Modelling timelines to elimination of sleeping sickness in the DRC accounting for possible cryptic human and animal transmission

Sleeping sickness (gambiense human African trypanosomiasis, gHAT) is a vector-borne disease targeted for global elimination of transmission (EoT) by 2030. There are, however, unknowns that have the potential to hinder the achievement and measurement of this goal. These include asymptomatic gHAT infections (inclusive of the potential to self-cure or harbour skin-only infections) and whether gHAT infection in animals can contribute to the transmission cycle in humans. Using modelling we explore how cryptic (undetected) transmission impacts the monitoring of progress towards as well as the achievement of the EoT goal. We have developed gHAT models that include either asymptomatic or animal transmission, and compare these to a baseline gHAT model without either of these transmission routes, to explore the potential role of cryptic infections on the EoT goal. Each model was independently calibrated using available historic human case data for 2000––2020 (obtained from the World Health Organization’s HAT Atlas) which includes routine data from active and passive screening for five different health zones in the Democratic Republic of the Congo (DRC). Our results suggest that when matched to past case data, we estimated similar numbers of new human infections between model variants, although human infections were slightly higher in the models with cryptic infections. We simulated the continuation of screen-confirm-and-treat interventions and found that forward projections from the animal and asymptomatic transmission models produced lower probabilities of EoT than the baseline model. Simulation of a (as yet to be available) screen-and-treat strategy found that removing a parasitological confirmation step was predicted to have a more noticeable benefit to transmission reduction under the asymptomatic model compared to the others. Our simulations suggest vector control could greatly impact all transmission routes in all models, although this resource-intensive intervention should be carefully prioritised. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Bill and Melinda Gates Foundation ([www.gatesfoundation.org][1]) through the Human African Trypanosomiasis Modelling and Economic Predictions for Policy (HAT MEPP) project \[OPP1177824 and INV-005121\] (CH, REC, MA, SAS, SEFS, EHC, MJK, KSR), and through the NTD Modelling Consortium \[OPP1184344\] (KSR, SEFS, MA, MJK). 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 The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Biomedical and Scientific Research Ethics Committee of the University of Warwick gave ethical approval for this work (application number BSREC 80/21-22) 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 Data cannot be shared publicly because they were aggregated from the World Health Organization's HAT Atlas which is under the stewardship of the WHO. Data are available from the WHO (contact neglected.diseases{at}who.int or visit [https://www.who.int/trypanosomiasis\_african/country/foci\_AFRO/en/][2]) for researchers who meet the criteria for access. Model code and outputs produced from this study are available through Open Science Framework . [1]: http://www.gatesfoundation.org [2]: https://www.who.int/trypanosomiasis_african/country/foci_AFRO/en/