K. Suzuki et Lo. Bakaletz, SYNERGISTIC EFFECT OF ADENOVIRUS TYPE-1 AND NONTYPABLE HAEMOPHILUS-INFLUENZAE IN A CHINCHILLA MODEL OF EXPERIMENTAL OTITIS-MEDIA, Infection and immunity, 62(5), 1994, pp. 1710-1718
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,