Otologic and systemic manifestations of experimental influenza A virus infection in the ferret.

In an effort to further validate an animal model and to better define the mechanisms relating viral upper respiratory tract infections and acute otitis media, we infected 10 ferrets intranasally with influenza A virus. Infection was monitored by cultures and antibody titers, illness was monitored by signs and temperatures, and otologic complications were monitored by otoscopy, tympanometry, and eustachian tube function testing. All animals became infected. Forced-response test results showed progressive increases in the passive function variables after inoculation. Inflation-deflation test results documented progressive impairment of active tubal function, which was accompanied by the development of middle ear underpressures. No otitis media was seen. The results suggest that influenza A virus infection results in progressive, subtotal occlusion of the eustachian tube lumen, which compromises the ventilatory function of the tube, thereby promoting the development of middle ear underpressures. These findings support the hypothesized pathophysiologic relationship between viral upper respiratory tract infections, eustachian tube dysfunction, middle ear underpressures, and acute otitis media. Given these pathophysiologic changes and previously documented physiologic similarities to the eustachian tube-middle ear system of human beings, we conclude that the ferret represents an appropriate animal model for studying the pathogenic processes related to viral upper respiratory tract infections, eustachian tube dysfunction, and otitis media and for testing of potential prophylactic and therapeutic regimens.