Mycobacterial Lung Diseases in Virginia: sequencing and clinical determinants of relapse and outcome

项目总结/摘要 非结核分枝杆菌肺病，主要是由于M。鸟类复合体（MAC），是一个日益增长的 在全国范围内，结核病是一个严重的临床问题，在发病率和死亡率方面，目前已超过国内结核病。也是 更难治疗，尽管药物治疗时间更长，结果也更差。在此背景下，NIH发布了一份 通知AI-17-016，要求申请NTM疾病。在这里，我们提出了一个建议，从大学的 弗吉尼亚州，与弗吉尼亚州卫生部和弗吉尼亚理工大学的合作者， 被引用的需求。首先，我们将对我们州所有的MAC分离株进行全基因组测序。 MAC肺病患者辨别复发与再感染以及获得的环境来源。 其次，我们将利用全州范围内的新MAC肺病患者队列，将临床结局与 MAC种类、药物敏感性、血清药物水平和生物膜生物测定。创新包括使用 全州范围流行病学队列，全基因组广泛初步数据的精确分辨率 测序，以辨别物种和混合感染，全面的全州血清药物监测 计划（正如我们已经为结核病所做的那样），以及分子诊断和基因型-表型 相关性总之，对于MAC肺病这一最令人烦恼的临床问题， 初步数据、独特专业知识、创新技术、紧密合作和协同目标。

PROJECT SUMMARY / ABSTRACT Nontuberculous mycobacterial lung diseases, primarily due to M. avium complex (MAC), is an increasing clinical problem nationwide and now overtakes domestic TB in terms of morbidity and mortality. It is also harder to treat and results in poorer outcomes despite longer drug regimens. In this context NIH issued a notice AI-17-016 to request applications for NTM diseases. Here we present a proposal from the University of Virginia, with collaborators at the Virginia Department of Health and Virginia Tech, that addresses many of the needs that were cited. First, we will perform whole genome sequencing of MAC isolates from all of our state's MAC lung disease patients to discern relapse versus reinfection and the environmental sources of acquisition. Second we will utilize a state-wide cohort of new MAC lung disease patients to correlate clinical outcomes with MAC species, drug susceptibility, serum drug levels, and biofilm bioassay. Innovation includes the use of a state-wide epidemiological cohort, exquisite resolution with extensive preliminary data of whole genome sequencing to discern species and mixed infections, a comprehensive state-wide serum drug monitoring program (as we have done already for TB), and expertise in molecular diagnostics and genotypic-phenotypic correlations. In sum, for this most vexing clinical problem of MAC lung disease we bring to bear extensive preliminary data, unique expertise, innovative technology, cohesive collaborations, and synergistic aims.