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（TB）在世界范围内造成的死亡人数比任何其他传染病都要多，但是在过去的影响 TB关于儿童的结核病经常被解雇或最小化。诊断不良和结核病报告（TB） 婴儿和儿童继续阻碍儿童和全球伯宁的结核病伯嫩的准确估计 在儿童中，结核病仍然很高。目前，由于 缺乏敏感的护理点诊断测试，可用测试的访问和使用少以及难度 从结核病儿童中获得痰液标本。此外，可用的临床测试需要足够 对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 这排除了它们在外围设置中的使用。对于低资源国家，许多人也禁止许多成本 结核负载很高。目前，对于儿童的低成本快速非输出性结核病诊断非常需要 可以在初级卫生保健水平上使用最低技能获得的更容易获得的样本，以便在 对于儿童的结核病诊断，替代性诊断是非常可取的。当孩子咳嗽时，他们 通常吞下痰。已经表明粪便是吞咽痰的最终目的地，是 可能是检测儿童结核病的有用标本。实际上，可行的分枝杆菌结核病（MTB） 已证明使用培养研究存在于粪便样品中。最近，有一个数字 试图将GenExpert®测试适应儿童的粪便。而对凳子标本的分析 GenExpert®有可能代表针对小儿结核的新诊断测试，其在外围设置中的使用严重 有限的。为了解决这个问题，我们设计并测试了快速，低成本的基于痰的诊断（REFTB） 对于可以修改以作为小儿粪便测试的外围设置。提议的广泛目标 该应用中的研究是将这种基于痰液的测试调整为基于粪便的小儿测试。基于 初步数据，我们认为，通过最少的优化，痰液REFTB测定可以轻松地从 痰液作为诊断测试。这些研究将着重于将基于痰液的剂适应 用于基于小儿粪便的测定法，并在小儿粪便材料中测试基于粪便的测定法。我们计划 检查儿童的非粪便材料进行干扰活动到REFTB测试和测试已知抑制剂 基于痰液的REFTB测试，以开发基于粪便的测试的优化试剂混合物。更长 术语我们计划继续开发以开发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。这项拟议的研究的完成将导致基于粪便的发展 小儿结核病诊断适用于低资源外围设置。这个基于粪便的小儿REFTB系统 克服了目前限制早期结核病检测的财务和地理障碍，因此有结核病儿童 目前，现在可以以低成本和快速的方式诊断出未诊断。

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)