Pathogenesis and Life Cycle

Four species of Plasmodium cause malaria in humans: P. vivax is the most common and has a wide distribution including temperate areas, P. falciparum is the second most common and occurs mostly in tropical areas, P. malariae is rare but once was common in Europe, and P. ovale is the rarest and occurs in Africa and Southeast Asia.

The Plasmodium life cycle (left) starts when female Anopheles mosquitoes suck blood from an infected host and develop thousands of sporozoites, which are inoculated into a new host. Sporozoites infect human liver cells, which rupture releasing merozoites that invade red blood cells. In P. vivax and P. ovale infection, hypnozoites can remain dormant in the liver for years and cause relapses. P. falciparum and P. malariae do not remain dormant in the liver but can recrudesce due to maintenance of low parasitemia (P. malariae can recrudesce for 30 years). Merozoites become trophozoites, which begin as small ring forms that grow, become more compact, and nearly fill the red blood cell. Pigment granules form as hemoglobin is metabolized. Division of the mature trophozoite produces a schizont composed of clumped pigment and merozoites that are released when the red blood cell ruptures. The released merozoites invade other red blood cells. Some merozoites develop into sexual forms: female (macrogametocyte) and male (microgametocyte) gametocytes, which await a mosquito bite to start the cycle again.