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: 8299862
• 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/8299862
• 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. 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.

描述（由申请人提供）：这是一项 NIOSH 指导研究科学家发展奖 (K01) 拨款提案，旨在促进 Christopher D. Heaney 博士、博士、硕士、W.K. 的职业生涯。北卡罗来纳大学凯洛格健康学者社区追踪博士后研究员，成为一名独立健康科学家。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拥有丰富的研究记录。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方面的重点培训相结合，成为基础科学、职业健康实践和人口研究领域的独立科学家。拟议职业发展的主题领域是将实验室科学与观察小组研究和 CBPR 方法相结合。新的学科培训将纳入我与北卡罗来纳州畜牧工人和家庭成员的 CBPR 现有记录中，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。在这个指导奖期间，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以及流行病学研究技能；参与正式的教学；参加多学科研讨会、期刊俱乐部和科学会议；与我的导师一起参与学习活动；并领导了一个项目，将非侵入性人畜共患病原体生物标志物整合到基于社区的参与性小组研究中。这些活我的导师、共同导师、合作者和咨询委员会成员将用他们互补的专业知识来补充我的培训，并共同全力帮助我实现更高的学科研究培训和职业发展目标，并确保我从指导科学家成功过渡到独立研究科学家。在第一年，我每周都会与导师 Drs. 会面。 Weber 和 Schmitz 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，合作导师 Schmitz 博士正在提供实验室设施和设备来运行 ELISA 和去鉴定唾液和血清，以进行抗 HEV 优化和加标实验。在第一年，我还将拜访北方 TGen 微生物组学和人类健康中心主任 Lance Price 博士，继续对从畜牧工人和家庭成员的鼻拭子中分离出的多重耐药金黄色葡萄球菌 (MDRSA) 进行多位点序列分型 (MLST) 和全基因组 SNP 分析 (WGSA) 培训。 我正在领导横断面的 CBPR 试点研究。为此，合作者普莱斯在我访问期间开放了他的实验室进行培训。在第一年和第二年，我将扩大与农村赋权社区帮助协会 (REACH) 的合作者 Devon Hall 发起的 CBPR 合作伙伴关系，从针对畜牧工人和家庭成员的 CBPR 横断面 MDRSA 患病率研究，到针对北卡罗来纳州畜牧工人和家庭成员的基于社区的参与性小组研究。 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 个月的基线和每两周一次的随访。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（咨询委员会成员兼北卡罗来纳大学医学和传染病教授）已同意协助 CBPR 小组研究参与者的医疗转诊和随访，这些参与者在通知携带状态后出现 MDRSA 和/或 HEV 感染症状（参见保护人类受试者中的计划）。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，能够完成拟议的活动，这些活动建立在与 IRB 批准的方案（来自北卡罗来纳州已资助的 CBPR 横断面 MDRSA 患病率研究）的强大 CBPR 合作伙伴关系的基础上。该信息库将为收集 CBPR 小组研究数据奠定基础，以描述牲畜暴露、病原体携带以及亚临床定植与感染症状的时间变化特征，这将大大改善目前对北卡罗来纳州集约畜牧生产地区畜牧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性流行病学研究中的因果推断，确定人畜共患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措施，并进一步促进 CBPR 与流行病学研究的结合，为政策制定提供信息。这项研究的短期效益将有助于对畜牧业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领域做出贡献。长期的好处是将鼻腔和唾液拭子中人畜共患病原体非侵入性测量的基础科学方法从实验室转化为社区，为与食用动物生产相关的职业健康政策提供信息。 公共卫生相关性：食用动物生产的工业化系统是新型抗菌药物耐药性细菌病原体的主要来源，这些病原体与人畜共患病毒一起属于全球最流行和新出现的传染病。准确估计食用动物生产工人和家庭成员新发传染病的负担对于确定病原体暴露的关键风险因素和减少暴露和感染风险的最佳干预点至关重要。这项基于社区的参与性小组研究的结果将有助于描述北卡罗来纳州畜牧业集约化生产地区畜牧工人及其家庭成员的牲畜接触、人畜共患病原体携带以及亚临床定植症状与感染之间关系的时间性质。