Background
Measles, mumps, rubella (German measles) and varicella (chickenpox) are infectious diseases caused by viruses. They are most common in children and young adults. They are not always serious, but can cause disability (such as deafness), complications and death. If pregnant women catch rubella, it may cause loss (miscarriage) of, or harm to, their unborn babies.
A vaccine is a medicine that prevents infection by a specific disease. The MMR (measles, mumps, rubella) vaccine protects people against all three of these infections (a combined vaccine). Doctors can vaccinate against chickenpox at the same time by mixing the chickenpox (varicella) vaccine with the MMR vaccine (MMRV) or giving it separately at the same time (MMR+V).
The MMR vaccine has reduced measles, mumps and rubella infections. However, some people think the MMR vaccine causes unwanted effects such as autism, swelling of the brain (encephalitis), meningitis, learning difficulties, type 1 diabetes, and other conditions. As a result, the number of children being vaccinated has fallen.
This is the 2019 update of a review first published in 2005 and previously updated in 2012.
Review question
We wanted to find out how effectively MMR, MMR+V and MMRV vaccines stop children (up to 15 years old) from catching measles, mumps, rubella and chickenpox. We also wanted to know if the vaccines cause unwanted effects.
Study characteristics
We looked for studies that assessed MMR, MMRV or MMR+V vaccines, given in any dose or time schedule, compared with not giving the vaccine, or giving a placebo vaccine (a sham treatment), to healthy children up to 15 years old. Studies needed to measure the number of cases of measles, mumps, rubella and chickenpox, and report whether children suffered any unwanted effects attributable to vaccination. We checked each study to make sure it used robust methods so that we could judge how reliable its results were.
Results
We found 138 studies with more than 23 million children. Fifty-one studies (10 million children) assessed how effective the vaccines were at preventing the diseases, and 87 studies (13 million children) assessed unwanted effects. In this 2020 update we have included 74 new studies published since 2012.
Measles: results from seven studies (12,000 children) showed that one dose of vaccine was 95% effective in preventing measles. Seven per cent of unvaccinated children would catch measles and this number would fall to less than 0.5% of children who receive one dose of vaccine.
Mumps: results from six studies (9915 children) showed that one dose of vaccine was 72% effective in preventing mumps. This rose to 86% after two doses, (3 studies, 7792 children). In unvaccinated children, 7.4% would catch mumps and this would fall to 1% if children were vaccinated with two doses.
The results for rubella (1 study, 1621 children) and chickenpox (one study, 2279 children) also showed that vaccines are effective. After one dose, vaccination was 89% effective in preventing rubella, using a vaccine with the BRD2 strain which is only used in China, and after 10 years the MMRV vaccine was 95% effective at preventing chickenpox infection.
Unwanted effects
Overall, the studies found that MMR, MMRV and MMR+V vaccines did not cause autism (2 studies 1,194,764 children), encephalitis (2 studies 1,071,088 children) or any other suspected unwanted effect.
Our analyses showed very small risks of fits due to high temperature or fever (febrile seizures) around two weeks after vaccination, and of a condition where blood does not clot normally (idiopathic thrombocytopenic purpura) in vaccinated children.
Certainty of the evidence
Our certainty (confidence) in the evidence is slightly limited by the design of most of the studies. Nonetheless, we judged the certainty of the evidence for the effectiveness of the MMR vaccine to be moderate, and that for the varicella vaccine to be high. Our certainty in the evidence for autism and febrile seizures was also moderate.
Conclusions
Our review shows that MMR, MMRV and MMR+V vaccines are effective in preventing the infection of children by measles, mumps, rubella and chickenpox, with no evidence of an increased risk of autism or encephalitis and a small risk of febrile seizure.
Search date
This review includes evidence published up to 2 May 2019.
Existing evidence on the safety and effectiveness of MMR/MMRV vaccines support their use for mass immunisation. Campaigns aimed at global eradication should assess epidemiological and socioeconomic situations of the countries as well as the capacity to achieve high vaccination coverage. More evidence is needed to assess whether the protective effect of MMR/MMRV could wane with time since immunisation.
Measles, mumps, rubella, and varicella (chickenpox) are serious diseases that can lead to serious complications, disability, and death. However, public debate over the safety of the trivalent MMR vaccine and the resultant drop in vaccination coverage in several countries persists, despite its almost universal use and accepted effectiveness. This is an update of a review published in 2005 and updated in 2012.
To assess the effectiveness, safety, and long- and short-term adverse effects associated with the trivalent vaccine, containing measles, rubella, mumps strains (MMR), or concurrent administration of MMR vaccine and varicella vaccine (MMR+V), or tetravalent vaccine containing measles, rubella, mumps, and varicella strains (MMRV), given to children aged up to 15 years.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2019, Issue 5), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to 2 May 2019), Embase (1974 to 2 May 2019), the WHO International Clinical Trials Registry Platform (2 May 2019), and ClinicalTrials.gov (2 May 2019).
We included randomised controlled trials (RCTs), controlled clinical trials (CCTs), prospective and retrospective cohort studies (PCS/RCS), case-control studies (CCS), interrupted time-series (ITS) studies, case cross-over (CCO) studies, case-only ecological method (COEM) studies, self-controlled case series (SCCS) studies, person-time cohort (PTC) studies, and case-coverage design/screening methods (CCD/SM) studies, assessing any combined MMR or MMRV / MMR+V vaccine given in any dose, preparation or time schedule compared with no intervention or placebo, on healthy children up to 15 years of age.
Two review authors independently extracted data and assessed the methodological quality of the included studies. We grouped studies for quantitative analysis according to study design, vaccine type (MMR, MMRV, MMR+V), virus strain, and study settings. Outcomes of interest were cases of measles, mumps, rubella, and varicella, and harms. Certainty of evidence of was rated using GRADE.
We included 138 studies (23,480,668 participants). Fifty-one studies (10,248,159 children) assessed vaccine effectiveness and 87 studies (13,232,509 children) assessed the association between vaccines and a variety of harms. We included 74 new studies to this 2019 version of the review.
Effectiveness
Vaccine effectiveness in preventing measles was 95% after one dose (relative risk (RR) 0.05, 95% CI 0.02 to 0.13; 7 cohort studies; 12,039 children; moderate certainty evidence) and 96% after two doses (RR 0.04, 95% CI 0.01 to 0.28; 5 cohort studies; 21,604 children; moderate certainty evidence). The effectiveness in preventing cases among household contacts or preventing transmission to others the children were in contact with after one dose was 81% (RR 0.19, 95% CI 0.04 to 0.89; 3 cohort studies; 151 children; low certainty evidence), after two doses 85% (RR 0.15, 95% CI 0.03 to 0.75; 3 cohort studies; 378 children; low certainty evidence), and after three doses was 96% (RR 0.04, 95% CI 0.01 to 0.23; 2 cohort studies; 151 children; low certainty evidence). The effectiveness (at least one dose) in preventing measles after exposure (post-exposure prophylaxis) was 74% (RR 0.26, 95% CI 0.14 to 0.50; 2 cohort studies; 283 children; low certainty evidence).
The effectiveness of Jeryl Lynn containing MMR vaccine in preventing mumps was 72% after one dose (RR 0.24, 95% CI 0.08 to 0.76; 6 cohort studies; 9915 children; moderate certainty evidence), 86% after two doses (RR 0.12, 95% CI 0.04 to 0.35; 5 cohort studies; 7792 children; moderate certainty evidence). Effectiveness in preventing cases among household contacts was 74% (RR 0.26, 95% CI 0.13 to 0.49; 3 cohort studies; 1036 children; moderate certainty evidence).
Vaccine effectiveness against rubella, using a vaccine with the BRD2 strain which is only used in China, is 89% (RR 0.11, 95% CI 0.03 to 0.42; 1 cohort study; 1621 children; moderate certainty evidence).
Vaccine effectiveness against varicella (any severity) after two doses in children aged 11 to 22 months is 95% in a 10 years follow-up (rate ratio (rr) 0.05, 95% CI 0.03 to 0.08; 1 RCT; 2279 children; high certainty evidence).
Safety
There is evidence supporting an association between aseptic meningitis and MMR vaccines containing Urabe and Leningrad-Zagreb mumps strains, but no evidence supporting this association for MMR vaccines containing Jeryl Lynn mumps strains (rr 1.30, 95% CI 0.66 to 2.56; low certainty evidence). The analyses provide evidence supporting an association between MMR/MMR+V/MMRV vaccines (Jeryl Lynn strain) and febrile seizures. Febrile seizures normally occur in 2% to 4% of healthy children at least once before the age of 5. The attributable risk febrile seizures vaccine-induced is estimated to be from 1 per 1700 to 1 per 1150 administered doses.
The analyses provide evidence supporting an association between MMR vaccination and idiopathic thrombocytopaenic purpura (ITP). However, the risk of ITP after vaccination is smaller than after natural infection with these viruses. Natural infection of ITP occur in 5 cases per 100,000 (1 case per 20,000) per year. The attributable risk is estimated about 1 case of ITP per 40,000 administered MMR doses.
There is no evidence of an association between MMR immunisation and encephalitis or encephalopathy (rate ratio 0.90, 95% CI 0.50 to 1.61; 2 observational studies; 1,071,088 children; low certainty evidence), and autistic spectrum disorders (rate ratio 0.93, 95% CI 0.85 to 1.01; 2 observational studies; 1,194,764 children; moderate certainty). There is insufficient evidence to determine the association between MMR immunisation and inflammatory bowel disease (odds ratio 1.42, 95% CI 0.93 to 2.16; 3 observational studies; 409 cases and 1416 controls; moderate certainty evidence).
Additionally, there is no evidence supporting an association between MMR immunisation and cognitive delay, type 1 diabetes, asthma, dermatitis/eczema, hay fever, leukaemia, multiple sclerosis, gait disturbance, and bacterial or viral infections.