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parasites ripen less regularly than in the cysted in the outer layer of the stomach wall, simple intermittent fevers, and the result is that There a remarkable evolution took place, with rupture of sporocysts is taking place all the large increase in size of the encysted parasite, time, poi-on such as I spoke of is being poured resulting after week or so in the production into the blood continuously, and we get a con- within each parasite of an enormous numb r tinued fever, or a fever which only occasionally of minute rod-like bodies, which were event remite to a slight extent, instead of the burst of ually set free in the body cavity of the mos- ague, with the succeeding complete intermission, quito by the rupture of the cyst coutaining | which characteris s the more benign types of them. These germinal rods were carried every- fever. Eo definite are the differences among where through the body by what corresponds the three main types of the parasite that it is to the blood-circulation in the mosquito, but possible by microscopic examination of a drop of tended to accumulate especially in the salivary blood from the finger of a fever patient to or poison glands, the glands that secrate the diagnose not merely the fact of malaria, but its acid fluid which the mosquito injects when it variety and the probable future course of the bites, and which causes the irritation of the illness. For some time after this, the method mosquito bite, and in the duct which leads of transmission of malaria from one human be- from these 'glands to the proboscis or mouth ing to another remained a mystery. It was of the insect. Finally, Ross caused mosquitoes found that blood containing the parasite of thus infected. +fter the period necessary for the marlaria, if inoculated in a healthy person, not evolution of the parasite just described had only reproduces the disease but produces elapsed, to bite healthy sparrows, whose blood invariably malaria of a type exactly correspond- he had ascertained to be free from proteosoma, ing with that inoculated. But how nature and succeeded in by this means infecting them with that parasite. This is now spoken of as effects this same object remained unknown.

I mentioned that most of the parasites in the the cycle of Ross. What Ross thus proved blood of a person suffering from malaria form for sparrow malaria, viz, that certain culex sporocysts, and by means of

spores the mosquitoes may carry the disease from one existence of the parasite within the infected bird to another, was eagerly followed up by person is maintained; but this is not true of all Italian scientists, among whom Grassi's name the parasites, certain of them on reaching ranks bigh, and very soon similar facts were maturity not going on to sporulation. These worked out in yet fuller detail, proving a pre- exceptional parasites, which in the malignant cisely similar relation between the anopheles type of malaria are crescentic in form, mosquito and buman malaria. Let me state it when observed under the microscope under briefly: anopheles mosquitoes are not naturally suitable conditions, were found to throw off infective. But if they ingest human blood con- little rapidly moving whip like processes, which taining malaria parasites, then at the end of a become detached and float free in the blood week or so, the period required for the evolu- fluid. In 1894, Dr. Patrick Manson suggested tion of the germimal rods, called sporozoites, that as these cells only develop their fl gella they become infective to any human being on some time after the blood has been drawn from whom they may feed, injecting the germs with the juice which they always inject be the body, and never possess them at the time of leaving the human body, this would probably fore they begin to suck blood. A man so infec- prove to be part of an extra-corporeal cycle of ted by the bite of an infected anopheles will, the parasite, and that these cells would be after an incubation period of a little over a found to have something to do with the trans- fortnight, during which the parasite is multiply- mission of the disease from one person to ing itself within his blood cells, develop

the malaria. another. He further suggested that as

A single infective bite is probably parasite lives only within the blood corpuscles, sufficient to convey the disease.

Meanwhile, at the other side of the globe, a and appears in none of the discharges, it must be carried by some blood-sucking insect, which young American patholgoist, named MacCallum, from its habits and the correspondence of its was studying at Baltimore another cognate distribution with that of malaria he believed parasite, named halteridium, which he found in would prove

to be the mosquito. The possibility the blood of crows, and which I find exists in of something of this nature being the truth pigeons in Hongkong, and he discovered in had before been suspected, but it was Manson | 1897 the actual destination of the free-swim- who definitely publicly propounded the theory.ming whip-like processes which I mentioned as Major Ronald Ross of the Indian Medical being given off by the flagellating form of the Service set to work to test Manson's theory. parasite. While watching certain parasites His method was to allow mosquitoes, which under the microscope he noticed that some of had been bred from the larval stage in his them gave off flagella as I have described, laboratory to secure that they should be free others, however, somewhat more granular in from any infection otherwise, to bite persons appearance, remaining quite passive. He saw a suffering from malaria, and then after vary-free flagellum approach one of the quiescent ing intervals to search in the bodies of the parasites, enter it, and become fused with insects thus fed with infected blood for evidence its substance. And then a remarkable change of the presence or development of the parasite. occurred. The hitherto entirely passive little For two long years he failed to find any trace animal became exceedingly active in its move- of it. Yet he persisted, and it is this persist- ments, and gradually became elongated and

its appearance.

MacCallum ence in the pursuit of the theory that bad laid wormlike in hold on him, in face of such utter failure, that recognised that what he had seen was a true constitutes one most admirable feature of Ross's sexual process in a very lowly form of animal life. Koch observed this fertilised form, work. At length, in August 1897, he tried a hitherto unused species of mosquito, belonging wormlike in shape, in a mosquito's stomach to the now well-known genus anopheles, and soon after feeding a culex on a sparrow infected Finally, Grassi traced found that, a day or two after they had been fed with proteosoma.

the whole process, step by step, in the case of with malarial blood, organisms similar to those of malaria were to be found encysted between human malaria, bringing together, and apply the layers of the stomach walls in the infected ing to the human parasite what had been worked insects. He had solved the problem of the out, bit by bit, as I have shown, by many transmission of malaria, although much detail workers, of various nationalities, in widely At no single still needed to be filled in. Just at this crucial separated parts of the world. moment Ross's research was interrupted by an point is the evidence incomplete. outbreak of plague, and when he was able to resume it early in 1898 it was not the fever season, and no cases of malaria were available. In these circumstances he turned his attention to the life-history of a parasite similar to the malaria parasite of man that causes a correspond- ing blood infection in sparrows and other small birds. He found that culer mosquitoes, which had given entirely negative results with human malaria, were able to be the hosts of the parasite of sparrow malaria, proteosoma, Briefly, Ross's resulta were as follows:-He fed mosquitoes on sparrows infected with the pro- teosoma. In insects so fed he found that the parasites made their way through the inner membrane of the stomach, and became en-

Briefly epitomised, the mosquito malaria theory is as follows:-The parasites of malaria, like many other parasitic organisms, have two cycles of development. One is asexual, by spore formation, providing for the propagation of the parasite within the human host. The other cycle is sexual, fertilisation taking place in the stomach of the mosquito, when infected blood has been ingested, and development taking place in the walls of the stomach. The germs pro- duced collect in great numbers in the salivary glands of the insect, and are injected with the poison when it bites a human being. And, finally, healthy persons thus bitten by infected anopheles themselves contract the disease a fortnight or three weeks later.

[December 20, 1902.

Let me invite your attention to this diagram kindly placed at my disposal by Dr. Hunter fron among those he uses for class purposes in the College of Medicine for Chinese f but I beg of you do not read his nomenclature. It was made in Germany:" There are a dozen different ways of describing what is here illus- trated, all of them admirable, but tending to terrific confusion when they happen to meet. "There are nine and As Kipling has it:

sixly ways of constructing tribal lays; of them is right." and every single one A public experiment was arranged in 1900 under the auspices of the Colonial Office, and under the direction of Dr. Manson, by whom it was suggested, to thoroughly test the mosquito- malaria theory, positively and negatively. It was no new experiment, for proof was already abounding, but it was a public popular demon- stration.

On

of the

Mosquitoes were infected in Italy with the parasites of benign tertian malaria; sent to London with all speed; and allowed to feed on Dr. Thurburn Manson, a son of Dr. Manson, and on Mr. R. Warren, of the London Tropical School. In each case fever developed exactly eighteen days after they were bitten by the infected mosquitoes, and the parasite of benign tertian malaria was found in their blood by competent independeat observers. the other hand, Dr. Sambon, one Lecturers at the London Tropical School, and Dr. Low, one of the most brilliant of its students, volunteered to spend the fever season of 1900 in the most deadly spot to be found in the Roman Campagna, with no protection against malaria other than the avoidance of mosquito-bites between sunset and sunrise, the hours during which anopheles usually feeds. This they secured by means of a care- fully constructed hut, whose windows were covered with wire gauze, into which they retired an hour before sunset each evening. They moved freely about the country in the daytime. They lived thrs in the district of Ostia, near the mouth of the Tiber, from 19th July to 19th October, 1900. ie., the whole of the severely malarious season; and retained perfect health. A control experiment was inadvert- ently made during their residence at Ostia, After the assasination of King Humbert, which occurred just then, fifteen or sixteen police agents were sent to Ostia to arrest suspected anarchists, and though they spent only part of a night in the district every man of them contracted fever a fortnight or so later, ... after the usual in- cubation period. Dr. Sambon and Dr. Low, with two companions, an artist and a servant, spent three months in their hut among the marshes, using no-quinine or other prophylactic, and not one of the four contracted malarial fever. Thus, positively and negatively, the Colonial Office experiment was entirely success= ful.

A most important point in its bearing on practical measures against the malaria-con- veying mosquito is that the mosquito does not transmit the parasite of malaria to its offspring. It might have been otherwise. In the case of the cognate parasite of a wasting disease of cattle, which is very widely spread over the world, though it is known as Texas fever, the tick which conveys the parasite from one animal to another transmits it to its young, so that the young tick is infective from the first. But ex- periment and observation in Italy, and else- where have rendered it certain mosquito does not do this, and that the insect to become infective must itself be first in- dividually infected, by feeding on a human being whose blood contains the parasite of malaria.

that the

And this leads me to mention of another important practical consideration. So far as is known, no other animal shares with man the tendency to be the intermediate host of the parasites of human malaria. Many animals, cattle, sheep, dogs, bats, monkeys, birds, frogs, etc., suffer from blood parasites akin to those of malaria; but the parasites are of quite distinct species. Koch specially investigated the possibility of transmitting malaria to the lower animals in Java, where he was able to experiment with animals closely allied to the human species, the orang-outang and hylobates, but he failed entirely to produce the disease in these higher apes, as other investigators have failed with other animals. This, of course, does not absolutely prove that no lower animal can be hospitable to the parasites of human

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