Feb 27, 2012 (CIDRAP News) – A recent set of articles in Vaccine has confirmed previous preliminary reports that young children who received influenza shots in the 2010-11 flu season had a slightly increased risk of a febrile seizure after vaccination, especially if they received a new pneumococcal vaccine at the same time.
In January 2011 the Centers for Disease Control and Prevention (CDC) reported a small increase in risk of febrile seizures in children aged 12 to 23 months who received a trivalent inactivated flu vaccine (TIV) and the new 13-valent pneumococcal conjugate vaccine (PCV13) on the same visit.
The Vaccine reports cite a significant increase in risk of seizures in children 6 to 59 months old shortly after vaccination with TIV, even without concomitant PCV13 vaccination. The excess risk was highest in 16-month-old children who received both vaccines concomitantly. It amounted to about 45 additional febrile seizure cases per 100,000 TIV doses on the day of or day after vaccination (days 0 to 1), compared with a control period defined as 14 to 20 days after vaccination.
A CDC official told CIDRAP News today that the number of febrile seizures in young children so far this flu season is about the same as last year.
The CDC stepped up its surveillance for febrile seizures in children who received the flu vaccine in 2010-11 after Australia and New Zealand found an increase in such events in 2010. Officials there reported higher-than-expected rates of febrile seizures, mainly in children under age 5 who received Fluvax, made by CSL Ltd.
The Vaccine articles include an initial report based on analysis of data from the Vaccine Adverse Event Reporting System (VAERS) and a study from the CDC's Vaccine Safety Datalink System (VSD), which gathers medical visit data from 10 managed care organizations across the country, covering 9.2 million Americans. The two reports are accompanied by a "discussion" article about the CDC and Food and Drug Administration (FDA) responses to the findings.
In the initial study, in the fall of 2010, CDC and FDA scientists examined VAERS data for signs of increased febrile seizures following TIV receipt in children younger than 5 years old. The number of such cases exceeded a predetermined threshold on Nov 23, and by Dec 10 the team had confirmed 43 febrile seizure cases after vaccination in children 6 to 23 months old.
Most of the cases appeared to be "typical uncomplicated febrile seizures," and all the children recovered. The CDC says febrile seizures in children are brief and generally have a good prognosis.
In the VSD study, the authors compared the rate of postvaccination febrile seizures on days 0 to 1 after vaccination to the rate on days 14 to 20 in a cohort of 206,174 children aged 6 to 59 months. They found nearly a sixfold increase in risk—an incidence rate ratio (IRR) of 5.9 (95% confidence interval [CI], 3.1-11.3)—for children who received TIV and PCV13 concomitantly.
The increases in risk attributed to TIV or PCV13 separately were smaller, the report says. The IRR for TIV (adjusted for PCV13) was 2.4 (95% CI, 1.2 to 4.7), while the IRR for PCV13 (adjusted for TIV) was 2.5 (95% CI, 1.3 to 4.7).
The risk estimates varied by age because of the varying baseline risk of seizures in young children, the report says. The peak increases, at age 16 months, were 12.5 per 100,000 doses for TIV without PCV13, 13.7 per 100,000 doses for PCV13 without TIV, and 44.9 per 100,000 doses for concomitant TIV and PCV13. The risk increase was lowest for 59-month-old children.
Abbigail Tumpey, a spokeswoman for the CDC's Division of Healthcare Quality Promotion, said today that surveillance results on febrile seizures in young children so far this flu season are similar to last year's.
"What we are seeing this year is consistent with last year (e.g., the number/type of VAERS reports are the same)," she commented by e-mail. "This would be as expected, since the vaccine formulation is the same. The Vaccine Safety Datalink is going to do a retrospective analysis when the season is over."
The findings have not prompted any change in the federal recommendations for flu and pneumococcal vaccination in young children, but federal officials called for warnings to healthcare providers and parents, according to the discussion article. The Advisory Committee on Immunization Practices (ACIP) recommended the warnings after a subcommittee studied the data.
The prescribing information for Fluzone TIV was updated for this season to include "febrile convulsions" in the postmarketing experience section, says the report, and the Vaccine Information Statement for TIV was updated to include similar information. The package insert for PCV13 notes that febrile seizures were seen in vaccinees during prelicensure clinical trials, the article says.
Leroy Z, Broder K, Menschik D, et al. Febrile seizures after 2010-11 influenza vaccine in young children, United States: a vaccine safety signal from the Vaccine Adverse Event Reporting System. Vaccine 2012 Mar;30(11):2020-23 [Abstract]
Tse A, Tseng HF, Greene SK, et al. Signal identification and evaluation for risk of febrile seizures in children following trivalent inactivated influenza vaccine in the Vaccine Safety Datalink Project, 2010-2011. Vaccine 2012 Mar;30(11):2024-31 [Abstract]
Broder KR, Martin DB, Vellozi C. Bridging the gap between data and public health needs. In the heat of a signal: responding to a vaccine safety signal for febrile seizures after 2010-11 influenza vaccine in young children, United States. (Discussion) Vaccine 2012 Mar;30(11):2032-4 [Citation]
Related Feb 23, 2011, CIDRAP News story