Abstract: Malaria remains a major concern of morbidity and mortality. Despite treating infected individuals with artemisinin-based combination therapies (ACTs), cerebral and severe malaria cause enormous mortality in children and adults. The only treatment option is parenteral administration of artemisinin or quinine with supportive symptomatic therapies. However, the fatality rate remains high despite parasite clearance emphasizing the need of adjunct therapy to prevent malaria mortality. In this invention, heme synthesized in the malaria parasite is shown to be associated with parasite virulence, disease severity and cerebral pathogenesis. Parasite heme enhances the formation of hemozoin—a parasite molecule associated with cerebral and severe malaria. Griseofulvin prevents experimental cerebral malaria (ECM) by inhibiting parasite heme synthesis and hemozoin formation, without affecting parasite growth. Griseofulvin exhibits synergy with arteether—the principal component of ACTs and prevents ECM.