Measles vaccine: Canadian immunization guide

Last partial content update: October 2018

October 2018: Updated recommendation:

The concentrations of anti-measles antibodies in human Ig products have shown trends of gradually declining and are no longer considered optimally protective using the previously recommended dosing strategies.

The chapter features new dosing and route of administration for measles Ig PEP in susceptible infants and individuals who are immunocompromised or pregnant.

Last complete chapter revision: April 2015

On this page

• Key information
• Epidemiology
• Immunizing agents available for use in Canada
• Immunogenicity, efficacy and effectiveness
• Recommendations for use
  • Table 1: Criteria for measles immunity
• Vaccination of specific populations
• Serologic testing
• Administration practices
• Storage and handling of immunizing agents
• Safety and adverse events
  • Common and local adverse events
  • Contraindications and precautions
• Selected references

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 susceptible 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 vaccine are generally mild and transient and include pain and redness at the injection site, fever less than 39°C, and rash. Reactions to MMRV vaccine include: pain and redness at the injection site and fever less than 39°C in 10% or more of vaccine recipients; measles-like, rubella-like or varicella-like rash, swelling at the injection site and fever greater than 39°C in less than 10% of vaccine recipients.
• When the first dose is administered to children 12 to 23 months of age as MMRV vaccine, there is a higher risk of fever and febrile seizures in the 7 to 10 days after vaccination when compared to separate administration of MMR and univalent varicella vaccine at the same visit. This risk is estimated at about 1 additional febrile seizure for every 2,300 to 2,800 doses of MMRV vaccine.

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 or after 1970.
• Adults born before 1970 can be presumed to have acquired natural immunity to measles; however, susceptible health care workers, travellers to destinations outside of North America, and military personnel should receive MMR vaccine, regardless of year of birth.

How

• Routine childhood immunization: 2 doses of any measles-containing (MMR or MMRV) vaccine. 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 no later than around school entry.
• Children and adolescents who are previously unimmunized: 2 doses of measles-containing vaccine. MMRV vaccine may be used in healthy children aged 12 months to less than 13 years.
• Susceptible adults born in or after 1970: 1 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 2 doses of MMR vaccine.
• Susceptible health care workers and military personnel born before 1970: 2 doses of MMR vaccine.
• Susceptible travellers to destinations outside of North America born before 1970: 1 dose of MMR vaccine.
• Susceptible students in post-secondary educational settings born before 1970: 1 dose of MMR vaccine should be considered.

Why

• People who have not had measles disease or who have not been vaccinated are at risk of infection.
• Complications of measles disease occur in about 10% of measles cases.

Significant revisions included in this chapter are highlighted in the Table of updates to the Canadian immunization guide.

Epidemiology

Disease description

Infectious agent

Measles (rubeola, red measles) is caused by measles virus, a member of the Paramyxoviridae family. For additional information about the measles virus, refer to the Pathogen Safety Data Sheet.

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 4 days 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

People who have not had measles disease or who have not been vaccinated are at risk of infection. In Canada, adults born before 1970 are generally presumed to have acquired natural immunity to measles.

Persons at greatest risk of exposure to measles

Adolescents and adults at greatest risk of exposure to measles include:

• travellers to destinations outside of North America
• health care workers
• military personnel
• students in post-secondary educational settings

Seasonal and temporal patterns

Historically, measles disease occurred 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. 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 and outbreaks continue to occur as a result of importations. Comprehensive updates on the epidemiology of measles in Canada are published annually in the Canadian Communicable Disease Report (CCDR) and weekly in the PHAC Measles & Rubella Monitoring Report.

Refer to measles for health professionals for more information, including disease description, distribution and epidemiology.

Immunizing agents available 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)
• ProQuad™ (live attenuated combined measles, mumps, rubella and varicella vaccine), Merck Canada 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 some other countries, measles vaccine alone is given.

Human immune globulin

• GamaSTAN®S/D (immune globulin [human]), Grifols Therapeutics Inc. (Ig)
• Gammagard®(immune globulin [human]), Shire Pharma Canada Inc. (Ig)
• Gamunex®(immune globulin [human]), Grifols Therapeutics Inc. (Ig)
• IGIVnex(immune globulin [human]), Grifols Therapeutics Inc. (Ig)
• Privigen®(immune globulin [human]), CSL Behring Canada Inc. (Ig)
• Panzyga®(immune globulin [human]), Octapharma Pharmazeutika Produktionsges MBH. (Ig)

All Ig products are only available through the Canadian Blood Services (CBS). For complete prescribing information, consult the CBS website and 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.

Immunogenicity, efficacy and effectiveness

Immunogenicity

In clinical studies a single injection of MMR vaccine induced measles antibodies in 95% of previously seronegative children.

In 12 month old children, a single dose of MMRV vaccine results in similar seroconversion rates as those achieved after concomitant administration of MMR vaccine and univalent varicella vaccine. A study of children receiving 2 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.

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 at least 95% of the population needs to be immunized to develop herd immunity.

There are no data regarding the long-term effectiveness of MMRV vaccine.

Recommendations for use

Healthy children (12 months to less than 18 years of age)

Schedule

Routine schedule

Healthy children (12 months to less than 13 years of age)

For routine immunization of children aged 12 months to less than 13 years, 2 doses of measles-containing vaccine, using either MMR or MMRV vaccine, should be administered. The first measles-containing vaccine dose should be administered at 12 to 15 months of age and the second dose at 18 months of age or any time thereafter, but no later than around school entry.

Catch-up and accelerated schedules

Children (12 months to less than 13 years of age)

Two doses of measles-containing vaccine, using either MMR or MMRV vaccine, should be administered to children less than 13 years of age who were not immunized on the routine schedule. For preschool aged children, 2 doses of measles-containing vaccine should be administered before school entry (4 to 6 years of age). The minimum interval between doses of measles-containing vaccine is 4 weeks.

Adolescents (13 to less than 18 years of age)

Measles-susceptible adolescents (refer to Table 1 for criteria for immunity) should receive 2 doses of MMR vaccine, given at least 4 weeks apart.

Healthy adults (18 years of age and older)

Measles-susceptible adults (refer to Table 1 for criteria for immunity) should receive 1 or 2 doses of MMR vaccine as appropriate for age and risk factors. If 2 doses are needed, MMR vaccine should be administered with a minimum interval of 4 weeks between doses.

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 or after 1970 who do not meet the definition of measles immunity (refer to Table 1 for criteria for immunity) should be immunized with 1 dose of MMR vaccine.

Table 1: Criteria for measles immunity

Routine immunization	Health care workers	Travellers to destinations outside North America	Students in post-secondary educational settings	Military personnel
Documentation of vaccination: Children 12 months to less than 18 years of age: 2 dosestable 1 note 1 Adults 18 years of age and older born in or after 1970: 1 dosetable 1 note 1,table 1 note 2 OR History of laboratory confirmed infection OR Laboratory evidence of immunity OR Born before 1970	Documentation of vaccination with 2 dosestable 1 note 1 (regardless of year of birth) OR History of laboratory confirmed infection OR Laboratory evidence of immunity	Documentation of vaccination: If born in or after 1970: 2 dosestable 1 note 1 If born before 1970: 1 dosetable 1 note 1 OR History of laboratory confirmed infection OR Laboratory evidence of immunity	Documentation of vaccination: If born in or after 1970: 2 dosestable 1 note 1 If born before 1970: consider 1 dosetable 1 note 1 if no documentation of receipt of measles-containing vaccine OR History of laboratory confirmed infection OR Laboratory evidence of immunity	Documentation of vaccination with 2 dosestable 1 note 1 (regardless of year of birth) OR History of laboratory confirmed infection OR Laboratory evidence of immunity
Table 1 notes Table 1 note 1 Measles-containing vaccine Return to table 1 note 1 referrer Table 1 note 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. Return to table 1 note 2 referrer

Specific populations

Persons with inadequate immunization records

Children and adults who are susceptible to measles, including those lacking adequate documentation of immunization, should be started on an immunization schedule appropriate for their age and risk factors. Measles-containing vaccine 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 persons with inadequate immunization records for additional information.

Pregnancy and breastfeeding

Immunity to measles should be reviewed in women of reproductive age and vaccination should be recommended to susceptible non-pregnant women. Women should delay pregnancy by at least 4 weeks following vaccination with MMR vaccine.

MMR and MMRV vaccines are generally contraindicated in pregnancy because there is a theoretical risk to the fetus. However, there is no evidence to demonstrate a teratogenic risk from the vaccines and termination of pregnancy should not be recommended following inadvertent immunization with either of these vaccines on the basis of fetal risks following maternal immunization. In some situations, potential benefits of vaccination with MMR vaccine may outweigh risks such as during measles or rubella outbreaks, in which case vaccination may be considered based on recommendations from public health officials. Pregnant women who are susceptible to measles should have vaccination offered post-partum.

Susceptible women who are breastfeeding should be vaccinated with MMR vaccine.

Refer to Post-exposure immunization and outbreak control for additional information about the use of Ig in the management of susceptible pregnant women exposed to measles. Refer to Blood products and timing of immunization for information about measles vaccination of post-partum women who have received Rh immune globulin (RhIg). Refer to Immunization in pregnancy and breastfeeding for additional information.

Patients in health care institutions

Susceptible residents of long-term care facilities should receive measles, mumps and rubella-containing vaccine as appropriate for their age and risk factors.

Refer to Immunization of patients in health care institutions for additional information.

Persons with chronic diseases

Age-appropriate measles-containing vaccine should routinely be provided to individuals with chronic diseases who are not immunocompromised.

Refer to Immunization of persons with chronic diseases for additional general information about vaccination of people with chronic diseases.

Immunocompromised persons

Individuals who are immunocompromised, either due to underlying conditions or immunosuppressive agents, are more susceptible to infections including measles. They may be more likely to experience more severe disease and complications. The safety and effectiveness of the measles vaccine is determined by the type of immunodeficiency and degree of immunosuppression. 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 physician with expertise in immunization or immunodeficiency is advised.

Refer to Immunization of immunocompromised persons and Post-exposure immunization and outbreak control for more information.

Travellers

Protection against measles is especially important for people planning travel. Travellers to destinations outside of North America, born in or after 1970, who do not meet the definition of measles immunity (refer to Table 1 for criteria for immunity) should receive 2 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, 2 additional doses of measles-containing vaccine must be administered after the child is 12 months old to ensure long lasting immunity to measles.

Travellers to destinations outside of North America, born before 1970, who do not meet the definition of measles immunity (refer to Table 1 for criteria for immunity) should receive 1 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 for additional 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 as necessary. 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 for additional 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 meet the definition of measles immunity (refer to Table 1 for criteria for immunity) should be vaccinated accordingly so that they have received 2 doses of MMR vaccine.

Refer to Immunization of Workers for additional information.

Booster doses and re-immunization

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

Post-exposure Prophylaxis (PEP) and Outbreak Control

MMR vaccine or Ig may be used for measles post-exposure immunization in susceptible persons. 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 provides only short-term protection and requires postponing the administration of MMR vaccine for 5 to 6 months. Long-term protection against measles is only provided following immunization with MMR vaccine. For a summary of measles PEP recommendations, refer to Table 2.

Despite the use of MMR vaccine or Ig for post-exposure management, measles infection may occur. Exposed individuals should be counseled regarding: signs and symptoms of measles; 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.

Measles-Mumps-Rubella vaccine

Susceptible, immunocompetent individuals 6 months of age and older who are exposed to measles may be protected from measles disease if they are given measles-mumps-rubella (MMR) vaccine within 72 hours of their exposure. When MMR vaccine is provided prior to 12 months of age, 2 additional doses of measles-containing vaccine must be administered after the child is 12 months old (and at least 4 weeks after the previous dose) to ensure long lasting immunity.

Human immune globulin

Prophylactic use of human immune globulin (Ig) has been shown to be effective in modifying or preventing disease if administered within 6 days after exposure to measles; however, when indicated, it should be given as soon as possible after exposure. Ig should be considered for the following groups of individuals if they are contacts of measles:

• susceptible pregnant women
• susceptible individuals who are immunocompromised
• susceptible infants ˂ 6 months of age
• susceptible immunocompetent infants 6-11 months old who present between 72 hours and 6 days after exposure

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.

Intramuscular immune globulin

IMIg should be provided to susceptible infants at a concentration of 0.5mL/kg, to a maximum dose of 15mL. For susceptible individuals who are pregnant or immunocompromised, IMIg can be provided at a concentration of 0.5mL/kg understanding that those weighing 30 kg or more will not receive the measles antibody concentrations that are considered to be fully protective. Large volumes (greater than 2mL for children or 3-5 mL for adults) should be divided and injected at 2 or more sites. In cases where injection volume is a concern and for recipients weighing 30 kg or more, IVIg can be considered

Intravenous immune globulin

IVIg can be considered in susceptible individuals who are pregnant or immunocompromised and weigh 30 kg or more. IVIg can be considered for infants for whom Ig is indicated, but IMIg injection volume is a concern. IVIg administration requires in-hospital administration and active patient monitoring over several hours of infusion, performed by appropriately trained staff. Providers of IVIg should review the respective product monographs and CBS guidelines prior to IVIg administration.

Table 2. Summary of updated measles PEP recommendations for susceptible contacts

Populations	Time since exposure to measlesFootnote *
	< 72 h	72h – 6 days
All infants 0-6 months oldFootnote 1	IMIg (0.5mL/kg)Footnote 2	IMIg (0.5mL/kg)Footnote 2
Susceptible immunocompetent infants 6-12 months old	MMR vaccineFootnote 1	IMIg (0.5mL/kg)Footnote 1Footnote 2
Susceptible immunocompetent individuals 12 months and older	MMR vaccine series	N/AFootnote 1Footnote 3
Susceptible pregnant individualsFootnote 4	IVIg (400mg/kg) or IMIg (0.5mL/kg), limited protection if 30kg or moreFootnote 5	IVIg (400mg/kg) or IMIg (0.5mL/kg), limited protection if 30kg or moreFootnote 5
Immunocompromised individuals 6 months and older	IVIg (400mg/kg) or IMIg (0.5mL/kg), limited protection if 30kg or moreFootnote 5Footnote 6	IMIg (0.5mL/kg), limited protection if 30kg or moreFootnote 5Footnote 6
Individuals with confirmed measles immunity	N/A	N/A
Footnotes Footnote 1 Two additional doses of MMR vaccine provided after 12 months of age are required for long-term protection. Return to footnote 1 referrer Footnote 2 If injection volume is a major concern, IVIg can be provided at a concentration of 400mg/kg. Return to footnote 2 referrer Footnote 3 Susceptible immunocompetent individuals 12 months of age and older are not a priority to receive Ig following measles exposure due to low risk of disease complications and the practical challenges of administration contact management Return to footnote 3 referrer Footnote * Provide MMR vaccine series postpartum for future protection. Return to footnote 4 referrer Footnote * For individuals 30kg or more, IMIg will not provide complete protection but may prevent some symptoms. Return to footnote 5 referrer Footnote * In HIV-infected individuals, measles antibody titre is known to decline more rapidly over time as compared to those who are not HIV-infected. 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 be considered for hematopoietic stem cell transplantation (HSCT) recipients, unless vaccinated post-HSCT and known to have an adequate measles antibody titre. Return to footnote 6 referrer Footnote * Ig should only be provided within 6 days of measles exposure; unless it is contraindicated, individuals who receive Ig should receive measles-containing vaccine after a specified interval, once the measles antibodies administered passively have degraded. For more information, refer to Blood Products, Human Immune Globulin and Timing of Immunization. Return to footnote * referrer

Outbreak control

Immunization with MMR vaccine is an integral element of a comprehensive measles outbreak prevention and management strategy. In a measles outbreak, susceptible individuals 6 months of age and older may receive MMR vaccine. However, if given between 6 months and less than 12 months of age, 2 additional doses of measles-containing vaccine must be administered after the child is 12 months old (and at least 4 weeks after the previous dose) to ensure long lasting immunity to measles. For detailed information on outbreak control beyond vaccination and post-exposure prophylaxis strategies, refer to guidelines for measles outbreak in Canada in the Canada Communicable Disease Report (CCDR).

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.

Administration Practices

Dose

Each dose of measles-containing vaccine is 0.5 mL.

Route of administration

MMR vaccine should be administered subcutaneously (SC). MMRV vaccine should be administered according to the product monograph.

Refer to Vaccine Administration Practices in Part 1 for additional information about pre-vaccination and post-vaccination counselling, vaccine preparation and administration technique, and infection prevention and control.

Refer to Passive Immunizing Agents in Part 5 for information about administration of Ig.

Interchangeability of vaccines

On the basis of expert opinion, the MMR vaccines authorized in Canada may be used interchangeably. Refer to Varicella Vaccine for information about interchangeability of MMRV vaccines. Refer to Principles of Vaccine Interchangeability for additional general information.

Concurrent administration with other vaccines

MMR vaccine may be administered concomitantly with, or at any time before or after, inactivated vaccines, live oral vaccines, or live intranasal influenza vaccine (LAIV). Refer to Influenza Vaccine for additional information about concurrent administration of MMR vaccine with LAIV.

MMR vaccine may be administered concomitantly with other routinely provided live parenteral vaccines. If not given concomitantly, a minimum interval of 4 weeks is recommended between administration of MMR and other live parenteral vaccines. This recommendation is to address the risk of interference from the vaccine given first on the vaccine given later.

Different injection sites and separate needles and syringes must be used for concomitant parenteral injections. Refer to Timing of Vaccine Administration for additional information about concurrent administration of measles-containing vaccine with other vaccines.

Storage and Handling of Immunizing Agents

Refer to Storage and Handling of Immunizing Agents in Part 1 for storage and handling recommendations for measles-containing vaccines.

Refer to Passive Immunizing Agents in Part 5 for storage and handling recommendations for Ig.

Safety and Adverse Events

Common and local adverse events

Measles-Mumps-Rubella vaccine

Adverse events following immunization with MMR vaccine 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 individuals not protected by the first dose. Six to 23 days after immunization with MMR vaccine, 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 immunization with MMR vaccine.

Measles-Mumps-Rubella-Varicella vaccine

Pain and redness at the injection site or fever less than 39°C occur in 10% or more of vaccine recipients. Rash, including measles-like, rubella-like and varicella-like rash, as well as swelling at the injection site and fever greater than 39°C, occur in 1% to less than 10% of vaccine recipients. As varicella-like rashes that occur within the first 2 weeks after immunization may be caused by wild-type virus (varicella virus circulating in the community), health care providers should obtain specimens from the vaccine recipient to determine whether the rash is due to natural varicella infection or to the vaccine-derived strain.

Rubella-containing vaccines

Acute transient arthritis or arthralgia may occur 1 to 3 weeks after immunization with rubella-containing vaccine, such as MMRV. It lasts for about 1 to 3 weeks, and rarely recurs. It 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.

Human immune globulin

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

Less common and serious or severe adverse events

Serious adverse events are rare following immunization and, in most cases, data are insufficient to determine a causal association. Anaphylaxis following vaccination with MMR or MMRV vaccine may occur but is very rare.

Immune Thrombocytopenic Purpura

Rarely, Immune Thrombocytopenic Purpura (ITP) occurs within 6 weeks after immunization with MMR or MMRV vaccine. In most children, post-immunization thrombocytopenia resolves within 3 months without serious complications. In individuals who experienced ITP with the first dose of MMR or MMRV vaccine, serologic status may be evaluated to determine whether an additional dose of vaccine is needed for protection. 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 the incidence observed with natural measles disease (1 per 1,000 cases).

Febrile seizures

When the first dose of measles-containing vaccine is administered to children 12 to 23 months as MMRV vaccine, there is a higher risk of fever and febrile seizures in the 7 to 10 days after vaccination when compared to separate administration of MMR and varicella vaccine at the same visit. This risk is estimated at about 1 additional febrile seizure for every 2,300 to 2,800 doses of MMRV vaccine.

Human immune globulin

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

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

Vaccine providers are asked to report the following adverse events following immunization (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 within 7 to 21 days after vaccination with MMRV vaccine.
• Any serious or unexpected adverse event 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 to Contents of Immunizing Agents Available for Use in Canada in Part 1 for lists of vaccines and passive immunizing agents available in Canada and their contents.

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.

Although the measles and mumps components of MMR and MMRV vaccines are produced in chick embryo cell culture and may contain traces of residual egg and chicken protein, the trace amount of egg or chicken protein in the vaccine appears to be insufficient to cause an allergic reaction in egg-allergic individuals. Skin testing is not recommended prior to vaccination 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. Prior egg ingestion is not a prerequisite for immunization with egg protein-containing vaccine. 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 can be contraindicated in persons with impaired immune function, including primary or secondary immunodeficiency disorders. Human Ig preparations should not be given to people with known isolated IgA deficiency unless the benefit outweighs the risk, in which case the product should be given with caution and under close observation. Refer to Immunization of immunocompromised persons in Part 3 for more information.MMR and MMRV vaccines are generally contraindicated during pregnancy because of the theoretical risk to the fetus. Refer to Pregnancy and breastfeeding.

Measles-containing vaccines are contraindicated in individuals with active, untreated tuberculosis (TB) as a precautionary measure. Although TB may be exacerbated by natural measles infection, there is no evidence that measles-containing vaccines have such an effect. Nonetheless, anti-tuberculous therapy for active TB disease is advisable before administering measles-containing vaccines and it may be prudent to avoid live viral vaccines in those with active TB disease until treatment is underway. Consultation with an expert in infectious diseases is recommended.

A history of febrile seizures or a family history of seizures 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 (medications derived from salicylic acid, such as 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 for additional information.

Drug interactions

Systemic antiviral therapy

Systemic antiviral therapy (such as acyclovir, valacyclovir, famciclovir) should be avoided in the peri-immunization period, as it may affect the reproduction of the vaccine virus and consequently 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 vaccine administration.

Tuberculin skin testing or Interferon Gamma Release Assay (IGRA)

The measles component in measles-containing vaccines can temporarily suppress tuberculin reactivity, resulting in false-negative results. If tuberculin skin testing or an 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 read.

Human immune globulin or other blood products

Passive immunization with human Ig or receipt of most other blood products can interfere with the immune response to MMR and MMRV vaccines.

Refer to Blood Products, Human Immune Globulin and Timing of Immunization in Part 1 for recommended intervals between the administration of Ig preparations or other blood products and MMR and MMRV vaccines.

Appendix A: List of abbreviations and acronyms

AEFI

Adverse events following immunization

ASA

acetylsalicylic acid

CBS

Canadian blood services

IGRA

interferon gamma release assay

IMIg

Intramuscular immune globuline

ITP

immune thrombocytopenic purpura

IVIg

intravenous immune globuline

MMR

measles, mumps, rubella

MMRV

measles, mumps, rubella, varicella

PEP

post-exposure prophylaxis

TB

tuberculosis

Selected References

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• 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.
• Nahirniak, S, Lazarus, A. Immune Globuline Products, in Clinical Guide to Transfusion. Canadian Blood Services 2016. Accessed July 2018 at : https://professionaleducation.blood.ca/en/transfusion/clinical-guide/immune-globulin-products
• Centers for Disease Control and Prevention. The Yellow Book: CDC Health Information for International Travel 2014. Accessed June 2015 at: http://wwwnc.cdc.gov/travel/page/yellowbook-home-2014
• 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.
• Centers for Disease Control and Prevention. The Pink Book: Epidemiology and Prevention of Vaccine Preventable Diseases. Updated 13th ed.; 2015. Accessed June 2015 at: http://www.cdc.gov/vaccines/pubs/pinkbook/index.html
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• 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.
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• De Serres G, Gay NJ, Paddy C et al. Epidemiology of transmissible diseases after elimination. Am J Epidemiol 2000;151(1):1039-48.
• 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.
• 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.
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• 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.
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• 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.