Transrenal DNA for point-of-care diagnosis of TB

用于结核病即时诊断的经肾 DNA

基本信息

批准号：
10443886
负责人：
Barry Ryan Lutz
金额：
$ 18.29万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-02 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10443886
关键词：
Adult Aerosols Base Pairing Biological Assay Cells Cessation of life Child Childhood Clinical Clinical Sensitivity Collection Communicable Diseases Coughing DNA Detection Development Diagnosis Disease Exhibits Exposure to Foundations Genomic Segment Gold Growth HIV HIV Seronegativity HIV Seropositivity HIV/TB Individual Kidney Length Libraries Low income Lung Methods Microscopy Mucous body substance Mycobacterium tuberculosis Outcome Study Patients Persons Population Preparation Pulmonary Tuberculosis Recovery Resources Sample Size Sampling Sensitivity and Specificity South Africa Specificity Specimen Sputum Testing Time Tuberculosis Tuberculosis diagnosis United States Urine Work accurate diagnosis base blood filter co-infection cohort design diagnostic accuracy disease diagnosis effective therapy human DNA improved laboratory development laboratory facility low and middle-income countries multiplex assay multiplex detection non-tuberculosis mycobacteria novel pilot test point of care point of care testing point-of-care diagnosis tuberculosis diagnostics tuberculosis treatment

项目摘要

ABSTRACT M. tuberculosis (Mtb) infects one-third of the world’s population, causes TB disease in 10 million people per year, and is responsible for 1.6 million deaths annually. While effective treatments for TB have been available for over 50 years, a major barrier to its control has remained the inability to reliably diagnose disease in low-resource TB-endemic settings. Most clinical tests require an adequate sample of sputum (mucus from the lungs) which may be difficult to obtain in patients without a cough, in children, and in HIV-infected individuals. Urine offers an attractive method for point-of-care TB diagnostics since it is abundant, simple to collect, and collection does not involve exposure to infectious aerosols. Transrenal DNA (trDNA) present in the urine offers a specific target that can be amplified for high sensitivity. The development of a PCR-based test of TB from urine, and its development as a point-of-care test, could have enormous impact on TB diagnostics. Aim 1. To improve detection of Mtb-specific trDNA using ultrashort PCR and multiplexing. Hypothesis: Amplification of shorter fragments and/or targeting multiple unique fragments will enable detection of low- concentrations samples, increasing sensitivity while maintaining specificity. Aim 2. To determine sensitivity and specificity of improved Mtb-specific trDNA detection in urine samples from adults and children in a TB-endemic setting. Hypothesis: Mtb trDNA is present in detectable quantities in urine from both adults and children with pulmonary TB regardless of HIV status, and our hybridization sequence-capture method can increase clinical sensitivity compared to previous TB trDNA studies.

抽象的结核病（MTB）感染世界人口的三分之一，每年引起1000万人结核病，并且每年有160万人死亡。 50年的主要障碍是对控制的一个主要障碍，无法在低资源中重新降低诊断疾病大多数临床测试都需要提供足够的痰液样本（肺部的粘液）在没有咳嗽的患者，儿童和HIV无关的患者中，可能会获得有吸引力的护理点结核病诊断方法，因为它很丰富，收集易于收集和收集涉及暴露于尿液中的跨性别DNA（trDNA）。可以扩增高灵敏度。作为一项护理点测试，可能会对结核病诊断物产生巨大影响。 AIM 1。使用Ultrashort PCR提高MTB特异性TRDNA的检测：假设。较短片段和/或靶向多个独特片段的扩增将使低 - 检测浓度样本，提高灵敏度，同时保持特异性。目标2。确定尿液中MTB特异性TrDNA检测的灵敏度和特异性在TB流行环境中的成人和儿童的样本。不论艾滋病毒状况如何与先前的TB TB TrDNA研究相比，杂交序列捕获方法可以增加临床捕获捕获捕获捕获捕获捕获捕获临床酶。