A very general symptom is anaemia, which is sometimes present to a marked extent, when it may lead to a fatal termination. This is the result of the very considerable destruction of the blood-corpuscles which takes place, the haemoglobin of which is absorbed by the parasites as nutriment. A universal feature connected with this mode of nutrition is the production, in the cytoplasm of the parasite, of a brown pigment, termed melanin; this does not represent reserve material, but is an excreted by-product derived from the haemoglobin. These pigment-grains are at length liberated into the blood-stream and become deposited in the various organs, spleen, liver, kidneys, brain, causing pronounced pigmentation.
Another type of fever, more acute and more generally fatal, is that produced by forms belonging to the genus Piroplasma, in cattle, dogs, horses and other domestic animals in different regions of the globe; and recently Wilson and Chowning have stated that the “spotted fever of the Rockies” is a human piroplasmosis caused by P. hominis. The disease of cattle is known variously as Texas-fever, Tristeza, Red-water, Southern cattle-fever, &c. In this type of illness the endogenous multiplication of the parasites is very great and rapid, and brings about an enormous diminution in the number of healthy red blood corpuscles. Their sudden destruction results in the liberation of large quantities of haemoglobin in the plasma, which turns deep-red in colour; and hence haemoglobinuria, which occurs only rarely in malaria, is a constant symptom in piroplasmosis.
The parasite of pernicious malaria, here termed Laverania malariae, will serve very well as a type of the general life-cycle (fig. 1). Slight differences shown by the other malarial parasites (Plasmodium) will be mentioned in passing, but the Example of the life-history. main divergences which other Haemosporidian types exhibit are best considered separately. With the bite of an infected mosquito, the minute sickle-like sporozoites are injected into the blood. They rapidly penetrate into the blood corpuscles, in which they appear as small irregular, more or less amoeboid trophozoites. A vacuole next arises in the cytoplasm, which increases greatly in size, and gives rise to the well-known, much discussed ring-form of the parasite, in which it resembles a signet-ring, the nucleus forming a little thickening to one side. Some authorities (e.g. Argutinsky) have regarded this structure as being really a greatly distended vesicular nucleus, and, to a large extent, indeed, an artifact, resulting from imperfect fixation; but Schaudinn considers it is a true vacuole, and explains it on the ground of the rapid nutrition and growth. Later on this vacuole disappears, and the grains of pigment make their appearance. The trophozoite is now large and full-grown, and has become rounded and ready for schizogony. The nucleus of the schizont divides several times (more or less directly, by simple or multiple fission) to form a number of daughter-nuclei, which take up a regular position near the periphery. Around these the cytoplasm becomes segmented, giving rise to the well-known corps en rosace. Eventually the merozoites, in the form of little round uninuclear bodies, are liberated from the now broken-down corpuscle, leaving behind a certain amount of residual cytoplasm containing the pigment grains. Besides the difference in the time taken by the complete process of schizogony in the various species (see above), there are distinctions in the composition of the rosettes. Thus, in Laverania, the number of merozoites formed is very variable; in Plasmodium vivax (the tertian parasite) there are only few (9 to 12) merozoites, but in P. malariae (the quartan form) they are more numerous, from 12 to 24. The liberated merozoites proceed to infect fresh blood corpuscles and a new endogenous cycle is started.
After asexual multiplication has gone on for some time, sexual forms become developed. According to Schaudinn, the stimulus which determines the production of gametocytes instead of schizonts is the reaction of the host (at the height of a fever period) upon the parasites. A young trophozoite which is becoming a gametocyte is distinguished from one which gives rise to a schizont by its much slower rate of growth, and the absence of any vacuoles in its cytoplasm. The gametocytes themselves are characterized by their peculiar shape, like that of a sausage, whence they are very generally known as “crescents.” Male and female gametocytes are distinguished (roughly) by the arrangement of the pigment-grains; in the former, they are fairly evenly scattered throughout the cytoplasm, but in the megagametocytes the pigment tends to be aggregated centrally, around the nucleus. As they become full-grown and mature, however, the gametocytes lose their crescentic form and assume that of an oval, and finally of a sphere. At the same time, they are set free from the remains of the blood corpuscle. The spherical stage is practically the limit of development in the Vertebrate host, although, sometimes, the nucleus of the microgametocyte may proceed to division. The “crescents” of the pernicious parasite afford a very important diagnostic difference from the gametocytes of both species of Plasmodium, which have the ordinary, rounded shape of the schizonts. In the case of the latter, points such as their slower growth, their less amoeboid character, and their size furnish the means of distinction.
When a gnat or mosquito sucks blood, all phases of the parasite in the peripheral circulation at that point may succeed in passing into the insect. If this occurs all trophic and schizogonic phases are forthwith digested, and the survival of the sexual phases depends entirely upon whether the insect is a gnat or mosquito. Only in the latter case can further development of the gametocytes go on; in other words, only the genus Anopheles, and not the genus Culex, furnishes specific hosts for the malarial parasites. This is a biological fact of considerable importance in connexion with the prophylactic measures against malaria. In the stomach of an Anopheles, the gametocytes quickly proceed to gamete-formation. The nucleus of the microgametocyte divides up, and the daughter-nuclei pass to the periphery. The surface of the body grows out into long, whip-like processes, of which there are usually 6 to 8 (probably the typical number is 8); each is very motile, in this respect strongly resembling a flagellum. This phase may also develop in drawn blood, which has, of course, become suddenly cooled by the exposure; and it seems evident that it is the change in temperature, from the warm to the cold-blooded host, which brings about the development of the actual sexual elements. Earlier observers regarded the phase just described as representing another parasite altogether, of a Flagellate nature—whence the well-known term, Polymitus-form; and even more recent workers, such as Labbé who connected it with the malarial parasite, failed to appreciate its true significance, and considered it rather as a degeneration-appearance. The micro-gametes soon liberate themselves from the residual cytoplasm of the parent and swim away in search of a megagamete; each is a very slender, wavy filament, composed largely of chromatic substance. The finer details of structure of the microgamete of a malarial parasite cannot be said, however, to be thoroughly known, and it is by no means impossible that its structure is really trypaniform, as, according to Schaudinn’s great work, is the case with the merozoites and sporozoites.
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| From Lankester’s Treatise on Zoology. | |
| Fig. 1.—Diagram of the complete life-cycle of the parasite of pernicious malaria,Laverania malariae, Gr. et Fel. The stages on the upper side of the dotted line arethose found in human blood; below the dotted line are seen the phases through whichthe parasite passes in the intermediate host, the mosquito. Plan and arrangementchiefly after Neveu-Lemaire; details of the figures founded on those of Grassi,Schaudinn (Leuckart’s Zoologische Wandtafeln), Ross and others. | |
I.-V. and 6-10 show the schizogony. VI.-XII., The sexual generation. XIII., The motile zygote. XIV.-XIX., Sporogony. I.-III., Young amoebulae in blood-corpuscles. IV., Older, actively amoeboid trophozoite. V., Still older, less amoeboid trophozoite. 6, Mature schizont. 7, Schizont, with nucleus dividing up. 8, Young rosette stage. 9, Fully formed rosette stage. 10, Merozoites free in the blood by breaking down of the corpuscle. VI., Young indifferent gametocyte. VII., a, Male crescent. VII., b, Female crescent. VIII., a and b, The gametocytes becoming oval. IX., a and b, Spherical gametocytes;in the male (IX. a) the nucleus has divided up. X., a and b, Formation of gametes;in the male (X. a) the so-calledflagella or male gametes (fl) arethrown out, one of them is seendetached; in the female (X. b) aportion of the nucleus has been expelled. | XI., A male gamete penetrating afemale gamete at a cone of receptionformed near the nucleus. XII., Zygote with two pronuclei in proximity. XIII., Zygote in the motile stage (vermicule or oökinete). XIV., Encysted zygote (oöcyst). XV., Commencing multiplication of the nuclei in the oöcyst. XVI., Oöcyst with numerous sporoblasts. XVII., Commencing formation of sporozoites. XVIII., Full-grown oocyst crammed with ripesporozoites; on one side the cyst has burstand the sporozoites are escaping. XIX., Free sporozoites, showing their changes of form. n, Nucleus of the parasite. p, Melanin pigment. fl, “Flagella.” sp. bl., Sporoblasts. r. n., Residual nuclei. r. p., Residual protoplasm. |
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| From Lankester’s Treatise on Zoology. | |
| Fig. 2.—Stomach of a mosquito,with cysts of Haemosporidia. (AfterRoss.) | |
oes, Oesophagus. st, Stomach. cy, Cysts. | Mt, Malpighian tubules. int, Intestine. |
The megagametocyte becomes a megagamete directly after a process of maturation, which consists in the expulsion of a certain amount of nuclear substance. The actual conjugation is quite similar to the process in Coccidia, and the resulting zygote perfectly homologous. In the present case, however, the zygote does not at once secrete an oöcyst, with a thick resistant wall; on the contrary, it changes its shape, and becomes markedly gregariniform and active, and is known for this reason as an ookinete. The ookinete passes through the epithelial layer of the stomach, the thinner and more pointed end leading the way, and comes to rest in the connective tissue forming the outer layer of the stomach-wall (fig. 2). Here it becomes rounded and cyst-like, and grows considerably; for only a thin, delicate cyst-membrane is secreted, which does not impede the absorption of nutriment. Meanwhile, the nucleus has divided into several, around each of which the cytoplasm becomes segmented. Each of these segments (“blastophores,” “zoidophores”) is entirely comparable to a sporoblast in the Coccidian oocyst, the chief difference being that it never forms a spore; moreover the segments or sporoblasts in the oocyst of a malarial parasite are irregular in shape and do not become completely separated from one another, but remain connected by thin cytoplasmic strands. Repeated multiplication of the sporoblast-nuclei next takes place, with the result that a great number of little nuclei are found all round the periphery. A corresponding number of fine cytoplasmic processes grow out from the surface, each carrying a nucleus with it, and in this manner a huge number of slender, slightly sickle-shaped germs or sporozoites (“blasts,” “zoids,” &c.) are formed. Each oocyst may contain from hundreds to thousands of sporozoites.
When the sporogony (which lasts about 10 days) is completed, the oocyst ruptures and the sporozoites are set free into the body-cavity, leaving behind a large quantity of residual cytoplasm, including pigment grains, &c. The sporozoites are carried about by the blood-stream; ultimately, however, apparently by virtue of some chemotactic attraction, they practically all collect in the salivary glands, filling the secretory cells and also invading the ducts. When the mosquito next bites a man, numbers of them are injected, together with the minute drop of saliva, into his blood, where they begin a fresh endogenous cycle.
There is only one other point with regard to the life-history that need be mentioned. With the lapse of time all trophic and schizogonic (asexual) phases of the parasite in the blood die off. But it has long been known that malarial patients, apparently quite cured, may suddenly exhibit all the symptoms again, without having incurred a fresh infection. Schaudinn has investigated the cause of this recurrence, and finds that it is due to the power of the megagametocytes, which are very resistant and long-lived, to undergo a kind of parthenogenesis under favourable conditions and give rise to the ordinary asexual schizonts, which in turn can repopulate the host with all the other phases. Microgametocytes, on the other hand, die off in time if they cannot pass into a mosquito.