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Molecular epidemiology of coxsackievirus A6 associated with outbreaks of hand, foot, and mouth disease in Tianjin, China, in 2013

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Abstract

Since 2008, Mainland China has undergone widespread outbreaks of hand, foot, and mouth disease (HFMD). In order to determine the characteristics of epidemics and enteroviruses (EV) associated with HFMD in Tianjin, in northern China, epidemiological and virological data from routine surveillance were collected and analyzed. In Tianjin, a persistent epidemic of HFMD was demonstrated during 2008-2013, involving 102,705 mild, 179 severe, and 16 fatal cases. Overall, 8234 specimens were collected from 7829 HFMD patients for EV detection during 2008-2013. Enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16) were the dominant serotypes during 2008-2012, and they were replaced by CV-A6 as the major causative agent in 2013. Phylogenetic analysis based on complete VP1 nucleotide sequences revealed that multiple CV-A6 lineages co-circulated in Tianjin, which grouped together with strains from China and other countries and split into two distinct clusters (clusters 1 and 2). Most Tianjin strains grouped in cluster 1 and were closely related to strains from several eastern and southern provinces of China during 2012 and 2013. Estimates from Bayesian MCMC analysis suggested that multiple lineages had been transmitted silently before the outbreaks at an estimated evolutionary rate of 4.10 × 10−3 substitutions per site per year without a specific distribution of rate variances among lineages. The sudden outbreak of CV-A6 in Tianjin during 2013 is attributed to indigenous CV-A6 lineages, which were linked to the wide spread of endemic strains around eastern and southern China.

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Acknowledgements

We appreciate the pediatricians reporting cases to the surveillance system for HFMD in the Tianjin metropolitan area. We thank all the staff members who were responsible for specimen collection and shipment at the CDCs of all districts of Tianjin for their excellent assistance. We also thank Dr. Steve Oberste (CDC, Atlanta) for the revision of this manuscript. This work was supported by grants from the Key Technologies Research and Development Program from the Ministry of Science and Technology (grant numbers: 2013ZX10004-202, 2012ZX10004201-003) and Tianjin Municipal Center for Disease Control and Prevention (Grant number: CDCKY1303).

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    Authors and Affiliations

    1. Key Laboratory of Medical Virology of Ministry of Health, Chinese Center for Disease Control and Prevention, Institute for Viral Disease Control and Prevention, 155 Changbai Road, Beijing, 102206, China

      Xiaojuan Tan, Baomin Zhang, Tianjiao Ji & Wenbo Xu

    2. Tianjin municipal Center for Disease Control and Prevention, 6 Huayue Road, Tianjin, 300171, China

      Li Li, Xu Su, Dongjing Yang, Likun Lv & Jiameng Li

    3. Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA, 30333, USA

      Jaume Jorba

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    Correspondence to Wenbo Xu.

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    X. Tan and L. Li contributed equally to this study.

    The findings and conclusions in this report are those of the author(s) and do not necessarily represent the views of CDC and other contributing agencies.

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    705_2015_2340_MOESM1_ESM.jpg

    Figure S1 ML tree of CV-A6 strains from this study based on partial VP1 nucleotide sequences (376 nucleotides). CV-A6 strains for which the complete VP1 nucleotide sequences were determined are indicated by ● (JPEG 1387 kb)

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    Tan, X., Li, L., Zhang, B. et al. Molecular epidemiology of coxsackievirus A6 associated with outbreaks of hand, foot, and mouth disease in Tianjin, China, in 2013. Arch Virol 160, 1097–1104 (2015). https://doi.org/10.1007/s00705-015-2340-3

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    • DOI: https://doi.org/10.1007/s00705-015-2340-3

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