Kristine Macartney1,2,3, Heather F Gidding1,4, Lieu Trinh5, Han Wang1, Aditi Dey1,2, Brynley Hull1, Karen Orr1,3, Jocelynne McRae1,3, Peter Richmond6,7, Michael Gold8,9, Nigel Crawford10,11, Jennifer A Kynaston12, Peter McIntyre1,2,3, Nicholas Wood1,2,3. 1. National Centre for Immunisation Research and Surveillance, Sydney, Australia. 2. School of Child and Adolescent Health, University of Sydney, Sydney, Australia. 3. The Children's Hospital at Westmead, Westmead, Australia. 4. School of Public Health and Community Medicine, UNSW Medicine, The University of New South Wales, Sydney, Australia. 5. Western Sydney Local Health District, Sydney, Australia. 6. School of Paediatrics and Child Health, University of Western Australia, Perth, Australia. 7. Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, Perth, Australia. 8. Department of Paediatrics, University of Adelaide, Adelaide, Australia. 9. Women's and Children's Hospital, Adelaide, Australia. 10. Royal Children's Hospital, Melbourne, Australia. 11. University of Melbourne, Melbourne, Australia. 12. Lady Cilento Children's Hospital, Brisbane, Australia.
Abstract
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.
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.
Authors: Ali Rowhani-Rahbar; Bruce Fireman; Edwin Lewis; James Nordin; Allison Naleway; Steven J Jacobsen; Lisa A Jackson; Alison Tse; Edward A Belongia; Simon J Hambidge; Eric Weintraub; Roger Baxter; Nicola P Klein Journal: JAMA Pediatr Date: 2013-12 Impact factor: 16.193
Authors: Brynley P Hull; Alexandra J Hendry; Aditi Dey; Frank H Beard; Julia M Brotherton; Peter B McIntyre Journal: Commun Dis Intell Q Rep Date: 2017-03-31
Authors: Simon J Hambidge; Sophia R Newcomer; Komal J Narwaney; Jason M Glanz; Matthew F Daley; Stan Xu; Jo Ann Shoup; Ali Rowhani-Rahbar; Nicola P Klein; Grace M Lee; Jennifer C Nelson; Marlene Lugg; Allison L Naleway; James D Nordin; Eric Weintraub; Frank DeStefano Journal: Pediatrics Date: 2014-06 Impact factor: 7.124
Authors: Nicola P Klein; Bruce Fireman; W Katherine Yih; Edwin Lewis; Martin Kulldorff; Paula Ray; Roger Baxter; Simon Hambidge; James Nordin; Allison Naleway; Edward A Belongia; Tracy Lieu; James Baggs; Eric Weintraub Journal: Pediatrics Date: 2010-06-29 Impact factor: 7.124
Authors: Kristine K Macartney; Heather F Gidding; Lieu Trinh; Han Wang; Jocelynne McRae; Nigel Crawford; Michael Gold; Anne Kynaston; Christopher Blyth; Zurynski Yvonne; Elizabeth Elliott; Robert Booy; Jim Buttery; Helen Marshall; Michael Nissen; Peter Richmond; Peter B McInytre; Nicholas Wood Journal: Vaccine Date: 2014-11-07 Impact factor: 3.641
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Authors: Karina A Top; Kristine Macartney; Julie A Bettinger; Ben Tan; Christopher C Blyth; Helen S Marshall; Wendy Vaudry; Scott A Halperin; Peter McIntyre Journal: Euro Surveill Date: 2020-06
Authors: Pasquale Stefanizzi; Sara De Nitto; Francesco Patano; Francesco Paolo Bianchi; Davide Ferorelli; Paolo Stella; Domenica Ancona; Vito Bavaro; Silvio Tafuri Journal: Hum Vaccin Immunother Date: 2020-02-10 Impact factor: 3.452