SYNERGISTIC EFFECT OF ADENOVIRUS TYPE-1 AND NONTYPABLE HAEMOPHILUS-INFLUENZAE IN A CHINCHILLA MODEL OF EXPERIMENTAL OTITIS-MEDIA

We recently reported the development of a chinchilla model of experime ntal otitis media (OM) that uses a pediatric clinical isolate of adeno virus type 1 (4) and in which an active infection with the wild-type s train was demonstrated. To expand upon these findings, this study was designed to determine whether we could demonstrate adenovirus infectio n-induced predisposition to bacterial OM in the chinchilla, as has bee n shown in human epidemiological studies (D. A. Clements, F.W. Henders on, and E. C. Neebe, p. 27-29, in D. J. Lim, C. D. Bluestone, J. O. Kl ein, D. J. Nelson, and P. L. Ogra, ed., Proceedings of the Fifth Inter national Symposium on Recent Advances in Otitis Media, 1993; F. W. Hen derson, A. M. Collier, M. A. Sanyai, et al., N. Engl. J. Med. 306:1377 -1383, 1982). In addition, we were interested in determining whether a ltering the order of pathogen acquisition would further affect the out come of disease incidence and severity. Toward this end, cohorts of ch inchillas were inoculated intranasally with a strain of nontypeable Ha emophilus influenzae (NTHi) (86-028NP) which colonizes the chinchilla nasopharynx but does not consistently induce culture-positive OM when inoculated intranasally (L. O. Bakaletz, T. M. Hoepf, D. J. Lim, and B . Tallan, Abstr. 90th Annu. Meet. Am. Sec. Microbiol. 1990, abstr. B-6 6, p. 37, 1990), adenovirus type 1 and then inoculated 7 days later wi th NTHi, NTI-Ii and then inoculated 7 days later with adenovirus type 1, or both pathogens concurrently. All cohorts were observed over a 35 -day period and assessed for incidence and severity of OM by several m ethodologies. The data collectively indicated that all animals receivi ng both pathogens developed OM of greater severity than those receivin g only a single agent. Adenovirus inoculation followed 7 days later by NTHi inoculation was the order of pathogen acquisition which induced the most prolonged presence of NTHi in both the nasopharynx and the mi ddle ear, the most severe tympanic membrane inflammation overall, and the most significant damage to and altered function of both middle ear and eustachian tube mucosae,