Evaluating Modes of Influenza Transmission (EMIT-2) using Innovative Technologies and Designs in Controlled Environments

项目摘要/摘要-总体组成部分 我们建议进行多学科研究，以全面评估接触、福美特、喷洒和 气溶胶传播及其如何与通风相互作用以促进人与人之间的流感传播 使用一套创新技术来改进采样、分级、培养和表征 流感病毒气雾剂。这些研究充分利用了我们高度多样化的生物工程专家团队--气溶胶 科学、人类挑战和临床试验、流感病毒学和免疫学、传染病 流行病学、空气生物学和计算流体力学。该提案围绕两项研究展开 项目和三个核心。在研究项目1中，“评估流感传播的模式”。 随机对照试验(EMIT-2-RCT)：我们将研究两种干预措施的影响：a)通风和空气 卫生和b)手部卫生和面罩，防止从 自然感染病例向血清易感志愿者传播。我们将使用RCT来检验假设 气溶胶传播是主要的传播方式，与发烧和全身性发热的频率较高有关 继发病例的症状，在没有血凝抑制抗体的情况下，抗体 针对其他目标将与预防感染和疾病密切相关。在研究项目2中， 《流感传播分析模型的开发与应用》我们将使用计算流体 动力学和新的气溶胶测量，以a)设计干预和采样战略 RCT使我们能够区分短距离和远程气溶胶传播与喷雾传播，b) 根据可测量的量来定义Wells-Riley气溶胶感染量，并在 在混合良好和不混合的室内空气条件下的受试者呼吸区水平，以及c)延长我们的 从模型到家庭和动物研究，并为公共卫生科学家创造实用的分析工具 收集数据并评估现场风险。研究项目将由先进的生物气雾剂提供支持 将开发新的病毒气溶胶采样和培养系统和方法的技术核心(ABTC) 环境和呼气采样，将验证RCT设计并为 分析模型。临床和生物统计核心(CBC)将提供临床基础设施，以执行 复杂的检疫研究。管理核心将管理这些紧密集成的组件以进行模塑 对流感在人与人之间传播的动态和驱动因素的跨学科见解。

Project Summary/Abstract – Overall Component We propose multidisciplinary studies to comprehensively evaluate the roles of contact, fomite, sprayborne, and aerosol transmission and how they interact with ventilation to facilitate human-to-human influenza transmission using a suite of innovative technologies for improved sampling, fractionation, culture, and characterization of influenza virus aerosols. These studies leverage our highly diverse team of experts in bioengineering, aerosol science, human challenge and clinical trials, influenza virology and immunology, infectious diseases epidemiology, aerobiology, and computational fluid dynamics. The proposal is organized around two research projects and three cores. In Research Project 1, “Evaluating Modes of Influenza Transmission using a Randomized Controlled Trial (EMIT-2-RCT)” we will study the impact of two interventions a) ventilation and air sanitation and b) hand hygiene and face shields on transmission of circulating seasonal influenza from naturally infected cases to serologically susceptible volunteers. We will use the RCT to test hypotheses that aerosol transmission is the dominant mode, is associated with greater frequency of fever and systemic symptoms in secondary cases, and that in the absence of hemagglutination inhibiting antibodies, antibodies against other targets will strongly correlate with protection from infection and disease. In Research Project 2, “Developing and Applying Analytical Models of Influenza Transmission” we will use computational fluid dynamics and novel new aerosol measurements to a) design interventions and sampling strategies for the RCT enabling us to distinguish short- and long-range aerosol transmission from sprayborne transmission, b) define the Wells-Riley aerosol quantum of infection in terms of measurable quantities and assess risk at the recipient breathing zone level in both well-mixed and non-well-mixed indoor air conditions, and c) extend our models to household and animal studies and create practical analytical tools for public health scientists to collect data and assess risk in the field. The Research Projects will be enabled by an Advanced Bioaerosol Technology Core (ABTC) that will develop new viral aerosol sampling and culture systems and methods for both ambient and exhaled breath sampling that will validate the RCT design and provide critical inputs to the analytical models. A Clinical and Biostatistics Core (CBC) will provide the clinical infrastructure to perform the complex quarantine studies. The Administrative Core will manage these tightly integrated components to mold transdisciplinary insights into the dynamics and drivers of influenza transmission between humans.