Life cycle of Plasmodium*

(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). Atovaquone-proguanil and primaquine have activity against hepatic-stage schizonts.
(3) Hypnozoites are a quiescent stage in the liver that exist only in the setting of P. vivax and P. ovale infection. This liver stage does not cause clinical symptoms, but with reactivation and release into the circulation, late-onset or relapsed disease can occur up to many months after initial infection. Primaquine is active against the quiescent hypnozoites of P. vivax and P. ovale.
(4) 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). Blood-stage schizonticides such as artemisinins, atovaquone-proguanil, doxycycline, mefloquine, and chloroquine interrupt schizogony within red cells.
(5) 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.