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

Nature volume 477, pages 462–465 (2011)Cite this article

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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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  1. Ankur Mutreja, Dong Wook Kim and Nicholas R. Thomson: These authors contributed equally to this work.

Authors and Affiliations

  1. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK,

    Ankur Mutreja, Nicholas R. Thomson, Thomas R. Connor, Nicholas J. Croucher, Simon R. Harris, Julian Parkhill & Gordon Dougan

  2. International Vaccine Institute, SNU Research Park, Bongchun 7 dong, Kwanak, Seoul 151-919, Korea,

    Dong Wook Kim, Je Hee Lee, Seon Young Choi, Eun Jin Kim, John D. Clemens & Cecil Czerkinsky

  3. Department of Pharmacy, College of Pharmacy, Hanyang University, Kyeonggi-do 426-791, Korea,

    Dong Wook Kim

  4. Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea,

    Je Hee Lee, Seon Young Choi & Jongsik Chun

  5. Centre for Microbiology Research, KEMRI at Kenyatta Hosp Compound, Off Ngong RoadPO Box 43640-00100, Kenya,

    Samuel Kariuki

  6. Department of Microbiology and Immunology and University of Gothenburg Vaccine Research Institute, The Sahlgrenska Academy at the University of Gothenburg, Box 435, 40530 Göteborg, Sweden,

    Michael Lebens & Jan Holmgren

  7. National Institute of Cholera and Enteric Diseases, P-33, CIT Scheme XM, Beliaghata, Kolkata 700 010, India,

    Swapan Kumar Niyogi, T. Ramamurthy & G. Balakrish Nair

  8. Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK,

    James L. N. Wood

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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.

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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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