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: 2449784
• 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/2449784
• 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); 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 begun a collaborative program to develop a field site near Alexandria for the study of pediatric ETEC diarrhea, and to evaluate the safety and immunogenicity of a promising killed oral ETEC vaccine candidate in preparation for a field trial of vaccine efficacy. This program of projects has followed two pediatric cohorts, one in Abees (Alexandria governorate) and the other in Abu Homos (Beheira governorate) to determine the age-specific incidence rate of ETEC diarrhea from birth to 35 months, by toxin and colonization factor (CFA) phenotype; and to evaluate the protective relationship between titers of serum IgG antibodies to ETEC toxins and CFAs and the risk of diarrhea due to ETEC manifesting these virulence factors. During two years of follow-up of 242 children in Abees, the incidence of ETEC diarrhea was found to be .9 episodes per child-year, and 88% of isolates expressed LT-only or ST-only. Approximately one-fourth of cases were due to an ETEC that expressed a recognized CFA antigen. Among the 286 children followed for one-year in Abu Homos, the incidence of ETEC was 1.4 episodes per child-year, with 80% of isolates expressing LT-only or ST-only, and ca. 40% of isolates expressed a CFA. A randomized, placebo-controlled Phase 2 study of killed oral ETEC vaccine, administered as a two-dose regimen to 76 adults in Benha, near Cairo, demonstrated the vaccine to be well-tolerated and to induce signficant musosal immune responses to vaccine antigens. A similarly designed trial of the vaccine, administered to 110 children aged 6-12 years in the same site was recently conducted. No serious reactions were noted, but definitive analyses await unblinding of the codes.

产肠毒素大肠杆菌（ETEC）腹泻在 年轻的埃及儿童，毒素表型分布均衡 从病原分离物中分离出来。 这些特征使得开发一个 评价ETEC流行病学和ETEC疫苗的现场 埃及 我们已经开始了一项合作计划， 研究小儿ETEC腹泻，并评估 口服ETEC灭活疫苗的安全性和免疫原性 为疫苗效力的实地试验做准备的候选人。 该项目计划遵循两个儿科队列，一个在Abees， 另一个在Abu Homos（Beheira省） 确定ETEC腹泻从出生起的年龄特异性发病率 至35个月，按毒素和定植因子（CFA）表型;以及 评估血清IgG滴度与保护性关系 ETEC毒素和CFA抗体以及ETEC引起的腹泻风险 表现出这些毒力因子。 在两年的随访期间， 在Abees的242名儿童中，发现ETEC腹泻的发病率为0.9 每儿童年的发病率，88%的分离株仅表达LT，或 ST仅大约四分之一的病例是由于ETEC， 表达公认的CFA抗原。在286名儿童中， 在Abu Homos的一年中，ETEC的发生率为1.4次/ 儿童年，80%的分离株仅表达LT或仅表达ST，约10%的分离株仅表达LT或ST。 40%的分离株表达CFA。 一项随机、安慰剂对照、口服致死ETEC的II期研究 疫苗，作为两剂方案给予76名成年人在本哈，附近 开罗，证明了疫苗是耐受性良好，并诱导 对疫苗抗原的显著的肌肉免疫应答。 类似 设计的疫苗试验，给110名6-12岁的儿童接种 最近在同一地点进行了一年的调查。 无严重反应 注意到，但明确的分析有待代码揭盲。