Haemosporidia

Haemosporidia, in zoology, an order of Ectospora, which although comparatively few in number and very inconspicuous in size and appearance, have of late years probably attracted greater attention and been more generally studied than any other Sporozoa; the reason being that they include the organisms well known as malarial parasites. In spite, however, of much and careful recent research—to a certain extent, rather, as a result of it—it remains the case that the Haemosporidia are, in some respects, the group of the Ectospora about which our knowledge is, for the time being, in the most unsatisfactory condition. Such important questions, indeed, as the scope and boundaries of the group, its exact origin and affinities, the rank and interclassification of the forms admittedly included in it, are answered quite differently by different workers. For example, one well-known Sporozoan authority (M. Lühe) has recently united the two groups, Haemosporidia and Haemoflagellates, bodily into one, while others (e.g. Novy and McNeal) deny that there is any connexion whatever between “Cytozoa” and Trypanosomes. Again, the inclusion or exclusion of forms like Piroplasma and Halteridium is also the subject of much discussion. The present writer accepts here the view that the Haemosporidia are derived from Haemoflagellates which have developed a gregariniform (Sporozoan) phase at the expense, largely or entirely, of the flagelliform one. The not inconsiderable differences met with among different types are capable of explanation on the ground that certain forms have advanced farther than others along this particular line of evolution. In other words, it is most probable that the Haemosporidia are to be regarded as comprising various parasites which represent different stages intermediate between, on the one side, a Flagellate, and on the other, a typical chlamydospore-forming Ectosporan parasite. While, however, it is easy enough sharply to separate off all Haemosporidia from other Ectospora, it is a very difficult matter to define their limits on the former side. Two principal criteria which a doubtful haemal parasite might very well be required to satisfy in order to be considered as a Haemosporidian rather than a Haemoflagellate are (a) the occurrence of schizogony during the “corpuscular” phase in the Vertebrate host, and (b) the formation of many germs (“sporozoites”) from the zygote; so long as these conditions were complied with, the present writer, at all events, would not feel he was countenancing any protozoological heresy in allowing for the possibility of a Flagellate (perhaps trypaniform) phase or features being present at some period or other in the life-cycle.1 To render this article complete, however, one or two well-known parasites, hitherto referred to this order, must also be mentioned, which, judged by the above (arbitrary) standard, are, it may be, on the Haemoflagellate side of the dividing line (e.g. Halteridium, according to Schaudinn).

The chief characters which distinguish the Haemosporidia from other Ectospora are the following. They are invariably blood parasites, and for part or all of the trophic period come into intimate relation with the cellular elements in the blood. There is always an alternation of hosts and of generations, an Invertebrate being the definitive host, in which sexual conjugation is undergone and which is to be regarded as the primary one, a Vertebrate being the intermediate or secondary one. The zygote or sporont is at first capable of movement and known as an ookinete. No resistant spores (chlamydospores) are formed, the ultimate germs or sporozoites always being free in the oocyst and not enclosed by sporocysts.

To Sir E. Ray Lankester is due the honour of discovering the first Haemosporidian, a discovery which did not take place until after most of the other kinds of Sporozoa were known. In 1871 this author described the parasite of the frog, which he later termed Drepanidium ranarum. The next discovery was the great and far-reaching one of Laveran, who in 1883 described all the characteristic phases of the malarial parasite which are met with in human blood. While regarding the organism as the cause of the disease, Laveran did not at once recognize its animal and Sporozoan nature, but considered it rather as a vegetable, and termed it Oscillaria malariae. As in the case of the Trypanosomes, we owe to Danilewsky (1885-1889) the first serious attempts to study the comparative anatomy and life-history of these parasites, from a zoological point of view. Danilewsky first named them Haemosporidia, and distinguished between Haemocytozoa and Leucocytozoa. To the brilliant researches of R. Ross and Grassi in the closing years of the 19th century is due the realization of the essential part played by the gnat or mosquito in the life-cycle and transmission of the parasites; and to MacCallum belongs the credit of first observing the true sexual conjugation, in the case of a Halteridium. Since then, thanks to the labours of Argutinsky and Schaudinn, our knowledge of the malarial parasites has steadily increased. Until quite recently, however, very little was known about the Haemosporidia of cold-blooded Vertebrates; but in 1903 Siegel and Schaudinn demonstrated that the same rôle is performed in their case by a leech or a tick, and since then many new forms have been described.

The Haemosporidia are widely distributed and of very general occurrence among the chief classes of Vertebrates. Among Invertebrates they are apparently limited to bloodsucking insects, ticks and leeches.2 As already stated, Occurrence: habitat; effects on host. the universal habitat of the parasites in the Vertebrate is the blood; as a result, of course, they are to be met with in the capillaries of practically all the important organs of the body; and it is to be noted that while certain phases (e.g. growing trophozoites, mature gametocytes) are found in the peripheral circulation, others (e.g. schizogonous “rosettes,” young gametocytes) occur in the internal organs, liver, kidneys, &c., where the circulation is sluggish. The relation of the parasites to the blood-cells varies greatly. Most attack, probably exclusively, the red blood corpuscles (haematids); a few, however, select the leucocytes, and are therefore known as Leucocytozoa. In the case of Mammalian and Avian forms (malarial parasites) Schaudinn and Argutinsky have shown that the trophic and schizogonic phases are not really endoglobular but closely attached to the corpuscle, hollowing out a depression or space into which they nestle; the gametocytes, on the other hand, are actually intercellular. Forms parasitic in cold-blooded Vertebrates, on the contrary, are always, so far as is known, endoglobular when in relation with the corpuscles; and the same is apparently the case with the Mammalian parasite, Piroplasma. Although in no instance so far described is the parasite actually intranuclear (as certain Coccidia are), in one or two cases (e.g. Karyolysus of lizards and certain species of Haemogregarina) it reacts markedly upon the nucleus and soon causes its disintegration. While many Haemosporidia (e.g. malarial parasites, with the exception of Halteridium) remain in connexion with the same corpuscle throughout the whole period of growth and schizogony, the new generation of merozoites first being set free from the broken-down cell, others (the Haemogregarines, broadly speaking, and also Halteridium) leave one corpuscle after a short time, wander about free in the plasma, and then seek out another; and this may be repeated until the parasite is ready for schizogony, which generally occurs in the corpuscle.

As in the case of Trypanosomes (q.v.), normally—that is to say, when in an accustomed, tolerant host, and under natural conditions—Haemosporidia are non-pathogenic and do not give rise to any ill-effects in the animals harbouring them. When, however, the parasites gain an entry into the blood of man or other unadapted animals,3 they produce, as is well known, harmful and often very serious effects. There are three recognized types of malarial fever, each caused by a distinct form and characterized by the mode of manifestation. Two, the so-called benign fevers, are intermittent; namely, tertian and quartan fever, in which the fever recurs every second and third day respectively. This is due to the fact that schizogony takes different lengths of time in the two cases, 48 hours in the one, 72 in the other; the height of the fever-period coincides with the break-down of the corpuscle at the completion of the process, and the liberation of great numbers of merozoites in the blood. The third type is the dangerous aestivo-autumnal or pernicious malaria, in which the fever is irregular or continuous during long periods.

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 are those found in human blood; below the dotted line are seen the phases through which the parasite passes in the intermediate host, the mosquito. Plan and arrangement chiefly 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-called flagella or male gametes (fl) are thrown out, one of them is seen detached; in the female (X. b) a portion of the nucleus has been expelled.

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XI., A male gamete penetrating a female gamete at a cone of reception formed 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 ripe sporozoites; on one side the cyst has burst and 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. (After Ross.)  
  
oes, Oesophagus.

st, Stomach.

cy, Cysts.

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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.  
  
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From Lankester’s Treatise on Zoology.  
Fig. 3.—Haemogregarina bigemina, Laveran, from the blood of blennies. (After Laveran, magnified about 1800 diameters.)  
  
a, The form of the parasite found free in the blood-plasma.

b, Parasite within a blood-corpuscle, preparing for division; the nucleus has already divided.

c, The parasite has divided into two rounded corpuscles, which assume the form of the free parasite, as seen in d, e and f.

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N, Nucleus of the blood-corpuscle.

n, Nucleus of the parasite. The outline of the blood-corpuscle is indicated by a thick black line.  
  
Various types of form are to be met with among the Haemosporidia. In one, characteristic of most (though not of absolutely all) parasites of warm-blooded Vertebrates, the trophozoites are of irregular amoeboid shape; hence this section Comparative Morphology; variations in the life-cycle where known. is generally known as the Haemamoebidae. In another type, characteristic of the parasites of cold-blooded Vertebrates, the body possesses a definite, vermiform, i.e. gregariniform shape, which is retained during the intracorpuscular as well as during the free condition; this section comprises the Haemogregarinidae. Allied to this latter type of form are the trophozoites of Piroplasma, which are normally pear-shaped; they differ, however, in being very minute, and, moreover, exhibit considerable polymorphism, rod-like (so-called bacillary) and ring-forms being of common occurrence. It is important to note that in a certain species of Haemogregarina (fig. 3) the young trophozoites markedly resemble Piroplasma in their pyriform appearance; and a further point of agreement between the two forms is mentioned below. Lastly there is the Avian genus Halteridium, the trophozoites of which are characteristically bean-shaped or reniform. True Haemogregarines also differ in other slight points from “Haemamoebae.” Thus the young endoglobular trophozoite does not exhibit a ring (vacuolar) phase; and the cytoplasm never contains, at any period, the characteristic melanin pigment above noted. In some species of Haemogregarina the parasite, while intracorpuscular, becomes surrounded by a delicate membrane, the cytocyst; on entering upon an active, “free” period, the cytocyst is ruptured and left behind with the remains of the corpuscle. A very interesting cytological feature is the occurrence, in one or two Haemosporidia, of nuclear dimorphism, i.e. of a larger and smaller chromatic body, probably comparable to the trophic and kinetic nuclei of a Trypanosome, or of the “Leishman-Donovan” bodies. Schaudinn was the first to notice this character, in Piroplasma canis, and his observation has since been confirmed by Lühe.4 Moreover, Brumpt has also noticed nuclear dimorphism in the ookinete of a species of Haemogregarina in a leech (as the Invertebrate host)—a highly important observation.

As regards the life-history, the endogenous (schizogonous) cycle is known in many cases. Sometimes schizogony takes the primitive form of simple binary (probably) longitudinal fission; this is the case in Piroplasma (fig. 4) and also in Haemogregarina bigemina just referred to. From this result the pairs of individuals (“twins”) so often found in the corpuscles. In addition, however, at any rate in Piroplasma, it is probable that multiple division (more allied to ordinary schizogony) also takes place; such is the case, according to Laveran, in P. equi, and the occurrence at times of four parasites in a corpuscle, arranged in a cruciform manner, is most likely to be thus explained. Labbé has described schizogony in Halteridium danilewskyi as taking place in a rather peculiar manner; the parasite becomes much drawn-out and halter-like, and the actual division is restricted to its two ends, two clumps of merozoites being formed, at first connected by a narrow strand of unused cytoplasm, which subsequently disappears. Some doubt, however, attaches to this account, as no one else appears to have seen the process. For the rest, schizogony takes place more or less in the customary way, allowing for variations in the mode of arrangement of the merozoites. It remains to be noted that in Karyolysus lacertarum, according to Labbé, two kinds of schizont are developed, which give rise, respectively, to micromerozoites and megamerozoites, in either case enclosed in a delicate cytocyst. This probably corresponds to an early sexual differentiation (such as is found among certain Coccidia (q.v.), the micromerozoites producing eventually micro-gametocytes, the others megagametocytes.  
  
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From Lankester’s Treatise on Zoology.  
Fig. 4.—Development and schizogony of Piroplasma bigeminum in the blood-corpuscles of the ox. (After Laveran and Nicolle.)  
  
a, Youngest form.

b, Slightly older.

c and d. Division of the nucleus.

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e and f, Division of the body of the parasite.

g, h, i, j, Various forms of the twin parasite.

k and l, Doubly infected corpuscles.  
  
It has now been recognized for some time that the sexual (exogenous) part of the life-cycle of all the Haemamoebidae takes place in an Invertebrate (Insectan) host, and is fundamentally similar to that above described in those cases where it has been followed. In contradistinction to the malarial parasites, this host, in the Avian forms (Haemoproteus and Halteridium)5 is a species of Culex and not of Anopheles; in other words, gamete-formation, conjugation and subsequent sporozoite-formation in these cases will only go on in the former. On the other hand, in the case of the Haemogregarines, it was thought until quite lately that the entire life-history, including conjugation and sporogony, went on in the Vertebrate host; and only in 1902 Hintze described what purported to be the complete life-history of Lankesterella (Drepanidium) ranarum undergone in the frog. This view was rendered obsolete by the work of Siegel and Schaudinn, who demonstrated the occurrence of an alternation of hosts and of generations in the case of Haemogregarina stepanovi, parasitic in a tortoise, and in Karyolysus lacertarum; the Invertebrate hosts, in which, in both cases, the sexual process is undergone, being respectively a leech (Placobdella) and a tick (Ixodes). With this discovery the main distinction (as supposed) between the Haemosporidia of warm and of cold-blooded Vertebrates vanished. It was further acknowledged by Schaudinn (under whom Hintze had worked) that the latter had been misled by Coccidian cysts and spores, which he took for those of Lankesterella. The gametogony and sporogony of Haemogregarina stepanovi in the leech agree in essential particulars with the process above described. The microgametes are extremely minute, and the sporozoites, which are developed in the salivary glands, where the motile ookinetes finally come to rest, are extremely “spirochaetiform”—the full significance of this latter fact being, perhaps, not appreciated.

Christophers recently described some remarkable phases which he regarded as belonging to the cycle of Haemogregarina gerbilli (one of the few Mammalian Haemogregarines known) in a louse (Haematopinus). In a private communication, however, the author states that he has probably mistaken phases in the development of an ordinary gregarine parasite in the louse for part of the life-cycle of this Haemogregarine.

The Mammalian parasite Piroplasma is the one about whose life-history our knowledge is most vague. Besides the typical and generally occurring forms, others have also been observed in the blood, but it is doubtful how far these are to be looked upon as normal; for instance, Bowhill and Le Doux have described, in various species, a phase in which a long, slender pseudopodial-like outgrowth is present, with a swelling at the distal end. It is, moreover, quite uncertain which are the sexual forms, comparable to gametocytes. Doflein regards large pear-shaped forms as such (megagametocytes?), which become spherical when maturing; and Nocard and Motas have figured amoeboid, irregular forms, with the nucleus fragmented and possessing flagella-like processes (possibly microgametes?). The Invertebrate host is well known to be, in the case of all species, a tick; thus bovine piroplasmosis (P. bigeminum) in America is conveyed by Rhipicephalus annulatus (Boophilus bovis), canine piroplasmosis (P. canis) in South Africa by Haemaphysalis leachi (and perhaps Dermacentor reticulatus), and so on. The manner in which the infection is transmitted by the tick varies greatly. In some cases (e.g. P. bigeminum and P. canis) only the generation subsequent to that which receives the infection (by feeding on an infected ox) can transmit it back again to another ox; in other words, true hereditary infection of the ova in the mother-tick is found to occur. The actual period in the life of the daughter-tick at which it can convey the infection apparently varies. On the other hand, in the case of East African coast-fever, Theiler found that hereditary infection does not occur, the same generation transmitting the parasite (P. parvum) at different periods of life. Little is certainly known regarding the phases of the parasite which are passed through in the tick. Lignières has observed a kind of multiple fission in the stomach, several very minute bodies, consisting mostly of chromatin, being formed, which may serve for endogenous reproduction. Koch has published an account of certain curious forms of P. bigeminum, in which the body is produced into many stiff, ray-like processes, giving the appearance of a star; according to him fusion of such forms takes place, and the resulting zygote becomes rounded, perhaps transitional to the pear-shaped forms.

The classification and nomenclature of the Haemosporidia are in a very unsettled condition. For an account of the various systems and modifications hitherto adopted, the article of Minchin (see under Sporozoa: Bibliography) should be consulted. Classification. With the realization that the life-history in the case of the “Haemamoebae” and the Haemogregarines is fundamentally similar in type, the chief reason for grouping them as distinct suborders has disappeared. It is most convenient to regard them as separate, but closely allied families, the Plasmodidae (“Haemamoebidae”) and the Haemogregarinidae. The Piroplasmata, on the other hand, constitute another family, which is better placed in a distinct section or sub-order. In addition there are, as already noted, two or three genera whose systematic position must be considered as quite uncertain. One is the well-known Halteridium of Labbé, parasitic in various birds; the type-species is H. danilewskyi (Gt. and Fel.). Another is the much-debated parasite of white blood-corpuscles (leucocytes), originally described in birds by Danilewsky under the name of Leucocytozoon, a form of which has been recently observed in Mammals.

In conclusion, the chief members of the above-mentioned families may be enumerated.

Fam. Plasmodidae (“Haemamoebidae”).

Genus Laverania, Gr. and Fel. (syn. Haemamoenas, Ross), for L. malariae, Gr. and Fel. (synn. L. s. Plasmodium, s. “Haemamoeba,” &c., praecox s. immaculatum, &c.), the parasite of pernicious malaria. Genus Plasmodium, March. and Celli (syn. “Haemamoeba”) for P. vivax and P. malariae, the tertian and quartan parasite, respectively. There is also a form known in apes, P. kochi. Genus Haemoproteus, Kruse (syn. Proteosoma), for H. danilewskyi (syn. Proteosoma grassi, Plasmodium praecox, &c.), parasitic in numerous birds. Recently, another form has been described, from reptiles, which Castellani and Willey have termed Haemocystidium simondi.

Remarks.—The distinguishing characters of the malarial parasites have been mentioned above. Some authorities would include Laverania in the genus Plasmodium, as differing only specifically from the other two forms. It has, moreover, been suggested by Sergent that all three are merely different phases of the same parasite, predominating at different seasons; this idea cannot be regarded, however, as in any way proved so far. From what is known of the morphology and mode of manifestation of these forms, the differences between Laverania and the two species of Plasmodium are considerably more pronounced than those between P. vivax and P. malariae; if the latter are to be considered as distinct species, the first-named is probably generically distinct. Lühe, it may be noted, in his recent comprehensive account of the Haematozoa, also takes this view. Lastly, whatever be the correct solution of the above problem, there is certainly not sufficient justification for including the Avian genus Haemoproteus, as also only a species of Plasmodium, which is done by some. Its different Vertebrate habitat, and also the fact that its Insectan definitive host is Culex and not Anopheles, differentiate it sharply from Laverania and Plasmodium.  
  
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From Lankester’s Treatise on Zoology.  
Fig. 5.—Haemoproteus danilewskyi, Kruse (parasite of various birds). × about 1200\. a, b, c and d from the chaffinch; d and e from the lark. (After Labbé.)  
  
a, Young trophozoite in a blood-corpuscle,

b and c, Older trophozoite.

d and e, Sporulation.

d, Precocious sporulation with few merozoites.

e, Sporulation of a full-grown schizont, with numerous merozoites.

f, Gametocyte.

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N, Nucleus of blood-corpuscle.

n, Nucleus of parasite.

p, Pigment.

mz, Merozoites.

r.p, Residual protoplasm.  
  
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From Lankester’s Treatise on Zoology.  
Fig. 6.—Haemogregarina stepanovi, Danilewsky (par. Emys and Cistudo), phases of the schizogony. (a-e and j after Laveran; f-i after Börner.) × 1000 to 1200 diameters.  
  
a, Blood-corpuscle with young trophozoite.

b, Older trophozoite.

c, Full-grown trophozoite, ready to leave the corpuscle.

d and e, Trophozoites free in the blood-plasma, showing changes of form.

f-i, Trophozoites, still within the blood-corpuscle (not drawn), showing the structure of the nucleus, the coarse chromatoid granules in the protoplasm and the manner in which the parasite grows into the U-shaped Haemogregarine without increase of body-mass.

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j, Commencement of sporulation; the nucleus has divided into eight nuclei, and the body of the parasite is beginning to divide up into as many merozoites within a blood-corpuscle.

N, Nucleus of the blood-corpuscle.

n, Nucleus of the parasite.  
  
Fam. Haemogregarinidae.—The different genera are characterized chiefly by their size relative to the blood-corpuscles, and their disposition in the latter. Here, again, it has been suggested to unite the various types all in one genus, Haemogregarina, but this seems at least premature when it is remembered how little is known in most cases of the life-cycle, which may prove to exhibit important divergences.

Genus Haemogregarina, Danilewsky (syn. Danilewskya, Labbé). The body of the parasite exceeds the blood-corpuscle in length, when adult, and is bent upon itself, like a U. A very great number of species are known, mostly from reptiles and fishes; among them may be mentioned H. stepanovi (fig. 6), from Emys and Cistudo, whose sexual-cycle in a leech has been worked out by Siegel (see above), H. delagei, from Raja, H. bigemina, from blennies, and H. simondi, from soles. Recently one or two Mammalian forms have been observed, H. gerbilli, from an Indian rat (Gerbillus), and H. jaculi, from the jerboa.

Genus Lankesterella, Labbé (syn. Drepanidium, Lankester). The parasite is not more than three-quarters the length of the corpuscle. L. ranarum from Rana is the type-species; another, recently described by Fantham, is L. tritonis, from the newt.  
  
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From Lankester’s Treatise on Zoology.  
Fig. 7.—Karyolysus lacertarum (Danil.), in the blood-corpuscles of Lacerta muralis, showing the effects of the parasite upon the nucleus of the corpuscle. In c and d the nucleus is broken up. N, Nucleus of the corpuscle; n, nucleus of the parasite, seen as a number of masses of chromatin, not enclosed by a distinct membrane. (After Marceau.)  
  
Genus Karyolysus, Labbé. The parasite does not exceed the corpuscle in length; the forms included in this genus, moreover, although not actually intranuclear, have a marked karyolytic and disintegrating action upon the nucleus of the corpuscle. The type-species is the well-known K. lacertarum, of lizards; another is K. (Haemogregarina) viperini, from Tropidonotus.

In the section of the Piroplasmata there is only the genus Piroplasma, Patton (synn. Babesia, Starcovici, Pyrosoma, Smith and Kilborne), the principal species of which are as follows: P. bigeminum, the cause of Texas cattle-fever, tick-fever (Rinder-malaria) of South Africa, and P. bovis, causing haemoglobinuria of cattle in Southern Europe; there is some uncertainty as to whether these two are really distinct; P. canis, P. ovis and P. equi associated, respectively, with those animals. Lately, a very small form, P. parvum, has been described by Theiler in Rhodesia, which causes East-African coast-fever; and another, P. muris, has been observed in white rats by Fantham.

Bibliography.—(The older literature is enumerated in most treatises on Sporozoa—see bibliography under Sporozoa). P. Argutinsky, “Malariastudien,” Arch. mikr. Anat. 59, p. 315, pls. 18-21 (1901), and op. cit. 61, p. 331, pl. 18 (1902); A. Balfour, “Haemogregarine of Mammals,” J. Trop. Med. 8, p. 241, 8 figs. (1905); C. A. Bentley, “Leucocytozoan of the Dog,” B.M.J. (1905), 1, pp. 988 and 1078; N. Berestneff, “Über einen neuen Blutparasiten der indischen Frösche,” Arch. Protistenk. 2, p. 343, pl. 8 (1903); “Über das ’Leucocytozoan’ danilewskyi,” op. cit. 3, p. 376, pl. 15 (1904); A. Billet, “Contribution à l’étude du paludisme et de son hématozoaire en Algérie,” Ann. Inst. Pasteur, 16, p. 186 (1902); (Notes on various Haemogregarines). C. R. Soc. Biol. 56, pp. 482, 484, 607 and 741 (1904); C. Börner, “Untersuchungen über Hämosporidien,” Zeitschr. wiss. Zool. 69, p. 398, 1 pl. (1901); T. Bowhill, “Equine piroplasmosis,” &c., J. Hyg. 5, p. 7, pls. 1-3 (1905); Bowhill and C. le Doux, “Contribution to the Study of ’Piroplasmosis canis,’” op. cit. 4, p. 217, pl. 11 (1904); E. Brumpt and C. Lebailly, “Description de quelques nouvelles espèces de trypanosomes et d’hémogrégarines,” &c., C. R. Ac. Sci. 139, p. 613 (1904); A. Castellani and A. Willey, “Observations on the Haematozoa of Vertebrates in Ceylon,” Spolia Zeylan. 2, p. 78, 1 pl. (1904), and Q. J. Micr. Sci. 49, p. 383, pl. 24 (1905); S. R. Christophers, “Haemogregarina gerbilli,” Sci. Mem. India, 18, 15 pp., 1 pl. (1905); H. B. Fantham, “Lankesterella tritonis, n. sp.,” &c., Zool. Anz. 29, p. 257, 17 figs. (1905); “Piroplasma muris,” &c., Q. J. Micr. Sci. 50, p. 493, pl. 28 (1906); C. Graham-Smith, “A new Form of Parasite found in the Red Blood-Corpuscles of Moles,” J. Hyg. 5, p. 453, pls. 13 and 14 (1905); R. Hintze, “Lebensweise und Entwickelung von Lankesterella minima,” Zool. Jahrb. Anat. 15, p. 693, pl. 36 (1902); S. James, “On a Parasite found in the White Blood-Corpuscles of Dogs,” Sci. Mem. India, 14, 12 pp. 1 pl. (1905); R. Koch, “Vorläufige Mitteilungen über die Ergebnisse einer Forschungsreise nach Ostafrika,” Deutsch. med. Wochenschr., 1905, p. 1865, 24 figs.; A. Labbé, “Recherches sur les parasites endoglobulaires du sang des vertébrés,” Arch. zool. exp. (3) ii. p. 55, 10 pls. (1894); A. Laveran, “Sur quelques hémogrégarines des ophidiens,” C. R. Ac. Sci. 135, p. 1036, 13 figs. (1902); “Sur une Haemamoeba d’une mésange (Parus major),” C. R. Soc. Biol. 54, p. 1121, 10 figs. (1902); “Sur la piroplasmose bovine bacilliforme,” C. R. Ac. Sci. 138, p. 648, 18 figs. (1903); “Contribution à l’étude de Haemamoeba ziemanni,” C. R. Soc. Biol. 55, p. 620, 7 figs. (1903); “Sur une hémogrégarine des gerboises,” C. R. Ac. Sci. 141, p. 295, 9 figs. (1905); (On different Haemogregarines) C. R. Soc. Biol. 59, pp. 175, 176, with figs. (1905); “Haemocytozoa. Essai de classification,” Bull. Inst. Pasteur, 3, p. 809 (1905); Laveran and F. Mesnil, “Sur les hématozoaires des poissons marins,” C. R. Ac. Sci. 135, p. 567 (1902); “Sur quelques protozoaires parasites d’une tortue d’Asie,” t.c. p. 609, 14 figs. (1902); Laveran and Nègre, “Sur un protozoaire parasite de Hyalomma aegyptium,” C. R. Soc. Biol. 58, p. 964, 6 figs. (1905); (for various earlier papers by these authors, reference should be made to the C. R. Ac. Sci. and C R. Soc. Biol. for previous years); C. Lebailly (On Piscine Haemogregarines) C. R. Ac. Sci. 139, p. 576 (1904), and C. R. Soc. Biol. 59, p. 304 (1905); J. Lignières, “Sur la ‘Tristeza,’” Ann. Inst. Pasteur, 15, p. 121, pl. 6 (1901); “La Piroplasmose bovine; nouvelles recherches,” &c., Arch. parasit. 7, p. 398, pl. 4 (1903); M. Lühe, “Die im Blute schmarotzenden Protozoen,” in Mense’s Handbuch der Tropenkrankheiten (Leipzig, 1906), 3, 1; F. Marceau, “Note sur le Karyolysus lacertarum,” Arch. parasitol. 4, p. 135, 46 figs. (1901); W. MacCallum, “On the Haematozoan Infection of Birds,” J. Exp. Med. 3, p. 117, pl. 12 (1898); G. Mauser, “Die Malaria perniciosa,” Centrbl. Bakter. (1) 32, Orig. p. 695, 3 pls. (1902); C. Nicolle (On various Reptilian Haemogregarines), C. R. Soc. Biol. 56, pp. 330, 608 and 912, with figs. (1904); Nicolle and C. Comte, “Sur le rôle ... de Hyalomma ... dans l’infection hémogrégarinienne,” op. cit. 58, p. 1045 (1905); Norcard and Motas, “Contribution à l’étude de la piroplasmose canine,” Ann. Inst. Pasteur, 16, p. 256, pls. 5 and 6 (1902); G. Nuttall and G. Graham-Smith, “Canine piroplasmosis,” J. Hygiene, p. 237, pl. 9 (1905); F. Schaudinn, “Der Generationswechsel der Coccidien und Hämosporidien,” Zool. Centrbl. 6, p. 675 (1899); “Studien über krankheitserregende Protozoen—II. Plasmodium vivax,” Arb. Kais. Gesundheitsamte, 19, p. 169, pls. 4-6 (1902); E. and E. Sergent (On different Haemogregarines), C. R. Soc. Biol. 56, pp. 130, 132 (1904), op. cit. 58, pp. 56, 57, 670 (1905); J. Siegel, “Die geschlechtliche Entwickelung von Haemogregarina,” &c., Arch. Protistenk. 2, p. 339, 7 figs. (1903); P. L. Simond, “Contribution à l’étude des hématozoaires endoglobulaires des reptiles,” Ann. Inst. Pasteur, 15, p. 319, 1 pl. (1901); T. Smith and F. Kilborne, “Investigations into the Nature, Causation and Prevention of Texas Cattle Fever,” Rep. Bureau Animal Industry, U.S.A., 9 and 10, p. 177, pls. (1893); A. Theiler, “The Piroplasma bigeminum of the Immune Ox,” J. Army Med. Corps, 3, pp. 469, 599, 1 pl. (1904); J. Vassal, “Sur une hématozoaire endoglobulaire nouveau d’un mammifère,” Ann. Inst. Pasteur, 19, p. 224, pl. 10 (1905); L. B. Wilson and W. Chowning, “Studies in Piroplasmosis hominis,” J. Infect. Diseases, 1, p. 31, 2 pls. (1904).

(H. M. Wo.)

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1 Compare, for example, the flagellated granules of certain Coccidia, which point unmistakably to a Flagellate ancestry.

2 A possible exception is a doubtful species of Haemogregarina, which has been described from the walls of the blood-vessels of an Annelid.

3 For an interesting account of the biological relations between parasites and their hosts, and the penalty Man pays for his roving propensities, the reader should see Lankester’s article in the Quarterly Review, July 1904.

4 This does away with one of the principal reasons on account of which some authorities consider Piroplasma (Leishmania) donovani as quite distinct from other Piroplasmata (see Trypanosomes).

5 It must not be forgotten that one species of Halteridium (H. [Trypanomorpha] noctuae) is said to have well-marked trypaniform phases in its life-cycle; these are preferably considered under Trypanosomes (q.v.), and therefore, to avoid repetition, are only thus alluded to here. Whether H. danilewskyi also becomes trypaniform in certain phases, and how far it really agrees with the criteria of a Haemosporidian above postulated, are matters which are not yet definitely known.

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