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EMIT: Evaluating Modes of Influenza Transmission using a Human Challenge Model

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Influenza transmission between humans is poorly understood. Although it is known that the human cough or sneeze produces particles in a continuum from <1um to >1000um diameter, the relative contribution of particles of differing sizes is unresolved. Current uncertainty has made the development of evidence-based infection control guidance difficult;the single most problematic issue being whether healthcare workers should wear surgical face-masks or N95 respirators when caring for influenza patients, i.e. whether droplet sprays (>10um diameter) or droplet nuclei (<10um) pose the greatest hazard. The Overall Objective is: to determine the relative importance of droplet nuclei in the transmission of influenza by using a quarantine-based human challenge model. Specific Aims are: To describe the distribution and infectious potential of respiratory particles of different sizes obtained from patients infected with naturally acquired influenza compared with volunteers deliberately infected with a wild-type influenza A/H3N2 virus;To study human-human transmission from volunteers deliberately infected with a wild- type influenza (donors) to susceptible volunteers (recipients), exposed under close living condition, with recipients randomized to no intervention or face-shields and hand hygiene to allow selective exposure to droplet nuclei only;To determine the secondary attack rate in recipients exposed 'unprotected'to infected donors, versus the secondary attack rates in recipients in whom exposure is only possible via droplet nuclei In a series of secure quarantines we will challenge healthy susceptible volunteers (donors) with a wild-type (GMQ) A/H3N2 virus by nasal inoculation. After donors'symptoms develop, we will expose other susceptible volunteers (recipients) for three days under close 'household-like'conditions, during which time recipients will be randomized to wear face-shields and practice hand hygiene, versus no intervention (controls). Secondary attack rates will be measured by PCR, culture and serology. We will standardize the environment (temperature and humidity) to optimize influenza transmission, and study in detail the aerobiological environment via sampling of exhaled breath and room air, and the touched environment via surface swabbing.

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