title: Systematic review of fever, febrile convulsions and serious adverse events following administration of inactivated trivalent influenza vaccines in children.
abstract: In 2010, increased febrile convulsions (FC) occurred after administration of inactivated trivalent influenza vaccine (TIV) in Australia. We systematically reviewed the rates of fever, FC and serious adverse events (SAEs) after TIV, focussing on published and unpublished clinical trial data from 2005 to 2012, and performed meta-analysis of fever rates. From 4,372 records in electronic databases, 18 randomised controlled trials (RCTs), 14 non-randomised clinical trials, six observational studies and 12 registered trials (five RCTs and seven non-randomised) were identified. In published RCTs, fever ≥ 38 °C rates after first dose of non-adjuvanted TIV were 6.7% and 6.9% for children aged 6–35 months and ≥ 3 years, respectively. Analysis of RCTs by vaccine manufacturer showed pooled fever estimates up to 5.1% with Sanofi or GlaxoSmithKline vaccines; bioCSL vaccines were used in two non-randomised clinical trials and one unpublished RCT and were associated with fever in 22.5–37.1% for children aged 6–35 months. In RCTs, FCs occurred at a rate of 1.1 per 1,000 vaccinated children. While most TIVs induced acceptably low fever rates, bioCSL influenza vaccines were associated with much higher rates of fever in young children. Future standardised study methodology and access to individual level data would be illuminating.
authors.affiliation: National Centre for Immunisation Research and Surveillance, The Children s Hospital at Westmead, New South Wales, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Li-Kim-Moy
authors.forename: J K
authors.initials: JK
authors.lastname: Yin
authors.forename: H
authors.initials: H
authors.lastname: Rashid
authors.forename: G
authors.initials: G
authors.lastname: Khandaker
authors.forename: C
authors.initials: C
authors.lastname: King
authors.forename: N
authors.initials: N
authors.lastname: Wood
authors.forename: K K
authors.initials: KK
authors.lastname: Macartney
authors.forename: C
authors.initials: C
authors.lastname: Jones
authors.forename: R
authors.initials: R
authors.lastname: Booy
mesh_terms: D002675:Child, Preschool; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis* / Q000453:epidemiology*; D005334:Fever / Q000139:chemically induced*; D006801:Humans; D007223:Infant; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D007251:Influenza, Human / Q000517:prevention & control*; D003294:Seizures, Febrile / Q000139:chemically induced*; D015164:Vaccines, Inactivated / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D007252:Influenza Vaccines; D015164:Vaccines, Inactivated