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Bacterial Determinants of Treatment Response in Mycobacteria Tuberculosis

结核分枝杆菌治疗反应的细菌决定因素

基本信息

批准号：
9918252
负责人：
MEGAN B MURRAY
金额：
$ 293.63万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-18 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9918252
关键词：
Address Adult Antibiotic Resistance Bacillus Biological Markers Cause of Death Childhood Clinical Clinical Research Communicable Diseases DNA Detection Development Diagnosis Diagnostic Disease Drug Controls Drug Tolerance Drug resistance Drug resistance in tuberculosis Early Diagnosis Early treatment Failure Genetic Determinism Goals Growth Human In Vitro Interdisciplinary Study Knowledge Lead Microscopy Mutation Mycobacterium tuberculosis Patient-Focused Outcomes Patients Pharmaceutical Preparations Phenotype Regimen Resistance Sampling Sputum Testing Tuberculosis World Health Organization base curative treatments design disease transmission effective therapy genetic signature improved molecular diagnostics novel diagnostics novel marker point-of-care diagnostics prevent programs rapid detection resistance mutation resistant strain stem tool treatment response tuberculosis diagnostics

项目摘要

Summary: Overview The recent development of rapid molecular diagnostics promises to revolutionize TB control. Such tests can be performed directly on sputum or other clinical samples and rely on the rapid detection of Mycobacteria tuberculosis (MTB) genetic signatures as well as drug resistance- associated mutations. Clinical studies demonstrate that they perform better than sputum smear microscopy and reliably identify resistance to several first line drugs. However, these tools suffer from two important limitations. First, current platforms are limited in their ability to extract MTB DNA directly from clinical samples. And secondly, there are major gaps in our knowledge of the genetic determinants of poor treatment responses. Here, we propose to address these gaps through a multi- disciplinary collaboration emphasizing discovery of new biomarkers of drug resistance and tolerance, the identification of optimal clinical sampling strategies directed toward detection of MTB DNA and the development of a sensitive micro-array based rapid diagnostic. Our long-term goal is to develop a diagnostic strategy that will improve the diagnosis of DR TB and stem the further spread of the disease. The immediate aims of this projects are to 1) discover and characterize novel biomarkers of TB drug resistance both through human studies and by phenotyping isogenic strains with introduced mutations; 2) continue late stage development of a novel diagnostic with which to detect MTB DR, 3) develop the most promising clinical sampling strategies with which to detect DNA from MTB and 4) develop and optimize a micro-array based near Point of Care diagnostic designed to detect adult and pediatric MTB and its drug resistance mutations.

摘要:概述