Popular Science Monthly/Volume 57/July 1900/Malaria and the Malarial Parasite
|MALARIA AND THE MALARIAL PARASITE.|
By PATRICK MANSON, M. D., LL. D.,
LECTURER ON TROPICAL DISEASES AT ST. GEORGE'S HOSPITAL AND CHARING-CROSS HOSPITAL MEDICAL SCHOOLS AND AT THE LONDON SCHOOL OF TROPICAL MEDICINE.
THIS lecture is devoted to a description of the parasite and of its life cycles. The existence of a parasite in malarial disease has been suspected for a long time, but only very recently have we had absolute assurance that such a parasite exists. Some time in the thirties Meckel described in the human blood certain black particles which he found in leucocytes and in certain pale, leucocyte-like bodies the nature of which he did not know. When he saw these bodies he certainly saw the malarial parasite. His observations were repeated and extended in the forties and the fifties by Frerichs and Virchow, and they, too, undoubtedly saw the malarial parasite. But it is one thing to see and quite another to recognize; discovery is recognition.
The discoveries of Laveran, Golgi, Marchiafava, Bignami and others resulted in considerable knowledge of the life history of the malarial parasite and of the correspondence between its life cycle and the clinical cycle of the disease. Laveran discovered the parasite; Golgi described the cycle of the tertian and quartan forms; the others added new data, especially concerning the more malignant parasites. The malarial parasite in its mature form has the appearance—I shall take the tertian parasite as a type—of a mass of pale protoplasm occupying practically the whole of the red blood corpuscles. Scattered through this mass of protoplasm are a number of black specks or little rods of intensely black pigment. Later in the life of the parasite a peculiar thing happens: all these little specks of black pigment concentrate usually towards the center of the organism whilst the pale protoplasm arranges itself into little spherules, the whole constituting what is known as the 'rosette body.' Later in the life of the parasite the surrounding blood corpuscle breaks away and this rosette body floats free in the liquor sanguinis and then breaks up into its constituent spores, setting free at the same time the black pigment clump. Phagocytes attack many of these free spores and probably absorb most of them, as well as the little pieces of pigment. The result is the pigmented leucocyte, so characteristic of malarial blood. A few of the spores escape and in virtue of some peculiar faculty, which is not at present understood, enter fresh blood corpuscles and appear there as pale specks in the hæmoglobin. These pale specks, if watched in perfectly fresh blood, are seen to be possessed of very active amœboid movement. They throw out pseudopodia in various directions and wander about through the hæmoglobin of the corpuscle. After a time they increase in size by assimilating the hæmoglobin. By and by there appear somewhere in the parasite those specks of black pigment which we saw in the mature animal. Later they increase still further in size until they come to occupy half, and finally nearly the whole, of the blood corpuscle. Again there is concentration of pigment and the formation of little sporules. This is the cycle, as described by Golgi, of the tertian and quartan parasite. The cycle of the tropical or æstivoautumnal parasite corresponds in plan almost exactly with that of the quartan and ordinary tertian parasite.
It was found that the life cycles of these parasites ran parallel with the clinical cycle of malarial disease. It was found that when the parasite had arrived at maturity the apyretic interval in an ague was about to conclude, and that when the parasite had arrived at the sporulating stage the patient had entered on the shivering stage of his fever. During that and the succeeding hot and sweating stage the spores had entered the red blood corpuscles, and when the parasite had ensconced itself in the red blood corpuscle and begun to grow, the fever had come to an end. It was found in tertian fever that the cycle of the parasite took forty-eight hours to complete, exactly the length of the cycle of the clinical phenomena. In quartan fever the cycle took seventy-two hours, exactly the length of the clinical cycle of that form of malarial disease. In the malignant or tropical fevers there was found to be a similar correspondence between the cycle of the parasite and the cycle of the disease. It was found that with each recurring paroxysm of fever there was a renewal of the life of the parasite, and that in this way the life of the parasite was continued from period to period and from cycle to cycle for weeks or even, especially in the case of quartan malaria, for months. Now this explains very well the way in which the malaria parasite contrives to maintain its existence in the human body, but it does not explain how it passes from host to host, neither does it explain certain appearances that Laveran and everybody else who has studied the subject have witnessed. In malarial blood you sometimes see that peculiar body, the flagellated body, which I have already alluded to as consisting of a sphere surrounded by from one to six or seven long tentacles or arms in a state of continual agitation. Neither does it explain the peculiar crescent-shaped body which also so pointedly arrested Laveran's attention. . . . Golgi's scheme leaves the passage of the parasite from host to host and also the nature of these two bodies unexplained. What relation have these two bodies to the life of the parasite? Their nature and purpose do not receive any illumination from Golgi's theory. You will find in all forms of malarial infection, if you look enough, the flagellated body; but, strange to say, you will not find it in malarial blood immediately after it is withdrawn from the body. It is only after an interval of minutes, perhaps a quarter of an hour, after the blood is withdrawn that these flagellated bodies appear. Whence do they come? If you make a preparation of malarial blood from a patient by pricking the finger and spreading a little of the blood on a slide, fixing it immediately with heat or alcohol and staining it, you will never see any of these flagellated organisms. But if the slip be kept moist and in a warm temperature for half an hour and then stained, the flagellated bodies will be seen, proving that they develop only after the escape of the parasite from the human body. Such a fact is very interesting and obviously has some significance in connection with the life of the parasite. Whence, I ask, come these flagellated bodies? If one of the crescent-shaped bodies is observed continuously, the following changes of shape may often be observed: It becomes shorter, loses its crescent shape and gives off flagella, which may break off and swim about by themselves. When they come in contact with a blood corpuscle they straighten themselves out and indulge in a peculiar vibratory movement, as if endeavoring to penetrate the corpuscle.
Many years ago King, in America, and others too numerous to mention suspected that the mosquito had something to do with malaria, but in what way they could not say. Not only civilized observers had this suspicion, but the savage natives of certain tropical countries had the same idea. Koch tells us that certain natives of German East Africa who lived in a mountainous, and therefore non-malarial, part noticed that when they descended to the malarial regions on the coast they acquired a fever which they called mibu.' They said that they were bitten there by certain insects which they also called 'mbu'—mosquito or gnat. They give the same name to the mosquito and to the fever, therefore obviously these savages associate the insect and the fever as cause and effect. Peasants in certain parts of Italy have the same idea, believing that the bite of the mosquito may be followed by the development of malarial fever.
Laveran, some years ago, in one of his numerous works on malarial fever, said that possibly the malarial parasite was cared for by the mosquito in the same way that the latter cares for the filaria of the blood. He did not, however, formulate a definite theory on the subject.
In 1894 I was engaged in working at malaria, following out Golgi's work and that of other Italians. I was particularly struck by the phenomena of exflagellation and more particularly by the fact that it occurred only when the blood had been removed from and was outside the human body. I reasoned that if this exflagellation occurs only outside the body, the purpose of the flagellated body must lie outside the human body, and that therefore the flagellated body must be the first phase of the malarial parasite outside the body, must be the first step that the malarial parasite takes in passing from one human host to another. There seemed to me to be a sort of logic in this. But how was the malarial parasite to pass from one human being to another? It was not provided while inside the human body with any organs of locomotion or penetration; as far as we know the parasite is never extruded in the excreta, neither does it habitually escape in hemorrhages. Therefore, the idea of a spontaneous escape of the parasite from the human body had to be dismissed. I therefore concluded that some extraneous agency must remove the parasite from the human body, so as to afford the opportunity for this flagellation which I had concluded must constitute the first step in its extra-corporeal life. In casting about for an organism which could effect this removal I, for many reasons similar in some respects to those that influenced the savage African, the Italian peasant, King, Laveran and others, came to the conclusion that the medium of removal and transit must be the mosquito. I was so impressed with the probabilities of this double hypothesis and with its extreme practical value, should it prove to be correct, that I endeavored to leave England for a time and to visit British Guiana or some such suitable malarial country where I might work out the idea. Unfortunately, that could not be accomplished, so I published my theory in the hope that it would appeal to someone who might enjoy the opportunities denied to me. At that time Surgeon-Major Ross was at home from India and we had many conversations on the subject. I described to him my hypothesis, the probabilities of which and the possibilities of which powerfully appealed to his highly logical and practical mind. He undertook, when he returned to India, to do his best either to establish or confute it. Accordingly he set to work in India experimenting with mosquitoes and malaria.
Eoss was stationed in Secunderabad, in the south of India, where there was abundant opportunity for experimental work—plenty of patients and plenty of mosquitoes. He got patients with crescent parasites in their blood and he got mosquitoes to bite them. He found that in the course of a few minutes after the blood had entered the insects' stomachs the crescent parasites proceeded to the formation of sphere and flagellated body. But he got no further. This experiment was repeated hundreds of times. Many of his preparations were sent to me, and I could confirm from them the accuracy of his statements on the subject. Ross was encouraged, for obviously we were on the right track. One day Ross, whose station had in the meantime been changed, caught some mosquitoes which had been feeding on a patient the subject of tertian malaria. He kept the mosquitoes and after a few days dissected them. He took the stomach out and placed it on a slip with a little salt solution, covered it with a cover-glass and examined it with a microscope. He was gratified to find lying amongst the transverse and longitudinal muscular fibres a number of spherical bodies, very sharply defined, and including a great many grains of intensely black pigment exactly like those of the malaria parasite. Eoss was at once struck with the similarity. After years of labor he believed he had at last seen the malaria parasite in the tissues of the mosquito, where we reasoned it ought to be; and he was right. At a subsequent experiment on the malarial patient he found exactly the same bodies, and on dissecting several mosquitoes at different intervals of time he found that the parasite, which originally was six micro-millimetres in diameter only, grew to sixty or eighty micro-millimetres, each parasite, notwithstanding its growth and the lapse of time, still containing the peculiar and most characteristic black pigment. Ross was now quite sure that he had found the extra-corporeal phase of the malarial parasite. Some of these preparations he sent home. I examined them and showed them to a number of friends in London familiar with the malarial parasite; they agreed with me, as Laveran also did, in believing that probably this indeed was the long-sought-for extra-corporeal phase of the malarial parasite. Ross at that time had great difficulty in getting opportunities for experiment on the human subject and in procuring proper mosquitoes. He found that the mosquitoes in which he had discovered these pigmented bodies were of a different species to those on which he had formerly experimented, and that in this circumstance lay the explanation of his lack of success earlier as well as the secret of his ultimate success. Failing to get sufficient opportunity for experimenting on human malaria he turned to bird malaria. He found that the sparrow of Calcutta, in a large proportion of instances, contained in its blood a malaria-like parasite. Ross procured a number of infected sparrows and let loose upon them a number of mosquitoes of a species belonging to the genus culex. These mosquitoes, after from one to ten days, he dissected and examined their stomachs. He found in the stomach-wall pigmented bodies exactly similar to those which he found in the stomach-walls of mosquitoes fed on human malarial blood. He found that they increased in size and in a week or ten days grew from six to eighty micro-millimetres in diameter. When they became of considerable size they protruded like warts from the surface of the insect's stomach and were included in a very definite capsule. At this stage the capsule was filled with a vast number of very minute rod-like bodies. These capsules, which now projected into the body cavity of the insect, being over-distended, ruptured and discharged the rod-like bodies into the body cavity of the mosquito. For a time Ross could get no further than this. He could not find what became of the rod-like bodies. One day, in dissecting the head of a mosquito, he encountered two small trilobed glands the ducts from which united to form a main duct. The glands lay on either side of the head and the common duct he traced to the base of the proboscis of the mosquito. This was the salivary gland of the mosquito. He found that the cells of the gland contained rod-like bodies exactly like those which he had found inside the parasitic capsules in the stomach-wall. He concluded that somehow these 'germinal rods' (for so he called them) had managed to find their way into the salivary gland of the mosquito. It immediately occurred to him that this might be the route by which the parasite escaped from the mosquito into its vertebrate host. No sooner had the idea occurred to Ross than he put it to the test of experiment. He selected a number of sparrows in whose blood he satisfied himself that there were no parasites and let loose upon them a number of mosquitoes which he had already infected with malarial parasites. He found after a week or ten days that the sparrows which were experimented upon sickened and many of them died; and in their blood he found the malarial parasite.
We now understand why the flagellated body is developed outside the human host: because its function lies outside the human host. We now understand why the flagella break away and enter the granular sphere: they impregnate it and start it on the road of development. We now understand why MacCallum's vermicule is beaked and endowed with powers of locomotion and penetration: that it may approach and penetrate the stomach of the mosquito. And we now know why the sporozooites, the 'germinal rods,' enter the mosquito's salivary gland: that they may be injected into vertebrate issue and so pass the parasite from vertebrate to vertebrate.
This is one of those fairy tales of science which people are inclined to doubt, but any one who has worked at the subject and taken the trouble to go through the long series of preparations which have been sent home from India can not for a moment have the slightest doubt that what Ross stated was absolutely true, and that not only for bird but for human malaria. So soon as the idea got abroad that the key to the way in which the malarial parasite is propagated had been found the Italians immediately set to work with renewed vigor and with the utmost skill. Almost at once they demonstrated that what happened in the case of Ross's sparrows happened also with the human subject: that the appropriate species of mosquito fed upon the human malarial subject and subsequently allowed to feed upon a non-malarial subject conveyed the malarial parasite and malarial disease, and that the appropriate species of mosquito belonged to the genus anopheles. There can not be the slightest doubt that the mosquito acts the part of transmitting agent as well as definitive host of the malarial parasite.
This is a piece of knowledge of the utmost importance to mankind, for we know that malarial disease in tropical countries—which, after all, in the future will be the most important parts of the world, seeing that they can produce more food than temperate countries and can therefore support a larger population—causes more deaths and more disposition to death by inducing cachectic states predisposing to other affections than all the other parasites affecting mankind put together. We know now in what way this parasite is acquired. Depend upon it, in time, in virtue of this knowledge, we will get enormous power over the disease and sooner or later we will be able to prevent the infection of man by the parasite. It is only a question of study and the application of the knowledge already acquired, only a question of money and perseverance and a little ingenuity, and these results will come. It may not be in ten years or twenty years, but sooner or later the energies of a considerable portion of scientific mankind now being expended in endeavoring to devise means for preventing the infection of men with the malarial germ by the mosquito will bear valuable fruit.
You can readily understand that it is of great importance to be able to recognize the special species of mosquito which convey malaria. The effective species as regards human malaria belong to the genus anopheles; species of the genus culex are effective in the case of sparrow malaria. Fortunately, these two genera are easily recognized even by the amateur zoölogist. If you find a mosquito clinging to the wall or other surface you can tell which genus it belongs to by its posture. If the body is stuck out nearly at right angles to the surface on which the insect is resting, it is an anopheles. If the body is almost parallel to the surface, it is a culex. There is another test which is easily applied if you have a pocket lens; in culex the two organs known as palpi are rudimentary and very short; whereas in anopheles those organs are almost as long as the proboscis. It should be remembered that the male mosquito is not a blood-sucker and therefore is not dangerous. It is the female anopheles which transmits the disease. The mosquito larvæ inhabit stagnant or slow-running water. If a mosquito larva be found with its head downwards, the body hanging at right angles to the surface of the water, it is a culex; if the body lies parallel to the surface of the water, it is an anopheles. There are other points of difference with which I need not now trouble you; those referred to suffice for diagnosis between the innocuous and the dangerous mosquitoes.
The facts regarding the malaria parasite which I have described are of great importance for many reasons. First, because they help us to understand the pathology and etiology of malaria. Secondly, they help us in diagnosis. Thirdly, our knowledge of the parasite is invaluable in directing treatment. Lastly, a knowledge of the life-history of the malarial parasite is of extreme value for the prevention of malarial disease, for could we by mechanical or other arrangements prevent the mosquito attacking the human body, we could prevent the malarial parasites from entering the human body; or if we could abolish the mosquito by drainage or other means from a country, then we might be sure that we would abolish the malaria of that country also. Attempts are being made to solve these practical problems. At the present moment such attempts are being actively made in Rome by Professor Celli and elsewhere by others. I have no doubt that in the course of a few years we shall get some very valuable results in this direction and that, thanks to this new-born knowledge about the malarial parasites, better times are rapidly approaching for malarial countries.
- Abstract of a lecture delivered at the Medical Graduates' College and Polyclinic, and printed in the Lancet of May 19.