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MICROBIOLOGY AND EPIDEMIOLOGY
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Six major species of Plasmodium cause nearly all cases of human disease: P. falciparum, P. vivax, two morphologically identical sympatric species of P. ovale, P. malariae, and P. knowlesi.
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P. falciparum, the cause of most cases of severe disease and most deaths, predominates in Africa, New Guinea, and Hispaniola.
P. vivax is more common in Central America.
P. falciparum and P. vivax are equally prevalent in South America, the Indian subcontinent, eastern Asia, and Oceania.
P. ovale makes up <1% of isolates outside Africa.
P. malariae is found in most areas (especially throughout sub-Saharan Africa) but is less common.
P. knowlesi (the monkey malaria parasite) can reliably be identified only by molecular techniques and is present in Borneo and Southeast Asia.
Malaria is the most important parasitic disease in humans, causing ∼1200 deaths each day.
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After introduction of sporozoites into the bloodstream by female anopheline mosquitoes, the parasite travels to the liver and reproduces asexually to form merozoites that infect RBCs. The merozoites transform into trophozoites, feed on intracellular proteins (principally hemoglobin), multiply 6- to 20-fold every 48 h (P. knowlesi, 24 h; P. malariae, 72 h), and cause the RBCs to rupture, releasing daughter merozoites. The process then repeats.
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Some parasites develop into long-lived sexual forms called gametocytes, whose uptake by another female anopheline mosquito allows transmission.
In P. vivax or P. ovale infection, dormant forms called hypnozoites remain in liver cells and may cause disease 2 weeks to >1 year later.
RBCs infected with P. falciparum may exhibit cytoadherence (attachment to venular and capillary endothelium), rosetting (adherence to uninfected RBCs), and agglutination (adherence to other infected RBCs). The result is sequestration of P. falciparum in vital organs, with consequent underestimation (through parasitemia determinations) of parasite numbers in the body. Sequestration is central to the pathogenesis of falciparum malaria but is not evident in the other human malarias.
In nonimmune individuals, infection triggers nonspecific host defense mechanisms such as increased splenic filtration.
– With repeated exposure to malaria, pts develop resistance to high-level parasitemia and disease but not to infection.
– Hemoglobinopathies (e.g., sickle cell disease, ovalocytosis, thalassemia) and G6PD deficiency are more common in endemic areas and protect against death from malaria.
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CLINICAL MANIFESTATIONS
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Pts initially develop nonspecific symptoms (e.g., headache, fatigue, myalgias) that are followed by fever.
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Febrile paroxysms at regular intervals are unusual and suggest infection with P. vivax or P. ovale.
Splenomegaly, hepatomegaly, mild anemia, and jaundice may develop.
The diagnosis of severe falciparum malaria requires one or more of the following: impaired consciousness/coma, severe normocytic anemia, renal failure, pulmonary edema, ARDS, circulatory shock, DIC, spontaneous bleeding, acidosis, hemoglobinuria, jaundice, repeated generalized convulsions, and a parasitemia level of >5%.