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Evidence for several waves of global transmission in the seventh cholera pandemic

Abstract

Vibrio cholerae is a globally important pathogen that is endemic in many areas of the world and causes 3–5 million reported cases of cholera every year. Historically, there have been seven acknowledged cholera pandemics; recent outbreaks in Zimbabwe and Haiti are included in the seventh and ongoing pandemic1. Only isolates in serogroup O1 (consisting of two biotypes known as ‘classical’ and ‘El Tor’) and the derivative O139 (refs 2, 3) can cause epidemic cholera2. It is believed that the first six cholera pandemics were caused by the classical biotype, but El Tor has subsequently spread globally and replaced the classical biotype in the current pandemic1. Detailed molecular epidemiological mapping of cholera has been compromised by a reliance on sub-genomic regions such as mobile elements to infer relationships, making El Tor isolates associated with the seventh pandemic seem superficially diverse. To understand the underlying phylogeny of the lineage responsible for the current pandemic, we identified high-resolution markers (single nucleotide polymorphisms; SNPs) in 154 whole-genome sequences of globally and temporally representative V. cholerae isolates. Using this phylogeny, we show here that the seventh pandemic has spread from the Bay of Bengal in at least three independent but overlapping waves with a common ancestor in the 1950s, and identify several transcontinental transmission events. Additionally, we show how the acquisition of the SXT family of antibiotic resistance elements has shaped pandemic spread, and show that this family was first acquired at least ten years before its discovery in V. cholerae.

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Figure 1: A maximum-likelihood phylogenetic tree of the seventh pandemic lineage of V. cholerae based on SNP differences across the whole core genome, excluding probable recombination events.
Figure 2: Transmission events inferred for the seventh-pandemic phylogenetic tree, drawn on a global map.

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Acknowledgements

This work was supported by The Wellcome Trust grant 076964. The IVI is supported by the Governments of Korea, Sweden and Kuwait. D.W.K. was partially supported by grant RTI05-01-01 from the Ministry of Knowledge and Economy (MKE), Korea and by R01-2006-000-10255-0 from the Korea Science and Engineering Foundation; and J.L.N.W. was supported by the Alborada Trust and the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security. Thanks to A. Camilli at Tufts University Medical School for providing the corrected N16961 sequence, to B.M. Nguyen at NIHE, Vietnam and M. Ansaruzzaman at ICDDR, Bangladesh for providing strains, and to M. Fookes at WTSI for training support.

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Authors

Contributions

A.M., D.W.K. and N.R.T. collected the data, analysed it and performed phylogenetic analyses and comparative genomics. J.H.L., S.Y.C., E.J.K. and J.C. analysed the CTX types. S.K., S.K.N. and T.R. were involved in strain collection and serogroup analysis. T.R.C. performed Bayesian analysis; N.J.C. and S.R.H. did the computational coding. J.L.N.W., J.D.C., C.C., G.B.K., J.H., N.R.T., J.P. and G.D. were involved in the study design. A.M., N.R.T., J.P., G.D., J.H., G.B.K., N.J.C., S.R.H., T.R.C., D.W.K. and M.L. contributed to the manuscript writing.

Corresponding author

Correspondence to Julian Parkhill.

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The authors declare no competing financial interests.

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Mutreja, A., Kim, D., Thomson, N. et al. Evidence for several waves of global transmission in the seventh cholera pandemic. Nature 477, 462–465 (2011). https://doi.org/10.1038/nature10392

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