Overview of human genetic susceptibility to malaria: From parasitemia control to severe disease.

Malaria is a life-threatening blood disease caused by the protozoan Plasmodium. Infection may lead to several different patterns of symptoms in the host: asymptomatic state, uncomplicated disease or severe disease. Severe malaria occurs mostly in young children and is a major cause of death. Disease is thought to result from the sequestration of parasites in the small blood vessels of the brain and the deregulation of key immune system elements. The cellular and molecular regulatory mechanisms underlying the pathogenesis of disease are however not fully understood. What is known it is that the genetic determinants of the host play an important role in the severity of the disease and the outcome of infection. Here we review the most convincing results obtained through genetic epidemiology studies concerning the genetic control of malaria in human caused by Plasmodium falciparum infection. The identification of genes conferring susceptibility or resistance to malaria might improve diagnosis and treatment.