Abstract
Inflammation and infections such as malaria affect estimates of micronutrient status. Medline, Embase, Web of Science, Scopus and the Cochrane library were searched to identify studies reporting mean concentrations of ferritin, hepcidin, retinol or retinol binding protein in individuals with asymptomatic or clinical malaria and healthy controls. Study quality was assessed using the US National Institute of Health tool. Random effects meta-analyses were used to generate summary mean differences. In total, forty-four studies were included. Mean ferritin concentrations were elevated by: 28·2 µg/l (95 % CI 15·6, 40·9) in children with asymptomatic malaria; 28·5 µg/l (95 % CI 8·1, 48·8) in adults with asymptomatic malaria; and 366 µg/l (95 % CI 162, 570) in children with clinical malaria compared with individuals without malaria infection. Mean hepcidin concentrations were elevated by 1·52 nmol/l (95 % CI 0·92, 2·11) in children with asymptomatic malaria. Mean retinol concentrations were reduced by: 0·11 µmol/l (95 % CI -0·22, -0·01) in children with asymptomatic malaria; 0·43 µmol/l (95 % CI -0·71, -0·16) in children with clinical malaria and 0·73 µmol/l (95 % CI -1·11, -0·36) in adults with clinical malaria. Most of these results were stable in sensitivity analyses. In children with clinical malaria and pregnant women, difference in ferritin concentrations were greater in areas with higher transmission intensity. We conclude that biomarkers of iron and vitamin A status should be statistically adjusted for malaria and the severity of infection. Several studies analysing asymptomatic infections reported elevated ferritin concentrations without noticeable elevation of inflammation markers, indicating a need to adjust for malaria status in addition to inflammation adjustments.
Highlights
Micronutrient deficiencies are a major public health burden, especially in low-income countries, and accurate prevalence estimates are important to guide planning and monitoring of nutritional interventions[1]
Ferritin values may differ by malaria infection status[10] after correcting for inflammation defined by raised C-reactive protein (CRP) and/or acid glycoprotein (AGP), and the updated WHO guidelines mention malaria as a possible factor for adjustment
This research estimated the effect of malaria on several biomarker values by performing a meta-analysis of studies comparing biomarker values in individuals infected with malaria and individuals without malaria infection
Summary
Micronutrient deficiencies are a major public health burden, especially in low-income countries, and accurate prevalence estimates are important to guide planning and monitoring of nutritional interventions[1]. Prevalence of micronutrient deficiencies can be incorrectly estimated because certain micronutrient biomarkers are affected by inflammation and infections such as malaria[2]. In children aged 6–59 months in Ghana, increasing malaria parasite density was significantly associated with decreasing serum retinol concentrations[11]. These reductions have been attributed largely to the inflammatory response. In young children in Liberia, Larson et al found a significant added effect of malaria on RBP concentrations and vitamin A deficiency prevalence estimates even after adjusting for CRP and AGP using the regression approach[12]. Taking into account the effect of malaria on micronutrient biomarkers has the potential to significantly modify the estimation of the prevalence of micronutrient deficiencies derived from large population-based surveys such as national micronutrient surveys. This research estimated the effect of malaria on several biomarker values (ferritin, hepcidin, retinol and RBP) by performing a meta-analysis of studies comparing biomarker values in individuals infected with malaria and individuals without malaria infection
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