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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.

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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.
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