strong to drive away the corpuscles in the vicinity. The undulatory movement caused by the play of the filament over the surface of a group of corpuscles may attract the attention of the observer before he sees the cilia. The motion does not persist long, in none of the specimens which I examined, for more than half an hour. In one instance, the flagella disappeared in the short interval between two observations, but I could not determine what became of them. I have not seen the free-swimming cilia described by Laveran, but Dr. Councilman tells me that he has confirmed this observation. I have not been able to discover either nucleus or vacuoles in the flagellate organism. Slight, irregular changes in outline occur, due to slow movements in the protoplasm.
(d) Small, round, pigmented bodies, from one-fourth to one-half the size of a red corpuscle, were not uncommon in some cases (Fig. 12).
Usually, they remained unchanged, but, in several instances, they showed amœboid movements. The smaller ones about equal in size the products of subdivision of the rosette form.
Before proceeding to discuss the nature of these bodies and their relation, I will briefly refer to the condition of the blood-corpuscles.
The red corpuscles showed no other notable alteration save that already described. 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
of two free pigmented bodies was watched during half an hour (Fig. 14). The blood-plaques were, as a rule, scanty, even when the anæmia was pronounced. No pigment was seen in them.
Types of Malaria Studied.—Of the seventy cases examined, a majority were instances of ordinary intermittent fever, chiefly quotidian and tertian, with two quartan cases. There was one case of remittent fever, one of comatose pernicious malarial fever, and the remainder were cases of malarial cachexia or chronic paludism, with occasional outbreaks of fever, with or without chills. In all of the cases, with the exception of seven, one or other of the forms above described was found in the blood.
Relation of the Forms to the Varieties of Malaria.—The pigmented amœboid bodies are met with in both acute and chronic cases, but they may be said to be specially characteristic of the more acute manifestations of the disease. In recent examples of quotidian or tertian ague which had not been under treatment, the amœboid intra-cellular forms were almost invariably present. I will refer subsequently in detail to the cases in which they were not found. 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; and each day the blood was carefully examiined, without finding other bodies than those in the vacuole or hyaline spaces. On October 1st, the patient began with ten grains of quinine twice a day, which was continued for five days. He had no chill after October 1st. On the 7th there were crescents in tolerable numbers, which persisted until the 27th, the date of the last examination.
The crescents appear to be associated with the more chronic forms of malaria, or with acute cases which have been under treatment for some time. Of eighteen cases in which they were present, in twelve there was a history of infection lasting from six weeks to six months. In many, the cachexia was marked, and the spleen greatly enlarged. In six instances the attacks were recent—under a month; but in every one of these cases quinine had been taken. As a rule, the crescents occur red alone in the blood; but there were cases observed in which the pigmented amœboid bodies, the rosette form, and the flagellate organisms, were also present. I did not find the crescents in any recent cases of intermittent fever which had not been under treatment.
The rosette form, with its peculiar segmentation, occurred in six cases, and always in association with the amœboid intra-cellular bodies. Case 31: tertian ague, examined in fourth attack; no medicine. Case 33: quotidian for seven days. Case 37: quotidian for six weeks, anæmic, and had a large spleen; took quinine one day. Case 39: quotidian for seven days. Case 58: quotidian, on and off, for six weeks, then stopped; now daily chill for a week. Case 60: quartan for three weeks. I have noted these details, as this form has not been much studied, and as Golgi seems inclined to ascribe to it an important connection with the development of the paroxysm. It was only observed in acute cases which had not been under treatment.
The flagellate organisms were present in seven cases, six of which were chronic forms, and one an acute case of three weeks' duration.
The small free pigmented bodies were very variable in numbers; they seemed more abundant in the chronic forms with cachexia.
Relation of those Forms to the Paroxysm.— Very many observations were made with a view of determining whether these organisms bore any definite relation to the remarkable periodic attacks which characterise acute malaria. For this purpose, in typical cases, examinations were made in the intervals of, just before, and in each stage of, the paroxysm. The results may be thus stated: there were instances, particularly if recent, in which the amœboid organisms were decidedly more numerous and larger before and during the paroxysms than in the intervals; there were others in which the number during the chill and hot stage was so small, that examples were very hard to find; in others again, slides taken before the attack and during each stage were negative, and yet insubsequent paroxysms the bodies were present in the blood. I think, on the whole, that the pigmented bodies in the red corpuscles are more numerous before and during an attack, but the difference is by no means striking, and I have repeatedly had to search long in slides prepared during a paroxysm for a single example. In acute cases which have lasted some weeks, and have had no medicine, the amœboid bodies have seemed to be quite as abundant at one time as another. Nor have I been able to see any special difference in the form of the bodies just before or during the chill, though in the early days of the attack they may be small and less distinctly pigmented, or indeed may present, as in Case 29, already referred to, the appearance of vacuoles containing small solid bodies.
The remarkable segmentation of the rosette form was in each instance met with during the paroxysm, and Golgi claims to have traced in five cases a series of changes corresponding to the stages of the attacks. In the intervals, the pigmented bodies gradually increase in size until they fill the affected red corpuscles, and finally the pigment collects in the centre, as shown at Fig. 9. The process of fission coincides with the onset and course of the paroxysm, and by the time of its conclusion the rosette forms disappear. In Case 60—a quartan ague—an attempt was made to follow these changes, with the following result. The patient, a lad of 18, had had malaria, on and off, for a year, but for three weeks before admission the chills had been recurring with regularity. On Saturday, the 6th, the blood was examined in the chill. The red corpuscles contained many large pigmented bodies, and the rosette forms were numerous, many in process of subdivision. On the 7th and 8th, he was free from fever, and the most careful examination of the blood failed to detect any forms but the ordinary pigmented intra-cellular bodies. They did not seem more numerous on the evening of the 8th than they were on the 7th. On the 9th, hourly examinations of the blood were made between 11a.m., when the fever began, and 4p.m. in the first two slides, there were very many pigmented bodies with the granules becoming concentrated, some with typical rosettes and a few in course of segmentation. In the specimens taken during the afternoon, the process of division was readily traced, and there were many of the small bodies in the field. On the 10th the note is: "No free bodies, all intra-cellular, tolerably numerous; no rosettes; no segmentation." On the 11th, several examinations were made, and then note reads, "absolutely none, save pigmented forms in the red." On the 12th, the slide at 8a.m. showed large number of pigmented bodies, some with the granules irregularly arranged, other with distinct rosette. Fever began at 12a.m.