The impact of a Hepatitis B birth dose vaccine on HBV immunogenicity and incidence in children in the DRC

项目总结 在过去的几十年里，病毒性肝炎已经成为全球主要的死亡原因，造成了更多的死亡 每年都比疟疾、艾滋病毒/艾滋病或肺结核更严重。当考虑到乙肝(乙肝)时，这一巨大的负担 疾病在很大程度上是由儿童感染引起的，因为90%感染乙肝病毒的婴儿将发展为慢性 有终身后遗症的肝炎。儿童乙肝病毒感染是通过垂直传播(从母亲传播到 分娩期间的儿童)和水平传播(在同一家庭的成员之间或 社区)。在撒哈拉以南非洲(SSA)，乙肝病毒仍然流行，儿童接种乙肝疫苗。 在6、10和14周大的时候。该时间表不能防止垂直传播，估计 在南非，每年有1%的新生儿(367,250名婴儿)在出生时继续感染乙肝病毒。管理 出生时的单价乙肝疫苗已被证明对垂直感染有高达95%的保护效果。 世卫组织西太平洋地区的传播。然而，很少有人对此进行研究。 描述在撒哈拉以南非洲地区提供出生剂量的乙肝疫苗的潜在影响 设置。我们这一项目的合作伙伴--刚果民主共和国卫生部 他们特别感兴趣的是了解是否采取全国性的乙肝出生剂量干预措施。 这项转译研究将提供对4剂乙肝疫苗系列的有效性和影响的估计。 (包括出生剂量)在刚果民主共和国。拟议的研究将利用之前收集的数据和干燥的血液 刚果民主共和国金沙萨省两个试验的斑点：出生剂量免疫原性研究和连续试验 质量改进研究。利用先进的流行病学方法和数学模型，这 该提案旨在1)比较12岁时对乙肝病毒获得保护性免疫的婴儿比例 年龄按疫苗剂量系列和母亲的乙肝病毒和艾滋病毒状况和2)模型的影响 采用国家四剂乙肝疫苗系列，包括出生剂量，对#年乙肝发病率的影响 刚果民主共和国的5岁以下儿童。这些结果将为免疫原性和潜力提供有价值的估计。 乙肝病毒出生剂量的影响将为刚果民主共和国和更大的撒哈拉以南非洲地区的疫苗政策提供信息。 通过完成这些研究目标，学员将获得一套独特的高级技能 流行病学方法、数学建模和疫苗干预研究。的专家导师 疫苗学、免疫学、建模和流行病学将支持学员成功完成 北卡罗来纳大学教堂分校的拟议研究、相关培训计划和医学博士学位 小山。这项F30奖学金将帮助申请者发展成为未来的跨学科医生-科学家 在传染病、婴儿健康和干预流行病学的交叉点执业。

PROJECT SUMMARY Over the past few decades, viral hepatitis has become a leading cause of death globally, causing more deaths each year than malaria, HIV/AIDS, or tuberculosis. When considering Hepatitis B (HBV), this large burden of disease is largely driven by childhood infections, as 90% of infants infected with HBV will develop chronic hepatitis with lifelong sequelae. Childhood HBV infection occurs through vertical transmission (from mothers to children during childbirth) and through horizontal transmission (between members of the same household or community). In sub-Saharan Africa (SSA), where HBV remains endemic, children are vaccinated against HBV at 6, 10, and 14 weeks of age. This schedule does not protect against vertical transmission, and an estimated 1% of newborns (367,250 infants) in SSA continue to be infected with HBV at birth each year. Administration of the monovalent HBV vaccine at birth has been shown to have up to 95% protective efficacy against vertical transmission in the WHO Western Pacific region. However, few studies have been conducted to characterize the potential impact of providing a birth dose of HBV vaccine in sub-Saharan African settings. Our partners for this project, the Ministry of Health in the Democratic Republic of the Congo (DRC) are particularly interested in understanding whether to adopt a national HBV birth dose intervention. This translational study will provide estimates of the effectiveness and impact of a 4-dose HBV vaccine series (including a birth dose) in the DRC. The proposed research will utilize previously collected data and dried blood spots from two trials in Kinshasa Province, DRC: the Birth Dose Immunogenicity Study and the Continuous Quality Improvement Study. Using advanced epidemiological methods and mathematical modeling, this proposal aims to 1) compare the proportion of infants who achieve protective immunity to HBV at 12 months of age by vaccine dose series and mothers' HBV and HIV status and 2) model the impact of adopting a national 4-dose HBV vaccine series, including the birth dose, on the incidence of HBV in children under 5 in the DRC. The results will provide valuable estimates of the immunogenicity and potential impact of an HBV birth dose that will inform vaccine policy in the DRC and greater sub-Saharan African region. Through the completion of these research aims, the trainee will gain a unique set of skills in advanced epidemiologic methods, mathematical modeling, and vaccine intervention research. Expert mentors in vaccinology, immunology, modeling, and epidemiology will support the trainee's successful completion of the proposed research, associated training plan, and MD/PhD degree at the University of North Carolina at Chapel Hill. This F30 fellowship will aid the applicant's development as a future interdisciplinary physician-scientist practicing at the intersection of infectious disease, infant health, and interventional epidemiology.