Hemoglobin C associated with protection from severe malaria in the Dogon of Mali, a West African population with a low prevalence of hemoglobin S

The malaria hypothesis proposes a survival advantage for individuals with h emoglobin variants in areas of endemic Plasmodium falciparum malaria. Hemog lobin C (HbC) is a possible example in West Africa, where this hemoglobin h as a centric distribution with high frequencies among certain populations i ncluding the Dogon ethnic group. To test whether HbC is associated with pro tection from malaria, we performed a case-control study in the Dogon of Ban diagara, Mali, HbC was present in 68 of 391 (17.4%) of uncomplicated malari a control cases, whereas it was detected in only 3 of 67 cases (4.5%) of se vere malaria (odds ratio [OR], 0.22; P = .01). Further, HbC was present in only 1 of 34 cases (2.9%) with cerebral manifestations, the most common pre sentation of severe malaria in this population (OR, 0.14; P = .03). Episode s of uncomplicated malaria and parasitemias (4800-205 050/mu L) were identi fied in cases of homozygous HbC (HbCC), which indicates that P falciparum p arasites are able to efficiently replicate within HbCC erythrocytes in vivo . These findings suggest that HbC does not protect against infection or unc omplicated malaria but can protect against severe malaria in the Dogon popu lation of Bandiagara, Mali. The data also suggest that the protective effec t associated with HbC may be greater than that of HbS in this population. ( Blood, 2000;96:2358-2363) (C) 2000 by The American Society of Hematology.