The role of unobserved cholera: implications for prevention and control

ABSTRACT Surveillance of many human pathogens relies primarily on clinical diagnosis of individuals who seek testing or care. In most contexts the number of unobserved infections is unknown, which poses a challenge in effectively mitigating transmission. Infections may go unobserved 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. This is true for Vibrio cholerae, a pathogen responsible for an estimated 3 million cholera cases and 100,000 deaths each year. 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 propose to do this by estimating the magnitude of V. cholerae infections that go unobserved by comparing patterns in clinical and serological data across various endemic and epidemic locations (aim 1), examining the degree to which individuals with mild symptoms who commonly go unobserved shed V. cholerae bacteria that may be transmitted (aim 2), and estimating the risk of infection following exposure to asymptomatic household contacts (aim 3). We expect to find high levels of unobserved infections, particularly in areas with barriers in access to healthcare. 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.