ETEC EPIDEMIOLOGY AND VACCINE RESEARCH IN LOWER EGYPT

下埃及的 ETEC 流行病学和疫苗研究

• 批准号: 6162522
• 负责人: J D CLEMENS
• 金额: --
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6162522
• 关键词: Egypt; Escherichia coli; age difference; antibody titering; bacterial antigens; bacterial vaccines; child (0-11); clinical research; diarrhea; disease /disorder proneness /risk; enterotoxins; epidemiology; human subject; immunization; infant human (0-1 year); interview; longitudinal human study; nonhuman therapy evaluation; phenotype; preschool child (1-5); vaccine development; virulence

Enterotoxigenic Escherichia coli (ETEC) diarrhea is hyperendemic among young Egyptian children, with a balanced distribution of toxin phenotypes from pathogenic isolates. These features make it logical to develop a field site for the evaluation of ETEC epidemiology and ETEC vaccines in Egypt. We are engaged in a collaborative program of research in lower Egypt designed to characterize ETEC diarrhea in a pediatric cohort and to test the safety and immunogenicity of a promising killed oral ETEC vaccine candidate in preparation for a field trial of vaccine efficacy. We have followed a cohort of children under 3 years with twice-weekly active surveillance in Abu Homos (Beheira governorate) to determine the age-specific incidence rate of ETEC diarrhea, by toxin and colonization factor (CFA) phenotypes. During 18 months of follow-up of 288 children in Abu Homos, ETEC was isoalted in 290 (24%) of the 1232 detected diarrheal episodes; the incidence rates of ETEC (episodes per child-year) were 1.5, 1.6, and 0.8 in the first, second, and third years of life. Concurrent with establishment of this surveillance, we conducted randomized, placebo-controlled Phase 2 studies of killed oral ETEC vaccine, administered as a two-dose regimen to 76 adults, 107 children aged 6-12 years, and and 106 children aged 2-5 years in Benha, near Cairo. Each of these studies demonstrated the vaccine to be well-tolerated and to induce significant musosal immune responses to vaccine antigens. A similarly designed trial of the vaccine, administered to infants will be launched during the coming months.

产肠毒素大肠杆菌(ETEC)腹泻是一种高度地方性腹泻 埃及儿童，毒素表型分布均衡 从致病菌株中分离出来。这些功能使得开发一个 年ETEC流行病学和ETEC疫苗评估现场 埃及。我们正在进行一项合作研究计划，研究对象是 埃及旨在确定ETEC腹泻的儿科队列特征，并 检测一种有希望的口服ETEC的安全性和免疫原性 候选疫苗正在为疫苗效力的现场试验做准备。 我们跟踪了一群3岁以下的儿童，每周两次 在阿布霍莫斯(贝海拉省)进行积极监测，以确定 ETEC腹泻的年龄别发病率，按毒素和定植 因子(CFA)表型。在对288名儿童18个月的随访中 在检测到的1232例腹泻中，有290例(24%)ETEC是等位的 ETEC发病率(每儿童年发病数)为1.5， 1.6和0.8，在生命的第一年、第二年和第三年。并发 随着这一监测的建立，我们进行了随机、 口服ETEC灭活疫苗的安慰剂对照第二阶段研究， 76名成人，107名6-12岁儿童接受双剂方案治疗 在开罗附近的本哈，有106名2-5岁的儿童。每一个 这些研究表明疫苗具有良好的耐受性和诱导性。 对疫苗抗原有显著的肌肉免疫反应。A类似的 为婴儿接种的疫苗的设计试验将启动 在接下来的几个月。