ArticleEBioMedicine2016
Anemia Offers Stronger Protection Than Sickle Cell Trait Against the Erythrocytic Stage of Falciparum Malaria and This Protection Is Reversed by Iron Supplementation.
Article in EBioMedicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 3 of them syntheses that pooled it.
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Who cites it
40 citing papers in PubMed, 3 syntheses or guidelines pooled it, 68 citations in OpenAlex.
- Improving reproducibility of Plasmodium falciparum culture: a large-language-model-driven literature review and a parasite growth variability assessment of donor red blood cells.Malaria journal · 2025Pooled it
- Impact of weekly iron-folic acid supplementation on nutritional status and parasitic reinfection among school-age children and adolescents in Sub-Saharan Africa: a systematic review and meta-analysis.Frontiers in pediatrics · 2024Pooled it
- Acknowledging the gap: a systematic review of micronutrient supplementation in infants under six months of age.Wellcome open research · 2020Pooled it
- Hepcidin-guided screen-and-treat interventions for young children with iron-deficiency anaemia in The Gambia: an individually randomised, three-arm, double-blind, controlled, proof-of-concept, non-inferiority trial.The Lancet. Global health · 2023Trial
- Hepcidin-guided screen-and-treat interventions against iron-deficiency anaemia in pregnancy: a randomised controlled trial in The Gambia.The Lancet. Global health · 2019Trial
- Micronutrient powder supplements combined with nutrition education marginally improve growth amongst children aged 6-23 months in rural Burkina Faso: A cluster randomized controlled trial.Maternal & child nutrition · 2019Trial
- The ferroportin Q248H mutation protects from anemia, but not malaria or bacteremia.Science advances · 2019Trial
- Host iron status and erythropoietic response to iron supplementation determines susceptibility to the RBC stage of falciparum malaria during pregnancy.Scientific reports · 2017Trial
- Why are iron chelators not as effective as artemisinin in killing malaria parasites?Parasites & vectors · 2026Article
- Host iron deficiency protects againstScience advances · 2026Article
- Is sickle cell trait truly benign? A case-control study of physical and mental health outcomes from the sickle cell belt of Eastern India.Journal of community genetics · 2026Article
- Major features of parasite adaptation revealed by genomes of Plasmodium falciparum population samples archived for over 50 years.Communications biology · 2026Article
- Targeting anemia-induced CD71Infection and immunity · 2025Article
- Multiplication rate variation of malaria parasites from hospital cases and community infections.Scientific reports · 2025Article
- Subnational mapping of anaemia and aetiologic factors in the West and Central African region.Public health nutrition · 2024Article
- Longitudinal changes in iron homeostasis in human experimental and clinical malaria.medRxiv : the preprint server for health sciences · 2023Article
- Biology of Anemia: A Public Health Perspective.The Journal of nutrition · 2023Article
- Article
- Exploring the host factors affecting asymptomatic Plasmodium falciparum infection: insights from a rural Burkina Faso study.Malaria journal · 2023Article
- Management of the Sickle Cell Trait: An Opinion by Expert Panel Members.Journal of clinical medicine · 2023Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
Abstract
backgroundIron deficiency causes long-term adverse consequences for children and is the most common nutritional deficiency worldwide. Observational studies suggest that iron deficiency anemia protects against Plasmodium falciparum malaria and several intervention trials have indicated that iron supplementation increases malaria risk through unknown mechanism(s). This poses a major challenge for health policy. We investigated how anemia inhibits blood stage malaria infection and how iron supplementation abrogates this protection.
methodsThis observational cohort study occurred in a malaria-endemic region where sickle-cell trait is also common. We studied fresh RBCs from anemic children (135 children; age 6-24months; hemoglobin <11g/dl) participating in an iron supplementation trial (ISRCTN registry, number ISRCTN07210906) in which they received iron (12mg/day) as part of a micronutrient powder for 84days. Children donated RBCs at baseline, Day 49, and Day 84 for use in flow cytometry-based in vitro growth and invasion assays with P. falciparum laboratory and field strains. In vitro parasite growth in subject RBCs was the primary endpoint.
findingsAnemia substantially reduced the invasion and growth of both laboratory and field strains of P. falciparum in vitro (~10% growth reduction per standard deviation shift in hemoglobin). The population level impact against erythrocytic stage malaria was 15.9% from anemia compared to 3.5% for sickle-cell trait. Parasite growth was 2.4 fold higher after 49days of iron supplementation relative to baseline (p<0.001), paralleling increases in erythropoiesis.
interpretationThese results confirm and quantify a plausible mechanism by which anemia protects African children against falciparum malaria, an effect that is substantially greater than the protection offered by sickle-cell trait. Iron supplementation completely reversed the observed protection and hence should be accompanied by malaria prophylaxis. Lower hemoglobin levels typically seen in populations of African descent may reflect past genetic selection by malaria.
fundingNational Institute of Child Health and Development, Bill and Melinda Gates Foundation, UK Medical Research Council (MRC) and Department for International Development (DFID) under the MRC/DFID Concordat.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.