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

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Vibrio cholerae is a globally important pathogen that is endemic in many areas of the world and causes 3–5million 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.

At a glance


  1. A maximum-likelihood phylogenetic tree of the seventh pandemic lineage of V.[thinsp]cholerae based on SNP differences across the whole core genome, excluding probable recombination events.
    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.

    The pre-seventh-pandemic isolate M66 was used as an outgroup to root the tree. Branches are coloured on the basis of the region of isolation of the strains. The branches representing the three major waves are indicated on the far right. The nodes representing the MRCAs of the seventh pandemic, and subsequent waves 2 and 3, are indicated with arrows and labelled with inferred dates. The presence and type of CTX and SXT elements in each strain are shown to the right of the tree. The presence of toxin-linked cryptic (TLC) and repeated sequence 1 (RS1) elements is shown, but their number and position, respectively, are arbitrarily assigned. Cases of sporadic intercontinental transmission are marked A–D. The dates shown are the median estimates for the indicated nodes, taken from the results of the BEAST analysis. The scale is given as the number of substitutions per variable site; asterisks indicate that no data were available.

  2. Transmission events inferred for the seventh-pandemic phylogenetic tree, drawn on a global map.
    Figure 2: Transmission events inferred for the seventh-pandemic phylogenetic tree, drawn on a global map.

    The date ranges shown for transmission events are taken from the BEAST analysis, and represent the median values for the MRCA of the transmitted strains (later bound), and the MRCA of the transmitted strains and their closest relative from the source location (earlier bound).


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Author information

  1. These authors contributed equally to this work.

    • Ankur Mutreja,
    • Dong Wook Kim &
    • Nicholas R. Thomson


  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, 1Gwanak-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. University of Cambridge, Department of Veterinary Medicine, Madingley Road, Cambridge CB3 0ES, UK

    • James L. N. Wood


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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