The life cycle of Plasmodium falciparum

Human infectionbegins with the injection of sporozoites into the bloodstream by infected female Anopheles spp. mosquitoes during a blood meal. Sporozoites travel to the liver and initially invade hepatocytes and multiply, which is known as pre-erythrocytic development. This is followed by the release of merozoites into the bloodstream, which initiates the asexual parasite multiplication stage (see the figure). The variation in the density of asexual parasites in the bloodstream of infected individuals in an area of moderate transmission intensity is shown in red (inset)⁸⁴. The duration of blood-stage infection is highly variable: many infections are cleared at an early stage, whereas others remain for several months³⁸. A fraction of merozoites form sexual gametocytes, which is the only parasite form that is capable of transmission from humans to mosquito vectors. Immature gametocytes (those in stages I–IV) are sequestered in the bone marrow and only mature gametocytes (stage V) circulate in peripheral blood. The density of mature gametocytes in peripheral blood is typically less than 100 gametocytes per μl of blood (light blue; inset)⁸⁵ and the vast majority are present at submicroscopic densities. Following ingestion by mosquitoes, each individual gametocyte forms one female macrogamete or up to eight male microgametes. In the mosquito midgut, gamete fusion produces a zygote that develops into a motile ookinete, which can penetrate the midgut wall and form oocysts. Oocyst densities in naturally infected mosquitoes that have fed on either microscopic or submicroscopic parasite carriers are typically in the range of 1–10 oocysts (brown; inset)⁸⁶. The oocysts enlarge over time and burst to release sporozoites that migrate to the mosquito salivary gland, from where they can infect humans during the next blood meal⁸⁷.