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

Although the α+ 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. T...

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Bibliographic Details
Published in:Blood 2005-07, Vol.106 (1), p.368-371
Main Authors: Williams, Thomas N., Wambua, Sammy, Uyoga, Sophie, Macharia, Alex, Mwacharo, Jedidah K., Newton, Charles R.J.C., Maitland, Kathryn
Format: Article
Language:English
Subjects:
alpha-Thalassemia - epidemiology
alpha-Thalassemia - genetics
Anemias. Hemoglobinopathies
Animals
Biological and medical sciences
Case-Control Studies
Diseases of red blood cells
Genetic Predisposition to Disease - epidemiology
Genotype
Hematologic and hematopoietic diseases
Heterozygote
Homozygote
Human protozoal diseases
Humans
Infectious diseases
Kenya - epidemiology
Malaria
Malaria, Falciparum - epidemiology
Malaria, Falciparum - genetics
Medical sciences
Parasitic diseases
Plasmodium falciparum
Protozoal diseases
Risk Factors
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Summary:Although the α+ 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 α+ 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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2005-01-0313