吉林地区妇女妊娠晚期及新生儿EB病毒感染状况研究

发布时间：2018-03-30 05:37

本文选题：EB病毒　切入点：先天感染　出处：《北京协和医学院》2014年博士论文

【摘要】：EB (Epstein-Barr)病毒感染与一些肿瘤疾病有密切的病因学关系,如Burkitt淋巴瘤、鼻咽癌等。该病毒在人群中感染极其普遍,感染后可以终身携带病毒抗体标记,迄今无有效的疫苗可以预防。经口唾液传播是目前公认的EB病毒主要传播途径,但EB病毒能否通过宫内、产道或乳汁垂直传播目前仍不明确。在中国的非鼻咽癌高发区——北方地区,对于婴幼儿EB病毒感染的流行病学调查资料十分匮乏。本研究收集吉林当地常住妇女妊娠晚期及其新生儿配对的血样本,并对该样本进行血清抗体、DNA水平的相关测定,掌握吉林地区妊娠晚期妇女及新生儿EB病毒感染状况。通过母婴检测结果对比,寻找EB病毒垂直传播的相关证据。为新生儿EB病毒感染筛查,改善EB病毒感染诊治水平及EB病毒疫苗的研发提供科学依据。研究共收集500对母婴样本,其中,母亲留取血清1.5ml,新生儿针刺足底留取滤纸干血片1张。样本进行酶联免疫吸附试验(ELISA),检测EB病毒抗体VCA-IgG, NA-IgG, EA-IgG, VCA-IgM,统计产妇及新生儿的抗EB病毒抗体阳性率,并据抗体谱分类将母亲区分为急性感染、既往感染和未感染三大类。此外,研究提取新生儿滤纸干血片DNA,采用实时荧光定量PCR方法检测EB病毒DNA拷贝数。对母婴临床资料进行回顾,按胎龄、出生方式、喂养方式等不同层面统计EB病毒的感染状况。运用统计学分析软件SAS9.2进行统计处理,组间比较采用X2检验,P0.05有统计学意义。研究结果显示,500对符合设定要求的母婴研究样本中,产妇有468例(93.6%)样本的抗体谱提示EB病毒感染,急性感染和既往感染分别有109例(21.8%)和359例(71.8%),产妇的EB病毒急性感染率在本地区存在季节差异,秋冬季的急性感染率(27.8%)高于春夏季(11.1%),差异具有统计学意义(P0.05)；新生儿样本中,提示EB病毒既往感染的EBV-CA-IgG抗体及EBNA-IgG抗体分别有466例(93.2%)和392例(78.4%)；提示EB病毒急性感染的EB-EA-IgG抗体及EBV-CA-IgM抗体分别有26例(5.2%)和4例(0.8%)。EB病毒抗体结合EBV-DNA检测结果分析,新生儿EB病毒感染率为0.4%；根据4种抗体的结果,伴随胎龄增加,新生儿VCA-IgG抗体的阳性率呈现缓慢升高的趋势,差异具有统计学意义(P0.05),在38周,VCA-IgG抗体阳性率首次超过90%,达到与成人相当的水平。母婴成对抗体检测结果对比方面,按出生方式区分,自然分娩出生的新生儿四种抗体的阳性率均略高于剖宫产的新生儿,但差异不具有统计学意义(P0.05)；按喂养方式区分,提示既往感染的EB-VCA-IgG抗体阳性率及该抗体母婴阳性匹配率在母乳喂养组中均高于非母乳喂养组,差异均具有统计学意义(P0.05),表明EB病毒存在母乳的垂直传播途径。研究考虑了生产方式及喂养方式对新生儿EB病毒抗体的影响。通过母婴成对结果对比,证明胎盘、乳汁等途径对EB病毒抗体垂直传播均会产生一定影响,进而影响新生儿的EB病毒感染状态。研究结果描绘2013年4月至12月吉林地区产妇及其新生儿EB病毒感染状况。该地区产妇EB病毒的感染率与目前公认的我国正常成年人感染率基本持平；但仍高于西方发达国家。产妇及新生儿EB病毒感染的数据在东北地区是第一次获得,既往无比较先例,可以作为基线数据,供今后研究参考。在500份新生儿研究样本中,EB病毒DNA弱阳性样本2例,占0.4%,低于抗体谱的阳性率。由于实时荧光定量PCR方法检测EB病毒DNA拷贝数仅在病毒活跃复制时才能检测到,在以无症状的病毒携带者为主的正常新生儿中进行筛查,其对病毒感染状态提示意义较为有限,需结合抗体谱及临床信息具体分析。滤纸干血片法检测新生儿EB病毒抗体及DNA,弥补了传统方式的不足,为未来扩大EB病毒感染筛查及开展新生儿EB病毒感染早期诊断提供了借鉴。
[Abstract]:Epstein - Barr virus ( EBV ) infection is closely related to some tumor diseases , such as Burkitt ' s lymphoma , nasopharyngeal carcinoma , etc . The virus is very common in the population and can carry virus antibody label for a lifetime after infection .

A total of 500 pairs of maternal and infant samples were collected from mother to infant . The positive rates of EB virus were detected by ELISA . The positive rates of EB virus were detected by ELISA . The results were analyzed by means of real - time fluorescence quantitative polymerase chain reaction ( RT - PCR ) , and the number of EB virus infection was analyzed by means of real - time fluorescence quantitative PCR .

The results showed that there were 468 cases ( 93.6 % ) of maternal and infant research samples which met the requirements of the setting , and there were 109 cases ( 21 . 8 % ) and 359 cases ( 71.8 % ) respectively . The acute infection rate of EB virus in the pregnant women was higher than that in the spring and summer ( 11.1 % ) , and the difference was statistically significant ( P0.05 ) .
The EBV - CA - IgG antibody and EBNA - IgG antibody of EBV - CA - IgG and EBNA - IgG were detected in 466 cases ( 93.2 % ) and 392 cases ( 78.4 % ) respectively .
The EBV - EA - IgG and EBV - CA - IgM antibodies were detected in 26 ( 5.2 % ) and 4 ( 0.8 % ) of EBV - CA - IgM antibodies , respectively . EBV - DNA detection results showed that the rate of EB virus infection was 0.4 % .
According to the results of four kinds of antibodies , the positive rate of the positive rate of IgG antibody of the newborn was increased slowly with the increase of the gestational age ( P0.05 ) . The positive rate of IgG antibody was over 90 % for the first time in 38 weeks , and reached the level corresponding to the adult .

The positive rates of four kinds of antibodies were slightly higher than those in cesarean section , but the difference was not statistically significant ( P0.05 ) .
The positive rate of Epstein - Barr virus ( EB ) and positive rate of maternal and infant positive rate of EB virus in breast feeding group were higher than that of non - breast feeding group ( P0.05 ) .

The results of the study depict the status of maternal and neonatal EB virus infection in Jilin area from April to December 2013 . The infection rate of maternal EB virus in the region is basically the same as that of the currently recognized normal adult infection rate in China ;
However , it is still higher than that of Western developed countries . The data of EB virus infection in maternal and newborn babies is the first time to be obtained in the north - east region and has no previous comparative precedent , which can be used as baseline data for future research and reference .

The positive rate of EB virus DNA was 0 . 4 % , which was lower than the positive rate of anti - EBV DNA in 500 newborn samples . The detection of EB virus DNA copy number was only detected by real - time fluorescence quantitative PCR .

Filter paper dry blood slice method detects EB virus antibody and DNA of newborn , makes up for the shortage of traditional methods , provides reference for the future expansion of EB virus infection screening and the early diagnosis of neonatal EB virus infection .

【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R714.7

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