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15 March 2007

Volume 44, Number 6
Clinical Infectious Diseases 2007;44:802–809
© 2007 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2007/4406-0007$15.00
DOI: 10.1086/511868
MAJOR ARTICLE

The Haptoglobin 2‐2 Genotype Is Associated with a Reduced Incidence of Plasmodium falciparum Malaria in Children on the Coast of Kenya

Sarah H. Atkinson,1,2

Tabitha W. Mwangi,1

Sophie M. Uyoga,1

Edna Ogada,1

Alex W. Macharia,1

Kevin Marsh,1

Andrew M. Prentice,2 and

Thomas N. Williams1,3,4

1KEMRI/Wellcome Trust Programme, Centre of Geographic Medicine Research, Kilifi District Hospital, Kilifi, Kenya; and 2Medical Research Council International Nutrition Group, Nutrition and Public Health Intervention Research Unit, London School of Hygiene and Tropical Medicine, London, and 3Nuffield Department of Medicine and 4Department of Paediatrics, John Radcliffe Hospital, Oxford, United Kingdom

Background.Haptoglobin (Hp) genotype determines the efficiency of hemoglobin clearance after malaria‐induced hemolysis and alters antioxidant and immune functions. The Hp2 allele is thought to have spread under strong selection pressure, but it is unclear whether this is due to protection from malaria or other diseases.

Methods.We monitored the incidence of febrile malaria and other childhood illnesses with regard to Hp genotype in a prospective cohort of 312 Kenyan children during 558.3 child‐years of follow‐up. We also conducted 7 cross‐sectional surveys to determine the prevalence of Plasmodium falciparum parasitemia.

Results.The Hp2/2 genotype was associated with a 30% reduction in clinical malarial episodes (adjusted incidence rate ratio, 0.67; for Hp2/2 vs. Hp1/1 and Hp2/1 combined). Protection increased with age; there was no protection in the first 2 years of life, 30% protection at 2 years of age, and 50% protection from 4–10 years of age. Children with the Hp1/1 genotype had a significantly lower rate of nonmalarial fever ( ).

Conclusions.Balancing selection pressures may have influenced the spread of the Hp gene. Our observations suggest that the Hp2 allele may have spread as a result of protection from malaria, and the Hp1 allele may be sustained by protection from other infections.

Received 8 September 2006; accepted 5 December 2006; electronically published 7 February 2007.

Reprints or correspondence: Dr. Sarah Atkinson, KEMRI/Wellcome Trust Programme, Centre of Geographic Medicine Research, Coast, PO Box 230, Kilifi District Hospital, Kilifi, Kenya ().

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