ABSTRACT

The life cycle of the malaria parasite is complex (Figure 2. 1). The sporozoites are transmitted to humans by the bite of infected female mosquitoes of the genus Anopheles. The sporozoites circulate for a short time in the blood stream, then invade liver cells, where they develop into exoerythrocytic schizonts during the next 5 to 15 days. Plasmodium vivax, P. ovale and P. cynomolgi have a dormant stage, the hypnozoite (Krotoski et aI. , 1982a and b), that may remain in the liver for weeks or many years before the development of exoerythrocytic schizogony. This results in relapses of infection. Plasmodium Jalciparum and P. malariae have no persistent phase. An exoerythrocytic schizont contains 10000 to 30 000 merozoites, which are released and invade the red blood cells. Erythrocyte invasion by merozoites is dependent on the interactions of specific receptors on the erythrocyte membrane with ligands on the surface of the merozoite. The entire invasion process takes about 30 seconds. The merozoite develops within the erythrocyte through ring, trophozoite and schizont (erythrocytic schizogony). The parasite modifies its host cell in several ways to enhance its survival. The erythrocyte containing the segmented schizont eventually ruptures and releases the merozoites, which invade additional erythrocytes. In the course of these events, some merozoites invade erythrocytes, become differentiated into sexual forms, which are macrogametocytes (female) and microgametocytes (male). The duration

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of gametocytogony is assumed to be approximately 4 to 10 days depending on the Plasmodium species. Maturc macrogametocytes taken into the midgut of the Anopheles mosquito escape from the erythrocyte to form macrogametes . Microgametocytes in the midgut exflagellate, each forms 8 micro gametes after a few minutes postinfection. The microgamete moves quickly to fertilize a macrogamete and forms a zygote. Within 1 8 to 24 hours, the zygote elongates into a slowly motile ookinete . The ookinete traverses the peri trophic membrane and the epithelial cell of the midgut, and then transforms into an oocyst beneath the basement membrane of the midgut epithelium. Between 7 and 1 5 days postinfection, depending on the Plasmodium species and ambient temperature, a single oocyst forms more than 1 0000 sporozoites . The motile sporozoites migrate into the salivary glands and accumulate in the acinar cells of the salivary glands . When an infected mosquito bites a susceptible vertebrate host, the Plasmodium life-cycle begins again.