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AT THE last meeting of this association it was my pleasure to contribute a paper on The Mosquito as a Definitive Host in Malaria. Since that time the general knowledge of the mosquito - malaria theory has become decidedly more definite. Methods of study and modes of technique have been perfected so that those of us who have taken up this phase of the great malaria problem have approached it with more intelligence and with a greater degree of confidence as to what we should find. A knowledge of the pathology and pathogenesis of disease must obviously precede and guide preventive and curative effort; this cannot be obtained, let it be said, without systematic and scientific research. The days of the casuist have passed.

In the past eighteen months the whole malaria question has been opened up and gone over carefully, systematically and scientifically, step by step, until today, having brushed aside error and doubt, having brought order out of chaos, we have the magnificently-interesting science, Malariology.

Read before Tri-State Med. Assn. (Miss. Ark. & Tenn.) Memphis, Nov. 14, 1900 VOL. XXI-9 113

The superficial can no longer, in obscure cases, take refuge behind malaria in diagnosis. The causative agent in paludism has brought about this deep scrutiny; and the results have been so plain and so simple, like the case of the Messiah and the Christian religion, the people-and any number of doctors -look for a sign.

The mosquito-malaria theory, as is well known, was dimly understood so far back as the sixteenth century. In 1807 it it is claimed for Crawford, of Baltimore, that he contributed a paper on the "Mosquital Origin of Malarial Disease" to the Baltimore Observer; a close search of the files of this publication, and his papers appearing in the Baltimore Medical and Physiological Recorder, by Drs. King and Thayer, did not lend support to the claim. Nott, of Mobile, in 1848, published a paper on yellow fever, and in touching on malaria writes as if the mosquito theory had already been advanced.

In 1883 King, of Washington, collected evidence on the subject and put it forward very elaborately, and it indeed is quite as valuable as that accumulated since, says Nuttall. Laveran followed with similar observations in 1891. Pfeiffer published Koch's views in 1892. Koch states that this idea occurred to him while investigating tropical diseases in India in 1883-4. Manson first became possessed of the idea in 1894. So it is that in their respective countries each of these men is hailed as the discoverer of the mosquito-malaria theory.

It was Surgeon-Major Ross of the Indian Medical Service who, in 1895, began to elucidate and prove what in England they call Manson's theory; and in September, 1897, after examining a thousand mosquitoes of all varieties, found the special mosquito for both avian and human malaria.

The Italians, Grassi, Bignami, Celli and others, following Ross' findings in 1898, really perfected and rounded out the mosquito-malaria theory.

In order to pursue the study of this important subject in its natural sequences it will be necessary to call to mind the parasitology of malaria. The sporulating or rosette form of the plasmodium carries on in the human economy as the temporary host. The youngest form is the hyalin body, which is at first free in the blood plasma; this obtains at the sporulation or

segmentation period. This hyalin body penetrates the cell wall of a red corpuscle and begins its destruction; at the beginning the hyalin may be seen as a round, bright, refractory spot, with a dancing motion in the center or to either side of the containing cell; at a little further advanced stage one or more grains of black or yellowish red pigment may be seen in the body of the hyalin body; this has been taken from the hemoglobin of the red cell; this we call a small pigment body; as it increases in size it is called a half grown or full grown pigment body. When it reaches full grown stage, then it is ready to divide again into more hyalin bodies-the sporulation or segmentation stage.

In the tertian parasite the full grown bodies are very large, and the parasite-infected red corpuscle swells and becomes decolorized and is readily detected by its size and large amount and rapid motion of its pigment.

The quartan-infected red cell shrinks, and its smallness of size, darker color, its smaller amount and coarseness of pigment, which is very lazy, attracts one's attention.

The tertian organism divides into eighteen or twenty spores (hyalins) in forty-eight hours; the quartan into eight or ten in seventy-two hours.

The estivo-autumnal parasite penetrating a red corpuscle sets up a more rapid necrobiosis of the containing cell, which shows crenation, spiculation, shrinks and becomes paler; the hyalin is brighter, more refractory, pigmentation comes late, which is thrown to the center, and segmentation occurs as in the tertian form; dividing into very much smaller hyalins, twelve to eighteen in twenty-four to forty-eight hours.

After four or five days of fever the characteristic crescent and ovoid bodies appear in the finger blood. These were about to be consigned as degenerate forms. Now we know that their destiny is to continue the life cycle of the estivoautumnal organism outside of the blood current.

The crescent and ovoid bodies form round bodies, which are nonsporulating, and are called by Grassi and Dionisi gameti; of these there are male and female-the latter is denominated macrogameti; these do not flagellate; the male microgametocyte develops flagella, which are thrown out as soon as they

are brought into the air or in contact with substance foreign to the blood current. The flagella are called microgameti. These flagella are the elements analogous to spermatozoa, which penetrate the macrogameti in a true sexual process; these in turn become fertilized and change their shape, becoming elongated vermiculi.

Grassi lays claim to a fourth variety of parasite, which he denominated hemameba immaculata. This was at first considered a subdivision of the estivo-autumnal form; it is said that Marchiafava and Bignami agree to this. Evidently this is the quotidian estivo-autumnal, so beautifully described by Craig, U. S. A. In this idea Craig also claims substantiation by Marchiafava and Bignami.

The flagella bearing parasite of the tertian and quartan fever is the round body which appears to slip out of the remnant red corpuscle, which does not divide, but holds its shape. Of these there are male and female.

The male soon puts out one or more flagella, having clubbed extremities, which slash and hammer around in the field, creating great commotion; this is the active flagellated body. Finally one of these flagella pulls away from the round body and may be seen making off through the corpuscular mass, crippling red corpuscles, causing them to give up more or less hemoglobin, until it finds a round (female) body; then it attacks it, and with a boring, relaxing and contracting motion penetrates it; this is called a passive flagellated body. This body changes its shape and takes on a spindle shape, threadlike form, fit for mosquito inhabitation. The active flagellated body, it should be mentioned, shrinks and becomes lost after its flagella pulls away from it.

It must here be borne in mind that these flagellated bodies do not come into existence until the plasmodia leave the blood vessels; their function, therefore, must be outside of the human body; coming from large parasites, mature forms, it is suggested that the flagella are flagellated spores, the extracorporeal homologues of the intracorporeal spores, and constitute the first phase of the extracorporeal life of the plasmodia. In the blood the sexual form of the plasmodium is always enclosed in a red corpuscle, and is therefore incapable

of leaving the body by its own efforts, and no instance has been recorded where it has been extruded or escaped in the excreta; it follows that this form or any other form must be removed from the circulation by some blood-eating animal or some suctorial insect.

The mosquito was considered the extracorporeal host first, because the malaria always appears and disappears with the mosquito season, and again it was well known that by avoiding the mosquito bite one would not get fever.

So in pursuance of this inductive reasoning and possessed of the idea of Smith's Texas cattle fever and Manson's filariasis, Ross' efforts and enterprise were rewarded as mentioned before. He found that Anopheles fed on blood from birds sick of proteosoma disease (bird malaria) developed small oval pigmented cells in their stomach walls; at the end of the week mosquitoes so infected were allowed to bite healthy birds, and at the end of another week these birds in turn fell sick, and smears of their blood showed proteosoma. The livers of such birds at death were heavily charged with black malarial pigment.

The oval-shaped cells develop from the elongated motile vermiculi as the estivo - autumnal, and the spindle-shaped, thread-like forms of the tertian and quartan flagellated bodies; these threads penetrate the stomach wall and become encysted, the so-called coccidia or oocysts. In the oocyst sporoblasts form and become germinal threads or sporozoits; these, when the oocysts rupture, are carried into the veneno-salivary gland of the mosquito, and thence back to its intermediate host.

Human malaria was first found September, 1897, by Ross, in two large "dapple-winged" (Anopheles) mosquitoes fed on crescent blood from a patient sick with estivo-autumnal malaria; soon after this he reported two other cases; all following exactly the same course of the proteosoma cells. These cells are seen to be in size in proportion to the length of time between the feeding and death of the insect, namely, 7 microns after two days, 17 microns after four days, 19 microns after five days, 25 microns after a week.

About this time Grassi, Bignami and Bastianelli took up

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