The 2010 trivalent influenza vaccine (TIV) manufactured by CSL Biotherapies (CSL) was associated with increased febrile reactions, including febrile convulsions, among Australian children.
CSL is one of the few manufacturers that use deoxycholate as the virus-splitting agent in the manufacture of TIV. Clusters of adverse events following immunisation (AEFI) have been previously linked to other deoxycholate-split TIV formulations in Europe and Canada.
We hypothesise that suboptimal virus splitting or other mechanisms related to the use of deoxycholate may have played a role in adverse events linked to the 2010 CSL TIV.
This hypothesis garners support from a recent United States Food and Drug Administration warning letter indicating that CSL failed to determine optimal splitting conditions for new virus strains and that assays to assess virus splitting had not been validated.
While there may be other causes, the use of deoxycholate should be further explored. Comprehensive and timely investigations of AEFI, especially those involving children, are necessary to prevent their recurrence and to maintain public confidence in vaccination programs.
- 1. Armstrong PK, Dowse GK, Effler PV, et al. Epidemiological study of severe febrile reactions in young children in Western Australia caused by a 2010 trivalent inactivated influenza vaccine. BMJ Open 2011; 30 May. doi: 10.1136/bmjopen-2010-000016.
- 2. Australian Technical Advisory Group on Immunisation. Clinical advice for immunisation providers on resumption of the use of 2010 trivalent seasonal vaccines in children less than 5 years of age, 30 July 2010. http://www.health.gov.au/internet/immunise/Publishing.nsf/content/immunise-atagi-statement-tiv (accessed Aug 2011).
- 3. Therapeutic Goods Administration. The TGA and the USA FDA agree about problems at CSL Biotherapies. Canberra: TGA, 2011. http://www.tga.gov.au/newsroom/btn-csl-tga-statement-110708.htm (accessed Aug 2011).
- 4. Furminger IGS. Vaccine production. In: Nicholson KG, Webster RG, Hay AJ, editors. Textbook of influenza. Oxford: Blackwell Science, 1998: 324-332.
- 5. Institute for Vaccine Safety. Excipients in vaccines. Baltimore: IVS, 2010. http://hopkinsvaccine.org/components-Excipients.htm (accessed Aug 2011).
- 6. Gross PA, Ennis FA, Gaerlan PF, et al. A controlled double-blind comparison of reactogenicity, immunogenicity and protective efficacy of whole-virus and split-influenza product vaccines in children. J Infect Dis 1977; 136: 623-632.
- 7. al-Mazrou A, Scheifele DW, Soong T, Bjornson G. Comparison of adverse reactions to whole-virion and split-virion influenza vaccines in hospital personnel. CMAJ 1991; 145: 213-218.
- 8. Skowronski DM, Strauss B, De Serres G, et al. Oculo-respiratory syndrome: a new influenza vaccine-associated adverse event? Clin Infect Dis 2003; 36: 705-713.
- 9. National Advisory Committee on Immunization. Supplementary statement for the 2001–2002 season: influenza vaccination of persons who experienced oculo-respiratory syndrome following previous influenza vaccination. Can Commun Dis Rep 2001; 27: 1-7.
- 10. Global Advisory Committee on Vaccine Safety. Oculorespiratory syndrome. Week Epi Rec 2003; 78: 17–24. http://www.who.int/wer/2003/en/wer7804.pdf (accessed Jul 2011).
- 11. Skowronski DM, De Serres G, Scheifele D, et al. Randomized, double-blind, placebo-controlled trial to assess the rate of recurrence of oculorespiratory syndrome following influenza vaccination among persons previously affected. Clin Infect Dis 2003; 37: 1059-1066.
- 12. Splia-Alegani S, Salmaso S, Rota MC, et al. Reactogenicity in the elderly of nine commercial influenza vaccines: results from the Italian SVEVA study. Vaccine 1999; 17: 1898-1904.
- 13. Tumova B, Schramlova J, Vitkova E, et al. Is the release control of influenza vaccine sufficient? In: Programs and abstracts of Options for the Control of Influenza III; Cairns, Queensland; 1996.
- 14. Tannock GA, Bryce DA, Hensley MJ, et al. Responses to one or two doses of a deoxycholate subunit influenza vaccine in a primed population. Vaccine 1984; 2: 100-106.
- 15. Therapeutic Goods Administration. Overview of vaccine regulation and safety monitoring and investigation into adverse events following 2010 seasonal influenza vaccination in young children. Attachment E: TGA influenza seasonal trivalent influenza vaccine laboratory investigation program. http://www.tga.gov.au/safety/alerts-medicine-seasonal-flu-101008.htm#attachments (accessed Aug 2011).
- 16. Centers for Disease Control and Prevention (US). ACIP recommendation for use of CSL influenza vaccine [media statement]. 6 Aug 2010. http://www.cdc.gov/media/pressrel/2010/s100806.htm (accessed Sep 2011).
- 17. Food and Drug Administration (US). Inspections, compliance, enforcement, and criminal investigations. Warning letter to Commonwealth Serum Laboratories (CSL) Ltd. June 15, 2011. http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm259888.htm (accessed Jul 2011).
- 18. Nolan T, Richmond PC, McVernon J, et al. Safety and immunogenicity of an inactivated thimerosal-free influenza vaccine in infants and children. Influenza Other Resp Viruses 2009; 3: 315-325.
- 19. Commonwealth Serum Laboratories. Influenza virus vaccine, 2010–2011 formula (STN BL 125254/181). Highlights of prescribing information. http://www.fda.gov/downloads/biologicsbloodvaccines/vaccines/approvedproducts/ucm220730.pdf (accessed Aug 2011).
- 20. ClinicalTrials.gov. A study to determine the immunogenicity and safety profile of CSL Limited’s influenza virus vaccine compared to a US licensed comparator influenza virus vaccine in a pediatric population. http://clinicaltrials.gov/ct2/show/results/NCT00959049 (accessed Aug 2011).
Publication of your online response is subject to the Medical Journal of Australia's editorial discretion. You will be notified by email within five working days should your response be accepted.