Although the measles-mumps-rubella, (MMR) and varicella (MMRV) vaccines were found to be most effective in preventing varicella zoster virus and measles, they were associated with an increased risk for aseptic meningitis, According to results of a systematic review and meta-analysis published in the Cochrane Database of Systematic Reviews.

Publication databases were searched through May 2019 for studies of the MMR/MMRV vaccine among children aged 15 years and younger. A total of 138 studies were included in the review, and the efficacy and safety profiles of both vaccines were assessed. Of note, only 51 studies included information about vaccine efficacy.

For measles, the protection from 1vaccine dose had an effectiveness of 95% (risk ratio [RR], 0.05; 95% CI, 0.02-0.13) and the protection from 2 doses had an effectiveness of 96% (RR, 0.04; 95% CI, 0.01-0.28). Although the effectiveness of the vaccine in protecting against measles among household contacts was decreased after the first (81%; RR, 0.19; 95% CI, 0.04-0.89) and second (86%; RR, 0.15; 95% CI, 0.03-0.75) vaccine doses, the effectiveness was found to be similar after 3 doses (96%; RR, 0.04; 95% CI, 0.01-0.23). The effectiveness in preventing measles after postexposure prophylaxis was 74% (RR, 0.26; 95% CI, 0.14-0.50).

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For protection against mumps, vaccines derived from Jeryl Lynn strain (RR, 0.23; 95% CI, 0.14-0.35) and Urabe strain (RR, 0.23; 95% CI, 0.12-0.44) were more effective compared with the Rubini strain (RR, 0.96; 95% CI, 0.55-1.65). The most effective protection against mumps was observed after two vaccine doses derived from the Jeryl Lynn strain (RR, 0.12; 95% CI, 0.04-0.35).

For rubella, the only outcome the researchers were able to calculate was the risk for secondary infection with any strain after vaccination (RR, 0.11; 95% CI, 0.03-0.42).

At 5 years, the protection against varicella with 2 vaccine doses had an RR of 0.05 (95% CI, 0.03-0.08), which remained stable at 10 years (RR, 0.05; 95% CI, 0.04-0.06). Of note, there was effectively no protection against moderate to severe infection at 5 years (95% CI, 0.00-0.02).

Among the 87 studies included in the review with information about vaccine safety, there was increased risk for febrile seizure (RR, 1.36), rash (RR, 1.49), lymphadenopathy (RR, 1.98), coryza (RR, 1.13), upper respiratory tract infection (RR, 1.44), and cough (RR, 1.99).

On analysis of case cross-over studies of the Urabe or Hoshino strains, the researchers found that the risk for aseptic meningitis was increased (RR, 4.00; 95% CI, 2.33-7.20). Similar findings were noted on analysis of studies using the Urabe strain (RR, 30.71; 95% CI, 13.45-70.10) and the Leninggrad-Zagreb strain (RR, 18.56; 95% CI, 12.09-28.51).

Among all studies included in the review, 38% had a decreased risk of bias, 40% had an unclear risk of bias, and 22% had an increased risk of bias.

This study was limited by its inclusion of studies with either an increased or unclear risk of bias.

According to the researchers, “existing evidence on the safety and effectiveness of MMR and MMRV vaccines supports current policies of mass immunization aimed at global measles eradication in order to [decrease] morbidity and mortality associated with measles, mumps, rubella, and varicella.”


Di Pietrantonj C, Rivetti A, Marchione P, Debalini MG, Demicheli V. Vaccines for measles, mumps, rubella, and varicella in children (review). Cochrane Database Syst Rev. 2021;11:CD004407. doi:10.1002/14651858.CD004407.pub5