Throughout the paroxysm, hourly examinations were made; rosette forms were abundant, and segmentation active. On the 13th and 14th, the ordinary forms were present, and in the paroxysm of the 15th, the segmenting bodies were again seen. the development of pneumonia interrupted the observations. It is worth noting that in this case the onset of the paroxysms was marked by an outbreak of the most intense urticaria. Blood and lymph from the wheals did not show any special changes.
Certainly the segmentation seems associated in some way with the paroxysm in these cases, but unless our observations have been faulty or very incomplete, there are many others in which there are no such changes in the attack. It is a point, however, to which the attention of observers should be carefully directed.
The crescents appear, as already stated, to be confined to the more chronic cases, or to those which have had treatment. They may persist for weeks or months. Thus in Case 56—a patient had irregular fever with what he called dumb chills, which had lasted for a month—for three weeks there was fever without chills, the temperature rising on some occasions to 103°. The crescents were numerous, and were not associated with other forms. With this his general condition was good, and he did not look anæmic. Under arsenic he improved, and the fever subsided, but the crescents were still in his blood six weeks from the date of the first observation.
Genuine paroxysms may occur in these chronic cases without the development of other forms than the crescents. This observation was repeatedly made in Case 25, a man with irregular malaria of many months' duration and occasional severe chills. The flagellate organisms did not seem to have any special relationship to the paroxysm, but they were so rarely seen that my observations on this point are not of much value.
Influence of Medicines on the Organisms.—Quinine invariably caused the pigmented bodies to disappear. In acute cases, which were usually studied during two or three paroxysms before the administration was begun, this observation was repeatedly confirmed. In a few days the corpuscles were entirely free; in several instances, the crescents appeared before the blood became normal. For example, Case 46 had his first chill on October 1st, and a daily recurrence until the 10th, when he came under observation. The pigmented bodies were abundant, and continued so on the 11th and 12th, when the temperature rose in the paroxysm to 105°. Quinine (twenty grains) was given on the morning of the 13th (which broke the chill), and repeated on succeeding days. The bodies were present on the 13th, and a few on the 14th. They were not found on subsequent days. In less acute cases the action of the quinine did not seem to be so prompt, and the crescents did not disappear so rapidly under its use. Certainly, in recent cases this medicine acts as a positive specific against these organisms, just as it does against the malady itself. Arsenic does not appear to influence the pigmented intra-cellular bodies. In a chronic case, without chills, but with irregular fever, the crescents persisted for over five weeks, although the patient had improved in general health and vigour, and was no longer anæmic. Thallin and antifebrin were given in some cases without any noticeable results. As is well known to practitioners in malarial regions, there are cases of intermittent fever which subside without special treatment. I have had several patients in whom, without any quinine, the chills stopped or recurred very irregularly. In Case 66, the crescents appeared in the blood, which at first contained only the intra-cellular forms.
Cases examined with Negative Result.—As before stated, there were eight instances of apparently true malaria in which the organisms were not found, and to these I shall now briefly refer. I would remark, in the first place, that we cannot always rely upon one, or even two, examinations of the blood for these bodies. They may be very scanty, or they may be present at one examination and absent at the next. For example, Case 41, a young man, aged 26, was admitted with a temperature of 104°. He had been cranberry-picking in New Jersey, and had been ill for a week with fever and indefinite pains, but no chills. He was so very dull, that as the fever persisted, typhoid was suspected, although, as a cranberry-picker, malaria was first thought of. 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. Four distinct paroxysms. Slides examined from fifth and sixth, taken in cold, hot, and sweating stages. No quinine. I did not see the case subsequently.
Case 20. Man, aged 40. First attack six months ago. Chills on and off for past three months. Blood examined three days after last chill. Had taken quinine for two days. Spleen enlarged.
Case 21. Man, aged 28. Examined on 17th, first chill on September 6th; four since. On 14th, took quinine grs. xxx, and has had gr. x. t. i. d. since.
Case 26. Man, aged 35. Chills for three weeks, at first quotidian, latterly tertian. Had taken medicine, but did not know the nature of it. Was admitted on 24th. Two examinations, negative; pigment in white corpuscles. On 25th quinine was given. Three subsequent examinations, without result.
Case 28. Man, aged 60. Admitted on 14th. Well-marked chills for eight weeks; had one when he came in, and four after. Blood examined on 28th, two slides. He had had quinine gr. xx each day since admission.
Case 38. Man, aged 70, resident of the almshouse for six years. First chill on 2nd, second on the 5th, third on 6th, when blood was examined, two slides.
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. This man also could not be followed, and I do not know his subsequent history.
The importance of excluding other causes for the paroxysmal chills was well illustrated by a case under the care of my colleague, Dr. J. H. Musser, which we regarded as one of malaria, but in which the pigmented bodies could not be found. The man had had chills on and off for several years; of late, the attacks had been more frequent and recurred more regularly. Quinine in medium-sized doses had no influence, but very large doses appeared to control the paroxysms. Their recurrence excited suspicions, and the discovery of pus in the urine, with decided pain on deep pressure in the lumbar region, indicated a more probable cause for the irregular chills.
Nature of the Organisms.—It is very evident that we are dealing here with structures unlike any others which have been described in human blood, and with bodies which have no relation whatever to the spirilla, micrococci, and bacteria of certain acute diseases. I would call attention to the remarkable unanimity in the description of these parasites by Laveran, Richard, Marchiafava and Celli, Councilman, Golgi, and myself. 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; one form, a flagellate organism, the Trypanosoma sanguinis, described by Grubyin 1843, is a well recognised monad; a second, the Drepanidium ranarum, of Lankester, is evidently a gregarine, possibly a larval form, as he suggests.[1] Having been long familiar with these bodies,[2] which were very abundant during several winters in the frogs in my labaratory at Montreal, I was at once struck with an apparent similarity to them of the forms found in malarial blood. The crescent-shaped body in particular resembles strongly certain of the gregarines, and I thought it possible that we had here an instance of a sporozoon becoming flagellate at one stage of its development as Rivolta affirms may be the case. I soon discovered, however, that there were other observations on hæmatoza which bore more directly on the subject, and rendered possible a more likely explanation. Mitrophanow,[3] in 1883, announced the discovery, in the blood of the carp and of the mud-fish, of parasites belonging to the flagellate infusoria. A description of these forms need not detain us, further than to note that they were polymorphic, and one stage was represented by an amœboid body without flagella.
In a report published by the Panjab Government, December 3rd, 1880, and in the Veterinary Journal, London, 1881-82, my friend, Dr. Griffith Evans, described a new and very fatal disease known as surra, which prevailed among horses, mules, and camels in India, and
