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Canadian Immunization Guide

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Part 4
Active Vaccines

Measles Vaccine

Key Information (Refer to text for details)

What

  • Measles occurs worldwide and is one of the most highly communicable diseases.
  • Canada has imported cases and occasional outbreaks of measles.
  • Measles vaccine is available as measles-mumps-rubella (MMR) or measles-mumps-rubella-varicella (MMRV) vaccine.
  • MMR vaccine or human immune globulin (Ig) may be used for measles post-exposure immunization in non-immune persons.
  • The efficacy of a single dose of measles vaccine given at 12 or 15 months of age is estimated to be 85% to 95%. With a second dose, efficacy is almost 100%.
  • Reactions to MMR and MMRV vaccine are generally mild and transient and include pain and redness at the injection site, low-grade fever and rash.

Who

  • Measles-containing vaccine is recommended for routine immunization of children and for immunization of children and adolescents who missed measles immunization on the routine schedule.
  • Measles-containing vaccine is recommended for susceptible adults born in 1970 or later.
  • Adults born before 1970 can be presumed to have acquired natural immunity to measles; however, non-immune health care workers, travellers and military personnel should receive MMR vaccine, regardless of year of birth.

How

  • Routine childhood immunization: administer two doses of measles-containing vaccine (MMR or MMRV); the first dose at 12 to 15 months of age and the second dose at 18 months of age or any time thereafter, but should be given not later than around school entry.
  • Children and adolescents who are previously unimmunized: administer two doses of measles-containing vaccine. The minimum interval between doses of MMR vaccine is 4 weeks. MMRV vaccine may be used in healthy children aged 12 months to 12 years. The recommended interval between 2 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.
  • Susceptible adults born in 1970 or later: administer one dose of MMR vaccine. Those who are at the greatest risk of measles exposure (travellers to destinations outside of North America, health care workers, students in post-secondary educational settings, and military personnel) should receive two doses of MMR vaccine.
  • Non-immune health care workers and military personnel born before 1970: administer two doses of MMR vaccine at least 4 weeks apart.
  • Non-immune travellers born before 1970: administer one dose of MMR vaccine.
  • Non-immune students born before 1970: consider administering one dose of MMR vaccine.

Why

  • Measles occurs worldwide and is one of the most highly communicable infectious diseases.
  • Complications of measles disease occur in about 10% of measles cases and death is estimated to occur in 1 to 2 of every 1,000 cases.
  • MMR and MMRV vaccines are safe and effective.

Since the publication of the 2006 Canadian Immunization Guide:

  • New recommendations have been made for measles vaccination of health care workers, travellers and military personnel.
  • 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.

Epidemiology

Disease description

Infectious agent
Measles (rubeola, red measles) is caused by measles virus, a member of the Paramyxoviridae family.

Reservoir
Humans

Transmission
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.

Risk factors
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.

Seasonal/temporal patterns
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.

Disease distribution

Measles occurs worldwide and is one of the most highly communicable infectious diseases. 

Measles has been eliminated in Canada since 1998; however, cases continue to occur as a result of importations.  From 1998 to 2013, 1429 confirmed measles cases were reported in Canada, with a median of 21.5 cases per year (range: 6 to 752). For more information about measles, including disease distribution and epidemiology in Canada refer to the Public health Agency of Canada measles web page. Comprehensive updates on the epidemiology of measles in Canada are published annually in the Canadian Communicable Diseases Report (CCDR). 

Preparations authorized for use in Canada

Measles-containing vaccines
  • M-M-R®II: (live, attenuated combined measles, mumps and rubella vaccine), Merck Canada Inc. (MMR)
  • PRIORIX®: (live, attenuated combined measles, mumps and rubella vaccine), GlaxoSmithKline Inc. (MMR)
  • PRIORIX-TETRA®: (live, attenuated combined measles, mumps, rubella and varicella vaccine), GlaxoSmithKline Inc. (MMRV)

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.

Human immune globulin
  • GamaSTAN® S/D: (immune globulin [human]), Grifols Therapeutics Inc. (Ig)

For complete prescribing information, consult the product leaflet or information contained within the product monograph available through Health Canada's Drug Product DatabaseExternal Link. 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.

Efficacy, Effectiveness and Immunogenicity

Efficacy and effectiveness

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.

Immunogenicity

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.

Recommendations for Use

Children (12 months to 17 years of age)

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.

Adults (18 years of age and older)

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.

Table 1 provides a summary of criteria for measles immunity. Refer to Schedule.

Table 1: This table provides a summary of criteria for measles immunity
Routine Health care workers Travellers to destinations outside North America Students in post-secondary educational settings Military personnel
Footnote 1
Measles-containing vaccine
Footnote 2
Refer to additional recommendations for health care workers, travellers to destinations outside of North America, students in post-secondary educational settings and military personnel.

Documentation of vaccination:

OR

History of laboratory confirmed infection

OR

Laboratory evidence of immunity

OR

Born before 1970

Documentation of vaccination with 2 dosesTable 1 - Footnote 1 (regardless of year of birth)

OR

History of laboratory confirmed infection

OR

Laboratory evidence of immunity

Documentation of vaccination:

OR

History of laboratory confirmed infection

OR

Laboratory evidence of immunity

Documentation of vaccination:

OR

History of laboratory confirmed infection

OR

Laboratory evidence of immunity

Documentation of vaccination with 2 dosesTable 1 - Footnote 1 (regardless of year of birth)

OR

History of laboratory confirmed infection

OR

Laboratory evidence of immunity

Persons with inadequate immunization records

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.

Pregnancy and breastfeeding

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.

Refer to Contraindications, Precautions. Refer to Immunization in Pregnancy and Breastfeeding in Part 3 for additional general information.

Persons/residents in health care institutions

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.

Immunocompromised persons

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.

Family or medical history

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.

Congenital (primary) immunodeficiency

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.

Complement deficiency

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.

Acquired (secondary) immunodeficiency

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)

  • Pre-transplantation: People awaiting HSCT should not receive measles, mumps and rubella-containing vaccine. Vaccination of donors immediately before stem cell harvest is not recommended as there is no evidence that immunity can be transferred from the donor to the recipient and there are no safety data.
  • Post-transplantation: Antibody titres to vaccine-preventable diseases decline after HSCT if the recipient is not re-vaccinated. Vaccination with MMR vaccine may be considered 24 months after transplantation provided there is no evidence of chronic graft-versus-host disease, immunosuppression has been discontinued for at least 3 months, and the person is considered immunocompetent by a transplant specialist. Serologic response should be checked after the first dose of MMR vaccine and a second dose should be given 3 months or more after the first dose if there is no seroconversion.

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.

Immunosuppressive therapy

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.

HIV-infected

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.

  • Children: HIV-infected children 12 months of age and older, and with Centers for Disease Control and Prevention (CDC) clinical category N, A, or B and immunologic category 1 or 2 (i.e., CD4 counts ≥15%) may receive two doses of MMR vaccine 3 to 6 months apart. Univalent varicella vaccine may be administered concomitantly with MMR vaccine at different injection sites using separate needles and syringes.
  • Adolescents and adults: immunization with two doses of MMR administered 3 months apart may be considered for susceptible HIV-infected adolescents and adults with CD4 cell count ≥200 x 106/L and CD4 percentage ≥15%.
Household contacts

Susceptible household contacts of immunocompromised people should receive a measles-containing vaccine as appropriate for age and risk factors.

Refer to Contraindications and Precautions. Refer to Immunization of Immunocompromised Persons in Part 3 for additional information.

Persons with chronic diseases
Hyposplenism or asplenia

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.

Chronic renal disease/dialysis

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.

Neurologic disorders

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.

Autoimmune disease

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.

Travellers

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 countriesExternal Link for additional information.

Refer to Immunization of Travellers in Part 3 for additional general information.

Persons new to Canada

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.

Workers

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.

Post-exposure immunization

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.

MMR vaccine

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.

Human immune globulin (Ig)

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:

  1. susceptible pregnant women,
  2. susceptible immunocompromised people, or
  3. children less than 6 months of age.

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 DatabaseExternal Link.

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.

Outbreak control

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.

Vaccine Administration

Dose, route of administration, and schedule

Dose
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.

Schedule

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.

Booster doses and re-immunization

Re-immunization with measles-containing vaccine after age and risk appropriate vaccination is not necessary.

Serologic Testing

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.

Storage requirements

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.

Simultaneous administration with other vaccines

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:

  • administer doses of varicella-containing vaccine at least 3 months apart for children 1 to 12 years of age. If rapid, complete protection against varicella is required, a minimum interval of 6 weeks between 2 doses may be used for children 1 to 12 years of age.
  • do not concomitantly administer varicella-containing vaccines with smallpox vaccine; administer varicella-containing vaccine and smallpox vaccine at least 4 weeks apart.

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.

Vaccine and immune globulin safety and adverse events

Refer to Vaccine Safety Part 2 for additional general information.

Common and local adverse events
MMR vaccine

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.

MMRV vaccine

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.

Rubella-containing vaccines

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.

Ig

Injection site pain and tenderness, urticaria, and angioedema may occur.

Less common and serious or severe adverse events
MMR and MMRV vaccines

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

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).

Febrile seizures

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.

Ig

Anaphylactic reactions, although rare, have been reported following the injection of human immune globulin.

Other reported adverse events and conditions

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.

Guidance on reporting Adverse Events Following Immunization (AEFI)

Vaccine providers are asked to report the following AEFI in particular, through local public health officials:

  • Febrile seizures within 30 days after vaccination with MMR or MMRV vaccine.
  • Varicella that is moderate (50 to 500 lesions) or severe (more than 500 vesicular lesions or associated complications or hospital admission) and occurs 7 to 21 days after vaccination with MMRV vaccine.
  • Any serious or unexpected adverse event felt to be temporally related to vaccination. An unexpected AEFI is an event that is not listed in available product information but may be due to the immunization, or a change in the frequency of a known AEFI.

Refer to Reporting Adverse Events Following Immunization (AEFI) in Canada and Vaccine Safety in Part 2 for additional information about AEFI reporting.

Contraindications and precautions

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:

  • M-M-R®II:neomycin, phenol red, porcine gelatin, residual components of chick embryo cell cultures
  • PRIORIX®:egg protein, neomycin
  • PRIORIX-TETRA®:egg protein, neomycin

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.

Drug interactions

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.

Other Considerations

Interchangeability of vaccines

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.

Selected References

  • Advisory Committee on Epidemiology. Guidelines for control of measles outbreaks in Canada. Can Commun Dis Rep 1995;21:189-95.
  • American Academy of Pediatrics. In: Pickering LK, Baker CJ, Kimberlin DW, et al. (editors). Red Book: 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009.
  • Bell A, King A, Pielak K et al. Epidemiology of measles outbreak in British Columbia — February 1997. Can Commun Dis Rep 1997;23:49-51.
  • Bellini WJ, Rota JS, Lowe LE et al. Subacute sclerosing panencephalitis: more cases of this fatal disease are prevented by measles immunization than was previously recognized. J Infect Dis 2005;192(10):1686-93.
  • Centers for Disease Control and Prevention. Use of Combination Measles, Mumps, Rubella and Varicella Vaccine. Recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep 2010;59(03):1-12.
  • Centers for Disease Control and Prevention. The Yellow Book: CDC Health Information for International Travel 2010. Accessed October 2010 at: http://wwwnc.cdc.gov/travel/content/yellowbook/home-2010.aspx
  • Centers for Disease Control and Prevention. Advisory Committee on Immunization Practices Provisional Recommendations for Measles-Mumps-Rubella (MMR) ‘Evidence of Immunity’ Requirements for Healthcare Personnel. 2009. Accessed October 2010 at: http://www.cdc.gov/vaccines/recs/provisional/downloads/mmr-evidence-immunity-Aug2009-508.pdf
  • Centers for Disease Control and Prevention. The Pink Book: Epidemiology and Prevention of Vaccine Preventable Diseases. Updated 11th ed.; May 2009. Accessed October 2010 at: http://www.cdc.gov/vaccines/pubs/pinkbook/default.htm
  • Centers for Disease Control and Prevention. Update: recommendations from the Advisory Committee on Immunization Practices (ACIP) regarding administration of combination MMRV vaccine. MMWR Morb Mortal Wkly Rep 2008;57:258-60.
  • De Serres G, Boulianne N, Meyer F et al. Measles vaccine efficacy during an outbreak in a highly vaccinated population: incremental increase in protection with age at vaccination up to 18 months. Epidemiol Infect 1995;115:315-23.
  • De Serres G, Sciberras J, Naus M et al. Protection after two doses of measles vaccine is independent of interval between doses. J Infect Dis 1999;180:187-90.
  • De Serres G, Gay NJ, Paddy C et al. Epidemiology of transmissible diseases after elimination. Am J Epidemiol 2000;151(1):1039-48.
  • Gay NJ, De Serres G, Farrington CP et al. Elimination of measles from the United States: an assessment through basic surveillance data. J Infect Dis 2004;189(Suppl 1):S36-42.
  • GlaxoSmithKline Inc. Product Monograph – PRIORIX-TETRA™. May 2010.
  • GlaxoSmithKline Inc. Product Monograph - PRIORIX®. November 2008.
  • Halsey NA, Hyman SL. Measles-mumps-rubella vaccine and autistic spectrum disorder: report from the New Challenges in Childhood Immunizations Conference convened in Oak Brook, Illinois, June 12-13, 2000. Pediatrics 2001;107:E84.
  • Institute of Medicine, Immunization Safety Review Committee (Stratton K, Gable A, Shetty P et al, eds.). Measles-mumps-rubella vaccine and autism. Washington DC: National Academy Press, 2001.
  • Jadavji T, Scheifele D, Halperin S. Thrombocytopenia after immunization of Canadian children, 1992 to 2001. Pediatr Infect Dis J 2003;22(2):119-22.
  • King A, Varughese P, De Serres G et al. Measles elimination in Canada. J Infect Dis 2004;189(Suppl 1):S236-42.
  • Madse KM, Hviid A, Vestergaard M et al. A population-based study of measles, mumps, and rubella vaccination and autism. N Engl J Med 2002;347(19):1477-82.
  • Mantadakis E, Farmaki E, Buchanan GR. Thrombocytopenic purpura after measles-mumps-rubella vaccination: a systematic review and guidance for management. J Pediatr 2010;156(4):623-8.
  • Markowitz L, Albrecht P, Orenstein WA et al. Persistence of measles antibody after revaccination. J Infect Dis 1992;166:205-8.
  • Merck Frosst Canada Ltd. Product Monograph - M-M-R® II. February 2009.
  • Miller E, Andrews N, Grant A et al. No evidence of an association between MMR vaccine and gait disturbance. Arch Dis Child 2005;90(3):292-6.
  • Murch SH, Anthony A, Casson DH et al. Retraction. Lancet 2004;363(4411):750.
  • National Advisory Committee on Immunization. Statement on measles-mumps-rubella-varicella vaccine. Can Commun Dis Rep 2010;36(ACS-9):1-22.
  • National Advisory Committee on Immunization. Updated recommendations for the use of varicella and MMR vaccines in HIV-infected individuals. Can Commun Dis Rep 2010;36(ACS-7):1-19.
  • Ratnam S, West R, Gadag V et al. Immunity against measles in school aged children: implications for measles revaccination strategies. Can J Public Health 1996;87:407-10.
  • Strauss B, Bigham M. Does measles-mumps-rubella (MMR) vaccination cause inflammatory bowel disease and autism? Can Commun Dis Rep 2001;27:65-72.
  • Talecris Biotherapeutics Inc. Product Monograph - GamaSTAN® S/D. September 2006.
  • Taylor B, Miller E, Lingam R et al. Measles, mumps and rubella vaccination and bowel problems or developmental regression in children with autism: population study. Br Med J 2002;324(7334):393-6

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