title: 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 pandemic. Only isolates in serogroup O1 (consisting of two biotypes known as 'classical' and 'El Tor') and the derivative O139 can cause epidemic cholera. 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 pandemic. 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.
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Ankur
authors.initials: A
authors.lastname: Mutreja
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Thomson
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Connor
authors.forename: Je Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Samuel
authors.initials: S
authors.lastname: Kariuki
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Croucher
authors.forename: Seon Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Simon R
authors.initials: SR
authors.lastname: Harris
authors.forename: Michael
authors.initials: M
authors.lastname: Lebens
authors.forename: Swapan Kumar
authors.initials: SK
authors.lastname: Niyogi
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Kim
authors.forename: T
authors.initials: T
authors.lastname: Ramamurthy
authors.forename: Jongsik
authors.initials: J
authors.lastname: Chun
authors.forename: James L N
authors.initials: JL
authors.lastname: Wood
authors.forename: John D
authors.initials: JD
authors.lastname: Clemens
authors.forename: Cecil
authors.initials: C
authors.lastname: Czerkinsky
authors.forename: G Balakrish
authors.initials: GB
authors.lastname: Nair
authors.forename: Jan
authors.initials: J
authors.lastname: Holmgren
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
mesh_terms: D002771:Cholera / Q000453:epidemiology* / Q000382:microbiology / Q000635:transmission*; D016680:Genome, Bacterial / Q000235:genetics; D006205:Haiti / Q000453:epidemiology; D006801:Humans; D016013:Likelihood Functions; D017720:Molecular Epidemiology; D058873:Pandemics / Q000706:statistics & numerical data*; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014734:Vibrio cholerae / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification*; D015030:Zimbabwe / Q000453:epidemiology