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Initially patients have fever, chills, sweating, headache, weakness, and other symptoms mimicking a “viral syndrome.” Later, severe disease may develop, with an abnormal level of consciousness, severe anemia, renal failure, and multisystem failure.
Plasmodia are protozoa. Only the species Plasmodium falciparum, P vivax, P malariae, and P ovale are usually infectious for humans. Of these, P falciparum is the most dangerous.
In nature, uninucleate sporozoites in the salivary glands of infected mosquitoes are injected into a human host when the mosquito feeds. The sporozoites rapidly invade liver parenchymal cells, where they mature into liver-stage schizonts, which burst to release 2,000 to 40,000 uninucleate merozoites. In P vivax and P ovale infections, maturation of the schizont may be delayed for 1 to 2 years. Each merozoite can infect a red blood cell. Within the red cell, the merozoite matures either into a uninucleate gametocyte--the sexual stage, infectious for Anopheles mosquitoes--or, over 48 to 72 hours, into an erythrocyticstage schizont containing 10 to 36 merozoites. Rupture of the schizont releases these merozoites, which infect other red cells. If a vector mosquito ingests gametocytes, the gametocytes develop in the mosquito gut to gametes, which undergo fertilization and mature in 2 to 3 weeks to sporozoites.
The fever and chills of malaria are associated with the rupture of erythrocytic-stage schizonts. In severe falciparum malaria, parasitized red cells may obstruct capillaries and postcapillary venules, leading to local hypoxia and the release of toxic cellular products. Obstruction of the microcirculation in the brain (cerebral malaria) and in other vital organs is thought to be responsible for severe complications. Cytokines (e.g., tumor necrosis factor) are also felt to be involved, but at present their role is unclear.
Both innate and acquired immunity occur. Innate immunity consists of various traits of erythrocytes that discourage infection. The sickle-cell trait protects against the development of severe P falciparum malaria, and the absence of Duffy antigen prevents infection by P vivax. Recurrent infections lead to the development of humoral and cellular immune responses against all Plasmodium stages. Acquired immunity does not prevent reinfection but does reduce the severity of disease.
Malaria is distributed worldwide throughout the tropics and subtropics.
Diagnosis depends primarily on the identification of plasmodia in thick and thin blood smears.
Treatment: The widespread resistance of P falciparum to chloroquine complicates treatment of falciparum malaria. Alternative drugs such as mefloquine, pyrimethamine/ sulfadoxine (FansidarR), quinine, quinidine, halofantrine and artemisinin derivatives (qinghaosu) are used. Chloroquine remains highly effective against P malariae and P ovale malaria, and against P vivax everywhere except Papua New Guinea and parts of Indonesia, where significant resistance has developed. Disease caused by P vivax and P ovale requires primaquine to eradicate latent liver forms of the parasite.
Prevention: Malaria may be prevented by chemoprophylaxis and personal protective measures against the mosquito vector and by community-wide measures to control the vector. Exposure to night-feeding Anopheles mosquitoes is reduced by using protective clothing, insect repellents, insecticides, insecticide-impregnated bed nets, etc. Mosquitoes may be reduced by destroying breeding places and by application of insecticides. Vaccines are being developed.
