Artemether is as effective as quinine in the treatment of cerebral malaria in children.

Tumor necrosis factor (TNF) is thought to playa key role in the pathogenesis of cerebral malaria. A double-blind, placebo-controlled trial of an anti-TNF monoclonal antibody (B-C7) comprised 610 Gambian children with cerebral malaria, with mortality and residual neurologic sequelae as primary study end points. Sixty (19.9%) of 302 children who received B-C7 died compared with 64 (20.8%) of 308 children who received placebo (adjusted odds ratio [OR], 0.90; 95% confidence interval [CI], 0.57-1.42). Residual neurologic sequelae were detected in 15 (6.8%) of 221 survivors from the B-C7 group and in 5 (2.2%) of 225 survivors of the placebo group (adjusted OR, 3.35; 95% CI, 1.08-10.4). The monoclonal antibody used in this study did not improve survival in cerebral malaria and was associated with a significant increase in neurologic sequelae. A possible explanation of the latter observation is that the antibody acts to retain TNF within the circulation and thereby prolongs its effects on vascular endothelium. Cerebral malaria in children has a case fatality rate of 10%-30% despite effective antimalarial treatment [1, 2]. Deaths in cases of cerebral malaria occur frequently in the first hours after admission, before antimalarial therapy has become effective. Recently, it has been shown that a fast-acting antimalarial agent, artemether, did not change this pattern, nor did it improve outcome [3]. Thus, there is a need to develop new forms of therapy for cerebral malaria. These should have antidisease properties and a fast onset of action and be given in conjunction with conventional antimalarial treatment. Recent studies strongly suggest that tumor necrosis factor (TNF) plays a key role in the pathogenesis of cerebral malaria. In clinical studies, an association has been found between plasma TNF levels and disease severity and outcome [4, 5], and it has been shown that children homozygous for the TNF2 allele, which has been associated with high TNF production, are more likely to develop cerebral malaria and die as a conse