Measles-mumps-rubella-varicella combination vaccine and the risk of febrile seizures

Since, 2007, the CDC’s Advisory Committee on Immunization Practices (AICP) has been investigating a possible link between the measles-mumps-rubella-varicella combination vaccine and an increase in febrile seizures.

The MMRV vaccine was licensed in the United States in September 2005 and given as an alternative to the MMR (measles, mumps, rubella) vaccine and varicella vaccine, given separately to children aged 12 months-12 years.

At the time of its licensure, use of MMRV vaccine was preferred for both the first and second doses over separate injections of each MMR vaccine and varicella vaccine, which was consistent with ACIP’s 2006 general recommendations on use of combination vaccines.

However, in July 2007, supplies of MMRV vaccine became temporarily unavailable as a result of manufacturing constraints unrelated to efficacy or safety. In February 2008, on the basis of preliminary data from two studies conducted postlicensure that suggested an increased risk for febrile seizures 5-12 days after vaccination among children aged 12-23 months who had received the first dose of MMRV vaccine compared with children the same age who had received the first dose of MMR vaccine and varicella vaccine administered as separate injections at the same visit, ACIP issued updated recommendations regarding MMRV vaccine use.

Those 12- to 23-month-olds who received their first dose of measles-containing vaccine, fever and seizure were elevated 7 to 10 days after vaccination. Vaccination with MMRV results in 1 additional febrile seizure for every 2300 doses given instead of separate MMR + varicella vaccines. Providers who recommend MMRV should communicate to parents that it increases the risk of fever and seizure over that already associated with measles-containing vaccines.

Studies of febrile seizures after vaccination with first dose of MMRV vaccine have not been done in older children, but experts agree that this increased risk of fever and febrile seizures during the 5 to 12 days after first dose vaccination likely also occurs in children aged 24-47 months .

Therefore, in June 2009, after consideration of the postlicensure data and other evidence, ACIP adopted new recommendations regarding use of MMRV vaccine.

Their recommendation is as follows:

The routinely recommended ages for measles, mumps, rubella and varicella vaccination continue to be age 12–15 months for the first dose and age 4–6 years for the second dose.

For the first dose of measles, mumps, rubella, and varicella vaccines at age 12–47 months, either measles, mumps, and rubella (MMR) vaccine and varicella vaccine or MMRV vaccine may be used. Providers who are considering administering MMRV vaccine should discuss the benefits and risks of both vaccination options with the parents or caregivers. Unless the parent or caregiver expresses a preference for MMRV vaccine, CDC recommends that MMR vaccine and varicella vaccine should be administered for the first dose in this age group.

For the second dose of measles, mumps, rubella, and varicella vaccines at any age (15 months–12 years) and for the first dose at age =48 months, use of MMRV vaccine generally is preferred over separate injections of its equivalent component vaccines (i.e., MMR vaccine and varicella vaccine). Considerations should include provider assessment, patient preference, and the potential for adverse events.

A personal or family (i.e., sibling or parent) history of seizures of any etiology is a precaution for MMRV vaccination. Children with a personal or family history of seizures of any etiology generally should be vaccinated with MMR vaccine and varicella vaccine.


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