Serosurveillance to improve estimates of burden and at-risk populations of cholera and COVID-19

Burden

Cholera remains a major global health problem, resulting in more than 100,000 deaths and several million cases annually. Bangladesh, which lies in the Ganges River Delta, is a hyper endemic country and has an estimated 300,000 cholera cases and over 4,500 deaths annually. In early 2020, the SARSCoV-2 pandemic shocked the world leading to over 43 million cases and over 1 million deaths globally by October 2020. In Bangladesh, by October 2020, there have been an estimated 400,000 cases and over 5,000 deaths. With the implementation of non-pharmaceutical interventions like social distancing, healthcare seeking behaviors have likely been affected resulting in the likely underestimation of both cholera and COVID-19 cases.

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. cholera 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 SARSCoV- 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 behaviours.

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 at two healthcare facilities and through 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.

Study Site

This study will be focused at two healthcare facilities, the Bangladesh Institute of Tropical Infectious Diseases (BITID) and the Sitakunda Upazila Health Complex (UHC), and their catchment population, the Sitakunda Upazila within the Chittagong District in South Eastern Bangladesh. Historical clinical and serologic surveillance from the district suggest that cholera incidence is relatively high compared to other parts of Bangladesh (e.g.,1.15 times the seroincidence than the mean for the country based on a serosurvey conducted in 2015) with two seasonal peaks in cholera admissions, the larger one typically starting in March and the smaller one towards the end of the calendar year. Clinical surveillance data from 2014-2018 illustrate that a greater number of patients with acute watery diarrhea visit BITID from April to June; on average approximately 4,000 individuals seek care at BITID for acute watery diarrhea within a single year. We anticipate that within a 18-month period,
approximately 9,000 patients will seek care at both BITID and the Sitakunda UHC.

Cholera remains a major global health problem, resulting in more than 100,000 deaths and several million cases annually. Bangladesh, which lies in the Ganges River Delta, is a hyper endemic country and has an estimated 300,000 cholera cases and over 4,500 deaths annually. In early 2020, the SARS-CoV-2 pandemic shocked the world leading to over 43 million cases and over 1 million deaths globally by October 2020. In Bangladesh, by October 2020, there have been an estimated 400,000 cases and over 5,000 deaths. With the implementation of non-pharmaceutical interventions like social distancing, healthcare seeking behaviors have likely been affected resulting in the likely underestimation of both cholera and COVID-19 cases.

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 at two healthcare facilities and through 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.

Our primary study outcome is the change in seroincidence between the first and third serosurvey to capture changes in cholera incidence over the course of the typical high and low season at the study site. Our secondary outcome is the prevalence of anti-SARS-CoV-2 antibodies among individuals in the first serosurvey. We will explore the associations between seropositivity (for cholera and SARS-COV-2) and different individual-, household- and community-level risk factors collected in the surveys, including WASH attributes and factors like population density, travel time (to the nearest city), distance to a major water body, community water and sanitation coverage, and poverty.