DAVID MODIANO*†, GAIA LUONI*, BIENVENU SODIOMON SIRIMA‡, JACQUES SIMPORɧ, FEDERICA VERRA†, AMADOU KONATɇ, ELENA RASTRELLI*, ANNA OLIVIERI*, CARLO CALISSANO*, GIACOMO MARIA PAGANOTTI*, LEILA D'URBANO*, ISSA SANOUII, ALPHONSE SAWADOGOII, GUIDO MODIANO¶ & MARIO COLUZZI*†
* Dipartimento di Scienze di Sanità
Pubblica, Sezione di Parassitologia, WHO Collaborating Centre for Malaria
Epidemiology and Control; and
† Istituto Pasteur Fondazione Cenci Bolognetti,
University of Rome "La Sapienza", 00185, Rome, Italy
‡ Centre National de Recherche et Formation
sur le Paludisme, Ministère de la Santé; and
§ Centre Medical Saint-Camille;
and
II Service de Pédiatrie, Centre
Hospitalier National Yalgado Ouedraogo, Ouagadougou, 01 BP 2208, Burkina
Faso
¶ Dipartimento di Biologia, Università
"Tor Vergata", 00133, Rome, Italy
Correspondence and requests for materials should be addressed to D.M. (e-mail: david.modiano@uniroma1.it).
Hemoglobin C (HbC; b6Glu
®
Lys) is common in malarious areas of West Africa, especially in Burkina
Faso. Conclusive evidence exists on the protective role against severe
malaria of hemoglobin S (HbS; b6Glu
®
Val) heterozygosity, whereas conflicting results for the HbC trait have
been reported and no epidemiological data exist on the possible role of
the HbCC genotype. In vitro studies suggested that HbCC erythrocytes
fail to support the growth of P. falciparum but HbC homozygotes
with high P. falciparum parasitaemias have been observed. Here we
show, in a large case–control study performed in Burkina Faso on 4,348
Mossi subjects, that HbC is associated with a 29% reduction in risk of
clinical malaria in HbAC heterozygotes (P = 0.0008) and of 93% in
HbCC homozygotes (P = 0.0011). These findings, together with the
limited pathology of HbAC and HbCC compared to the severely disadvantaged
HbSS and HbSC genotypes and the low bS
gene frequency in the geographic epicentre of bC,
support the hypothesis that, in the long term and in the absence of malaria
control, HbC would replace HbS in central West Africa.