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Protection against malaria in the hemoglobinopathies

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


The history of genetics and the study of malaria are inextricably linked. The burden of disease due to malaria across much of the world has selected for a series of very visible traits of major medical importance, including the alleles of genes encoding hemoglobin, red cell enzymes, and membrane proteins. Furthermore, as might be expected from the intricate life cycle of the parasite in the human host, it now appears that many other genes may also influence the outcome of infection, including some that modulate the immune responses and others that encode for endothelial proteins.

The genetic resistance to malarial infection, particularly falciparum malaria, associated with the hemoglobinopathies, will be reviewed here. Resistance associated with abnormalities in red cell surface antigens or cytoskeleton is discussed separately. (See "Protection against malaria by abnormalities in red cell surface antigens and cytoskeletal proteins".)


Plasmodium falciparum malaria, the deadly form of malaria, has a life cycle that includes alternating hosts: a sexual cycle in the insect vector (a female) Anopheles mosquito and a human cycle that includes a liver stage and an erythrocytic stage. Genetic resistance to the blood stage has been extensively documented, but the association of HLA class I allotypes with protection from malaria suggests genetic traits resistance also during the hepatic stage of infection [1,2].

Genetic resistance to P. falciparum malaria at the erythrocytic stage may involve one or more of the following mechanisms:

Inhibition of merozoite entry into the red cell [3]


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