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Vaccine. 2011 Jul 18;29(32):5107-13. doi: 10.1016/j.vaccine.2011.05.054. Epub 2011 Jun 1.

Trivalent influenza vaccine and febrile adverse events in Australia, 2010: clinical features and potential mechanisms.

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School of Paediatrics & Child Health, University of Western Australia, Perth, WA, Australia.



Increased numbers of children presenting with febrile adverse events following trivalent influenza vaccine (TIV) were noted in Australia in 2010. We describe the epidemiology and clinical features of the adverse events and explore the biological basis for the adverse events using an in vitro model.


Children presenting to a tertiary paediatric hospital in 2010 with adverse events within 72 h of TIV were retrospectively reviewed. Demographics, clinical features, physiological variables and outcomes were examined. Plasma cytokine and chemokine levels were examined in a subgroup of children with vaccine-related febrile convulsions. Peripheral blood mononuclear cells of age-matched children were stimulated with different TIV preparations. Inflammatory cytokine and chemokine analysis was performed on cultured supernatants.


Vaccine-related febrile adverse events were identified in 190 children. Most occurred in healthy children (median age: 1.5 years) within 12 h of vaccination. Twenty-eight (14.7%) required hospital admission. High temperature ≥39.0 °C (101/190; 53%), vomiting (120/190; 63%) and convulsions (38/190; 20%) were common. All children presenting had received Fluvax(®) or Fluvax Junior(®). In the in vitro model, IFN-α, IL-1β, IL-6, IL-10, IP-10 and MIP-1α levels were significantly higher when measured at 6 and 24 h in cultures stimulated with Fluvax(®) compared with alternative 2010 TIV preparations.


Numerous febrile adverse events (including febrile seizures) were observed following Fluvax(®) or Fluvax Junior(®) in 2010. Clear differences in cytokine production were observed when peripheral blood mononuclear cells were stimulated with Fluvax(®) compared with alternate TIV preparations. Increased awareness of these potential adverse events is required to ensure earlier detection and prevention in the future.

[Indexed for MEDLINE]

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