EV-A71灭活疫苗上市后福建省手足口病流行病学特征及EV-A71基因特征研究

Epidemiological Characteristics of Hand,Foot,and Mouth Disease and Genotype Characteristics of EV-A71 in Fujian Province(China)After Marketing of the EV-A71 Inactivated Vaccine

手足口病(Hand,foot and mouth disease,HFMD)是以手、足、口腔等部位的皮疹或疱疹为主要症状的传染性疾病,肠道病毒A71型(Enterovirus A71,EV-A71)及柯萨奇病毒16型(Coxsakievirus A16,CVA16)是其最主要的致病病原,为了了解在EV-A71疫苗上市之后,福建省HFMD流行情况及EV-A71基因型特征的变化情况,利用HFMD监测系统对福建省2016-2020年的HFMD发病数据及EV-A71感染所致HFMD数据进行统计学分析。对上送的EV-A71阳性样本进行细胞分离,将所获毒株的VP1区核苷酸序列进行扩增测序,分析其与疫苗株间的核苷酸及氨基酸差异性,并构建系统进化树。结果显示,2016-2020福建省HFMD年发病率分别为228.81/10万、227.25/10万、243.57/10万、130.10/10万、67.62/10万。发病人群以散居儿童为主,各年度所占比例分别为80.74%、78.23%、77.05%、73.76%、64.40%。福建省HFMD年平均发病率为179.47/10万,龙岩地区发病率最高为281.21/10万,莆田地区发病率最低为87.63/10万。除2020年外,福建省HFMD发病在每年的5~7月份及9~10月份出现两次流行高峰。各个年度HFMD原构成中,其它肠道病毒占比均超过50%。HFMD人群中,EV-A71感染率居于全省前三位的是南平市4.98/10万、龙岩市2.66/10万、莆田市1.68/10万;HFMD实验室确诊病例中,EVA71感染人群比例居于前三的是莆田市50.60%,南平市27.02%,福州市26.04%。EV-A71处于C4a分支上,与疫苗株相比,VP1区的平均核苷酸百分比差异逐年增大,氨基酸差异主要在283位及293位上。本次研究表明,福建省HFMD发病率和重症率呈下降趋势。其它肠道病毒已成为流行的优势血清型,但在上半年第一次流行高峰时期,仍存在EV-A71或CVA16暴发流行的风险。福建省EV-A71毒株属于C4a基因亚型,有随时间进化的趋势。VP1区重要氨基酸位点相较疫苗株未发生改变,为疫苗的有效性及应用提供了参考。

Hand,foot and mouth disease(HFMD)is an infectious disease characterized by skin rashes and herpes on hands,feet and mouth.Enterovirus A71(EV-A71)and Coxsakievirus A16(CVA16)are the main pathogenic agents.In order to get the prevalence of HFMD and the changes of EV-A71 genotype characteristics in Fujian province(China)after the launch of EV-A71 vaccine,the incidence data of HFMD and HFMD caused by EV-A71 infection in Fujian Province from 2016 to 2020 were analyzed statistically through a surveillance system for HFMD.We isolated EV-A71-positive samples and sequenced the nucleotides of the VP1 region.The differences in nucleotides and amino acids between the virus strains and vaccine strains were analyzed,and then a phylogenetic tree was constructed.Results showed that HFMD incidence(per 100,000individuals)in Fujian Province in 2016,2017,2018,2019,and 2020 was 228.81,227.25,243.57,130.10,and 67.62,respectively.Most of the patients were children,and the proportion in each year was 80.74%,78.23%,77.05%,73.76,and 64.40%,respectively.The average annual incidence of HFMD in Fujian Province was 179.47 per 100,000,the highest was in Longyan Province(281.21 per 100,000),and the lowest was in Putian Province(87.63 per 100,000).HFMD incidence in Fujian Province was revealed in two epidemic peaks:May to July and September to October.Other EVs accounted for>50%of the pathogenic components of HFMD in each year.Among HFMD populations,the top-three regions for EV-A71 infection were Nanping(4.98 per 100,000),Longyan(2.66 per 100,000),and Putian(1.68 per 100,000).The top-three regions for EV-A71 proportion were Putian(50.60%),Nanping(27.02%),and Fuzhou(26.04%).EV-A71 isolates were on the branch of C4a genotype.Compared with the vaccine strain,the mean percentage difference in nucleotides of the VP1 region increased year-by-year,and the difference in amino acids was mainly at the sites of 283 and 293.Above results indicated the incidence and severity of HFMD in Fujian Province decreased from2016 to 2020.Other EVs have emerged as dominant serotypes,but there remains a risk of EV-A71 or CVA16outbreaks during the first half of the year,especially from May to July.The EV-A71 strain in Fujian Province belonged to the C4a genotype.There are likely two chains of transmission,and a tendency of evolution over time.Compared with the vaccine strain,the important amino-acid sites in the VP1 region did not change,which provides a reference for study of the efficacy and application of the vaccine.