Pandemic Vibrio cholerae and the Environmental Reservoir Hypothesis-Outstanding Questions Central to Global Cholera Control.

Despite global cholera cases rising to more than 560,000 in 2024, there remains no consensus on a fundamental aspect of cholera epidemiology: whether pandemic Vibrio cholerae forms long-term environmental reservoirs which become the source of future outbreaks. This knowledge gap prevents optimal disease forecasting, resource allocation and outbreak response in a variety of at-risk settings, from places experiencing annual cholera outbreaks (such as the Democratic Republic of the Congo) to those where the disease seemingly reappears after an absence (such as Haiti). Here, we provide a new framework on links between pandemic cholera and ecological parameters, demonstrating a complex and perhaps time-limited relationship between pathogen and environment. The framework in turn illustrates several outstanding questions which can be addressed to better understand whether, when and how environmental reservoirs perpetuate cholera, thereby helping to advance global cholera control.