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 Blood, 1 July 2005, Vol. 106, No. 1, pp. 368-371.
Prepublished online as a Blood First Edition Paper on March 15, 2005; DOI 10.1182/blood-2005-01-0313.

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RED CELLS
Brief report

Both heterozygous and homozygous {alpha}+ thalassemias protect against severe and fatal Plasmodium falciparum malaria on the coast of Kenya

Thomas N. Williams, Sammy Wambua, Sophie Uyoga, Alex Macharia, Jedidah K. Mwacharo, Charles R. J. C. Newton, and Kathryn Maitland

From the Kenya Medical Research Institute (KEMRI), Centre for Geographic Medicine Research, Kilifi, Kenya; Nuffield Department of Clinical Medicine and Department of Paediatrics, University of Oxford, John Radcliffe Hospital; Neurosciences Unit, Institute of Child Health, University College, London; and Department of Paediatrics, Faculty of Medicine and the Wellcome Trust Centre for Clinical Tropical Medicine, Imperial College, London, United Kingdom.

Although the {alpha}+ thalassemias almost certainly confer protection against death from malaria, this has not been formally documented. We have conducted a study involving 655 case patients with rigorously defined severe malaria and 648 controls, frequency matched on area of residence and ethnic group. The prevalence of both heterozygous and homozygous {alpha}+ thalassemia was reduced in both case patients with severe malaria (adjusted odds ratios [ORs], 0.73 and 0.57; 95% confidence intervals [95% CIs], 0.57-0.94 and 0.40-0.81; P = .013 and P = .002, respectively, compared with controls) and among the subgroup of children who died after admission with severe malaria (OR, 0.60 and 0.37; 95% CI, 0.37-1.00 and 0.16-0.87; P = .05 and P = .02, respectively, compared with surviving case patients). The lowest ORs were seen for the forms of malaria associated with the highest mortality—coma and severe anemia complicated by deep, acidotic breathing. Our study supports the conclusion that both heterozygotes and homozygotes enjoy a selective advantage against death from Plasmodium falciparum malaria.


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