Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 24, Number 4—April 2018
Research

Emerging Coxsackievirus A6 Causing Hand, Foot and Mouth Disease, Vietnam

Nguyen To Anh, Le Nguyen Truc Nhu, Hoang Minh Tu Van, Nguyen Thi Thu Hong, Tran Tan Thanh, Vu Thi Ty Hang, Nguyen Thi Han Ny, Lam Anh Nguyet, Tran Thi Lan Phuong, Le Nguyen Thanh Nhan, Nguyen Thanh Hung, Truong Huu Khanh, Ha Manh Tuan, Ho Lu Viet, Nguyen Tran Nam, Do Chau Viet, Phan Tu Qui, Bridget Wills, Sarawathy Sabanathan, Nguyen Van Vinh Chau, Louise Thwaites, H. Rogier van Doorn, Guy Thwaites, Maia A. Rabaa, and Le Van TanComments to Author 
Author affiliations: Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam (N.T. Anh, L.N.T. Nhu, H.M.T. Van, N.T.T. Hong, T.T. Thanh, V.T.T. Hang, N.T.H. Ny, L.A. Nguyet, B. Wills, S. Sabanathan, L. Thwaites, H.R. van Doorn, G. Thwaites, M.A. Rabaa, L.V. Tan); Hospital for Tropical Diseases, Ho Chi Minh City (T.T.L. Phuong, P.T. Qui, N.V.V. Chau); Children’s Hospital 1, Ho Chi Minh City (L.N.T. Nhan, N.T. Hung, T.H. Khanh); Children’s Hospital 2, Ho Chi Minh City (H.M. Tuan, H.L. Viet, N.T. Nam, D.C. Viet); University of Oxford, Oxford, United Kingdom (L. Thwaites, H.R. van Doorn, G. Thwaites, M.A. Rabaa)

Main Article

Figure 4

Skyline plots depicting the relative genetic diversity of CV-A6 over time. A) Result obtained from the analysis of viral capsid protein 1 sequences of global strains; B) result obtained from the analysis of complete coding sequences of Vietnam strains. Blue shading indicates 95% highest posterior density interval. Arrows in panel A indicate worldwide CV-A6 outbreaks and associated fluctuations in relative genetic diversity ; map (obtained from https://mapchart.net) illustrates the countries in w

Figure 4. Skyline plots depicting the relative genetic diversity of CV-A6 over time. A) Result obtained from the analysis of viral capsid protein 1 sequences of global strains; B) result obtained from the analysis of complete coding sequences of Vietnam strains. Blue shading indicates 95% highest posterior density interval. Arrows in panel A indicate worldwide CV-A6 outbreaks and associated fluctuations in relative genetic diversity ; map (obtained from https://mapchart.net) illustrates the countries in which CV-A6–associated HFMD outbreaks have been recorded to date (3). No sequences from Cuba, Singapore, or the United States fulfilled the selection criteria for the skyline plot and phylogenetic analyses (see Methods section). CV, coxsackievirus.

Main Article

References
  1. Xing  W, Liao  Q, Viboud  C, Zhang  J, Sun  J, Wu  JT, et al. Hand, foot, and mouth disease in China, 2008-12: an epidemiological study. Lancet Infect Dis. 2014;14:30818. DOIPubMedGoogle Scholar
  2. Khanh  TH, Sabanathan  S, Thanh  TT, Thoa  PK, Thuong  TC, Hang  V, et al. Enterovirus 71-associated hand, foot, and mouth disease, Southern Vietnam, 2011. Emerg Infect Dis. 2012;18:20025. DOIPubMedGoogle Scholar
  3. Bian  L, Wang  Y, Yao  X, Mao  Q, Xu  M, Liang  Z. Coxsackievirus A6: a new emerging pathogen causing hand, foot and mouth disease outbreaks worldwide. Expert Rev Anti Infect Ther. 2015;13:106171. DOIPubMedGoogle Scholar
  4. Oberste  MS, Peñaranda  S, Maher  K, Pallansch  MA. Complete genome sequences of all members of the species Human enterovirus A. J Gen Virol. 2004;85:1597607. DOIPubMedGoogle Scholar
  5. Ogi  M, Yano  Y, Chikahira  M, Takai  D, Oshibe  T, Arashiro  T, et al. Characterization of genome sequences and clinical features of coxsackievirus A6 strains collected in Hyogo, Japan in 1999-2013. J Med Virol. 2017;89:1395403. DOIPubMedGoogle Scholar
  6. Puenpa  J, Chieochansin  T, Linsuwanon  P, Korkong  S, Thongkomplew  S, Vichaiwattana  P, et al. Hand, foot, and mouth disease caused by coxsackievirus A6, Thailand, 2012. Emerg Infect Dis. 2013;19:6413. DOIPubMedGoogle Scholar
  7. He  SZ, Chen  MY, Xu  XR, Yan  Q, Niu  JJ, Wu  WH, et al. Epidemics and aetiology of hand, foot and mouth disease in Xiamen, China, from 2008 to 2015. Epidemiol Infect. 2017;145:186574. DOIPubMedGoogle Scholar
  8. Montes  M, Artieda  J, Piñeiro  LD, Gastesi  M, Diez-Nieves  I, Cilla  G. Hand, foot, and mouth disease outbreak and coxsackievirus A6, northern Spain, 2011. Emerg Infect Dis. 2013;19. DOIPubMedGoogle Scholar
  9. Fujimoto  T, Iizuka  S, Enomoto  M, Abe  K, Yamashita  K, Hanaoka  N, et al. Hand, foot, and mouth disease caused by coxsackievirus A6, Japan, 2011. Emerg Infect Dis. 2012;18:3379. DOIPubMedGoogle Scholar
  10. Österback  R, Vuorinen  T, Linna  M, Susi  P, Hyypiä  T, Waris  M. Coxsackievirus A6 and hand, foot, and mouth disease, Finland. Emerg Infect Dis. 2009;15:14858. DOIPubMedGoogle Scholar
  11. Brown  BA, Oberste  MS, Alexander  JP Jr, Kennett  ML, Pallansch  MA. Molecular epidemiology and evolution of enterovirus 71 strains isolated from 1970 to 1998. J Virol. 1999;73:996975.PubMedGoogle Scholar
  12. Lu  J, Zeng  H, Zheng  H, Yi  L, Guo  X, Liu  L, et al. Hand, foot and mouth disease in Guangdong, China, in 2013: new trends in the continuing epidemic. Clin Microbiol Infect. 2014;20:O4425. DOIPubMedGoogle Scholar
  13. Mao  Q, Wang  Y, Bian  L, Xu  M, Liang  Z. EV-A71 vaccine licensure: a first step for multivalent enterovirus vaccine to control HFMD and other severe diseases. Emerg Microbes Infect. 2016;5:e75. DOIPubMedGoogle Scholar
  14. Ku  Z, Liu  Q, Ye  X, Cai  Y, Wang  X, Shi  J, et al. A virus-like particle based bivalent vaccine confers dual protection against enterovirus 71 and coxsackievirus A16 infections in mice. Vaccine. 2014;32:4296303. DOIPubMedGoogle Scholar
  15. Li  J, Liu  G, Liu  X, Yang  J, Chang  J, Zhang  W, et al. Optimization and characterization of candidate strain for Coxsackievirus A16 inactivated vaccine. Viruses. 2015;7:3891909. DOIPubMedGoogle Scholar
  16. Caine  EA, Fuchs  J, Das  SC, Partidos  CD, Osorio  JE. Efficacy of a trivalent hand, foot, and mouth disease vaccine against enterovirus 71 and coxsackieviruses A16 and A6 in mice. Viruses. 2015;7:591932. DOIPubMedGoogle Scholar
  17. Puenpa  J, Vongpunsawad  S, Österback  R, Waris  M, Eriksson  E, Albert  J, et al. Molecular epidemiology and the evolution of human coxsackievirus A6. J Gen Virol. 2016;97:322531. DOIPubMedGoogle Scholar
  18. Mirand  A, le Sage  FV, Pereira  B, Cohen  R, Levy  C, Archimbaud  C, et al. Ambulatory pediatric surveillance of hand, foot and mouth disease as signal of an outbreak of coxsackievirus A6 infections, France, 2014–2015. Emerg Infect Dis. 2016;22:188493. DOIPubMedGoogle Scholar
  19. Tan  X, Li  L, Zhang  B, Jorba  J, Su  X, Ji  T, et al. Molecular epidemiology of coxsackievirus A6 associated with outbreaks of hand, foot, and mouth disease in Tianjin, China, in 2013. Arch Virol. 2015;160:1097104. DOIPubMedGoogle Scholar
  20. Geoghegan  JL, Tan  V, Kühnert  D, Halpin  RA, Lin  X, Simenauer  A, et al. Phylodynamics of enterovirus A71-associated hand, foot, and mouth disease in Viet Nam. J Virol. 2015;89:88719. DOIPubMedGoogle Scholar
  21. Nguyen  AT, Tran  TT, Hoang  VM, Nghiem  NM, Le  NN, Le  TT, et al. Development and evaluation of a non-ribosomal random PCR and next-generation sequencing based assay for detection and sequencing of hand, foot and mouth disease pathogens. Virol J. 2016;13:125. DOIPubMedGoogle Scholar
  22. Edgar  RC. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 2004;32:17927. DOIPubMedGoogle Scholar
  23. Nguyen  LT, Schmidt  HA, von Haeseler  A, Minh  BQ. IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Mol Biol Evol. 2015;32:26874. DOIPubMedGoogle Scholar
  24. Lanave  C, Preparata  G, Saccone  C, Serio  G. A new method for calculating evolutionary substitution rates. J Mol Evol. 1984;20:8693. DOIPubMedGoogle Scholar
  25. Tamura  K, Nei  M. Estimation of the number of nucleotide substitutions in the control region of mitochondrial DNA in humans and chimpanzees. Mol Biol Evol. 1993;10:51226.PubMedGoogle Scholar
  26. Yang  F, Yuan  J, Wang  X, Li  J, Du  J, Su  H, et al. Severe hand, foot, and mouth disease and coxsackievirus A6-Shenzhen, China. Clin Infect Dis. 2014;59:15045. DOIPubMedGoogle Scholar
  27. Tee  KK, Lam  TT, Chan  YF, Bible  JM, Kamarulzaman  A, Tong  CY, et al. Evolutionary genetics of human enterovirus 71: origin, population dynamics, natural selection, and seasonal periodicity of the VP1 gene. J Virol. 2010;84:333950. DOIPubMedGoogle Scholar
  28. Chang  LY, Tsao  KC, Hsia  SH, Shih  SR, Huang  CG, Chan  WK, et al. Transmission and clinical features of enterovirus 71 infections in household contacts in Taiwan. JAMA. 2004;291:2227. DOIPubMedGoogle Scholar
  29. Xu  L, Zheng  Q, Li  S, He  M, Wu  Y, Li  Y, et al. Atomic structures of Coxsackievirus A6 and its complex with a neutralizing antibody. Nat Commun. 2017;8:505. DOIPubMedGoogle Scholar

Main Article

Page created: March 16, 2018
Page updated: March 16, 2018
Page reviewed: March 16, 2018
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external