Combined measles-mumps-rubella-varicella vaccine and febrile convulsions: the risk considered in the broad context

ABSTRACT

Introduction

Studies on quadrivalent measles, mumps, rubella, and varicella (MMRV) vaccines have indicated a twofold increased relative risk of febrile convulsion (FC) after the first dose compared to MMR and V administered at the same medical visit (MMR+V).

Areas covered

This narrative review contextualizes FC occurrence after the first MMRV vaccine dose from a clinical perspective and outlines approaches to attenuate FC occurrence post-vaccination.

Expert opinion

While the relative FC risk increases after the first dose of MMRV compared to MMR+V vaccine in measles-naïve infants, the attributable risk is low versus the overall FC risk in the pediatric population triggered by other causes, like natural exposure to pathogens or routine vaccination. No increased risk of FC has been reported after MMRV co-administration with other routine vaccines compared to MMRV alone. Based on our findings and considering the MMRV vaccination benefits (fewer injections, higher coverage, better vaccination compliance), the overall benefit-risk profile of MMRV vaccine is considered to remain positive. Potential occurrence of FC in predisposed children (e.g. with personal/family history of FC) may be attenuated if they receive MMR+V instead of MMRV as the first dose. It is also important to monitor vaccinees for fever during the first 2 weeks post-vaccination.

Plain Language Summary

Children under 5 years of age can sometimes have convulsions when they get a fever during illness or after vaccination. These are called febrile convulsions, and, in most cases, they leave no lasting damage, and the child outgrows them. After a combined vaccine against four childhood illnesses (measles, mumps, rubella, and varicella) became available, concerns appeared that measles-naïve children who received a first dose of this vaccine had a higher risk of febrile convulsions than children vaccinated with two separate vaccines (one against measles, mumps, and rubella, and one against varicella) administered during the same medical visit. However, this risk is low: during the first or the second week after the first vaccine dose, 1 additional child out of approximately 2500 children who receive the combined vaccine will have a febrile convulsion compared to those receiving 2 separate vaccines. In comparison, febrile convulsions due to any cause will appear in 1 out of 25 children younger than 5 years, and in 1 out of 43 children with measles. The combined vaccine has certain advantages over separate vaccines: children receive fewer injections and are more likely to be fully vaccinated against all four diseases. Children who had febrile convulsions before, or with a close relative who had febrile convulsions could be at higher risk of febrile convulsions after the first dose of the combined vaccine. Provided the informed consent from their parents or legal guardians, these children must receive separate vaccines, while all other children may receive the combined vaccine.

GRAPHICAL ABSTRACT

KEYWORDS:

• Children
• febrile convulsion
• febrile seizure
• measles-mumps-rubella-varicella vaccine
• MMRV
• risk management
• varicella vaccination

Article highlights

• The relative risk of febrile convulsion after the first MMRV dose is twofold higher compared to MMR+V in measles-naïve infants.

• However, the incidence of febrile convulsion after the first MMRV dose contributes marginally to the overall rate of febrile convulsion in toddlers.

• The overall safety profile of MMRV vaccine as first dose remains acceptable when assessed in a broader context.

Declaration of interests

G Casabona, O Berton, and T Singh are employees of GSK, hold shares in this company, and declare financial/non-financial relationships and activities. P Bonanni received payment or honoraria as a participant at advisory boards and speaker sponsored by GSK, MSD, Pfizer, Seqirus, AstraZeneca, Janssen, and Sanofi Pasteur and as a member of a Data Safety Monitoring Committee for a Shigella investigational vaccine with GSK Vaccines Institute for Global Health (GVGH). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Authors’ contributions

All authors were involved in the conception and design of this review article. All authors were involved in data analyses and interpretation, and in writing the article. All authors contributed to the review of the paper for important intellectual content and have approved it for submission and publication.

Acknowledgments

Authors thank Akkodis platform for editorial assistance and manuscript coordination, on behalf of GSK. Botond Nagy provided medical writing support and Gil Costa provided graphic support.

This work has already been presented at the 40th Annual meeting of the European Society for Paediatric Infectious Diseases (9–13 May 2022) as an E-poster EP079/#1126 entitled “Combined Measles-Mumps-Rubella-Varicella vaccine and febrile convulsions: the risk considered in the broad context” and authored by Giacomo Casabona (presenting author), Olivia Berton, Markus Knuf, and Paolo Bonanni.

Trademark

Priorix-Tetra is a trademark owned by or licensed to the GSK group of companies. ProQuad is a trademark of Merck & Co., Inc..

Additional information

Funding

This work was funded by GlaxoSmithKline Biologicals SA. GlaxoSmithKline Biologicals SA covered the costs associated with the development and the publishing of the present manuscript.