我国婴幼儿人群中6种肠道病毒血清流行病学研究

Seroepidemiology of six enteroviruses among infants and children in China

目的了解引起手足口病(hand,foot and mouth disease,HFMD)的主要6种人类肠道病毒(enteroviru,EV)在我国婴幼儿人群中的流行情况,分析相同血清型EV重复感染以及不同血清型EV的感染特点,为HFMD多价疫苗的研发提供依据.方法采用前瞻性队列研究的方法,对江苏省某地EV-A71疫苗Ⅲ期临床试验的181名6~35月龄婴幼儿在2012-2014年进行为期2年的随访.随访期间对受试者采集4次血清,采用微量细胞病变法检测血清中的肠道病毒A组71型(EV-A71)、柯萨奇病毒A组6型(CV-A6)、柯萨奇病毒A组10型(CV-A10)、柯萨奇病毒A组16型(CV-A16)、柯萨奇病毒B组3型(CV-B3)和柯萨奇病毒B组5型(CV-B5)中和抗体效价.对随访期间的HFMD发病病例采集咽拭子和肛拭子,采用实时定量PCR法和巢式PCR法鉴别EV.结果在随访结束时,CV-A10的血清累积阳性率和中和抗体GMT最高(82.2%,120.4).随访期间共有81人发生125次相同血清型EV的重复感染(中和抗体阳性者的中和抗体4倍及以上增高),其中CV-A10的重复感染率最高(27.8%,50/180).虽然相同血清型EV可重复感染,但未见同种病原感染后的再次发病;68.5%(124/181)的受试者至少感染了两种EV,2.2%(4/181)的受试者感染了5种EV.共发现25例HFMD发病病例(7例EV-A71,14例CV-A16,CV-A6、CV-A10、CV-B3和CV-B5各1例),患者均为轻症,未见重症病例.结论该地区婴幼儿人群中EV流行强度高,EV具有一定的相同血清型及不同血清型的重复感染率,值得进一步研究.

Objective To understand the epidemics of human enterovirus (EV) among infants and children in China,analyze the infection characteristics of the same and different serotypes of EV and provide argument for the necessity of multivalent hand,foot and mouth disease (HFMD) vaccine development.Methods A pro-spective cohort study of 181healthy participants aged from 6to 35months was conducted from January,2012 to January,2014in Jiangsu province of China.Cytopathogenic effect (CPE) method was used to detect EV-A71,CV-A6,CV-A10,CV-A16,CV-B3and CV-B5neutralizing antibodies (NTAbs) in the serum collected from all four scheduled visits during the two years follow-up.The throat or rectal swabs from the HFMD cases were taken for pathogen detection by using real-time PCR and nested RT-PCR.Results CV-A10was found to be the predominant pathogen with the highest seropositivity rates (82.2%) and GMT (120.4) at the end of the studies.During the two years followed-up,125cases out of 81participants were re-infected by the same serotype of EV (NTAb titer from the positive participant increased by at least four-fold); of which,the high-est was CV-A10 (27.8%) .Although the re-infection could be caused by the same serotype of EV,no recurrent HFMD cases were observed.In addition,68.5%of participants were infected by at least two serotypes of EV,2.2% by five serotypes of EV.A total of 25cases of HFMD were found,including 7cases of EV-A71,14 cases of CV-A16,and 1case of CV-A6,CV-A10,CV-B3and CV-B5,respectively.The symptoms were mild,and no severe complications were recorded.Conclusions EV infections were very common in China.The high re-infection rate of the same serotype and the different serotypes of the major HFMD-related EV in Chi-nese children should be further investigated.