The Effect of a Monoclonal Antibody to Tumor Necrosis Factor on Survival From Childhood Cerebral Malaria

J Infect Dis. 1996 Nov;174(5):1091-7. doi: 10.1093/infdis/174.5.1091.

Abstract

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Child
  • Child, Preschool
  • Double-Blind Method
  • Female
  • Humans
  • Infant
  • Malaria, Cerebral / complications
  • Malaria, Cerebral / mortality
  • Malaria, Cerebral / therapy*
  • Male
  • Nitric Oxide / physiology
  • Tumor Necrosis Factor-alpha / physiology*

Substances

  • Antibodies, Monoclonal
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide