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

Abstract

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.

Viral diseases of ferrets

“…Clinical signs appear 48 hours postinfection and include anorexia, malaise, fever, sneezing, and serous nasal discharge [1,56]. Infection usually is mild in adult ferrets compared with neonates who can be severely ill [57]. Conjunctivitis, photosensitivity, and unilateral otitis also may be seen [1,58].…”

“…Usually, influenza virus is confined to the bronchial and bronchiolar tissues [53,60]. The disease may be fatal in 1-to 2-day-old ferret kits secondary to bronchiolitis, pneumonia, and aspiration of material from the upper respiratory tract [57,61,62]. Lancefield group C hemolytic streptococci have been involved in secondary bacterial pneumonia [56].…”

Histological and serological evidence of disease among invasive, non-native stoats Mustela erminea

“…Potential causes of pneumonia in mustelids are numerous (Fox, 1998) and there is evidence of viral-bacterial synergism in the symptoms of severe pneumonia (Jakeman et al, 1991). Mink and ferrets are also susceptible to avian influenza (Buchman et al, 1995;Englund and af Segerstad, 1998). During a review of diseases of stoats and related mustelids, McDonald and Larivière (2001) identified a range of diseases in which horizontal transmission may occur through the respiratory tract, perhaps the best known of which are tuberculosis and paratuberculosis caused by Mycobacterium spp.…”

Prevention of otitis media caused by viral upper respiratory tract infection: Vaccines, antivirals, and other approaches

“…The cause of eustachian-tube dysfunction during a vURI is debated. Histologic studies in chinchillas document extension of the virus infection to the luminal mucosa, but eustachian-tube function tests in infected ferrets, children, and adults evidence mucosal swelling, possibly caused by NGI [65][66][67]. Attempts to preserve adequate eustachiantube function (and ambient ME pressure) during a vURI using oral decongestants in children and adults have not been successful [68].…”