SynthesisThe Lancet. Infectious diseases2012
Haemoglobinopathies and the clinical epidemiology of malaria: a systematic review and meta-analysis.
Synthesis in The Lancet. Infectious diseases, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 188 papers, 7 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
188 citing papers in PubMed, 7 syntheses or guidelines pooled it, 339 citations in OpenAlex.
- Phenome- and laboratory-wide meta-analyses of sickle cell trait reveal multi-system disease associations.American journal of human genetics · 2026Pooled it
- 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
- Variant effect predictors: a systematic review and practical guide.Human genetics · 2024Pooled it
- Plasmodium spp. mixed infection leading to severe malaria: a systematic review and meta-analysis.Scientific reports · 2020Pooled it
- Effect of ABO blood group on asymptomatic, uncomplicated and placental Plasmodium falciparum infection: systematic review and meta-analysis.BMC infectious diseases · 2019Pooled it
- Clinical Outcomes Associated With Sickle Cell Trait: A Systematic Review.Annals of internal medicine · 2018Pooled it
- Artemisinin Therapy for Malaria in Hemoglobinopathies: A Systematic Review.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Pooled it
- Plasma folate dynamics in Plasmodium falciparum-infected African children treated with artemisinin combination therapy and single low-dose primaquine or placebo.Malaria journal · 2025Trial
- Sickle cell anaemia and severe Plasmodium falciparum malaria: a secondary analysis of the Transfusion and Treatment of African Children Trial (TRACT).The Lancet. Child & adolescent health · 2022Trial
- Lessons learnt from the first controlled human malaria infection study conducted in Nairobi, Kenya.Malaria journal · 2015Trial
- Controlled human malaria infection of Tanzanians by intradermal injection of aseptic, purified, cryopreserved Plasmodium falciparum sporozoites.The American journal of tropical medicine and hygiene · 2014Trial
- Ascaris co-infection does not alter malaria-induced anaemia in a cohort of Nigerian preschool children.Malaria journal · 2013Trial
- Sickle cell haemoglobin status shapes malaria parasite genotype in asymptomatic infections.Nature microbiology · 2026Article
- Impact of Sickle Cell Hemoglobin Genotypes on Clinical Outcomes AmongHealth science reports · 2026Article
- Reactivation of the embryonic ζ-globin gene ameliorates severe forms of α-thalassemia.Nature genetics · 2026Article
- Elevated Plasmodium falciparum sexual conversion in HbAC and HbAS red blood cells in naturally infected malaria patients.PLoS pathogens · 2026Article
- α-Thalassemia in Oraons-indigenous tribal population from Jharkhand, India: insights to common deletions.Human genetics · 2026Article
- Presenilin-1 Affects Melanoma Cell Behavior in an Amyloid Precursor Protein-Rich, Alzheimer's Disease-like, Microenvironment.International journal of molecular sciences · 2026Article
- Temporal patterns of haemoglobin phenotypes among Nigerian university students based on ten years of surveillance data.Scientific reports · 2026Article
- Mechanistic insights into subclinicaliScience · 2026Review
128 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundHaemoglobinopathies can reduce the risk of malaria syndromes. We aimed to quantify the relation between different haemoglobin mutations and malaria protection to strengthen the foundation for translational studies of malaria pathogenesis and immunity.
methodsWe systematically searched the Medline and Embase databases for studies that estimated the risk of malaria in patients with and without haemoglobinopathies up to Sept 9, 2011, and identified additional studies from reference lists. We included studies that enrolled mainly children or pregnant women and had the following outcomes: Plasmodium falciparum severe malaria, uncomplicated malaria, asymptomatic parasitaemia, or pregnancy-associated malaria, and Plasmodium vivax malaria. Two reviewers identified studies independently, assessed quality of the studies, and extracted data. We produced odds ratios (ORs; 95% CIs) for case-control studies and incidence rate ratios (IRRs; 95% CIs) for prospective studies. We did the meta-analysis with a random-effects model when equivalent outcomes were reported in more than one study.
findingsOf 62 identified studies, 44 reported data for haemoglobin AS, 19 for haemoglobin AC and CC, and 18 for α-thalassaemia. Meta-analysis of case-control studies showed a decreased risk of severe P. falciparum malaria in individuals with haemoglobin AS (OR 0·09, 95% CI 0·06-0·12), haemoglobin CC (0·27, 0·11-0·63), haemoglobin AC (0·83, 0·67-0·96), homozygous α-thalassaemia (0·63, 0·48-0·83), and heterozygous α-thalassaemia (0·83, 0·74-0·92). In meta-analysis of prospective trials only haemoglobin AS was consistently associated with protection from uncomplicated malaria (IRR 0·69, 95% CI 0·61-0·79); no haemoglobinopathies led to consistent protection from asymptomatic parasitaemia. Few clinical studies have investigated β-thalassaemia, haemoglobin E, P. vivax malaria, or pregnancy-associated malaria.
interpretationHaemoglobin AS, CC, and AC genotypes and homozygous and heterozygous α-thalassaemia provide significant protection from severe malaria syndromes, but these haemoglobinopathies differ substantially in the degree of protection provided and confer mild or no protection against uncomplicated malaria and asymptomatic parasitaemia. Through attenuation of severity of malaria, haemoglobinopathies could serve as a model for investigation of the mechanisms of malaria pathogenesis and immunity.
fundingUS National Institute of Allergy and Infectious Diseases.
Indexed as
Identifiers
What OpenQuestion holds
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.