Complement activation in severe Plasmodium falciparum malaria

Abstract

We determined indices of plasma complement activation (C3, C4, Bb, C4d, iC3b, and SC5b-9), levels of tumor necrosis factor (TNF) and interleukin-6, and the APACHE H score in 23 patients with complicated Plasmodium falciparum malaria. On admission, plasma concentrations of Bb, SC5b-9, and C4d were markedly increased compared to healthy control subjects (n = 24) (4.5 ± 1.9 vs 1.5 ± 0.6 mg/L; 1125.7 ± 496.9 vs 183.2 ± 76.5 μg/L; and 15.7 ± 5.7 vs 7.2 ± 1.4 mg/L, P < 0.01 for all). In contrast C3 and iC3b concentrations were decreased (631.4 ± 247 vs 947.3 ± 243.2 and 105 ± 17.9 vs 151.3 ± 14.5 mg/L; P < 0.01 for both). Plasma C4 concentrations in malaria were not different from normal controls. Plasma Bb, C3, and iC3b levels normalized on day 7 of treatment, whereas SC5b-9 and C4d levels remained elevated. A significant correlation between elevated TNF levels and Bb (r = 0.507) and SC5b-9 (r = 0.448, P < 0.01 for both) and a negative correlation between iC3b and SC5b-9 and TNF levels existed (r = -0.537 and r = -0.466, P < 0.01 for both). In addition, a significant correlation between C3 and iC3b (r = 0.689) and C4 and C4d (r = 0.737) existed. However, no relation between clinical disease severity and complement fragments existed. The results demonstrate that both the classical and the alternative pathways of the complement system are profoundly activated in complicated malaria.