April-july-2016

Use of Combination Measles, Mumps, Rubella, and Varicella Vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP)

Author:Dr. Puneet Kalra

Introduction
To prevent measles, mumps, rubella, and varicella, the Advisory Committee on Immunization Practices (ACIP) recommends a 2-dose vaccine schedule in childhood, with the first dose administered at age 12--15 months and the second dose at age 4--6 years

The availability of MMRV vaccine since September 2005 meant that two vaccination options were available to implement the ACIP recommendation for vaccination of children aged 12 months--12 years:
  1. trivalent measles, mumps, rubella vaccine (MMR, M-M-RII, Merck & Co., Inc.) and monovalent varicella vaccine administered as two separate injections or
  2. combination MMRV vaccine administered as one injection.
onsistent with ACIP's 2006 general recommendations on immunization, use of the combination MMRV vaccine was preferred over separate injections of equivalent component vaccines (MMR vaccine and varicella vaccine) The two vaccination options are considered to provide the same protection against the four diseases. In MMRV vaccine prelicensure studies conducted among children aged 12--23 months, fever and rash had been reported at a greater rate 0--42 days following vaccination among children who received a first dose of MMRV vaccine (n =4,497) than among children who received first doses of MMR vaccine and varicella vaccine (n = 2,038)

. In light of these findings, to evaluate if an increased risk for febrile seizures might be associated with the first dose of MMRV vaccine, postlicensure studies were done. Preliminary data from these two studies presented to ACIP in February 2008 suggested a 2.3-times higher risk for febrile seizures among children aged 12--23 months during the 5--12 or 7--10 days after administration of the first dose of MMRV vaccine compared with administration of the first dose of MMR vaccine and varicella vaccine at the same time .

On the basis of these preliminary data, in February 2008, ACIP issued updated recommendations expressing no preference for use of MMRV vaccine over separate injections of equivalent component vaccines (i.e., MMR vaccine and varicella vaccine) for both the first and second dose .

ACIP also established a workgroup to evaluate postlicensure and other safety data regarding the risk for febrile seizures after MMRV vaccine and formulate policy options for use of MMRV vaccine for consideration by ACIP. In June 2009, after consideration of final data from the postlicensure studies and other evidence, ACIP adoptednew recommendations regarding use of MMRV vaccine. This report provides these recommendations and replaces the 2008 recommendations for the use of MMRV vaccine

Vaccine Safety
Risk for Febrile Seizure After First Dose of MMRV Vaccine MMR vaccine is associated with an increased risk for febrile seizures during the first 2 weeks after vaccination when the peak in replication of the live attenuated measles virus occurs (6--12 days) In the MMRV vaccine prelicensure studies conducted among children aged 12--23 months resulted in a higher rate of vaccine-associated fever or measles-like rashes after the first dose of MMRV the reasons for which are not fully understood but might suggest a more vigorous immune response in response to an increase in measles virus replication. Because of the known association between fever and febrile seizures postlicensure studies were done among larger populations of vaccinated children than were feasible during prelicensure studies to evaluate if a risk for febrile seizures might be associated with the first dose of MMRV vaccine which assessed the febrile seizure risk in different populations . Postlicensure data do not suggest that children who received MMRV vaccine as a second dose had an increased risk for febrile seizures after vaccination compared with children who received a second dose of MMR vaccine and varicella vaccine at the same visit.

Clinical Importance of Febrile Seizure
Febrile seizures occur most commonly with the fevers caused by typical childhood illnesses (e.g., middle-ear infections, viral upper respiratory tract infections, and roseola) but can be associated with any condition that results in fever, including vaccination. MMR vaccine is associated with an increased risk for febrile seizures occurring 8--14 days after vaccination among children aged <7 years. Parents and caregivers of children who have a first febrile seizure are likely to seek medical attention, which commonly includes a visit to an emergency department. The prognosis for young children who have febrile seizures generally is excellent . The majority (>90%) ofchildren who have a febrile seizure will not develop epilepsy.

Immunogenicity and Efficacy of MMRV Vaccine
MMRV vaccine was licensed on the basis of noninferior immunogenicity of the antigenic components compared with simultaneous administration of MMR vaccine and varicella vaccine . Formal studies to evaluate the clinical efficacy of MMRV vaccine have not been performed;

Vaccine Coverage
Maintaining high vaccination coverage is important for disease control. Combination vaccines reduce the number of injections children receive and have the potential to improve vaccination coverage and timeliness of vaccination. However, evidence is limited about the impact of the use of newer combination vaccines on vaccination coverage. Summary and Rationale for MMRV Vaccine Recommendations Two postlicensure studies and other related data support the conclusion that use of MMRV vaccine amongchildren aged 12--23 months results in a higher risk for fever and febrile seizures during the 5--12 days after thefirst dose compared with the use of MMR vaccine and varicella vaccine at the same visit. The approximately twofold increased risk results in an estimated one additional febrile seizure per 2,300--2,600 children vaccinated with the first dose of MMRV vaccine compared with those who receive the first dose with MMR vaccine and varicella vaccine. Although data regarding the risk for febrile seizures after administration of the first dose of MMRV vaccine are available only for children aged 12--23 months, the increased risk for febrile seizures during the 5--12 days postvaccination is likely to be present among children aged ≤47 months because that is the biologic window of vulnerability for febrile seizures in children (approximately 97% of febrile seizures occur in childrenaged <4 years)

Use of Antipyretics for Prevention of Febrile Seizures
Studies have not demonstrated that antipyretics (e.g., acetaminophen or ibuprofen) prevent febrile seizures . Parents and caregivers should be counseled about the possibility of fever after receipt of a measles containing vaccine and educated on timing and measures to control it.

Summary of recommendations for measles, mumps, rubella and varicella (MMRV) vaccineuse
  • 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.