Understanding the nature and diversity of Vibrio cholerae at its global source

Burden

Cholera is a deadly disease with approximately 3-5 million cases and over 1,00,000 deaths annually worldwide. Cholera is a seasonal disease caused by the bacterium V. cholerae which is autochthonous to the aquatic environment. Although it is well established that the disease transmits through water rapidly giving rise to large epidemics, factors contributing to the seasonality of cholera by activating the bacterium persisting in biofilms and in association with planktons in the environment and linkage between archived and newly disseminating 7PET sublineages, remain a longstanding question to answer.

Knowledge gap

Combined these data suggest that areas of high cholera incidence in Africa and during the 1990’s in Latin America, can be viewed as sinks for the epidemic cholera causing lineage 7PET and not the original source. Whilst data supporting this are substantive, we lack a detailed whole genome view of the environmental isolates of V. cholerae (O1, O139, and non-O1/non-O139) from Inland, coastal and estuarine environments of West Bengal and Northern regions of India and Bangladesh, the South Asian ‘hotspot’ of epidemic cholera.

Relevance

Unveiling the natural climatic factors that contribute to the seasonal epidemics of cholera would be of preventive implication. If we are to understand the drivers behind the emergence and spread of newly disseminating 7PET sublineages then we must focus attention on the Ganges Delta region, understanding how and where its unique ecology supports the emergence and spread of epidemic V. cholerae.

Hypothesis

The environmental Vibrio cholerae population in the Bay of Bengal supports the emergence of pandemic cholera

Objectives:

The specific objectives of this project are as follows:

• Generate a long term genomic view of environmental V. cholerae in Bangladesh from live archived samples to understand their evolutionary dynamics and their relationship to 7PET epidemic V. cholerae
• Link genome evolution of V. cholerae to environmental conditions and flux

Methods

Environmental surveillance will be conducted at six river sites of Dhaka, the capital of Bangladesh; five pond and one river sites of Mathbaria, coastal village of Bangladesh; and six river sites of Chhatak, a northern district of Bangladesh. Environmental water samples will be collected bi-weekly during seasonal epidemics of cholera i.e. during March-May and September-November at Dhaka and Mathbaria, September-November at Chhatak and monthly during the rest of the year. The samples will be monitored for environmental parameters such as temperature, turbidity, pH, salinity, total dissolved solids and conductivity. Samples will be transferred to icddr,b central Laboratory at Dhaka at ambient temperature for further analyses (Alam et al. 2006a). Toxigenic V. cholerae will be isolated from the water samples following standard culture methods, and characterized locally at icddr,b (Alam et al. 2006b, c) and also, shipped to Wellcome Sanger Institute, UK for whole genome sequencing.

Outcome measures/variables

Through the collaboration this proposal brings together expertise in high throughput genomics and world leading cholera environmental microbiology and public health in three countries. This will enable a much-needed multidisciplinary research programme to understand the emergence of 7PET. Expected outcomes are i) the publication of research findings in International journals ii) deposition of genome scale data sets in databases for future use iii) a comprehensive genomic understanding of how the 7PET lineage emerge from this region to cause outbreaks globally v) data that will inform cholera control strategies through the WHO Global Task Force for cholera control.

Genome sequencing data can reliably be used for source tracking and mode and route of transmission of a pathogen. The 7th pandemic El Tor is transmitted globally, but the sources is believed to be Asia. We designed this study to have a comprehensive genomic view to understand how the 7PET lineage emerges from this region and spread globally; aim is to control cholera.

A comprehensive genomic view will allow us to understand how the 7PET lineage emerges from this region to cause outbreaks globally; and to inform cholera control strategies through the WHO Global Task Force for cholera control.