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Blood, 1 October 2000, Vol. 96, No. 7, pp. 2358-2363
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Hemoglobin C associated with protection from severe malaria in
the Dogon of Mali, a West African population with a low prevalence
of hemoglobin S
Aarti Agarwal,
Aldiouma Guindo,
Yacouba Cissoko,
James G. Taylor,
Drissa Coulibaly,
Abdoulaye Koné,
Kassoum Kayentao,
Abdoulaye Djimde,
Christopher V. Plowe,
Ogobara Doumbo,
Thomas E. Wellems, and
Dapa Diallo
From the National Institute of Allergy and Infectious
Diseases and the National Cancer Institute, National Institutes of
Health, Bethesda, MD; the Hematology Laboratory and Malaria Research
and Training Center, Department of Epidemiology of Parasitic Disease,
Faculty of Medicine, Pharmacy and Odonto-Stomatology, Bamako, Mali; and
the Division of Geographic Medicine, University of Maryland School of
Medicine, Baltimore, MD.
The malaria hypothesis proposes a survival advantage for
individuals with hemoglobin variants in areas of endemic
Plasmodium falciparum malaria. Hemoglobin C (HbC) is a
possible example in West Africa, where this hemoglobin has a centric
distribution with high frequencies among certain populations including
the Dogon ethnic group. To test whether HbC is associated with
protection from malaria, we performed a case-control study in the Dogon
of Bandiagara, Mali. HbC was present in 68 of 391 (17.4%) of
uncomplicated malaria control cases, whereas it was detected in only 3 of 67 cases (4.5%) of severe 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 presentation of
severe malaria in this population (OR, 0.14; P = .03).
Episodes of uncomplicated malaria and parasitemias (4800-205 050/µL)
were identified in cases of homozygous HbC (HbCC), which indicates that
P falciparum parasites are able to efficiently
replicate within HbCC erythrocytes in vivo. These findings suggest that
HbC does not protect against infection or uncomplicated malaria but can
protect against severe malaria in the Dogon population of Bandiagara,
Mali. The data also suggest that the protective effect associated with
HbC may be greater than that of HbS in this population.
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