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: 6541307
• 负责人: Malla R. Rao
• 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/6541307
• 关键词: Egypt; Escherichia coli; Escherichia coli infections; active immunization; adolescence (12-20); adult human (21+); age difference; antibody titering; bacterial antigens; bacterial vaccines; child (0-11); diarrhea; disease /disorder proneness /risk; enterotoxins; epidemiology; human subject; human therapy evaluation; interview; longitudinal human study; patient oriented research; phenotype; 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.

产肠毒素大肠杆菌（ETEC）腹泻在年轻的埃及儿童中是高地方性的，从致病分离株中获得的毒素表型分布平衡。这些特点使得在埃及建立一个评价ETEC流行病学和ETEC疫苗的现场站点是合乎逻辑的。我们在下埃及参与了一项合作研究计划，旨在确定ETEC腹泻在儿童队列中的特征，并测试一种有希望的口服灭活ETEC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现场试验做准备。我们在Abu Homos （Beheira省）对397名3岁以下儿童进行了每周两次的主动监测，通过毒素和定菌因子（CFA）表型确定ETEC腹泻的年龄特异性发病率。在对儿童30个月的随访中，在25%的腹泻发作中分离出ETEC；ETEC（每儿童年发作数）在第一、第二和第三年的发病率分别为1.7、1.6和0.7。在建立这一监测的同时，我们在开罗附近的Benha进行了口服灭活ETEC疫苗的随机、安慰剂对照2期研究，以两剂方案给药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。这些研究都证明疫苗具有良好的耐受性，并诱导对疫苗抗原的显著粘膜免疫反应。1999年1月，在Abu Homos开始了疫苗的III期试验，该试验将评估疫苗的安全性、免疫原性和临床疗效。192名6-18个月大的儿童随机接受疫苗或安慰剂，并继续监测潜在的不良反应和腹泻结果。2000年1月，又有161名儿童随机接受疫苗或安慰剂，他们也仍处于监测之中。2000年6月，启动了ETEC疫苗的第二阶段试验，以评估其与扩大免疫规划（EPI）疫苗（即百白破、脊髓灰质炎和乙型肝炎疫苗）一起施用时的安全性和免疫原性。