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Tumor necrosis factor (TNF) is thought to play a 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.

Original publication

DOI

10.1093/infdis/174.5.1091

Type

Journal article

Journal

The Journal of infectious diseases

Publication Date

11/1996

Volume

174

Pages

1091 - 1097

Addresses

Medical Research Council Laboratories, Fajara, Netherlands.

Keywords

Humans, Malaria, Cerebral, Nitric Oxide, Tumor Necrosis Factor-alpha, Antibodies, Monoclonal, Double-Blind Method, Child, Child, Preschool, Infant, Female, Male