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EFFECT OF INFLUENZA A VIRUS INFECTION ON NASOPHARYNGEAL COLONIZATION AND OTITIS MEDIA INDUCED BY TRANSPARENT OR OPAQUE PHENOTYPE VARIANTS OF STREPTOCOCCUS PNEUMONIAE IN THE CHINCHILLA MODEL BACKGROUND: Otitis media (OM) is one of the most common childhood diseases. The prevalence, medical care costs, and hearing-related morbidity of OM are significant. Streptococcus pneumoniae, the primary etiological agent, has been isolated from approximately 20 to 50% of middle-ear effusions from children with OM (4). The process whereby S. pneumoniae becomes established in the human nasopharynx and then affects the transition from a colonized to a diseased state in the middle ear is not yet known. Many children with OM experience an antecedent viral upper-respiratory-tract infection, and viruses are also recognized as important etiological agents of OM, either alone or in combination with bacterial pathogens. Influenza A virus, adenovirus, and respiratory syncytial virus are the primary respiratory-tract viruses associated with this disease (5, 6). A recent study with adult human volunteers indicates that influenza A virus infection promotes significant colonization of the nasopharynx by S. pneumoniae (21). GOAL: This study was designed to further assess the effects of influenza A virus on adherence, the kinetics of colonization, and invasion of the middle ear by isogenic opaque and transparent variants of S. pneumoniae type 6A in the chinchilla model of OM. PROCEDURE: A total of 48 healthy chinchillas (Chinchilla lanigera) (220 to 450 g) free of middle-ear disease, as determined by otoscopyand tympanometry, were used in these studies. Two cohorts of 12 chinchillas each were inoculated intranasally (i.n.) with influenza A virus followed 7 days later by i.n. inoculation with the S. pneumoniae type 6A opaque or transparent variant. Another two cohorts of 12 chinchillas each were inoculated i.n. with diluent only (without influenza A virus) followed 7 days later by i.n. inoculation of either opaque or transparent S. pneumoniae; these cohorts served as controls. Three chinchillas (preselected and randomized) from each cohort were evaluated for NP colonization and OM at each of four different time periods after S. pneumoniae type 6A inoculation as described below. The ability of influenza A virus to promote NP colonization by S. pneumoniae and development of OM was compared for the opaque and transparent variants. All experiments were performed in duplicate. CONCLUSION: The results from the present study indicate that the effects of influenza A virus on the pathogenesis of experimentalS. pneumoniae-induced OM vary depending on the opacity phenotype of the S. pneumoniae inoculum.