Since the publication of the 2006 Canadian Immunization Guide a new combined multivalent vaccine (measles-mumps-rubella-varicella vaccine [MMRV]) has become available for children aged 12 months to 12 years.
For additional information, refer to the National Advisory Committee on Immunization (NACI) Statements: Statement on Measles-Mumps-Rubella-Varicella Vaccine and Updated Recommendations for the use of Varicella and MMR Vaccines in HIV-infected Individuals.
Rubella (German measles) is caused by rubella virus, a ribonucleic acid (RNA) virus of the Togaviridae family.
Rubella virus is highly communicable and is transmitted by droplet spread or direct contact with nasopharyngeal secretions of infected people. Transplacental transmission from an infected mother to her fetus during pregnancy may result in Congenital Rubella Syndrome (CRS) in the infant. Infants with CRS may shed the virus in their urine and nasopharyngeal secretions for 1 year or more. The incubation period for rubella is from 14 to 17 days (range, 14 to 21 days). The period of communicability extends from 1 week before to at least 4 days after the onset of rash. People who recover from rubella have lifetime immunity.
People of any age who have not been successfully vaccinated or have not had rubella disease are at risk of being infected. In Canada, routine infant immunization programs have resulted in sustained high rates of immunity in the general population, but the risk of limited transmission resulting from importation still exists.
Historically, the incidence of rubella peaked in the spring and winter months in temperate zones, but now is limited to sporadic cases and outbreaks.
Spectrum of clinical illness
Rubella results in a transient erythematous rash, post-auricular and suboccipital lymphadenopathy, arthralgia and low-grade fever. As symptoms are non-specific, it may be mistaken for infection due to other viruses. Adult infection is frequently accompanied by transient polyarthralgia or polyarthritis. Serious complications are rare, and up to 50% of infections are subclinical.
Rubella infection in pregnancy may give rise to CRS, which can result in miscarriage, stillbirth and fetal malformations, including congenital heart disease, cataracts, deafness and mental retardation. Fetal infection can occur at any stage of pregnancy, but the risk of fetal damage following maternal infection is particularly high in the earliest months after conception (85% in the first trimester) with progressive diminution of risk thereafter, and it is very uncommon after the 20th week of pregnancy. Infected infants who appear normal at birth may later show eye, ear or brain damage.
Rubella occurs worldwide; however, during the last decade, rubella vaccination programs have greatly reduced incidence rates of rubella in most industrialized countries. By 2008, 66% of World Health Organization (WHO) member countries had included rubella in their childhood immunization schedule. In 2003, the Pan American Health Organization established a goal to eliminate indigenous rubella and CRS from the WHO region of the Americas by 2010. By October 2008, all 38 countries and territories in the Americas, with the exception of Haiti, had introduced MMR vaccine into routine immunization schedules. Beginning in 2009, Haiti planned to introduce measles-rubella (MR) vaccine into its routine immunization program after completion of a one-time MR mass vaccination campaign. In the region of the Americas, the average annual number of cases for the period of 2003 to 2008 dropped 92% compared with the annual number of cases for the period of 1997 to 2002.
In Canada, the MMR immunization program for infants was introduced in April 1983 and has resulted in sustained high rates of immunity in the general population. In addition, measles elimination strategies employed since the mid-1990s have indirectly resulted in a reduction in the proportion of the population that is rubella susceptible because of the use of rubella-containing vaccines for the two dose routine immunization program and measles elimination catch-up campaigns.
The average annual number of rubella cases reported in Canada decreased from approximately 5,300 (1971-1982), to about 1,800 (1983-1997), to less than 30 (1998 -2004). From 2006 to 2010, on average fewer than 5 cases were reported annually.
In 2005, the incidence rate of rubella in Canada increased to about 10 per 1,000,000 with the majority of cases occurring in a large outbreak in southwestern Ontario (refer to Recent outbreaks). The average annual incidence rate of rubella has decreased from 2.1 per 1,000,000 in 1998 to 0.29 per 1,000,000 in 2010.
From 1996 to 2010, fewer than 3 cases of CRS were reported each year in Canada and most of these infants were born to foreign-born women. There have been no CRS cases due to exposure to rubella in Canada since 2000. Since that time, the six CRS cases reported were imported from other countries.
In the two decades following the 1983 introduction of routine infant rubella immunization, epidemics of rubella continued to occur every 3 to 10 years. Many of these outbreaks, including one involving over 3,900 cases in Manitoba in 1997, differentially affected males aged 15 to 24 years of age who were not immunized because of pre-1983 selective rubella immunization programs of girls only in some jurisdictions. Since the late 1990s, outbreaks have largely been restricted to isolated clusters of unimmunized people, including those who decline immunization for religious or philosophical reasons.
In 2005, there was a rubella outbreak involving 309 laboratory-confirmed cases in an unimmunized southwestern Ontario community. The outbreak was attributed to under-vaccination of persons in a community that is philosophically opposed to immunization. Over 60% of the cases were in unimmunized children aged 5 to 14 years. Ten cases involved pregnant women, but no cases of CRS were reported. As a result of high immunization rates in the general population, spread of the outbreak to the surrounding community was limited.
In Canada, rubella vaccine is only available in combination with measles and mumps vaccine (MMR) or measles, mumps and varicella vaccine (MMRV). In many countries outside of Canada, measles vaccine alone is given and rubella vaccination is not offered.
For complete prescribing information, consult the product leaflet or information contained within Health Canada’s authorized product monographs available through the Drug Product Database. Refer to Table 1 in General Considerations in Part 1 for a list of all vaccines available for use in Canada and their contents.
The duration of protection following immunization with rubella-containing vaccine is not known, but studies indicate that the duration of both cellular and humoral immunity exceeds 20 years. Asymptomatic rubella re-infection, manifest by a rise in antibody, has been observed in some vaccinees. Asymptomatic re-infection has also been observed in women with naturally acquired immunity associated with very low antibody titres. There are no data regarding the efficacy of MMRV vaccine.
In clinical trials, 95% or more of vaccinees aged 12 months and older developed serologic evidence of rubella immunity after a single dose of rubella-containing vaccine. Titres are generally lower than those observed in natural rubella infection. Long-term persistence of anti-measles, anti-mumps, anti-rubella and anti-varicella antibodies following MMRV vaccinations are under evaluation.
One dose of rubella-containing vaccine should be given for routine immunization of children and for immunization of children and adolescents who missed rubella immunization on the routine schedule. MMRV vaccine may be used in children aged 12 months to 12 years.
Adults who do not have documented evidence of receiving rubella-containing vaccine on or after their first birthday, or laboratory evidence of immunity, or a history of laboratory confirmed rubella infection should be immunized with one dose of MMR vaccine.
Rubella immunization recommendations differ from measles and mumps recommendations. Because the available preparations all contain measles, mumps and rubella, extra rubella vaccinations may be administered when following the recommendations for measles and mumps vaccination.
Individuals who have one or more of the following are considered immune to rubella. Individuals who do not have ANY of the following are considered susceptible to rubella:
The following groups are priorities for rubella immunization:
A second dose of MMR or MMRV vaccine (as appropriate for age and risk factors) may be recommended for measles and mumps protection (MMR and MMRV) and varicella protection (MMRV) in certain people. Although a second dose of the rubella component is not considered necessary for elimination of CRS, it is not harmful and may benefit the 1% to 5% of people who do not respond to primary immunization. Refer to Measles Vaccine, Mumps Vaccine and Varicella (Chickenpox) Vaccine in Part 4 for additional information and to Schedule.
Children and adults lacking adequate documentation of immunization should be considered unimmunized and started on an immunization schedule appropriate for their age and risk factors, unless known to be immune based on laboratory testing. MMR or MMRV vaccine as appropriate may be given regardless of possible previous receipt of the vaccine because additional adverse events associated with repeated immunization have not been demonstrated. Refer to Immunization of Children and Adults with Inadequate Immunization Records in Part 3 for additional general information.
Immunity to measles, mumps and rubella should be reviewed in women of reproductive age, and vaccination should be recommended to non-pregnant susceptible women. Women should delay pregnancy by 4 weeks following vaccination with MMR vaccine.
MMR and MMRV vaccines are contraindicated in pregnancy because there is theoretical risk to the fetus; however, there is no evidence demonstrating a teratogenic risk from such vaccines. In one study, there was no evidence of CRS in any of the offspring of 226 women inadvertently vaccinated during pregnancy. Termination of pregnancy should not be recommended following inadvertent immunization with rubella-containing vaccine on the basis of fetal risks following maternal immunization.
Women who are breastfeeding can be vaccinated with MMR vaccine.
Susceptible residents of long-term care facilities should receive measles, mumps and rubella-containing vaccine as well as all routine immunizations appropriate for their age and risk factors. Refer to Immunization of Patients in Health Care Institutions in Part 3 for additional general information.
In general, immunocompromised persons should not receive live vaccines because of the risk of disease caused by the vaccine strains. When considering immunization of an immunocompromised person, approval from the individual’s attending physician should be obtained before vaccination. For complex cases, referral to a physician with expertise in immunization and/or immunodeficiency is advised. Refer to Immunocompromised persons in Measles Vaccine in Part 4.
Susceptible household contacts of immunocompromised people should receive a rubella-containing vaccine as appropriate for age and risk factors.
People with conditions such as autism spectrum disorders or demyelinating disorders (including multiple sclerosis) should receive all routinely recommended immunizations, including MMR or MMRV vaccine. Refer to Immunization of Persons with Chronic Diseases in Part 3 for additional general information.
Protection against rubella is important for people planning travel to rubella-endemic areas. Susceptible travellers should receive one dose of rubella-containing vaccine.
Rubella incidence rates in WHO member countries are available at: Vaccine-preventable diseases
Refer to Immunization of Travellers in Part 3 for additional general information.
Health care providers who see persons newly arrived in Canada should review the immunization status and update immunization for these individuals. In many countries outside of Canada, mumps and rubella vaccines are in limited use and measles vaccine alone is given. Refer to Immunization of Persons New to Canada in Part 3 for additional general information.
It is recommended that all health care workers be immune to rubella. Health care workers who do not have documented evidence of receiving one dose of rubella-containing vaccine on or after their first birthday, or laboratory evidence of immunity, or a history of laboratory confirmed rubella disease should receive one dose of MMR vaccine. Refer to Immunization of Workers in Part 3 for additional general information.
Post-exposure MMR vaccination does not prevent or alter the clinical severity of rubella after exposure; however, if exposure to rubella does not cause infection, post-exposure vaccination with MMR vaccine should induce protection against subsequent infection. There is no evidence of increased risk of adverse reactions from immunization with MMR vaccine if an individual is already immune to one or more components of the vaccine or infected by rubella virus.
Passive immunization with human immune globulin (Ig) is not effective in preventing rubella. Ig given soon after exposure to rubella may modify or suppress symptoms but may not prevent infection, including congenital infection. Therefore, the routine use of Ig in susceptible women exposed to rubella early in pregnancy is not recommended.
During rubella outbreaks, susceptible people should be given MMR vaccine promptly without prior serologic testing. In consultation with public health officials, it may be appropriate to vaccinate pregnant women.
Each dose is 0.5 mL.
Route of administration
MMR vaccine should be administered subcutaneously; MMRV can be administered subcutaneously or intramuscularly. Refer to Vaccine Administration Practices in Part 1 for additional information.
Children(12 months to 12 years of age)
For routine immunization of children aged 12 months to 12 years, one dose of rubella-containing vaccine (MMR or MMRV) should be administered at 12 to 15 months of age.
Adolescents (13 to 17 years of age)
Rubella-susceptible adolescents should receive one dose of MMR vaccine.
Adults (18 years of age and older)
Rubella-susceptible adults should receive one dose of MMR vaccine.
Re-immunization with rubella-containing vaccine after documented receipt of one dose of rubella-containing vaccine is not necessary. However, if a booster dose is given, it is not harmful and may benefit individuals who do not respond to primary immunization.
Serologic testing is not routinely recommended before or after receiving rubella-containing vaccine.
Pregnant women should be serologically screened for rubella antibodies, unless there is documented evidence of receipt of a rubella-containing vaccine. Those found to be non-immune serologically should be vaccinated with one dose of MMR vaccine in the immediate post-partum period, before discharge from hospital. Women who have been appropriately immunized post-partum do not need to be serologically screened for rubella antibodies either post-immunization or in subsequent pregnancies. Women who have been found to be serologically positive in one pregnancy do not need to be screened again in subsequent pregnancies.
M-M-R® II: Maintain vaccine at +10°C or colder during shipment. Freezing during shipment will not affect potency of the vaccine. Protect the vaccine from light. Before reconstitution, store the vial of vaccine at +2°C to +8°C or colder. The diluent may be stored in the refrigerator or at room temperature and must not be frozen.
PRIORIX®: Store in a refrigerator at +2°C to +8°C. The diluent may be stored separately at room temperature. Protect from light
PRIORIX-TETRA®: Store the vaccine and diluent in a refrigerator at +2°C to +8°C and do not freeze. Protect the vaccine from light.
Refer to Storage and Handling of Immunizing Agents in Part 1 for additional general information.
MMR or MMRV vaccine may be administered concomitantly with routine childhood vaccines or live intranasal influenza vaccine (LAIV). Different injection sites and separate needles and syringes must be used for concomitant parenteral injections. If not given concomitantly, a minimum interval of 4 weeks is recommended between administration of two live vaccines to address the hypothetical risk of interference from the vaccine given first on the vaccine given later.
Refer to Timing of Vaccine Administration in Part 1 for additional general information.
Refer to Vaccine Safety in Part 2 for additional general information.
Adverse events following MMR immunization occur less frequently and are less severe than those associated with natural disease. Adverse reactions are less frequent after the second dose of vaccine and tend to occur only in those not protected by the first dose. Six to 23 days after MMR immunization, approximately 5% of immunized children experience malaise and fever (with or without rash) lasting up to 3 days. Parotitis, rash, lymphadenophy, and joint symptoms also occur occasionally after MMR immunization.
Pain and redness at the injection site and/or low-grade fever occur in 10% or more of vaccinees. Rash including measles-like, rubella-like and varicella-like rash, as well as swelling at the injection site and moderate fever (greater than 39°C), occur in 1% to less than 10% of vaccinees. As varicella-like rashes that occur within the first two weeks after immunization may be caused by wild-type virus, health care providers should obtain specimens using viral transport media from a lesion of the vaccinee to ensure varicella disease is not confused with a reaction to vaccination.
Acute transient arthritis or arthralgia may occur 1 to 3 weeks after immunization with rubella-containing vaccine, lasts for about 1 to 3 weeks, and rarely recurs. This is more common in post-pubertal girls, among whom arthralgia develops in 25% and arthritis in 10% after immunization with rubella-containing vaccine. There is no evidence of increased risk of new onset, chronic arthropathies or neurologic conditions.
Serious adverse events are rare following immunization and, in most cases, data are insufficient to determine a causal association. As with other vaccines, anaphylaxis following vaccination with MMR or MMRV vaccine may occur but is very rare.
Immune Thrombocytopenic Purpura (ITP)
Rarely, ITP occurs within 6 weeks after immunization with MMR or MMRV vaccine. In most children, post-immunization thrombocytopenia resolves within three months without serious complications. In individuals who experienced ITP with the first dose of MMR or MMRV vaccine, serologic status may be evaluated to determine whether an additional dose of vaccine is needed. The potential risk to benefit ratio should be carefully evaluated before considering vaccination in such cases.
Encephalitis has been reported in association with administration of measles vaccine in approximately 1 per million doses distributed in North America which is much lower than that observed with natural measles disease (1 per 1,000 cases).
Recent studies have found a higher risk of febrile seizures with the first dose of a MMRV vaccine (ProQuad®, Merck, not authorized for use in Canada) when compared to the concomitant administration of MMR and univalent varicella vaccine. Data from the United States (US) estimated that the risk of febrile seizures in the 5 to 12 days following the first dose of this MMRV vaccine is 1 for every 2,600 vaccinated children aged 12 to 23 months. Experience with the MMRV vaccine available in Canada is more limited; however, one study showed an additional risk of febrile seizures with MMRV vaccine compared to MMR and univalent varicella vaccines given as two separate products administered concomitantly. The risk with the Canadian vaccine was smaller than the risk found with the US product. Close surveillance and further investigation are underway.
In the mid to late 1990s, researchers from the United Kingdom reported an association between MMR vaccine and inflammatory bowel disease and MMR vaccine and autism. Rigorous scientific studies and reviews of the evidence have been done worldwide, and there is now considerable evidence to refute those claims. In 2010, the original study suggesting a link between the MMR vaccine and autism was retracted.
Vaccine providers are asked to report the following AEFI in particular, through local public health officials:
Refer to Reporting Adverse Events Following Immunization (AEFI) in Canada in Vaccine Safety Part 2 for additional information about AEFI reporting.
With the exception of egg allergy (see below), MMR and MMRV vaccines are contraindicated in persons with a history of anaphylaxis after previous administration of the vaccine and in persons with proven immediate or anaphylactic hypersensitivity to any component of the vaccine or its container. Refer to Table 1 in General Considerations in Part 1 for lists of all vaccines available for use in Canada and their contents. For mumps-containing vaccines, potential allergens include:
In situations of suspected hypersensitivity ornon-anaphylactic allergy to vaccine components, investigation is indicated which may involve immunization in a controlled setting. Consultation with an allergist is advised.
The measles and mumps components of MMR and MMRV vaccines are produced in chick embryo cell culture and may contain traces of egg protein. The amount of egg protein in the vaccine appears to be insufficient to cause an allergic reaction in egg-allergic individuals. Skin testing is not recommended prior to vaccination. MMR or MMRV vaccine can be administered in the routine manner to people who have a history of anaphylactic hypersensitivity to hens’ eggs. Prior egg ingestion is not a prerequisite for immunization. For all vaccines, immunization should be performed by personnel with the capability and facilities to manage adverse events post-vaccination. Refer to Anaphylactic Hypersensitivity to Egg and Egg-Related Antigens in Part 2 for additional information.
Children with a known or suspected family history of congenital or hereditary immunodeficiency that is a contraindication to vaccination with live vaccine should not receive live vaccines unless their immune competence has been established.
MMRV vaccine is contraindicated in persons with impaired immune function, including primary or secondary immunodeficiency disorders. Refer to Immunocompromised persons.
MMR and MMRV vaccines are contraindicated during pregnancy. Refer to Pregnancy and lactation.
MMR vaccine is contraindicated in individuals with active, untreated tuberculosis. While tuberculosis may be exacerbated by natural measles infection, there is no evidence that measles-containing vaccines, such as MMR or MMRV, have such an effect.
A history of febrile convulsions or a family history of convulsions is not a contraindication for the use of MMRV vaccine.
Administration of MMR or MMRV vaccine should be postponed in persons with a severe acute illness. Immunization should not be delayed because of minor acute illness, with or without fever.
It is recommended to avoid the use of salicylates (e.g., acetylsalicylic acid [ASA]) for 6 weeks after immunization with MMRV vaccine because of an association between wild-type varicella, salicylate therapy and Reye’s syndrome.
Refer to General Contraindications and Precautions in Part 2 for additional general information.
Systemic antiviral therapy (such as acyclovir, valacyclovir, famciclovir) should be avoided in the peri-immunization period, as it may reduce the efficacy of varicella-containing vaccine such as MMRV. On the basis of expert opinion, it is recommended that people taking long-term antiviral therapy should discontinue these drugs, if possible from at least 24 hours before administration of MMRV vaccine and should not restart antiviral therapy until 14 days after.
The measles component in measles-containing vaccines can temporarily suppress tuberculin reactivity, resulting in false-negative results. If tuberculin skin testing or an Interferon Gamma Release Assay (IGRA) test is required, it should be done on the same day as immunization or delayed for at least 4 weeks after measles vaccination. Vaccination with measles-containing vaccine may take place at any time after tuberculin skin testing has been performed and/or read.
Passive immunization with human immune globulin or receipt of most blood products can interfere with the immune response to MMR and MMRV vaccines. These vaccines should be given at least 14 days prior to administration of an immune globulin or blood product, or delayed until the antibodies in the immune globulin or blood product have degraded. If the interval between administration of vaccine and subsequent administration of an immune globulin or blood product is less than 14 days, immunization should be repeated after the recommended interval. The recommended interval between administration of an immune globulin or blood product and subsequent immunization varies, depending on the immune globulin preparation or blood product. Palivizumab (RSVAb) and washed red blood cell transfusion do not interfere with the antibody response to MMR or MMRV vaccines. Refer to Recent Administration of Human Immune Globulin Products in Part 1 for additional general information.
On the basis of expert opinion, the MMR vaccines authorized in Canada may be used interchangeably. Refer to Principles of Vaccine Interchangeability in Part 1 for additional general information.