The risk of febrile seizures following influenza and 13-valent pneumococcal conjugate vaccines

Grace M Lee,Sandra Deluccia,Lingling Li,W Katherine Yih,Rong Chen Tilney,Claudia Coronel-Moreno,Meghan A Baker,Susan Gruber,Christopher Jankosky,David Menschik,Nancy D Lin,Nandini Selvam,Noelle M Cocoros,Lauren Zichittella,Alison Tse Kawai,Mano S Selvan,Cheryl N Mcmahill-Walraven,Hana Lipowicz

doi:10.1016/j.vaccine.2020.01.046

Abstract

BackgroundEvidence on the risk of febrile seizures after inactivated influenza vaccine (IIV) and 13-valent pneumococcal conjugate vaccine (PCV13) is mixed. In the FDA-sponsored Sentinel Initiative, we examined risk of febrile seizures after IIV and PCV13 in children 6–23 months of age during the 2013–14 and 2014–15 influenza seasons. MethodsUsing claims data and a self-controlled risk interval design, we compared the febrile seizure rate in a risk interval (0–1 days) versus control interval (14–20 days). In exploratory analyses, we assessed whether the effect of IIV was modified by concomitant PCV13 administration. ResultsAdjusted for age, calendar time and concomitant administration of the other vaccine, the incidence rate ratio (IRR) for risk of febrile seizures following IIV was 1.12 (95% CI 0.80, 1.56) and following PCV13 was 1.80 (95% CI 1.29, 2.52). The attributable risk for febrile seizures following PCV13 ranged from 0.33 to 5.16 per 100,000 doses by week of age.The age and calendar-time adjusted IRR comparing exposed to unexposed time was numerically larger for concomitant IIV and PCV13 (IRR 2.80, 95% CI 1.63, 4.83), as compared to PCV13 without concomitant IIV (IRR 1.54, 95% CI 1.04, 2.28), and the IRR for IIV without concomitant PCV13 suggested no independent effects of IIV (IRR 0.94, 95% CI 0.63, 1.42). Taken together, this suggests a possible interaction between IIV and PCV13, though our study was not sufficiently powered to provide a precise estimate of the interaction. ConclusionsWe found an elevated risk of febrile seizures after PCV13 vaccine but not after IIV. The risk of febrile seizures after PCV13 is low compared to the overall risk in this population of children, and the risk should be interpreted in the context of the importance of preventing pneumococcal infections.

Highlights

In February 2010, the Food and Drug Administration (FDA) licensed the 13-valent pneumococcal conjugate vaccine (PCV13) for use in children aged 6 weeks through 59 months
AES reported to Vaccine Adverse Event Reporting System (VAERS) following PCV13 were consistent with adverse events (AEs) previously observed in pre-licensure clinical trials and other post-licensure studies of PCV13
PCV13 was associated with an increased risk of febrile seizures (FS) (IRR adjusted for age, calendar time and concomitant inactivated influenza vaccine (IIV), 1.80, 95% CI 1.29, 2.52)

Summary

Introduction

In February 2010, the Food and Drug Administration (FDA) licensed the 13-valent pneumococcal conjugate vaccine (PCV13) for use in children aged 6 weeks through 59 months. Introduction of pneumococcal conjugate vaccines (PCV) to the Canadian childhood routine immunization schedules (RIS) resulted in significant benefits. In Quebec, 7-valent (PCV7), 10-valent (PCV10) and 13-valent (PCV13) pneumococcal conjugate vaccines were successively used for children immunization according to a 2 + 1 doses schedule. To increase understanding of post vaccine nasopharyngeal (NP) carriage, persistence of vaccine serotypes, strategies for molecular identification of SP have been developed. These methods most often rely on the identification of the SP autolysin gene lytA through non-quantitative PCR or semi-quantitative real-time PCR (RTPCR). We conducted a community-wide study to determine the extent of antibiotic prescription rates (APRs) following PCV implementation

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