| Summary: | <p>Abstract</p> <p>Background</p> <p>It is controversial to what degree α<sup>+</sup>-thalassaemia protects against episodes of uncomplicated malaria and febrile disease due to infections other than <it>Plasmodium</it>.</p> <p>Methods</p> <p>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 α<sup>+</sup>-thalassaemia and those with a normal genotype, using Cox regression models that accounted for multiple events per child.</p> <p>Results</p> <p>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 α<sup>+</sup>-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, α<sup>+</sup>-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.</p> <p>Conclusions</p> <p>In this population, the association between α<sup>+</sup>-thalassaemia and malaria depends on age. Our data suggest that protection by α<sup>+</sup>-thalassaemia is conferred by more efficient acquisition of malaria-specific immunity.</p>
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