Hospital-Associated Respiratory Virus Infections: Molecular Epidemiology, Clinical Outcomes, and Cost-Effectiveness of Interventions

项目摘要/摘要 医院相关呼吸道病毒感染(HA-RVI)导致发病率、死亡率和医疗保健增加 成本，但这些感染往往被低估或误诊，特别是对呼吸道病毒 流行性感冒。HA-RVI通过适当的治疗和感染控制措施是可以预防的，但 不完整的诊断会导致错失干预机会。利用这些机会 可能需要额外的诊断性检测和扩大感染控制措施。这个 目前尚不清楚这些方法在多大程度上具有成本效益。因此，有必要定义 医院环境中呼吸道病毒的负担和临床影响，以提供最佳诊断和治疗 和感染预防策略。该项目的总体目标是支持Josh Petrie博士 发展医疗保健流行病学专业知识、最先进的分子方法和先进的 建模技术。这一目标将通过重点培训和职业发展来实现。 医疗保健流行病学、下一代测序、生物信息学、成本效益分析、 以及由一支优秀的导师团队监督的数学建模。这些技能是由 培训和职业发展目标将通过有指导的研究来加强，以实现 以下具体目标：(1)界定社区获得性疾病和医院感染的流行病学和负担-- 相关呼吸道病毒感染和比较病毒种类对临床的影响；(2)提高敏感性 以及病例定义的特异性，以通过结合临床、 流行病学和分子数据；以及(3)确定呼吸道病毒增加的成本效益 利用数学模型筛选和扩大感染控制措施，以减少HA-RVI。完成 将代表着皮特里博士在实现他的目标的道路上的下一步 建立独立研究计划的长期目标，该计划使用多学科实验室和 调查流感和其他呼吸道病毒传播的分析方法。预期中的 拟议项目的研究成果是：1)鉴定呼吸道病毒，除了 流感引起的HA-RVI数量最多，并导致最严重的临床后果； 2)开发方法学，通过整合临床、 流行病学和分子数据；以及3)确定具有成本效益的诊断检测和干预措施 预防HA-RVI的实施战略。拟议的研究具有重要意义，因为它是预期的 这项工作的结果以及以此为基础的未来研究将导致发病率的降低， 死亡率和与HA-RVI相关的医疗费用。这项研究的创新之处在于它关注的是一个 重要呼吸道病毒小组及其跨学科方法的使用，从而允许新的 研究的途径。

PROJECT SUMMARY / ABSTRACT Hospital-associated respiratory virus infections (HA-RVI) lead to increased morbidity, mortality, and healthcare costs, but these infections are often under- or misdiagnosed particularly for respiratory viruses other than influenza. HA-RVI are preventable through appropriate treatment and infection control measures, but incomplete diagnosis leads to missed opportunities for intervention. Taking advantage of these opportunities for intervention might require additional diagnostic testing and expanded infection control measures. The degree to which these approaches would be cost-effective is unclear. Therefore, there is a need to define the burden and clinical impact of respiratory viruses in the hospital setting to inform optimal diagnostic, treatment and infection prevention strategies. The overall objective of this project is to support Josh Petrie, PhD in the development of expertise in healthcare epidemiology, state-of-the-art molecular methods, and advanced modeling techniques. This objective will be completed through focused training and career development activities in healthcare epidemiology, next generation sequencing, bioinformatics, cost-effectiveness analysis, and mathematical modeling that is overseen by an excellent team of mentors. The skills developed by the training and career development objectives will be strengthened by mentored research to accomplish the following Specific Aims: (1) Define the epidemiology and burden of community-acquired and hospital- associated respiratory virus infections and compare clinical impact by viral species; (2) Improve the sensitivity and specificity of case definitions to identify hospital-associated influenza cases by integrating clinical, epidemiologic, and molecular data; and (3) Determine the cost-effectiveness of increased respiratory virus screening and expanded infection control measures to reduce HA-RVI using mathematical models. Completion of the training and research programs will represent the next step on Dr. Petrie's path toward achieving his long term goal of establishing an independent research program that uses multidisciplinary laboratory and analytic methodologies to investigate the transmission of influenza and other respiratory viruses. The expected research outcomes of the proposed project are, 1) identification of respiratory viruses that, in addition to influenza, are responsible for the greatest number of HA-RVI and result in the most severe clinical outcomes; 2) development of methodology for improved identification of HA-RVI through integration of clinical, epidemiologic, and molecular data; and 3) determination of cost-effective diagnostic testing and intervention implementation strategies for HA-RVI prevention. The proposed research is significant because it is expected that the outcomes of this work and future studies that build upon it, will lead to reductions in morbidity, mortality, and healthcare costs associated with HA-RVI. This research is innovative both in its focus on a large panel of important respiratory viruses and its use of cross-disciplinary methodology that allows for new avenues of research.