Introduction Oral cholera vaccines (OCVs), though in short supply globally, can effectively reduce the risk of cholera caused by pandemic Vibrio cholerae O1, which is highly variable in space and time. Few cholera surveillance systems perform systematic confirmatory testing for V. cholerae, which limits the efficient selection of vaccination campaign targets and public health impact of OCV. Methods We developed a spatial modeling framework that simulates vaccine targeting and changing cholera susceptibility and burden for 35 countries in Africa from 2022-2035. We explored the relative gains in efficiency across 18 vaccination scenarios that varied by their vaccination targeting approach and confirmatory testing capacity. Efficiency was calculated as the number of true cholera cases averted per 1,000 fully vaccinated persons. Results Scenarios with more restrictive targeting- defined by greater bacteriological confirmation capacity, smaller geographic targeting scale, and higher incidence rate thresholds- were associated with higher vaccination campaign efficiency. The most restrictive scenario averted 9.41 (95% PI: 7.76-11.88) cases per 1,000 fully vaccinated persons. This was 10 times more efficient than the least restrictive scenario, which vaccinated roughly 20 times as many people and only averted about 2 times as many cases. Scenarios that based targeting according to clinical surveillance averted the most cases, at the cost of using many more vaccines. Across modeled countries, scenarios with national laboratory confirmation at the national level had substantially improved efficiency compared to clinical surveillance alone, while district-level laboratory capacity yielded only minor additional gains. Conclusion Less restrictive targeting of vaccination campaigns averts the most cholera cases, while district-level bacteriological confirmation capacity that enables targeting of districts with the highest burden of true cholera represents the most efficient use of vaccine. Nevertheless, these modeling scenarios represent simplified versions of complex logistical and decision-making challenges in cholera surveillance and vaccine distribution. In reality, building testing capacity at levels in-between the national and district-levels is likely to best balance surveillance data quality with feasibility.

The authors have declared no competing interest.

HX, ASA, and ECL received funding support from Gavi. This work was carried out as part of the Vaccine Impact Modelling Consortium (www.vaccineimpact.org), but the views expressed are those of the authors and not necessarily those of the Consortium or its funders. The funders were given the opportunity to review this paper prior to publication, but the final decision on the content of the publication was taken by the authors. This work was supported, in whole or in part, by the Bill & Melinda Gates Foundation, via the Vaccine Impact Modelling Consortium [Grant Number INV-009125]. Under the grant conditions of the Foundation, a Creative Commons Attribution 4.0 Generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission.

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