Cerebral malaria the most ominous clinical syndrome caused by Plasmodium falciparum is difficult to manage medically. Even under optimal conditions, morbidity and mortality rates exceed 25 percent. The pathogenesis of CM is unclear, but is it thought to be primarily an anoxic event, caused by the sequestration of parasitized red blood cells in brain capillaries and venules. Sequestration occurs when the parasitized erythrocytes bind to vascular endothelium; this binding, when reproduced in vitro and in animal models, can be reversed and inhibited by specific antimalarial antibody. The broad goal of this project is to improve the management of falciparum malaria in children, the age group at highest risk in endemic areas.
The specific aims are: 1) To prepare immune globulin suitable for intravenous use, using, as the source, plasma collected for adult blood donors. The original pool of plasma, collected during the January-June 1988 """"""""season"""""""", was discovered to be HIV-seropositive and an extra year will be required to collect the volume of plasma required for the purification process. 2) To conduct a double blind, placebo-controlled trial of intravenous immune globulin (IVIG) as an adjunct to standard quinine therapy for CM. Children at highest risk of dying or developing brain damage can now be identified. A total 60 IVIG recipients and 60 controls will be required to detect a decrease in mortality from 50 percent to 25 percent.
| Taylor, T E; Borgstein, A; Molyneux, M E (1993) Acid-base status in paediatric Plasmodium falciparum malaria. Q J Med 86:99-109 |
| Taylor, T E; Molyneux, M E; Wirima, J J et al. (1992) Intravenous immunoglobulin in the treatment of paediatric cerebral malaria. Clin Exp Immunol 90:357-62 |
| Grau, G E; Taylor, T E; Molyneux, M E et al. (1989) Tumor necrosis factor and disease severity in children with falciparum malaria. N Engl J Med 320:1586-91 |
