During the intraerythrocytic phase, the merozoite develops into a trophozoite (ring form), which then enlarges and begins to divide. Nuclear division initiates the schizont stage. Each schizont contains 6 to 24 merozoites, depending on the species. Proliferation of the merozoites leads to rupture of the erythrocyte, and the cycle begins again. A small number of the merozoites that enter red blood cells develop into male and female gametocytes. These do not rupture the red blood cells and require ingestion by the anopheline mosquito for further development.
Fertilization of the gametocytes occurs within the stomach of the mosquito. The parasite then undergoes several additional changes that lead to the production of sporozoites. Their inoculation into a new human host starts the cycle again.
In P. vivax and P. ovale, some sporozoites may remain dormant in hepatic cells for months or years; these are referred to as hypnozoites. When they do begin to proliferate, they may cause a relapse, often long after the primary infection. Such relapses do not occur with p. falciparum or P. malariae. The four species also differ in disease manifestations.
The immune response to malaria also is quite complex. Shortly after infection, antibodies that react with a wide variety of parasite antigens can be detected in the blood; however, this serologic response does not indicate a significant degree of immunity to subsequent infection. Reinfections usually are clinically less severe, as judged by the fever curve, although this effect is minor. individuals reexposed to infected mosquitoes have repeated episodes of malaria (Miller et al., 1984).
Repeated infections eventually lead to a relative increase in immunity, however, which is made apparent by the profound difference between the clinical manifestations of malaria in young children and in adults. Young children have the most severe attacks, often resulting in death if untreated. By adulthood, most individuals who live in endemic areas have developed a degree of immunity such that reinfection results in a relatively mild disease. After repeated episodes of infection, some individuals may become almost entirely refractory to challenge with P. falciparum (Miller et al., 1984). Nevertheless, absolute immunity is difficult to establish; instead, a continuum appears to exist from high susceptibility to high resistance.
Immunity to malaria is largely antibody-mediated. The classic studies by Cohen et al. (1961) in The Gambia indicated that antiparasitic activity could be transferred with IgG from donors in endemic areas, but not with control IgG from Europeans. The antiparasitic activity of immune serum also can be demonstrated in in vitro experiments (Chulay et al., 1981).
The immune response to sporozoites, the stage of the parasite responsible for transmission of disease from mosquito to man, is of great interest. Antibodies to sporozoites can be found in individuals