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

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 United States National Institute of Health tool. Random-effects meta-analyses were used to generate summary mean differences. In total, 44 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 to 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.

Health outcomes associated with micronutrient-fortified complementary foods in infants and young children aged 6–23 months: a systematic review and meta-analysis

“… 60 Therefore, biomarkers of iron and vitamin A status should be statistically adjusted for malaria and the severity of infection. 61 Most of the included studies in our systematic review were done in malaria-endemic areas; however, none reported adjustments for malaria. Thus, the effect of malaria on our results cannot be accurately judged.…”

A Practical Guide to Adjust Micronutrient Biomarkers for Inflammation Using the BRINDA Method

“…Addressing the role of inflammation in assessing micronutrient status is essential to interpret micronutrient deficiencies correctly [14]. The BRINDA method has been used in various studies and national surveys [23][24][25] and included in WHO ferritin guidelines [14] and CDC's Micronutrient Manual and Toolkit [15]. The evidence gained from the BRINDA project has provided important insights to research, policy, and programming [26].…”

“…The role of malaria as a binary variable does not affect the results of BRINDA inflammation adjustment on a series of micronutrient biomarkers, namely, ferritin, sTfR, retinol, RBP, and zinc, using the latest BRINDA database. However, the stage of malaria infection may influence the results for the BRINDA inflammation adjustment method [ 24 ] and warrants more consideration in the future. Although the BRINDA inflammation adjustment method has not been applied within clinical settings, research on its utility in this setting is warranted.…”

Increased erythroferrone levels in malarial anaemia

“…Iron homeostasis is dependent on a complex interplay of physiological mediators 1,2 and is highly sensitive to inflammatory diseases, such as malaria (e.g. Plasmodium falciparum malaria) 3 . Severe malaria disease is frequently accompanied by anaemia due to haemolysis of parasitized erythrocytes 4 .…”

“…Plasmodium falciparum malaria). 3 Severe malaria disease is frequently accompanied by anaemia due to haemolysis of parasitized erythrocytes. 4 In the acute situation, this contributes to the disease burden since tissue oxygenation and energy metabolism are impaired.…”