[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Original Investigation
October 2017

Evaluation of Combination Measles-Mumps-Rubella-Varicella Vaccine Introduction in Australia

Author Affiliations
  • 1National Centre for Immunisation Research and Surveillance, Sydney, Australia
  • 2School of Child and Adolescent Health, University of Sydney, Sydney, Australia
  • 3The Children’s Hospital at Westmead, Westmead, Australia
  • 4School of Public Health and Community Medicine, UNSW Medicine, The University of New South Wales, Sydney, Australia
  • 5Western Sydney Local Health District, Sydney, Australia
  • 6School of Paediatrics and Child Health, University of Western Australia, Perth, Australia
  • 7Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, Perth, Australia
  • 8Department of Paediatrics, University of Adelaide, Adelaide, Australia
  • 9Women’s and Children’s Hospital, Adelaide, Australia
  • 10Royal Children’s Hospital, Melbourne, Australia
  • 11University of Melbourne, Melbourne, Australia
  • 12Lady Cilento Children’s Hospital, Brisbane, Australia
JAMA Pediatr. 2017;171(10):992-998. doi:10.1001/jamapediatrics.2017.1965
Key Points

Question  What is the effect of introduction of combination measles-mumps-rubella-varicella vaccine at age 18 months as the second dose of measles-containing vaccine on vaccine coverage and risk of vaccine-associated febrile seizures in Australia?

Findings  A national cohort study of vaccine coverage before and after measles-mumps-rubella-varicella vaccine introduction showed improvement in uptake and timeliness for all 4 vaccine components. Despite the peak incidence of all-cause febrile seizures occurring at age 18 months and a known increased risk of febrile seizures following the first dose, in a self-controlled case series analysis including 1471 children, use of measles-mumps-rubella-varicella vaccine at 18 months was not associated with an increased risk of febrile seizures.

Meaning  Measles-mumps-rubella-varicella combination vaccine was safely incorporated into the Australian National Immunisation Program schedule and improved population-level protection against these serious viral diseases.


Importance  Incorporating combination vaccines, such as the measles-mumps-rubella-varicella (MMRV) vaccine, into immunization schedules should be evaluated from a benefit-risk perspective. Use of MMRV vaccine poses challenges due to a recognized increased risk of febrile seizures (FSs) when used as the first dose in the second year of life. Conversely, completion by age 2 years of measles, mumps, rubella, and varicella immunization may offer improved disease control.

Objective  To evaluate the effect on safety and coverage of earlier (age 18 months) scheduling of MMRV vaccine as the second dose of measles-containing vaccine (MCV) in Australia.

Design, Setting, and Participants  Prospective active sentinel safety surveillance comparing the relative incidence (RI) of FSs in toddlers given MMRV and measles-mumps-rubella (MMR) and a national cohort study of vaccine coverage rates and timeliness before and after MMRV vaccine introduction were conducted. All Australian children aged 11 to 72 months were included in the coverage analysis, and 1471 Australian children aged 11 to 59 months were included in the FS analysis, with a focus on those aged 11 to 23 months.

Main Outcomes and Measures  MMRV vaccine safety, specifically, the RI of FSs after MMRV vaccine at age 18 months, compared with risk following MMR vaccine and vaccine uptake for 2-dose MCV and single-dose varicella vaccine, focusing on timeliness.

Results  Of the 1471 children, the median age at first FS was 21 months (interquartile range [IQR], 14-31 months). Three hundred ninety-one children were aged 11 to 23 months and had at least 1 FS included in the analysis; of these, 207 (52.9%) were male. A total of 278 children (71.1%) had received MMR followed by MMRV vaccine, 97 (24.8%) had received MMR vaccine only, and 16 (4.1%) had received neither vaccine. There was no increased risk of FSs (RI, 1.08; 95% CI, 0.55-2.13) in the 5 to 12 days following MMRV vaccine given as the second MCV to toddlers. Febrile seizures occurred after dose 1 of MMR vaccine at a known low increased risk (RI, 2.71; 95% CI, 1.71- 4.29). Following program implementation, 2-dose MCV coverage at age 36 months exceeded that obtained at age 60 months in historical cohorts recommended to receive MMR vaccine before school entry, and on-time vaccination increased by 13.5% (from 58.9% to 72.4%). Despite no change in the scheduled age of varicella vaccine, use of MMRV vaccine was associated with a 4.0% increase in 1-dose varicella vaccine coverage.

Conclusions and Relevance  To our knowledge, this is the first study to provide evidence of the absence of an association between use of MMRV vaccine as the second dose of MCV in toddlers and an increased risk of FSs. Incorporation of MMRV vaccine has facilitated improvements in vaccine coverage that will potentially improve disease control.