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Molecular epidemiology of enteroviruses associated with severe hand, foot and mouth disease in Shenzhen, China, 2014-2018

Authors
  • Chen, Long1
  • Xu, Shao-Jian2
  • Yao, Xiang-Jie1
  • Yang, Hong1
  • Zhang, Hai-Long1
  • Meng, Jun1
  • Zeng, Han-Ri3
  • Huang, Xu-He3
  • Zhang, Ren-Li1
  • He, Ya-Qing1
  • 1 Institute of Pathogen Biology, Shenzhen Center for Disease Control and Prevention,
  • 2 District Key Laboratory for Infectious Disease Prevention and Control, Longhua District Center for Disease Control and Prevention, Shenzhen, 518109 China
  • 3 Guangdong Provincial Institution of Public Health, Guangdong Provincial Center for Disease Control and Prevention,
Type
Published Article
Journal
Archives of Virology
Publisher
Springer-Verlag
Publication Date
Jul 14, 2020
Pages
1–15
Identifiers
DOI: 10.1007/s00705-020-04734-z
PMID: 32666145
PMCID: PMC7360124
Source
PubMed Central
License
Unknown

Abstract

In this study, we investigated the epidemiology and molecular characteristics of enteroviruses associated with severe hand, foot and mouth disease (HFMD) in Shenzhen, China, during 2014-2018. A total of 137 fecal specimens from patients with severe HFMD were collected. Enterovirus (EV) types were determined using real-time reverse transcription polymerase chain reaction (RT-PCR), RT nested PCR, and sequencing. Sequences were analyzed using bioinformatics programs. Of 137 specimens tested, 97 (70.8%), 12 (8.8%), and 10 (7.3%) were positive for EV-A71, coxsackievirus A6 (CVA6), and CVA16, respectively. Other pathogens detected included CVA2 (2.9%, 4/137), CVA10 (2.9%, 4/137), CVA5 (0.7%, 1/137), echovirus 6 (E6) (0.7%, 1/137) and E18 (0.7%, 1/137). The most frequent complication in patients with proven EV infections was myoclonic jerk, followed by aseptic encephalitis, tachypnea, and vomiting. The frequencies of vomiting and abnormal eye movements were higher in EV-A71-infected patients than that in CVA6-infected or CVA16-infected patients. Molecular phylogeny based on the complete VP1 gene revealed no association between the subgenotype of the virus and disease severity. Nevertheless, 12 significant mutations that were likely to be associated with virulence or the clinical phenotype were observed in the 5’UTR, 2Apro, 2C, 3A, 3Dpol and 3’UTR of CVA6. Eight significant mutations were observed in the 5’UTR, 2B, 3A, 3Dpol and 3’UTR of CVA16, and 10 significant mutations were observed in the 5’UTR, VP1, 3A and 3Cpro of CVA10. In conclusion, EV-A71 is still the main pathogen causing severe HFMD, although other EV types can also cause severe complications. Potential virulence or phenotype-associated sites were identified in the genomes of CVA6, CVA16, and CVA10. Electronic supplementary material The online version of this article (10.1007/s00705-020-04734-z) contains supplementary material, which is available to authorized users.

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