An infant mouse model of influenza-driven nontypeable Haemophilus influenzae colonization and acute otitis media suitable for preclinical testing of novel therapies

Nontypeable Haemophilus influenzae (NTHi) is a Gram-negative bacterium that exhibits opportunistic pathogenic behavior in humans (1). Asymptomatic nasopharyngeal colonization with NTHi is common and transient in children, with carriage frequencies ranging from ~15% to 100% depending upon age and geographic region (2–5). NTHi can also cause a range of diseases including sinusitis, conjunctivitis, pharyngitis, meningitis, bacteraemia, pneumonia, and otitis media (OM) (6, 7). Globally, NTHi is the predominant pathogen associated with chronic OM with effusion, recurrent acute OM, or acute OM with failure to treat (8). Early and dense NTHi colonization is associated with the development of acute and recurrent OM (6, 9–13). Triggers for the development of asymptomatic NTHi colonization into OM are thought to involve virus-induced inflammation, which permits proliferation and dissemination of NTHi from the nasopharynx along the Eustachian tube and into the middle ear (14, 15).