Cerebral Malaria, the Role of Adhesion Molecules in Its Pathogenesis

Cerebral malaria (CM), a complication in Plasmodium falciparum infection, causes high mortality among children in malaria endemic areas, with coma as major clinical symptom. Conventional explanation for the pathogenesis of the coma in CM is obstruction of small blood vessels in the brain by parasitized red blood cells which are sequestered there, that cause inadequate blood supply causing hypoxia and ischemia. Sequestration of parasitized rbc is started with the adherence of p-rbc to the endothelial cells lining blood vessels called cytoadherence, a specific ligand-receptor process involving adhesion molecules expressed on the surface of vascular endothels (i.e. CD 36, thrombospondin, ICAM-1, VCAM-1, E-selectin, Chondroitin-4-sulfate) and molecules on the surface of p-rbc which are related to the infecting parasites (e.g., Pf-EMP-1, Pf-HRP-1), followed or enhanced by rosette formation of normal rbc around p-rbc. Rosetting could involve similar p-rbc molecules involved in cytoadherence and facilitated by several serum proteins. The expression of adhesion molecules on the surface of endothelial cells is stimulated by parasite antigens and up-regulated by cytokines especially TNF-α (and IFN-γ). Efforts have been done to search antibody and medicine that could prevent cytoadherence and/or disrupt rosetting, and to control the production and effects of TNF-α.