Malaria host response

Enwere, G. C., Ota M. O. and Obaro S. K. The host response in malaria and depression of defence against tuberculosis. Annals of Tropical Medicine and Parasitology 93 669-678 1999. 

Burt RA, Baldwin TM, Marshall VM, Foote SJ 1999 Temporal expression of an H2-linked locus in host response to mouse malaria. Immunogenetics 50 278-285 Casanova JL, Abel L 2004 The human model a genetic dissection of immunity to infection in natural conditions. Nat Rev Immunol 4 55-66... 

The common symptoms of malaria are due to the rupture of erythrocytes when erythrocytic schizonts mature (Fig. 6.2a). This release of parasite material triggers a host immune response, which in turn induces the formation of inflammatory cytokines, reactive oxygen intermediates and other cellular products. These pro-inflammatory molecules play a prominent role in pathogenesis, and are probably responsible for the fever, chills, sweats, weakness and other systemic symptoms associated with malaria. In P. falciparum malaria, infected erythrocytes adhere to the endothelium of capillaries... 

A striking feature of P. falciparum, the unicellular parasite responsible for the most virulent and widespread form of human malaria, is that it hosts the GC-poorest (22% GC) nuclear genome known so far (Poliak et al., 1982, McCutchan et al., 1984). This genome, which only comprises 3 Mb of DNA (Weber, 1988) organized in 14 chromosomes (Kemp et al., 1987 Wellems et al., 1987), is, therefore, an excellent model for studying compositional constraints and their effects. 

Malaria parasites have a complex life cycle that permits drug action at several points. Plasmodium species that infect humans P falciparum, P malariae, P ovale, P vivax) tire spread by the female Anopheles mosquito and, after inoculation into the human host, undergo a primary developmental stage in the liver (primary tissue phase). They then enter the blood and parasitize erythrocytes (erythrocytic phase). P falciparum and P malariae have only one cycle of liver cell invasion thereafter, multiplication is confined to erythrocytes. The other species have a dormant hepatic stage (in which they become bypnozoites) that is responsible for recurrent infections and relapses after apparent recovery of the host from the initial infection. 

Plasmodium vivax, the cause of benign tertian malaria, produces milder clinical attacks than those of P. falciparum, and death is uncommon even in untreated cases. The build-up of immunity in the host rapidly controls the infection and schizonts disappear from the blood stream. The exo-erythro-cytic forms in the liver, unaffected by immunity, continue asexual division and reinvade the circulation when immunity has fallen once more these relapses are characteristic of vivax malaria and occur for at least two years after the primary infection. Infections due to P. ovale also follow a tertian pattern, but are much milder and more responsive to therapy than those due to P. vivax and relapses are less frequent. Infections due to both these parasites often display a prolonged incubation period between the primary infection and the development of malarial symptoms. P. vivax is widely distributed north and south of the equator, extending from the tropics to the temperate zones, while P. ovale is restricted to tropical Africa and the western Pacific. 

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