There is great variety of malaria parasites that infect vertebrates from birds to mammals. However, in humans malaria is caused by four species: 1. P.vivax 2. P.malariae 3. P.falciparum 4. P.ovale. Historically (particularly in Former Soviet medical literature) these four parasites have been described as: 1. benign tertian for P.vivax 2. quartan for P.malariae 3. malignant tertian, tropical, pernicious for P.falciparum and 4. ovale tertian for P.ovale. In order to complete their life cycle, all malaria parasites require the presence of both mosquito and human (2 hosts) as the definitive (sexual development) and the intermediate host correspondingly. Throughout the evolution of malaria parasite, it has adopted 3 basic strategies of successful cycle passage:

    Strategy I: intensive replication (ex' sporogony, tissue and erythrocytic schizogony)
    Strategy II: cell invasion (ex' merozoites, sporozoites)
    Strategy III: sexual differentiation (ex' macro- microgametocytes)

The life cycle of all species that infect humans is basically the same (Fig1.). There is an exogenous asexual phase in the mosquito called sporogony during which the parasite multiplies. Blood fed female mosquito takes up both erythrocytes infected with the asexual stages of the malaria parasite as well as the sexual forms - gametocytes.
Within the gut of mosquito, gametocytes, triggered by temperature decrease and other chemofactors, escape the erythrocytes and fuse together forming the zygote. Subsequent transformation of zygote into ookinete is necessary for the parasite to penetrate the mosquito gut wall. However, it reaches no further than the basal membrane. The next step in the cycle is the formation of oocyst. This progressively enlarging cell eventually ruptures the basal membrane releasing multiple sporozoites that later infect mosquito salivary glands.
On average, out of 8,000-32,000 sprozoites released by oocyst only about 1000 are found in the salivary glands and approximately 20 sprozoites are inoculated during in any single mosquito bite. However, it has been shown that single sporozoite is sufficient to produce human infection.

Fig1. Malaria life cycle

As a result of mosquito bite, the sporozoites may start invading the liver cells (hepatocytes) as soon as 2 minutes after inoculation. However, on average, infectious sporozoites are recovered from the blood 30 minutes after the bite. Many sprorozoites may be eaten by macrophages, particularly by Kupfer cells (liver macrophages), although the majority of parasites escape phagocytosis and inadvertently invade the liver cells. Further development follows either the immediate multiplication (pre-erythrocytic schyzogony in the liver cells) or the formation of hypnozoites (arrested, dormant forms). Hypnozoites are specific for only 2 plasmodium parasites:
P. vivax and P. ovale. In both cases the primary blood invasion is delayed for months and if happens later on, it would signify a relapse of malaria.
P. falciparum and P. malariae sporozoites do not form hypnozoites, and they develop directly into the pre-erythrocytic schizonts in the liver. Pre-erythrocytic schyzogony takes about 6-16 days after infection (shortest for P. falciparum and longest for P. malariae). In general, the tissue schizogony in humans reminds the development of the oocyst inside the mosquito. The matured schizont contains 30,000-50,000 merozoites. Upon the rupture of schizont (and subsequently the hepatocyte), the merozoites escape and within minutes (about 15 min) they rapidly enter the erythrocytes. Inside the erythrocytes (RBCs), merozoites differentiate into the early intra-erythrocytic forms named trophozoites. When observed in the microscope, these forms of parasite have ring-like appearance. Trophozoite nucleus and cytoplasm divide, forming a schizont. Segmentation of schizont nucleus and cytoplasm forms merozoites. Schizogony becomes complete when schizont ruptures, releasing new merozoites into the blood stream causing fever. Subsequently, merozoites invade other RBSc and the cycle of schizogony is repeated. The duration of the asexual schizogonic cycle differs between human malarias. It is usually 48-50 hours in case of P. vivax, P. ovale, and P. falciparum, but 72 hours in P. malariae, which results in different species-based fever pattern. This very fever pattern was used to distinguish between tertian (48 hours) and quartan (72 hours) malaria. However, this periodicity does not always hold, especially early in the infection, because:

  1. liver schizonts may mature at different rates (from sporozoites inoculated during the same mosquito bite), producing separate "waves" of merozoites
  2. multiple infections may take place from different mosquito bites. With synchrony, periods of fever or febrile paroxysms assume a more definite 3 (tertian) or 4 (quatrain) - day pattern

Repeated asexual multiplication inside the RBCs increases parasite density which is normally slowed down by the host immune response. At some point of parasite development, merozoites may differentiate into the sexual forms, called gametocytes.


© 2002. Malaria in Armenia.
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