Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2020 Mar;145(3):e20191909.
doi: 10.1542/peds.2019-1909. Epub 2020 Feb 6.

Fever After Influenza, Diphtheria-Tetanus-Acellular Pertussis, and Pneumococcal Vaccinations

Emmanuel B Walter  1   2 , Nicola P Klein  3 , A Patricia Wodi  4 , Wes Rountree  2 , Christopher A Todd  2 , Amy Wiesner  3 , Jonathan Duffy  4 , Paige L Marquez  4 , Karen R Broder  4
Affiliations
Randomized Controlled Trial

Fever After Influenza, Diphtheria-Tetanus-Acellular Pertussis, and Pneumococcal Vaccinations

Emmanuel B Walter et al. Pediatrics. 2020 Mar.

Abstract

Background: Administering inactivated influenza vaccine (IIV), 13-valent pneumococcal conjugate vaccine (PCV13), and diphtheria-tetanus-acellular pertussis (DTaP) vaccine together has been associated with increased risk for febrile seizure after vaccination. We assessed the effect of administering IIV at a separate visit from PCV13 and DTaP on postvaccination fever.

Methods: In 2017-2018, children aged 12 to 16 months were randomly assigned to receive study vaccines simultaneously or sequentially. They had 2 study visits 2 weeks apart; nonstudy vaccines were permitted at visit 1. The simultaneous group received PCV13, DTaP, and quadrivalent IIV (IIV4) at visit 1 and no vaccines at visit 2. The sequential group received PCV13 and DTaP at visit 1 and IIV4 at visit 2. Participants were monitored for fever (≥38°C) and antipyretic use during the 8 days after visits.

Results: There were 110 children randomly assigned to the simultaneous group and 111 children to the sequential group; 90% received ≥1 nonstudy vaccine at visit 1. Similar proportions of children experienced fever on days 1 to 2 after visits 1 and 2 combined (simultaneous [8.1%] versus sequential [9.3%]; adjusted relative risk = 0.87 [95% confidence interval 0.36-2.10]). During days 1 to 2 after visit 1, more children in the simultaneous group received antipyretics (37.4% vs 22.4%; P = .020).

Conclusions: In our study, delaying IIV4 administration by 2 weeks in children receiving DTaP and PCV13 did not reduce fever occurrence after vaccination. Reevaluating this strategy to prevent fever using an IIV4 with a different composition in a future influenza season may be considered.

Trial registration: ClinicalTrials.gov NCT03165981.

PubMed Disclaimer

Conflict of interest statement

POTENTIAL CONFLICT OF INTEREST: Dr Klein reports potential conflicts due to support received from GlaxoSmithKline, Sanofi Pasteur, Pfizer, Merck, Protein Science (now Sanofi Pasteur), Dynavax, and MedImmune; the other authors have indicated they have no potential conflicts of interest to disclose.

Figures

FIGURE 1
FIGURE 1
Consolidated Standards of Reporting Trials diagram.
FIGURE 2
FIGURE 2
Percentage of days with fever (temperature ≥ 38.0°C) on days 1 to 2 and days 3 to 8 after visits 1 and 2 by study group (PP population).
FIGURE 3
FIGURE 3
Percentage of days with antipyretic use on days 1 to 2 and days 3 to 8 after visits 1 and 2 by study group (PP population).
FIGURE 4
FIGURE 4
Solicited systemic symptoms (days 1–8) by study group (PP population). A, After visit 1. B, After visit 2.
See this image and copyright information in PMC

References

    1. Tapiainen T, Heininger U. Fever following immunization. Expert Rev Vaccines. 2005;4(3):419–427 - PubMed
    1. Barlow WE, Davis RL, Glasser JW, et al. ; Centers for Disease Control and Prevention Vaccine Safety Datalink Working Group . The risk of seizures after receipt of whole-cell pertussis or measles, mumps, and rubella vaccine. N Engl J Med. 2001;345(9):656–661 - PubMed
    1. Tse A, Tseng HF, Greene SK, Vellozzi C, Lee GM; VSD Rapid Cycle Analysis Influenza Working Group . 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;30(11):2024–2031 - PubMed
    1. Li R, Stewart B, McNeil MM, et al. . Post licensure surveillance of influenza vaccines in the Vaccine Safety Datalink in the 2013-2014 and 2014-2015 seasons. Pharmacoepidemiol Drug Saf. 2016;25(8):928–934 - PMC - PubMed
    1. Shimabukuro TT. Influenza end-of-season update: 2017-2018 influenza vaccine safety monitoring. In: Proceedings from the Advisory Committee on Immunization Practices meeting; June 20–21, 2018; Atlanta, GA.

Publication types

MeSH terms

Substances

Associated data