Non-Invasive Zoonotic Pathogen Exposure & Outcome Biomarkers

描述(由申请者提供)：这是一项NIOSH指导研究科学家发展奖(K01)的拨款建议，旨在促进Christopher D.Heaney博士的职业生涯，他是北卡罗来纳大学W.K.凯洛格健康学者-社区跟踪博士后研究员，成为一名独立的健康科学家。我是一名训练有素的流行病学家和微生物学家，在基于社区的参与性研究(CBPR)和环境流行病学方面有着重要的研究记录。我的目标是将我现有的经验与微生物学、免疫学和人畜共患病病原体的分子流行病学方面的重点培训结合起来，成为一名从事基础科学、职业健康实践和人口研究的独立科学家。拟议的职业发展的主题领域是将板凳科学与观察性小组研究和CBPR的方法相结合。新的学科培训将被整合到我与北卡罗来纳州畜牧业工人和家庭成员的现有CBPR记录中，以研究牲畜接触、人畜共患病原体携带以及亚临床定植与感染症状之间的时间性质关系。在这个导师奖期间，我将通过以下方式扩展我的临床微生物学、免疫学培训和流行病学研究技能：来自人畜共患传染病医生、临床免疫学家、微生物学家和职业健康流行病学家的导师；参与正式的教学；参加多学科研讨会、杂志俱乐部和科学会议；与我的导师一起参与研究活动；以及领导一个项目，将非侵入性人畜共患病病原体生物标记物整合到基于社区的参与性小组研究中。这些活动将由北卡罗来纳大学医院职业健康服务诊所主任、流行病学、医学、儿科和传染病教授、北卡罗来纳大学医学院临床微生物学/免疫学副主任、病理学和实验室医学副教授约翰·施密茨博士、医学硕士、公共卫生硕士大卫·韦伯博士监督。我的导师、合作导师、合作者和咨询委员会成员将以他们互补的专业知识补充我的培训，他们共同致力于帮助我实现更高学科的研究培训和职业发展目标，并确保我成功地从被指导的科学家过渡到独立的研究科学家。在第一年，我将每周与导师Weber博士和Schmitz博士会面，开发、优化和验证检测唾液中戊型肝炎病毒(HEV)抗体(抗HEV)的ELISA。为此，共同导师施密茨博士正在提供实验室设施和设备，以运行ELISA以及用于抗HEV优化和尖峰实验的未鉴定唾液和血清。在第一年，我还将拜访合作者、北TGen微生物和人类健康中心主任Lance Price博士，继续培训从畜牧业工人和家庭成员的鼻拭子中分离出的耐多药金黄色葡萄球菌(MDRSA)的多位点序列分型(MLST)和全基因组SNP分析(WGSA)，这是我领导的一项横断面CBPR试点研究。为此，合作者普莱斯在我访问期间提供了他的实验室进行培训。在第一年和第二年，我将扩大我与农村赋权社区帮助协会(REACH)的合作者Devon Hall发起的CBPR伙伴关系-从CBPR在畜牧业工人和家庭成员中的横断面MDRSA流行率研究，到北卡罗来纳州畜牧业工人和家庭成员的社区参与式小组研究。CBPR小组研究将涉及200名畜牧业工人和家庭成员，他们将接受为期4个月的基线和两周一次的跟踪调查。在第二年和第三年，我将每周与Weber博士和Schmitz博士及其合作者会面，将唾液抗HEV-ELISA和MDRSA基因分型方法(MLST和WGSA)整合到CBPR小组研究中。Weber博士(主要导师)和Stanley Lemon医学博士(咨询委员会成员、北卡罗来纳大学医学和传染病教授)已同意协助CBPR小组研究参与者在接到携带状态通知后出现MDRSA和/或HEV感染症状的医疗转介和跟进(见《保护人类受试者计划》)。在我的导师、共同导师和合作者的支持下，我处于独特的地位，可以完成拟议的活动，这些活动建立在强大的CBPR伙伴关系的基础上，IRB批准的方案来自北卡罗来纳州已经资助的CBPR横断面MDRSA流行率研究。这一信息库将为收集CBPR小组研究数据奠定基础，以表征牲畜暴露、病原体携带和亚临床定植与感染症状的时间变化--这将极大地改善目前对北卡罗来纳州畜牧生产集约区畜牧业工人和家庭成员人畜共患病原体暴露负担的估计。拟议的研究具有新颖性和创新性，因为它有可能推进观察流行病学研究中的因果推断，确定人畜共患病病原体暴露的关键风险因素和减少暴露和感染风险的干预点，并进一步促进CBPR与流行病学研究15的结合，为政策制定提供信息。这项研究的短期好处将是对畜牧业工人和家庭成员中两种新出现的人畜共患病病原体的时间趋势和负担这一未充分研究的领域的贡献。长期的好处将是将鼻拭子和唾液拭子中人畜共患病病原体的非侵入性测量的基础科学方法从工作台转化到社区，为与食用动物生产相关的职业卫生政策提供信息。

DESCRIPTION (provided by applicant): This is a NIOSH Mentored Research Scientist Development Award (K01) grant proposal intended to promote the career of Dr. Christopher D. Heaney, PhD, MS, a W.K. Kellogg Health Scholar-Community Track post- doctoral fellow at the University of North Carolina, into an independent health scientist. I am a trained epidemiologist and microbiologist with a significant track record of research in community-based participatory research (CBPR) and environmental epidemiology. My goal is to integrate my existing experience with focused training in microbiology, immunology, and the molecular epidemiology of zoonotic pathogens, to become an independent scientist at the interface of basic science, occupational health practice, and population research. The topical area for the proposed career development is integration of bench science with methods for observational panel studies and CBPR. New disciplinary training will be integrated into my existing track record of CBPR with livestock workers and household members in NC to study the temporal nature of relationships between livestock exposure, zoonotic pathogen carriage, and symptoms of subclinical colonization versus infection. During this mentored award, I will expand my clinical microbiology and immunology training and epidemiologic research skills through mentorship from zoonotic infectious diseases physicians, clinical immunologists, microbiologists, and occupational health epidemiologists; engagement in formal didactics; attending multidisciplinary seminars, journal clubs, and scientific meetings; participation in study activities with my mentors; and by leadership of a project that integrates non-invasive zoonotic pathogen biomarkers into a community-based participatory panel study. These activities will be supervised by primary mentor Dr. David Weber MD, MPH, Director of the Occupational Health Services Clinic at UNC Hospitals and Professor of Epidemiology, Medicine, Pediatrics, and Infectious Diseases and co-mentor Dr. John Schmitz, PhD, Associate Director of Clinical Microbiology/Immunology and Associate Professor of Pathology and Laboratory Medicine at the UNC School of Medicine. My mentor, co-mentor, collaborators, and advisory committee members will supplement my training with their complementary expertise, and together are fully committed to helping me reach my higher disciplinary research training and career development goals, and ensuring my successful transition from mentored to independent research scientist. During year 1, I will meet weekly with mentors Drs. Weber and Schmitz to develop, optimize and validate an ELISA for detection of hepatitis E virus (HEV) antibodies (anti-HEV) in saliva. For this purpose co-mentor Dr. Schmitz is making available laboratory facilities and equipment to run ELISAs and de- identified saliva and serum for anti-HEV optimization and spiking experiments. In year 1, I will also visit collaborator Lance Price, PhD, Director of the Center for Microbiomics and Human Health at TGen, North, to continue training in multi-locus sequence typing (MLST) and whole genome SNP analysis (WGSA) of multidrug-resistant Staphylococcus aureus (MDRSA) isolated from nasal swabs of livestock workers and household members in an ongoing cross-sectional CBPR pilot study I am leading. For this purpose collaborator Price is making available his laboratory during my visit for training. During years 1 and 2, I will expand a CBPR partnership I initiated with collaborator Devon Hall of the Rural Empowerment Association for Community Help (REACH) - from a CBPR cross-sectional MDRSA prevalence study among livestock workers and household members to a community-based participatory panel study among livestock workers and household members in NC. The CBPR panel study will involve 200 livestock worker and household member participants with baseline and biweekly follow-ups for a period of 4 months. In years 2 and 3, I will meet weekly with Drs. Weber and Schmitz and collaborators to integrate the salivary anti-HEV ELISA and MDRSA genotyping methods (MLST and WGSA) into the CBPR panel study. Dr. Weber (primary mentor) and Stanley Lemon, MD (advisory committee member and Professor of Medicine and Infectious Diseases at UNC) have agreed to assist with medical referral and follow-up of CBPR panel study participants who develop symptoms of MDRSA and/or HEV infection after notification of carriage status (see plan in Protection of Human Subjects). With the support of my mentor, co-mentor, and collaborators, I am uniquely positioned to complete the proposed activities which build upon a strong CBPR partnership with IRB-approved protocols from an already-funded CBPR cross-sectional MDRSA prevalence study in NC. This information base will build a foundation to collect CBPR panel study data to characterize the temporal variation of livestock exposure, pathogen carriage, and symptoms of sub-clinical colonization versus infection - which will greatly improve current estimates of the burden of zoonotic pathogen exposure in livestock workers and household members in a region with intensive livestock production - NC. The proposed research is both novel and innovative because of its potential to advance causal inference in observational epidemiologic research, identify key risk factors of zoonotic pathogen exposure and points of intervention to reduce exposures and infection risks, and further promote the integration of CBPR with epidemiologic research15 to inform policy-making. The short-term benefits from this study will be a contribution to the under-studied area of the temporal trends and burden of two emerging zoonotic pathogens in livestock workers and household members. The long-term benefits will be translation of basic science methods for non-invasive measurement of zoonotic pathogens in nasal and saliva swabs from the bench to community to inform occupational health policies related to food animal production.