Epidemiological study of severe febrile reactions in young children in Western Australia caused by a 2010 trivalent inactivated influenza vaccine

Abstract

BackgroundThe 2010 influenza vaccination program for children aged 6 months to 4 years in Western Australia (WA) was suspended following reports of severe febrile reactions, including febrile convulsions, following vaccination with trivalent inactivated influenza vaccine (TIV).MethodsTo investigate the association between severe febrile reactions and TIV, three studies were conducted: (i) rates of febrile convulsions within 72 h of receiving TIV in 2010 were estimated by vaccine formulation and batch; (ii) numbers of children presenting to hospital emergency departments with febrile convulsions from 2008 to 2010 were compared; and (iii) a retrospective cohort study of 360 children was conducted to compare the reactogenicity of available TIV formulations.FindingsIn 2010, an estimated maximum of 18 816 doses of TIV were administered and 63 febrile convulsions were recorded, giving an estimated rate of 3.3 (95% CI 2.6 to 4.2) per 1000 doses of TIV administered. The odds of a TIV-associated febrile convulsion was highly elevated in 2010 (p<0.001) and was associated with the vaccine formulations of one manufacturer—Fluvax and Fluvax Junior (CSL Biotherapies). The risk of both febrile convulsions (p<0.0001) and other febrile reactions (p<0.0001) was significantly greater for Fluvax formulations compared to the major alternate brand. The risk of febrile events was not associated with prior receipt of TIV or monovalent 2009 H1N1 pandemic vaccine. The biological cause of the febrile reactions is currently unknown.InterpretationOne brand of influenza vaccine was responsible for the increase in febrile reactions, including febrile convulsions. Until the biological reason for this is determined and remediation undertaken, childhood influenza vaccination programs should not include Fluvax-type formulations and enhanced surveillance for febrile reactions in children receiving TIV should be undertaken.

Systematic review of fever, febrile convulsions and serious adverse events following administration of inactivated trivalent influenza vaccines in children

“…However, bioCSL TIVs had significantly higher fever after first doses in children aged six months to eight years, across three studies conducted from March 2005 through to May 2010, particularly in an RCT (NCT00959049) comparing bioCSL's Afluria and a comparator TIV [60], subsequently published after our literature search and review (Table 6). Observational studies from 2010 in Australia and New Zealand documented similar findings comparing bioCSL TIV to other manufacturers [58,62].…”

“…Of the 4,372 studies initially identified (Figure), 18 RCTs [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39], 14 non-randomised clinical trials [40][41][42][43][44][45][46][47][48][49][50][51][52][53], and six observational studies [54][55][56][57][58][59] were eligible for inclusion. The clinical trial registry search yielded 12 additional relevant studies (five RCTs and seven nonrandomised trials).…”

“…The six included observational studies [54][55][56][57][58][59] are summarised in Table 7. A study of inactivated virosomaladjuvanted TIV (Inflexal V) in 966 vaccinated children reported fever in 0.52%, without comparison data from the unvaccinated cohort [54].…”

“…One retrospective observational cohort study in children in Western Australia (WA) from 2010 reported on the rate of fever seen with bioCSL TIV [58]. Data linkage of TIV-associated FC cases and vaccine exposure recorded in the Australian Childhood Immunisation Register, was added to data obtained from vaccine providers or primary caregivers.…”

Comparison of text-messaging to voice telephone interviews for active surveillance of adverse events following immunisation

“…For example, in Western Australia an unexpected spike in adverse events following trivalent 61 influenza vaccination in children in 2010 resulted in an 84% reduction in influenza vaccine 62 uptake in young children [7,8]. This example serves as a reminder of the necessity of 63 vigilant vaccine safety programs and the importance of rapid signal response.…”