Mass drug administration of praziquantel lowers the susceptibility of school-aged children to Schistosoma mansoni in endemic areas.

BACKGROUND: Schistosomiasis remains a significant public health challenge in endemic regions, leading to substantial morbidity. While regular mass drug administration (MDA) of praziquantel (PZQ) is a cornerstone schistosomiasis control programs in endemic areas, emerging evidence suggests that its benefits may extend beyond mere parasite killing. we sought to determine whether sustained PZQ MDA promotes the development of protective immunity in school-aged children. Building on previous observations in animal models where repeated cycles of S. mansoni infection followed by PZQ treatment enhanced host resistance to reinfection, we hypothesized that repeated MDA of PZQ in endemic settings similarly promotes the development of protective anti-schistosome immunity. Accordingly, this study aimed to translate these observations into real-world evidence and investigate the broader association between regular PZQ administration on schistosomiasis infections, burden dynamics, and associated health outcomes in SAC. METHODS: We performed a cross-sectional study on previously collected samples from school-aged children in schistosomiasis-endemic regions who received repeated MDA of PZQ. Levels of plasma antibodies and cytokines were measured by ELISA. RESULTS: Analysis of previously collected samples and data from cumulative annual rounds of PZQ treatment demonstrated that regular administration significantly reduced the odds of elevated parasite burdens upon reinfection (AOR = 0.16, 95% CI = 0.01-0.61), and improved hemoglobin levels (AOR = 2.58, 95% CI = 1.22-8.05) and academic performance (AOR = 2.39, 95% CI = 1.11-7.09) in SAC. However, it did not significantly reduce the likelihood of liver fibrosis (AOR = 1.73, 95% CI = 0.45-14.53). Mechanistically, repeated PZQ treatment of SAC was associated with heightened arginine/proline metabolism that translated into higher protective IgE levels (p = 0.002) and increased type-2 cytokine production. CONCLUSION: Our study highlights a previously underappreciated advantage of sustained PZQ treatment in SAC from schistosomiasis-endemic areas. Regular deworming with PZQ may rapidly rewire the host to foster the development of protective immune responses, mitigating the risks of heavy reinfection and its sequelae, underscoring the overlooked benefits of PZQ treatment for integrated public health strategies against schistosomiasis.