Malaria Infection Affects the Interpretation of Biomarkers of Iron and Vitamin A Status, Even After Adjusting for Systemic Inflammation, but Does Not Affect Plasma Zinc Concentrations

Abstract

Objectives: To assess how asymptomatic malaria infection affects the interpretation of biomarkers of iron, vitamin A and zinc status after adjustment for elevated acute phase proteins (APP). Methods: Plasma ferritin (pF), transferrin receptor (sTfR), retinol binding protein (RBP) and zinc (pZn) concentrations were measured among 451 asymptomatic children aged 6-23 months in Burkina Faso, and adjusted for elevated APP (C-reactive protein ≥5 mg/L and/or alpha-1-acid-glycoprotein ≥1g/L) based on a four-group categorical model, as per Thurnham. Histidine-rich protein II (HRP2) concentrations >0.75 ng/mL were considered indicative of current or recent malaria parasitemia. Results: 57.4% of children had at least one elevated APP, and 48.5% had elevated HRP2. After adjusting for APP, children with elevated HRP2 had higher pF (23.5+1.5 vs. 11.1+0.8 µg/L, P<0.001) and lower RBP (0.79+0.01 vs. 0.92+0.01 µmol/L, P<0.001) vs. those without. Controlling for APP, there were no differences in pZn among those with and without elevated HRP2 (62.9+0.8 vs. 62.9+0.8 µg/dL, P=0.98). sTfR did not differ by APP status when controlling for HRP2, but was increased in children with elevated HRP2 vs. those without (17.6+0.5 vs. 12.3+0.4mg/L, P<0.0001). After adjusting for HRP2, along with APP, the estimated prevalence of iron deficiency (pF<12 µg/L) increased from 38.7% to 50.6% and vitamin A deficiency (RBP<0.84µmol/L) decreased from 33.4% to 27.7%. Conclusions: Current or recent malaria parasitemia affects indicators of micronutrient status, even after adjusting for APP. Adjusting indicators of iron and vitamin A status based only on APP may inaccurately estimate the prevalence of micronutrient deficiencies in settings with a high prevalence of malaria and inflammation.