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Genome Sequencing Sheds Light on Cholera Lineages Contributing to Outbreaks

NEW YORK (GenomeWeb) – Two new studies published today in Science sequencing the genomes of Vibrio cholerae isolates have highlighted cholera strains that particularly contribute to cholera epidemics, and retrace the origins of V. cholerae strains behind recent outbreaks of the disease in Africa and Latin America.

"We are now getting a real sense of how cholera is moving across the globe, and with that information we can inform improved control strategies as well as basic science to better understand how a simple bacterium continues to pose such a threat to human health," Wellcome Trust Sanger Institute researcher Nicholas Thomson, senior author on both papers, said in a statement.

Both O1 and O139 serogroups can cause cholera, an acute intestinal infection marked by severe diarrhea and dehydration. But one lineage in particular has been implicated in the so-called seventh cholera pandemic: an El Tor biotype falling in the O1 serogroup that is known as the 7P El Tor strain (7PET). The lineage appears to have originated in Indonesia in the early 1960s, contributing to numerous global outbreaks in the decades since.

For one of the new studies, Thomson and his colleagues from the Pasteur Institute, the Sanger Institute, and elsewhere, investigated the dynamics of the seventh pandemic using new and available genome sequences for nearly 1,100 V. cholerae isolates, including hundreds of isolates from the 7PET strain collected in 45 countries in Africa over the course of almost five decades.

Based on their analysis of new and published genome sequences in Africa, the team concluded that 7PET isolates originating in Asia have entered Africa 11 or more different times, often landing in West Africa and East/Southern Africa.

"Our results show that multiple new versions of 7PET bacteria have entered Africa since the 1970s," Pasteur Institute and Sanger Institute researcher Francois-Xavier Weill, corresponding author on that Science study, said in a statement. "Once introduced, cholera outbreaks follow similar paths when spreading across that continent. The results give us a sense of where we can target specific regions of Africa for improved surveillance and control."

In a related study, also appearing in Science, Thomson and Weill led a team that used genome sequencing to assess more than 250 V. cholerae isolates collected in more than a dozen Latin American countries during outbreaks and between-outbreak periods from 1974 to 2014, including 164 7PET and 88 non-7PET isolates.

"Despite advances in our understanding of the global epidemiology of cholera," the authors wrote, "we still face unanswered questions about the relationships between local and global V. cholerae populations."

With the help of a phylogenetic analysis that included hundreds more global V. cholerae isolates, the researchers unraveled the web of V. cholerae lineages that have caused disease in the Americas. Along with a handful of 7PET lineage introductions to the region, for example, they identified seven local lineages that have caused some cholera cases in the Americas without prompting massive outbreaks.

"Our data show that when a 7PET pandemic strain enters into Latin America from elsewhere, it can cause massive epidemics, like those seen in Peru in the 1990s and Haiti in 2010. However, we now know that other strains already in this region can still make people sick, but seem to not have this epidemic potential," that study's first author Daryl Domman, a post-doctoral researcher at the Sanger Institute, said in a statement.

In Yemen, meanwhile, a cholera outbreak that is currently underway has claimed roughly 2,000 lives so far, according to the World Health Organization, with some 600,000 cases suspected between April and September of this year alone.

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