Effect of a+-thalassaemia on episodes of fever due to malaria and other causes: a communitybased cohort study in Tanzania

Background: It is controversial to what degree a+-thalassaemia protects against episodes of uncomplicated malaria and febrile disease due to infections other than Plasmodium. Methods: In Tanzania, in children aged 6-60 months and height-for-age z-score < -1.5 SD (n = 612), rates of fevers due to malaria and other causes were compared between those with heterozygous or homozygotes a +-thalassaemia and those with a normal genotype, using Cox regression models that accounted for multiple events per child. Results: The overall incidence of malaria was 3.0/child-year (1, 572/526 child-years); no differences were found in malaria rates between genotypes (hazard ratios, 95% CI: 0.93, 0.82-1.06 and 0.91, 0.73-1.14 for heterozygotes and homozygotes respectively, adjusted for baseline factors that were predictive for outcome). However, this association strongly depended on age: among children aged 6-17 months, those with a+-thalassaemia experienced episodes more frequently than those with a normal genotype (1.30, 1.02-1.65 and 1.15, 0.80-1.65 for heterozygotes and homozygotes respectively), whereas among their peers aged 18-60 months, a+-thalassaemia protected against malaria (0.80, 0.68-0.95 and 0.78, 0.60-1.03; p-value for interaction 0.001 and 0.10 for hetero- and homozygotes respectively). No effect was observed on non-malarial febrile episodes. Conclusions: In this population, the association between a+-thalassaemia and malaria depends on age. Our data suggest that protection by a+-thalassaemia is conferred by more efficient acquisition of malaria-specific immunity