Since the publication of the 2006 Canadian Immunization Guide:
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.
Measles (rubeola, red measles) is caused by measles virus, a member of the Paramyxoviridae family.
Measles is one of the most highly communicable infectious diseases with greater than 90% secondary attack rates among susceptible persons. The virus is transmitted by the airborne route, respiratory droplets, or direct contact with nasal or throat secretions of infected persons. The incubation period is about 10 days (range, 7 to 18 days). The interval from exposure to appearance of rash averages 14 days. Cases are infectious from 1 day before the beginning of the prodromal period to 4 days after rash onset. People who recover from measles have permanent immunity to the disease.
All persons who have not had measles disease or who have not been successfully vaccinated are at risk of infection. In Canada, adults born before 1970 are generally presumed to have acquired natural immunity to measles. Individuals at greatest risk of exposure to measles include travellers to destinations outside of North America, health care workers, students in post-secondary educational settings, and military personnel.
Historically, measles disease occurs primarily in late winter and spring in temperate zones. It is now restricted to sporadic cases and outbreaks.
Spectrum of clinical illness
Symptoms of measles include prodromal fever, cough, coryza, conjunctivitis, Koplik spots (white spots on the inner lining of the mouth) and a rash that typically begins on the face, advances to the trunk and then to the arms and legs. Complications such as otitis media and bronchopneumonia occur in about 10% of reported cases, even more commonly in those who are poorly nourished and chronically ill, and in infants less than 1 year of age. Measles encephalitis occurs in approximately 1 of every 1,000 reported cases and may result in permanent brain damage. Measles infection can cause subacute sclerosing panencephalitis (SSPE), a rare but fatal disease. In developed countries, death is estimated to occur in 1 to 2 of every 1,000 cases of measles. Measles during pregnancy results in a higher risk of premature labour, spontaneous abortion and low birth weight infants. Measles in an immunocompromised person may be severe.
Measles occurs worldwide and remains a serious and common disease in developing countries. According to the World Health Organization (WHO), measles is a leading cause of vaccine preventable deaths in children worldwide.
The global goal of reducing mortality due to measles by 90% by 2010 (compared with levels in 2000) was not reached. Measles was largely eliminated from the Western Hemisphere by 2002; however, in 2011 there were large measles outbreaks worldwide. There were over 26,000 cases in the WHO European Region with the highest number reported in France (more than 14,000 cases). Large outbreaks have also occurred in Africa, mostly in the Democratic Republic of the Congo, with more than 106,000 cases and 1,100 deaths.
Before the introduction of measles vaccine in 1963 to 1964, measles occurred in cycles with an increasing incidence every 2 to 5 years. At that time, an estimated 300,000 to 400,000 cases occurred annually. Since the introduction of vaccine, the incidence of measles has declined markedly in Canada (refer to Figure 1). Between 1989 and 1995, in spite of very high immunization coverage, there were many outbreaks involving predominately children who had received one dose of measles vaccine. It was estimated that 10% to 15% of immunized children remained unprotected after a single dose given at 12 months of age.
In 1996 to 1997, in an effort to reach the goal of measles elimination, every Canadian province and territory added a second dose of measles-containing vaccine to its routine immunization schedule, and most conducted catch-up programs in school-aged children with measles or measles/rubella vaccine. These interventions achieved immunization coverage for the second dose in excess of 85%, reducing the proportion of vulnerable children to a level that does not sustain endemic measlestransmission. By 1998, endemic transmission of measles was interrupted.
Figure 1: Reported incidence rate of confirmed measles cases, Canada 1924-2011Figure 1 - Footnote 1
Since the introduction of the two dose measles-containing vaccine schedule, outbreaks in Canada have been a result of importation from other countries.
In 2007, there was an outbreak in Quebec with 94 confirmed measles cases. The laboratory results suggested there were two separate importations. More than one-half of cases were between the ages of 1 and 10 years. Where immunization status was known, nearly all of the cases were individuals who had not received two doses of measles-containing vaccine.
In 2008, there was an outbreak in Ontario of 53 confirmed measles cases. About one-third of the cases were less than 10 years of age. Where immunization status was known, nearly all of the cases were not immunized.
In the spring of 2010, an outbreak in British Columbia resulted in 77 confirmed measles cases. Infants and children under 5 years of age were disproportionately affected, as were adults aged 30 to 39 years. Where immunization status was known, 59% of cases had not been vaccinated, 29% had received one dose of measles-containing vaccine and 12% had received two doses of measles-containing vaccine.
In Canada in 2011, measles importations led to a large outbreak involving more than 700 cases, largely in Quebec. The majority of the cases were between the ages of 10 and 19 years old. Where immunization status was known, approximately 80% of cases were not adequately immunized for their age.
Refer to the Public health Agency of Canada Vaccine-Preventable Diseases webpage for the most recent information about the epidemiology of measles in Canada.
In Canada, measles vaccine is only available in combination with mumps and rubella vaccine (MMR) or mumps, rubella and varicella vaccine (MMRV). In many countries outside of Canada measles vaccine alone is given.
For complete prescribing information, consult the product leaflet or information contained within the product monograph available through Health Canada's Drug Product Database. Refer to Contents of Immunizing Agents Available for Use in Canada in Part 1 for lists of vaccines and passive immunizing agents available for use in Canada and their contents.
The efficacy of a single dose of measles-containing vaccine given at 12 or 15 months of age is estimated to be 85% to 95%. With a second dose, efficacy in children approaches 100%. However, measles outbreaks have occurred in populations with high immunization coverage rates. Due to the high infectivity of measles (each case may infect 12 to 18 others) at least 95% of the population needs to be immunized to develop herd immunity. There are no data regarding the efficacy of MMRV vaccine.
In clinical studies a single injection of MMR vaccine induced measles antibodies in 95%, mumps antibodies in 96%, and rubella antibodies in 99% of previously seronegative children.
In a study of 12 month old children, a single dose of MMRV vaccine resulted in a seroconversion rate for measles, mumps, rubella and varicella of 98%, 97%, 98% and 93%, respectively. The seroconversion rates and geometric mean titres for individual components were not significantly different from those achieved after MMR plus univalent varicella vaccines or MMR vaccine alone. A study of children receiving two doses of MMRV vaccine during the second year of life noted seropositivity for measles, mumps, rubella and varicella of 99%, 97.4%, 100% and 99.4% respectively by the third year post-vaccination. Long-term persistence of anti-measles, anti-mumps, anti-rubella and anti-varicella antibodies following MMRV vaccinations are under evaluation.
Two doses of measles-containing vaccine should be given for routine immunization of children and for immunization of children and adolescents who have missed measles immunization on the routine schedule. MMRV vaccine may be used in children aged 12 months to 12 years.
Routine immunization: adults born before 1970 are generally presumed to have acquired natural immunity to measles; however, some of these individuals may be susceptible.
Adults without contraindications, born in 1970 or later who do not have documented evidence of receiving measles-containing vaccine on or after their first birthday, or laboratory evidence of immunity, or a history of laboratory confirmed measles infection should be immunized with one dose of MMR vaccine.;
Health care workers, regardless of their year of birth, who do not have documented evidence of receiving two doses of measles-containing vaccine on or after their first birthday, or laboratory evidence of immunity, or a history of laboratory confirmed measles disease should receive two doses of MMR vaccine. Refer to Workers.
Students in post-secondary educational settings, born in 1970 or later, who do not have documented evidence of receiving two doses of measles-containing vaccine on or after their first birthday, or laboratory evidence of immunity, or a history of laboratory confirmed measles disease should receive two doses of MMR vaccine. In students born before 1970, administration of one dose of MMR vaccine should be considered.
Military personnel, regardless of their year of birth, who do not have documented evidence of receiving two doses of measles-containing vaccine on or after their first birthday, or laboratory evidence of immunity, or a history of laboratory confirmed measles disease should receive two doses of MMR vaccine.
Travellers to destinations outside of North America, born in 1970 or later, who do not have documented evidence of receiving two doses of measles-containing vaccine on or after their first birthday, or laboratory evidence of immunity, or a history of laboratory confirmed measles disease should receive two doses of measles-containing vaccine. Travellers born before 1970 who do not have documented evidence of receiving a measles-containing vaccine on or after their first birthday, or laboratory evidence of immunity, or a history of laboratory confirmed measles disease should receive one dose of MMR vaccine. Refer to Travellers.
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. Ideally, the immunization status of women intending to become pregnant should be reviewed and vaccines updated as necessary prior to conception. Women should delay pregnancy by at least 28 days following vaccination with a live vaccine.
MMR and MMRV vaccines should generally not be given during pregnancy because of the theoretical risk of disease transmission to the fetus; however, there is no evidence demonstrating a teratogenic or other risk from such vaccines. There was no evidence of Congenital Rubella Syndrome in any of the offspring of 226 women inadvertently vaccinated during pregnancy. Inadvertent immunization with MMR vaccine is not a reason for pregnancy termination. In some situations, potential benefits of MMR vaccination may outweigh risks such as during measles or rubella outbreaks, in which case vaccination may be considered.
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 with a live vaccine, approval from the individual’s attending physician should be obtained before vaccination. For complex cases, referral to a consultant with expertise in immunization or immunodeficiency is advised.
People who have a suspicious history for immunodeficiency disorders (e.g., known or suspected family history of congenital immunodeficiency disorder or HIV infection, or history of failure to thrive and recurrent infections) should not be immunized with a live vaccine until they have been fully investigated and T cell dysfunction ruled out. Immunodeficiency states may be undiagnosed in young children presenting for routine immunizations, which include live vaccines. This is particularly important to consider in infants receiving live vaccines before 12 months of age. A history of negative prenatal screening of the infant’s mother for HIV should be obtained before administering a live vaccine. If a mother has not received routine prenatal care in Canada, the possibility of undiagnosed HIV infection should be considered.
Live vaccines are generally not recommended for people with congenital immunodeficiency states although some exceptions exist.
B cell deficiency
MMR vaccine, as appropriate for age, should be considered if the individual is not receiving regular immune globulin replacement therapy which may affect the efficacy of the vaccine.
T cell, natural killer T cell, and mixed cellular and antibody defects (e.g., Severe Combined Immune Deficiency [SCID])
All live vaccines, including MMR and MMRV, are contraindicated in people with defects in T cell function.
Phagocytic and neutrophil disorders (e.g., congenital neutropenia, leukocyte adhesion and migration defects, chronic granulomatous disease)
Children with phagocytic or neutrophil disorders may be vaccinated with MMR vaccine as appropriate for age.
There are no contraindications to the use of MMR vaccine in individuals with complement deficiency disorders. Immunity can decrease over time. Measurement of antibody titres and re-immunization, if needed, should be considered.
Malignant hematologic disorders
MMR and MMRV vaccines are contraindicated in individuals with severe immunodeficiency due to blood dyscrasias, lymphomas, leukemias of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems and in people undergoing immunosuppressive treatment for malignancy. Children with Acute Lymphocytic Leukemia (ALL) may be vaccinated with MMR vaccine if the disease has been in remission for at least 12 months, the child's total lymphocyte count is at least 1.2 × 109/L, the child is not receiving radiation therapy, and maintenance chemotherapy can be withheld for at least 1 week before to 1 week after immunization.
Malignant solid tumours
MMR and MMRV vaccines are contraindicated in people undergoing immunosuppressive treatment for any malignant solid tumours.
Hematopoietic stem cell transplantation (HSCT – autologous or allogeneic)
Solid organ transplantation
If possible, individuals being considered for solid organ transplantation should receive immunizations recommended for their age before the transplantation is performed. MMR vaccine may be given to infants as early as 6 months of age if transplantation is anticipated before 12 to 15 months of age. MMR vaccine should be given at least 4 weeks before solid organ transplantation and, in general, is not recommended after transplantation.
Vaccination status for measles, mumps and rubella should be reviewed for immunocompetent persons who might be anticipating initiation of immunosuppressive treatments or who have diseases that might lead to immunodeficiency. Refer to Immunization of Immunocompromised Persons in Part 3 for a list of immunosuppressive medications.
If indicated, MMR vaccine should be administered at least 4 weeks before the initiation of immunosuppressive therapy to reduce the risk of disease caused by the vaccine strain. If MMR vaccine cannot be given prior to initiation of immunosuppressive therapy, a period of at least 3 months should elapse after immunosuppressive drugs (except high-dose systemic corticosteroids) have been stopped before administration of live vaccines to reduce the risk of disease caused by the vaccine strain. A period of at least 4 weeks should elapse between discontinuation of high-dose systemic steroids and the administration of MMR vaccine. The interval between discontinuation of immunosuppressive drugs and MMR vaccine administration may vary with the intensity of the immunosuppressive therapy, underlying disease and other factors.
If immunosuppressive therapy cannot be stopped, live vaccines are generally contraindicated, although the risk-to-benefit ratio may favour immunization if only low doses of immunosuppressive drugs are required and there is significant risk of development of disease. The safety and efficacy of live, attenuated vaccines during low dose intermittent or maintenance therapy with immunosuppressive drugs (other than corticosteroids) are unknown. Immunosuppressive drugs have been reported to cause reactivation of latent tuberculosis infection and predisposition to other opportunistic infections. Therefore, until additional information becomes available, avoidance of MMR vaccines during intermittent or low dose chemotherapy or other immunosuppressive therapy is prudent.
Corticosteroid therapy is not a contraindication to administering live vaccine when steroid therapy is short-term (i.e., less than 14 days); or a low-to-moderate dose (less than 2 mg/kg/day for a child or less than 20 mg/day of prednisone or its equivalent per day for an adult); or long-term, alternate-day treatment with short-acting preparations; or maintenance physiologic replacement therapy; or administered topically, inhaled, or locally injected (e.g., joint injection).
In general, live attenuated vaccines are contraindicated during monoclonal antibody treatment or in infants exposed to monoclonal antibodies. Monoclonal antibodies taken during pregnancy will be transferred to the fetus and their effects may persist after birth. Infants who have been exposed to monoclonal antibodies, either during pregnancy or from breastfeeding, should have B-cell enumeration. B cell enumeration should be normal before vaccination with live vaccines. Consultation with an immunologist is advised. Vaccination status should be reviewed prior to commencing monoclonal antibodies.
An infectious disease specialist/immunologist should be consulted for advice on MMR immunization in HIV-infected people. There are no contraindications to the use of MMR vaccine early in the course of illness; however, MMR vaccine is contraindicated in persons with advanced HIV/AIDS. The safety and immunogenicity of MMRV vaccine in HIV-infected individuals has not been evaluated, and MMRV vaccine cannot be routinely recommended.
Susceptible household contacts of immunocompromised people should receive a measles-containing vaccine as appropriate for age and risk factors.
Hyposplenic or asplenic (congenital absence, surgical removal or functional [e.g., sickle cell disease]) individuals should be immune to measles, mumps and rubella or should receive MMR or MMRV vaccine as appropriate.
Individuals with chronic renal disease or undergoing dialysis should be immune to measles, mumps and rubella or should receive MMR or MMRV vaccine as appropriate.
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 as appropriate.
Individuals with autoimmune disease not being treated with immunosuppressive drugs are not considered significantly immunocompromised and should receive MMR immunization following consultation with their physician. Rheumatic disease modifying agents such as hydroxychloroquine, sulfasalazine, or auranofin are not generally identified as immunosuppressive.
Refer to Immunization of Persons with Chronic Diseases in Part 3 for additional general information.
Protection against measles is especially important for people planning travel to destinations outside of North America. Travellers born in 1970 or later who do not have documented evidence of receiving two doses of measles-containing vaccine on or after their first birthday, or laboratory evidence of immunity, or a history of laboratory confirmed measles disease should receive two doses of measles-containing vaccine.
Measles vaccine should be given at an earlier age than usual for children travelling to countries outside of North America. MMR vaccine may be given as early as 6 months of age; however, two additional doses of measles-containing vaccine must be administered after the child is 12 months old to ensure long lasting immunity to measles.
Travellers born before 1970, who do not have documented evidence of receiving measles-containing vaccine on or after their first birthday, or laboratory evidence of immunity, or a history of laboratory confirmed measles disease should receive one dose of MMR vaccine.
Measles is endemic in many countries. Refer to measles incidence rates in WHO member countries for additional information.
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. A Canadian study showed that more than one-third of new immigrants and refugees, particularly women, were susceptible to measles, mumps, or rubella. 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 measles. Health care workers, regardless of their year of birth, who do not have documented evidence of receiving two doses of measles-containing vaccine on or after their first birthday, or laboratory evidence of immunity, or a history of laboratory confirmed measles disease should be vaccinated accordingly so that they have received two doses of MMR vaccine.
Refer to Immunization of Workers in Part 3 for additional general information.
Measles may continue to be imported into Canada. Outbreaks may occur in susceptible populations. For practical purposes, all individuals attending the same school or facility should be considered contacts.
Susceptible, immunocompetent individuals 12 months of age and older who are exposed to measles may be protected from measles disease if they are given MMR vaccine within 72 hours of their exposure. MMR vaccine may be recommended for children between 6 months to less than 12 months of age for post-exposure management if it is given within 72 hours of exposure; however, two additional doses of measles-containing vaccine must be administered after the child is 12 months old (and at least 28 days from the previous dose) to ensure long lasting immunity to measles.
Prophylactic use of Ig has been shown to be effective in modifying or preventing disease if administered within 6 days after exposure to measles, however, it should be given as soon as possible after exposure when indicated. Ig should be considered for contacts of measles who are:
Measles-containing vaccine is contraindicated in groups 1 and 2 and effectiveness and safety has not been established in group 3. Ig should also be considered for susceptible immunocompetent contacts of measles who are 6 months of age and older and who present more than 72 hours after exposure (when MMR vaccine no longer provides post-exposure protection) but within 6 days after exposure (when Ig may still provide post-exposure protection).
In HIV infected individuals, measles antibody titre is known to decline more rapidly over time as compared to those who are HIV uninfected. A dose of Ig should be considered in HIV infected individuals with severe immunosuppression after a known exposure to confirmed measles, even with documented previous MMR immunization. Regardless of vaccination status pre-transplant, Ig should also be considered for hematopoietic stem cell transplantation (HSCT) recipients, unless vaccinated post HSCT and known to have an adequate measles antibody titre.
In assessing the extent of measles exposure and deciding between MMR vaccine and Ig for post-exposure management, it is important to consider that Ig only provides short-term protection and requires postponing the administration of MMR vaccine for 5 to 6 months. If longer- term protection against measles is required because of ongoing measles transmission in the community, MMR vaccine may be the preferred choice. It is important to note that despite the use of MMR vaccine or Ig for post-exposure management, measles infection may still occur. Exposed individuals should be counseled regarding signs and symptoms of measles; counseling should include avoiding contact with others should they become ill with symptoms compatible with measles and the need to seek medical care, including advising health care workers of the possibility of measles before going to a health care setting so that appropriate precautions can be taken. For detailed information regarding infection prevention and control, refer to the Guidelines for the Prevention and Control of Measles Outbreaks in Canada.
The recommended dose of Ig for healthy individuals exposed to measles is 0.25 mL/kg of body weight given by the IM route. The dose for exposed individuals who are immunocompromised is 0.5 mL/kg of body weight. A maximum dose of 15 mL should not be exceeded. For complete prescribing information, consult the product leaflet or information contained within the product monograph available through Health Canada’s Drug Product Database.
Individuals receiving replacement IVIg (400 mg/kg of body weight or higher) are considered protected and do not require Ig if the last dose of IVIg was received within the three weeks prior to measles exposure.
Unless it is contraindicated, individuals who receive Ig should receive measles-containing vaccine after specified intervals, once the measles antibodies administered passively have degraded. For recommendations on the interval between administration of an Ig preparation or blood product and vaccination with measles-containing vaccine, refer to Blood Products, Human Immune Globulin and Timing of Immunization in Part 1.
Refer to Passive Immunizing Agents in Part 5 for additional general information.
Immunization with MMR vaccine is an integral element of a comprehensive measles outbreak prevention and management strategy. In a measles outbreak, MMR vaccine can be provided at any time starting from 6 months of age. However if given between 6 months and less than 12 months of age, two additional doses of measles-containing vaccine must be administered after the child is 12 months old (and at least 28 days from the previous dose) to ensure long lasting immunity to measles. For detailed information on outbreak control, refer to the Guidelines for the Prevention and Control of Measles Outbreaks in Canada.
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, two doses of measles-containing vaccine (MMR or MMRV) should be administered. The first dose of measles-containing vaccine should be administered at 12 to 15 months of age and the second dose at 18 months of age or any time thereafter, but should be given no later than around school entry.
The recommended minimum interval between doses of MMR vaccine is 4 weeks. Children who previously received a single dose of MMR vaccine should receive a second dose at least 4 weeks after the first dose. The recommended interval between two doses of MMRV vaccine is at least 3 months; a minimum interval of 6 weeks between doses may be used if rapid, complete protection is required.
Adolescents (13 to 17 years of age)
Measles-susceptible adolescents should receive two doses of MMR vaccine given at least 4 weeks apart.
Adults (18 years of age and older)
Measles-susceptible adults should receive one or two doses of MMR vaccine as appropriate for age and risk factors (refer to Table 1). If two doses are needed, MMR vaccine should be administered with a minimum interval of 4 weeks between doses.
Re-immunization with measles-containing vaccine after age and risk appropriate vaccination is not necessary.
Serological testing may be indicated to confirm the diagnosis of measles or to determine immune status. Serologic testing is not recommended before or after receiving measles-containing vaccine. If serology is inadvertently done subsequent to appropriate measles immunization and does not demonstrate immunity, measles re-immunization is not necessary.
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. Refer to Passive Immunizing Agents Part 5 for information regarding Ig storage requirements.
Live vaccines given by the parenteral route may be administered concomitantly with all other vaccines during the same visit using different injection sites and separate needles and syringes. In general, if two live parenteral vaccines are not administered concomitantly, there should be a period of at least 4 weeks before the second live parenteral vaccine is given. Exceptions are varicella-containing vaccines, such as MMRV vaccine:
Oral and intranasal vaccines can be given at the same time as, or any time before or after any other live vaccine, regardless of the route of administration of the other live vaccine.
Refer to Timing of Vaccine Administration in Part 1 for additional general information.
Refer to Vaccine Safety 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, lymphadenopathy, and joint symptoms also occur occasionally after MMR immunization.
Pain and redness at the injection site 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 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 females, 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.
Injection site pain and tenderness, urticaria, and angioedema may occur.
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, 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®, 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.
Anaphylactic reactions, although rare, have been reported following the injection of human immune globulin.
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 found to be fraudulent and 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 and Vaccine Safety in Part 2 for additional information about AEFI reporting.
MMR and MMRV vaccines and Ig are contraindicated in persons with a history of anaphylaxis after previous administration of the product and in persons with proven immediate or anaphylactic hypersensitivity to any component of the product (with the exception of egg allergy for MMR and MMRV vaccines [refer below]), or its container. Refer to Contents of Immunizing Agents Available for Use in Canada in Part 1 for lists of vaccines and passive immunizing agents available for use in Canada and their contents. For measles-containing vaccines, potential allergens include:
In situations of suspected hypersensitivity or non-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 residual egg protein. The trace amount of egg protein in the vaccine appears to be insufficient to cause an allergic reaction in egg-allergic individuals. Prior egg ingestion is not a prerequisite for immunization with egg protein-containing vaccine. Skin testing is not recommended prior to vaccination as it does not predict reaction to the vaccine. MMR or MMRV vaccine can be administered in the routine manner to people who have a history of anaphylactic hypersensitivity to hens’ eggs. For all vaccines, immunization should always 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 breastfeeding.
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 seizures 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 severe acute illness. Persons with a minor acute illness (with or without fever) may be vaccinated.
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 Contraindications, Precautions and Concerns in Part 2 and Passive Immunizing Agents Part 5 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 Ig 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 Ig preparation or blood product, or delayed until the antibodies in the Ig preparation or blood product have degraded. If the interval between administration of vaccine and subsequent administration of an Ig preparation or blood product is less than 14 days, the vaccine dose should be repeated after the recommended interval. The recommended interval between administration of an Ig preparation or blood product and subsequent immunization varies, depending on the Ig preparation or blood product. If the vaccine is given too early following Ig or blood product administration, it should be repeated after the appropriate interval has passed. Palivizumab (RSVAb) and washed red blood cell transfusion do not interfere with the antibody response to MMR or MMRV vaccines. Refer to Blood Products, Human Immune Globulin and Timing of Immunization 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.