A novel diagnostic tool to aid vaccine evaluation and surveillance of enterotoxigenic E. coli and Shigella

一种新型诊断工具，有助于产肠毒素大肠杆菌和志贺氏菌的疫苗评估和监测

• 批准号: 9751198
• 负责人: Subhra Chakraborty
• 金额: $ 16.38万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2021-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9751198
• 关键词: 5 year old; Affect; Age; Agreement; Area; Biological Assay; Cessation of life; Child; Child Health; Communicable Diseases; Complex; Computers; Country; DNA; Detection; Diagnostic; Diagnostic Procedure; Diagnostic Sensitivity; Diagnostic tests; Diarrhea; Disease; Disease Surveillance; Electricity; Enzyme-Linked Immunosorbent Assay; Epidemiology; Equipment; Evaluation; Feces; Freeze Drying; Freezing; Gel; Gene Duplication; Genes; Hospitals; Hot Spot; Hour; Impaired cognition; Incubators; India; Infection; Laboratories; Laboratory Study; Mediating; Methods; Modification; Patients; Pediatric Hospitals; Performance; Phase III Clinical Trials; Policy Maker; Predictive Value; Preparation; Public Health; Reaction; Reader; Recurrence; Resources; Rotavirus; Running; Sampling; Sensitivity and Specificity; Shigella; Shigella Infections; Standardization; Testing; Time; Training; Trust; Tube; United States National Institutes of Health; Vaccines; Work; aged; base; burden of illness; care seeking; cognitive development; comparative; cost; disability; duplicate genes; enterotoxigenic Escherichia coli; improved; instrument; novel; novel diagnostics; performance tests; recruit; scale up; stool sample; tool; vaccine candidate; vaccine development; vaccine effectiveness; vaccine evaluation; validation studies

Project Summary Enterotoxigenic Escherichia coli (ETEC) and Shigella (ES) are the leading causes of moderate-to-severe diarrhea among children < 5 years of age in impoverished areas of the world. Recurrence of infection results in death, stunting, impaired cognitive development and long-term disability. Due to the huge impact of ES in children, vaccine development has been prioritized and accelerated in recent years. As promising vaccine candidates for ES move toward field trials in endemic areas, an improved understanding of the epidemiology of ES and identify the hotspots of these diseases are critical to plan Phase 3 trials and to assess the potential benefits of vaccine use. A critical constraint is the complex diagnostic methods currently required for detecting ES infections. These methods are neither sufficiently sensitive nor standardized and are not feasible in resource poor settings (RPS) where these infections are endemic. Therefore, the country-specific burden of ES is not readily available. Consequently regional public health officials and policy makers lack a clear appreciation of the impact that ES have on child health in their countries. Therefore, a diagnostic method which is sensitive, rapid and feasible for RPS is critically important and urgently required. Our recent work suggests that a direct detection from stool method LAMPES, is simple, easy to use and rapid. With limited training, we anticipate it can be carried out in basic laboratories and fields. Here we propose to evaluate the performance of our novel assay LAMPES and compare with the existing detection methods for ES using stool samples from children with and without diarrhea in an endemic setting, Kolkata, India. Given, this assay is rapid, sensitive, specific, easy to use, mostly equipment and electricity free, easy to scale up we believe LAMPES is an ideal tool to fill the gap in vaccine evaluation and ES disease surveillance in the endemic countries.

项目概要 产肠毒素大肠杆菌 (ETEC) 和志贺氏菌 (ES) 是中度至重度腹泻的主要原因 世界贫困地区 5 岁以下儿童腹泻。感染复发会导致 死亡、发育迟缓、认知发展受损和长期残疾。由于ES的巨大影响 近年来，疫苗的开发已被优先考虑并加速。作为有前途的疫苗 ES候选者转向流行地区的现场试验，加深了对流行病学的了解 ES 并确定这些疾病的热点对于计划 3 期试验和评估潜力至关重要 使用疫苗的好处。一个关键的限制是目前检测所需的复杂诊断方法 ES 感染。这些方法既不够灵敏，也不够标准化，在实际应用中不可行。 这些感染在资源匮乏的环境（RPS）中流行。因此，特定国家的 ES 负担 不容易获得。因此，地区公共卫生官员和政策制定者缺乏明确的认识 了解 ES 对本国儿童健康的影响。因此，一种诊断方法 灵敏、快速、可行对于RPS来说至关重要且迫切需要。我们最近的工作表明 从粪便中直接检测的方法LAMPES，简单、易用、快速。在有限的训练下，我们 预计可以在基础实验室和现场进行。在这里我们建议评估 我们的新型检测 LAMPES 并与使用来自粪便样本的现有 ES 检测方法进行比较 印度加尔各答，流行病环境下患有或不患有腹泻的儿童。鉴于此测定法快速、灵敏、 具体、易于使用、大部分设备和电力免费、易于扩展，我们相信 LAMPES 是理想的选择 填补流行国家疫苗评估和 ES 疾病监测空白的工具。

项目成果

Evaluation of a simple, rapid and field-adapted diagnostic assay for enterotoxigenic E. coli and Shigella.

• DOI: 10.1371/journal.pntd.0010192
• 发表时间: 2022-03
• 期刊: PLoS neglected tropical diseases
• 影响因子: 3.8
• 作者: Connor S;Velagic M;Zhang X;Johura FT;Chowdhury G;Mukhopadhyay AK;Dutta S;Alam M;Sack DA;Wierzba TF;Chakraborty S
• 通讯作者: Chakraborty S