title: Both heterozygous and homozygous alpha+ thalassemias protect against severe and fatal Plasmodium falciparum malaria on the coast of Kenya.
abstract: 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.
authors.affiliation: Wellcome Trust/Kenya Medical Research Institute (KEMRI), Centre for Geographic Medicine Research, Kilifi, Kenya. twilliams@kilifi.mimcom.net
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Williams
authors.forename: Sammy
authors.initials: S
authors.lastname: Wambua
authors.forename: Sophie
authors.initials: S
authors.lastname: Uyoga
authors.forename: Alex
authors.initials: A
authors.lastname: Macharia
authors.forename: Jedidah K
authors.initials: JK
authors.lastname: Mwacharo
authors.forename: Charles R J C
authors.initials: CR
authors.lastname: Newton
authors.forename: Kathryn
authors.initials: K
authors.lastname: Maitland
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007630:Kenya / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000235:genetics*; D010963:Plasmodium falciparum; D012307:Risk Factors; D017085:alpha-Thalassemia / Q000453:epidemiology* / Q000235:genetics*