The Plasmodium falciparum-infected red blood cell

Abstract

Plasmodium falciparum, the most virulent of the human malaria parasites, causes up to one million deaths per year. The parasite spends part of its lifecycle inside the red blood cells (RBCs) of its host. As it grows it ingests the RBC cytoplasm, digesting it in an acidic vacuole. Free haem released during haemoglobin digestion is detoxified by conversion to inert crystals of haemozoin. Malaria pathology is evident during the blood stage of the infection and is exacerbated by adhesion of infected RBCs to blood vessel walls, which prevents splenic clearance of the infected cells. Cytoadherence is mediated by surface-exposed virulence proteins that bind to endothelial cell receptors. These 'adhesins' are exported to the RBC surface via an exomembrane system that is established outside the parasite in the host cell cytoplasm. Antimalarial drugs that interfere with haem detoxification, or target other parasite-specific processes, have been effective in the treatment of malaria, but their use has been dogged by the development of resistance. Similarly, efforts to develop an effective blood vaccine are hindered by the variability of surface-exposed antigens.Cell factsPlasmodium falciparum invades RBCs and develops through the 'ring' and 'trophozoite' stages, then divides to form an average of ∼20 daughter cells in the 'schizont' stage.The intraerythrocytic P. falciparum parasite consumes up to 70% of the host cell haemoglobin in an acidic digestive vacuole, generating a crystalline by-product called haemozoin.Plasmodium- infected RBCs rely almost entirely on glycolysis for energy.The parasite establishes an exomembrane system in the host RBC cytoplasm and this provides a pathway for trafficking proteins, including virulence determinants, to the RBC surface.Adhesion of P. falciparum-infected RBCs to blood vessel walls helps avoid splenic clearance and contributes to the clinical symptoms of the disease, including fatal complications.Quinoline antimalarials inhibit haemozoin formation leading to a build-up of toxic haematin.Artemisinin-related antimalarials are thought to be activated by haemoglobin digestion products.Parasites have developed resistance to quinoline antimalarials and there are recent reports of reduced sensitivity to artemisinin-related antimalarials. Show more