Impact of a multi-pronged cholera intervention in an endemic setting

Cholera is a bacterial water-borne diarrheal disease that causes high morbidity in sub-Saharan Africa and Asia. It is transmitted via the fecal-oral route and can be prevented with vaccination and Water, Sanitation, and Hygiene (WASH) improvements. WASH improvements are resource and time intensive but provide long lasting benefits. Vaccination campaigns can be implemented more rapidly than WASH but provide only temporary immunity; cholera vaccines are effective in epidemic settings but their utility in endemic settings is unclear. The city of Kalemie in the Democratic Republic of Congo, on the shore of Lake Tanganyika, is a cholera endemic area with annual outbreaks. Both seasonal mobility and the lake, which is a bacterial reservoir, promote transmission, though their relative contributions are unknown. In 2013-2016 Kalemie received a targeted vaccination campaign and WASH improvements. We assessed the short-term impact of this intervention to guide future control strategies in endemic settings. We fit a Susceptible-Infected-Recovered-Susceptible model with a compartment for the aquatic bacterial population. We estimated the number of cases avoided by each arm of the intervention, explored alternative vaccination strategies, and investigated the relative contributions of mobility and environmentally-based transmission in local cholera dynamics. We estimated that vaccination and WASH improvements prevented 3,484 cases (95% Credible Interval: 2,412-4,833) over a 118-week period. We showed that vaccination could prevent more cases by altering the timing and increasing the target population size. We found that transmission was primarily environmentally-driven and that removing environmental exposure or reducing environmental contamination could decrease local transmission. Together, the targeted nature of the vaccination campaign, the modest scale of WASH improvements, and the high background immunity of the population limited the impact of the intervention. Constant environmentally-driven force of infection maintains high levels of cholera immunity in the population and decreases the impact of vaccination in this endemic area. Author summary Cholera is a major global health concern that causes high morbidity. It is a bacterial water-borne disease that can be transmitted via the fecal-oral route or the ingestion of contaminated water. Hence, both population mobility and environmental exposure can promote cholera persistence. The primary tools to prevent cholera include vaccination and Water, Sanitation, and Hygiene (WASH) improvements. The effectiveness of these interventions is well understood in epidemic settings, but their impact in endemic settings is unclear. Achieving cholera elimination requires disentangling the contributors to transmission, specifically population mobility and aquatic reservoirs, and assessing the impact of interventions performed in endemic settings. This study focuses on Kalemie, a cholera endemic city in the Democratic Republic of Congo, on shore of a lake that serves as a potential environmental reservoir. It quantifies the short-term impact of an intervention that used targeted vaccination and WASH. The study shows that the impact of vaccination was dampened by very high background immunity due to constant environmental exposure. This suggests that WASH improvements should be the primary intervention in such settings despite the time- and resource-intensive nature of implementation. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by the joint National Institutes of Health (NIH) - National Science Foundation (NSF) - National Institute of Food and Agriculture (NIFA) Ecology and Evolution of Infectious Disease (award R01TW012434 to NB), NSF DEB RAPID (award 2202872 to NB), and NSF DMS (award 2015273 to EH). Funders had no role in the 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 Ethical Review Board of the University of Lubumbashi gave ethical approval the study protocol to assess the impact of the vaccination campaign (study protocol ethical number: UNILU/CEM/028/2013) and its extension (study protocol ethical number: UNILU/CEM/050/2015). Individuals provided informed consent to be part of the vaccine coverage survey. Pennsylvania State University Institutional Review Board determined the post-intervention handling and analyses of these anonymized data was Not Human Research (STUDY00015621). 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 weekly aggregated number of suspected cholera cases can be requested by contacting Klaudia Porten (Klaudia.PORTEN@epicentre.msf.org). All additional data and code necessary to reproduce the analysis and the figures are available online at https://github.com/bhartilab/cholera_kalemie