In this family the zygote is active (an ookinete), secreting a flexible membrane which is stretched during development. The life cycle involves 2 hosts, 1 of which is vertebrate and the other invertebrate. The parasites are found in the cells of the circulatory system of vertebrates and of the digestive system of invertebrates. The oocysts are large and contain many sporocysts, each with 4 to 12 or more sporozoites. There is a single genus, Hepatozoon.
In this genus schizogony takes place in the viscera of a vertebrate, and the gametocytes are either in the leucocytes or erythrocytes, depending on the species. Fertilization and sporogony occur in a tick, mite, louse, tsetse fly, mosquito or other blood-sucking invertebrate, depending again on the species. The microgametocyte forms 2 microgametes. A synonym of this generic name is Leucocytogregarina.
Species of Hepatozoon have been described from mammals, reptiles and birds. They are especially common in rodents.
The vertebrate hosts become infected by eating the invertebrate hosts. The sporozoites are released in the intestine, penetrate its wall and pass via the blood stream to the liver, lungs, spleen or bone marrow; different species prefer different organs. The sporozoites enter the tissue cells and become schizonts, which divide by multiple fission to produce a number of merozoites. There are several asexual generations in the visceral cells, but their number is known in only a few cases. The last generation merozoites enter the blood cells and become gamonts. These look alike; presumably the female is a macrogamete and the male a microgametocyte, but no evidence is available on this point.
No further development takes place until the parasites reach the alimentary tract of the intermediate host. The gamonts then leave their host cells, associate in syzygy, and the microgametocyte forms 2 non-flagellate microgametes. These are relatively large, but smaller than macrogametes. One of them fertilizes the macrogamete, and the resultant ookinete penetrates the intestinal wall and comes to lie in the haemocoel. Here it grows considerably and becomes an oocyst. Several nuclear divisions take place in the sporont within the oocyst wall. The daughter nuclei migrate to its periphery, and each one buds off to form a sporoblast, leaving a large residual mass. The sporoblasts then form a wall around themselves, becoming sporocysts. Sporozoites develop in the sporocysts, their number depending on the species. When the vertebrate host ingests the invertebrate one, the oocysts and sporocysts rupture in its intestine, releasing the sporozoites.
It is possible that trans-placental infection may also occur, at least in some species. At any rate, Clark (1958) found a full-blown infection with H. griseisciuri in a 36-hour-old grey squirrel which had been born in a mite-free environment.
Synonyms: Leucocytozoon canis, Haemogregarina canis, Haemogregarina rotundata, Haemogregarina chattoni, Hepatozoon felis.
Hosts: Dog, cat, jackal, hyena and palm civet or musang (Paradoxurus hermaphroditus). The forms described from the cat, jackal and hyena under the names H. felis, H. rotundata and H. chattoni, respectively, are practically indistinguishable morphologically, and are probably all the same species. Laird (1958) believed that the form he found in the palm civet in Malaya was H. canis.
Location: The schizonts are in the spleen, bone marrow and to a lesser extent in the liver. The gamonts are in the polymorphonuclear leucocytes.
Geographic Distribution: India, Malaya, Singapore, Indochina, Central Africa, North Africa, Middle East, Italy. This species is well known in dogs, but has been reported from cats only by Patton (1908) in Madras (Laird, 1959).
Morphology: The gamonts in the leucocytes are elongate rectangular bodies with rounded ends measuring about 8 to 12 by 3 to 6 u, and with a central, compact nucleus. Their cytoplasm stains pale blue and their nucleus dark reddish with Giemsa stain. They are surrounded by a delicate capsule. They may emerge from the leucocytes and capsule and lie free in citrated blood. Leitao (1945) saw schizonts in the circulating blood which he said were difficult to distinguish from platelets.
Life Cycle: The life cycle of H. canis was worked out by Christophers (1906, 1907, 1912) and Wenyon (1911). Schizogony takes place in the spleen and bone marrow, and Rau (1925) saw it in the liver also. There are several types of schizonts. One type produces a small number (usually 3) of large merozoites, another type produces a large number of small merozoites, and intermediate types produce merozoites of intermediate numbers and size. The small merozoites are the ones which enter the leucocytes to form gamonts.
The vector is the brown dog tick, Rhipicephalus sanguineus. Both the nymph and adult can transmit the infection, but there is no transovarian transmission. The oocysts are found in the haemocoel. They are about 100 u in longest diameter and contain 30 to 50 sporocysts 15 to 16 u long, each containing about 16 banana-shaped sporozoites and a residual body. Dogs become infected by eating infected ticks.
Pathogenesis: H. canis has often been found in apparently healthy dogs, but it may also cause serious disease and death (Rau, 1925; Rahimuddin, 1942). The principal signs are irregular fever, progressive emaciation, anemia and splenomegaly. Lumbar paralysis has also been reported. Affected dogs may die in 4 to 8 weeks.
Diagnosis: Hepatozoonosis can be diagnosed by identifying the gamonts in stained blood smears or in stained smears of spleen pulp, bone marrow or liver.
Prevention and Control: Since H. canis is transmitted by the brown dog tick, elimination of ticks will eliminate the disease.
Other species of Hepatozoon
Hepatozoon muris (Balfour, 1905) occurs in the wild and laboratory Norway rat and black rat thruout the world. Schizogony takes place in the parenchymal cells of the liver, and the gamonts are found in the monocytes and rarely in the polymorphonuclear leucocytes. The vector is the spiny rat mite, Echinolaelaps echidninus. Massive infections may cause marked degenerative changes in the liver and death, but little or no effect has been observed in lightly infected wild rats.
Hepatozoon musculi (Porter, 1908) was reported from the white mouse in England. It differs from H. muris in that schizogony takes place only in the bone marrow.
Hepatozoon cuniculi (Sangiorgi, 1914) was reported from the domestic rabbit in Italy. Its gamonts are found in the leucocytes and its schizonts in the spleen.
Hepatozoon griseisciuri Clark, 1958 is common in the grey squirrel (Sciurus carolinensis) in the United States. Clark (1958) described its life cycle. Schizogony takes place in the spleen, liver and bone marrow, and the gamonts are found in the monocytes. The natural vector is the mite, Euhaemogamasus ambulans, but Echinolaelaps echidninus can act as a vector experimentally.