河北某村HCV感染横断面调查及分子流行病学研究

发布时间：2018-04-27 21:16

本文选题：丙型肝炎病毒 + 危险因素　；参考：《中国疾病预防控制中心》2017年硕士论文

【摘要】：丙型肝炎病毒(HCV)是一种严重危害人类健康的病原体,可通过血液及血制品、静脉注射及母婴垂直等途径传播。HCV感染可导致慢性肝炎、肝硬化甚至肝癌,已对人类健康造成严重危害。目前全球HCV流行率约为2.5%,且地区间流行率差异显著。HCV分为6个基因型,100多个亚型,不同亚型HCV常依赖特定的途径传播,这也导致了不同地区、不同人群中HCV流行株基因型存在差异。中国HCV流行现状并不乐观。由于资料有限,对于中国一般人群中HCV流行率的报道并不准确,有报道的中国一般人群中HCV流行率介于0.39%-2.5%。中国丙型肝炎病毒流行株主要有1、2、3、6型,而其中又以1b亚型为主。在北方地区2a型HCV是仅次于1b型HCV最常见的流行株,而在南方部分省份尤其是长江三角洲地区和珠江三角洲地区,6a亚型已经取代2a亚型成为第二常见的HCV流行株,且新发6a型HCV感染呈上升趋势。本研究的研究对象为河北某村。此村为我实验室丙肝研究现场,我们最早于1994对该村所有人群进行了一次横断面调查,之后又分别于2005年和2014年对该村村民进行过血清学调查。对该村HCV患者长期动态的观察对于HCV自然史的研究具有重要意义。本研究的目的是了解河北某村HCV感染情况,探寻该村HCV传播的原因,推断该村村民HCV感染的危险因素,为HCV的防控及HCV感染者的管理提供基础资料。本研究总共分为两部分。第一部分是对该村人群进行的横断面调查,利用统计学方法推断该村村民HCV感染的危险因素。本部分研究使用1994年获得的数据,首先对危险因素进行logistic单因素检验,有统计学意义的变量再进行多因素logistic回归分析。研究发现,仅献血浆史(OR=26.214)、混合献血史(OR=11.397)以及献血浆年数(OR=1.182)为该村村民HCV感染的危险因素,我们推测20世纪80-90年代的非法采血活动是导致该村HCV流行的原因。第二部分是分子流行病学研究,利用生物信息学方法对获得的HCV RNA序列进行分析,了解该村HCV基因型的分布,推断该村HCV起源。我们选用2014年获得的血清标本,抽提RNA并采用巢式PCR的方法获得C-E1区和NS5B区序列,测序。系统发生分析发现该村仅存在1b、2a两种亚型的HCV,1b为主要流行亚型(75%)。分子进化分析发现1b型HCV起源复杂多样,2a型HCV来源较单一。MCC树及BSP曲线图显示该村HCV感染爆发时期约为1985～1995年间,与中国中部地区非法采血活动盛行的时间相符,推断由于村民参与非法采血活动而导致了 HCV在该村的传播流行。综上所述,兴盛于80年代末至90年代初的非法采血活动导致了该村HCV的流行,加强血制品管理,规范采血活动,严格筛选献血员对于HCV的防控具有重要意义。
[Abstract]:Hepatitis C virus (HCV) is a serious human health pathogen, which can be transmitted by blood and blood products, intravenous injection and vertical transmission of mother and child. HCV infection can lead to chronic hepatitis, liver cirrhosis and even liver cancer. Has caused serious harm to human health. At present, the global prevalence of HCV is about 2.5%, and there are significant differences between regions. There are more than 100 subtypes of HCV genotypes. Different subtypes of HCV often rely on specific routes for transmission, which leads to different regions. The genotypes of HCV epidemic strains were different in different populations. The prevalence of HCV in China is not optimistic. Because of the limited data, the report on the prevalence rate of HCV in the general population of China is not accurate. The reported prevalence rate of HCV in the general population of China is between 0.39 and 2.5. The main epidemic strains of hepatitis C virus in China are 1B subtype and 1b subtype. Type 2a HCV is the most common epidemic strain after type 1b HCV in northern China, while subtype 2a has replaced 2a subtype as the second most common prevalent strain of HCV in some southern provinces, especially in the Yangtze River Delta and the Pearl River Delta. The new type 6 a HCV infection showed an increasing trend. The research object of this study is a village in Hebei province. This village is the site of hepatitis C research in our laboratory. We first carried out a cross-sectional survey of all the people in the village in 1994, and then carried out serological investigation on the villagers in 2005 and 2014 respectively. Long-term dynamic observation of HCV patients in this village is of great significance to the study of HCV natural history. The purpose of this study was to understand the situation of HCV infection in a village in Hebei province, to find out the causes of HCV transmission in this village, to infer the risk factors of HCV infection in the village, and to provide basic information for the prevention and control of HCV and the management of HCV infection. This study is divided into two parts. The first part is a cross-sectional survey of the village population, using statistical methods to infer the risk factors of HCV infection. In this part, the data obtained in 1994 were used to test the risk factors by logistic single factor test, and then multivariate logistic regression analysis was carried out on the statistically significant variables. It was found that the risk factors of HCV infection in the village were only the plasma donation of ORX 26.214m and the mixed blood donation history of 11.397). We speculated that the illegal blood collection activity in the 80-90 's was the cause of the epidemic of HCV in this village. The second part is molecular epidemiology study. The HCV RNA sequence was analyzed by bioinformatics method, and the distribution of HCV genotypes in the village was understood, and the origin of HCV was inferred. We selected the serum samples obtained in 2014, extracted RNA and obtained the sequence of C-E1 region and NS5B region by nested PCR, and sequenced them. Phylogenetic analysis showed that there were only two subtypes of HCV1b in this village. Molecular evolution analysis showed that the origin of 1b type HCV was more complex and diverse than that of single HCV source. MCC tree and BSP curve showed that the outbreak period of HCV infection in this village was about 1985 / 1995, which was consistent with the time of illegal blood collection in central China. It is inferred that the spread of HCV in the village was caused by villagers' participation in illegal blood collection activities. To sum up, the illegal blood collection activities that flourished from the late 1980s to the early 1990s led to the prevalence of HCV in the village. It is of great significance to strengthen the management of blood products, standardize the blood collection activities and strictly screen blood donors for the prevention and control of HCV.
【学位授予单位】：中国疾病预防控制中心
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R512.63;R181.3

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