INCREASED SERUM PHOSPHOLIPASE A2 ACTIVITY IN MALAWIAN CHILDREN WITH FALCIPARUM MALARIA

Abstract

Malaria is a multisystem disease with a mortality rate of 5 to 30% even with optimal treatment. Earlier studies have shown increased circulating levels of TNF in the plasma of patients as an independent predictor of severe or fatal disease. TNF has already been shown to facilitate the release of proinflammatory enzyme phospholipase A2 from various cells in vitro. Because both TNF and PLA2 are increased in patients with septicemia and because TNF levels are already shown to be increased in patients with malaria, the authors studied the relationship between TNF levels, severity of disease, and PLA2 activity. Seventy-five children (age 3 months to 10 years) with severe malaria due to Plasmodium falciparum and 34 controls (age 2 to 5 years) taking part in the malaria survey at a school in the same region in Malawi were included in the study. The children were afebrile and aparasitemic. Many of these children had cerebral malaria with coma. Twenty patients had uncomplicated falciparum malaria and 55 had cerebral malaria. Ten of them (all with cerebral malaria) died. In addition to examining the children, particularly for neurological status, laboratory studies obtained included the blood count, hematocrit, leukocyte count, thick blood smears for quantitative evaluation of parasitemia, and measurement of PLA2 activity. Mean plasma PLA2 activity in 34 healthy controls was 424 U/mL, whereas in the 75 patients with malaria the mean value was 53 804 U/mL. In the 45 children who were available for follow-up 1 month later after treatment the mean plasma PLA2 activity was 2546 U/mL. The high mean plasma level was not different between children with cerebral malaria and those with uncomplicated malaria. However the PLA2 activity in 28 children with profound coma was much higher than in other patients with malaria. The initial plasma PLA2 activity was predictive of outcome. Patients who had levels higher than 60 000 U/mL had a higher mortality rate (33%) compared with those with values less than 60 000 U at (8.3%). There was also a significant correlation between TNF and plasma PLA2 activity. Pretreatment serum PLA2 activity also correlated with the intensity of parasitemia. The cerebral spinal fluid PLA2 activity was not elevated even in those patients with severe malaria. The biological role of this observation is unclear. However, selective inhibition of PLA2 may be a new target for future therapy because PLA2 is proinflammatory enzyme.