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）转化研究和具体挑战主题，151-AI-106：重点关注高优先级病原体（流感）的转化研究和重点关注耐药机制的基础研究。大流行性流感仍然是一个重要威胁——我们目前正处于世界卫生组织全球流感防范计划的第三阶段警报之下。在此阶段，我们的基本任务之一是测试和优化公共卫生干预策略，以减少流感传播。这些策略中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装备。不幸的是，由于对口罩使用的合规性有限以及对非常大样本量的要求，使用这些方法的经验测试的传统有效性研究大多缺乏信息。因此，我们需要一种植根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，医学研究所最近的一份报告指出，缺乏有关流感传播方式的基本数据，造成了严重的知识差距。因此，我们建议解决这一关键的基础知识差距，测试具体的干预策略，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生物颗粒收集新技术（美国临时专利申请号 61/162,395），在对两个流感季节的 220 例自然发生的季节性流感病例的研究中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、说话和自发咳嗽时排出的呼吸道飞沫。我们将表征含有传染性病毒的飞沫的大小分布，并观察宿主因素（例如哮喘）、病毒类型和毒株以及耐药性对病毒脱落到呼吸道飞沫中的影响。我们还将测试外科口罩限制传染性飞沫释放的有效性，以及这种效果是否取决于类型、菌株、耐药性和宿主特征。我们将利用这些基本数据来研究大小呼吸道飞沫的作用，并研究宿主因素和病毒类型的相互作用如何影响传染性呼吸道飞沫的脱落。这些数据还将提供比较基线，以确定实验性人类感染是否准确模仿自然获得的野生型感染者的病毒脱落。如果没有这些基本数据，就不可能知道流感传播的大型实验研究是否充分代表了现实世界中可能的传播模式。因此，该项目将增进我们对季节性流感传播机制的了解；类型、毒株、合并感染和耐药性对大小呼吸道飞沫中病毒释放的影响；并提供必要的证据，将传播机制的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。它将就哪些公共卫生措施可能有效限制流感大流行期间的传播提供指导。该项目将评估外科口罩是否可以限制流感患者传染性病毒的释放，并为确定何时以及是否需要能够捕获细颗粒气溶胶的呼吸器来保护治疗流感患者的医护人员提供依据。