ArticlePloS one2018
Associations between erythrocyte polymorphisms and risks of uncomplicated and severe malaria in Ugandan children: A case control study.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 2 of them syntheses that pooled it.
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Who cites it
10 citing papers in PubMed, 2 syntheses or guidelines pooled it, 13 citations in OpenAlex.
- Exploring the protective effects of thalassemia against malaria in Africa: a systematic review.Systematic reviews · 2026Pooled it
- Pooled it
- Association of TNF-Alpha, MBL2, NOS2, and G6PD with Malaria Outcomes in People in Southern Ghana.Genetics research · 2022Article
- Evolutionary history of sickle-cell mutation: implications for global genetic medicine.Human molecular genetics · 2021Review
- Article
- Associations between Aminoquinoline Resistance Genotypes and Clinical Presentations of Plasmodium falciparum Infection in Uganda.Antimicrobial agents and chemotherapy · 2020Article
- Variations in killer-cell immunoglobulin-like receptor and human leukocyte antigen genes and immunity to malaria.Cellular & molecular immunology · 2020Review
- Changes in the clinical presentation and outcomes of patients treated for severe malaria in a referral French university intensive care unit from 2004 to 2017.Annals of intensive care · 2020Article
- Associations between red blood cell variants and malaria among children and adults from three areas of Uganda: a prospective cohort study.Malaria journal · 2020Article
- Impact of Hemoglobin S Trait on Cell Surface Antibody Recognition ofOpen forum infectious diseases · 2019Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundEvidence for association between sickle cell and alpha thalassemia trait and severe malaria is compelling. However, for these polymorphisms associations with uncomplicated malaria, and for G6PD deficiency associations with uncomplicated and severe malaria, findings have been inconsistent. We studied samples from a three-arm case-control study with the objective of determining associations between common host erythrocyte polymorphisms and both uncomplicated and severe malaria, including different severe malaria phenotypes.
methodWe assessed hemoglobin abnormalities, α-thalassemia, and G6PD deficiency by molecular methods in 325 children with severe malaria age-matched to 325 children with uncomplicated malaria and 325 healthy community controls. Conditional logistic regression was used to measure associations between specified genotypes and malaria outcomes.
resultsNo tested polymorphisms offered significant protection against uncomplicated malaria. α-thalassemia homozygotes (_α/_α) had increased risk of uncomplicated malaria (OR 2.40; 95%CI 1.15, 5.03, p = 0.020). HbAS and α-thalassemia heterozygous (_α/αα) genotypes protected against severe malaria compared to uncomplicated malaria (HbAS OR 0.46; 0.23, 0.95, p = 0.036; _α/αα OR 0.51; 0.24, 0.77; p = 0.001) or community (HbAS OR 0.23; 0.11, 0.50; p<0.001; _α/αα; OR 0.49; 0.32, 0.76; p = 0.002) controls. The α-thalassemia homozygous (_α/_α) genotype protected against severe malaria when compared to uncomplicated malaria controls (OR 0.34; 95%CI 0.156, 0.73, p = 0.005), but not community controls (OR 1.03; 0.46, 2.27, p = 0.935). Stratifying by the severe malaria phenotype, compared to community controls, the protective effect of HbAS was limited to children with severe anemia (OR 0.17; 95%CI 0.04, 0.65; p = 0.009) and that of _α/αα to those with altered consciousness (OR 0.24; 0.09, 0.59; p = 0.002). A negative epistatic effect was seen between HbAS and _α/αα; protection compared to uncomplicated malaria controls was not seen in individuals with both polymorphisms (OR 0.45; 0.11, 1.84; p = 0.269). G6PD deficiency was not protective against severe malaria.
conclusionAssociations were complex, with HbAS principally protective against severe anemia, _α/αα against altered consciousness, and negative epistasis between the two polymorphisms.
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