冀天娇;居昱;程文隽;陈敏玫;张勇;肖金波;张珂艺;刘宏图;许文波;

• 1:国家脊髓灰质炎实验室世界卫生组织西太平洋区脊髓灰质炎参比实验室国家卫生健康委员会医学病毒和病毒病重点实验室中国疾病预防控制中心病毒病预防控制所
• 2:广西重大传染病防控与生物安全应急响应重点实验室广西壮族自治区疾病预防控制中心
• 3:国家病毒相关肿瘤室国家卫生健康委员会医学病毒和病毒病重点实验室中国疾病预防控制中心病毒病预防控制所

摘要(Abstract)：

手足口病（Hand,foot and mouth disease,HFMD）是一种由肠道病毒引起的儿童常见传染病，近年来在亚太地区尤其是东南亚地区发生了多起HFMD的大暴发，而我国广西壮族自治区与越南接壤，往来密切。为了解其边境地区HFMD的流行概况和病原学构成，比较该地区病原优势基因型与相邻地区的变异与进化关系。本研究选取与越南接壤的百色、崇左、防城港作为研究对象，收集其2018-2020年HFMD疫情资料进行流行病学分析，并随机采集这三个地市的375份手足口病患儿的临床标本进行荧光定量PCR鉴定，对阳性毒株进行VP1编码区基因扩增及测定，获得的序列与GenBank上下载的各基因型/亚型的代表序列构建系统发生树。结果显示2018-2020年，广西边境地区的报告发病数、重症数、重症比例（重症/发病）和重症率均呈下降趋势，5岁以下儿童为主要发病人群，除2020年以外，其发病流行曲线呈典型的双峰分布。病原谱分析显示，整体上以其他EV为优势循环血清型，且CVA6、CVA16、CVA10和EVA71为该地区的优势病原。同时，2018-2020年期间广西边境流行的EVA71、CVA16、CVA6和CVA10的优势基因亚型分别为C4a、B1b、D3a和C2，且与东南亚临近国家同基因型的流行株具有较近的亲缘关系，提示病毒共同循环进化。而边境地区环境复杂、人员往来密切，因此加强边境地区手足口病的监测及预警系统的建设是西南边境地区手足口病防控的关键。

关键词(KeyWords)： 手足口病;边境地区;流行特征;病原学特点

Abstract:

Keywords:

基金项目(Foundation): “十三五”科技重大专项（项目号：2018ZX10101002-004-006），题目：“一带一路”重要传染病流行规律和预警应对技术研究-东南亚地区手足口防控技术推广应用;“十三五”科技重大专项（项目号：2018ZX10201002-003-003），题目：手足口病流行特征及变异变迁规律的研究~~

作者(Authors): 冀天娇;居昱;程文隽;陈敏玫;张勇;肖金波;张珂艺;刘宏图;许文波;

DOI: 10.13242/j.cnki.bingduxuebao.004109

参考文献(References)：

• [1] W. Xing,Q. Liao,C. Viboud,J. Zhang,J. Sun,J. T.Wu,Z. Chang,F. Liu,V. J. Fang,Y. Zheng,B. J.Cowling,J. K. Varma,J. J. Farrar,G. M. Leung&H.Yu. Hand,foot,and mouth disease in China,2008-12:an epidemiological study[J]. Lancet Infect Dis,2014,14(4):308-318.
• [2] X. W. Li,X. Ni,S. Y. Qian,Q. Wang,R. M. Jiang,W. B. Xu,Y. C. Zhang,G. J. Yu,Q. Chen,Y. X.Shang,C. S. Zhao,H. Yu,T. Zhang,G. Liu,H. L.Deng,J. Gao,X. G. Ran,Q. Z. Yang,B. L. Xu,X.Y. Huang,X. D. Wu,Y. X. Bao,Y. P. Chen,Z. H.Chen,Q. Q. Liu,G. P. Lu,C. F. Liu,R. B. Wang,G. L. Zhang,F. Gu,H. M. Xu,Y. Li&T. Yang.Chinese guidelines for the diagnosis and treatment of hand,foot and mouth disease(2018 edition)[J]. World J Pediatr,2018,14(5):437-447.
• [3] Wee Ming Koh,Tiffany Bogich,Karen Siegel,Jing Jin,Elizabeth Y. Chong,Chong Yew Tan,Mark IC Chen,Peter Horby&Alex R. Cook. The epidemiology of hand,foot and mouth disease in asia:a systematic review and analysis[J/OL]. The Pediatric Infect Dis J,2016,35(10):e285-e300.
• [4] T. H. Khanh,S. Sabanathan,T. T. Thanh,Le PK Thoa,T. C. Thuong,Vt Hang,J. Farrar,T. T. Hien,Nv Chau&H. R. van Doorn. Enterovirus 71-associated hand, foot, and mouth disease, Southern Vietnam,2011[J]. Emerg Infect Dis,2012,18(12):2002-2005.
• [5] K. B. Chua&A. R. Kasri. Hand foot and mouth disease due to enterovirus 71 in Malaysia[J]. Virol Sin,2011,26(4):221-228.
• [6] Y. Wu,A. Yeo,M. C. Phoon,E. L. Tan,C. L. Poh,S. H. Quak&V. T. Chow. The largest outbreak of hand;foot and mouth disease in Singapore in 2008:the role of enterovirus 71 and coxsackievirus A strains[J/OL]. Int J Infect Dis,2010,14(12):e1076-1081.
• [7] Y. Zhang,Z. Zhu,W. Yang,J. Ren,X. Tan,Y.Wang,N. Mao,S. Xu,S. Zhu,A. Cui,Y. Zhang,D.Yan,Q. Li,X. Dong,J. Zhang,Y. Zhao,J. Wan,Z.Feng,J. Sun,S. Wang,D. Li&W. Xu. An emerging recombinant human enterovirus 71 responsible for the2008 outbreak of hand foot and mouth disease in Fuyang city of China[J]. Virol J,2010,7:94.
• [8] J. F. Chen,R. S. Zhang,X. H. Ou,F. M. Chen&B.C. Sun. The role of enterovirus 71 and coxsackievirus A strains in a large outbreak of hand,foot,and mouth disease in 2012 in Changsha,China[J]. Int J Infect Dis,2014,28:17-25.
• [9] Y. Song,Y. Zhang,T. Ji,X. Gu,Q. Yang,S. Zhu,W. Xu,Y. Xu,Y. Shi,X. Huang,Q. Li,H. Deng,X.Wang,D. Yan,W. Yu,S. Wang,D. Yu&W. Xu.Persistent circulation of Coxsackievirus A6 of genotype D3 in mainland of China between 2008 and 2015[J]. Sci Rep,2017,7(1):5491.
• [10]阳益萍，陈敏玫，居昱，王晶，黄君，谭毅.2008-2014年广西手足口病流行病学及病原分布特征[J].应用预防医学，2015,21(06):365-368+372.
• [11]董蓬玉，徐鹏，刘晓强，刘宏，何国忠.我国西南边境地区重点传染病的流行和防控现状[J].医学与社会，2017,30(02):45-48.
• [12]A. Cui,C. Xu,X. Tan,Y. Zhang,Z. Zhu,N. Mao,Y. Lu&W. Xu. The development and application of the two real-time RT-PCR assays to detect the pathogen of HFMD[J/OL]. PLoS One,2013,8(4):e61451.
• [13]P. He,Y. Li,J. Luo,H. Wang,Y. Yan&Z. Chen.Development and application of a duplex real-time rt-pcr assay for simultaneous detection of coxsackievirus a6 and coxsackievirus A10[J]. Ann Clin Lab Sci,2017,47(2):178-183.
• [14]M. S. Oberste,K. Maher,A. J. Williams,N. DybdahlSissoko,B. A. Brown,M. S. Gookin,S. Penaranda,N. Mishrik, M. Uddin&M. A. Pallansch. Speciesspecific RT-PCR amplification of human enteroviruses:a tool for rapid species identification of uncharacterized enteroviruses[J]. J Gen Virol,2006,87(Pt 1):119-128.
• [15]Te Deng,Yong Huang,Shicheng Yu,Jing Gu,Cunrui Huang, Gexin Xiao, Yuantao Hao&Cécile Viboud.Spatial-temporal clusters and risk factors of hand,foot,and mouth disease at the district level in Guangdong Province,China[J/OL]. PLoS One,2013,8(2):e56943-e56943.
• [16]刘洋，李刚，高燕琳，史芸萍，王超，谢春艳，虎霄.北京市手足口病流行特征分析及气象因素对其发病的影响[J].公共卫生与预防医学，2021,32(04):12-17.
• [17]Q. Gao,Z. Liu,J. Xiang,M. Tong,Y. Zhang,S.Wang,Y. Zhang,L. Lu,B. Jiang&P. Bi. Forecast and early warning of hand,foot,and mouth disease based on meteorological factors:Evidence from a multicity study of 11 meteorological geographical divisions in mainland China[J]. Environ Res,2021,192:110301.
• [18]S. Lai,N. W. Ruktanonchai,L. Zhou,O. Prosper,W.Luo,J. R. Floyd,A. Wesolowski,M. Santillana,C.Zhang,Du X,H. Yu&A. J. Tatem. Effect of nonpharmaceutical interventions to contain COVID-19 in China[J]. Nature,2020,585(7825):410-413.
• [19]曾汉日，郑焕英，刘冷，陈晓丽，李彩霞，方苓，吴诗微，李晖，柯昌文.2010-2016年广东省手足口病非EV71非CVA16肠道病毒病原谱分析[J].国际病毒学杂志，2018,25(06):374-378.
• [20]张曼，陈淑红，张勇，宋洋，许军，孙巍，杨明，韩振志，肖金波，路环环，许文波，刘志军，杨倩.2015~2018年柯萨奇病毒A组6型在黑龙江省的持续流行[J/OL].病毒学报，2020,36(02):201-206.DOI:10.13242/j.cnki.bingduxuebao.003665.
• [21]Tianjiao Ji,Taoli Han,Xiaojuan Tan,Shuangli Zhu,Dongmei Yan,Qian Yang,Yang Song,Aili Cui,Yan Zhang,Naiying Mao,Songtao Xu,Zhen Zhu,Dandan Niu, Yong Zhang&Wenbo Xu. Surveillance,epidemiology,and pathogen spectrum of hand,foot,and mouth disease in mainland of China from 2008 to2017[J]. Biosafety and Health,2019,1(1):32-40.
• [22]黄克强，张勇，许文波.全球EV-A71的基因型分布[J/OL].病毒学报，2017,33(03):469-476.DOI:10.13242/j.cnki.bingduxuebao.003168.
• [23]LNT Nhan,T. H. Khanh,NTT Hong,Van HMT,LNT Nhu,NTH Ny,L. A. Nguyet,T. T. Thanh,N.T. Anh,VTT Hang,P. T. Qui,H. L. Viet,T. H.Tung,D. Q. Ha,H. M. Tuan,G. Thwaites,NVV Chau,L. Thwaites,N. T. Hung,H. R. van Doorn&L.V. Tan. Clinical, etiological and epidemiological investigations of hand, foot and mouth disease in southern Vietnam during 2015-2018[J/OL]. PLoS Negl Trop Dis,2020,14(8):e0008544.
• [24]T. Ji,Y. Guo,W. Huang,Y. Shi,Y. Xu,W. Tong,W. Yao,Z. Tan,H. Zeng,J. Ma,H. Zhao,T. Han,Y. Zhang,D. Yan,Q. Yang,S. Zhu,Y. Zhang&W.Xu. The emerging sub-genotype C2 of CoxsackievirusA10 Associated with Hand, Foot and Mouth Disease extensively circulating in mainland of China[J]. Sci Rep,2018,8(1):13357.