Molecular epidemiological study on Vibrio cholerae causing seasonal and off-season cholera outbreaks in Dhaka, 2007-2018

Burden

Cholera has been well-established as a seasonal disease that varies in the patterns of infections. The seasonal outbreaks of cholera occurs in multiple endemic foci of Bangladesh, most showing a single annual peak like in other cholera affected regions of the world. However, cholera shows two distinct seasonal peaks, one before (March – May) and the other after (September – November) the annual monsoon [6] in Dhaka and Matlab, Bangladesh. V. cholerae has been established as an autochthonous flora of brackish waters and estuarine ecosystems [11] where the bacterium shares niche, and is found in association with plankton [12]. Although sea surface temperature has been shown to have a degree of correlation with the incidence of cholera in Bangladesh [13], little is known about how these factors contribute to the seasonal cholera outbreaks in the freshwater environments of Dhaka and Matlab, which are 50km apart, and 350 km away from the coast of Bay of Bengal. Historically, most major epidemics have originated in the coastal regions, including the O139 Bengal outbreaks that originated in the Bay of Bengal villages of India and Bangladesh. In Dhaka and Matlab, endemic cholera occurs in distinctive two-peak pattern, before and after the monsoon [1,14], although the diseases continues even beyond the defined seasons and can appear as off-season peaks affecting many.

Knowledge gap

In August 2007, Bangladesh suffered flooding, which was accompanied by a large diarrhea outbreak in Dhaka city just prior to the usual fall peak that followed. During this outbreak, the ICDDR,B Dhaka hospital treated a record number of cholera patients peaking at 1045 patients per day, with 70% suffering from severe dehydration. Although V. cholerae O1 ET was the etiological agent, the detail characteristics of the bacterium causing increasing severity of cholera including the natural factors driving the off-season epidemics remain important to be explored.

Relevance

This study will generate important data on the climate factors, and phenotypic (antibiogram), molecular, and phylogenetic characteristics of V. cholerae ET associated with the severe disease outbreak of seasonal and off-season cholera. The data will aid in formulating therapeutic intervention and preventive measures against the deadly disease.

Hypothesis

The seasonal and off-season cholera outbreaks have different hydro-climatic drivers in Bangladesh, and the increased severity of 2007 flood outbreak might be the result of fecal-oral transmission of hyper-infectious V. cholerae.

Objectives

• To study the phenotypic, molecular, and phylogenetic characteristics of V. cholerae associated with severe disease outbreak of seasonal and off-season cholera in 2007.
• To analyze the regional hydroclimatological data for over 30-35 years (1980s – 2018) to understand the natural driver(s) of cholera.

Methods

An estimated 1000 V. cholerae strains from seasonal and off-season cholera outbreaks in 2007 and in the subsequent years, up to 2018, would be included in this study. V. cholerae strains will be collected from routine 2% hospital surveillance samples at Dhaka hospital of icddr,b at an estimated number of 80 – 100 strains/year for phenotypic, molecular and phylogenetic analyses, including multilocus genetic screening by simplex and multiplex-PCR, sequence-typing of the genes (namely ctxB), pulsed-field gel electrophoresis (PFGE), and whole genome sequencing (WGS). No patient data will be collected in this study other than the date of hospital enrolment to keep temporal records of the infections. Role of climate and related factors e.g., hydroclimatological data such as annual water flow in the major basins, temperature, rainfall, humidity etc. associated with the unusual incidence of cholera cases suffering from severe disease will also be determined.

This study was designed to characterize V. cholerae responsible for the seasonal and off-season cholera outbreaks in Dhaka.

Unveiling the clonal type responsible for seasonal and off-season cholera outbreaks is crucial to decide intervention and preventive measures against cholera.