Revisiting the impact of Schistosoma mansoni regulating mechanisms on transmission dynamics using SchiSTOP, a novel modelling framework

Background The transmission cycle of Schistosoma is remarkably complex, including sexual reproduction in the human hosts and asexual reproduction in the intermediate host (freshwater snails). Patterns of rapid recrudescence after treatment and stable low transmission are often observed, hampering the achievement of control targets. Current mathematical models commonly assume regulation of transmission to occur at worm level through density-dependent egg production. However, conclusive evidence on this regulating mechanism is weak, especially for S. mansoni. In this study, we explore the interplay of different regulating mechanisms and their ability to explain observed patterns in S. mansoni epidemiology. Methodology/Principal findings We developed SchiSTOP: a hybrid stochastic agent-based and deterministic modelling framework to reproduce S. mansoni transmission in an age-structured human population. We implemented different models with regulating mechanisms at: i) worm-level (density-dependent egg production), ii) human-level (anti-reinfection immunity), and iii) snail-level (density-dependent snail dynamics). Additionally, we considered two functional choices for the age-specific exposure to water bodies. We compared the ability of each model to reproduce observed epidemiological patterns pre- and post-control, and we compared the successful models in their predictions of the impact of school-based and community-wide treatment. Simulations confirmed that assuming at least one regulating mechanism is required to reproduce a stable endemic equilibrium. Snail-level regulation was necessary to explain stable low transmission. Only models combining snail- and human-level regulation with an age-exposure function informed with water contact data were successful in reproducing observed patterns. However, the predicted probability of reaching the control targets varied across successful models. Conclusions/Significance The choice of regulating mechanisms in schistosomiasis dynamics largely determines the model-predicted feasibility to reach control targets. Overall, the models that successfully explained observed patterns for S. mansoni suggest that reaching the control targets may be more challenging than currently thought. Conclusions highlight the importance of regulating mechanisms to be included in transmission models used for policy. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The authors gratefully acknowledge funding from the European Marie Skłodowska-Curie fellowship H2020-MSCA-IF-2018-846873. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The study does not make use of collected and reported field data.