title: Live attenuated influenza virus increases pneumococcal translocation and persistence within the middle ear.
abstract: BACKGROUND
  Infection with influenza A virus (IAV) increases susceptibility to respiratory bacterial infections, resulting in increased bacterial carriage and complications such acute otitis media, pneumonia, bacteremia, and meningitis. Recently, vaccination with live attenuated influenza virus (LAIV) was reported to enhance subclinical bacterial colonization within the nasopharynx, similar to IAV. Although LAIV does not predispose to bacterial pneumonia, whether it may alter bacterial transmigration toward the middle ear, where it could have clinically relevant implications, has not been investigated.
  
  
  METHODS
  BALB/c mice received LAIV or phosphate-buffered saline 1 or 7 days before or during pneumococcal colonization with either of 2 clinical isolates, 19F or 7F. Middle ear bacterial titers were monitored daily via in vivo imaging.
  
  
  RESULTS
  LAIV increased bacterial transmigration to and persistence within the middle ear. When colonization followed LAIV inoculation, a minimum LAIV incubation period of 4 days was required before bacterial transmigration commenced.
  
  
  CONCLUSIONS
  While LAIV vaccination is safe and effective at reducing IAV and coinfection with influenza virus and bacteria, LAIV may increase bacterial transmigration to the middle ear and could thus increase the risk of clinically relevant acute otitis media. These data warrant further investigations into interactions between live attenuated viruses and naturally colonizing bacterial pathogens.
authors.affiliation: Medical Scientist Training Program, Emory University School of Medicine Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mina
authors.affiliation: Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia.
authors.forename: Keith P
authors.initials: KP
authors.lastname: Klugman
authors.affiliation: Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Rosch
authors.affiliation: Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: McCullers
mesh_terms: D000818:Animals; D018988:Bacterial Translocation; D007113:Immunity, Innate; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D008807:Mice, Inbred BALB C; D010033:Otitis Media / Q000276:immunology / Q000382:microbiology*; D011008:Pneumococcal Infections / Q000276:immunology / Q000382:microbiology*; D013296:Streptococcus pneumoniae / Q000502:physiology; D014611:Vaccination; D062690:Vaccines, Live, Unattenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D007252:Influenza Vaccines; D062690:Vaccines, Live, Unattenuated
keywords: acute otitis media; bacterial transmigration; coinfection; live attenuated influenza virus; middle ear bacterial colonization; pneumococcus