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: 6290249
• 负责人: JOHN 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/6290249
• 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 have been 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, which commenced in January 1999.We have followed a cohort of 397 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 30 months of follow-up of the children, ETEC was isolated in 25% of diarrheal episodes; the incidence rates of ETEC (episodes per child-year) were 1.7, 1.6, and 0.7 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, 106 children aged 2-5 years, and 95 children aged 6-18 months in Benha, near Cairo. Each of these studies demonstrated the vaccine to be well-tolerated and to induce significant mucosal immune responses to vaccine antigens. In January 1999, a Phase III trial of the vaccine that will assess the safety, immunogenicity, and clinical efficacy of the vaccine, was initiated in Abu Homos. 192 children 6-18 months of age were randomized to receive either vaccine or placebo, and surveillance for potential adverse effects and diarrheal outcomes continues. - Enterotoxigenic Escherichia coli, diarrhea, Egypt, vaccine, clinical trial - Human Subjects & Human Subjects: Interview, Questionaires, or Surveys Only

肠源性大肠杆菌（ETEC）腹泻在埃及幼儿中高流行，致病性分离株的毒素表型分布均衡。这些特征使得在埃及开发一个评价ETEC流行病学和ETEC疫苗的现场研究中心是合乎逻辑的。我们一直在下埃及参与一项合作研究计划，旨在描述儿科队列中ETEC腹泻的特征，并测试一种有希望的口服ETEC灭活疫苗候选疫苗的安全性和免疫原性，为疫苗有效性的田间试验做准备，我们在阿布霍莫斯对397名3岁以下的儿童进行了每周两次的主动监测，（Beheira省），通过毒素和定植因子（CFA）表型确定ETEC腹泻的年龄特异性发病率。在30个月的儿童随访期间，25%的腹泻事件中分离出ETEC;在生命的第一年、第二年和第三年，ETEC的发生率（每儿童年的事件数）分别为1.7、1.6和0.7。在建立该监测的同时，我们在开罗附近的Benha对76名成人、107名6-12岁儿童、106名2-5岁儿童和95名6-18个月儿童进行了口服灭活ETEC疫苗的随机、安慰剂对照II期研究，以两剂方案给药。这些研究均证明疫苗耐受性良好，并诱导对疫苗抗原的显著粘膜免疫应答。1999年1月，在Abu Homos启动了疫苗的第三期试验，以评估疫苗的安全性、免疫原性和临床疗效。192名6-18个月大的儿童被随机分配接受疫苗或安慰剂，并继续监测潜在的不良反应和腹泻结果。- 肠源性大肠杆菌，腹泻，埃及，疫苗，临床试验-人类受试者和人类受试者：仅访谈，问卷调查或调查