Exploring the protective effects of thalassemia against malaria in Africa: a systematic review

Introduction: Thalassemia, a hereditary blood disorder characterized by abnormal hemoglobin production, is prevalent in malaria-endemic regions, particularly among individuals of African descent. This hemoglobinopathy is believed to confer protection against malaria, reducing the severity of the disease and its associated complications. This systematic review and meta-analysis aimed to evaluate the protective effects of thalassemia against malaria, drawing insights from studies conducted in Africa between 2013 and 2025. Methods: This review adhered to the PRISMA guidelines and has been registered on PROSPERO. A comprehensive literature search was conducted via PubMed, Scopus, Cochrane Library, Embase and Google Scholar, supplemented by manual reference checks. Boolean search terms such as “thalassemia,” “malaria,” and “Africa” were used. The meta-analysis was conducted via R version 4.4.1, and a random effects model was used to calculate pooled odds ratios (ORs). Heterogeneity was assessed via the I2 statistic, and publication bias was evaluated via funnel plots and Egger’s test. Results: Among the 4,957 screened articles, 15 studies met the inclusion criteria, with eight providing sufficient data for meta-analysis. The meta-analysis indicated that thalassemic individuals had lower odds (OR: 0.856) of developing malaria than non-thalassemic individuals. Mechanistically, alpha thalassemia has been shown to reduce cytoadhesion and rosette formation and enhance immune clearance, with favorable interactions observed with the haptoglobin phenotype (Hp2-1). Conclusion: Although the pooled estimate suggested a protective trend, the association was not statistically significant and was characterized by substantial heterogeneity across studies. While these findings underscore the evolutionary link between hemoglobinopathies and malaria resistance, further research is needed to elucidate molecular pathways and broader implications of thalassemia. Systematic review registration: PROSPERO CRD420261294712.