1-3岁儿童乙肝疫苗无应答与接种剂量、隐匿性乙肝感染的关联研究

发布时间：2018-03-02 07:42

本文关键词： 乙肝疫苗无应答疫苗剂量婴儿期体重隐匿性乙型肝炎　出处：《新疆医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:了解乌鲁木齐市乙肝疫苗剂量由5μg提高到10μg后的疫苗无应答情况,探讨疫苗接种剂量、婴儿期体重、隐匿性乙肝感染(OBI)对乙肝疫苗无应答的影响,为降低婴幼儿乙肝疫苗无应答率做出贡献。方法:连续纳入新疆医科大学第一附属医院预防保健科2013年12月—2015年6月完成乙肝疫苗免疫接种的1-3岁常规体检儿童,监护人知情同意后查看疫苗接种本确定乙肝疫苗接种剂量,面访填写问卷,采集静脉血样本。使用ELISA法检测乙肝六项、巢式PCR扩增HBV S区并测序,使用MEGA7.0进行分子进化特征分析。应用SPSS17.0进行一般统计学分析,使用R软件建立Logistic回归模型分析并计算交互作用指标RERI(相对超危险度比)、AP(归因比)、S(交互作用指数),Bootstrap法估计其可信区间。结果:共调查1023名儿童,平均年龄1.26±0.47岁,乙肝疫苗无应答率为15.44%(158/1023)。1.不同累积接种剂量间无应答率差异有统计学意义,P0.001;20μg、25μg、30μg组相对于15μg的OR分别为:0.463(0.293-0.732),0.259(0.126-0.530),0.217(0.132-0.356)。2.应答组与无应答组:42天、3月龄、6月龄、12月龄平均体重差异有统计学意义(P0.05)。42天、3月龄、6月龄体重右偏离者(即超重)较正常者OR分别为1.260(1.135-1.398),1.515(1.246-1.842),1.414(1.171-1.708)。控制出生体重进行协方差分析发现:应答与无应答组之间接种期(0-6月)体重增长量差异有统计学意义,P0.001,无应答组大于应答组。3.使用R软件,建立Logistic回归模型结果表明:乙肝疫苗累积接种剂量与接种期体重增长量均对乙肝疫苗无应答有影响,而后计算相加交互作用指标RERI=16.358(0.331~230.885)AP=0.673(0.123~0.846),S=3.231(1.219~6.553),表明两者存在相加的交互作用即协同作用。4.儿童OBI感染率为7.82%(80/1023),应答组与无应答组间OBI感染率差异无统计学意义。5.可以分型的79例OBI中,C基因型为优势基因型;在HBV S区共发生27次突变,其中10次发生在 a‖决定簇。6.对乙肝疫苗无应答的158名儿童进行随访,补种率87.34%(138/158),再次抽血检测的随访率36.08%(57/158);复测57名儿童乙肝表面抗体均为阳性,其中63.16%(36/57)的儿童呈高应答状态。7.了解未随访的儿童家长64.92%(101/158)拒绝随访的原因,经过故障树分析发现:拒绝随访以主观因素为主,对随访人员的不信任,认为研究人员专业素质较弱,对课题的不了解为主要原因。结论:乙肝疫苗接种剂量、接种期体重增长量均影响乙肝疫苗无应答,且疫苗剂量低、接种期体重增长过快两者同时存在时可协同增加乙肝疫苗无应答的风险;需重视1-3岁儿童中隐匿性乙肝感染的危害性。
[Abstract]:Objective: to investigate the nonresponse of hepatitis B vaccine in Urumqi from 5 渭 g to 10 渭 g, and to explore the effect of vaccine dose, infant weight and occult hepatitis B infection (OBI) on the non-response to hepatitis B vaccine. Methods: children aged 1-3 years who had completed hepatitis B vaccine immunization from December 2013 to June 2015 were included in the Department of Prevention and Health of the first affiliated Hospital of Xinjiang Medical University. After informed consent, the guardian checked the vaccination book to determine the dose of hepatitis B vaccine, filled out the questionnaire, collected venous blood samples, detected six hepatitis B patients by ELISA method, amplified the HBV S region by nested PCR and sequenced it. We use MEGA7.0 to analyze the characteristics of molecular evolution. We use SPSS17.0 to do general statistical analysis. R software was used to establish Logistic regression model to analyze and calculate the interaction index (RERI). Results: a total of 1 023 children with an average age of 1.26 卤0.47 years were investigated. The non-response rate of hepatitis B vaccine was 15.440.158 / 1023 / 1.1.There was significant difference in non-response rate between different cumulative doses of inoculation. The OR of 30 渭 g group of 20 渭 g of 20 渭 g or 20 渭 g of P0.001g was 0.4630.293-0.732U 0.2590.126-0.530U 0.2170.132-0.356m 路2.There was significant difference in average body weight between the responding group and the non-responder group at the age of 6 months or 12 months old at the age of 3 months or 3 months, respectively. There was a significant difference between the response group and the non-responding group in the age of 6 months and 12 months old. There was a significant difference between the response group and the non-responding group in the mean body weight of 6 months old and 12 months old, respectively. The OR of those with right deviation (i.e. overweight) of 3 months and 6 months of age were 1.260 / 1.135-1.398U 1.515 / 1.246-1.842 respectively. The covariance analysis of birth weight control showed that there was a difference in body weight gain between responders and non-responders during the vaccination period (0-6 months). P 0.001. The non-response group is larger than the Respondent group .3.Using R software, The results of Logistic regression model showed that the cumulative dose of hepatitis B vaccine and the increase of body weight during inoculation period had influence on the non-response of hepatitis B vaccine. Then the additive interaction index, RERI 16.358 / 0.331n / 230.885A, was calculated. There was no significant difference in OBI infection between the responding group and the non-responding group. There was no significant difference in OBI infection between the responding group and the non-responding group. The results showed that there was an additive interaction between the two groups, I. e., synergistic effect. 4. The infection rate of OBI in children was 7.8280 / 10235.There was no significant difference in OBI infection rate between the responding group and the non-responding group. There were 79 cases of OBI that could be classified into two groups. There was no significant difference in the OBI infection rate between the responding group and the non-responding group. There were 79 cases of OBI. The C genotype was the dominant genotype. A total of 27 mutations occurred in the HBV S region, 10 of which occurred in the HBV determinant cluster. 6. 158 children who did not respond to hepatitis B vaccine were followed up. The supplementation rate was 87.34%, 138 / 158%, and the follow-up rate was 36.08%, 57 / 158%, 57 / 158%, respectively, and 57 children were tested positive for hepatitis B surface antibodies. 63.16% of the children were in a high response state. 7. To understand the reasons why the parents of the children who had not been followed up 64.92% 101- 158) refused to follow up. Through the fault tree analysis, it was found that the rejection of follow-up was mainly subjective factors, distrust of the follow-up personnel, and thought that the professional quality of the researchers was relatively weak. Conclusion: the dose of hepatitis B vaccine and the increase of body weight during inoculation period all affect the non-response of hepatitis B vaccine, and the dose of vaccine is low. Excessive weight gain during inoculation period can increase the risk of hepatitis B vaccine nonresponse when both of them exist simultaneously, and we should pay attention to the harm of occult hepatitis B infection in children aged 1-3 years.
【学位授予单位】：新疆医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R186;R725.1

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