Plasmodium

The key to the Plasmodium life cycle is the Anopheles mosquito, the only genera of mosquito able to support replication of the parasite. Human infection begins following release of infectious sporozoites from a female Anopheles spp. mosquito while she takes a blood meal. Sporozoites disseminate to the liver, infect hepatocytes and over the next 7 to 16 days, differentiate and replicate into thousands of merozoites, all contained within a intracytoplasmic vesicle referred to as the schizont. The schizont, along with the host hepatocyte, ultimately ruptures, releasing thousands of merozoites into the bloodstream. Some Plasmodium species (i.e., P. vivax and P. ovale) can persist in a dormant phase within hepatocytes and lead to relapse infections months to years following initial infection. Released merozoites infect erythrocytes and undergo asexual replication, resulting in formation of a schizont and eventual rupture of the erythrocyte, allowing for invasion of new erythrocytes. Depending on the species, this erythrocyte invasion cycle occurs every 1 to 3 days, coinciding with febrile episodes. A small fraction of merozoites form male and female gametocytes, which also circulate in the bloodstream and are the forms that are infectious to the mosquito. Following ingestion by a female Anopheles mosquito, the gametocytes mature and fuse to form a zygote, which eventually develops into an oocyst harboring the human-infectious sporozoite forms. The sporozoites are released and travel to the mosquito salivary glands in preparation for the next blood meal, completing the parasite life cycle.

The clinical manifestations of Malaria begin upon rupture of the merozoites from erythrocytes. Following synchronization of erythrocyte rupture, the onset of febrile episodes stabilizes, occurring every 48 hours in cases of P. falciparum, P. vivax and P. ovale infections and every 72 hours in cases of P. malariae infection. Initial malarial infections present nonspecifically with fever, tachycardia, headache, chills, nausea, anorexia, and fatigue. Among the five species associated with human disease, P. falciparum causes the greatest morbidity and mortality, followed by P. vivax.