Plasmodium knowlesi life cycle

(1) Plasmodium-infected Anopheles mosquito bites a human and transmits sporozoites into the bloodstream. (2) Sporozoites migrate through the blood to the liver where they invade hepatocytes and divide to form multinucleated schizonts (pre-erythrocytic stage). (3) The schizonts rupture and release merozoites into the circulation where they invade red blood cells. Within red cells, merozoites mature from ring forms to trophozoites to multinucleated schizonts (erythrocytic stage). (4) Some merozoites differentiate into male or female gametocytes. These cells are ingested by the Anopheles mosquito and mature in the midgut, where sporozoites develop and migrate to the salivary glands of the mosquito. The mosquito completes the cycle of transmission by biting another host. Transmission is predominantly zoonotic. Human-mosquito-human transmission has been demonstrated in a laboratory setting but has not yet been proven to occur in the natural environment.