【摘要】 目的:分析2014-2018年吉林省长春市手足口病流行特征及肠道病毒71型(EV-A71VP1基因特征,探讨其流行规律,为及时调整防控策略提供参考依据。方法:利用中国疾病预防控制信息系统中的数据,采用描述性流行病学方法对2014-2018年吉林省长春市手足口病疫情数据进行分析。收集2014-2018年吉林省长春市医疗机构报告手足口病临床诊断病例咽拭子标本,采用实时荧光定量PCR （RT-qPCR）法检测标本中总肠道病毒、肠道病毒71型（EV-A71）和柯萨奇病毒A组16型（Cox-A16）,确定型别。对EV-A71的VP1区扩增并测序,比对构建系统进化树,分析同源性和氨基酸变异位点。结果:2014-2018年吉林省长春市累计报告手足口病病例12 685例,发病率呈现先降后升趋势,2016年达到高峰,之后呈逐年递降趋势。每年流行趋势基本相同,呈单峰分布,有明显的季节性。吉林省长春市14个县区均有病例报告,年均报告发病率前3位的地区为高新区（129.14/10万）、宽城区（102.17/10万）和经开区（100.98/10万）。病例中,男性比例明显高于女性,以5岁以下儿童为主。吉林省长春市EV-A71阳性样本各月份均有检出。2014年3-9月和2017年5月-2018年5月,手足口病毒型别以EV-A71为主,且呈逐渐上升趋势。测序获得EV-A71序列146条,其中除2017年3条序列和2018年7条序列属于EV-A71的B5亚型外,其余序列均属于C4亚型中的C4a亚型。VP1区145氨基酸位点为E,2018年2株检测到VP1^104D,另外3株检测到VP1^218R,其余各株主要毒理位点和抗原性位点未发生变异,EV-A71的B5亚型较C4亚型有VP1^43E、VP1^58T和VP1¹⁸⁴T3个氨基酸位点差异。结论:吉林省长春市手足口病发病主要发生在5岁以下男性幼童,引发手足口病流行的肠道病毒以EV-A71为主,主要为C4a亚型,也有少部分B5亚型的流行,部分氨基酸变异位点需持续监测,以免造成大范围流行。更多还原

【Abstract】 Objective:To investigate the epidemiological characteristics of hand-foot-mouth disease（HFMD）and the genetic characteristics of VP1 coding gene of enterovirus A71（EV-A71）in Changchun City of Jilin Province during 2014-2018,and to explore its epidemic law and provide reference to adjust measures of disease control and prevention promptly. Methods:Using data from China disease Control and Prevention Information System,the epidemiological data of the hand-foot-mouth disease were analyzed with descriptive epidemiological method. The throat swab speimens of the patients with hand-foot-mouth disease were collected from Changchun medical institutions from 2014 to 2018. Real-time fluorescence quantitative PCR（RT-PCR）was used to detect the total enterovirus,enterovirus 71（EV-A71）and Coxsackieevirus 16（CV-A16） in the speimens to confirm the types. The VP1 regions of EV-A71 were amplificated and sequenced and the phylogenetic tree was constructed. The homology sites and amino acid variation sites were analyzed. Results:From 2014 to 2018,a total of 12 685 cases were reported in Changchun City of Jilin Province with the incidence decreasing first and then increasing,reaching a peak in 2016 and decreasing year by year thereafter. The epidemic trend was basically the same,showing a single peak distribution,with obvious seasonal. The cases were reported in 14 counties and districts of Changchun City,and the top three areas with annual incidence were high-tech zone（129. 14/100 000）,broad urban area（102. 17/100 000） and economic development zone（100. 98/100 000）. The proportion of male cases was significantly higher than that of female cases,and the majority of cases were children under 5 years old. The EV-A71 positive samples were detected every month in Changchun City. During the study period from March to September 2014 and from May 2017 to May 2018,EV-A71 was the main causative agent of handfoot-mouth disease,showing a gradually upward trend. A total of 146 EV-A71 sequences were obtained,136 of the EV-A71 strains samples belonged to C4a subtypes of subgenogroup C4,whereas 10 of the EV-A71 strains samples belonged to subgenogroup B5 of EV-A71. The position 145 amino acids of VP1 region was E;VP1^104D was found in two strains,and VP1^218R was found in the other three strains in 2018;the other toxicological sites and the main antigenicity sites did not change. Compared with the C4 subtype,B5 subtype had three amino acid differences(VP1^43E,VP1^58T and VP1^184T). Conclusion:Hand-foot-mouth disease is a common infectious disease,which in Changchun City of Jilin Province mainly occurs among the children younger than 5 years old. It is mainly caused by C4a subtype of EV-A71,and a small part of B5 subtype is prevalent,some amino acid variant sites need to be continuously monitored to avoid the pandemics.更多还原