Open Access Review

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

Jacobien Veenemans15, Esther JS Jansen1, Amrish Y Baidjoe1, Erasto V Mbugi2, Ayşe Y Demir3, Rob J Kraaijenhagen3, Huub FJ Savelkoul1 and Hans Verhoef14*

Author Affiliations

1 Wageningen University, Cell Biology and Immunology Group, Wageningen, The Netherlands

2 Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania, Tanzania

3 Meander Medical Centre, Laboratory for Clinical Chemistry and Haematology, Amersfoort, The Netherlands

4 London School of Hygiene and Tropical Medicine, London, UK

5 Laboratory for Microbiology and Infection Control, Amphia Hospital, Breda, The Netherlands

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Malaria Journal 2011, 10:280  doi:10.1186/1475-2875-10-280

Published: 22 September 2011

Abstract

Background

It is controversial to what degree α+-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 α+-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 α+-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+-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 α+-thalassaemia and malaria depends on age. Our data suggest that protection by α+-thalassaemia is conferred by more efficient acquisition of malaria-specific immunity.