Abstract:
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.
