Molecular aspects of severe malaria

Human infections with Plasmodium falciparum may result in severe forms of m alaria. The widespread and rapid development of drug resistance in P. falci parum and the resistance of the disease-transmitting mosquitoes to insectic ides make it urgent to understand the molecular background of the pathogene sis of malaria to enable the development of novel approaches to combat the disease. This review focuses on the molecular mechanisms of severe malaria caused by the P falciparum parasite. The nature of severe malaria and the d eleterious effects of parasite-derived toxins and host-induced cytokines ar e introduced. Sequestration, brought about by cytoadherence and rosetting i s linked to severe malaria and is mediated by multiple receptors on the end othelium and red blood cells. P. falciparum erythrocyte membrane protein 1 (PfEMP1) is the ligand responsible for a majority of binding interactions, and the multiply adhesive features of this sticky molecule are presented. A ntigenic variation is also a major feature of PfEMP1 and of the surface of the P falciparum-infected erythrocyte. Possible mechanisms of P. falciparum antigenic variation in asexual stages are further discussed. We conclude t his review with a perspective and suggestions of important aspects for futu re investigations.