Pathogenesis of Plasmodium falciparum malaria: the roles of parasite adhesion and antigenic variation.
Malaria results in up to 2.5 million deaths annually, with young children and pregnant women at greatest risk. The great majority of severe disease is caused by Plasmodium falciparum. A characteristic feature of infection with Pfalciparum is the accumulation or sequestration of parasite-infected red blood cells (RBCs) in various organs, such as the brain, lung and placenta, and together with other factors is important in the pathogenesis of severe forms of malaria. Sequestration results from adhesive interactions between parasite-derived proteins expressed on the surface of infected RBCs and a number of host molecules on the surface of endothelial cells, placental cells and uninfected RBCs. Some receptors for parasite adhesion have been implicated in particular malaria syndromes, such as intercellular adhesion molecule 1 in cerebral malaria and chondroitin sulfate A and hyaluronic acid in placental infection. The principal parasite ligand and antigen on the RBC surface, P falciparum erythrocyte membrane protein 1 encoded by a multigene family termed var, is clonally variant, enabling evasion of specific immune responses. An understanding of these host-parasite interactions in the context of clinical disease and immunity may reveal potential targets to prevent or treat severe forms of malaria.
Beeson
J G
JG
Department of Medicine, University of Melbourne, Post Office Royal Melbourne Hospital, Victoria, Australia.
Brown
G V
GV
D000818:Animals; D000940:Antigenic Variation; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D006790:Host-Parasite Interactions; D006801:Humans; D007155:Immunologic Factors / Q000502:physiology; D016778:Malaria, Falciparum / Q000175:diagnosis / Q000209:etiology* / Q000276:immunology / Q000469:parasitology; D008954:Models, Biological; D010963:Plasmodium falciparum / Q000276:immunology / Q000472:pathogenicity*; D011247:Pregnancy
D015815:Cell Adhesion Molecules; D007155:Immunologic Factors