MALARIA

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It has been said that one-half the mortality of the human race is due to 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 HÆmamoebidÆ, 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 HÆmamoeba, the former being called HÆmamoeba vivax, the latter HÆmamoeba 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 Amoeba (Fig. 1). The movements and change of shape consequent on them are termed amoeboid, and the organism in this stage is known as an amoebula. These amoebulÆ 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 amoebulÆ 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 amoebula 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

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.)
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.)

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.
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 amoebula, 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 amoebulÆ 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.

HÆmamoeba 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 HÆmamoeba 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 amoebulÆ 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 HÆmamoeba 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 amoebulÆ 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 amoebulÆ 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.

It is a well-established belief in many malarious countries that the mosquito plays a part in the infection. The negroes of the Usambara Mountains, who acquire the disease when they descend to the plains, even use the same word to denote the disease and the mosquito. In Assam, in Italy, and in Southern Tyrol, the belief in the mosquito origin of malaria obtains. Experienced travellers, like Livingstone, Emin Pasha, and General Gordon, insisted on the importance of mosquito-nets, thinking that the netting ‘acted as a filter against the malarial poison,’ and knowing by experience that its presence diminished the tendency to the disease. The whole epidemiological evidence was put together in a masterly essay on the mosquito theory, read before the Philosophical Society of Washington in 1883, by Professor A. F. A. King. There was thus a considerable body of opinion in favour of the mosquito-malaria theory, when, in 1894, Manson explained his views to Major Ross, at that time a surgeon in the Indian Medical Service.

Manson’s own epoch-making researches on Filaria—another human parasite whose intermediate host is the mosquito—no doubt strengthened his faith and helped to encourage Major Ross, who in 1895 began in Secunderabad a series of investigations, which, after much weary work, were crowned with brilliant success. The difficulties of the work were very great. Hardly anything was known about the great number of gnats and mosquitoes which are found all over India, and it was often impossible to have them accurately determined. Then no one could predict the appearance of the parasite within the body of the mosquito—if it were there—or in what part of the body it should be looked for. The mosquito had to be searched cell by cell. The difficulty of dissecting a mosquito is great even in temperate climes, and when we recollect that hundreds of all the available species were dissected in the most malarious districts in India, we must recognize that it was only a faith akin to that which moves mountains which sustained the courage and stimulated the perseverance of the tireless worker. For nearly two years and a half Major Ross searched in vain. No matter what species of mosquito he worked at, the results were negative. A less determined man would long ago have abandoned the research; Major Ross only tried new methods. At Sigur Ghat, near Ootacamund, a peculiarly malarious district, he noticed for the first time a mosquito with spotted wings which laid boat-shaped eggs. Shortly afterwards he was able to feed eight specimens of this mosquito on a patient whose blood contained the parasites in the gametocyte stage—and it should have been mentioned above that all mosquitoes dissected were first fed upon the blood of malarious patients. Six of these insects were searched through and through, organ by organ, but without result. The seventh showed certain unusual cells in the outer surface of the stomach, which contained a few granules of the characteristic black pigment or melanin of malarial fever. The eighth and last specimen showed the same characteristic cells with the same characteristic pigment; but the peculiar cells, quite unlike anything hitherto met with in the mosquito’s body, were larger and further developed. ‘These fortunate results practically solved the malaria problem.’

Without following in detail the various stages of the further investigations carried on by Major Ross, we must endeavour to give an account of the final results obtained by him and later investigators. Being unable to obtain material for the study of malaria in man owing to the scare caused by the outbreak of plague amongst the natives, Ross worked out the life-history of an allied organism which causes malaria in birds. It is to the brilliant researches of the Italian school—prominent among whom are Grassi, Bastianelli, and Bignami—that we owe the first complete accounts of the life-history of the human parasite. It has already been explained that some of the parasites do not form spores, but persist in a more or less unchanged condition whilst in the blood of man as gametocytes. We have also seen that when removed from the human body some of these gametocytes throw off actively mobile filiform bodies. In 1897 MacCallum of Baltimore showed what these filiform bodies really are. Certain of the gametocytes do not produce them, but lie passively still on the microscope-slide, or in the blood within the mosquito’s stomach. These are destined to form the female cell; the filamentous bodies which break off from the first-named gametocyte were seen by MacCallum to fuse with them, and, in fact, to play the part of the male cell or spermatozoÖn. This, in fact, happens when a mosquito feeds on a malarious patient. The gametocytes, unchanged in the blood of man, as soon as they reach the stomach of the insect, swell and burst from their red corpuscle. The male gametocyte throws off the filiform bodies, which actively swim about seeking a female gametocyte (Fig. 2, 1). When found they fuse with it, and thus produce a fertilized cell or zygote (Fig. 2, 3). This zygote is produced on the microscope-slide, and in the alimentary canal of certain mosquitoes, but so far as is known at present it undergoes further development only in the stomach of the various species of the mosquito genus Anopheles. In all other cases it dies or is digested. In Anopheles, however, the zygote travels to the walls of the stomach, pierces the inner coats and comes to rest underneath the muscular tunic which ensheaths that organ (Fig. 2, 4 and 5).

At first the zygote is very small, about the size of a red blood-corpuscle; but it grows, and in the course of about a week it has, roughly speaking, increased to five hundred times its original bulk (Fig. 3, 1 and 3). Its contents have not only increased, but have divided into some eight or twelve cells, called meres; and each of these meres has given off round its periphery a number of filiform cells, called blasts (Fig. 3, 2). The structure of the mere, with its coating of blasts, may be easily understood by a zoologist when it is mentioned that it very closely resembles that stage in the formation of the spermatozoa of the earth-worm just before the spermatozoa separate themselves from the blastophor; the lay mind may gain a better idea of its appearance by recalling the head of a mop. As the zygote, still resting on the outside of the mosquito’s stomach, matures, the cells which are giving rise to the blasts diminish in size and disappear, leaving the capsule packed with thousands of minute filiform slightly spindle-shaped blasts (Fig. 3, 3). Then the capsule bursts and the blasts make their way into the body-cavity, or space between the stomach and the wall of the mosquito’s body. It is not known whether they have any movement of their

FIG. 3.—FORMATION OF THE BLASTS OF HÆMOMENAS PRÆCOX (ROSS) WITHIN THE BODY OF THE MOSQUITO ANOPHELES. MAGNIFIED 2,000 TIMES. AFTER ROSS AND FIELDING-OULD. No. 1, The full-grown zygote dividing up into meres; No. 2, an isolated mere which has developed its filiform bodies or blasts; No. 3, the zygote crammed with blasts is bursting; No. 4, the blasts are making their way into the salivary gland of the mosquito a, through it into the oesophagus b, and finally into the proboscis c. To face page 144.
FIG. 3.—FORMATION OF THE BLASTS OF HÆMOMENAS PRÆCOX (ROSS) WITHIN THE BODY OF THE MOSQUITO ANOPHELES. MAGNIFIED 2,000 TIMES. AFTER ROSS AND FIELDING-OULD.
No. 1, The full-grown zygote dividing up into meres; No. 2, an isolated mere which has developed its filiform bodies or blasts; No. 3, the zygote crammed with blasts is bursting; No. 4, the blasts are making their way into the salivary gland of the mosquito a, through it into the oesophagus b, and finally into the proboscis c.
To face page 144.

own, but in some way or another they make their way into the salivary glands of the insect and accumulate in the cells which secrete the saliva. Thence the blasts pass into the salivary duct and down the grooved proboscis of the insect (Fig. 3, No. 4). The next time the mosquito has a meal off a man, some of these blasts will be washed into the man’s blood by the saliva which causes the irritation set up by a mosquito’s bite. It is known that when an infected insect bites a healthy man malaria ensues; and though the blasts have not hitherto been seen to enter the blood-corpuscles, they certainly give rise to the disease, and it can hardly be doubted that they force their way into the red corpuscles and form the young amoebulÆ which we described at the beginning of this article.

The appended scheme will perhaps make clear the very diverse phases of the somewhat polymorphic organisms. Those stages which occur in the blood of man are printed in ordinary type, but those which occur in the mosquito are in italics:

The foregoing account of this varied and romantic life-history is no hypothetical one. With the exception that, so far as we know, no one has yet seen the blasts enter the corpuscles and become amoebulÆ, every stage in the story has been verified over and over again by competent observers, and their observations are now accepted by all whose opinion in such matters has weight. Further, the facts here recorded are not peculiar to parasites in man. Allied forms of Protozoa attack other vertebrates, and, in fact, the first hÆmatozoÖn whose life-history was thoroughly worked out by Ross was the HÆmamoeba (Proteosoma) relicta, which causes a malaria-like disease in birds, and is conveyed from one bird to another by means of the common gnat, Culex pipiens. Again, the parasite which causes so much loss to stock-owners, the Texas fever organism, Pyrosoma bigeminum, is, thanks to the researches of Smith and Kilborne, now known to be conveyed from one ox to another by the cattle-tick, BoÖphilus bovis. Thus, however strange the life-history of the malarial parasite may seem to the unscientific, it is very much what might have been expected by zoologists who have worked on allied organisms, and it is vouched for in its main features by the most expert workers in England, France, America, Italy, and Germany. The whole literature of the subject of transmission of disease by insects has been ably sifted and brought together by Dr. Nuttall in a monograph whose title is mentioned in the Bibliography.

For two years and a half Major Ross dissected mosquitoes, looking for traces of the malaria organism and finding none, but at last found what he sought in a species of mosquito that had hitherto escaped his attention. This means that, like most other parasites, the HÆmamoebidÆ will develop in one kind of animal and in one kind only. If taken up by another kind they are simply digested. The mosquito with the

ANOPHELES MACULIPENNIS. MALE, IN CHARACTERISTIC ATTITUDE.
ANOPHELES MACULIPENNIS.
MALE, IN CHARACTERISTIC ATTITUDE.

ANOPHELES MACULIPENNIS. FEMALE. To face page 146.
ANOPHELES MACULIPENNIS.
FEMALE.
To face page 146.

spotted wings and boat-shaped eggs undoubtedly belonged to the genus appropriately named Anopheles; and only the species of this genus, so far as we know, are capable of conveying the infection from man to man. In their bodies only will the gametocytes develop. If swallowed by other biting insects or by leeches, etc., they disintegrate, and are no more.

The word mosquito has no scientific import; derived from the Spanish or Portuguese, it simply means ‘little fly’; it is used popularly to denote a gnat which bites, and most gnats bite when they have a chance. The word is sometimes extended to include certain midges. The Dipterous family, CulicidÆ, to which the gnat belongs, contains, according to Major Giles, some 242 species, divided amongst 8 genera. The great majority of species, some 160, however, belong to the genus Culex; Anopheles includes 30; whilst the remainder are divided amongst the other 6 genera, none of which are large. The collections which have been made at the British Museum, and which were worked out by Mr. Theobald, contain many species of Anopheles new to science; so that we have now some half hundred species of the genus ‘which has been hopelessly convicted of being the medium by which the malaria parasite is transmitted from person to person.’ According to the last-named authority, we have in England 17 species of Culex, and 2 of Anopheles, A. bifurcatus and A. maculipennis (claviger), though some authorities are inclined to add a third, A. nigripes. Five other species, belonging to the smaller genera of CulicidÆ, make a total of some 24 species of gnat or mosquito found in England. Culex pipiens, probably the commonest gnat the wide world over, conveys the parasite Proteosoma, or, as Ross now calls it, HÆmamoeba relicta, of the avian malaria from bird to bird; but it will not carry the parasite of human malaria. Indeed, 14 different species of Culex have been tried in this respect, and in each case with negative results. The same nice adjustment of parasite to host is found in Anopheles. It will not convey the bird malaria, that is to say, the gametocytes are destroyed in its body, but it is readily infected by the human parasite, and at the present date a considerable number of species have been successfully tried, and this not only in Europe, but in Africa, India, and the United States.

Anopheles is obviously worth studying. It has now been found very commonly distributed in England, A. maculipennis abounding in the eastern counties. Its boat-shaped eggs, laid, not as are those of the genus Culex, in little rifts, but singly, give rise to a charming little larvÆ, whose diet of minute algÆ gives a greenish tint to the centre of the body, which elsewhere is of a brownish hue. When at rest, these small larvÆ float on the water parallel with the surface, and not hanging down into the water as does the larval Culex. They have a most beautiful arrangement of minute hairs, arranged like the ribs of an umbrella turned inside out, along the upper surface of their backs, and by the action of these hairs they hang on to the surface-film. Their breathing organs open near the tail, but are not produced into the long respiratory tube by which the Culex larva can be so easily recognized. They possess the most marvellous arrangements on the head for setting up currents conveying food to the mouth, and, in fact, they afford one of the most charming objects of ‘animated nature’ that one could desire to watch. After some days, varying in number according to the temperature, the larva turns into one of those curious active Dipterous pupÆ which are well known in the case of other gnats. Like the larva, the pupa floats at the surface of the water. When mature its integument splits along the back; then the perfect insect steps out, rests a moment to dry its wings, and sails away into the air.

It is very doubtful if the male Anopheles, which can easily be distinguished from the female by its bushy feathered tentacles, quite visible to the naked eye, ever sucks blood. The habit in the female is possibly prompted by a desire to obtain material for the growth of the ova. Out of the numerous genus Culex only four species are known in which the male bites; and it is probable that malaria is always conveyed from man to man by the activity of the female. It is difficult to say how long mosquitoes live in the imago state—certainly, if fed, for many weeks. The earlier collectors, not knowing how to feed them, used to cork them up in glass tubes, and then, noticing in a day or two that the poor insect had died, retired to their studies and wrote moral essays on the brevity of life, or learned treatises on the duration of life in relation to the methods of ovipositing. Now we feed the imagos—as a rule, on bananas—and they live well in confinement. The fertilized female survives the winter, hibernating in some dusky corner, and it is probable that some of the eggs also carry the species over the cold months from autumn to the following spring.

It should, perhaps, be mentioned that the infected mosquito does not transmit the parasites to its offspring. This was an important point to ascertain, because it is known that the tick which causes Texas fever does transmit its parasite to the young ticks, and they in turn communicate the disease to the oxen. A somewhat similar case of the transference from parent to offspring of an organism causing disease is that of the PÉbrine, caused by a parasite which attacks silkworms, and which is conveyed by the infected ova from one generation to another.

The above short rÉsumÉ of the life-history and habits of Anopheles has been given as a prelude to the important question: What can be done to diminish malaria? A few years ago, before we understood the cause of the disease, much had been done to lessen it. While aiming at other objects, we drove malaria out of England by draining. Now that we know the secret of the disease we can direct our efforts more intelligently. There are two points exposed to attack. The first is the sporulating organism in the blood of man, the second is the insect. If we could eliminate the organism from man, the mosquito would be saved much suffering, and would be powerless to infect man; or, if we could prevent the mosquito from access to man, either by guarding him against its bites or by killing off the insect, the hÆmotozoÖn would, in the course of time, gradually die out.

Both methods should be tried. Malarious patients should, so far as possible, be treated with quinine, and no effort should be spared to free their system from the parasite. Special precautions, such as hanging up mosquito curtains, etc., should be taken to prevent the access of the mosquito to the patient; otherwise he acts as a centre of infection. It is almost equally important to protect the healthy man living in a malarious place. The mosquito net must be carefully made, and let down over the bed well before sunset; its free edges should be tucked under the mattress, and the greatest care should be taken to prevent the ingress of a mosquito, especially when slipping within the curtains. Punkahs should be employed as much as possible; they certainly tend to keep the Anopheles at a distance. In the summer of 1899 an experiment was initiated by Sir Patrick Manson which must convince even those least open to conviction that malaria is preventable if proper precautions be taken. That the bite of an infected mosquito can convey malaria may be taken as proved by the voluntary submission of Mr. T. P. Manson to the experiment, as recounted in the Times.[5] This gentleman allowed himself to be bitten, in this country, by insects previously fed on malarious patients; and in due course the disease—tertian ague—showed itself in him. To prove the other side of the case required even more courage and endurance. During the spring of 1899, Dr. Low and Dr. Sambon, of the London School of Tropical Medicine, with Signor Terzi, an Italian artist, and two servants, have been living in a mosquito-proof hut, near Ostia, in the Roman Campagna, and remained in perfect health. The spot selected for this experiment is so malarious that the Romans regard spending a single night there as equivalent to contracting a virulent type of malaria. Yet, when Professor Grassi and several other experts visited the mosquito-proof hut on September 12, 1900, they found the inhabitants in perfect health—a fact which they telegraphed, with their salutations, to Sir Patrick Manson, ‘who first formulated the mosquito-malarial theory.’ The conditions under which Dr. Low and Dr. Sambon and their Italian companions lived were all directed to the avoidance of being bitten by mosquitoes. During the daytime they were allowed out of their hut, because the chance of being bitten in broad daylight is so small that it may be neglected; but they were ‘gated’ an hour before sunset, and were not allowed out until an hour after sunrise. The mosquitoes were kept out of the hut by the use of wire-gauze doors and windows. By these precautions contact between mosquito and man has been avoided, and man has now lived for months in one of the most malarious spots in Europe without acquiring a trace of malaria. It is most satisfactory to record that a similar success has attended the efforts of the Italian authorities to improve the state of things in the great plain of Salerno. Visitors to Paestum and Battipaglia cannot fail to have noticed how malaria has marked that district as its own. By taking such precautions as are indicated above, the peasants and railway signalmen have, during the last few years, for the first time, escaped the disease; whilst for the first time newcomers to the district have failed to contract it. The intelligent activity of the Italian Government, and the well-known interest taken in the question by the King and Queen of Italy, cannot fail to have a profoundly beneficial effect upon the lives of some of the poorest and most hard-working of European peasantry.

The problem in Africa is more complex, owing to the fact that the native population is thoroughly permeated with the parasite. Mr. Christophers and Dr. Stephens, in their ‘Further Reports to the Malaria Committee,’ have shown that the children of natives are in the great majority of cases infected with malaria. In one village where the Anopheles was found in ‘considerable numbers,’ 90 per cent. of the babies suffered, 57 per cent. of the children up to eight years, 28 per cent. of the children up to twelve years, after which age the children were ‘very rarely infected.’ This is but one example out of many, all tending to show that after a time a certain immunity to the disease is acquired, and, further, that travellers should as far as possible avoid the neighbourhood of native villages, and, above all, decline to sleep in native huts.

The destruction of the mosquito, at any rate in neighbourhoods inhabited by man, is a matter of difficulty, but is worth attempting. To expect to destroy the mature insect seems a vain thing, but the larva can be more easily dealt with. Anopheles—unlike the common gnat, which breeds close to houses, in cisterns, garden fountains, old tubs, drains, etc.—prefers rain-water puddles, natural hollows by the roadside, small ponds, and rice-fields. We have occasionally found the larvÆ of Anopheles and Culex in the same water in England, but this is probably exceptional. In England, so far as our experience goes, the Anopheles larvÆ are usually met with in shallow water easily heated by the sun’s rays; and we have always found them in association with the common green water-weed Spirogyra, though they are not known to eat this.

Attention to the standing water round houses or near towns will do much to diminish the scourge of mosquitoes. All pots and pans containing water should be regularly turned out once a week, and puddles should be brushed out. The larva takes some seven days to develop, so that once a week suffices to destroy each brood. All useless water should be drained away and stagnant ponds filled up. The introduction of fish has markedly diminished the number of mosquitoes around the late Mr. Hanbury’s celebrated garden at La Mortela on the Riviera. They eagerly devour the larvÆ, and should be made use of in all large areas of water. For smaller areas some ‘culicide’ should be tried, and more experiments in this direction are urgently needed. One of the simplest remedies known is kerosene oil. A piece of rag tied to a stick should be dipped into the oil, and then applied to the surface of the water. The oil diffuses in a fine film over the surface and clogs the breathing tubes of the larval insect; it possibly interferes with the action of the surface tension—at any rate, the larvÆ die. Fresh tar has the same effect. This ‘painting’ of the water must be renewed once a week. Wells and cisterns should be kept closed. A more careful selection of the site for houses, and a more liberal use of wire-netting mosquito shutters, will do much to minimize the risk to Europeans in malarious districts.

The various remedies suggested above have been tried with success in different parts of the world. The writer has been assured by an old inhabitant of Colombo that the mosquitoes have distinctly diminished in number in parts of that town since the custom of storing water near the houses was abandoned. During the summer of 1900 the authorities at Sassari in Sardinia claim to have ‘practically exterminated the mosquitoes ... by killing the larvÆ in the swamps with petroleum, and the flies with chlorine and other destructive chemicals.’[6]

The extinction of malaria in England is a kind of by-product of the draining operations which restored to the agriculturist large tracts of land in the fen districts and elsewhere. The breeding-places of the mosquitoes were dried up and their numbers materially lessened; at the same time the parasite was killed in an increasing number of patients. Thus the mosquitoes which survived had fewer opportunities of infecting themselves, and as time went on the parasite was ultimately eliminated. Anopheles, though in diminished numbers, is still with us, and is especially to be found in those parts of England once infested with the malaria; but the parasite has disappeared.

                                                                                                                                                                                                                                                                                                           

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