Pearls & Parasites

by Sir A. E. Shipley

Hæmamœba vivax, which causes the tertian fever, passes through the various stages of its life-history in man in forty-eight hours; hence the febrile paroxysm occurs every second day. Malaria is usually of the tertian type, and this is certainly the most common form in temperate climates. Occasionally the infection has been repeated, and we may find that there are two groups of the parasite present in the blood, which arrive at the sporulating stage on alternate days; in this case the febrile symptoms manifest themselves every day, and the type of malaria is designated ‘quotidian intermittent fever.’ In this case, if a single dose of quinine be administered at the right time, one group of parasites is killed off and the quotidian fever is reduced to a tertian. There may occasionally be more than two groups present, or the parasites may for some reason have failed to arrange themselves in groups, in which case the fever becomes irregular or continuous.

In the quartan fever the parasite Hæmamœba malariæ takes seventy-two hours to complete its cycle in man, and the paroxysms occur every three days—that is, there are two days without febrile symptoms, followed by a day when there is a paroxysm. This form is common in Sicily and in certain parts of Italy—for instance, around Pavia. Just as in the tertian fever, so in quartan there may be a second infection, in which case paroxysms arise on two successive days, followed by a day of intermission of the fever. If a third group be present, we have a quotidian fever. The æstivo-autumnal fever, due to Hæmomenas præcox, is noted by a marked irregularity in its clinical symptoms. It usually sets in during August, September, or October, and is attended by much more serious results than are the regular intermittent fevers. The pernicious or malignant form of malaria, rarely seen in temperate climates, but common in the tropics, is caused—in many cases, though perhaps not in all—by the same parasite.

From what has been above described, it is evident that when once the parasite has obtained entrance to the blood it may remain and multiply for years. The parasite is, however, very susceptible to the poisonous action of quinine, and this is especially the case at the time when sporulation has just taken place and the spores are being set free in the blood. Quinine seems to have little or no effect on the organisms whilst they are inside the blood-corpuscle, but shortly before the paroxysm is due it should be administered. Quinine is amongst the very few absolutely trustworthy specifics known to medical science. It seems to have been introduced into Europe in the year 1640 by the Countess of Chinchon, a small town south-east of Madrid. The Countess was Vice-Queen of Peru, and in 1638 was cured of a tertian fever by the use of Peruvian bark. Shortly afterwards she started for Europe with a supply of the drug, but unfortunately died on the voyage. About a hundred years later Linnæus named the plant after this lady, but acting on erroneous information omitted the first ‘h’ in the name, and called the plant Cinchona. According to some authorities the word ‘quinine’ is derived from ‘quina,’ the Spanish spelling of the Peruvian word ‘kina,’ which signified bark.

But to come back to the parasite. It was mentioned above that the amœbulæ become either sporocytes or gametocytes. We have followed the fate of the former and must now turn our attention to the latter. In the genus Hæmamœba the gametocyte has a general resemblance to the sporocyte before its nucleus divides and it begins to form spores; and it is impossible to predict which amœbulæ will become sporocytes and which will become gametocytes. In Hæmomenas, however, the gametocyte can be recognized at an early stage. In this genus some of the amœbulæ become globular and ultimately form spores, whilst others become elongated and slightly curved; in fact, they assume the shape of minute sausages. These are the gametocytes. It is on this difference in shape that Ross has founded his new genus for the parasite of the æstivo-autumnal fever, all the essential characters of which had, however, been previously recognized by Italian and American observers.

So long as the gametocytes remain in the blood of the patient they undergo no further development; on being liberated from the cell into the fluid of the blood, they degenerate and die; but if they be removed, even only on to a microscope-slide, they begin to develop. They escape from the red corpuscle in which they have hitherto been confined, and some of them—the male gametocytes—are then seen suddenly to emit long filaments ([Fig. 1], 10). These filaments can be watched under a high power struggling violently to free themselves from the cell which has given rise to them. Ultimately they succeed, and breaking loose, at once dart away amongst the corpuscles and other debris on the slide. So long ago as 1880 Laveran had seen these bodies, but until 1897 their nature was quite misunderstood. This formation of the filaments or flagella, sometimes called ‘flagellation,’ can only take place at comparatively high temperatures. This has an important relation to the seasonal variation in the prevalence of the disease.

Hitherto in this article we have only studied the malarial parasite inside the body, with the exception that we have just seen that, should it get out, certain cells undergo a further development and produce mobile filaments. It occurred to many that these filaments might be spores, which were in some way carried into the blood of man. Later research showed that this is not their true meaning; but, acting on some such belief, Dr. Patrick Manson propounded the hypothesis that the spores may be conveyed to man by the intervention of some blood-sucking insect; and the brilliant and laborious researches of Major Ross, undertaken with the view of establishing the truth or falsehood of this hypothesis, have within the last few years cleared up the whole question of the transmission of the disease from one patient to another.

It is a well-established belief in many malarious countries that the mosquito plays a part in the infection. The negroes of the Usambara Mountains, who acquire the disease when they descend to the plains, even use the same word to denote the disease and the mosquito. In Assam, in Italy, and in Southern Tyrol, the belief in the mosquito origin of malaria obtains. Experienced travellers, like Livingstone, Emin Pasha, and General Gordon, insisted on the importance of mosquito-nets, thinking that the netting ‘acted as a filter against the malarial poison,’ and knowing by experience that its presence diminished the tendency to the disease. The whole epidemiological evidence was put together in a masterly essay on the mosquito theory, read before the Philosophical Society of Washington in 1883, by Professor A. F. A. King. There was thus a considerable body of opinion in favour of the mosquito-malaria theory, when, in 1894, Manson explained his views to Major Ross, at that time a surgeon in the Indian Medical Service.

Manson’s own epoch-making researches on Filaria—another human parasite whose intermediate host is the mosquito—no doubt strengthened his faith and helped to encourage Major Ross, who in 1895 began in Secunderabad a series of investigations, which, after much weary work, were crowned with brilliant success. The difficulties of the work were very great. Hardly anything was known about the great number of gnats and mosquitoes which are found all over India, and it was often impossible to have them accurately determined. Then no one could predict the appearance of the parasite within the body of the mosquito—if it were there—or in what part of the body it should be looked for. The mosquito had to be searched cell by cell. The difficulty of dissecting a mosquito is great even in temperate climes, and when we recollect that hundreds of all the available species were dissected in the most malarious districts in India, we must recognize that it was only a faith akin to that which moves mountains which sustained the courage and stimulated the perseverance of the tireless worker. For nearly two years and a half Major Ross searched in vain. No matter what species of mosquito he worked at, the results were negative. A less determined man would long ago have abandoned the research; Major Ross only tried new methods. At Sigur Ghat, near Ootacamund, a peculiarly malarious district, he noticed for the first time a mosquito with spotted wings which laid boat-shaped eggs. Shortly afterwards he was able to feed eight specimens of this mosquito on a patient whose blood contained the parasites in the gametocyte stage—and it should have been mentioned above that all mosquitoes dissected were first fed upon the blood of malarious patients. Six of these insects were searched through and through, organ by organ, but without result. The seventh showed certain unusual cells in the outer surface of the stomach, which contained a few granules of the characteristic black pigment or melanin of malarial fever. The eighth and last specimen showed the same characteristic cells with the same characteristic pigment; but the peculiar cells, quite unlike anything hitherto met with in the mosquito’s body, were larger and further developed. ‘These fortunate results practically solved the malaria problem.’

Without following in detail the various stages of the further investigations carried on by Major Ross, we must endeavour to give an account of the final results obtained by him and later investigators. Being unable to obtain material for the study of malaria in man owing to the scare caused by the outbreak of plague amongst the natives, Ross worked out the life-history of an allied organism which causes malaria in birds. It is to the brilliant researches of the Italian school—prominent among whom are Grassi, Bastianelli, and Bignami—that we owe the first complete accounts of the life-history of the human parasite. It has already been explained that some of the parasites do not form spores, but persist in a more or less unchanged condition whilst in the blood of man as gametocytes. We have also seen that when removed from the human body some of these gametocytes throw off actively mobile filiform bodies. In 1897 MacCallum of Baltimore showed what these filiform bodies really are. Certain of the gametocytes do not produce them, but lie passively still on the microscope-slide, or in the blood within the mosquito’s stomach. These are destined to form the female cell; the filamentous bodies which break off from the first-named gametocyte were seen by MacCallum to fuse with them, and, in fact, to play the part of the male cell or spermatozoön. This, in fact, happens when a mosquito feeds on a malarious patient. The gametocytes, unchanged in the blood of man, as soon as they reach the stomach of the insect, swell and burst from their red corpuscle. The male gametocyte throws off the filiform bodies, which actively swim about seeking a female gametocyte ([Fig. 2], 1). When found they fuse with it, and thus produce a fertilized cell or zygote ([Fig. 2], 3). This zygote is produced on the microscope-slide, and in the alimentary canal of certain mosquitoes, but so far as is known at present it undergoes further development only in the stomach of the various species of the mosquito genus Anopheles. In all other cases it dies or is digested. In Anopheles, however, the zygote travels to the walls of the stomach, pierces the inner coats and comes to rest underneath the muscular tunic which ensheaths that organ ([Fig. 2], 4 and 5).

At first the zygote is very small, about the size of a red blood-corpuscle; but it grows, and in the course of about a week it has, roughly speaking, increased to five hundred times its original bulk ([Fig. 3], 1 and 3). Its contents have not only increased, but have divided into some eight or twelve cells, called meres; and each of these meres has given off round its periphery a number of filiform cells, called blasts ([Fig. 3], 2). The structure of the mere, with its coating of blasts, may be easily understood by a zoologist when it is mentioned that it very closely resembles that stage in the formation of the spermatozoa of the earth-worm just before the spermatozoa separate themselves from the blastophor; the lay mind may gain a better idea of its appearance by recalling the head of a mop. As the zygote, still resting on the outside of the mosquito’s stomach, matures, the cells which are giving rise to the blasts diminish in size and disappear, leaving the capsule packed with thousands of minute filiform slightly spindle-shaped blasts ([Fig. 3], 3). Then the capsule bursts and the blasts make their way into the body-cavity, or space between the stomach and the wall of the mosquito’s body. It is not known whether they have any movement of their