Evaluating Modes of Influenza Transmission using a Randomized Controlled Trial (EMIT-2-RCT)

项目摘要/摘要-使用随机化的 对照试验 “使用随机对照试验评估流感传播模式（EMIT-2-RCT）” 研究项目解决了一个关键的知识差距，缺乏有关机制的确切证据， 传播，特别是病毒气溶胶（空气传播或气溶胶传播）的重要性， 接触-污染物和喷雾（也称为液滴）传播。该项目的总体目标是 评估病毒气溶胶释放和通风如何相互作用以促进人与人之间的流感 传播，并提供在缺乏或低血凝情况下保护相关性的见解 使用一种新的研究设计，对抑制（HI）抗体进行研究。在这样做时，我们直接解决NIAID的目标1.1 战略计划。我们的中心假设是，传染性气溶胶是流感的主要贡献者 通风和减少气溶胶暴露与这两种攻击的减少有关 发病率和疾病严重程度。我们在量化传染性呼出气溶胶方面具有独特的优势， Gesundheit-II以前在PI的实验室开发，并与一个 高度多学科的团队。我们将全面评估通过直接接触，污染物， 喷雾传播的滴剂和气溶胶作为促进传播的因素， 7组对照试验，每组4名自然感染供体和18名受体。临床和 生物统计学核心将提供基础设施，以招募和筛选参与者以及临床监督 隔离设施的一部分在每个组中，我们将随机分配一半的收件人到一个手 屏蔽干预第一年的第一组将处于低通风环境中。2-4年，我们将 每年进行两个暴露组，一个在低通风环境中，一个在高通风环境中 室内环境用紫外线杀菌，空气卫生。具体而言，我们将：（1）识别主导模式 在一项随机对照研究中， 空气卫生-通风和手卫生-面罩干预试验;（2）确定 气溶胶暴露对疾病严重程度的影响;（3）研究血清学和粘膜抗体水平的影响 流感传播，易感性和免疫反应感染的情况下，缺乏或非常 低水平的血凝抑制抗体。这项独特的随机对照试验将提供一个 对气溶胶在传播中的作用进行明确评估，并提供关键数据， 非药物干预措施，并评估疫苗的效力和治疗对传播的影响。

Project Summary/Abstract – Evaluating Modes of Influenza Transmission using a Randomized Controlled Trial The “Evaluating Modes of Influenza Transmission using a Randomized Controlled Trial (EMIT-2-RCT)” research project addresses a key knowledge gap, the lack of definitive evidence regarding the mechanisms of transmission, in particular the importance of viral aerosols (airborne or aerosol transmission) as compared with contact - fomite and sprayborne (also called droplet) transmission. The overall objective of this project is to evaluate how viral aerosol shedding and ventilation interact to facilitate human-to-human influenza transmission and provide insights into correlates of protection in the setting of absent or low hemagglutination inhibiting (HI) antibodies using a novel study design. In doing so, we directly address objective 1.1 of the NIAID strategic plan. Our central hypothesis is that infectious aerosols are a major contributor to influenza transmission and that ventilation and reduced aerosol exposure are associated with reduction of both attack rates and disease severity. We are uniquely positioned to quantify infectious exhaled breath aerosols with the Gesundheit-II previously developed in the PI’s lab and to extend these measurements in collaboration with a highly multidisciplinary team. We will comprehensively evaluate exposure via direct contact, fomites, sprayborne drops, and aerosols as factors facilitating transmission by conducting a novel randomized controlled trial of seven groups with 4 naturally infected Donors and 18 Recipients per group. The Clinical and Biostatistics Core will provide the infrastructure to recruit and screen the participants and the clinical oversight of the quarantine facility. Within each group, we will randomize half of the Recipients to a hand hygiene–face shield intervention. The first group in year-1 will be in a low ventilation environment. In years 2-4 we will conduct two exposure groups per year, one in a low ventilation environment and one in a high ventilation environment with upper-room germicidal UV air sanitation. Specifically, we will: (1) Identify the dominant mode of transmission using naturally infected Donors with community acquired infection in a randomized controlled trial of air sanitation-ventilation and hand hygiene–face shield interventions; (2) Determine the impact of aerosol exposure on disease severity; and (3) Investigate the impact of serologic and mucosal antibody levels on influenza transmission, susceptibility and immunologic response to infection in the setting of absent or very low levels of hemagglutination inhibiting antibodies. This unique randomized controlled trial will provide a definitive assessment of the role of aerosols in transmission and provide critical data on which to build effective non-pharmaceutical interventions and assess efficacy of vaccine and therapeutic impacts on transmission.