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Protection against malaria by abnormalities in red cell surface antigens and cytoskeletal proteins

David J Roberts, MA, MB, D Phil
Section Editors
Stanley L Schrier, MD
Johanna Daily, MD, MSc
Deputy Editors
Jennifer S Tirnauer, MD
Elinor L Baron, MD, DTMH


Most red cell genetic defects in human populations (eg, thalassemia, G6PD deficiency, sickle cell anemia) appear to be due to the exposure to malaria, a disease estimated to have arisen about 3000 years ago with the emergence of agriculture [1-3]. Humans exhibit variable susceptibility to malarial infection; most of the resistance to this infection is either genetic, environmental, based upon previous exposure, or access to therapy.

A study of the relative importance of each of these factors to the overall burden of malarial disease in human populations was examined in Sri Lanka. Longitudinal studies showed that 20 percent of the variation in the intensity of disease was explained by repeatable differences between patients and approximately half was attributable to host genetics [4]. A similar analysis in Africa demonstrated 25 percent of the total variation in the incidence of hospital admission for malaria was explained by additively-acting host genes, with 2 percent of this variation due to presence of the sickle cell trait [5].

The role of certain blood group antigens in malarial infection and genetic resistance to malaria associated with abnormalities in the red cell cytoskeleton will be reviewed here. The overall subject of anemia in malaria, as well as malarial resistance associated with the hemoglobinopathies (eg, hemoglobins S, C, E, thalassemia), are discussed separately. (See "Anemia in malaria" and "Protection against malaria in the hemoglobinopathies".)

Development of a malaria vaccine based upon various malarial antigens and/or their receptors is discussed separately. (See "Malaria in endemic areas: Epidemiology, prevention, and control", section on 'Vaccine development'.)


Plasmodium falciparum malaria, the deadly form of malaria, has a life cycle that includes a sexual cycle in an Anopheles mosquito and a human cycle that includes a liver stage and an obligatory erythrocytic stage. Genetic resistance is much better defined for the erythrocytic stage and may involve one or more of the following mechanisms:


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Literature review current through: Sep 2016. | This topic last updated: Oct 20, 2015.
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