Investigating The Causal Relationship Between Iron Status And Malaria In African Children

Muriuki, John Muthii (2020). Investigating The Causal Relationship Between Iron Status And Malaria In African Children. PhD thesis The Open University.



Iron deficiency (ID) and malaria are co-existing and common causes of ill health in African children. In this thesis, I aimed to determine: 1) a more accurate estimate of the burden of ID in African children by adjusting for the influence of infections on iron biomarkers; 2) whether malaria causes ID; 3) whether iron status influences malaria risk; and 4) whether a mutation in the ferroportin coding gene, FPN Q248H, influences iron status, anaemia and risk of malaria.

Among 4,853 children from community-based cohorts across Africa, the overall prevalence of ID was 52% using an inflammation and malaria regression-corrected estimate of ID, compared to a WHO-defined estimate of 34%. This WHO unidentified burden of ID increased with age and was highest in countries with high prevalence of inflammation and malaria, where up to a quarter of iron-deficient children were misclassified as iron replete. Transferrin saturation (TSAT) was least affected by inflammation and malaria and TSAT <11% most closely predicted the regression-corrected ID.

In Mendelian randomisation analyses, sickle cell trait, a polymorphism conferring protection against malaria, was associated with a 30% reduction in ID in 7453 malaria-exposed African
children but not in 3207 non-malaria exposed African-Americans. Genetically determined malaria risk was associated with a 2.5-fold increase in ID per unit increase in log-incidence rate of malaria. This suggests that an intervention that halves the risk of malaria episodes would reduce ID by 47% in African children.

In 2683 Kenyan and Ugandan children, ID defined using either low ferritin or TSAT was associated with 33% and 21% reduction in malaria risk respectively. The FPN Q248H mutation which increases intracellular iron export, was associated with 23% and 25% protection from ID and anaemia, respectively, but there was little evidence of protection from malaria. This work demonstrates the complex relationship between iron and malaria.

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