TRANSMISSION DYNAMICS OF CA-MRSA AMONG HOUSEHOLD MEMBERS AND THE HOME ENVIRONMENT

描述(由申请者提供)：这份K23职业发展奖的申请书提出了一个为期四年的计划，为候选人提供以患者为导向的研究、保护时间和高级流行病学、生物统计学和基于社区的参与性研究的课程方面的指导培训。该候选人的长期目标是成为一名学术医学中心的独立内科科学家，研究社区相关耐甲氧西林金黄色葡萄球菌(CA-MRSA)的流行病学和驱动葡萄球菌传播的分子机制，从而开发预防和治疗CA-MRSA感染的新方法。拟议的工作将在华盛顿大学和圣路易斯儿童医院的维多利亚·弗雷泽医学博士的指导下进行，维多利亚·弗雷泽是一位在传染病流行病学方面颇有成就的临床调查员。由经验丰富的临床和基础研究人员组成的教师咨询委员会将促进候选人的研究和职业发展。从浅表皮肤脓肿到侵袭性感染，CA-MRSA的流行菌株在具有免疫能力的个人，特别是儿童中会导致显著的发病率和死亡率。已观察到CA-MRSA感染聚集在家庭中。然而，影响CA-MRSA定植和感染的家庭定植压力和传播、卫生和行为危险因素以及环境污染之间的相互作用尚未明确。必须定义这些风险因素，以制定以证据为基础的指南，以阻断CA-MRSA的传播并预防感染。了解这些变量的影响将为改善健康和减轻CA-MRSA定植和疾病负担的实践提供信息。初步研究表明，CA-MRSA感染和定植的指标患者的家庭成员也被CA-MRSA定植。将对135名感染CA-MRSA的儿童患者及其家庭成员进行为期一年的前瞻性队列研究。使用混合效应Logistic回归模型，将阐明多个水平上的危险因素之间的关系(包括家庭定植压力、宿主行为习惯和家庭表面的污染)，以确定与CA-MRSA定植、感染和传播风险最大的因素。提出了三个综合的具体目标：1)确定一年来CA-MRSA在儿科指标患者及其家庭接触者中的定植和感染的传播动态，并确定CA-MRSA定植对随后CA-MRSA感染的贡献；2)确定导致CA-MRSA在家庭内传播、定植和感染的卫生和行为习惯；以及3)确定环境污染和家庭特征在家庭CA-MRSA传播中的作用。

DESCRIPTION (provided by applicant): This application for a K23 Career Development Award proposes a four-year program to provide the candidate with mentored training in patient-oriented research, protected time, and coursework in advanced epidemiology, biostatistics, and community-based participatory research. The long- term goals of the candidate are to become an independent physician-scientist at an academic medical center, investigating the epidemiology of community-associated methicillin-resistant Staphylococcus aureus (CA- MRSA) and the molecular mechanisms driving staphylococcal transmission, leading to the development of novel methods for the prevention and treatment of CA-MRSA infections. The proposed work will be performed at Washington University and St. Louis Children's Hospital under the mentorship of Victoria Fraser, M.D., an accomplished clinical investigator in infectious diseases epidemiology. A faculty advisory committee consisting of experienced clinical and basic researchers will facilitate the candidate's research and career development. Epidemic strains of CA-MRSA cause significant morbidity and mortality among immunocompetent individuals, especially children, ranging from superficial cutaneous abscesses to invasive infections. CA- MRSA infections have been observed to cluster in households. However, the interplay of household colonization pressure and transmission, hygiene and behavioral risk factors, and environmental contamination influencing CA-MRSA colonization and infection has not been specified. These risk factors must be defined to develop evidence-based guidelines to interrupt CA-MRSA transmission and prevent infections. Understanding the impact of these variables will inform practice to improve health and decrease the burden of CA-MRSA colonization and disease. Preliminary studies demonstrate that household members of index patients with CA-MRSA infection and colonization are also colonized with CA-MRSA. A one-year prospective cohort study of 135 pediatric patients with CA-MRSA infection and their household members will be performed. Using mixed effects logistic regression modeling, the relationships among risk factors at multiple levels (including household colonization pressure, host behavioral practices, and contamination of household surfaces) will be elucidated to identify factors conferring the greatest risks for CA-MRSA colonization, infection, and transmission. Three integrated specific aims are proposed: 1) Define the transmission dynamics of CA-MRSA colonization and infection among pediatric index patients and their household contacts over one year, and determine the contribution of CA-MRSA colonization to subsequent CA-MRSA infection; 2) Identify hygiene and behavioral practices contributing to CA-MRSA transmission, colonization, and infection within households; and 3) Determine the role of environmental contamination and household characteristics in household CA-MRSA transmission.