Tuesday 4 May 2004
Life Cycle and Pathogenesis
P. vivax, P. ovale, and P. malariae cause low parasitemia, mild anemia, and, in rare instances, splenic rupture and nephrotic syndrome. P. falciparum causes high levels of parasitemia, severe anemia, cerebral symptoms, renal failure, pulmonary edema, and death. The life cycles of the Plasmodium species are similar, although P. falciparum differs in ways that contribute to its greater virulence.
The infectious stage of malaria, the sporozoites, is found in the salivary glands of female mosquitoes. When the mosquito takes a blood meal, sporozoites are released into the human’s blood and within minutes attach to and invade liver cells by binding to the hepatocyte receptor for the serum proteins thrombospondin and properdin.
Within liver cells, malaria parasites multiply rapidly, so as many as 30,000 merozoites (asexual, haploid forms) are released when each infected hepatocyte ruptures. P. vivax and P. ovale form latent hypnozoites in hepatocytes, which cause relapses of malaria long after initial infection.
Once released from the liver, Plasmodium merozoites bind by a parasite lectinlike molecule to sialic residues on glycophorin molecules on the surface of red blood cells. Within the red blood cells, the parasites grow in a membrane-bound digestive vacuole, hydrolyzing hemoglobin through secreted enzymes.
The trophozoite is the first stage of the parasite in the red blood cell and is defined by the presence of a single chromatin mass. The next stage, the schizont, has multiple chromatin masses, each of which develops into a merozoite.
On lysis of the red blood cell, the new merozoites infect additional red blood cells. Although most malaria parasites within the red blood cells develop into merozoites, some parasites develop into sexual forms called gametocytes that infect the mosquito when it takes its blood meal.