title: Shedding of Ann Arbor strain live attenuated influenza vaccine virus in children 6-59 months of age.
abstract: BACKGROUND
  A trivalent, Ann Arbor strain, live attenuated influenza vaccine (LAIV) is approved for use in children 24 months of age and older in a number of countries. The incidence, duration, and other parameters of viral shedding after vaccination with LAIV have not been fully described in children ≤ 5 years of age.
  
  
  METHODS
  An open-label, single-arm, multicenter, phase 2 study assessed viral shedding and safety in 200 children 6-59 months of age after a single, intranasal dose of LAIV in 2006. Participants were enrolled into 2 age groups: 6-23 months (n=100) and 24-59 months (n=100) of age. Viral shedding, reactogenicity, and adverse events were assessed for 28 days postvaccination. Serious adverse events and significant new medical conditions were monitored for 180 days postvaccination.
  
  
  RESULTS
  Viral shedding was detected by culture in 79% (95% CI, 73-84) of vaccine recipients and occurred more frequently in children 6-23 months of age (89%) compared with children 24-59 months of age (69%). In total, 157 subjects shed vaccine, which was confirmed by RT-PCR as A/H1N1 for 128 subjects, A/H3N2 for 72 subjects, and B for 74 subjects. The incidence of shedding was highest on day 2 (59% in the 6-23 month age group; 41% in the 24-59 month age group) and most shedding occurred 1-11 days postvaccination; shedding after 11 days was infrequent and occurred almost exclusively in children 6-23 months of age. Mean titers of shed vaccine virus peaked on day 2 and were generally <10(3.0) median tissue culture infective dose/mL for both groups. Reactogenicity events peaked on day 2; runny/stuffy nose was reported most frequently (63% of all subjects).
  
  
  CONCLUSIONS
  Most children 6-59 months of age vaccinated with Ann Arbor strain LAIV shed ≥ 1 vaccine virus within 11 days of vaccination. Shedding was less common in children 24-59 months of age, a population for whom LAIV is approved for use. Titers of shed vaccine were low, which may explain why secondary transmission of LAIV was observed very infrequently in a previous controlled study conducted with young children in a daycare setting.
authors.affiliation: MedImmune, LLC, One MedImmune Way, Gaithersburg, MD 20878, USA. malloryr@MedImmune.com
authors.forename: Raburn M
authors.initials: RM
authors.lastname: Mallory
authors.forename: Tingting
authors.initials: T
authors.lastname: Yi
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Ambrose
mesh_terms: D000281:Administration, Intranasal; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology; D009980:Influenza A virus / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D009981:Influenza B virus / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D007251:Influenza, Human / Q000517:prevention & control* / Q000821:virology; D008297:Male; D016896:Treatment Outcome; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage* / Q000276:immunology; D017201:Virus Shedding
chemical_list: D007252:Influenza Vaccines; D014613:Vaccines, Attenuated