city Powell1) noted that for nine months in the year the sub-tertian and tertian parasites occurred in approximately equal numbers; in July, August, and September the tertian was more frequent than the subtertian in the proportion of about 3:2; while throughout the year the quartan parasite was rarely found (usually less than 1 per cent.). Again, in West and East Africa the quartan parasite is very rare; in Central Africa the parasite is almost exclusively the sub-tertian; in tropical South America, all forms are met with; in the West Indies, the Philippines, and in parts of Malaya, the quartan parasite is common. Although, therefore, taking certain districts, seasonal variations do occur, in many others the parasites are almost exclusively of one, or of one or two types throughout the year.

Inoculation experiments, though they are not very numerous, practically always result in the inoculated person developing a type of fever and of parasite the same as those of the person from whom the infected blood used for the inoculation was derived, and are in favour of the hypothesis of plurality of parasites. Clinically, malarial fever may show some change in type, but this is not associated with a change in character of the parasite. Broadly speaking, each type of fever is associated with a parasite having definite characters.

There is a tendency for all forms of malarial fever at the first onset to be severe and more or less continuous, periodicity becoming more evident later, but although there may be some change in type of the fever, the parasites from the first retain the characteristics of the particular type, provided re-infection do not occur. Thus, in Manson's experiment, in which mosquitoes were infected in Rome with parasites from a case of benign tertian fever, conveyed to London and allowed to infect two young Englishmen (T. Manson and Warren), the fever at first was more or less continuous, but parasites of the tertian type were present from the first and retained these characters throughout, the fever afterwards becoming distinctly tertian.

As regards the co-existence of different species of parasite in an individual and in turn predominating we have definite evidence that this can and does occur. Thus I have here a temperature chart kindly lent me by Dr. Daniels of a case in which both tertian and subtertian parasites were found to be present together and coincidently. At first, however, the fever was tertian, i. e., the tertian parasites predominated and exerted their effect; later, however, the fever became sub-tertian, and the sub-tertian parasites predominated. I feel sure that in those cases in which the fever apparently changes its type, and in which re-infection can be excluded, a careful examination would show the co-existence of both types of parasite.

The argument of similarity of pathological anatomy in the different types of malarial fever has little weight, for many quite distinct diseases are associated with pathological changes of much the same character. Could any Could any one distinguish measles, whooping-cough, and simple bronchitis in the majority of instances from one another by the

1) Ind. Med. Gazette. XXXIX. 1904. March.

pathological changes alone? There are, however, distinct differences in the blood changes in the different types of malarial fevers.

Personally I am a pluralist, and in this view I follow the lead of Grassi, Manson, Daniels, Lühe1), Ziemann2), Schaudinn3), Ruge1), Mannaberg), and many others.

The differences between the parasites of the several types of fever in morphology, movement, development in the erythrocytes, and schizogony, in the gametocytes and in sporogony, seem to me to be so marked as to constitute differences of specific rank. In fact if these differences be not of specific rank, then I think that many parasites which every one holds to be distinct species would have to be considered as mere varieties, e. g., the Spirochaetae of the relapsing fevers and of African tick fever, many Piroplasmata, etc. I would distinguish at least three spezies 6), viz.

1. Plasmodium malariae, the parasite of quartan fever,

2. Plasmodium vivax, the parasite of benign tertian fever, 3. Laveriania malariae, the parasite of sub-tertian (i. e., tropical, malignant, or aestivo-autumnal) fever.

The two genera Plasmodium and Laverania are distinguished by the differences in the gametocytes, spheroidal in the first, crescentic in the second.

As regards Laverania malariae, the parasite of sub-tertian fevers, it is quite possible that this is not a single species, but two or more species or at least varieties. The length of the cycle of the development of the parasite cannot be followed, and this point therefore does not help. The amount of pigment also is probably not of much importance, for pigment is excretory and therefore variable in amount. But there are distinct differences in different cases in the number of spores, in the effects upon the erythrocytes, in the amount of anaemia produced, and in the occurrence of albuminuria (Daniels). Thus in British Guiana, parasites with a small number of spores (6-8) are not infrequent, and in a particular case, all the parasites will probably have either few or many spores, but an admixture of the few and many spored parasites does not usually occur. The so-called brassy bodies" also occur only in certain districts, e. g., in West Africa and in Malaya; in many localities they are never seen.

H. M. Smith) describes à peculiar form of the malarial parasite in cases of a pernicious type in the Philippines. The parasites were hyaline non-pigmented and intracellular; no crescents, extra-cellular nor segmenting forms were seen. The parasite appeared as a hyaline

1) Handbuch der Tropenkrankheiten. Bd. II. S. 220.

2) Ibidem. S. 281.

3) Arbeiten a. d. Kaiserl. Gesundheitsamt. Bd. XIX. 1902. S. 169.

4) Handbuch der path. Mikroorganismen, Kolle und Wassermann, Ergänzungsband. H. 2. S. 391.

5) Art. „Malaria" in Nothnagels Practice of Medicine. English Transl. p. 195. 6) Plasmodium, Marchiafava and Celli. Laverania, Grassi and Feletti. The specific name of the sub-tertian parasite may be falciparum (Welch), but I have no time to discuss questions of nomenclature.

7) American Medicine. 1905. October.

disc of an oval spindle form, sharply defined outline and highly refractive, and at the centre of each a dark dot was present. It tapered at each end, no amoeboid motion was observed, but it moved around or across the infected corpuscle. It stained with difficulty and possessed no nucleus nor chromatin dot. No other form of para

site was found.

These were probably Cropper's bodies", structures observed by Cropper) in malarial fever in Palestine. Nuttall and Graham Smith2) have encountered similar bodies in canine piroplasmosis, but offer no opinion on their nature. Evidently the peculiar bodies observed by Smith are no new form or species of the malaria parasite; it is doubtful, indeed, if they be parasites at all.

As regards latency of malarial infection, the occurrence of an attack long after the primary attack and without re-infection, many theories have been propounded.

Bignami considers that the plasmodia may exist in some latent form, perhaps encapsulated, in the spleen or other organs, which is set free under certain favourable conditions, reproduces the parasites and so gives rise to a relapse.

Schaudinn states that recurrences are due to parthenogenesis of the unfertilised macrogametes in the host, eventually leading to the formation of schizonts which become attached to the erythrocytes, undergo schizogony, and so produce the infection of the relapse.

Craig) believes that a process of intra-corpuscular asexual conjugation of the malarial plasmodia occurs (previously described by Ewing) from which a resting or zygote form of the plasmodium is produced which is resistant to quinine and other injurious influences. This zygote form remains dormant until conditions are favourable, when young plasmodia develop and cause a recurrence.

Craig describes the process as taking place in three stages. 1. Two young hyaline rings before the formation of pigment come in contact and the protoplasm of two adjacent pseudopodia begins to fuse; the chromatin masses remain separated. 2. The chromatin masses become situated in the protoplasm of one organism, formed by the gradual union of the protoplasm of the two. The complete union of the protoplasm of the two plasmodia results in a more or less perfect ring-shaped organism, slightly larger than either of the two original parasites, and containing two chromatin masses. 3. The third stage is characterised by the union of the two chromatin masses.

In cases treated at once with a sufficiency of quinine, intracorpuscular conjugation is never seen and in such cases relapses are very rare, if they ever occur.

There is no doubt that the appearances, described by Ewing and by Craig to occur, but their interpretation is another matter. Edmond Sergent), for example, suggests that the process may be one of division rather than of conjugation.

Either Bignami's hypothesis of encapsulation or that of Schaudinn of parthenogenesis seems to me to be the most likely explanation of malarial latency that has at present been suggested.

The question of the variation of virulence of the malaria parasite is a difficult one and one on which we possess little definite information. That malaria differs much in intensity in different districts, at different seasons, and in different epidemics is undeniable. Such variations might depend on 1. variations in the virulence of the parasite itself, 2. variations in the susceptibility or tolerance of the human host, 3. variations in the mosquito host, attenuating the virus, or altering the dose of virus inoculated.

Of variations in the virulence of the malaria parasite itself we have little direct evidence, but from analogy with other micro-parasites it can hardly be doubted that it exists.

Variation in susceptibility and tolerance of the human host undoubtedly does exist, both individual and racial. The native races of tropical countries on the whole are decidedly less susceptible than the white races and the negro races are particularly so. Now the malaria. parasite is kept alive in tropical countries by infection, often latent, of the natives, and the native races being relatively insusceptible, we may perhaps assume that such parasites would be more virulent than the parasites inhabiting a more congenial soil, and this would partly account for the intensity of malaria in tropical countries.

There is an analogy in the case of piroplasmosis in the East, e. g., in Hongkong and the Philippines. The cattle here seem generally to harbour piroplasmata in small numbers but do not suffer any ill effect. After inoculation with a view to the prevention of rinderpest, however, the animals in many cases developed Texas fever. In Malaya, also, is was found that in cattle in the later stages of rinderpest piroplasmata may be present in numbers. These instances show that the cattle in these districts while susceptible to infection with the piroplasma are under ordinary conditions tolerant of its effects, and thus a distinction must be made between susceptibility to infection and tolerance of such infection. It would therefore, perhaps, be more correct to say that natives are more tolerant to the effects of, than less susceptible to infection by, the malaria parasite, particularly as native children in most countries are highly susceptible to infection, and adult native negroes from non-malarial Barbadoes are highly susceptible to infection when they go to a malarial country.

As regards the mosquito host, it has been suggested that an immunity to the development of the parasite may be acquired by the mosquito and would account for the extinction and absence of malaria. in certain districts where the disease was formerly prevalent and where the conditions for its development still exist. There may be some truth in this hypothesis but there is no definite proof of it. There is no evidence that the mosquito host is injuriously affected by the development of the parasite within it, though Daniels has noted that individual mosquitoes seem to vary much in their susceptibility to infection by Proteosoma. Some species of Anophelinae may be more favourable than others for the development of the parasite. Ed.