20+ years of mass drug administration against urogenital schistosomiasis on the Zanzibar islands: Is praziquantel still efficacious?

Background On the Zanzibar islands, Tanzania, mass drug administration (MDA) with praziquantel against Schistosoma haematobium infections has been implemented regularly since the early 2000s. Elimination of schistosomiasis as a public health problem has been achieved in most areas, with the goal of interruption of transmission. The RESIST project investigates the extent to which MDA-driven selection for praziquantel resistance is occurring and contributing to persistent transmission hotspots. Methodology As part of RESIST, the efficacy of praziquantel treatment was assessed in two schools on Pemba between October 2024 and March 2025. Longitudinal parasitological surveys were conducted before and two weeks after school-based MDA with praziquantel (40 mg/kg). Up to six urine samples per study participant were collected on different days pre- and post-MDA and examined for S. haematobium eggs by urine filtration microscopy. In a per-protocol analysis, drug efficacy was categorised as adequate, inconclusive, or reduced, based on hypothesis testing. A generalized linear mixed model was used to assess the association between pre-MDA infection intensity and drug efficacy at the individual level. Principal findings Pre-MDA, S. haematobium prevalence was 14.3% (62/434) in School 1 and 37.8% (233/617) in School 2. Post-MDA prevalence was 0.5% (2/434) and 9.6% (59/617), respectively. Egg reduction rates were 99.8% (90% confidence interval (CI): 99.2-100%) in School 1 and 94.8% (90% CI: 88.6-98.6%) in School 2, which were classified as adequate and inconclusive, respectively. In School 2, drug efficacy at the individual level was negatively associated with pre-MDA infection intensity. Conclusion/significance The efficacy of praziquantel on Pemba remains higher than the 90% threshold for optimal drug efficacy set by the World Health Organization. While the inconclusive efficacy results for School 2 can at least partially be explained by the variation in the participants pre-MDA infection intensities, further investigations are warranted to account for the disparity in praziquantel efficacy on Pemba. Trial registration: ISRCTN, ISRCTN59331501. Registered 24 October 2024, https://www.isrctn.com/ISRCTN59331501.