Immunopathogenesis of polymicrobial otitis media

Abstract

OM, or inflammation of the middle ear, is a highly prevalent infection in children worldwide. OM is a multifactorial disease with multiple risk factors, including preceding or concurrent viral URT infection. Hence, OM is also a polymicrobial disease. The mechanisms by which viruses predispose to bacterial OM are replete; however, all are predicated on the general principle of compromise of primary host airway defenses. Thus, despite an as-yet incomplete understanding of the molecular mechanisms involved in bacterial superinfection of a virus-compromised respiratory tract, the URT viruses are known to induce histopathology of airway mucosal epithelium, up-regulate expression of eukaryotic receptors used for bacterial adherence, alter the biochemical and rheological properties of airway mucus, and affect innate and acquired host immune functions, among others. Although discussed here in the context of OM, during preceding or concurrent viral infection of the human respiratory tract, viral impairment of airway defenses and the resulting predisposition to subsequent bacterial coinfection are also known to be operational in the mid and lower airway as well.

Viral-Bacterial Interactions and Risk of Acute Otitis Media Complicating Upper Respiratory Tract Infection

“…The majority of AOM episodes occur as complications of viral upper respiratory tract infection (URI) (10,17). Viral URI increases the risk of bacterial AOM by promoting the replication of bacteria and increasing inflammation in the nasopharynx and Eustachian tube, which subsequently facilitates bacterial entry into the middle ear space (4). Respiratory viruses can coinfect the middle ear with bacterial AOM pathogens and have been identified as the sole causative agent of AOM (19,29).…”

“…Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis colonize the nasopharynx and are the three most frequent AOM pathogens (9). While AOM is often considered a bacterial infection, its pathogenesis involves complex interactions among viruses and bacteria (4). The majority of AOM episodes occur as complications of viral upper respiratory tract infection (URI) (10,17).…”

Adenoid Reservoir for Pathogenic Biofilm Bacteria

“…An early childhood history of COM can result in auditory and verbal disabilities that exert influence into late childhood, rendering treatment of recurrent otitis media (ROM) and otitis media with effusion (OME) desirable (2,4,5,6,67). Repeated cycles of antibiotics for treatment of COM make it the leading reason for antibiotic usage in children (2).…”

Chronic Otitis Media: Microbial Environment During Viral Infection and Genetics of Host Susceptibility

“…29,30 The role of viruses on predisposition to bacterial OM has been shown to be due to multiple mechanisms including effects on bacterial adherence and colonization [31][32][33] , ET function 17,34 , antibiotic efficacy 35 , and mucociliary transport 36 . 37 Viruses most commonly detected in nasopharyngeal secretions of children with AOM include adenoviruses, influenza, respiratory syncytial virus (RSV), enterovirus, coronavirus, rhinovirus, and parainfluenza virus. 38,39 Host factors found to contribute to COME/ROM include ET obstruction, naïve immune systems, gender, age, race, and host genetics.…”

“…150 For example, viral infection of the URT is a predisposing risk that is thought to allow for pathogenic bacteria in the nasopharynx to induce inflammation and permit microbial invasion of the mucosa in the middle ear causing otitis media. 37 144,158 The disease model of a virus predisposing the host to a secondary bacterial infection is thought to be an oversimplification, with a much more complex dynamic being more likely. 139 Understanding the relationships between microbes of the URT, especially during perturbations, would give us insight into the pathogenesis of URT infections.…”