Risk of fever after pediatric trivalent inactivated influenza vaccine and 13-valent pneumococcal conjugate vaccine

JAMA Pediatr. 2014 Mar;168(3):211-9. doi: 10.1001/jamapediatrics.2013.4469.


Importance: An observational study found an increased risk of febrile seizure on the day of or 1 day after vaccination (days 0-1) with trivalent inactivated influenza vaccine (TIV) in the 2010-2011 season; risk was highest with simultaneous vaccination with TIV and 13-valent pneumococcal vaccine (PCV13) in children who were 6 to 23 months old. Text messaging is a novel method for surveillance of adverse events after immunization that has not been used for hypothesis-driven vaccine safety research.

Objective: To prospectively evaluate whether children receiving TIV and PCV13 simultaneously had higher rates of fever on days 0 to 1 than those receiving either product without the other.

Design, setting, and participants: Prospective observational cohort study of parents of children 6 to 23 months old recruited from 3 medical center-affiliated clinics in New York City from November 1, 2011, through April 5, 2012. A total of 530 of 614 eligible participants (86.3%) were enrolled. Parents were texted on the night of vaccination (day 0) and the 7 subsequent nights (days 1-7) to report their child's temperature. We used log-binomial regression to calculate adjusted relative risks (aRRs) and excess risk for fever on days 0 to 1, adjusted for age group, past influenza vaccination and simultaneous receipt of selected inactivated vaccines.

Exposures: Receipt of TIV and/or PCV13.

Main outcome(s) and measure(s): Temperature of 38°C or higher on days 0 to 1 after vaccination.

Results: On days 0 to 1, children receiving TIV and PCV13 simultaneously had higher rates (37.6%) of fever (temperature ≥38°C) than those receiving TIV (7.5%; aRR, 2.69; 95% CI, 1.30-5.60) or PCV13 (9.5%; aRR, 2.67; 95% CI, 1.25-5.66). The excess risk of fever after TIV and PCV13 was 20 and 23 per 100 vaccinations compared with TIV without PCV13 and PCV13 without TIV, respectively. Fever rates for days 2 to 7 were similar across groups. For days 0 to 1, 74.8% of the text messages were confirmed delivered; for another 9.0%, delivery status was unknown. Response rates were 95.1% and 90.9% for days 0 and 1 for confirmed delivered messages, respectively.

Conclusions and relevance: Simultaneous TIV and PCV13 administration was associated with higher transient increased fever risk than administration of either vaccine without the other product. Text messaging to prospectively assess a specific vaccine adverse event has potential for enhancing prelicensure and postlicensure monitoring of adverse events after immunization and deserves further study.

Trial registration: clinicaltrials.gov Identifier: NCT01467934.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Female
  • Fever / chemically induced*
  • Humans
  • Infant
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / adverse effects*
  • Influenza, Human / prevention & control*
  • Male
  • New York City / epidemiology
  • Pneumococcal Vaccines / administration & dosage
  • Pneumococcal Vaccines / adverse effects*
  • Prospective Studies
  • Reaction Time
  • Risk Factors
  • Text Messaging
  • Treatment Outcome


  • 13-valent pneumococcal vaccine
  • Influenza Vaccines
  • Pneumococcal Vaccines

Associated data

  • ClinicalTrials.gov/NCT01467934