(Top) Life cycle of Plasmodium falciparum and gametocyte development. (Top) Life cycle of Plasmodium falciparum and gametocyte development. Malaria parasites enter the human bloodstream in the form of sporozoites that are injected by infected female Anopheles mosquitoes taking a blood meal. The majority of sporozoites migrate to the liver, where they invade hepatocytes and multiply. Merozoites are formed that are released into the bloodstream, where they invade red blood cells, initiating the asexual multiplication cycle. A fraction of merozoites that are released from infected red blood cells form gametocytes, the transmissible parasite form. The formation and maturation of gametocytes take place in five morphologically recognizable stages. Early-stage gametocytes are sequestered, and only mature stage V gametocytes circulate in the peripheral blood, where they can be taken up by mosquitoes. Once ingested by mosquitoes, each individual gametocyte forms 1 female macrogamete or up to 8 male microgametes. In the mosquito midgut, the fusion of gametes results in the formation of a zygote that develops into a motile ookinete that can penetrate the midgut wall to form oocysts. The oocysts enlarge over time and burst to release sporozoites that migrate to the mosquito salivary gland, rendering the mosquito infectious to human beings. (Bottom) The five developmental stages of P. falciparum gametocytes and mature P. vivax gametocytes. (The P. falciparum gametocyte photographs are reprinted from reference 410 with permission; the P. vivax gametocyte photographs are courtesy of Debbie Nolder, Malaria Reference Laboratory, London School of Hygiene and Tropical Medicine, United Kingdom, reproduced with permission.)‏ Teun Bousema, and Chris Drakeley Clin. Microbiol. Rev. 2011; doi:10.1128/CMR.00051-10