Serosurveillance to improve estimates of burden and at-risk populations of cholera

Knowledge gap

To meet the ambitious goals set by the WHO of reducing cholera as a public health threat by 2030 and reduce cholera in the hyper endemic setting of Bangladesh, improving our methods for counting cholera cases and infections is critical for control planning. At present, most cholera burden estimates are derived from passive clinical based surveillance, which only captures a portion of true cases and infections due to barriers to healthcare seeking. While we have recently developed methods to estimate V. cholerae infection incidence at the population-level, some fundamental questions still remain on how to interpret this data in relation to clinical incidence. Furthermore, we know little about how the COVID-19 pandemic has affected healthcare seeking for cholera or what the seroprevalence of SARS-CoV-2 is in the population.

Relevance

Results from this study will improve our knowledge of cholera incidence in Bangladesh to aid the distribution of interventions like the oral cholera vaccine. Refining our methods for estimating cholera burden will additionally improve how we estimate cholera burden in other countries and estimate future vaccine demand. This study will also result in the estimation of the seroprevalence of SARS-CoV-2 infection in the study region in Bangladesh which will help inform the implementation of interventions like vaccination and improve our understanding of how the COVID-19 pandemic has disrupted healthcare seeking behaviors.

Objectives

The primary objective of this study is to improve and refine our methods for estimating correlates of cholera burden from cross-sectional serosurveys though enhanced clinical surveillance of cholera and serial serosurveys. A secondary objective of this study is to better understand the maturity of the SARS-COV-2 epidemic in this population by measuring the prevalence of SARS-COV-2 antibodies in the population and estimating key individual-, household- and community-level risk factors for infection.

Methods

The current national cholera surveillance program will be enhanced by recording and testing all individuals seeking care for suspected cholera, inpatient or outpatient, at the Bangladesh Institute of Tropical Infectious Diseases (BITID) and the Sitakunda Upazila Health Complex (UHC), for cholera. A study staff will be present at each health centre to monitor all points of triage and search for suspected cholera cases. In the second portion of the study we will enroll randomly selected households and follow ~1,632 individuals longitudinally across three time points to capture the low and high season of cholera. At each time point, participants will be administered a questionnaire regarding healthcare seeking and water and sanitation related behaviors and blood will be collected to measure seroincidence.

Outcome measures/variables

The questionnaire and blood collection will be conducted 3 times at each household selected for the cholera outcome. This will help to capture changes over the course of the typical high season for cholera at the study site while allowing for us to capture detailed surveillance data for the 6-month period before the initial survey. Our primary study outcome is the change in seroincidence between the first and third serosurvey. Estimation of the prevalence of anti-SARS-CoV-2 antibodies among individuals in the first serosurvey will give us good precision around plausible estimates of seroprevalence consistent with recent findings in Bangladesh.

In this study in Sitakunda, Bangladesh, we are trying to understand how to use antibody levels in people’s blood collected at a single point in time in a survey to estimate the rate of infections with Vibrio cholerae O1. Given that a large fraction of infections lead to mild disease or are asymptomatic, we are also studying how to translate infection rates to burden of disease.

This study will help us understand how seroepidemiology can be used to track changes in cholera over time complementing clinical cholera surveillance efforts