Molecular Diagnostic Tools for Patient Oriented Field Studies in Infectious Disea

描述(由申请人提供)：我是弗吉尼亚大学传染病系的临床医生研究员，现提交这份修订后的K24提案，以便将我的研究更深入地转移到以患者为中心的研究(POR)中，并提供受保护的时间来指导这些学员。在完成ID奖学金后的11年里，我在几个热带传染病领域制定了一个研究计划，现在主要集中在分子诊断工具的开发上。目前得到资助的工作包括筛选各种潜在肠道病原体的化验小组(盖茨基金会)和基于聚合酶链式反应的耐多药结核病二线药物敏感性测试(R01)。随着成熟的分子诊断技术和协作临床站点的到位，现在是K24将这些诊断技术应用到精心设计的POR研究中的好时机，以便向临床重要领域提供信息，如发展中国家的腹泻原因和耐多药结核病的适当治疗。具体目标包括(1)使用我们对肠道病原体的分子诊断，与现场站点的合作，以及一系列统计方法(优势比、定量负荷和前瞻性分析)和干预研究，以推断哪些是与发展中国家儿童腹泻有关的主要病原体，以及(2)利用我们的分子结核病药物敏感性测试以及与MDR TB现场站点的合作，量化药物敏感性周转时间和有效MDR TB方案的改善。这笔赠款将使我能够在POR要素方面获得必要的培训，包括临床试验设计和纵向生物统计学，并将为指导ID研究员和该司内外的初级教员提供急需的保护时间。此外，我建议利用这个K24创建的项目和我作为研究副主席的角色，将医学系、公共卫生科学系和儿科系聚集在一起，作为改善全校POR指导的平台。

DESCRIPTION (provided by applicant): I am a Clinician Investigator in the Division of Infectious Diseases at University of Virginia and am submitting this revised K24 proposal to move my research more deeply into patient oriented research (POR) and to provide protected time to mentor such trainees. In the 11 years since completion of ID fellowship I have developed a research program in several domains of tropical infectious diseases, now largely focused on the development of molecular diagnostic tools. Currently funded work includes a panel of assays to screen for the wide array of potential enteropathogens (Gates Foundation) and a PCR-based susceptibility test for second line drugs against MDR Tuberculosis (R01). With mature molecular diagnostics and collaborative clinical sites in place, now is an opportune time for this K24 to take these diagnostics to carefully designed POR studies in order to inform clinically important areas such as the cause of diarrhea in developing countries and proper treatment for MDR Tb. Specific Aims include (1) using our molecular diagnostics on enteropathogens, collaborations with field sites, and a range of statistical methods (odds ratios, quantitative loads, and prospective analysis) and intervention studies to infer what are the major pathogens associated with childhood diarrhea in developing countries and (2) using our molecular Tuberculosis drug susceptibility tests and collaborations with MDR Tb field sites to quantify improvements in drug susceptibility turnaround time and time-to-active MDR Tb regimen. This grant will allow me to gain needed training in elements of POR including clinical trial design and longitudinal biostatistics and will offer much-needed protected time for mentoring ID fellows and junior faculty in the Division and beyond. Furthermore I propose to use the program created by this K24 and my role as Vice-Chair for Research to bring together Departments of Medicine, Public Health Sciences, and Pediatrics as a platform for improvements in POR mentoring across the School.