A prospective cohort study on the risk of HBV infection in preschool children without immune response to hepatitis B vaccine
-
摘要:
目的 评估学龄前儿童乙肝疫苗无应答者未来感染乙肝病毒(hepatitis B virus,HBV)的风险。 方法 采用前瞻性队列研究的方法,选取南宁市江南区64家幼儿园内、已经按照0、1、6程序全程接种了三针乙肝疫苗的2~5岁儿童,在2015年3~5月期间抽血检测乙肝病毒表面抗原(hepatitis B surface antigen,HBsAg)和乙肝病毒表面抗体(hepatitis B surface antibody,抗-HBs),HBsAg阴性儿童为本次研究对象。根据儿童抗-HBs是否阳性,分成暴露组(抗-HBs阴性)和对照组(抗-HBs阳性)。研究开始于2015年6月1日,结束于2016年6月1日,在2016年6月1~30日对儿童进行随访检测血清HBsAg阳性率,比较两个组的HBsAg阳性率。 结果 纳入队列的无应答组人数1 907名,排除随访期间再次接种乙肝疫苗的83人,该队列人数实际为1 824,研究结束时失访151人,实际随访到的人数是1 673人,期间共有5名小孩HBsAg转成阳性,感染率为0.30%(5/1673);纳入队列的应答组人数2 054名,研究结束时失访140人,随访到人数为1914,他们均未检测出HBsAg;研究结束时无应答组HBsAg阳性率高于应答组(P=0.023)。 结论 乙肝疫苗无应答者未来存在感染HBV的风险。 Abstract:Objective To evaluate the risk of hepatitis B virus(HBV) infection among preschool children who were the non-responders to hepatitis B vaccine in future. Methods A prospective cohort study was conducted. Children aged 2 to 5 years were selected from 64 kindergartens.These children were inoculated three doses of hepatitis b vaccine at 0, 1 and 6 months after birth. Hepatitis B surface antigen (HBsAg) and Hepatitis B surface antibody (anti-HBs) were detected during the period from March to May 2015. The children who were HBsAg negative were enrolled in the study. The subjects were divided into exposure group (anti-HBs negative) and control group (anti-HBs positive). The follow-up began on June 1, 2015 and ended on June 1, 2016. Serum HBsAg of children in the cohort was then collected and detected from June 1 to 30, 2016. At the end of the study, the HBsAg positive rates between two groups were compared. Results 83 children who received hepatitis B vaccine again during the follow-up period were excluded from 1 907 non-responders. The actual number in non-responders group was 1 824. 151 children were lost at the end of the study. The actual number of follow-up was 1 673 and 5 children were found to be positive for HBsAg and the infection rate was 0.30% (5/1673). In the respondent goup, 2 054 were enrolled and followed. Finally, 140 children were lost and none of the remaining 1 914 people were HBsAg positive at the end of the study. HBsAg positive rate was higher in the non-responder group than in the responder group (P=0.023). Conclusion There is a risk of HBV infection in the children who are non-responders to hepatitis B vaccine in future. -
表 1 纳入队列儿童的一般情况
Table 1. General situation of children in the beginning of study
年龄(岁) 无应答组 应答组 纳入队列的总人数 男 女 合计 男 女 合计 2~ 95 63 158 65 73 138 296 3~ 346 264 610 289 251 540 1 150 4~ 365 273 638 428 315 743 1 381 5~6 228 190 418 379 254 633 1 051 合计 1 034 790 1 824 1 161 893 2 054 3 878 表 2 研究结束时队列儿童随访的一般情况
Table 2. General situation of children at the end of follow-up
年龄(岁) 无应答组 应答组 研究结束时总人数 纳入队列时总人数 失访人数 男 女 合计 男 女 合计 2~ 85 58 143 49 62 111 254 296 42 3~ 326 238 564 263 239 502 1 066 1 150 84 4~ 345 253 598 417 297 714 1 312 1 381 69 5~6 204 164 368 359 228 587 955 1 051 96 合计 960 713 1 673 1 088 826 1 914 3 587 3 878 291 -
[1] 沙花燕, 杜丽, 温亮, 等. 乙型肝炎流行动态及研究进展[J]. 解放军预防医学杂志, 2017, 35(9): 1149-1153. DOI: 10.13704/j.cnki.jyyx.2017.09.041.Sha HY, Du L, Wen L, et al. Epidemic dynamics and research progress of hepatitis B[J]. J Prev Med Chin PLA, 2017, 35(9): 1149-1153. DOI: 10.13704/j.cnki.jyyx.2017.09.041. [2] 孙国栋, 王安辉, 王宇飞, 等. 武威市某社区人群HBsAg携带者自发性再激活的流行病学特征[J]. 中华疾病控制杂志, 2017, 21(4): 332-335. DOI: 10.16462/j.cnki.zhjbkz.2017.04.003.Sun GD, Wang AH, Wang YF, et al. Epidemiological characteristics of the spontaneous reactivation of HBV carriers in community population in Wuwei City[J]. Chin J Dis Control Prev, 2017, 21(4): 332-335. DOI: 10.16462/j.cnki.zhjbkz.2017.04.003. [3] Tujios SR, Lee WM. Update in the management of chronic hepatitis B[J]. Curr Opin Gastroenterol, 2013, 29(3): 250-256. DOI: 10.1097/MOG.0b013e32835ff1e9. [4] 陈红燕, 李秀, 彭松绪, 等. 慢性乙型肝炎及HBeAg状态对母婴结局的影响研究[J]. 中华疾病控制杂志, 2018, 22(6): 617-620. DOI:10. 16462/j.cnki.zhjbkz.2018.06.018.Chen HY, Li X, Peng SX, et al. Impact of chronic hepatitis B and HBeAg status on maternal and infant outcomes[J]. Chin J Dis Control Prev, 2018, 22(6): 617-620. DOI:10. 16462/j.cnki.zhjbkz.2018.06.018. [5] 张万华. 乙型肝炎疫苗免疫低或无应答相关因素及策略的研究进展[J]. 右江医学, 2006, (3): 310-312. doi: 10.3969/j.issn.1003-1383.2006.03.051Zhang WH. Research progress on related factors and strategies of low or no response to hepatitis B vaccine[J]. Youjiang Med J, 2006, (3): 310-312. doi: 10.3969/j.issn.1003-1383.2006.03.051 [6] Wu Z, Yao J, Bao H, et al. The effects of booster vaccination of hepatitis B vaccine on children 5-15 years after primary immunization: a 5-year follow-up study[J]. Hum Vaccin Immunother, 2018, 14: 1251-1256. DOI: 10.1080/21645515.2018.1426419. [7] 林素琴. 乙肝疫苗接种无或弱应答遗传因素研究进展[J]. 中外医学研究, 2015, 13(16): 154-156. DOI: 10.14033/j.cnki.cfmr.2015.16.089.Lin SQ. The research progress on genetic factors with no or low response to hepatitis B vaccination[J]. Chinese and Foreign Medical Research, 2015, 13(16): 154-156. DOI: 10.14033/j.cnki.cfmr.2015.16.089. [8] 詹思延. 流行病学[M]. 第七版. 北京: 人民卫生出版社, 2012: 68-69.Zhan SY. Epidemiology[M]. Seventh Edition. Beijing: People's Medical Publishing House, 2012: 68-69. [9] 崔富强, 龚晓红, 陈园生, 等. 中国不同省份1992~2006年乙型肝炎疫苗预防接种进展及乙型肝炎病毒表面抗原携带率变化分析[J]. 中国疫苗和免疫, 2012, 18(1): 6-13. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGJM201201005.htmCui FQ, Gong XH, Chen YS, et al. Vaccination progress of hepatitis B vaccine and epidemiology changes of carrying rate of hepatitis B surface antigen by province in China, 1992-2006[J]. Chinese Journal Vaccines and Immunization, 2012, 18(1): 6-13. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGJM201201005.htm [10] 于艳丽, 张明五, 余运贤. 乙肝疫苗接种无(弱)应答影响因素研究进展[J]. 中国公共卫生, 2013, 29(1): 148-152. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGGW201301055.htmYu YL, Zhang MW, Yu YX. The study of influence factors on no (low) response to hepatitis B vaccination[J]. Chin J Public Health, 2013, 29(1): 148-152. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGGW201301055.htm [11] 周宇晨. 导致乙肝疫苗无应答机制研究进展[J]. 生物学通报, 2011, 46(10): 10-13. https://www.cnki.com.cn/Article/CJFDTOTAL-SWXT201110002.htmZhou YC. Research progress on non-response mechanism of hepatitis B vaccine[J]. Biology Bulletin, 2011, 46(10): 10-13. https://www.cnki.com.cn/Article/CJFDTOTAL-SWXT201110002.htm [12] Nelson NP, Easterbrook PJ, McMahon BJ. Epidemiology of hepatitis B virus infection and impact of vaccination on disease[J]. Clin Liver Dis, 2016, 20(4): 607-628. DOI: 10.1016/j.cld.2016.06.006. [13] Aghasadeghi MR, Banifazl M, Aghakhani A, et al. No evidence for occult HBV infection in hepatitis B vaccine non-responders[J]. Iran J Microbiol, 2014, 6(5): 350-353. http://search.ebscohost.com/login.aspx?direct=true&db=aph&AN=100606226&site=ehost-live [14] Van DP, Van HK. A review of the long-term protection after hepatitis A and B vaccination[J]. Travel Med Infect Dis, 2007, 5(2): 79-84. DOI: 10.1016/j.tmaid.2006.04.004. [15] 刘和平. 125名新生儿接种乙肝疫苗及低/无应答者再免疫效果分析[J]. 实用预防医学, 2016, 23(3): 350-352. DOI: 10.3969/j.issn.1006-3110.2016.03.030.Liu HP. Re-immunization effect analysis of 125 newborns with low/no immune response to hepatitis B vaccine[J]. Pract Prev Med, 2016, 23(3): 350-352. DOI: 10.3969/j.issn.1006-3110.2016.03.030.