The effect of a monoclonal antibody to tumor necrosis factor on survival from childhood cerebral malaria.
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.
van Hensbroek
M B
MB
Medical Research Council Laboratories, Fajara, Netherlands.
Palmer
A
A
Onyiorah
E
E
Schneider
G
G
Jaffar
S
S
Dolan
G
G
Memming
H
H
Frenkel
J
J
Enwere
G
G
Bennett
S
S
Kwiatkowski
D
D
Greenwood
B
B
D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007223:Infant; D016779:Malaria, Cerebral / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide