Translational Research: From Mechanisms of Influenza Transmission to Prevention

转化研究：从流感传播机制到预防

• 批准号: 7988354
• 负责人: Donald Kirby Milton
• 金额: $ 47.85万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-26 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7988354
• 关键词: Prevention; Translational Research; flu transmission

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (15) Translational Research and specific Challenge Topic, 151-AI-106: Translational research focused on high priority pathogens (influenza) and basic research focused on resistance mechanisms. Pandemic influenza remains an important threat - we are currently under a Phase 3 Alert of the WHO Global Influenza Preparedness Plan. During this phase, one of our essential tasks is to test and optimize public health intervention strategies to reduce transmission of influenza. Key among these strategies is social distancing and use of personal protective equipment including surgical masks. Unfortunately, traditional effectiveness research using empirical tests of these approaches has been mostly uninformative because of limited compliance with mask use and a requirement for very large sample sizes. Thus, we need a translational approach, rooted in basic science about how influenza is transmitted, to design and test interventions. An Institute of Medicine report, however, recently pointed out that basic data on how influenza is transmitted is lacking, posing a critical knowledge gap. Therefore, we propose to address that critical basic knowledge gap, test a specific intervention strategy, and to translate our findings into public health recommendations. We propose to use a new technology that we recently developed for biological particle collection (U.S. Provisional Patent Application No. 61/162,395) to make fundamental observations on infectious respiratory droplets in a study of 220 naturally occurring seasonal influenza cases over two influenza seasons. We will collect respiratory droplets shed by participants while breathing normally, talking, and spontaneously coughing. We will characterize the size distribution of droplets containing infectious virus and observe the impact of host factors (e.g. asthma), virus type and strain, and drug resistance on virus shedding into respiratory droplets. We will also test the effectiveness of surgical masks to limit the release of infectious droplets and whether this effect is dependent on type, strain, drug resistance, and host characteristics. We will use these basic data to examine the roles of large and small respiratory droplets and examine how the interaction of host factors and virus type impact the shedding of infectious respiratory droplets. These data will also provide a baseline for comparison to determine whether experimental human infections accurately mimic the viral shedding of people with naturally acquired, wild-type infections. Without this basic data, it will not be possible to know whether large experimental studies of influenza transmission adequately represent likely modes of transmission in the real world. Thus, this project will improve our understanding of the mechanisms of transmission for seasonal influenza; the effect of type, strain, co-infection, and drug resistance on virus release in large and small respiratory droplets; and provide evidence necessary to translate knowledge of transmission mechanisms into infection control recommendations for hospitals and the general public. PUBLIC HEALTH RELEVANCE: This project will address a critical knowledge gap about how influenza is transmitted. It will provide guidance on what public health measures are likely to be effective for limiting transmission during an influenza pandemic. The project will evaluate whether surgical masks can limit release of infectious virus from influenza patients, and provide a basis for determining when and if respirators capable of capturing fine particle aerosols are needed to protect health care workers treating influenza patients.

描述（由申请人提供）：本申请涉及广泛的挑战领域（15）转化研究和特定挑战主题，151-AI-106：转化研究的重点是高优先病原体（流感）和基础研究，而基础研究的重点是抵抗机制。大流行性流感仍然是一个重要的威胁 - 我们目前正处于WHO全球流感准备计划的第三阶段警报。在此阶段，我们的重要任务之一是测试和优化公共卫生干预策略，以减少流感的传播。这些策略的关键是社会疏远和使用包括手术口罩在内的个人防护设备。不幸的是，使用这些方法的经验测试进行的传统有效性研究主要是不明智的，因为遵守面具的使用和对非常大的样本量的要求。因此，我们需要一种翻译方法，它植根于基础科学，介绍了如何传播流感，设计和测试干预措施。然而，医学研究所报告最近指出，缺乏流感传播的基本数据，构成了关键的知识差距。因此，我们建议解决关键的基本知识差距，测试特定的干预策略，并将我们的发现转化为公共卫生建议。我们建议使用我们最近开发的一种新技术（美国临时专利专利应用程序号61/162,395），以对220个自然存在的季节性流感案例在两个流感季节中进行，对传染性呼吸液滴进行基本观察。我们将收集参与者脱落的呼吸液滴，同时正常呼吸，说话和自发咳嗽。我们将表征含有感染性病毒的液滴的尺寸分布，并观察宿主因子（例如哮喘），病毒类型和菌株的影响，以及耐药性对将病毒脱落到呼吸液滴中的影响。我们还将测试手术口罩的有效性，以限制传染性液滴的释放，以及这种作用是否取决于类型，应变，耐药性和宿主特征。我们将使用这些基本数据来检查大小呼吸液滴的作用，并研究宿主因子和病毒类型的相互作用如何影响传染性呼吸液滴的脱落。这些数据还将提供一个基线，以确定实验性人类感染是否准确地模仿具有自然获得的，野生型感染的人的病毒脱落。没有这些基本数据，就不可能知道对流感传播的大量实验研究是否足以代表现实世界中的传播模式。因此，该项目将提高我们对季节性流感传播机制的理解。类型，应变，共感染和耐药性对大和小呼吸液滴中病毒释放的影响；并提供必要的证据将传播机制知识转化为医院和公众的感染控制建议。 公共卫生相关性：该项目将解决有关流感如何传播的关键知识差距。它将提供有关哪些公共卫生措施可能有效限制流感大流行期间传播的指导。该项目将评估手术口罩是否可以限制流感患者的感染性病毒的释放，并为确定何时以及是否需要捕获精细颗粒气溶胶的呼吸器来保护治疗流感患者的医疗保健工作者。