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: 6671904
• 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/6671904
• 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. The population was followed up for a two period. Results of the trial suggest that the vaccine failed to protect against diarrhea due to ETEC in this population, protective efficacy 20% (95%CI -29%;50%). 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. Acute sera prior to immunization and sera after each vaccine dose were obtained for evaluation of antbody responses to each of the component vaccines. Data from this trial are currently being analyzed.

产肠毒素大肠杆菌(ETEC)腹泻在埃及儿童中高度流行，病原菌的毒素表型分布均衡。这些特点使得在埃及开发一个用于评估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腹泻在儿科队列中的特征，并测试一种有希望的口服ETEC疫苗候选疫苗的安全性和免疫原性，为1999年1月开始的疫苗效力现场试验做准备。我们在阿布霍莫斯(贝海拉省)跟踪了397名3岁以下儿童的队列，每周两次积极监测，以确定ETEC腹泻的年龄特定发病率，根据毒素和定居因子(CFA)表型。在对儿童的30个月的随访中，25%的腹泻发作中分离到ETEC；ETEC的发病率(每儿童一年的发作)在生命的第一、第二和第三年分别为1.7、1.6和0.7。在建立这项监测的同时，我们在开罗附近的本哈对口服ETEC灭活疫苗进行了随机、安慰剂对照的第二阶段研究，以两剂方案接种76名成年人、107名6-12岁的儿童、106名2-5岁的儿童和95名6-18个月大的儿童。这些研究中的每一项都证明疫苗具有良好的耐受性，并能诱导对疫苗抗原的显著粘膜免疫反应。1999年1月，在阿布霍莫斯启动了疫苗的第三阶段试验，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接种，并继续监测潜在的不良反应和腹泻结果。2000年1月，另外161名儿童被随机接受疫苗或安慰剂。对这些人口进行了两个时期的跟踪调查。试验结果表明，该疫苗在该人群中未能预防ETEC引起的腹泻，保护效果为20%(95%CI-29%；50%)。2000年6月，启动了ETEC疫苗的第二阶段试验，以评估其安全性和免疫原性，并与扩大的免疫规划(EPI)疫苗一起接种。DTP、脊髓灰质炎和乙肝疫苗。免疫前的急性血清和每次疫苗剂量后的血清用于评估对每种成分疫苗的抗体反应。这项试验的数据目前正在分析中。

项目成果

Oral, inactivated, whole cell enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine: results of the initial evaluation in children. PRIDE Study Group.

口服灭活全细胞产肠毒素大肠杆菌加霍乱毒素 B 亚单位疫苗：儿童初步评估结果。

• DOI: 10.1086/314543
• 发表时间: 1999
• 期刊: The Journal of infectious diseases.
• 作者: Savarino,SJ;Hall,ER;Bassily,S;Brown,FM;Youssef,F;Wierzba,TF;Peruski,L;El-Masry,NA;Safwat,M;Rao,M;ElMohamady,H;Abu-Elyazeed,R;Naficy,A;Svennerholm,AM;Jertborn,M;Lee,YJ;Clemens,JD
• 通讯作者: Clemens,JD

Induction of systemic antifimbria and antitoxin antibody responses in Egyptian children and adults by an oral, killed enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine.

通过口服灭活产肠毒素大肠杆菌加霍乱毒素 B 亚单位疫苗，在埃及儿童和成人中诱导全身抗菌毛和抗毒素抗体反应。

• DOI: 10.1128/iai.69.5.2853-2857.2001
• 发表时间: 2001
• 期刊: Infection and immunity
• 影响因子: 3.1
• 作者: Hall,ER;Wierzba,TF;Ahrén,C;Rao,MR;Bassily,S;Francis,W;Girgis,FY;Safwat,M;Lee,YJ;Svennerholm,AM;Clemens,JD;Savarino,SJ
• 通讯作者: Savarino,SJ

Epidemiology of enterotoxigenic Escherichia coli diarrhea in a pediatric cohort in a periurban area of lower Egypt.

• DOI: 10.1086/314593
• 发表时间: 1999-02
• 期刊: The Journal of infectious diseases
• 作者: R. Abu-Elyazeed;T. Wierzba;A. Mourad;L. Peruski;B. Kay;M. Rao;A. Churilla;A. L. Bourgeois;A. Mortagy;S. Kamal;S. Savarino;James R. Campbell;J. Murphy;A. Naficy;J. Clemens