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

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Abstract
Cholera has affected human populations for centuries, and the agent responsible, Vibrio cholerae, continues to infect millions each year. Using whole genome phylogeny, it is now shown that the current seventh epidemic originated in the Bay of Bengal in the 1950s and has spread through the world in three independent waves. 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.