Measuring the impact of malaria infection on indicators of iron and vitamin A status: a systematic literature review and meta-analysis

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 center dot 2 mu g/l (95 % CI 15 center dot 6, 40 center dot 9) in children with asymptomatic malaria; 28 center dot 5 mu g/l (95 % CI 8 center dot 1, 48 center dot 8) in adults with asymptomatic malaria; and 366 mu g/l (95 % CI 162, 570) in children with clinical malaria compared with individuals without malaria infection. Mean hepcidin concentrations were elevated by 1 center dot 52 nmol/l (95 % CI 0 center dot 92, 2 center dot 11) in children with asymptomatic malaria. Mean retinol concentrations were reduced by: 0 center dot 11 mu mol/l (95 % CI -0 center dot 22, -0 center dot 01) in children with asymptomatic malaria; 0 center dot 43 mu mol/l (95 % CI -0 center dot 71, -0 center dot 16) in children with clinical malaria and 0 center dot 73 mu mol/l (95 % CI -1 center dot 11, -0 center dot 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.