Translational Research: From Mechanisms of Influenza Transmission to Prevention

描述（由申请人提供）：该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：转化研究侧重于高优先级病原体（流感）和基础研究侧重于耐药性机制。大流行性流感仍然是一个重要威胁——我们目前处于世卫组织全球流感防范计划的第3级警报之下。在这一阶段，我们的基本任务之一是测试和优化公共卫生干预战略，以减少流感的传播。这些战略的关键是保持社交距离和使用包括外科口罩在内的个人防护设备。不幸的是，使用这些方法的实证测试的传统有效性研究大多缺乏信息，因为口罩使用的依从性有限，并且需要非常大的样本量。因此，我们需要一种基于关于流感如何传播的基础科学的转化方法来设计和测试干预措施。然而，医学研究所的一份报告最近指出，缺乏关于流感如何传播的基本数据，造成了严重的知识鸿沟。因此，我们建议解决这一关键的基本知识差距，测试具体的干预策略，并将我们的研究结果转化为公共卫生建议。我们建议使用我们最近开发的生物颗粒收集新技术（美国临时专利申请号61/ 162395），对两个流感季节220例自然发生的季节性流感病例进行研究，对传染性呼吸道飞沫进行基本观察。我们将收集参与者在正常呼吸、说话和自发咳嗽时的呼吸道飞沫。我们将描述含传染性病毒飞沫的大小分布特征，并观察宿主因素（如哮喘）、病毒类型和毒株以及耐药性对病毒进入呼吸道飞沫的影响。我们还将测试医用口罩在限制传染性飞沫释放方面的有效性，以及这种效果是否取决于病毒类型、毒株、耐药性和宿主特征。我们将利用这些基础数据来研究大飞沫和小飞沫的作用，并研究宿主因素和病毒类型的相互作用如何影响传染性飞沫的脱落。这些数据还将为比较提供基线，以确定实验性人类感染是否准确地模拟自然获得的野生型感染的病毒脱落。没有这些基本数据，就不可能知道流感传播的大型实验研究是否足以代表现实世界中可能的传播模式。因此，这个项目将提高我们对季节性流感传播机制的理解；类型、毒株、合并感染和耐药性对大、小飞沫病毒释放的影响；并提供必要证据，将传播机制知识转化为针对医院和公众的感染控制建议。

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.