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Cholera Sequencing Uncovers Multiple Strains Circulating in Bangladesh

NEW YORK (GenomeWeb) – Numerous sublineages of cholera circulate endemically in Dhaka, Bangladesh, according to a new whole-genome sequencing study.

There are an estimated 3 million to 5 million worldwide annual cases of cholera caused by the Vibrio cholerae bacterium, and they lead to between 100,000 and 120,000 deaths, according to UNICEF.

For a new study published today in Nature Genetics, an international team of researchers collected more than 300 cholera isolates from patients in Dhaka between 2002 and 2005 for sequencing analysis. Cholera is endemic to a number of regions of the world, including South Asia, and causes seasonal cases in places like Dhaka. As the team reported, it found that multiple sublineages of the seventh pandemic V. cholerae El Tor (7PET) strain were circulating in the region and traced their most recent common ancestors back 30 years. In addition, the team found that cholera strains infecting members of the same household were highly similar.

"Using genomics, we found that cholera is easily transmitted within the household. Preventing this spread within the household could enormously reduce cholera outbreaks and highlights the need for prioritizing local control strategies," first author Daryl Domman, from the Wellcome Sanger Institute said in a statement. "This could have a huge impact, not only on the individual households, but also on the entire region."

The researchers collected 303 bacterial isolates from 224 patients in 103 households. After sequencing each sample, they compared the isolates' genomes to the V. cholerae O1 El Tor N16961 reference genome to identify SNVs. Through a phylogenetic analysis, they found that there were six 7PET strains circulating in Dhaka, including two serotype O1 Ogawa sublineages, two O1 Inaba sublineages, and two O139 serogroup sublineages.

While one sublineage, B1, was present over the course of the entire study, the prevalence of the others changed over time, which the researchers noted was consistent with surveillance data. They did not find any geographic clustering of the isolates.

When the researchers restricted their analyses to individuals from the same household, they found that bacteria belonging to the same sublineage caused more than three-quarters of those same-household cases. Overall, isolates found in the same household were more similar to each other — differing by a median one SNV — than to isolates from other households.

Additionally, V. cholerae sampled from the same household within six days of each other — bacterial shedding peaks two days after the onset of symptoms — were highly clonal. This strongly suggested to the researchers that these second household infections were due to within-household transmissions of the disease or exposure to a common source.

When the researchers added their Dhaka cholera samples to a phylogenetic tree of cholera samples collected from around the globe between 1957 and 2014, the analysis highlighted a complex history of cholera in South Asia and a network of disease transmission in the region. For instance, in 2005, a strain of cholera appeared in Dhaka that was resistant to streptomycin, tetracycline, and erythromycin, but that that strain had been observed in Kolkata some 10 years prior.

In addition, the researchers found that all the main cholera sublineages circulating in South Asia could trace their most recent common ancestor back to 1989, just after a severe diarrheal epidemic swept Bangladesh in 1987 and 1988. This suggested to the researchers that after that event, several successful sublineages emerged and continue to persist in the region.

The researchers added that their genomic findings could help inform disease control efforts. "Our fine-scale genomic data can help identify which control strategies could have the most impact, and we provide genetic tools to measure the effectiveness of household and local interventions in reducing outbreaks," co-senior author Nick Thomson from the Sanger Institute added.