Non-invasive zoonotic pathogen exposure and outcome biomarkers with follow-up in

描述（由申请人提供）：这是一个NIOSH指导研究科学家发展奖（K01）资助提案，旨在促进Christopher D. Heaney博士，博士，硕士，北卡罗来纳大学W.K. Kellogg健康学者-社区跟踪博士后，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，在社区参与性研究（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原体分子流行病学的重点培训结合起来，成为一名独立的基础科学、职业卫生实践和人口研究的科学家。拟议职业发展的主题领域是将实验科学与观察小组研究和CBPR方法相结合。新的学科培训将整合到我现有的北卡罗来纳州畜牧工人和家庭成员的CBPR跟踪记录中，以研究牲畜暴露、人畜共患病原体携带以及亚临床定植与感染症状之间关系的时间性质。在这个导师奖期间，我将通过人畜共患传染病医生、临床免疫学家、微生物学家和职业卫生流行病学家的指导，扩大我的临床微生物学和免疫学培训和流行病学研究技能；参与正式教学；参加多学科研讨会、期刊俱乐部和科学会议；与导师一起参加学习活动；并领导了一个将非侵入性人畜共患病原体生物标志物整合到社区参与性小组研究中的项目。这些活动将由主要导师David Weber博士，医学博士，北卡罗来纳大学医院职业卫生服务诊所主任，流行病学，医学，儿科和传染病教授，以及联合导师John Schmitz博士，临床微生物学/免疫学副主任，北卡罗来纳大学医学院病理学和检验医学副教授监督。我的导师，共同导师，合作者和顾问委员会成员将以他们互补的专业知识补充我的培训，并共同致力于帮助我达到更高的学科研究培训和职业发展目标，并确保我从导师成功过渡到独立的研究科学家。在第一年，我将每周与导师dr。Weber和Schmitz将开发、优化和验证用于检测唾液中戊型肝炎病毒（HEV）抗体（抗HEV）的ELISA。为此，共同导师Schmitz博士正在提供实验室设施和设备，以运行elisa和去鉴定唾液和血清，用于抗hev优化和尖峰实验。在第一年，我还将访问合作者Lance Price博士，他是北TGen微生物学和人类健康中心主任，继续在我领导的一项正在进行的横断面CBPR试点研究中，对从畜牧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）进行多位点序列分型（MLST）和全基因组SNP分析（WGSA）进行培训。为此，合作者Price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）的合作者德文·霍尔（Devon Hall）发起的CBPR伙伴关系——从畜牧业工人和家庭成员的CBPR横断面MDRSA患病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性小组研究。CBPR小组研究将涉及200名畜牧工人和家庭成员参与者，并进行为期4个月的基线随访和每两周随访。在第二年和第三年，我将每周与博士见面。Weber和Schmitz及其合作者将唾液抗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（北卡罗来纳大学医学和传染病咨询委员会成员和教授）同意协助医学转诊和随访CBPR小组研究参与者，这些参与者在通报携带状态后出现MDRSA和/或HEV感染症状（见人类受试者保护计划）。在我的导师、共同导师和合作者的支持下，我处于独特的位置，可以完成拟议的活动，这些活动建立在强有力的CBPR伙伴关系和irb批准的协议基础上，这些协议来自北卡罗来纳州已经资助的CBPR横断面MDRSA流行研究。该信息库将为收集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，这将大大改善目前对畜牧业集约化生产地区（NC）畜牧工人和家庭成员人畜共患病原体暴露负担的估计。该研究具有创新性，因为它有可能推进观察性流行病学研究的因果推断，确定人畜共患病原体暴露的关键危险因素和减少暴露和感染风险的干预点，并进一步促进CBPR与流行病学研究的整合，从而为决策提供信息。这项研究的短期效益将有助于对畜牧工人和家庭成员中两种新出现的人畜共患病原体的时间趋势和负担的研究不足。长期利益将是将基础科学方法转化为对鼻拭子和唾液拭子中人畜共患病病原体的非侵入性测量，从工作台到社区，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. PUBLIC HEALTH RELEVANCE: Industrialized systems of food animal production are major sources of novel antimicrobial drug-resistant bacterial pathogens which along with zoonotic viruses are among the most globally prevalent and emerging infectious diseases. Establishing accurate estimates of the burden of emerging infectious diseases in food animal production workers and household members is essential to identifying key risk factors of pathogen exposure and optimal points of intervention to reduce exposures and infection risks. Results of this community- based participatory panel study will help characterize the temporal nature of relationships between livestock exposure, zoonotic pathogen carriage, and symptoms of subclinical colonization versus infection in livestock workers and their household members in a region with intensive livestock production - North Carolina.