title: Alpha(+)-thalassemia protects African children from severe malaria.
abstract: The high frequency of alpha(+)-thalassemia in malaria-endemic regions may reflect natural selection due to protection from potentially fatal severe malaria. In Africa, bearing 90% of global malaria morbidity and mortality, this has not yet been observed. We tested this hypothesis in an unmatched case-control study among 301 Ghanaian children with severe malaria and 2107 controls (62% parasitemic). In control children, alpha(+)-thalassemia affected neither prevalence nor density of Plasmodium falciparum. However, heterozygous alpha(+)-thalassemia was observed in 32.6% of controls but in only 26.2% of cases (odds ratio [OR], 0.74; 95% confidence interval [CI], 0.56-0.98). Protection against severe malaria was found to be pronounced comparing severe malaria patients with parasitemic controls (adjusted OR in children < 5 years of age, 0.52; 95% CI, 0.34-0.78) and to wane with age. No protective effect was discernible for homozygous children. Our findings provide evidence for natural selection of alpha(+)-thalassemia in Africa due to protection from severe malaria.
authors.affiliation: Institute of Tropical Medicine, Charité, Humboldt University, Berlin, Germany. frank.mockenhaupt@charite.de
authors.forename: Frank P
authors.initials: FP
authors.lastname: Mockenhaupt
authors.forename: Stephan
authors.initials: S
authors.lastname: Ehrhardt
authors.forename: Sabine
authors.initials: S
authors.lastname: Gellert
authors.forename: Rowland N
authors.initials: RN
authors.lastname: Otchwemah
authors.forename: Ekkehart
authors.initials: E
authors.lastname: Dietz
authors.forename: Sylvester D
authors.initials: SD
authors.lastname: Anemana
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bienzle
mesh_terms: D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003140:Communicable Disease Control; D003141:Communicable Diseases / Q000150:complications / Q000453:epidemiology; D005260:Female; D005869:Ghana; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000097:blood* / Q000453:epidemiology / Q000517:prevention & control*; D008297:Male; D015999:Multivariate Analysis; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D017085:alpha-Thalassemia / Q000097:blood* / Q000150:complications / Q000453:epidemiology / Q000235:genetics*