Clinical and molecular aspects of severe malaria.
The erythrocytic cycle of Plasmodium falciparum presents a particularity in relation to other Plasmodium species that infect man. Mature trophozoites and schizonts are sequestered from the peripheral circulation due to adhesion of infected erythrocytes to host endothelial cells. Modifications in the surface of infected erythrocytes, termed knobs, seem to facilitate adhesion to endothelium and other erythrocytes. Adhesion provides better maturation in the microaerophilic venous atmosphere and allows the parasite to escape clearance by the spleen which recognizes the erythrocytes loss of deformability. Adhesion to the endothelium, or cytoadherence, has an important role in the pathogenicity of the disease, causing occlusion of small vessels and contributing to failure of many organs. Cytoadherence can also describe adhesion of infected erythrocytes to uninfected erythrocytes, a phenomenon widely known as rosetting. Clinical aspects of severe malaria, as well as the host receptors and parasite ligands involved in cytoadherence and rosetting, are reviewed here. The erythrocyte membrane protein 1 of P. falciparum (PfEMP1) appears to be the principal adhesive ligand of infected erythrocytes and will be discussed in more detail. Understanding the role of host receptors and parasite ligands in the development of different clinical syndromes is urgently needed to identify vaccination targets in order to decrease the mortality rates of this disease.
Kirchgatter
Karin
K
Núcleo de Estudos em Malária, Superintendência de Controle de Endemias (SUCEN), Instituto de Medicina Tropical de São Paulo (IMTSP), Universidade de São Paulo (USP), São Paulo, SP 05403-000, Brazil. karink@usp.br
Del Portillo
Hernando A
HA
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D004730:Endothelium, Vascular / Q000469:parasitology; D004912:Erythrocytes / Q000469:parasitology*; D006790:Host-Parasite Interactions; D006801:Humans; D016778:Malaria, Falciparum / Q000150:complications / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D012397:Rosette Formation; D012720:Severity of Illness Index