Chapter XI: Appendix: “Rhizopods in Poliomyelitis acuta.” (5)

The sporoblasts are originally naked, but each soon secretes a homogeneous membrane, the sporocyst, in which it becomes enveloped (fig. 67, XVIII). After the segmentation of the nucleus the contents divide into two sickle-shaped sporozoites, in addition to which there is generally also a residual body (fig. 67, XIX).

This terminates the development. The spores are intended for the infection of other hosts. If they reach the intestine of suitable hosts, either free or enclosed in the oöcyst wall, the action of the intestinal juices causes them to open and permits the escape of the sporozoites (fig. 67, XX). The latter move exactly like the merozoites and soon make their way into epithelial cells (fig. 67, I), where they become schizonts, and thus repeat the life cycle.

Although our knowledge of the development of the coccidia is but of
recent date, yet it already extends to a large number of species,
which exhibit various deviations from the cycle of development
described above. For instance, in addition to differences in the
gametocytes, the schizonts of _Adelea_ and _Cyclospora_ also show
differentiation and give rise to macromerozoites and micromerozoites,
whilst in _Adelea_ and _Klossia_ a precocious association of the
gametocytes precedes the true copulation of the ripe gametes.

The classification of the Coccidiidea is based chiefly on the number of sporozoites found in each spore, and the number of sporocysts (spores) found in one oöcyst. Léger[173] recognises two great legions, the Eimeridea and the Adeleidea, the former comprising the greater number of genera, including the genus of most economic importance, _Eimeria_. It must be noted that, though a member of this genus may be frequently referred to as _Coccidium_, strictly it should be termed _Eimeria_, that name having priority. The name of the disease resulting from the action of such parasites is, however, established and remains as coccidiosis.

[173] _Arch. f. Protistenkunde_ (1911), xxii, p. 71.

Certain of the more important of the Coccidiidea may now be considered.

Genus. *Eimeria*, Aimé Schneider, 1875.

Syn.: _Psorospermium_, Rivolta, 1878; _Cytospermium_, Rivolta,
1878; _Coccidium_, R. Leuckart, 1879; _Pfeifferia_, Labbé, 1894;
_Pfeifferella_, Labbé, 1899.

The Eimeria belong to Léger’s old family, the Tetrasporocystidæ, which comprises forms producing oöcysts with four sporocysts, each containing two sporozoites. The cysts are spherical or oval, as are also usually the schizonts. The members of the genus are confined chiefly to vertebrate hosts, the more important economically occurring in mammals and birds. From the mammalian hosts very rarely the parasites may reach man. _Eimeria_ (_Coccidium_) _avium_ of wild birds and poultry, and _Eimeria stiedæ_ parasitic in rabbits, may be considered. There is a general similarity in their life-cycles and each is of great practical importance.

*Eimeria avium*, Silvestrini and Rivolta.

_Eimeria avium_ is responsible for fatal epizoötics among game birds
such as grouse, pheasants and partridges, and domestic poultry such
as fowls, ducks, pigeons and turkeys, and can pass from any one of
these hosts to any of the others with the same effect. The organism
is parasitic in the alimentary tract of the host, affecting more
especially the small intestine (duodenum) and the cæca, but in
some cases penetrating to the liver and multiplying there (as in
turkeys), producing necrotic cheesy patches, that ultimately become
full of oöcysts. The gut is rendered very frail by the action of
the parasites, its mucous membrane is greatly injured, and is often
reduced to an almost structureless pulp, riddled with parasites
(fig. 68). Infection is conveyed from host to host by the ingestion
of food or drink contaminated with the oöcysts voided in the fæces of
infected birds. Oval oöcysts from 24 µ to 35 µ long and from 14 µ to
20 µ broad are the means of infection. The oöcysts develop internally
four sporocysts or spores, from each of which two sporozoites are
produced. The life-history[174] presents two phases: (1) The asexual
multiplicative phase, schizogony, for the increase in numbers of the
parasites within the same host; (2) the reproductive phase, following
the formation of gametes (gametogony), leading to the production of
resistant oöcysts, destined for the transference of the parasite to
new hosts (sporogony).

[174] Fantham, H. B. (1910), “The Morphology and Life History of _Eimeria_ (_Coccidium_) _avium_, a Sporozoön causing a fatal disease among young Grouse,” _Proc. Zool. Soc. Lond._, 1910, pp. 672–691, 4 plates. Also Fantham, H. B. (1911), “Coccidiosis in British Game Birds and Poultry,” _Journ. Econ. Biol._, vi, pp. 75–96.

The oöcysts usually reach the duodenum unharmed, with food or
drink. Under the influence of the powerful digestive juices
(especially the pancreatic) now encountered, the oöcysts soften,
as do the sporocysts, and ultimately two sporozoites emerge from
each sporocyst. The sporozoites are from 7 µ to 10 µ long, and each
is vermicular with a uniform nucleus (fig. 69, A). After a short
period of active movement in the gut, each sporozoite penetrates an
epithelial cell (figs. 68 _spz_, 69, B), and once within, gradually
becomes rounded (fig. 69, B, C). It grows rapidly, feeding on the
contents of the host cell and living as a trophozoite (fig. 69,
_D_). When the parasite is from 10 µ to 12 µ in diameter, usually
multiplication by schizogony (fig. 69, E-H) begins. The nucleus
of the parent cell, now called a schizont, divides into a number
of portions that become arranged at the periphery (fig. 69, E).
Cytoplasm collects around each nucleus (fig. 69, E, F) and gradually
a group of daughter individuals (merozoites) is produced (fig. 69,
G), the nucleus of each merozoite showing a karyosome.

The merozoites of _Eimeria avium_ are arranged “en barillet,” like
the segments of an orange (figs. 68 _mz_, 69, G), therein differing
from those of _E. schubergi_, which are arranged “en rosace.” They
separate from one another (fig. 69, H), penetrate other epithelial
cells, where they may, in turn, become schizonts. Eight to fourteen
merozoites are usually formed by each schizont, twenty have been
found, while in cases of intense infection when space has become
limited, the number may be only four.

After a number of generations of merozoites have been formed, a limit
is reached both to the multiplicative capacity of the parasite and to
the power of the bird to provide the invader with food. Consequently,
resistant forms of the parasite are necessary, and the trophozoites
begin to show sexual differentiation instead of forming schizonts,
that is, gametogony commences.

Certain trophozoites store food and become large and granular. These
are macrogametocytes (fig. 69, I, ♀). The microgametocytes (fig. 69,
I, ♂) are smaller and far less granular. The macrogametocyte
continues to grow, and becomes loaded with chromatoid and plastinoid
granules (fig. 69, J, ♀), while the microgametocyte has its nucleus
divide to form a number of bent, rod-like portions (fig. 69, J, ♂).
The macrogametocyte gives rise to a single macrogamete, which forms
a cyst wall for itself, leaving a thin spot (micropyle) for the
entry of the male (fig 69, K, ♀). The microgametocyte gives rise to
numerous small, biflagellate microgametes (fig. 69, K, ♂) around a
large, central residual mass, from which they ultimately break free,
and swim away. When a macrogamete is reached, the microgamete enters
through the micropyle (fig. 69, L)--which then closes, thus excluding
the other males--and applies itself to the female nucleus (fig. 69,
M). Nuclear fusion occurs, the oöcyst (encysted zygote) being thus
produced. Sporogony then ensues. The oöcyst (fig. 69, N) at first
has its contents completely filling it. They then concentrate into
a central spherical mass (fig. 69, O) which gradually becomes
tetranucleate (fig. 69, P). Cytoplasm collects around each nucleus,
and four sporoblasts are thus formed (fig. 69, Q). Each sporoblast
becomes oval (fig. 69, R) and produces a sporocyst. Ultimately two
sporozoites are formed in each sporocyst or spore, at first lying
tête-bêche (fig. 69, S), but finally twisting to assume the position
most convenient for emergence (fig. 69, T) when they reach a new
host. The period of the life-cycle of _Eimeria avium_ (as well as
the details of the life-cycle) was determined by Fantham to be from
eight to ten days, of which period schizogony occupies four to five
days.

The method of infection[175] is contaminative, by way of food or
drink. Young birds are especially susceptible to infection. Certain
birds, particularly older ones, may act as reservoirs of oöcysts,
being continuously infected themselves, without showing any marked
ill effects from the parasite, but being highly infectious to
other birds. Much moisture retards the development of sporocysts
considerably. The duration of vitality of the infective oöcysts has
been determined experimentally to extend well over two years, and in
certain cases longer. _Eimeria avium_ is the causal agent of “white
diarrhœa” or “white scour” in fowls, and of “blackhead” in turkeys.

[175] Fantham, H. B. (1910), “Experimental Studies on Avian Coccidiosis, especially in relation to young Grouse, Fowls and Pigeons,” _Proc. Zool. Soc. Lond._, 1910, pp. 722–731, 1 plate.

_Eimeria avium_ of birds and _E. stiedæ_ of rabbits closely resemble one another, but are not the same parasite, for _E. avium_ is not infective to rabbits, nor _E. stiedæ_ to poultry.

*Eimeria stiedæ*, Lindemann, 1865.

Syn.: _Monocystis stiedæ_, Lindemann, 1865; _Psorospermium cuniculi_,
Rivolta, 1878; _Cytospermium hominis_, Rivolta, 1878; _Coccidium
oviforme_, Leuckart, 1879; _Coccidium perforans_, Leuckart, 1879;
_Coccidium cuniculi_.

_Eimeria stiedæ_ is parasitic in the gut epithelium (fig. 70), liver, and epithelium of the bile ducts of rabbits, and is usually considered to be the parasite very occasionally found in man. The life-cycle resembles that of _Eimeria avium_ in its general outlines (see fig. 69) and therefore will not be detailed in full here. The oöcysts (fig. 71) are large, elongate-oval, greenish in fresh preparations and vary in size from 24 µ to 49 µ long and 12·8 µ to 28 µ broad, the gut forms being usually smaller than those occurring in the liver, owing to the more confined space in which they are formed. Formerly, the parasites in the liver were described under the name of _Coccidium oviforme_, while those from the intestine were termed _Coccidium perforans_. This distinction has now broken down.

The oöcysts[176] are thick-walled, somewhat flattened at one pole, where a large micropyle is present. Four egg-shaped spores (sporocysts) are formed within, each about 12 µ to 15 µ long and 7 µ broad (fig. 72). The oöcysts are voided with the fæces. Sporogony takes, in nature, about three days in the excrement. Fæcal contamination of the food of rabbits results, and coccidian oöcysts are swallowed. Under the influence of the pancreatic juice of a new host, the sporozoites (fig. 72, _a_--_c_) are liberated from the spores and proceed to attack the epithelium and multiply within it, as in the case of _Eimeria avium_. From the gut, infection spreads to the liver, where multiplication of the parasite goes on actively, resulting in the formation of the whitish coccidial nodules, which may be very conspicuous (fig. 74). Proliferation of the connective tissue may occur around the coccidial nodules, which then contain large numbers of oöcysts in various stages of development. It is said that the oöcysts in the older nodules do not seem to be capable of further development. Schizogony (fig. 73) and gametogony in all stages can be found in both liver and gut.

[176] For an account of the life-cycle of _Eimeria stiedæ_ consult Wasielewski, Th. von (1904), “Studien und Photogramme zur Kenntnis der pathogenen Protozoen,” Heft. 1 (Coccidia), 118 pp., 7 plates, Leipzig: J. A. Barth. Also, Metzner, R. (1903), _Arch. f. Protistenk._, ii, p. 13.

Young rabbits often die of intestinal coccidiosis before infection of the liver occurs. The repeated schizogony of _Eimeria stiedæ_ in the gut is sufficient to cause death.

The disease of cattle popularly known as “red dysentery” is also
ascribed to the action of _Eimeria stiedæ_. The fæces of infected
cattle show blood clots of various sizes and in severe cases watery
diarrhœa is present. Acute cases end fatally in about two days.
Numerous oöcysts, considered to be those of _Eimeria stiedæ_, occur
in the fæces, and there is a heavy infection of the gut, especially
the large intestine and rectum, all stages of the parasite being
found in the epithelium. It is suspected that cattle contract the
disease by feeding on fresh grass contaminated with oöcysts. The
disease is recorded from Switzerland and from East Africa.

As before mentioned, _Eimeria stiedæ_ is considered to be the organism found in a few cases in man, possibly acquired by eating the insufficiently cooked livers of diseased rabbits. These cases may now be described.

(_a_) *Human Hepatic Coccidiosis.*

(1) Gubler’s Case. A stone-breaker, aged 45, was admitted to a Paris
hospital suffering from digestive disturbances and severe anæmia.
On examination the liver was found to be enlarged and presented a
prominent swelling, which was regarded as being due to Echinococcus.
At the autopsy of the man, who succumbed to intercurrent peritonitis,
twenty cysts were found averaging 2 to 3 cm. in diameter, and one
measuring 12 to 15 cm. The caseous contents consisted of detritus,
pus corpuscles, and oval-shelled formations, which were considered to
be Distoma eggs, but which, in accordance with Leuckart’s conjecture,
proved to be Coccidia.[177]

[177] Gubler, A., “Tumeurs du foie déterm. par des œufs d’helm....” _Mem. Soc. Biol._, Paris, 1858, v, 2; and _Gaz. med. de Paris_, 1858, p. 657; Leuckart, R., _Die menschl. Paras._, 1863, 1ST edition, i, pp. 49, 740.

(2) Dressler’s Case (Prague). Relates to three cysts, varying from
the size of a hemp-seed to that of a pea, and containing Coccidia,
found in a man’s liver.[178]

[178] Leuckart, R., _Die menschl. Paras._, 1863, 1st edition, i, p. 740.

(3) Sattler’s Case (Vienna). Coccidia were in this case observed in
the dilated biliary duct of a human liver.[179]

[179] Leuckart, R., _Die Paras. d. mensch._, 1879, 2nd edition, p. 281.

(4) Perls’ Case (Giessen). Perls discovered Coccidia in an old
preparation of Sömmering’s agglomerations.[180]

[180] Leuckart, R., _ibid._, p. 282.

(5) Silcock’s Case (London).[181] The patient, aged 50, who had
fallen ill with serious symptoms, exhibited fever, enlarged liver
and spleen, and had a dry, coated tongue. At the autopsy numerous
caseous centres, mostly immediately beneath the surface, were found,
while the contiguous parts of the liver were inflamed. Microscopical
examination demonstrated numerous Coccidia in the hepatic cells as
well as in the epithelium of the biliary ducts. A deposit of Coccidia
was likewise found in the spleen, which the parasites had probably
reached by means of the blood-stream.[182]

[181] Silcock, “A Case of Parasit. by Psorospermia,” _Trans. Path. Soc._, London, 1890, xli, p. 320.

[182] Pianese has confirmed the fact that Coccidia actually occur in the blood of the hepatic veins of infected rabbits.

(_b_) *Human Intestinal Coccidiosis.*

In two cadavers at the Pathological Institute in Berlin, Eimer[183]
found the epithelium of the intestine permeated by Coccidia. Railliet
and Lucet’s case may be traced back to intestinal Coccidia, which
were found in the fæces of a woman and her child, who had both
suffered for some time from chronic diarrhœa.[184] In other cases
(Grassi, Rivolta), where only the existence of Coccidia in the fæces
was known, it is doubtful whether the parasites originated in the
intestine or in the liver.

[183] _Die ei- u. kugelf. Psorosp. d. Wirbelt._, 1870, p. 16.

[184] Railliet and Lucet, “Obs. s. quelq. Cocc. intest.,” _C. R. Soc. Biol._, Paris, 1890, p. 660; Railliet, _Trait. Zool. med. et agric._, 2e éd., 1895, p. 140.

(_c_) *Doubtful Cases.*

To these belong Virchow’s case[185] where, in the liver of an elderly
woman, a thick walled tumour measuring 9 to 11 mm. was found.
Among the contents of this tumour there were oval formations 56 µ
long, surrounded by two membranes and enclosing a number of round
substances. Virchow considered these foreign bodies to be eggs of
pentastomes in various stages of development, others consider them to
be Coccidia.

[185] _Arch. f. path. An._, xviii, 1860, p. 523.

The Coccidia which Podwyssotzki claims to have seen in the liver of
a man, not only in the liver cells, but also in the nuclei, are also
problematic.[186] The parasite was called _Caryophagus hominis_.

[186] Podwyssotzki, “Ueb. d. Bedeut. d. Coccid. in d. Path. Leber des Menschen,” _Centralbl. f. Bakt._, vi, 1889, p. 41.

Again, other explanations can be given to an observation by Thomas,
on the occurrence of _Coccidium oviforme_ in a cerebral tumour of a
woman aged 40. The growth was as large as a pea and surrounded by a
bony substance.[187]

[187] Thomas, J., “Case of Bone Formation in the Human Brain, due to the Presence of _Coccidium oviforme_,” _Journal Boston Soc. Med. Sc._, iii, 1899, p. 167; _Centralbl. f. Bakt._ [I] xxviii, 1900, p. 882.

Genus. *Isospora*, Aimé Schneider, 1881.

Syn.: _Diplospora_, Labbé, 1893.

Belonging to the section _Disporea_, that is, forming only two spores, each with four sporozoites.

*Isospora bigemina*, Stiles, 1891.

Syn.: “_Cytospermium villorum intestinalium canis et felis_,”
Rivolta, 1874; “_Coccidium Rivolta_,” Grassi, 1882; _Coccidium
bigeminum_, Stiles, 1891.

This parasite lives in the intestinal villi of dogs, cats, and the polecat (_Mustela putorius_, L.). According to Stiles,[188] the oöcyst divides into two equal ellipsoidal portions or sporoblasts which become spores and then each forms four sporozoites. The oöcysts of this species vary from 22 µ to 40 µ in length and from 19 µ to 28 µ in breadth. Each spore is 10 µ to 18 µ long and contains four sporozoites. The parasites live and multiply, not only in the gut epithelium, but also in the connective tissue of the intestinal submucosa. Wasielewski has seen merozoites in the gut of the cat.

[188] “Notes on Paras.,” No. II, _Journ. of Comp. Med. and Vet. Sci._, 1892, xiii, p. 517.

_Isospora bigemina_ (fig. 75) appears to occur also in man, for Virchow published a case which was communicated to him by Kjellberg, and attributed the illness to this parasite.[189] Possibly also it would be more correct to ascribe the observation of Railliet and Lucet, which is mentioned under “Human Intestinal Coccidiosis,” p. 148, to this species, as the Coccidia in that case were distinguished by their diminutive size (length 15 µ, breadth 10 µ). The case communicated by Grunow may also possibly refer to _Isospora bigemina_.[190] Roundish or oval structures of 6 µ to 13 µ in diameter occurred in the mucous membrane of the gut and in the fæces of a case of enteritis.

[189] _Arch. f. path. An._, 1860, xviii, p. 527.

[190] Grunow, “Ein Fall von Protozoën (Coccidien?) Erkrankung des Darmes,” _Arch. f. exper. Path. und Pharm._, 1901, xlv, p. 262.

DOUBTFUL SPECIES.

In literature many other statements are found as to the occurrence
of Coccidia-like organisms in different diseases of man. In some
of the cases the parasites proved to be fungi. This was the case
with the parasites of a severe skin disease of man, formerly called
_Coccidioides immitis_ and _Coccidioides pyogenes_. Other statements
are founded on misapprehensions, or are still much disputed. If
reference is here made to “_Eimeria hominis_,” R. Blanchard, 1895,
this is done on the authority of the investigator mentioned. The
structures in question are nucleated spindle-shaped bodies of very
different lengths (18 µ to 100 µ), which either occurred isolated or
were enclosed in large globular or oval cysts, alone or with a larger
tuberculated body (“residual body”). These formations were found by
J. Künstler and A. Pitres in the pleural exudation removed from a man
by tapping. The man was employed on the ships plying between Bordeaux
and the Senegal River.

Blanchard looks upon the fusiform bodies as merozoites and the cysts
as schizonts of a Coccidium. On the other hand, Moniez declares the
spindle bodies to be the ova and the supposed residual bodies to be
“floating ovaries” of an Echinorhynchus.

Severi’s “monocystid Gregarines,” which were taken from the lung
tissue of a still-born child, are also quite problematical.

No less doubtful are the bodies which Perroncito calls _Coccidium
jalinum_, and which he found in severe diseases of the intestine in
human beings, pigs, and guinea-pigs; Borini also reported another
case.

Order. *Hæmosporidia*, Danilewsky emend. Schaudinn.

The Hæmosporidia are a group of blood parasites, comprising forms differing greatly among themselves. Some of the forms need much further investigation. However, there are certain true Hæmosporidia which present close affinities with the Coccidia, leading Doflein to use the term *Coccidiomorpha* for the two orders conjoined.

The Hæmosporidia present the following general characteristics:--

(1) They are parasites of either red or white blood corpuscles of vertebrates during one period of their life-history.

(2) They exhibit alternation of generations--asexual phases or schizogony alternating with sexual phases or sporogony--as do the Coccidia.

(3) There is also an alternation of hosts in those cases which have so far been completely investigated. The schizogony occurs in the blood or internal organs of some vertebrates while the sporogony occurs in an invertebrate, such as a blood-sucking arthropod or leech.

(4) Unlike the Coccidia, resistant spores in sporocysts are not generally produced, such protective phases in the life-cycle being unnecessary, as the Hæmosporidia are contained within either the vertebrate or invertebrate host during the whole of their life.

The Hæmosporidia may be considered for convenience under five main types:--

(1) The _Plasmodium_ or _Hæmamœba_ type. This includes the malarial parasites of man and of birds. The asexual multiplicative or schizogonic phases occur inside red blood corpuscles and are amœboid. They produce distinctive, darkish pigment termed melanin or hæmozoin. Infected blood drawn and cooled on a slide may exhibit “exflagellation” of the male gametocytes, _i.e._, the formation of filamentous male gametes. The invertebrate host is a mosquito. The malarial parasites of man are discussed at length on p. 155. Similar pigmented hæmamœboid parasites have been described in antelopes, dogs, and other mammals, and even reptiles.

(2) The _Halteridium_ type. The trophozoite stage inside the red blood corpuscle is halter-shaped. Pigment is produced, especially near the ends of the organism. The parasites occur in the blood of birds. The invertebrate host of _H. columbæ_ of pigeons in Europe, Africa, Brazil and India, is a hippoboscid fly, belonging to the genus _Lynchia_.

Halteridium parasites are common in the blood of passerine birds, such as pigeons, finches, stone owls, Java sparrows, parrots, etc. The Halteridium embraces or grows around the nucleus of the host red cell without displacing the nucleus. Young forms and multiplicative stages of _H. columbæ_ have been found in leucocytes in the lungs of the pigeon (fig. 76, _8_-_12_). Male and female forms (gametocytes) are seen in the blood (fig. 76, _3a_, _3b_). The cytoplasm of the male gametocytes is pale-staining and the nucleus is elongate, while the cytoplasm of the females is darker and the nucleus is smaller and round. Formation of male gametes from male gametocytes (the so-called process of “exflagellation”) may occur on a slide of drawn infected blood, also fertilization, and formation of the oökinete, as first seen by MacCallum. The correct generic name for Halteridia is, apparently, _Hæmoproteus_. Wasielewski (1913), working on _H. danilewskyi_ (var. _falconis_), in kestrels, finds that the halteridium may be pathogenic to nestlings. The cycle of _H. noctuæ_ described by Schaudinn (1904) lacks confirmation. The account of the life-cycle of _H. columbæ_ given by Aragão (1908) is illustrated in fig. 76. It agrees with the work of Sergent (1906–7) and Gonder (1915). Mrs. Adie (1915) states that the cycle in _Lynchia_ is like that of a _Plasmodium_.

(3) The _Leucocytozoön_ type. The trophozoites and gametocytes occur within mononuclear leucocytes and young red cells (erythroblasts) in the blood of birds. Laveran and França consider that the Leucocytozoa occur in erythrocytes. The host cells are often greatly altered by the parasites, becoming hypertrophied and the ends usually drawn into horn-like processes (fig. 77), though some remain rounded. Leucocytozoa are limited to birds, and very rarely produce pigment. Male and female forms (gametocytes) are distinguishable in the blood (fig. 77), and the formation of male gametes (“exflagellation”) may occur in drawn blood.

The Leucocytozoa were first seen by Danilewsky in 1884. They are usually oval or spherical. It is not easy sometimes to distinguish the altered host cell from the parasite, as the nucleus of the former is pushed to one side by the leucocytozoön. The cytoplasm of the female parasite stains deeply, and the nucleus is rather small, containing a karyosome. In the male the cytoplasm stains lightly and the nucleus is larger, with a loose, granular structure.

Many species of Leucocytozoa are recorded, but schizogony has only been described by Fantham (1910)[191] in _L. lovati_ in the spleen of the grouse (_Lagopus scoticus_), and by Moldovan[192] (1913) in _L. ziemanni_ in the internal organs of screech-owls.

[191] _Annals Trop. Med. and Parasitol._, iv, p. 255.

[192] _Centralbl. f. Bakt._, Orig., lxxi, p. 66.

M. and A. Leger[193] (1914) propose to classify Leucocytozoa, provisionally, according as the host cells are fusiform or rounded.

[193] _Bull. Soc. Path. Exot._, vii, p. 437.

(4) The _Hæmogregarina_ type. Included herein are many parasites of red blood corpuscles, with a few (the leucocytogregarines) parasitic in the white cells of certain mammals and a few birds. They are not amœboid but gregarine-like, vermicular or sausage-shaped (fig. 78). They do not produce pigment. They are widely distributed among the vertebrata, but are most numerous in cold-blooded vertebrates (fishes, amphibia and reptiles). The hæmogregarines of aquatic hosts are transmitted by leeches, those of terrestrial hosts by arthropods.

The nucleus of hæmogregarines is usually near the middle of the parasite, but may be situated nearer one end. The body of the parasite may be lodged in a capsule (“cytocyst”). There is much variation in size and appearance among hæmogregarines. Some are small (_Lankesterella_); some attack the nucleus of the host cell (_Karyolysus_); others have full grown vermicules larger than the containing host corpuscle, and so the hæmogregarines bend on themselves in the form of *U* (fig. 78, _b_). Schizogony often occurs in the internal organs of the host, sometimes in the circulating blood.

The hæmogregarines occurring in the white cells (mononuclears or polymorphonuclears) of mammals have been referred to a separate genus, _Leucocytogregarina_ (Porter) or _Hepatozoön_ (Miller). Such leucocytogregarines are known in the dog (fig. 79), rat, mouse, palm-squirrel, rabbit, cat, etc. Schizogony of these forms occurs in the internal organs, such as the liver, lung and bone-marrow of the hosts. They are apparently transmitted by ectoparasitic arthropods, such as ticks, mites, and lice.

A few hæmogregarines are known to be parasitic in the red blood corpuscles of mammals. Such are _H. gerbilli_ in the Indian field rat, _Gerbillus indicus_; _H. balfouri_ (_jaculi_) in the jerboa, _Jaculus jaculus_, and a few species briefly described from marsupials. These parasites do not form pigment.

Strict leucocytic gregarines have been described from a few birds by Aragão and by Todd.

The sporogony of hæmogregarines is only known in a few cases, and in those affinity with the Coccidia is exhibited. In fact, the Hæmogregarines are now classified by some authors with the Coccidia.

(5) The _Babesia_ or _Piroplasma_ type. These are small parasites of red blood corpuscles of mammals. They do not produce pigment. They are pear-shaped, round or amœboid in Babesia, bacilliform and oval in other forms referred to this group. Piroplasms are transmitted by ticks. These parasites are described at length on p. 172.

THE MALARIAL PARASITES OF MAN.

Malaria, otherwise known as febris intermittens, chill-fever, ague, marsh fever, paludism, etc., is the name given to a disease of man, which begins with fever. It has been known since ancient times and is distributed over almost all the world, although very unevenly, but does not occur in waterless deserts and the Polar regions. In many places, especially in the civilized countries of Central Europe, the disease is extinct or occurs only sporadically, and large tracts of land have become free from malaria.

The rhythmical course of the fever is characteristic. It begins apparently suddenly with chilliness or typical shivering, whilst the temperature of the body rises, the pulse becomes low and tense and the number of beats of the pulse increases considerably. After half to two hours the heat stage begins. The patient himself feels the rise of his temperature (shown by feeling of heat, dry tongue, headache, thirst). The temperature may reach 41°C or more. At the same time there is sensitiveness in the region of the spleen and enlargement of that organ. After four to six hours an improvement takes place, and with profuse perspiration the body temperature falls rapidly, not often below normal. After the attack the patient feels languid, but otherwise well until certain prodromal symptoms (heaviness in the body, headache) which were not noticed at first, denote the approach of another attack of fever, which proceeds in the same way.

The intervals between the attacks are of varying length which permit of a distinction in the kinds of fever. If the attacks intermit one day, occurring on the first, third and fifth days of the illness and always at the same time of day, it is termed _febris tertiana_; if two days occur between fever days, it is called _febris quartana_. In the case of the fever recurring daily, later writers speak of typical _febris quotidiana_. But a quotidian fever may arise when two tertian fevers differing by about twenty-four hours exist at the same time (_febris tertiana duplex_). The patient has a daily attack, but the fever of the first, third and fifth days differs in some point (hour of occurrence, height of temperature, duration of cold or hot stage) from the fever of the second, fourth and sixth days. Similarly, two or three quartan fevers which differ by about twenty-four hours each may be observed together (_febris quartana duplex_ or _triplex_); in the latter case the result is also a quotidian fever.

Two kinds of tertian fever are differentiated--a milder form occurring especially in the spring (spring tertian fever), and a more severe form appearing in the summer and autumn in warmer districts, especially in the tropics (_summer or autumn fever_, _febris æstivo-autumnalis_, _febris tropica_, _febris perniciosa_). The latter often becomes a quotidian fever.

All the afore-mentioned infections are termed acute. They are distinguished from the very different _chronic malarial infection_ by the frequent occurrence of relapses, which finally lead to changes of some organs and particularly of the blood. The relapses are then generally marked by an irregular course of fever.

The term masked malaria is used when any disturbance of the state of health of a periodic character shows itself and disappears after treatment with quinine.[194] Generally it is a question of neuralgia.

[194] Quinine is still almost exclusively the remedy used in the treatment of malaria. It is prepared from the bark of the cinchona tree. This important remedy was introduced into Europe in 1640 from Ecuador by Juan del Vego, physician of the Countess del Cinchon.

That intermittent fever was an infectious disease, although
not one which was transmitted direct from man to man, had been
assumed for a long time. Therefore it was natural, at a time when
bacteriology was triumphing, to look for a living agent causing
infection in malaria, which search was, seemingly, successful (Klebs,
Tomasi-Crudeli, 1879). Hence it was not surprising that the discovery
of the real malarial parasites in November, 1880, by the military
doctor A. Laveran[195] in Constantine (Algeria), at first met with
violent opposition, even after Richard (1882) had confirmed it and
Marchiafava, Celli, Grassi and others, had further extended it.
Not that the existence of structures found in the blood of malaria
patients by Laveran and Richard was denied; on the contrary, the
investigations of the opponents furnished many valuable discoveries,
but the organisms were differently interpreted and considered to be
degeneration products of red blood corpuscles. Only when Marchiafava
and Celli (1885) saw movements in the parasites, which Laveran called
_Oscillaria malariæ_ and later _Hæmatozoön malariæ_, was their animal
nature admitted and the parasites were named _Plasmodium malariæ_.
Shortly before this, Gerhardt (1884) had stated that the disease
could be transmitted by the injection of the blood of a malarial
patient to a healthy person.

[195] The discovery of Laveran is in no way lessened by the fact that one investigator or another (according to Blanchard [_Arch. de Paras._, vii, 1903, p. 152], P. F. H. Klencke in 1843) had seen, mentioned and depicted malarial parasites. (_Neue phys. Abhandl. auf. selbständ. Beob. gegr._, Leipzig, 1843, p. 163, fig. 25). In 1847 Meckel had recognized that the dark colour of the organs in persons dead of malaria was due to pigment. Virchow in 1848 stated that this pigment occurred in blood cells. Kelsch in 1875 recognized the frequency of melaniferous leucocytes in the blood of malarial patients. Beauperthuy (1853) noticed that in Guadeloupe there was no malaria at altitudes where there were no “insectes tipulaires,” and suggested that the disease was inoculated by insects.

This supplied the starting point for further investigations, which
were made not exclusively, but principally, by Italian investigators
(Golgi, Marchiafava and Celli, Bignami and Bastianelli, Grassi and
Feletti, Mannaberg, Romanowsky, Osier, Thayer and others). In 1885
Golgi described the asexual cycle in the blood, in the case of the
quartan parasite. These investigations, after attention had been
drawn by Danilewsky (1890) to the occurrence of similar endoglobular
parasites in birds, were extended to the latter (Grassi and Feletti,
Celli and Sanfelice, Kruse, Labbé and others).

The result was as follows: Malaria in man (and birds) is the result
of peculiar parasites included in the _Sporozoa_ by Metchnikoff,
which parasites live in the erythrocytes, grow in size and finally
“sporulate,” that is, separate into a number of “spores” which leave
the erythrocytes and infect other blood corpuscles. Morphologically
and biologically several species (and respectively several varieties)
of malarial parasites may be distinguished, on which the different
intermittent forms depend. Transmission of the blood of patients to
healthy people produces a malarial affection which corresponds in
character to the fever of the patient from whom the inoculation was
made. The combined types of fever (tertiana duplex, quartana duplex
or triplex) are explained by the fact that the patient harbours
two or three groups of parasites which differ in their development
by about twenty-four hours, whilst the irregular fevers depend on
deviation from the typical course of development of the parasites. In
addition to stages of the parasites which could easily be arranged
in a developmental series concurrent with the course of the disease,
other phases of the parasites also became known, such as spheres,
crescents, polymitus forms, which seemed not to be included in the
series and, therefore, were very differently interpreted.

The decision reached at the beginning of the last decade of the
last century, which found expression in comprehensive statements
(Mannaberg, Ziemann and others), only concerned a part of the
complete development of the malarial parasites. No one could with
any degree of certainty demonstrate how man became infected, nor
were there reliable hypotheses based on analogy with other parasites
concerning the exit of the excitants of malaria from the infected
person and their further behaviour. Numerous hypotheses had been
advanced, but none was able to elucidate the various observations
made from time to time in dealing with malaria. One hypothesis only
seemed to have a better foundation. Manson (1894), who knew from
his own experience the part played by mosquitoes in the development
of Filaria from the blood of man, applied this also to the malarial
parasites living in the blood, whereby at least the way was indicated
by which the Hæmosporidia could leave man. The parasites were said
finally to get into water through mosquitoes which had sucked the
blood of malarial patients, and the germ spread thence to men who
drank the water. In some cases the parasites were supposed to reach
man by the inhaling of the dust of dried marshes. On the other
hand, Bignami believed that the mosquitoes were infected in the
open air by malarial parasites which occurred there in an unknown
stage and the insects transmitted the germs to man when biting. R.
Koch combined both hypotheses, without, however, producing positive
proof. R. Ross, then (1897–8) an English military doctor in India,
was the first to succeed in this. He had been encouraged by Manson
to study the fate of malarial _Plasmodia_ which had entered the
intestine of mosquitoes with malaria-infected blood, especially in
the case of the _Plasmodium_ (_Proteosoma_) living in the blood of
birds. He showed that the _Proteosoma_ penetrate the intestinal wall
of the mosquitoes, grow and develop into large cysts which produce
innumerable rod-like germs, which burst into the body cavity and
penetrate the salivary glands. Ross allowed mosquitoes to suck the
blood of birds affected by malaria, and some nine days later, let
the infected mosquitoes which had been isolated suck healthy birds.
After five to nine days _Proteosoma_ were found to occur in the blood
of the birds used. The _Proteosoma_ and _Halteridium_ of birds were
also further investigated by MacCallum (1897–8), Koch and others, and
important results followed.

In any case Ross (1898) had clearly established the importance
of mosquitoes in the spread of malaria among birds. It was now
only a question of proving whether, and how far, mosquitoes were
concerned with human malaria. Ross himself worked to this end. Here
the experiments of Italian investigators (Bignami, Bastianelli,
Grassi)[196] were of importance. These investigators studied the fate
of malarial parasites in man, produced malaria in men experimentally
by the bites of infected mosquitoes, and established that only
mosquitoes belonging to the genus _Anopheles_ were concerned, and
not species of _Culex_. These latter are only able to transmit
_Proteosoma_ to birds. It is true that _Culex_ can ingest the
human malarial parasites, but the latter do not develop in them.
Development only occurs in species of _Anopheles_. In _Anopheles_
(and similarly for _Proteosoma_ in _Culex_) sexual reproduction takes
place; crescents, spheres and polymitus forms are necessary stages of
development in the mosquito.

[196] Grassi, B. (1901), “Die Malaria,” 250 pp., 8 plates. G. Fischer, Jena.

With these discoveries the campaign against malaria became more
definite. It was directed partly against the transmitters, whose
biology and life-cycle were more thoroughly investigated, instead of
merely against the infection of the adult _Anopheles_. The latter do
not, as was believed for some time, transmit the malarial germs to
their offspring. They always infect themselves from human beings,
whereby the relapses appearing in early summer, and the latent
infection, especially of children of natives, play a principal part
(Stephens and Christophers, Koch). Further, the crusade was directed
against the infection of man by the bites of _Anopheles_. Important
results have been obtained in these directions. Low and Sambon in
1900 lived in a mosquito-screened hut in a malarial part of the
Roman Campagna for three of the most malarious months and did not
contract the disease. In the same year Dr. P. T. Manson was infected
with malaria by infected mosquitoes sent from Italy. The rôle of
mosquitoes having been proved, it may be hoped that ultimately the
eradication of malaria, or at least a considerable restriction of it,
will be achieved.

It is of importance to record that, although malarial parasites occur
in mammals (monkeys, bats, etc.) the human ones are not transmissible
to mammals, not even to monkeys. The species, therefore, are specific
to the different hosts (Dionisi, Kossel, Ziemann, Vassall).

An important work dealing with the modern applications of the
mosquito-malaria theory in all parts of the Tropics was published by
Sir Ronald Ross in 1911. It is entitled “The Prevention of Malaria”
(John Murray, London, 21s.).

DEVELOPMENT OF THE MALARIAL PARASITES OF MAN.

The commencement of the developmental cycle and of the infection of man, is the sporozoites (fig. 80, _1_) which are passed into the blood of a person by the bite of an infected mosquito. Prior to this the parasites collect in the excretory ducts of the salivary glands (fig. 80, _27_) of the _Anopheles_. The sporozoites are elongate and spindle-shaped, 10 µ to 20 µ long and 1 µ to 2 µ broad, with an oval nucleus situated in the middle. They are able to glide, perform peristaltic contractions, or curve laterally. Schaudinn has studied the penetration of the red blood corpuscles (fig. 80, _2_) by the sporozoites in the case of the living tertian parasite. The process takes forty to sixty minutes in drawn blood. After its entrance the parasite, which is now called a trophozoite, contracts, and becomes an active amœbula (fig. 80, _3_). It develops a food vacuole and grows at the expense of the invaded blood corpuscle (fig. 80, _4_), which is shown by the appearance of pigment granules (transformed hæmoglobin) in it. When the maximum size is attained, multiplication by schizogony (fig. 80, _5_-_7_) begins with a division of the nucleus, which is followed by further divisions of the daughter nuclei, the number of which varies up to 16 or even 32, depending on the species of the parasite. Then the cytoplasm divides into as many portions as there are nuclei, the result being a structure suggestive of the spokes of a wheel or of a daisy, the centre of the resulting rosette being occupied by dark pigment. Finally, the parts separate from one another, leaving behind a residual body containing the pigment, and the daughter forms issue into the blood plasma as merozoites (fig. 80, _7_). They are actively amœboid (fig. 80, _8_) and soon begin to enter other blood corpuscles of their host, for the entry into which thirty to sixty minutes are necessary, according to Schaudinn’s observations.[197]

[197] It should be remembered that some authors (Laveran, Argutinsky, Panichi, Serra) argue against the intra-globular position of malarial parasites and state that they only adhere outwardly to the red blood corpuscles. These views have recently been revived by Mary Rowley-Lawson, and she states that the malarial parasite is “extracellular throughout its life-cycle and migrates from red corpuscle to red corpuscle destroying each before it abandons it.” (_Journ. Exper. Med._, 1914, xix, p. 531.)

Here they behave like sporozoites which previously entered and again produce merozoites. This process is repeated until the number of parasites is so large that, at the next migration of the merozoites, the body of the person infected reacts with an attack of fever,[198] which is repeated with the occurrence of the next or following generations.

[198] The incubation period, that is, the time between infection and the first attack of fever, is ten to fourteen days; with severe infection fewer days (minimum 5 to 6) are needed.

The growth and schizogony last different times, according to the species of the parasite, about forty-eight hours in the case of the parasite of febris tertiana or tropica, and seventy-two hours for the quartan parasite. The various intermittent forms produced by them depend on this specific difference in the malarial parasites.

The schizogony can, however, only be repeated a certain number of times, supposing that the disease has not been checked prematurely by the administration of quinine, which is able to kill the parasites. It appears that after a number of attacks of fever the conditions of existence in man are unfavourable for the malarial parasites, and this brings about the production of other forms which have long been known, but also long misunderstood (spheres, crescents, polymitus). The merozoites in this case no longer grow into schizonts, or at least not all of them, but become sexual individuals called gametocytes (fig. 80, _9_-_12_), which only start their further development when they have reached the intestine of _Anopheles_. This does not take place in every case, nor with all the gametocytes which exist in the blood of patients with intermittent fever. Of those parasites which remain in the human blood the male ones (microgametocytes) soon perish, the females (macrogametocytes) persist for some long time, and perhaps at last acquire the capacity of increasing by schizogony. They might thus form merozoites which behave in the body as if they had proceeded from ordinary schizonts (fig. 80, _13c_-_17c_). If their number increases sufficiently, in course of time the patient, who was apparently recovering, has a new series of fever attacks, or relapses, without there having been a new infection. This is the view of Schaudinn, who from researches of his own concluded that relapses were brought about by a sort of parthenogenetic reproduction of macrogametocytes. R. Ross, on the contrary, believes that in the relatively healthy periods the number of parasites in the blood falls below that necessary to provoke febrile symptoms; relapses then result merely from increase in the numbers of the parasites present in the individual. Ross’s view is now generally accepted.

If the gametocytes, which are globular, or in the pernicious or malignant tertian parasite crescentic (fig. 81), gain access to the intestine of an Anopheline,[199] they mature. The macrogametocytes extrude a part of their nuclear substance (fig. 80, _13a_, _14a_) and thereby become females or macrogametes. The microgametocytes, on the other hand, undergo repeated nuclear division, preparation for this being made apparently whilst in the blood of man. This results in the formation of threadlike bodies which move like flagella and finally detach themselves from the residual body (fig. 80, _13b_, _14b_). These are the males or microgametes[200] (fig. 80, _15b_).

[199] Schizonts ingested about the same time perish in the intestine of the mosquito.

[200] If the microgametocytes are sufficiently mature the formation of microgametes occurs in the blood of man as soon as it is taken from the blood-vessel and has been cooled and diluted. Such a stage is called a _Polymitus_ form, and the process has been called “exflagellation.”

Copulation takes place in the stomach of the Anopheline (fig. 80, _16_). A microgamete penetrates a macrogamete and coalesces with it. The fertilized females elongate very soon and are called oökinetes or “vermicules” (figs. 80, _17_; 82). They penetrate the walls of the stomach, pierce the epithelium (fig. 80, _18_, _19_), and remain lying between it and the superficial stratum (tunica elastico-muscularis). Then they become rounded and gradually develop into cysts which grow larger and are finally visible to the naked eye, being called oöcysts (figs. 80, _20_-_24_; 83). Their size at the beginning is about 5 µ, the maximum that they attain is 60 µ, only exceptionally are they larger.

The sporulation (figs. 80, _21_-_25_; 84), which now follows, begins with repeated multiple fission of the nucleus. Long before the definitive number of nuclei, which varies with the individual, is attained the protoplasm, according to Grassi, begins to segment around the individual large nuclei but without separating completely into cell areas. According to Schaudinn, however, there is a condensation of the outstanding protoplasmic strands. It is certain that the number of nuclei increases with simultaneous decrease in size. They soon appear on the surface of the strands or sporoblasts, surround themselves with some cytoplasm and then elongate (fig. 84). In this manner the sporozoites are formed and break away from the unused remains of the cytoplasmic strands of the sporoblasts (fig. 80, _26_). The number of the sporozoites in an oöcyst varies from several hundreds to ten thousand.

The sporulation is influenced in its duration by the external
temperature (Grassi, Jansci, Schoo). In the tertian parasite it takes
place quickest at a temperature of 25° to 30° C. and takes eight to
nine days. A temperature a few degrees lower has a retarding effect
(eighteen to nineteen days at 18° to 20° C). A still lower one has a
restraining or even destructive effect. Temperatures over 35° C. also
exercise a harmful effect. The malignant tertian parasite seems to
need a somewhat higher temperature and the quartan parasite a lower
one.

The sporozoites of the various malarial parasites show no specific differences. They were stated by Schaudinn to occur in three forms, and these were described as indifferent (neuter), female and male. There is, however, little or no evidence for this hypothetical differentiation. The last were said to perish prematurely, that is, in the oöcyst. The others after the rupture of the oöcysts enter the body cavity of the Anophelines, whence they are carried along in the course of the blood. Finally they penetrate the salivary glands (fig. 80, _27_) probably by their own activity, break through their epithelia and accumulate in the salivary duct (fig. 80, _27_). At the next bite by the mosquito they are transmitted to the blood-vessels of man.

THE SPECIES OF MALARIAL PARASITES OF MAN.

In view of the differences in opinion regarding “species” and
“varieties,” the dispute whether the malarial parasites of man
represent one species with several varieties, or several species is
almost superfluous. If necessary two genera may be distinguished.

The parasites of the tertian and quartan fever are alike in that their gametocytes have a rounded shape (figs. 80, _12_, _13_), whilst the corresponding stages of the pernicious or malignant tertian parasites are crescentic (figs. 81, 88). These differences are used by some writers as the distinguishing characteristic of two genera: _Plasmodium_, Marchiafava and Celli, 1885, for the first mentioned species; _Laverania_, Grassi and Feletti, 1889, for the pernicious or malignant tertian parasite. Whether there is a genuine quotidian fever and accordingly a special quotidian parasite is still disputed.

These parasites are treated in practical detail in Stephens and
Christophers’ “Practical Study of Malaria,” 3rd edition, 1908.

*Plasmodium vivax*, Grassi and Feletti, 1890.

Syn.: _Hæmamœba vivax_, Grassi and Feletti, 1890; _Plasmodium
malariæ_ var. _tertianæ_, Celli and Sanfelice, 1891; _Hæmamœba
laverani_ var. _tertiana_, Labbé, 1894; *Hæmosporidium tertianum*,
Lewkowitz, 1897; _Plasmodium malariæ tertianum_, Labbé, 1899:
_Hæmamœba malariæ_ var. _magna_, Laveran, 1900, p.p.; _Hæmamœba
malariæ_ var. _tertianæ_, Laveran, 1901.

This species, _P. vivax_,[201] is the causal agent of the simple or spring tertian fever and is, therefore, named directly the tertian or benign tertian parasite (figs. 80, _3_-_8_; 85). During the afebrile period in the patient, the young trophozoites or amœbulæ appear on or in the red blood corpuscles as pale bodies of 1·5 µ to 2 µ diameter which at first show only slow amœboid movements. Their nucleus is difficult to recognize in the early stage. Soon the food vacuole is formed and this grows concomitantly with the trophozoite and the parasite has a ring-like appearance. Afterwards the vacuole diminishes, and at this period the first brownish melanin granule appears. From this time the activity and number of the pigment granules increase with continuous growth. When the parasite has grown to about one-third the diameter of the erythrocyte the latter shows characteristic red Schüffner’s dots or “fine stippling,” after staining with Romanowsky’s solution. Later, after about twenty-four hours, the blood corpuscles begin to grow pale, then to increase in size, and after thirty-six hours, that is, about twelve hours before the next attack of fever, schizogony of the parasite is initiated by the division of the nucleus. The parasite at this time occupies half to two-thirds of the enlarged blood corpuscle. The daughter nuclei continue dividing until sixteen, and occasionally twenty-four, daughter nuclei are produced. The pigment which, up till now lies nearer the periphery, moves to the middle, while the nuclei lie nearer the surface.

[201] See Schaudinn, F. (1902), _Arb. a. d. kaiserl. Gesundheits._, xix, pp. 169–250, 3 plates.

Around each nucleus a portion of cytoplasm collects and thus young merozoites are produced. These separate from each other and from the little residual masses[202] which contain the melanin and pass from the blood corpuscles, which now can hardly be recognized, to the blood plasma, where they soon attack new erythrocytes.

[202] The pigment masses (melanin or hæmozoin) are taken up by the leucocytes, particularly the mononuclear ones, and are carried especially to the spleen, and also to the liver and the bone-marrow. From this circumstance arises the well-known pigmentation of the spleen in persons who have suffered from malaria.

The migration of the merozoites initiates a new attack of fever and two groups of tertian parasites in the blood, differing in development by about twenty-four hours, are the conditions for febris tertiana duplex.

After a lengthy duration of fever the gametocytes (figs. 80, _9_--_12_) appear. They are uninucleate. The microgametocytes are about the size of fully developed schizonts, the macrogametocytes are somewhat larger. Their further development takes place in Anophelines.

The chief distinctive characteristics of the simple tertian parasite, as seen in infected blood, are:--(1) The infected red-cell is usually enlarged; (2) the presence of fine red granules known as Schüffner’s dots in the red blood corpuscles, after Romanowsky staining; (3) the fragile appearance of the parasite compared with other species. Large forms are pigmented, irregular and “flimsy-looking,” sometimes appearing to consist of separate parts. Irregularity of contour is common.

Ahmed Emin[203] (1914) has described a small variety of _P. vivax_.

[203] _Bull. Soc. Path. Exot._, vii, p. 385.

*Plasmodium malariæ*, Laveran.

Syn.: _Oscillaria malariæ_, Laveran, p.p., 1883; _Hæmamœba malariæ_,
Gr. et Fel., 1890; _Plasmodium malariæ_ var. _quartanæ_, Celli et
Sanfel., 1891; _Hæmamœba laverani_ var. _quartana_, Labbé, 1894;
_Hæmosporidium quartanæ_, Lewkowitz, 1897; _Plasmodium malariæ
quartanum_, Labbé, 1899; _Plasmodium golgii_, Sambon, 1902;
_Laverania malariæ_, Jancso, 1905 nec Grassi et Fel. 1890; _Hæmomœba
malariæ_ var. _quartanæ_; Lav., 1901.

_Plasmodium malariæ_ is the parasite of quartan malaria (fig. 86). The trophozoites of the quartan parasite differ from the corresponding stages of the tertian parasite in that their motility is less and soon ceases. They differ also in their slower growth, by the early disappearance of the food vacuole, by the more marked formation of the dark brown pigment, and by the fact that the red blood corpuscles attacked are not altered either in colour or size.

When the parasites have grown almost to the size of the erythrocytes schizogony occurs. The pigment granules arrange themselves in lines radiating towards the centre and the merozoites are also radially disposed in groups of 6, 8, 10 or even 12, but are often arranged less regularly. The whole development, growth and schizogony, occupies seventy-two hours.