© Cambridge University Press 2011. Introduction There are four species of Plasmodium that naturally infect humans, but only P. falciparum is associated with epilepsy, although seizures are reported during acute P. vivax infections. Plasmodium falciparum is the most severe form of malaria and is responsible for most of the neurological complications. It accounts for almost all the mortality and neurological sequelae following malaria infections. Epidemiology of malaria It is estimated that P. falciparum infects over 2 billion people in the world, causing 500 million clinical episodes of malaria, with more than 1 million deaths per year (Snow et al. 2005). Over 70% of the infections occur in young children living in sub-Saharan Africa, most of whom live in endemic areas where they can receive up to 300 bites from infected mosquitoes per year. There are differences in the clinical presentation between African children and non-immune individuals. In particular, seizures during acute infections and neurological sequelae following severe malaria are more common in African children than non-immune individuals (Newton and Warrell 1998). Pathogenesis of malaria The erythrocyte stages of P. falciparum are responsible for the acute symptoms and probably the development of epilepsy. One of the unique features of P. falciparum is that the late stages of the erythrocytic cycle, i.e., schizonts, sequester within the vascular beds of the internal organs, particularly the brain.