浙江省2002-2018年病毒性脑膜炎病原学与分子流行病学特征  

Etiology and molecular-epidemiological characteristics of viral meningo-encephalitis in Zhejiang province,2002-2018

作　　者：缪梓萍[1] 严菊英[1] 孙逸[1] 陈寅[1] 龚黎明[1] 葛琼[1] 史雯[1] 潘军航[1] 茅海燕[1] 张严峻[1] Miao Ziping;Yan Juying;Sun Yi;Chen Yin;Gong Liming;Ge Qiong;Shi Wen;Pan Junhang;Mao Haiyan;Zhang Yanjun(Zhejiang Provincial Center for Disease Control and Prevention,Hangzhou 310051,China)

机构地区：[1]浙江省疾病预防控制中心,杭州310051

出　　处：《中华流行病学杂志》2020年第4期562-566,共5页Chinese Journal of Epidemiology

基　　金：国家科技重大专项(2017ZX10103008-002)。

摘　　要：目的了解2002-2018年浙江省病毒性脑膜炎病原学及分子流行病学特征。方法从设立的监测点医院采集疑似病毒性脑膜炎患者样本2173份,其中脑脊液1718份、粪便455份,用荧光定量PCR方法检测脑脊液中人类肠道病毒(HEV)、腮腺炎病毒(MuV)、单纯疱疹病毒(HSV)、巨细胞病毒(CMV)和乙型脑炎病毒(JEV)核酸,粪便样本只检测HEV;用ELISA方法检测脑脊液中上述5种病毒IgM抗体;对HEV核酸阳性样本扩增病毒VP1基因和测序,确定病毒型别并进行进化分析。结果在2002-2018年2173份样本中检出HEV核酸阳性871份(40.1%),其中脑脊液1718份、阳性654份(38.1%),粪便455份、阳性217份(47.7%);871份HEV核酸阳性样本,VP1扩增测序阳性670份,其中HEV-A 5份、HEV-B 665份,涉及23个病毒血清型,分别为柯萨奇病毒(CV)A组CVA4、CVA6、CVA9、CVA10,CVB组1~5,埃可病毒(EchoV;E)E3、E4、E6、E7、E9、E11、E14、E16、E18、E21、E25、E30、E33和肠道病毒(EV)-71,位于前3位的分别为E30、E6和CVB5,该3个血清型间隔若干年呈现病毒活动性增强的趋势。从2012-2015和2018年795份脑脊液中检出HEV核酸阳性374份、MuV 6份、HSV和CMV均为5份,对其中的368份脑脊液同时检测5种病毒IgM抗体,HEV抗体阳性2份、JEV 6份、MuV 1份。670份HEV中除1份EV-71外,EchoV 517份、CV 152份,两者之比为3.4∶1,两类病毒间隔3~5年存在优势株交替变化的趋势。VP1进化树显示,浙江省HEV位于HEV-A和HEV-B分支上,E30存在h和i基因亚型。结论浙江省病毒性脑膜炎的主要病原为HEV-B;EchoV检出率明显高于CV,两类病毒存在交替变化的趋势;优势血清型E30、CVB5和E6间隔若干年呈现病毒活动性增强的趋势;监测点HEV活动强度与病毒性脑膜炎暴发疫情的发生两者之间在时间上有较好的相关性。Objective To understand the pathogens and molecular-epidemiologic characteristics of viral meningo-encephalitis in Zhejiang province during 2002 to 2018.Methods All the samples were collected from suspected patients admitted to the hospitals under the monitoring program.Of the total samples,2173 were cerebrospinal fluids while the other 455 were stool specimens.Cerebrospinal fluid(CSF)samples were subject to real-time qPCR for the detection of Human enterovirus(HEV),Mumps virus(MuV),Herpes simplex virus(HSV),Cytomegalovirus(CMV)and Japanese encephalitis virus(JEV).Stool sample were subject to real-time qPCR for HEV.ELISA was used to detect the IgM antibodies in CSF,in the 5 kinds of virus mentioned above.VP1 genes from all RNA-positive specimen were amplified,sequenced,for typing and for evolution analysis.Results 871(40.1%)of the 2173 samples were detected as HEV nucleic acid positive during 2002 to 2018.654(38.1%)of the 1718 CSF sample were HEV nucleic acid positive while 217(47.7%)of the 455 stool sample were HEV nucleic acid positive.Among the total positive nucleic acid sample,670 of them were VP1 sequence positive,including 5 HEV-A and 665 HEV-B.There were 23 HEV serotypes,including Coxsackievirus(CV)CVA4,CVA6,CVA9,CVA10,CVB1-5,Echovirus(EchoV;E)E3,E4,E6,E7,E9,E11,E14,E16,E18,E21,E25,E30,E33 and EV-71.The top three serotypes went to E30,E6 and CVB5.These three serotypes presented enhanced viral activity in every several years.795 CSF samples were detected as virus nucleic acid positive,including 374 HEV,6 MuV,5 HSV and 5 CMV,from 2012 to 2015 and in 2018.5 kinds of IgM antibodies were detected simultaneously in 368 CSF samples,including 2 HEV positive,6 JEV positive and 1 MuV positive for 5 viruses,respectively.Except for EV-71,there were 517 EchoV and 152 CV viruses presented,with the ratio of 3.4∶1.These two kinds of viruses alternately changed for each predominant epidemic strains in every 3-5 years.Based on VP1,results from the phylogenetic tree showed that HEV from Zhejiang province clustered into HE

关 键 词：病毒性脑膜炎 肠道病毒 埃可病毒 柯萨奇病毒 

分 类 号：R181[医药卫生—流行病学] R51[医药卫生—公共卫生与预防医学]