Genetic resistance to malaria

Human genetic resistance to malaria refers to inherited changes in the DNA of humans which are thought to be due to pressure from evolving alongside the parasites that cause malaria (parasites of the genus Plasmodium). These DNA changes confer a selective survival advantage by increasing resistance to disease. Since malaria infects red blood cells, these genetic changes are most commonly alterations to molecules essential for red blood cell function (and therefore parasite survival), such as [hemoglobin] or other cellular proteins or enzymes of red blood cells. These alterations generally protect red blood cells from invasion by Plasmodium parasites or replication of parasites within the red blood cell.

Malaria has placed the strongest known [Evolutionary pressure|selective pressure] on the [human genome] since the origination of [agriculture] within the past 10,000 years.Plasmodium falciparum was probably not able to gain a foothold among African populations until larger sedentary communities emerged in association with the evolution of domestic agriculture in Africa (the agricultural revolution). Several inherited variants in erythrocytes have become common in formerly malarious parts of the world as a result of selection exerted by this parasite. This selection was historically important as the first documented example of disease as an agent of natural selection in humans. It was also the first example of genetically controlled innate immunity that operates early in the course of infections, preceding adaptive immunity which exerts effects after several days. In malaria, as in other diseases, innate immunity leads into, and stimulates, adaptive immunity.

One of the key reasons for the high fatality rate in P. falciparum malaria is the occurrence of so-called cerebral malaria. Patients become confused, disoriented and often lapse into a terminal coma. Clumps of malaria-infested red cells adhere to the endothelium and occlude the microcirculation of the brain with deadly consequences. The P. falciparum parasite alters the characteristics of the red cell membrane, making them more "sticky". Clusters of parasitized red cells exceed the size of the capillary circulation blocking blood flow and producing cerebral hypoxia. Cerebral malaria accounts for 80% of malaria deaths. Thalassemic erythrocytes adhere to parasitized red cells much less readily than do their normal counterparts. This alteration would lessen the chance of developing cerebral malaria.

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