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Evaluation of Combination Measles-Mumps-Rubella-Varicella Vaccine Introduction in Australia.
JAMA Pediatr. 2017 10 01; 171(10):992-998.JP

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.

Authors+Show Affiliations

National Centre for Immunisation Research and Surveillance, Sydney, Australia. School of Child and Adolescent Health, University of Sydney, Sydney, Australia. The Children's Hospital at Westmead, Westmead, Australia.National Centre for Immunisation Research and Surveillance, Sydney, Australia. School of Public Health and Community Medicine, UNSW Medicine, The University of New South Wales, Sydney, Australia.Western Sydney Local Health District, Sydney, Australia.National Centre for Immunisation Research and Surveillance, Sydney, Australia.National Centre for Immunisation Research and Surveillance, Sydney, Australia. School of Child and Adolescent Health, University of Sydney, Sydney, Australia.National Centre for Immunisation Research and Surveillance, Sydney, Australia.National Centre for Immunisation Research and Surveillance, Sydney, Australia. The Children's Hospital at Westmead, Westmead, Australia.National Centre for Immunisation Research and Surveillance, Sydney, Australia. The Children's Hospital at Westmead, Westmead, Australia.School of Paediatrics and Child Health, University of Western Australia, Perth, Australia. Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, Perth, Australia.Department of Paediatrics, University of Adelaide, Adelaide, Australia. Women's and Children's Hospital, Adelaide, Australia.Royal Children's Hospital, Melbourne, Australia. University of Melbourne, Melbourne, Australia.Lady Cilento Children's Hospital, Brisbane, Australia.National Centre for Immunisation Research and Surveillance, Sydney, Australia. School of Child and Adolescent Health, University of Sydney, Sydney, Australia. The Children's Hospital at Westmead, Westmead, Australia.National Centre for Immunisation Research and Surveillance, Sydney, Australia. School of Child and Adolescent Health, University of Sydney, Sydney, Australia. The Children's Hospital at Westmead, Westmead, Australia.No affiliation info available

Pub Type(s)

Evaluation Study
Journal Article

Language

eng

PubMed ID

28806450

Citation

Macartney, Kristine, et al. "Evaluation of Combination Measles-Mumps-Rubella-Varicella Vaccine Introduction in Australia." JAMA Pediatrics, vol. 171, no. 10, 2017, pp. 992-998.
Macartney K, Gidding HF, Trinh L, et al. Evaluation of Combination Measles-Mumps-Rubella-Varicella Vaccine Introduction in Australia. JAMA Pediatr. 2017;171(10):992-998.
Macartney, K., Gidding, H. F., Trinh, L., Wang, H., Dey, A., Hull, B., Orr, K., McRae, J., Richmond, P., Gold, M., Crawford, N., Kynaston, J. A., McIntyre, P., & Wood, N. (2017). Evaluation of Combination Measles-Mumps-Rubella-Varicella Vaccine Introduction in Australia. JAMA Pediatrics, 171(10), 992-998. https://doi.org/10.1001/jamapediatrics.2017.1965
Macartney K, et al. Evaluation of Combination Measles-Mumps-Rubella-Varicella Vaccine Introduction in Australia. JAMA Pediatr. 2017 10 1;171(10):992-998. PubMed PMID: 28806450.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of Combination Measles-Mumps-Rubella-Varicella Vaccine Introduction in Australia. AU - Macartney,Kristine, AU - Gidding,Heather F, AU - Trinh,Lieu, AU - Wang,Han, AU - Dey,Aditi, AU - Hull,Brynley, AU - Orr,Karen, AU - McRae,Jocelynne, AU - Richmond,Peter, AU - Gold,Michael, AU - Crawford,Nigel, AU - Kynaston,Jennifer A, AU - McIntyre,Peter, AU - Wood,Nicholas, AU - ,, PY - 2017/8/15/pubmed PY - 2017/10/7/medline PY - 2017/8/15/entrez SP - 992 EP - 998 JF - JAMA pediatrics JO - JAMA Pediatr VL - 171 IS - 10 N2 - 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. SN - 2168-6211 UR - https://www.unboundmedicine.com/medline/citation/28806450/Evaluation_of_Combination_Measles_Mumps_Rubella_Varicella_Vaccine_Introduction_in_Australia_ L2 - https://jamanetwork.com/journals/jamapediatrics/fullarticle/10.1001/jamapediatrics.2017.1965 DB - PRIME DP - Unbound Medicine ER -