Malaria Exacerbates Inflammation-induced Bias in Ferritin and Soluble Transferrin Receptor Values.

ABSTRACT

Objectives: In the context of malaria and inflammation, the utility of ferritin and soluble transferring receptor (sTfR), as indicators of iron status may be compromised. In this study, we evaluated the effects of correcting for malaria and inflammation on the prevalence of iron deficiency (ID) as estimated by a) ferritin and b) sTfR. Methods: The analyses used baseline data from 1085 children, 4-8 y, who participated in a carotenoid biofortified maize flour trial in rural Zambia. For each biomarker, we compared the prevalence of ID with the prevalence corrected for a) CRP and AGP only; and b) CRP, AGP and concurrent malaria. Inflammation was defined as CRP>5mg/L and/or AGP>1g/L. Malaria was defined by microscopy. Children were first stratified into groups defined by inflammation and malaria status. Correction factors were then generated by dividing the group geometric means by that of the reference group (those free of both malaria and inflammation). Correction factors were applied to each individual concentration to generated corrected concentrations. Results: For ferritin, the unadjusted prevalence of ID (WHO age-specific cut-offs) increased from 7.3% to 9.5% (p<0.01) and 10.3 %( p<0.01), respectively, after correcting for CRP/AGP only, and CRP, AGP and concurrent malaria combined. For sTfR, the unadjusted ID prevalence (cutoff >8.3 mg/l) decreased from 28% to 21% (p<0.01) after correcting CRP/AGP only, and 19% (p<0.01) after correcting for CRP, AGP and concurrent malaria. Conclusions: Our findings highlight the need to account for both malaria and inflammation when interpreting ferritin and sTfr concentrations in malaria endemic regions.