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Prevalence of Coxsackievirus A6 and Enterovirus 71 in Hand, Foot and Mouth Disease in Nanjing, China in 2013

Hu, Ya-Qian MS*†; Xie, Guang-Cheng MS; Li, Dan-Di PhD; Pang, Li-Li PhD; Xie, Jing MS; Wang, Peng MS*; Chen, Ying MS*; Yang, Jing MS*; Cheng, Wei-Xia PhD*; Zhang, Qing MS; Jin, Yu MD*; Duan, Zhao-Jun PhD

The Pediatric Infectious Disease Journal: September 2015 - Volume 34 - Issue 9 - p 951–957
doi: 10.1097/INF.0000000000000794
Original Studies

Background: Although hand, foot and mouth disease (HFMD) has been strongly associated with enterovirus 71 (EV71), coxsackievirus A16 (CVA16) and other enteroviruses, studies regarding coxsackievirus A6 (CVA6) infection in HFMD are limited. The aim of this study was to identify the major etiological agents causing HFMD in Nanjing in 2013 and explore the clinical and genetic characteristics of the prevalent enterovirus (EV) types in HFMD.

Methods: A total of 394 throat swabs were collected from hospitalized children diagnosed with HFMD from April to July 2013. EVs were detected by reverse transcription polymerase chain reaction of 5′ UTR sequences. Genotyping and phylogenetic analysis were based on VP4 sequences. Demographic and clinical data were obtained.

Results: Of the specimens, 68.5% (270/394) were positive for EVs. The genotypes and detection rates were CVA6, 30.00% (81/270); EV71, 17.41% (47/270); HRV, 11.11% (30/270); CVA10, 3.33% (9/270); CVA2, 1.11% (3/270); CVA16, 0.74% (2/270); EV68, 0.37% (1/270); echovirus 6, 0.37% (1/270); echovirus 9, 0.37% (1/270), respectively. Patients infected with CVA6 displayed symptoms atypical of HFMD, including larger vesicles on their limbs and buttocks. Phylogenetic analysis revealed 2 genetically distinct CVA6 strains that circulated independently within the region. Patients infected with CVA6 were more likely to have abnormal periphery blood white blood cell and C-reactive protein levels, while EV71 was more likely to infect the central nervous system, as indicated by clinical manifestations and white blood cell analysis of cerebrospinal fluid.

Conclusions: Multiple EV genotypes contributed to HFMD in Nanjing in 2013, and CVA6 was the dominant genotype. The clinical presentation of CVA6 infection differs from that of EV71 infection in HFMD.

Supplemental Digital Content is available in the text.

From the *Nanjing Children’s Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; and National Institute for Viral Disease Control and Prevention, Chinese Center for Viral Disease Control and Prevention, Beijing, People’s Republic of China.

Accepted for publication June 1, 2015.

Supported by a China Mega-Project for Infectious Disease (2013ZX10004-101) and the Prevention and Control of Novel Influenza Virus (2014ZX10004002) funded by the Ministry of Science and Technology of the People’s Republic of China and the Natural Science Foundation of Jiangsu Province (BK20141078).

Ya-Qian Hu and Guang-Cheng Xie contributed equally to the article.

The authors have no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (

Address for correspondence: Zhao-Jun Duan, PhD, National Institute for Viral Disease Control and Prevention, Chinese Center for Viral Disease Control and Prevention, 155 Changbai Rd, Changping District, Beijing, People’s Republic of China. or Yu Jin, PhD, Nanjing Children’s Hospital, Nanjing Medical University, 72 Guangzhou Rd, Nanjing, People’s Republic of China.

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