in failure.
_Hæmamœba vivax_, which causes the tertian fever, passes through the
various stages of its life-history in man in forty-eight hours; hence
the febrile paroxysm occurs every second day. Malaria is usually of the
tertian type, and this is certainly the most common form in temperate
climates. Occasionally the infection has been repeated, and we may find
that there are two groups of the parasite present in the blood, which
arrive at the sporulating stage on alternate days; in this case the
febrile symptoms manifest themselves every day, and the type of malaria
is designated ‘quotidian intermittent fever.’ In this case, if a single
dose of quinine be administered at the right time, one group of
parasites is killed off and the quotidian fever is reduced to a tertian.
There may occasionally be more than two groups present, or the parasites
may for some reason have failed to arrange themselves in groups, in
which case the fever becomes irregular or continuous.
In the quartan fever the parasite _Hæmamœba malariæ_ takes
seventy-two hours to complete its cycle in man, and the paroxysms occur
every three days--that is, there are two days without febrile symptoms,
followed by a day when there is a paroxysm. This form is common in
Sicily and in certain parts of Italy--for instance, around Pavia. Just
as in the tertian fever, so in quartan there may be a second infection,
in which case paroxysms arise on two successive days, followed by a day
of intermission of the fever. If a third group be present, we have a
quotidian fever. The æstivo-autumnal fever, due to _Hæmomenas præcox_,
is noted by a marked irregularity in its clinical symptoms. It usually
sets in during August, September, or October, and is attended by much
more serious results than are the regular intermittent fevers. The
pernicious or malignant form of malaria, rarely seen in temperate
climates, but common in the tropics, is caused--in many cases, though
perhaps not in all--by the same parasite.
From what has been above described, it is evident that when once the
parasite has obtained entrance to the blood it may remain and multiply
for years. The parasite is, however, very susceptible to the poisonous
action of quinine, and this is especially the case at the time when
sporulation has just taken place and the spores are being set free in
the blood. Quinine seems to have little or no effect on the organisms
whilst they are inside the blood-corpuscle, but shortly before the
paroxysm is due it should be administered. Quinine is amongst the very
few absolutely trustworthy specifics known to medical science. It seems
to have been introduced into Europe in the year 1640 by the Countess of
Chinchon, a small town south-east of Madrid. The Countess was Vice-Queen
of Peru, and in 1638 was cured of a tertian fever by the use of Peruvian
bark. Shortly afterwards she started for Europe with a supply of the
drug, but unfortunately died on the voyage. About a hundred years later
Linnæus named the plant after this lady, but acting on erroneous
information omitted the first ‘h’ in the name, and called the plant
Cinchona. According to some authorities the word ‘quinine’ is derived
from ‘quina,’ the Spanish spelling of the Peruvian word ‘kina,’ which
signified bark.
But to come back to the parasite. It was mentioned above that the
amœbulæ become either sporocytes or gametocytes. We have followed the
fate of the former and must now turn our attention to the latter. In
the genus _Hæmamœba_ the gametocyte has a general resemblance to the
sporocyte before its nucleus divides and it begins to form spores; and
it is impossible to predict which amœbulæ will become sporocytes and
which will become gametocytes. In _Hæmomenas_, however, the gametocyte
can be recognized at an early stage. In this genus some of the
amœbulæ become globular and ultimately form spores, whilst others
become elongated and slightly curved; in fact, they assume the shape of
minute sausages. These are the gametocytes. It is on this difference in
shape that Ross has founded his new genus for the parasite of the
æstivo-autumnal fever, all the essential characters of which had,
however, been previously recognized by Italian and American observers.
So long as the gametocytes remain in the blood of the patient they
undergo no further development; on being liberated from the cell into
the fluid of the blood, they degenerate and die; but if they be removed,
even only on to a microscope-slide, they begin to develop. They escape
from the red corpuscle in which they have hitherto been confined, and
some of them--the male gametocytes--are then seen suddenly to emit long
filaments (Fig. 1, 10). These filaments can be watched under a high
power struggling violently to free themselves from the cell which has
given rise to them. Ultimately they succeed, and breaking loose, at once
dart away amongst the corpuscles and other debris on the slide. So long
ago as 1880 Laveran had seen these bodies, but until 1897 their nature
was quite misunderstood. This formation of the filaments or flagella,
sometimes called ‘flagellation,’ can only take place at comparatively
high temperatures. This has an important relation to the seasonal
variation in the prevalence of the disease.
Hitherto in this article we have only studied the malarial parasite
inside the body, with the exception that we have just seen that, should
it get out, certain cells undergo a further development and produce
mobile filaments. It occurred to many that these filaments might be
spores, which were in some way carried into the blood of man. Later
research showed that this is not their true meaning; but, acting on some
such belief, Dr. Patrick Manson propounded the hypothesis that the
spores may be conveyed to man by the intervention of some blood-sucking
insect; and the brilliant and laborious researches of Major Ross,
undertaken with the view of establishing the truth or falsehood of this
hypothesis, have within the last few years cleared up the whole question
of the transmission of the disease from one patient to another.