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 Blood, 1 October 2004, Vol. 104, No. 7, pp. 2003-2006.
Prepublished online as a Blood First Edition Paper on June 22, 2004; DOI 10.1182/blood-2003-11-4090.

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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Brief report

{alpha}+-thalassemia protects African children from severe malaria

Frank P. Mockenhaupt, Stephan Ehrhardt, Sabine Gellert, Rowland N. Otchwemah, Ekkehart Dietz, Sylvester D. Anemana, and Ulrich Bienzle

From the Institute of Tropical Medicine, Charité, Humboldt University, Berlin, Germany; Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany; Tamale Teaching Hospital, Tamale, Ghana; the School of Medicine and Health Sciences, University for Development Studies, Tamale, Ghana; the Institute for International Health, Free University & Humboldt University, Berlin, Germany; and the Regional Health Administration, Takoradi, Ghana.

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.


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