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

非侵入性人畜共患病原体暴露和结果生物标志物以及随访

• 批准号: 8523050
• 负责人: Christopher D Heaney
• 金额: $ 10.8万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8523050
• 关键词: Non; invasive; zoonotic; pathogen; exposure

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.

描述（由申请人提供）：这是NIOSH指导的研究科学家发展奖（K01）赠款提案，旨在促进Christopher D. Heaney博士博士，MS，A W.K. Kellogg Health Scholar-Community Track北卡罗来纳大学的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，在社区参与性研究（CBPR）和环境流行病学方面具有重大的研究记录。我的目标是将我现有的经验与人畜共患病原病原体的微生物学，免疫学和分子流行病学的重点培训相结合，以成为基础科学，职业健康实践和人群研究界面的独立科学家。拟议职业发展的主题领域是将基准科学与观察小组研究和CBPR的方法整合在一起。新的纪律训练将与我现有的CBPR往绩融为一体，与NC中的牲畜工人和家庭成员一起研究，以研究牲畜暴露，人畜共患病原体运输以及亚临床定殖与感染的症状之间关系的时间性质。在这项指导奖中，我将通过人畜共患病医生，临床免疫学家，微生物学家和职业健康流行病学家的指导来扩展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；与我的导师一起参加学习活动；并通过一个将非侵入性人畜共患病原体生物标志物纳入社区参与式小组研究的项目。这些活动将由主要导师David Weber博士MD，MPH，UNC医院职业卫生服务诊所的主任，流行病学，医学，儿科和传染病学教授，以及临床微生物学/免疫学/免疫学/免疫学和学院医学院临床医学专业医学的副主任John Schmitz博士博士。我的导师，同事，合作者和咨询委员会成员将以他们的补充专业知识来补充我的培训，并完全致力于帮助我实现更高的纪律研究培训和职业发展目标，并确保从指导到独立研究科学家的成功过渡。在第一年，我将每周与导师Drs见面。 Weber和Schmitz开发，优化和验证ELISA以检测唾液中的丙型肝炎病毒（HEV）抗体（抗HEV）。为此，施密茨博士正在提供实验室设施和设备，以运行ELISAS并识别出唾液和血清，以进行抗HEV优化和尖峰实验。在第一年，我还将访问北部TGEN的微生物和人类健康中心主任Lance Price，博士继续接受多层次序列分型（MLST）和整个基因组SNP分析（MLST）和整个基因组SNP分析（WGSA）（WGSA）的多剂量抗药性葡萄球菌（MDRSA）隔离的niv and and and and and and and and snp snp and and and and。我领导的横断面CBPR试点研究。为此，合作者价格在我访问培训期间为他的实验室提供。在第1和2年级，我将扩大与农村授权社区帮助协会（REACH）合作者Devon Hall发起的CBPR合作伙伴关系 - 从CBPR横断面的MDRSA Pristisy研究中，牲畜工作者和家庭成员对NC的牲畜和家庭成员的一项基于社区的参与性小组成员。 CBPR小组研究将涉及200名牲畜工人和家庭成员参与者进行基线和每两周的随访时间为4个月。在第2和3年，我将每周与Drs见面。 Weber和Schmitz以及合作者将唾液抗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）和医学博士Stanley Lemon（UNC的咨询委员会成员兼医学和感染性疾病教授）已同意协助对CBPR小组研究参与者进行医学转诊和随访，以开发MDRSA和/或HEV感染症状后，通知后，请参阅《人类受试者的计划》。在我的导师，同事和合作者的支持下，我独特地定位了拟议的活动，这些活动是基于与IRB批准的协议建立在NC中本已资助的CBPR横截面MDRSA Percrence研究中的IRB批准协议的基础上。该信息基础将建立一个基础，以收集CBPR面板研究数据，以表征牲畜暴露，病原体运输的时间变化，以及次临床定植与感染的症状 - 这将大大改善当前对畜牧业和家庭成员在强烈的Livestock Production Livestock Productuck Productuck Production the地区的人畜共患病原体负担的估计。拟议的研究既新颖又创新，因为它有潜力提高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风险因素和干预点以减少暴露和感染风险，并进一步促进CBPR与流行病学研究的整合，以告知流行病学研究15。这项研究的短期收益将是对畜牧业和家庭成员中两种新兴人畜共患病原体的临时趋势和负担的贡献。长期的好处将是将基础科学方法转化，用于从替补席上对鼻和唾液拭子中人畜共患病原体的非侵入性测量，以告知与食品动物生产有关的职业健康政策。