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

乙型肝炎出生剂量疫苗对刚果民主共和国儿童乙型肝炎免疫原性和发病率的影响

基本信息

批准号：
10455457
负责人：
Samantha Tulenko
金额：
$ 3.96万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10455457
关键词：
AIDS/HIV problem Adopted Africa South of the Sahara African Age Age-Months Asia Birth Blood Categories Cause of Death Cessation of life Child Childbirth Childhood Childhood Acute Lymphocytic Leukemia Chronic Hepatitis Communicable Diseases Communities Data Data Analyses Democratic Republic of the Congo Development Disease Doctor of Philosophy Dose Effectiveness Epidemiologic Methods Epidemiology Fellowship Future Government Grant HIV Health Hepatitis B Hepatitis B Antibodies Hepatitis B Incidence Hepatitis B Infection Hepatitis B Prevalence Hepatitis B Transmission Hepatitis B Vaccines Horizontal Disease Transmission Hour Household Immunity Immunology Incidence Infant Infant Health Infection Infectious Disease Epidemiology Intervention Intervention Studies Knowledge Life Malaria Measures Mentors Modeling Morbidity - disease rate Mothers Newborn Infant North Carolina Physicians Policies Postdoctoral Fellow Province Randomized Research Schedule Scientist Series Spottings Training Tuberculosis Universities Vaccinated Vaccines Vertical Disease Transmission Viral hepatitis burden of illness career cohort epidemiological model global health immunogenicity infant infection interest intervention program markov model mathematical model member mortality prevent protective efficacy secondary analysis skills translational study vaccination schedule vaccinology

项目摘要

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.

项目概要过去几十年来，病毒性肝炎已成为全球主要死亡原因，导致更多人死亡每年的发病率都高于疟疾、艾滋病毒/艾滋病或肺结核。当考虑乙型肝炎 (HBV) 时，这种巨大的负担该疾病主要是由儿童感染引起的，因为 90% 感染 HBV 的婴儿会发展为慢性肝炎并伴有终生后遗症。儿童乙型肝炎病毒感染通过垂直传播（从母亲到分娩期间的儿童）和通过水平传播（同一家庭成员之间或社区）。在乙肝病毒仍然流行的撒哈拉以南非洲 (SSA)，儿童接种了乙肝疫苗 6、10 和 14 周龄时。该时间表不能防止垂直传播，并且估计 SSA 每年有 1% 的新生儿（367,250 名婴儿）在出生时继续感染 HBV。管理出生时接种单价乙型肝炎疫苗已被证明对垂直感染具有高达 95% 的保护效力世界卫生组织西太平洋地区的传播。然而，很少有人进行研究描述在撒哈拉以南非洲地区提供出生剂量乙肝疫苗的潜在影响设置。我们该项目的合作伙伴是刚果民主共和国 (DRC) 卫生部特别有兴趣了解是否采取国家乙型肝炎出生剂量干预措施。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）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来自刚果金沙萨省两项试验的斑点：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，该提案旨在 1) 比较 12 岁时获得乙肝病毒保护性免疫力的婴儿比例按疫苗剂量系列和母亲的 HBV 和 HIV 状况划分的月龄，以及 2) 建立模型的影响采用全国 4 剂 HBV 疫苗系列（包括出生剂量）对 HBV 发病率有影响刚果民主共和国 5 岁以下儿童。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、数学模型和疫苗干预研究。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/博士学位爬坡道。该 F30 奖学金将帮助申请人发展成为未来的跨学科医师科学家在传染病、婴儿健康和介入流行病学的交叉领域从事实践。