Abstract
BACKGROUND: Urogenital schistosomiasis caused by Schistosoma haematobium affects over 100 million people globally, with potential long-term genetic and immunological consequences poorly understood in endemic populations. This study investigates genetic damage and immune dysregulation in infected individuals from a hyperendemic region in Nigeria. OBJECTIVE: To quantify genetic damage markers and characterize immune system alterations in individuals with confirmed S. haematobium infection compared to uninfected controls from Atisbo Local Government Area, Oyo State, Nigeria. METHODS: This cross-sectional study included 240 participants (120 infected, 120 controls) aged 15–65 years, selected using multi-stage cluster sampling. Genetic damage was assessed using comet assay, micronucleus testing, and chromosomal aberration analysis. Immune profiling included Th1/Th2 cytokines, immunoglobulins, and complement components. Multivariate regression models identified independent predictors of genetic damage. RESULTS: Infected individuals demonstrated markedly elevated genetic damage: comet tail moment 15.7 ± 4.2 versus 6.3 ± 2.1 (Cohen’s d = 2.80, p < 0.001), micronucleus frequency 8.4 ± 2.7 versus 3.1 ± 1.2 per 1000 cells (d = 2.41, p < 0.001), and chromosomal abnormalities 12.3% versus 4.1% (p < 0.001). Pronounced Th2 polarization was evident with IL-4 increased 4.1-fold, IL-5 4.6-fold, and IL-13 4.1-fold, while IFN-γ was reduced by 65% (all p < 0.001, FDR-adjusted). S. haematobium infection independently predicted genetic damage (β = 8.42, 95% CI: 7.51–9.33, p < 0.001) after adjusting for age, BMI, hemoglobin, and sex, explaining 73% of the variance in tail moment values. CONCLUSIONS: S. haematobium infection causes substantial genetic damage and Th2-dominant immune dysregulation with potentially serious long-term health consequences. These findings provide scientific justification for intensified control efforts, enhanced post-treatment monitoring, and cancer surveillance programs in endemic populations. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12865-025-00749-w.