Elevated seroprevalence and risk of Toxoplasma gondii infection in patients with beta-thalassemia major: a systematic review and meta-analysis

Toxoplasma gondii infection may pose substantial risks to immunocompromised individuals, including patients with beta-thalassemia major, who are exposed to repeated allogeneic blood transfusions and disease-related immune dysregulation. This systematic review and meta-analysis aimed to estimate the seroprevalence of T. gondii and the associated risk in this population compared with healthy controls. Following PRISMA guidelines, PubMed, Scopus, and Web of Science were searched from inception to July 24, 2025. Eligible case-control and cross-sectional studies reporting T. gondii IgG or IgM seropositivity were included. Data were independently extracted by two reviewers. Pooled estimates were calculated using random-effects models, with heterogeneity assessed using I² and Cochran’s Q tests. Publication bias was evaluated using funnel plots, Begg’s and Egger’s tests, and trim-and-fill analysis. Methodological quality was appraised with the design-specific Joanna Briggs Institute (JBI) critical appraisal checklists. Leave-one-out sensitivity analysis and subgroup analyses by study design, diagnostic assay, and region were performed. Fourteen studies (11 case-control, 3 cross-sectional) were included from 45 initial records. The pooled prevalence of T. gondii infection in patients with beta-thalassemia major was 21.5% (95% CI: 16.2–27.9%; I² = 94.0%), with seroprevalence rates of 30.0% (95% CI: 22.5–38.8%; I² = 92.3%) for IgG and 4.8% (95% CI: 2.3–9.7%; I² = 88.8%) for IgM. The overall pooled risk ratio (RR) was 2.30 (95% CI: 1.73–3.05), with subgroup RRs of 2.05 (95% CI: 1.49–2.82) for IgG and 3.46 (95% CI: 1.89–6.34) for IgM. Eight studies were rated as high quality, one as moderate quality, and five as low quality, and the pooled prevalence was not inflated by the lower-quality studies. Meta-regression revealed no significant effect of publication year or sample size on heterogeneity. Leave-one-out sensitivity analysis confirmed the robustness of the pooled estimates, while subgroup analysis identified study design as a potential source of heterogeneity. Funnel plot asymmetry (Begg’s p = 0.0007; Egger’s p < 0.0001) indicated possible publication bias, and trim-and-fill analysis suggested potential missing studies for risk-ratio outcomes. In this meta-analysis of observational studies, patients with beta-thalassemia major showed significantly elevated T. gondii seroprevalence and risk relative to healthy controls. Given the observational nature of the included studies, transfusion-related transmission and disease-associated immune dysregulation are plausible but unproven contributors to this association. These findings support further evaluation of donor screening and preventive strategies in this vulnerable population, rather than establishing a direct causal mechanism.