The role of unobserved cholera: implications for prevention and control

Surveillance of many human pathogens, including Vibrio cholerae, relies primarily on clinical diagnosis of individuals who seek testing or care. Infections may go unobserved in these passive surveillance systems for a number of reasons, including mild and asymptomatic infections not captured by clinical surveillance as well as symptomatic infections not captured due to factors such as barriers in access to healthcare or limited testing resources. Previous studies in Bangladesh have shown that unobserved infections account for at least half of V. cholerae infections and that individuals with asymptomatic infection shed less V. cholerae in their stool compared to symptomatic cholera. The extent to which this impacts our ability to prevent and control outbreaks, and whether these findings apply to other populations, is unknown. In this study we aim to address this gap in our knowledge by investigating the contribution of unobserved infections to cholera burden and transmission in multiple populations. We will to do this by estimating the magnitude of V. cholerae infections that go unobserved by comparing patterns in clinical and serological data across published studies from various endemic and epidemic locations (aim 1), examining the degree to which individuals with no or mild symptoms shed V. cholerae bacteria that may be transmitted among individuals in Uvira, Democratic Republic of the Congo (aim 2), and estimating the risk of infection following exposure to asymptomatic household contacts of cholera cases in Dhaka, Bangladesh (aim 3). We expect to find high levels of unobserved infections, particularly in areas with barriers to healthcare access. We also anticipate that mild/asymptomatic infections will be associated with bacterial shedding and ongoing transmission, but to a lesser extent than cases with more severe symptoms. Alternatively, since people with mild/asymptomatic infections are less likely to receive antibiotics and often continue to go about their daily routines, we may find increased bacterial shedding and secondary infections in these cases. In either scenario, these results will provide important insights into the degree to which unobserved infections contribute to V. cholerae persistence and spread, as well as their role in our efforts to mitigate outbreaks. Our long-term goal is to better understand the underlying host, microbial, and socio-demographic factors that lead to infections going unobserved so that we can design more effective prevention and control strategies.

Cholera surveillance and control strategies rely primarily on detecting symptomatic cases that seek care; mild infections and infections in individuals with barriers in access to healthcare are often unobserved. This project aims to examine the degree to which unobserved infections contribute to the burden and transmission of Vibrio cholerae. The approaches used in this study will lay the groundwork for addressing critical questions about the host, microbial, and socio-demographic factors that contribute to infections going unobserved, ultimately leading to more effective mitigation strategies.

Results from this study will help us to refine cholera burden estimates and to better understand whether current control strategies, which target symptomatic cholera, are enough to mitigate transmission.