Adverse Events In Children Associated with 2010 Southern Hemisphere Seasonal Influenza Vaccine

Background:  There was an unprecedented increase in reports of fever and febrile seizures in young children associated with CSL’s 2010 southern hemisphere influenza vaccine (TIV). 

Objectives:  To describe the activities undertaken to investigate the  events in young children associated with 2010 CSL TIV, highlight clinical trial data and report outcomes of root cause investigations to guide planning for use of CSL TIV in the US in 2011. 

Methods:  We reviewed post-marketing surveillance and CSL clinical trial data. We undertook in vitro and in vivo studies to evaluate cytokine and temperature responses to various formulations of TIV and individual vaccine strain components. 

Results:  There was a disproportionate increase in post-marketing adverse event reports for CSL TIV in 2010. The Australian regulator received 1,397 reports for CSL TIV compared to 67 for Solvay TIV and 16 for sanofi-pasteur TIV. Of these, the majority were in children < 18 years and most related to fever. In pooled data from CSL TIV clinical trials, fever was reported in 30.2% (350/1159) of children ≥ 6 months to < 3 years and 30.2% (189/625) in children ≥ 3 years to < 5 years. Fever was lower in children ≥ 5 to < 9 years (range: 9.8 to 16.7%). Scientific investigations included in vitro blood assays (adult and pediatric), non-human primate and ferret studies. Preliminary in vitro study results demonstrated increases in several pro-inflammatory cytokines and chemokines. Additional preclinical studies are ongoing.

Conclusions:  The increased reports of febrile events associated with CSL’s 2010 TIV was unexpected and not predicted by previous clinical trial or post-marketing data. No safety signals were identified in adult or elderly populations. While a root cause has yet to be identified, investigations are ongoing and will be important to guide the use of CSL TIV in children in the upcoming influenza season.