α+‐Thalassemia Protects against Anemia Associated with Asymptomatic Malaria: Evidence from Community‐Based Surveys in Tanzania and Kenya
1Cell Biology and Immunology Group and 2Division of Human Nutrition, Wageningen University, Wageningen, 3Meander Medical Centre, Amersfoort, and 4University Medical Centre Nijmegen, Nijmegen, The Netherlands; 5Institute of Tropical Medicine and International Health, Charité–University Medicine Berlin, Berlin, Germany; 6Kenyan Institute of Medical Research, Nairobi, Kenya; 7Kilimanjaro Christian Medical Centre, Moshi, Tanzania
Background.
In hospital‐based studies, α+‐thalassemia has been found to protect against severe, life‐threatening falciparum malaria. α+‐Thalassemia does not seem to prevent infection or high parasite densities but rather limits progression to severe disease—in particular, severe malarial anemia. We assessed to what extent α+‐thalassemia influences the association between mild, asymptomatic Plasmodium falciparum infection and hemoglobin concentration.
Methods.The study was based on 2 community‐based surveys conducted among afebrile children (0.5–8 years old; 
) in Kenya and Tanzania.
Results.Among children without inflammation (whole‐blood C‐reactive protein concentration 
10 mg/L), P. falciparum infection was associated with only small reductions in hemoglobin concentration, and effects were similar across α‐globin genotypes. By contrast, the reduction in hemoglobin concentration associated with P. falciparum infection accompanied by inflammation was larger and strongly depended on genotype (normal, −21.8 g/L; heterozygous, −16.7 g/L; and homozygous, −4.6 g/L). Relative to children with a normal genotype, this difference in effect was 5.1 g/L (95% confidence interval [CI], −1.0 to 11.1 g/L) for heterozygotes and 17.2 g/L (95% CI, 8.3 to 26.2 g/L) for homozygotes (estimates are adjusted for study site, age, height‐for‐age z score, and iron deficiency).
Conclusions.α+‐Thalassemia limits the decline in hemoglobin concentration that is associated with afebrile infections, particularly those that are accompanied by inflammation.
Received 6 December 2007; accepted 25 February 2008; electronically published 26 June 2008.
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Potential conflicts of interest: none reported.
Financial support: Netherlands Organisation of Scientific Research, Foundation for the Advancement of Tropical Research (grants W 93–413, WAO 93–441, and PRIOR); UNICEF; Unilever Food and Health Research Institute; Cornelis Visser Foundation.