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Increased Serum Phospholipase A₂ Activity in Malawian Children with Falciparum Malaria

Some clinical manifestations of severe malaria resemble those of sepsis and there may be mediators of the host response that are common to both sepsis and malaria. Phospholipase A₂(PLA₂), a proinflammatory enzyme whose expression is induced by tumor necrosis factor (TNF), has been implicated in the pathogenesis of complications of the sepsis syndrome. We examined levels of circulating PLA₂ in Plasmodium falciparum malaria and studied the association of PLA₂ with disease severity. Plasma PLA₂ and TNF were measured in 75 Malawian children with P. falciparum malaria. The mean (SD) plasma PLA₂ activity in children with acute malaria was 53,804 (37,256) units/ml as compared with 424 (349) units/ml in 34 healthy controls (P < 0.00001). The mean PLA₂ activity in 45 convalescent patients was 2,546 (7,372) units/ml (P < 0.00001). In 48 patients with pretreatment PLA₂ activity less than 60,000 units/ml, mortality was 8.3%, while in 27 patients with pretreatment PLA₂ levels greater than 60,000 units/ml, mortality was 33.3% (P = 0.008). There were significant correlations between PLA₂ and TNF (r = 0.471, P < 0.01), density of parasitemia (r = 0.443, P < 0.0001) and a decrease in hematocrit (r = 0.352, P < 0.005). These data show that P. falciparum malaria is associated with a markedly increased circulating PLA₂, especially in patients with severe disease, as manifested by high parasite burden, anemia, coma, and death.

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