Changing Molecular Epidemiology of Vibrio cholerae Outbreaks in Shanghai, China

Abstract

V. cholerae is the causative agent of cholera, a life-threatening disease characterized by severe, watery diarrhea. The 7th pandemic started in Indonesia in 1961 and spread globally, currently infecting 1.3 million to 4 million people annually. Here, we applied whole-genome sequencing to analyze a long-term collection of V. cholerae clinical strains to reveal the phylogenetic background and evolutionary dynamics of the 7th pandemic in Shanghai, which had undergone breathtakingly rapid development in the last half-century. All but one of the Shanghai 7th-pandemic strains fell into five “stages” that were dominant in Shanghai and appeared to be closely related to 7th-pandemic strains of South or Southeast Asia. Our findings extended the understanding of the dynamics of the evolution and transmission of the 7th-pandemic clones in East Asia and the relationship between social changes and cholera epidemiology. The 7th cholera pandemic began in 1961 in Sulawesi, Indonesia, and then spread around the world in at least three waves. However, the lack of genome sequences for Vibrio cholerae strains under long-term surveillance in East Asia, especially in China, has restricted our understanding of the dynamics of the intracountry and intercountry evolution and transmission of the 7th-pandemic clones. In this study, we obtained the genome sequences of 60 V. cholerae strains isolated in Shanghai, the largest port in the world and the largest city in China, from 1961 to 2011. Our whole-genome-based phylogeny of 7th-pandemic strains revealed that all but one fell into five “stages,” most of which are single clades and share independent ancestors. Each stage dominated in succession for a period, with little overlap between them. In addition, two near-identical Shanghai strains belonging to a pre-7th-pandemic precursor and 4 nontoxigenic O1/O139 strains attributed to independent recombination events at the O-antigen loci were present. The major lineages of the 7th pandemic in Shanghai appeared to be closely related to V. cholerae strains isolated from South or Southeast Asia. Stage succession was consistently related to changes in society and human activity, implying that human-caused niche change may play a vital role in the cholera dynamics in Shanghai. IMPORTANCE V. cholerae is the causative agent of cholera, a life-threatening disease characterized by severe, watery diarrhea. The 7th pandemic started in Indonesia in 1961 and spread globally, currently infecting 1.3 million to 4 million people annually. Here, we applied whole-genome sequencing to analyze a long-term collection of V. cholerae clinical strains to reveal the phylogenetic background and evolutionary dynamics of the 7th pandemic in Shanghai, which had undergone breathtakingly rapid development in the last half-century. All but one of the Shanghai 7th-pandemic strains fell into five “stages” that were dominant in Shanghai and appeared to be closely related to 7th-pandemic strains of South or Southeast Asia. Our findings extended the understanding of the dynamics of the evolution and transmission of the 7th-pandemic clones in East Asia and the relationship between social changes and cholera epidemiology.