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: 6432594
• 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/6432594
• 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. In January 2000, an additional 161 children were randomized to receive either vaccine or placebo, and they also remain under surveillance. In June 2000, a Phase II trial of the ETEC vaccine was initiated to evaluate its safety and immunogenicity when administered in conjunction with the expanded program on immunization (EPI) vaccines viz. DTP, Polio and Hepatitis B vaccines.

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1999年1月开始的疫苗有效性田间试验做准备。我们对Abu Homos（Beheira省）的397名3岁以下儿童进行了每周两次的主动监测，以确定毒素和定植因子（CFA）表型的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。2000年1月，又有161名儿童被随机分配接受疫苗或安慰剂，他们也仍在接受监测。 2000年6月，启动了ETEC疫苗的II期试验，以评价其与扩大免疫计划（EPI）疫苗（即百白破三联疫苗、脊髓灰质炎疫苗和B型肝炎疫苗）联合接种时的安全性和免疫原性。