Development of a Rapid Low-Cost Fecal-based TB Diagnostic for Children

开发基于粪便的儿童结核病快速低成本诊断方法

• 批准号: 10080649
• 负责人: Jeffrey D. Cirillo
• 金额: $ 24.4万
• 依托单位: PULMONESCENCE DIAGNOSTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10080649
• 关键词: Address; Area; Bacteria; Biological Assay; Cause of Death; Cessation of life; Child; Childhood; Clinical; Clinical Trials; Communicable Diseases; Communities; Coughing; Country; Data; Deglutition; Destinations; Detection; Development; Diagnosis; Diagnostic; Diagnostic Reagent; Diagnostic tests; Feces; Fractionation; Fund Raising; Geography; Goals; Health Personnel; Healthcare; Human; Human Resources; Infant; Infectious Agent; Infrastructure; Literature; Mycobacterium tuberculosis; Peripheral; Phase; Power Sources; Primary Health Care; Problem Solving; Process; Publishing Peer Reviews; Pulmonary Tuberculosis; Reagent; Reporting; Research; Resources; Sampling; Sensitivity and Specificity; Source; Specificity; Specimen; Sputum; System; Technology; Testing; Training; Translations; Triage; Tuberculosis; academic review; base; cost; design; experience; global health; inhibitor/antagonist; novel diagnostics; point-of-care diagnostics; product development; skills; stool sample; tuberculosis diagnostics

Project Summary Tuberculosis (TB) causes more deaths worldwide than any other infectious disease, yet in the past, the impact of TB on children has been often dismissed or minimized. Poor diagnosis and reporting of tuberculosis (TB) in infants and children continue to hinder accurate estimates of the TB burden in children and the worldwide burden of tuberculosis remains high among children. The diagnosis of TB in children is challenging at present due to a lack of a sensitive point-of-care diagnostic tests, low access to and use of available tests, and difficulties of obtaining sputum specimens from children with TB. Moreover, available clinical tests need sufficient infrastructure support for the testing process such as a stable power supply, trained personnel, or lab facilities which preclude their use in peripheral settings. Many are also cost prohibitive for low resource countries where TB load is high. Currently, there is a great need for low cost rapid non-sputum TB diagnostics for children and a more accessible sample that can be obtained with minimal skill at primary health care level for use in an alternative diagnostic would be highly desirable for the diagnosis of TB in children. When children cough, they usually swallow the sputum. It has been shown that feces, the ultimate destination of swallowed sputum, is potentially a useful specimen for detection of TB in children. Indeed, viable Mycobacterium tuberculosis (Mtb) has been shown to be present in fecal samples using culture studies. More recently, there has been a number of attempts to adapt the GeneXpert® test to feces from children. While the analysis of stool specimens by GeneXpert® potentially represents a new diagnostic test for pediatric TB, its use in peripheral settings is severely limited. To solve this problem, we have designed and tested a rapid, low cost sputum-based diagnostic (REFtb) for peripheral settings that could be modified for use as a pediatric fecal test. The broad objective of the proposed research in this application is to adapt this sputum-based test to a fecal-based pediatric test. Based on preliminary data, we believe that with minimal optimization the sputum REFtb assay can easily be adapted from sputum to fecal matter as a diagnostic test. These studies will focus on adapting the sputum-based regents for use in a pediatric fecal-based assay and testing the fecal-based assay in pediatric fecal material. We plan to examine nonTB fecal material from children for interference activities to the REFtb test and test known inhibitors of the sputum-based REFtb test in order to develop an optimized reagent mix for the fecal-based test. Longer term we plan to continue development to develop a shelf-stable pediatric test and test the shelf-stable diagnostic in preliminary clinical trials. Completion of this proposed research will result in the development of a fecal-based pediatric TB diagnostic suitable for low resource peripheral settings. This fecal-based pediatric REFtb system overcomes the financial and geographical barriers that currently limit early TB detection so children with TB that currently go undiagnosed can now be diagnosed in a low-cost and rapid manner.

项目摘要 结核病在全世界造成的死亡人数比任何其他传染病都多，但在过去， 结核病对儿童的影响常常被忽视或被最小化。结核病的诊断和报告不足， 婴儿和儿童的结核病继续阻碍对儿童结核病负担和全球结核病负担的准确估计 结核病在儿童中的发病率仍然很高。儿童结核病的诊断目前具有挑战性， 缺乏敏感的护理点诊断测试，现有测试的获得和使用率低， 从结核病患儿身上采集痰液标本。此外，现有的临床试验需要足够的 测试过程的基础设施支持，例如稳定的电源、训练有素的人员或实验室设施 这妨碍了它们在外围设备中的使用。对于低资源国家来说， TB负荷很高。目前，非常需要用于儿童的低成本快速无痰结核病诊断， 在初级卫生保健一级，用最低限度的技能就可以获得更容易获得的样本， 对于儿童结核病的诊断，替代诊断是非常需要的。当孩子咳嗽时， 通常会吞下痰。已经表明，粪便，吞咽痰液的最终目的地， 可能是检测儿童结核病的有用样本。事实上，存活的结核分枝杆菌（Mtb） 已显示存在于使用培养研究的粪便样本中。最近，有一些 尝试将GeneXpert®检测用于儿童粪便。而粪便标本的分析， GeneXpert®可能代表一种新的儿科结核病诊断测试，其在外周环境中的使用严重 有限公司为了解决这个问题，我们设计并测试了一种快速，低成本的基于肿瘤的诊断（REFtb） 用于外围设置，其可以被修改以用作儿科粪便测试。建议的广泛目标 本申请的研究是使这种基于粪便的测试适应于基于粪便的儿科测试。基于 根据初步数据，我们认为，只要进行最小限度的优化，痰液REFtb检测就可以很容易地从 把痰液和粪便混合作为诊断测试这些研究将侧重于调整基于埃隆图姆的摄政者， 用于儿科粪便基测定和在儿科粪便材料中测试粪便基测定。我们计划 检查儿童的非结核粪便物质对REFtb检测的干扰活性，并检测已知的抑制剂 以开发用于粪便检测的优化试剂混合物。长 我们计划继续开发一种货架稳定的儿科测试，并测试货架稳定的诊断 在初步临床试验中。完成这项拟议的研究将导致发展粪便为基础的 儿科结核病诊断适用于低资源的外围设备。这种基于粪便的儿科REFtb系统 克服目前限制早期结核病检测的财政和地理障碍，使患有结核病的儿童 目前尚未诊断的疾病现在可以以低成本和快速的方式得到诊断。

项目成果

Stabilization of Tuberculosis Reporter Enzyme Fluorescence (REFtb) Diagnostic Reagents for Use at the Point of Care.

• DOI: 10.3390/diagnostics12071745
• 发表时间: 2022-07-19
• 期刊: Diagnostics (Basel, Switzerland)