Influenza virus may be transmitted through the respiratory route by inhalation of an aerosol of non-sedimenting droplets, or by deposition of sedimenting droplets in the upper respiratory tract. Whichever of these is the predominant route for infection with influenza virus has been subject of continuing debate, resulting in detailed studies of aerosol versus droplet exposure. A decisive knowledge gap preventing a satisfying conclusion is absence of a well defined human dose response model for influenza virus. This study uses a hierarchical approach generalizing over twelve human challenge studies collected in a literature search. Distinction is made between aerosol and intranasal inoculation. The results indicate high infectivity via either route, but intranasal inoculation leads to about 20 times lower infectivity than when the virus is delivered in an inhalable aerosol. A scenario study characterizing exposure to airborne virus near a coughing infected person in a room with little ventilation demonstrates that with these dose response models the probabilities of infection by either aerosol or sedimenting droplets are approximately equal. Droplet transmission results in a slightly higher illness risk due to the higher doses involved. Establishing a dose response model for influenza provides a firm basis for studies of interventions reducing exposure to different classes of infectious particles. More studies are needed to clarify the role of different modes of transmission in other settings.
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