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

项目摘要 在过去的几十年里，病毒性肝炎已成为全球死亡的主要原因，造成更多的死亡 比疟疾、艾滋病和肺结核都多。当考虑到B肝炎（HBV），这种巨大的负担， 这种疾病主要是由儿童感染引起的，因为90%感染HBV的婴儿会发展成慢性乙型肝炎。 有终身后遗症肝炎。儿童HBV感染通过垂直传播（从母亲到 分娩期间的子女）和横向传播（同一家庭成员之间或 社区）。在HBV仍然流行的撒哈拉以南非洲（SSA）， 在6、10和14周龄时。这一时间表并不能防止垂直传播， 每年，南威尔士州1%的新生儿（367，250名婴儿）在出生时继续感染乙型肝炎病毒。总局 在出生时接种单价HBV疫苗已显示出对垂直感染具有高达95%的保护效力， 世卫组织西太平洋区域的传播。然而，很少有研究表明， 描述在撒哈拉以南非洲地区提供出生剂量HBV疫苗的潜在影响 设置.本项目的合作伙伴是刚果民主共和国卫生部 特别感兴趣的是了解是否采取国家HBV出生剂量干预。 这项转化研究将提供4剂HBV疫苗系列的有效性和影响的估计 （包括出生剂量）。拟议中的研究将利用以前收集的数据和干血 来自刚果民主共和国金沙萨省两项试验的斑点：出生剂量免疫原性研究和连续免疫原性研究。 质量改进研究。利用先进的流行病学方法和数学建模， 该提案旨在1）比较12岁时获得HBV保护性免疫的婴儿比例， 月龄的疫苗剂量系列和母亲的HBV和HIV状态和2）模型的影响， 采用国家4剂乙肝疫苗系列，包括出生剂量， 刚果民主共和国5岁以下儿童。结果将提供有价值的估计免疫原性和潜在的 HBV出生剂量的影响，将告知刚果民主共和国和撒哈拉以南非洲地区的疫苗政策。 通过完成这些研究目标，学员将获得一套独特的技能， 流行病学方法、数学建模和疫苗干预研究。专家导师在 疫苗学、免疫学、建模和流行病学将支持受训者成功完成 在北卡罗来纳州查珀尔大学进行研究，制定相关的培训计划，并获得医学博士/博士学位 之丘这个F30奖学金将帮助申请人的发展，作为一个未来的跨学科的物理学家，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.