William Osler

“ Our knowledge of the animal parasites infesting the blood has been of late enriched by observations which show that certain of these hæmatozoa, as they are called, are more widely distributed and more important than we had hitherto supposed. Parasites belonging to the spirozoa, and to the nematode and trematode worms, have long been known to occur in the blood of various animals. Recent investigations prove that the flagellate protozoa are also not uncommon blood parasites, and it is possible that they may be the pathogenic organisms of certain diseases. ”

“ The spleen-pulp contained free pigment and many large cells, some of which were filled with dark granules, while in others there were bodies identical with the small pigmented forms so abundant in the blood during life. The marrow presented similar changes. The number of red corpuscles containing the pigmented bodies was not great, nor were the capillaries of the liver or the brain stuffed with them, as in the instances of pernicious malaria just referred to. ”

“ The flagellate form is doubtless the adult condition; and it is interesting to note, in contrast to the hæmatoaoza of the rat and of the surra disease, the comparative infrequency of its occurrence. Laveran met with it ninety-two times in four hundred and thirty-two cases, and Councilman eleven times in eighty cases. The steps in development remain to be worked out. It seems clear, however, that the pigmented amœboid form may become transformed into a sporocyst (represented by the rosette form and its changes) , or into an encysted body (resting form) , the crescent. ”

“ Attempts to isolate and grow these hæmatozoa outside the body have failed. Marchiafava and Celli have shown that the inoculation of healthy persons with blood taken from a case of malaria is followed inavariable time by genuine ague paroxysms, in which the blood contains the parasites; but in regions where malaria is prevalent such experiments are not wholly free from objections. A series of negative observations on undoubted cases of malaria would be convincing. ”

“ They frequently present rapid Brownian movements. Occasionally a vacuole may be seen in the interior of the body. In several instances the bodies appeared to be enclosed in a clear space—vacuole—in the stroma. When first seen they are more or less spherical, but, as already stated, the outline may be indistinct. The pigment granules may be seen to alter their position in relation to each other. If the margin of the body is carefully observed, slow changes can be seen, which gradually bring about alterations in shape. ”

“ The number of corpuscles so affected varies extremely in different cases. In some instances they are readily found after a search of a moment or two, but, in other cases, a prolonged examination may be necessary. Only one is usually present in each corpuscle, but two or three, or even four, may occupy the stroma. They vary greatly in size, the smaller ones not occupying a fourth of the corpuscle, while the larger ones may almost fill it. A delicate contour line can usually be seen separating the body from the stroma ”

“ They are not attached, and they never show any motion. Joining the ends of the crescents—or, more correctly, at a little distance from the points—a narrow line can often be seen on the concave margin (Fig.7, e) . The body of the crescent appears made up of a structureless, homogeneous material, in the centre of which is a prominent collection of pigment granules. This, with the peculiar form, makes these bodies very easily recognisable in the blood, even when closely surrounded by the corpuscles. The pigment is very dark in colour, distinctly granular, and varies somewhat in its arrangement. ”

“ Golgi suggests that the spores, resulting from the segmentation, pass to the spleen, and there attack the red corpuscles, in which they develop into the amœboid forms. As at present the data are not available for a final decision, a further consideration of these points need not detain us. There is sufficient evidence to show that the various forms are only phases in the life-history of one of the flagellate protozoa, belonging to the order Flagellata-Pantostomata. Mitrophanow suggests a new genus, Hæmatomonas, to include the monad hæmatozoa ”

“ I think it highly probable that they do, and that they, with the hyaline unpigmented bodies, are the immature forms. The spore-like structures which result from the segmentation of the rosette form do not resemble the small solid bodies seen in the red corpuscles, but are rather like the tiny free pigmented forms which, in some cases, were abundant in the plasma. Of the latter, various sizes are found, and it is possible that from them the adult flagellate bodies arise. ”

“ Laveran's original description is well-nigh complete, and subsequent workers have done little else than confirm his results, though to Marchiafava and Celli is due the credit of insisting upon the amœboid character of the intra-cellular form. Before discussing the relation of the forms to each other, it will be necessary to take a brief review of cognate organisms occurring in the blood, upon which recent investigations throw an important light.
It has been known for some years that hæmatozoa exist in the frog ”

“ Case 52. Man, aged 25. Chills and fever for six days. Blood examined in chill, and on the following day. Had had quinine.
Thus, in five of these cases quinine had been taken, and they may be counted out. In Case 10, the child was brought from the country, and only one examination was made. Case 11 was undoubtedly a case of quotidian ague, and the examination of slides taken from each stage of the fifth and sixth paroxysm was negative. I did not see the patient, and further examinations were not made. In Case 38, the bodies were not found on two occasions. ”

“ The pigmented organism evidently destroys the vitality, and consumes the hæmoglobin, for the affected cells become pale, often spherical, and, finally, are reduced to the condition of mere shells except in cases of pronounced anæmia, the variations of the corpuscles in size and outline were not great. The colourless corpuscles were in some cases increased in number, and in very many instances contained dark granules. In several specimens, they were observed to contain the pigmented organisms. In Case 40, a crescent had been included (Fig. 13) , and, in Case 51, the process of inclusion ”

“ These movements, which appear to be amœboid in character, can often be traced with great ease. They are well represented at Fig.1, and, better still, at Fig.2. Changes in position of the body in the corpuscle result from them. They are decidedly slower than the amœboid movement of the colourless corpuscle. ”

“ The hyaline non-pigmented forms, and the vacuoles containing solid bodies, also occur in the acute cases; indeed, these latter forms were the only alterations noted in several instances. Thus, in Case 29, a man aged 48 was admitted to the Philadelphia Hospital September 27th, in a chill. He had had a paroxysm ten days before, and had suffered with malaria several years previously. The blood examined during the hot stages showed no pigmented bodies, but numerous corpuscles containing the vacuoles shewn in Figs. 5 and 6. The chills occurred on the 28th, 29th, 30th, and October lst ”

“ The blood was examined on three occasions with negative results, but on the fourth observation, five days after admission, and when the temperature had fallen to normal, crescents were found, which continued in the blood until he was thoroughly cinchonised. The cases are as follows:
Case 10. Child, aged 5; chills and fever in Maryland nine months ago, occasional chills since, the last two weeks ago; spleen 4 inches vertical diameter; had taken quinine, none recently. One examination.
Case 11. Man, aged 19; never malarial before. ”