Febrile seizures following measles and varicella vaccines in young children in Australia

Abstract

Background

Febrile seizures (FS) are common in childhood with incidence peaking in the second year of life when measles and varicella-containing vaccines are administered. This study aimed to examine the vaccine-attributable risk of FS following separate administration of MMR and monovalent varicella vaccines (VV) prior to a planned change to MMRV as the second dose of measles-containing vaccine at 18 months of age.

Methods

All FS cases in children aged <5 years from 1st January 2012 to 30th April 2013 were identified from emergency department (ED) and inpatient databases at five Australian tertiary paediatric hospitals participating in PAEDS (Paediatric Active Enhanced Disease Surveillance). Immunization records were obtained from the Australian Childhood Immunization Register (ACIR). The relative incidence (RI) of FS following MMR dose 1 (MMR1) and VV in children aged 11–23 months was determined using the self-controlled case series (SCCS) method and used to calculate attributable risk.

Results

There were 2013 FS episodes in 1761 children. The peak age at FS was 18 months. The risk of FS was significantly increased 5–12 days post receipt of MMR1 at 12 months (RI = 1.9 [95% CI: 1.3–2.9]), but not after VV at 18 months (RI = 0.6 [95% CI: 0.3–1.2]. The estimated excess annual number of FS post MMR1 was 24 per 100,000 vaccinated children aged 11–23 months (95% CI = 7–49 cases per 100,000) or 1 per 4167 doses.

Conclusions

Our study detected the expected increased FS risk post MMR1 vaccine at 12 months, but monovalent varicella vaccine at age 18 months was not associated with increased risk of FS. This provides baseline data to assess the risk of FS post MMRV, introduced in Australia as the second dose of measles-containing vaccine at 18 months of age in July 2013.

Introduction

Febrile seizures (FS) are dramatic but common acute neurologic events with a cumulative all-cause incidence of up to 5% by age 5 years [1]. Most FS are due to viral infections, but when attributed to recent vaccine receipt, can cause both parent and provider confidence in the safety of vaccines to be impacted [1]. For more than a decade, a significant but low risk of FS in the 5–12 days post dose 1 of the measles–mumps–rubella (MMR) vaccine [2], [3], [4], [5] and in the first 48-hours following whole cell pertussis containing vaccines [1], [5] has been recognized. More recently, studies have identified a risk of FS after seasonal influenza vaccine [6], [7], 13-valent pneumococcal conjugate vaccine [7] and the new combination measles–mumps–rubella–varicella (MMRV) vaccine [8], [9], [10], [11]. In Australia, the 2010 temporary suspension of seasonal influenza vaccination use in children <5 years following an unexpected excess of febrile seizures from one influenza vaccine brand (Fluvax, bioCSL, Parkville, VIC, Australia) has heightened concern of FS as a potential adverse event following immunization [6].

In Australia MMRV vaccine given at 18 months of age replaced the second dose of MMR at 4 years and monovalent varicella vaccine at 18 months on the National Immunization Program (NIP) in July 1st 2013. MMRV was scheduled as the second dose of measles-containing vaccine at 18 months of age for two main reasons; (1) the early evidence of a 2-fold increased risk of FS following MMRV as the first dose of a measles-containing vaccine compared to MMR and varicella vaccine administered separately [8], [10]; and (2) data from clinical studies showing no increase in fever incidence when MMRV was given as the second dose of measles-containing vaccine in the second year of life [12], [13]. To assess the risk of FS before and after this schedule change, sentinel surveillance for FS is being conducted at multiple paediatric hospital sites in the Paediatric Active Enhanced Disease Surveillance (PAEDS) network [14]. The aims of this study were; (1) to describe the epidemiology, relative incidence and vaccine attributable risk of FS following MMR (dose 1 and 2) and VV (only dose) given separately prior to MMRV introduction and; (2) to assess the capacity of the sentinel surveillance network to detect FS risk post inclusion of MMRV on the NIP.