title: Effect of α(+)-thalassaemia on episodes of fever due to malaria and other causes: a community-based cohort study in Tanzania.
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.
authors.affiliation: Wageningen University, Cell Biology and Immunology Group, Wageningen, The Netherlands. hans.verhoef@wur.nl
authors.forename: Jacobien
authors.initials: J
authors.lastname: Veenemans
authors.forename: Esther J S
authors.initials: EJ
authors.lastname: Jansen
authors.forename: Amrish Y
authors.initials: AY
authors.lastname: Baidjoe
authors.forename: Erasto V
authors.initials: EV
authors.lastname: Mbugi
authors.forename: Ayşe Y
authors.initials: AY
authors.lastname: Demir
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Kraaijenhagen
authors.forename: Huub F J
authors.initials: HF
authors.lastname: Savelkoul
authors.forename: Hans
authors.initials: H
authors.lastname: Verhoef
mesh_terms: D000367:Age Factors; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005335:Fever of Unknown Origin / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D007223:Infant; D008288:Malaria / Q000453:epidemiology* / Q000473:pathology*; D008297:Male; D015233:Models, Statistical; D011446:Prospective Studies; D013636:Tanzania / Q000453:epidemiology; D017085:alpha-Thalassemia / Q000150:complications*