Cerebral malaria (CM), the most ominous clinical syndrome caused by P. falciparum, is particularly difficult to manage medically; even under optimal conditions, mortality rates exceed 25 percent. CM is felt to be primarily an anoxic event, caused by the sequestration of paratsitized red blood cells (PRBCs) in brain capillaries and venules. Sequestration occurs as a result of binding of PRBCs to vascular endothelium; such binding, when reproduced in vitro can be reversed by specific antimalarial antibody. Furthermore, PRBCs can be 'flushed out' of deep tissue in squirrel monkeys with malaria when specific antibody is adminstered intravenously. Malaria is hyperendemic throughout Malawi. As a result, it is a common cause of morbidity and mortality in children over 6 months of age, but most adults are 'semi-immune'. Malaria treatment and control are major national health priorities in Malawi. The broad aim of this project is to improve the management of servere malaria in children.
The specific aims are: 1. To re-assess the clinical description of childhood CM in order to clearly define the syndrome, and to identify objective criteria by which responses to a therapeutic trial can be evaluated. 2. To determine the efficacy of intravenously administered immune globulin as an adjunct to standard therapy for CM. The project will commence with a descriptive study of CM, based at the central hospital in Blantyre, Malawi. Plasma from local Malawian blood donors will be collected and screened for various blood-born diseases and for the ability to interfere with in vitro PRBC adherence. The appropriate samples will be pooled, and the globulin fraction prepared for human use by Merieux Laboratories. The Cohn-Oncley fractionation process employed in the purification results in a product which carries no discernible risk of transmitting HIV infection. All patients will be randomly allocated, in a double-blind fashion, to receive, in addition to the standard treatment either immunoglobulin or a placebo. They will be observed for signs of clinical improvement, complications and eventual outcome using a planned sequential analysis.
