ArticlePloS one2015
Negative Epistasis between Sickle and Foetal Haemoglobin Suggests a Reduction in Protection against Malaria.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Multi-centric origins and gene flow shape the diversity of β-thalassemia mutations in Southern East Asia.Nature communications · 2025Article
- Human genetic variations conferring resistance to malaria.Journal of translational medicine · 2025Review
- Mature beyond their years: young children who escape detection of parasitemia despite living in settings of intense malaria transmission.Biochemical Society transactions · 2024Review
- Improved Biorepository to Support Sickle Cell Disease Genomics and Clinical Research: A Practical Approach to Link Patient Data and Biospecimens from Muhimbili Sickle Cell Program, Tanzania.Biopreservation and biobanking · 2024Article
- IgG and IgM responses to the Plasmodium falciparum asexual stage antigens reflect respectively protection against malaria during pregnancy and infanthood.Malaria journal · 2024Article
- F-erythrocytes promote Plasmodium falciparum proliferation in sickle cell disease.American journal of hematology · 2023Article
- Does fetal hemoglobin inhibit the malarial parasite Plasmodium falciparum?American journal of hematology · 2022Article
- Suspected Severe Malaria in a Sudanese Patient Affected by Sickle Cell Disease Who Was Treated with Hydroxyurea.Pathogens (Basel, Switzerland) · 2021Article
- Evolutionary history of sickle-cell mutation: implications for global genetic medicine.Human molecular genetics · 2021Review
- Fetal hemoglobin in sickle cell anemia.Blood · 2020Review
- Hemoglobin E, malaria and natural selection.Evolution, medicine, and public health · 2019Review
- A ten year review of the sickle cell program in Muhimbili National Hospital, Tanzania.BMC hematology · 2018Article
- Variants in the non-coding region of the TLR2 gene associated with infectious subphenotypes in pediatric sickle cell anemia.Immunogenetics · 2018Article
- The genomic landscape of African populations in health and disease.Human molecular genetics · 2017Review
- Prevalence of polymorphisms in glucose-6-phosphate dehydrogenase, sickle haemoglobin and nitric oxide synthase genes and their relationship with incidence of uncomplicated malaria in Iganga, Uganda.Malaria journal · 2017Article
- Sickle cell disease in Africa: an overview of the integrated approach to health, research, education and advocacy in Tanzania, 2004-2016.British journal of haematology · 2017Review
- An Expert Review of Pharmacogenomics of Sickle Cell Disease Therapeutics: Not Yet Ready for Global Precision Medicine.Omics : a journal of integrative biology · 2016Review
- Fetal Hemoglobin Modifies the Disease Manifestation of SevereMediterranean journal of hematology and infectious diseases · 2016Article
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Authors and funding
12 authors at 5 institutions in 4 countries.
Funding
Abstract
backgroundHaemoglobin variants, Sickle (HbS) and foetal (HbF) have been associated with malaria protection. This study explores epistatic interactions between HbS and HbF on malaria infection.
methodsThe study was conducted between March 2004 and December 2013 within the sickle cell disease (SCD) programme at Muhimbili National Hospital, Tanzania. SCD status was categorized into HbAA, HbAS and HbSS using hemoglobin electrophoresis and High Performance Liquid Chromatography (HPLC). HbF levels were determined by HPLC. Malaria was diagnosed using rapid diagnostic test and/or blood film. Logistic regression and generalized estimating equations models were used to evaluate associations between SCD status, HbF and malaria.
findings2,049 individuals with age range 0-70 years, HbAA 311(15.2%), HbAS 241(11.8%) and HbSS 1,497(73.1%) were analysed. At enrolment, malaria prevalence was significantly higher in HbAA 13.2% compared to HbAS 1.24% and HbSS 1.34% (p<0.001). Mean HbF was lower in those with malaria compared to those without malaria in HbAA (0.43% vs 0.82%) but was the reverse in HbSS (8.10% vs 5.59%). An increase in HbF was associated with a decrease in risk of malaria OR=0.50 (95%CI: 0.28, 0.90; p=0.021) in HbAA, whereas for HbSS the risk of malaria increased OR=2.94 (1.44, 5.98; p=0.003). A similar pattern was seen during multiple visits; HbAA OR=0.52 (0.34, 0.80; p=0.003) vs HbSS OR=2.01 (1.27, 3.23; p=0.003).
conclusionHigher prevalence of malaria in HbAA compared to HbAS and HbSS confirmed the protective effect of HbS. Lower prevalence of malaria in HbAA with high HbF supports a protective effect of HbF. However, in HbSS, the higher prevalence of malaria with high levels of HbF suggests loss of malaria protection. This is the first epidemiological study to suggest a negative epistasis between HbF and HbS on malaria.
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