Understanding the impact of malaria on the interpretation of micronutrient biomarkers

Accurate estimates of population micronutrient status are needed to guide policies, programmes, and the choice of interventions to prevent and control micronutrient deficiencies. It is widely accepted that some micronutrient biomarker concentrations should be corrected for inflammation status with the use of inflammation marker concentrations, to improve the specificity with which deficiency is indicated. However, there is evidence to suggest that malaria infection could have an inflammation- independent, additive effect on certain biomarkers, particularly ferritin, which complicates the assessment of iron status in malaria-endemic areas. OŌen, the population groups with greater risk of micronutrient deficiencies also have greater risk of contracting malaria. This research started with a systematic literature review, finding that micronutrient biomarkers are affected by malaria infection, and the intensity of this relationship varied according to the stage of infection. Then, an analysis of cross-sectional data from representative population-based surveys (eight datasets, n=7,886 children) investigated the relationship between malaria, ferritin concentrations, and inflammation. Inflammaton-adjusted ferritin concentrations were 44% (95% CI 39, 52; p<0.001) greater in malaria- infected children, compared to uninfected children. Age and malaria exposure, the two main determinants of malaria immunity, were shown to modify this association. The potential role of malaria immunity in mediating the relationship between malaria and micronutrient biomarkers was explored further through an analysis of the 2015 Malawi micronutrient survey dataset. This analysis demonstrated a clear pattern of association between low level of immunity and greater changes in ferritin concentrations during malaria infection. The results of this research indicate the need to account for malaria in the assessment of iron status in malaria-endemic areas, particularly in populations with low immunity to malaria. The findings have potential applications for research on the epidemiology and aetiology of micronutrient deficiencies, and in population micronutrient surveillance, particularly in malaria endemic areas.