Febrile seizures following seasonal influenza vaccination

Increased occurrence of febrile seizures with a seasonal influenza vaccine

GACVS reviewed progress by the Australian Therapeutic Goods Administration (TGA) and the company that manufactures Fluvax (CSL, Parkville, Victoria, Australia) a trivalent influenza vaccine (TIV) vaccine which, in 2010, was associated with an increased risk of fever and febrile seizures, particularly in children aged < 5 years.⁶ This resulted in a 3-month suspension of the Australian influenza vaccination programme for children. Subsequent investigations confirmed that no other TIVs were associated with this increased risk. Fluvax is now contraindicated in children aged <5 years and avoided in those aged <9 years.

The manufacturer has conducted several analyses in order to clarify the etiological mechanism of increased pyrogenicity of this specific vaccine product in children. It appeared that most of the signal being measured was coming from virus lipid mediated delivery of small degraded RNA fragments and that this was particularly evident with the B/Brisbane strain and to a lesser extent, the A/California strain used in the 2010 TIV. Their studies also showed that modifying the manufacturing process to increase the percentage of the splitting agent used for the B strain resulted in a decreased lipid content and lead to an overall reduction in the in–vitro cytokine signature produced. The company informed GACVS of a planned modification to the vaccine manufacturing process that will be implemented in 2014. It is expected that this modification will lead to a reduction or elimination of the possible contributing factors and therefore a reduction in the additional pyrogenicity in children.

GACVS also noted that given the evolving number of population groups for whom trivalent influenza vaccines are being recommended (young children and pregnant women in particular), there is a need to enhance post-marketing surveillance to rapidly detect any increased local and systemic reactogenicity that may arise with a particular vaccine product. GACVS concurred with several regulatory authorities decision to contraindicate the use of the present CSL vaccine in children aged <5 years. The committee also took note of measures mandated by TGA to reduce inadvertent vaccination, which have included a number of programmatic measures including package labelling. GACVS noted these events illustrate the importance of post-licensure brand-specific safety surveillance which presents particular challenges with seasonal influenza vaccines.

⁶ See No. 29, 2013, pp. 301–312.

Full report of GACVS meeting of 11-12 December 2013, published in the WHO Weekly Epidemiological Record on 14 February 2014

Febrile seizures after seasonal influenza vaccine in Australia

Australia’s regulatory authority provided a summary of the increased number of reports of fever and febrile convulsions in children aged <5 years following administration of the 2010 seasonal inactivated infl uenza vaccine (Fluvax) made by CSL (Parkville, Victoria, Australia). No clinical or epidemiological factors have yet been identifi ed that explain the increase. Vaccine testing has shown no abnormalities, but testing continues. The Chief Medical Offi cer of Australia advised suspending the use of all 2010 seasonal infl uenza vaccines in healthy children aged <5 years. For children with medical risk factors, the Chief Medical Offi cer advised using monovalent A (H1N1) 2009 vaccine or seasonal 2010 vaccine made by other manufacturers. Australia will apprise GACVS of any additional information. GACVS has not been made aware of reports of increased fever or febrile convulsions from other 2010 seasonal vaccines but noted the importance of reviewing data on the use of the vaccines elsewhere in the southern hemisphere, as well as data that will be collected during the use of 2010 seasonal vaccines in the northern hemisphere.

Full report GACVS meeting of 16-17 June 2010, published in the WHO Weekly Epidemiological Record on 23 July 2010

Statement on Fluzone and febrile seizures

The U.S. Food and Drug Administration and Centers for Disease Control and Prevention have recently detected an increase in the number of reports to the Vaccine Adverse Event Reporting System (VAERS) of febrile seizures following vaccination with the trivalent inactivated influenza vaccine, Fluzone. The reported febrile seizures have mainly been seen in children younger than 2 years of age.

GACVS has been informed about this finding and notes that in the cases reported, all children recovered with no lasting effects seen. It is also noted that no increase in VAERS reports of febrile seizures in people older than 2 years of age has been detected.

Based on the information presented, GACVS concurs that further investigation is needed to clarify the nature and magnitude of any increased risk, but on the basis of the data currently available does not recommend any change to the WHO recommendations for the use of seasonal influenza vaccine (http://www.who.int/wer/2005/wer8033.pdf). GACVS will continue reviewing data related to these reports as they become available.