Measles, mumps, and rubella immunization in infants, children, and adolescents

INTRODUCTION — Childhood and adolescent immunizations are one of the most effective means of preventing serious illness. Combination measles, mumps, and rubella (MMR) immunization in infants, children, and adolescents will be discussed here. MMR immunization in adults is discussed separately. (See "Measles, mumps, and rubella immunization in adults".)

MEASLES, MUMPS, AND RUBELLA DISEASE

●Measles – The measles virus causes an acute infection characterized by fever, cough, coryza, conjunctivitis, rash (picture 1A-B), and enanthem (picture 2A-B) that may be followed by severe complications, including encephalitis. (See "Measles: Clinical manifestations, diagnosis, treatment, and prevention".)

●Mumps – The mumps virus causes an acute viral syndrome with parotid swelling (picture 3). Mumps infection usually is self-limited but may be associated with complications, including orchitis and oophoritis, aseptic meningitis, and encephalitis. (See "Mumps", section on 'Clinical manifestations'.)

●Rubella – The rubella virus causes German measles, a generally mild infection with a characteristic rash (picture 4) that can affect both children and adults. However, rubella infection early in pregnancy can cause congenital anomalies (eg, hearing loss; cataracts (picture 5); cardiac disease; and neurodevelopmental effects, including intellectual disability and autism spectrum disorder [ASD]). (See "Rubella", section on 'Clinical manifestations' and "Rubella in pregnancy" and "Congenital rubella", section on 'Clinical features'.)

VACCINE EFFECTIVENESS — Routine immunization with measles, mumps, and rubella-containing vaccine is effective in preventing measles, mumps, and rubella infections, as indicated by the decline in the number of cases of measles, mumps, and rubella in the United States following the introduction of these vaccines in the 1960s (figure 1A-C) [1,2].

●Measles – In a meta-analysis of cohort studies, the effectiveness of one dose of measles-containing vaccine in children was 95 percent (95% CI 87-98 percent) after one dose and 96 percent (95% CI 71-99 percent) after two doses [2].

Global measles vaccination is estimated to have prevented more than 25 million deaths during 2000 to 2019 [3,4]. Measles incidence decreased from 145 to 18 cases per one million population between 2000 and 2016; however, in 2019, measles incidence increased fivefold compared with 2016. Unfortunately, millions of children failed to receive measles vaccines during the coronavirus disease 2019 (COVID-19) pandemic. As a result, measles cases increased 18 percent and measles deaths increased 43 percent in 2022.

Measles outbreaks predominantly occur in unvaccinated individuals [5-7]. When measles occurs in individuals who received ≥2 doses of measles-containing vaccine, it is less severe than in those who received only one dose or who are unvaccinated [6]. (See "Measles: Epidemiology and transmission", section on 'Measles control'.)

Measles immunization programs have also been associated with decreased childhood morbidity and mortality from nonmeasles infectious diseases [8-11], perhaps by preventing the loss of immune memory cells that occurs with natural measles infection [12-16]. (See "Measles: Clinical manifestations, diagnosis, treatment, and prevention", section on 'Immune suppression and secondary infection'.)

●Mumps – In a meta-analysis of cohort studies, the effectiveness of Jeryl-Lynn strain mumps-containing vaccine in children was 72 percent (95% CI 38-87 percent) after one dose and 86 percent (95% CI 73-93 percent) after two doses [2].

Despite the effectiveness of mumps immunization, mumps outbreaks occur. Outbreaks of mumps in vaccinated populations raise concern about waning immunity [17,18]. (See "Mumps", section on 'Outbreaks'.)

●Rubella – In systematic review, the effectiveness of rubella vaccine in children was 89 percent (95% CI 58-97 percent) in a single cohort study [2].

Endemic rubella and congenital rubella syndrome were eliminated from the United States in 2005 and from the rest of the Americas in 2015 [19,20]. However, sporadic cases of rubella continue to be reported in the United States, particularly among immigrant populations [21,22]. (See "Rubella", section on 'Outbreaks'.)

VACCINE FORMULATIONS

●Monovalent vaccines – Single antigen (ie, monovalent) formulations of measles, mumps, and rubella vaccines are available for use in countries that have not yet implemented routine immunization against rubella and/or mumps. In countries that have implemented routine infant immunization against measles, mumps, and rubella, the World Health Organization recommends the combination measles, mumps, and rubella vaccine [23].

●Combination vaccines – Two types of combination measles, mumps, and rubella-containing vaccines are available for use in countries that routinely immunize against measles, mumps, and rubella [1]:

•MMR – Measles-mumps-rubella vaccine (MMR) is a live attenuated vaccine that includes measles, mumps, and rubella [1,24]. In the United States, MMR is licensed for routine use in individuals ≥12 months of age. Two formulations are available in the United States:

-M-M-R II contains Edmonston-Enders measles strain, Jeryl-Lynn mumps strain, and Wistar RA 27/3 rubella strain.

-Priorix contains Schwartz measles strain, Jeryl-Lynn derived mumps strain, and Wistar RA 27/3 rubella strain.

M-M-R II and Priorix can be used interchangeably [24]. Both formulations contain small amounts of neomycin. M-M-R II contains gelatin, but Priorix does not [1,24].

•MMRV – Measles-mumps-rubella-varicella virus vaccine (MMRV) is a live attenuated vaccine that includes measles (Edmonston-Enders strain), mumps (Jeryl-Lynn vaccine strain), rubella (Wistar RA 27/3 vaccine strain), and varicella (Oka strain). In the United States, it is licensed for use in children 12 months through 12 years of age.

MMRV contains small amounts of neomycin [1].

INDICATIONS AND SCHEDULES

United States

Routine immunization — In the United States, routine immunization with measles-mumps-rubella vaccine (MMR) or measles-mumps-rubella-varicella virus vaccine (MMRV) consists of two doses: the first at age 12 through 15 months and the second at age 4 through 6 years [1].

●First dose – The first dose is usually given at age 12 to 15 months following the decline of passively acquired maternal measles antibody, which interferes with the immune response [25,26].

In a prospective randomized trial, antimeasles antibody developed in 87 percent of children vaccinated at 9 months, 95 percent of those vaccinated at 12 months, and 98 percent of those vaccinated at 15 months of age [25]. In several studies, the median seroconversion rates for measles, mumps, and rubella after one dose of MMR were ≥94 percent; immunity appears to be long lasting (table 1) [27-36].

Although systematic reviews of clinical studies and a subsequent observational study indicate that administration of the first dose of measles-containing vaccine to infants before nine months of age is safe and immunogenic, it is associated with lower antibody titers, antibody functionality, and effectiveness than administration at ≥9 months of age [37-39]. Thus, in the United States and other countries where endemic measles has been eliminated and measles vaccine coverage is high, early administration of the first dose is indicated only for high-risk infants (eg, in an outbreak, measles exposure, or international travel). (See 'International travel and outbreaks' below and 'Measles postexposure prophylaxis' below.)

Delay of the first dose beyond age 12 to 15 months increases the duration of susceptibility and has contributed to large measles outbreaks in the United States [40-43]. Delay of the first dose of MMR beyond 15 months of age has also been associated with an increased risk of seizures in the 7 to 10 days after immunization [44,45]. (See 'Adverse effects' below.)

●Second dose – Although the second dose is usually recommended at age 4 to 6 years, it can be given sooner. The timing depends on the formulation [1]:

•MMR can be given ≥28 days after the first dose, provided that both doses are given at ≥12 months of age

•MMRV can be given ≥3 months after the previous dose of varicella-containing vaccine, provided that both doses are given at ≥12 months of age

When reviewing immunization records, MMRV doses that were given ≥28 days after the first dose of varicella-containing vaccine need not be repeated [46].

The second dose of measles, mumps, and rubella-containing vaccine may elicit an antibody response in children who do not respond to the first dose. Nearly all children who do not respond to the first dose respond to the second [47,48]. The second dose is routinely administered before school entry (four to six years) because the risk of measles is greater in school-age than in preschool children and the risk of adverse events is lower at four to six years than in older children [49].

●Potential indications for a third dose – A third dose of MMR is not routinely recommended but may be indicated:

•During a mumps outbreak (see 'International travel and outbreaks' below)

•If the first dose of MMR was given before age 12 months (eg, for international travel, during an outbreak, or for postexposure prophylaxis); doses administered before age 12 months are considered invalid and should be repeated at ≥12 months of age (see 'International travel and outbreaks' below and 'Measles postexposure prophylaxis' below)

Catch-up immunization

●Evidence of immunity – In children and adolescents in the United States, evidence of immunity is established by any of the following (table 2) [1]:

•Documentation of age-appropriate vaccination with a live attenuated vaccine:

-For measles – Two doses of measles-containing vaccine, both administered at ≥12 months of age, separated by ≥28 days (doses administered before 12 months of age are not counted).

-For mumps – Two doses of mumps-containing vaccine, both administered at ≥12 months of age, separated by ≥28 days (doses administered before 12 months of age are not counted).

-For rubella – One dose of rubella-containing vaccine administered at ≥12 months of age.

Evidence of rubella immunity in pregnant people is discussed separately. (See "Immunizations during pregnancy", section on 'Preconception immunization'.)

Parent- or caregiver-reported doses are not valid without appropriate documentation.

•If serologic testing is performed, serologic evidence of immunity (ie, positive serum measles, mumps, and rubella immunoglobulin [Ig] G).

•Laboratory confirmation of measles, mumps, or rubella disease (ie, detection of measles viral ribonucleic acid [RNA] by reverse transcriptase polymerase chain reaction, detection of measles virus-specific IgM, or a fourfold increase in measles IgG in acute and convalescent specimens) [50].

Clinical diagnosis without laboratory confirmation is insufficient evidence of immunity. (See "Measles: Clinical manifestations, diagnosis, treatment, and prevention", section on 'Diagnosis' and "Mumps", section on 'Diagnosis' and "Rubella", section on 'Diagnosis'.)

●Indications for catch-up or revaccination – Catch-up immunization is indicated for children who lack appropriate evidence of immunity to measles, mumps, or rubella (table 2) or whose immunization status is unknown [1].

Serologic testing is not necessary before catch-up vaccination. However, if it is performed in postpubertal females, those who have negative rubella serology despite age-appropriate vaccination should receive an additional dose of MMR vaccine (maximum of three doses). Serologic testing is not necessary after the third dose. In observational studies, administration of a third dose of MMR has not been associated with increased rates of adverse effects [51-54].

Other individuals with age-appropriate measles, mumps, and rubella immunization who lack serologic evidence of immunity do not need catch-up vaccination.

●Catch-up schedule – The catch-up regimen varies with age, the number of previous doses administered at ≥12 months of age, and whether varicella vaccine is needed (table 3).

International travel and outbreaks

●International travel or measles outbreak – Early administration of the first and/or second dose of MMR is recommended for [1,50]:

•Children traveling outside the United States. (See "Immunizations for travel", section on 'Measles, mumps, and rubella'.)

•Children living in or traveling to areas where there is a measles outbreak.

A measles outbreak is defined as ≥3 cases linked in time and space [55]; the Centers for Disease Control and Prevention maintains a current list of measles cases and outbreaks in the United States [1,50].

In these settings [1,50]:

•Children 6 through 11 months should receive one dose of MMR. Children who receive the first dose of MMR before age 12 months should receive two additional doses, separated by at least 28 days, beginning at age 12 to 15 months.

•Children ≥12 months of age should receive two doses of MMR separated by at least 28 days, with the first dose administered on or after the first birthday.

By ≥6 months of age, most infants have lost maternal antibodies and are susceptible to measles [56,57]. Administration of the first dose of measles-containing vaccine to infants before nine months of age is safe and immunogenic, but effectiveness is lower than administration at ≥9 months of age [37,38]. (See 'Routine immunization' above.)

●Mumps outbreak – During a mumps outbreak:

•Children who are incompletely immunized against mumps should receive age-appropriate immunization (figure 2). (See 'Catch-up immunization' above.)

•Children who previously received two doses of mumps-containing vaccine and are identified by public health authorities to be at increased risk of mumps (eg, due to intense exposure) should receive a third dose of mumps-containing vaccine [58]. (See "Mumps", section on 'Prevention'.)

Other countries — The World Health Organization (WHO) recommends:

●Vaccination against measles for all susceptible children and adults [59]; the first dose of measles vaccine is recommended at age 9 months for children from countries with ongoing measles transmission and at age 12 months for children from countries with low levels of measles transmission.

WHO recommendations for postexposure prophylaxis for individuals with contraindications to measles vaccine (eg, age <6 months) are similar to those in the United States. (See 'Measles postexposure prophylaxis' below.)

●Vaccination against mumps in countries with a well-established childhood vaccination program and the capacity to maintain high levels of vaccination coverage, and where the reduction of mumps incidence is a public health priority [60].

●Introduction of rubella-containing vaccines in countries that have not already done so if they can achieve coverage levels of ≥80 percent; rubella-containing vaccines can be introduced in conjunction with accelerated measles control and elimination activities [61].

Routine immunization schedules vary from country to country. Schedules for individual countries are available through the European Center for Disease Prevention and Control [62] or the WHO [63].

Measles postexposure prophylaxis — Postexposure prophylaxis with MMR vaccine or immune globulin may prevent or modify the clinical course of measles in children without evidence of immunity (table 2) [1]. (See 'Catch-up immunization' above.)

In a meta-analysis of two cohort studies including 283 children [64,65], having at least one dose of measles vaccine was 74 percent effective (95% CI 50-86 percent) in preventing measles after exposure [2]. In observational studies, the effectiveness of measles postexposure prophylaxis ranges from 69 to 100 percent for immune globulin administered intramuscularly (IGIM) [64,66-69].

Indications and regimens — Regimens for measles postexposure prophylaxis for children without evidence of measles immunity vary according to age, time of exposure, and specific contraindications to MMR vaccine (eg, severe immunodeficiency, pregnancy) [1,50]:

●Infants 0 through 5 months of age – IGIM 0.5 mL/kg (maximum dose 15 mL) within six days of exposure

●Infants 6 through 11 months of age – Either:

•MMR vaccine within 72 hours of exposure (preferred), or

•IGIM 0.5 mL/kg (maximum dose 15 mL) between four and six days of exposure

Infants age 6 through 11 months who receive MMR vaccine for postexposure prophylaxis should receive two additional doses, separated by at least 28 days, beginning at age 12 to 15 months.

MMR vaccination for infants who receive IGIM for prophylaxis should be deferred until six months after IGIM. (See 'Recent receipt of blood or immune globulin' below.)

●Children ≥12 months of age with no doses of MMR vaccine – First dose of MMR vaccine within 72 hours of exposure

Although postexposure prophylaxis is not indicated ≥72 hours after exposure, catch-up MMR immunization should be provided. (See 'Catch-up immunization' above.)

●Children ≥12 months of age with one dose of MMR vaccine – Give second dose of MMR vaccine ≥28 days after the previous dose

●Pregnant people who are nonimmune (measles IgG negative) – Intravenous immune globulin (IVIG) 400 mg/kg within six days of exposure

●Children with severely immunocompromising conditions

•Conditions – Severely immunocompromising conditions include [1,70]:

-Severe primary immunodeficiency

-Hematopoietic cell transplant until at least 12 months after completion of immunosuppressive therapy (possibly longer for those who developed graft -versus-host disease); consultation with the treating provider is suggested

-Treatment for acute lymphoblastic leukemia within and until ≥6 months of completion of immunosuppressive therapy

-Receiving cancer chemotherapy or certain biologic immune modulators (eg, tumor necrosis factor-alpha blockers, rituximab); consultation with the treating provider is suggested

-Post solid organ transplantation; consultation with the treating provider is suggested

-Receiving corticosteroid therapy equivalent to ≥2 mg/kg per day (or ≥20 mg per day of prednisone for persons who weigh >10 kg) for ≥14 consecutive days

-AIDS or HIV with severe immunosuppression (ie, CD4+ T lymphocyte [CD4] percentage <15 percent [all ages] or CD4 count <200/microL [age >5 years])

•Prophylaxis regimen – The postexposure prophylaxis regimen for individuals with severely immunocompromising conditions varies with age:

-<12 months of age – IGIM 0.5 mL/kg (maximum dose 15 mL) within six days of exposure

-≥12 months – IVIG 400 mg/kg within six days of exposure

Measles post exposure prophylaxis is not necessary for children who are receiving either:

-Regular IVIG replacement therapy at a dose of 400 mg/kg if the exposure occurred within three weeks of the last infusion, or

-Weekly subcutaneous immune globulin if the exposure occurred after they received ≥200 mg/kg for two consecutive weeks

Postexposure quarantine — People without measles immunity or severely immunocompromised people who are exposed to measles should quarantine at home after exposure to measles (confirm that household members are immune to measles) [50].

The duration of quarantine depends upon whether the exposed person received postexposure prophylaxis and the type of prophylaxis:

●IGIM or IVIG prophylaxis – 28 days after last exposure (IGIM and IVIG prolong the incubation period)

●MMR vaccine prophylaxis – First dose: 21 days after last exposure; second dose: quarantine not indicated

●No prophylaxis (eg, >6 days since exposure) – 21 days after last exposure

ADMINISTRATION

Contraindications — Contraindications to administration of measles-mumps-rubella vaccine (MMR) and measles-mumps-rubella-varicella virus vaccine (MMRV) include (table 4) [1,70]:

●Severe allergic reaction – Severe allergic reaction (eg, anaphylaxis) after a previous dose of MMR or varicella vaccine (for MMRV) or to a vaccine component (eg, neomycin, gelatin) is a contraindication. (See "Allergic reactions to vaccines".)

●Pregnancy – Postpubertal females should be counseled to avoid becoming pregnant for 28 days after MMR because of the theoretic risk of congenital rubella syndrome [1]. However, it is not necessary to perform a pregnancy test before administering MMR to a postpubertal female who reports that they are not pregnant and not trying to become pregnant. (See "Rubella in pregnancy" and "Immunizations during pregnancy", section on 'Measles, mumps, rubella'.)

●Certain immunodeficiencies – Individuals with immunodeficiency are at risk for severe complications following immunization with live attenuated virus vaccines (eg, encephalitis, pneumonitis) [71-75]. (See "Immunizations in patients with inborn errors of immunity".)

Immune deficiencies that are contraindications to MMR or MMRV include:

•Primary or acquired immunodeficiency (eg, cellular immunodeficiency, hypogammaglobulinemia, HIV infection with severe immune suppression)

HIV infection with severe immunosuppression is defined as CD4+ T lymphocyte [CD4] percentage <15 percent at any age or, if CD4 percentage not available, [70,76]:

-CD4 count <750/microL for children ≤12 months of age

-CD4 count <500/microL for children 1 through 5 years of age

-CD4 count <200/microL for children >5 years of age

•Blood dyscrasia, leukemia, lymphoma, or other malignant neoplasms affecting the bone marrow or lymphatic system.

The use of MMR in patients with cancer and in the pre- and posttransplant setting for solid organ and allogeneic hematopoietic cell transplant recipients is discussed separately. (See "Immunizations in adults with cancer" and "Immunizations in solid organ transplant candidates and recipients" and "Immunizations in hematopoietic cell transplant candidates, recipients, and donors".)

•Systemic immunosuppressive therapy, including large daily doses of corticosteroids (equivalent to ≥2 mg/kg per day or ≥20 mg per day of prednisone for persons who weigh >10 kg) for ≥14 consecutive days [77]; MMR should be avoided for at least one month after high-dose corticosteroid therapy. Children receiving large daily or alternate-day corticosteroids for <14 days may receive MMR immediately after discontinuation, although some experts suggest delaying MMR for two weeks.

Lower doses of systemic corticosteroids, maintenance physiologic doses (ie, replacement therapy), and local corticosteroid injections (eg, joint, tendon) are not a contraindication to MMR [77].

Other examples of systemic immunosuppressive therapies that are contraindications to MMR include antitumor necrosis factor agents (eg, infliximab, adalimumab, golimumab) [70]. MMR should be avoided within two weeks before initiation of immunosuppression.

•Family history of congenital or hereditary immunodeficiency in parents or siblings unless the immune competence of the vaccine recipient has been substantiated clinically or verified in a laboratory.

Special circumstances — Special circumstances may affect the timing of routine immunization.

Recent receipt of blood or immune globulin — The receipt of parenterally administered immune globulin or antibody-containing blood products can blunt or block the host response to certain live virus vaccines.

For most children and adolescents, the suggested interval between receipt of immune globulin or antibody containing blood products and administration of MMR or MMRV varies between 3 and 11 months, depending upon the product (table 5) [46,78,79]. MMR or MMRV vaccine can be administered before the suggested interval if the child is at high risk of measles (eg, in an outbreak setting, before international travel), but the dose is not counted as valid [46]. The child should receive another dose after the suggested interval.

Postpartum administration of MMR to females who received anti-D (Rho) immune globulin or blood products during the last trimester of pregnancy or at delivery is discussed separately. (See "Immunizations during pregnancy", section on 'Postpartum immunization'.)

If immune globulin or blood products must be given within 14 days after administration of MMR, another dose of the vaccine should be administered after the interval suggested in the table (table 5) [79].

Current illness — Whether MMR/MMRV should be administered to children with current illness depends upon the severity of the illness:

●Moderate to severe illness – We suggest that MMR/MMRV be delayed in children with moderate to severe illness (eg, illnesses more severe than upper respiratory tract infection, otitis media, gastroenteritis), with or without fever, unless the vaccine is being administered for measles exposure. (See 'Measles postexposure prophylaxis' above.)

Delay of vaccination of children with moderate to severe illness avoids superimposing any adverse effects of the vaccine on the underlying illness and mistakenly attributing a manifestation of the underlying illness to the vaccine [1].

●Mild illness – MMR/MMRV can be safely administered to children with mild illness, with or without fever (eg, upper respiratory infection, otitis media, diarrhea); seroconversion is not affected by mild illness [80-82]. Failure to vaccinate children with minor illnesses results in delayed immunization and increased duration of susceptibility [83].

Tuberculosis testing — Tuberculin testing should be performed before, at the same visit as, or four to six weeks after MMR/MMRV vaccination [1]. These vaccines may temporarily reduce tuberculin skin test sensitivity [84].

The effect of live virus vaccination on interferon gamma release assay (IGRA) is uncertain [1]. Pending additional information, the Advisory Committee on Immunization Practices (ACIP) suggests that IGRA testing be performed on the same day or four to six weeks after administration of MMR/MMRV.

Planned immunosuppressive therapy — If possible, MMR/MMRV should be given ≥4 weeks before planned systemic immunosuppressive therapy (eg, infliximab, adalimumab, golimumab) [70]. It should be avoided within two weeks before initiation of immunosuppressive therapy.

History of thrombocytopenia — Children with a history of immune thrombocytopenia or nonimmune-mediated thrombocytopenia may have an increased risk of clinically significant thrombocytopenia following immunization with MMR or MMRV [1].

●First dose – Decisions regarding administration of the first dose of MMR to children with a history of thrombocytopenia are made on a case-by-case basis contingent upon the assessment of risks and benefits. In many cases, the benefits outweigh the risks.

Factors to be considered in the decision include:

•Among children with a history of thrombocytopenia, the magnitude of risk of recurrence with the first dose of MMR vaccine is unknown [85-88] but likely to be small. In small series of children with a history of immune thrombocytopenia, recurrences were not observed within six weeks of receipt of MMR [89-91].

•The child's likelihood of exposure to measles, mumps, and rubella (eg, plans for international travel, level of MMR vaccination coverage in the child's school and community, etc).

●Second dose – For children who develop thrombocytopenia after the first dose of MMR, serologic testing can be performed to determine whether the second dose of MMR is necessary.

•Children with protective levels of antibody to measles, mumps, and rubella do not need to receive the second dose.

•For children who lack protective levels of antibody to measles, mumps, or rubella, decisions regarding administration of the second dose of MMR are made on a case-by-case basis based upon the assessment of risks and benefits.

Antiviral medications — Antiviral drugs active against herpes viruses (eg, acyclovir, valacyclovir) may interfere with response to varicella-containing vaccines. If possible, these antiviral agents should be discontinued ≥24 hours before administration of varicella-containing vaccines (eg, MMRV) and avoided for 21 days after vaccination [92,93].

Other special circumstances

●Egg allergy – Egg allergy is not a contraindication to MMR or MMRV. Children with egg allergy can safely receive MMR/MMRV without prior skin testing or special protocols [1]. (See "Allergic reactions to vaccines", section on 'Measles, mumps, and rubella'.)

●History of measles, mumps, or rubella infection – Children who have a history of measles, mumps, or rubella infection that was diagnosed without laboratory confirmation should be vaccinated as if they have not had infection [1]. (See 'Routine immunization' above.)

Children with laboratory confirmation of measles, mumps, or rubella disease are considered to be immune to that particular disease and need not be vaccinated against it. However, they generally receive two doses of MMR vaccine because monovalent vaccines for measles, mumps, and rubella are not available in the United States.

●HIV infection without severe immunosuppression – For children with HIV infection who are not severely immunocompromised and have no evidence of measles, mumps, and rubella immunity, two doses of MMR should be administered [1,70,76]. (See 'Catch-up immunization' above.)

Absence of severe immunosuppression is defined according to age as follows:

•≤5 years – CD4 percentage is ≥15 percent for at least six months; or, if CD4 percentage not available, CD4 count ≥750/microL for at least six months while ≤12 months of age or CD4 count ≥500/microL for at least six months while one through five years of age

•>5 years – CD4 percentage ≥15 percent and CD4 count of ≥200/microL for at least six months if both tests are available; or, if only one test is available, CD4 percentage ≥15 percent or CD4 count of ≥200/microL

MMRV is not recommended for children with HIV infection because it has not been studied in this population [70,76].

Individuals with perinatal HIV infection who received MMR before 1996 (when effective antiretroviral therapy [ART] was established) may be at risk for measles, mumps, and rubella [94]. Such individuals who do not have evidence of immunity to measles, mumps, and rubella should receive two doses of MMR, at least 28 days apart, once effective ART has been established [1]. Effective ART is defined by receiving ART for ≥6 months and lack of severe immunosuppression as defined above. The response to MMR is better in HIV-infected children who are receiving ART and have an undetectable viral load [95-98]. (See 'Catch-up immunization' above.)

●Immunocompromised contact – MMR can be given to children with household contacts who are immunocompromised; the contacts are at increased risk for severe complications from natural measles infection [70,99]. A 2007 literature review found no evidence of secondary transmission of measles, mumps, or rubella vaccine viruses from healthy vaccinees caring for or living with immunocompromised contacts [100]. (See "Measles: Clinical manifestations, diagnosis, treatment, and prevention", section on 'Complications'.)

●Juvenile idiopathic arthritis – Immunization of children with juvenile idiopathic arthritis is discussed separately. (See "Oligoarticular juvenile idiopathic arthritis", section on 'Immunizations'.)

●International adoption – Issues related to MMR immunization of children internationally adopted to the United States are discussed separately. (See "International adoption: Immunization considerations", section on 'Immunizations for international adoptees'.)

Choice between MMR and MMRV — Children age 12 months through 12 years who are due for measles, mumps, rubella, and varicella vaccines may receive either MMRV or separate MMR and varicella vaccines (administered at the same visit but at different sites). For dose 1 in children 12 through 47 months, the Centers for Disease Control and Prevention suggests that MMR and varicella vaccines be administered separately [101]. The choice may be individualized according to caregiver preference, age, and dose (algorithm 1) [102]. The Centers for Disease Control and Prevention provides information and a fact sheet to help caregivers understand their options.

When caregivers do not have a preference, we follow the recommendations of the ACIP [102]:

●First dose:

•Age 12 through 47 months: We suggest separate MMR and varicella vaccines to MMRV; there is a slightly increased risk of febrile seizures with MMRV [102]. MMRV is an alternative for caregivers who wish to avoid an extra injection.

•Age 48 months through 12 years: We suggest MMRV.

•Personal or family (sibling or parent) history of any type of seizures (any age): We suggest separate MMR and varicella vaccines.

●Second dose: We suggest MMRV.

Whether MMRV is administered for the first, second, or both the first and second dose, the immunogenicity of MMRV is similar to that of separate MMR and varicella vaccines [103]. However, several large postlicensure studies identified an approximately twofold increased risk of febrile seizures one to two weeks after the first dose with MMRV than with separate injections of MMR and varicella, with approximately one additional febrile seizure for every 2300 to 2800 doses of MMRV [102,104-106]. In other postlicensure studies, MMRV was not associated with increased risk of febrile seizures when administered to children age 4 to 6 years or as the second dose to toddlers [107,108].

Dose, route, and site

●Dose – The dose for MMR and MMRV is 0.5 mL [109].

●Route – All forms of MMR, including MMRV, can be administered subcutaneously with a 5/8 inch (1.6 cm), 23- to 25-gauge needle.

Some formulations also have been approved for intramuscular (IM) administration [110,111]. Refer to local product information. IM injections are administered with a 22- to 25-gauge needle; the suggested needle length varies with age, sex, weight, and site of administration (table 6) [110,111].

Immunogenicity appears to be similar with IM and subcutaneous administration [112]. If a formulation intended for subcutaneous use is administered IM, the dose need not be repeated.

●Site – The site of administration varies with age and route.

•Subcutaneous injections

-<12 months – Anterolateral thigh

-≥12 months – Upper outer triceps

•IM injections

-<12 months – Anterolateral thigh

-12 months through 2 years – Anterolateral thigh is preferred, but the deltoid muscle can be used if the muscle mass is adequate

-≥3 years – The deltoid muscle is preferred, but the anterolateral thigh can also be used

Administration with other vaccines — MMR may be administered at the same visit as other routine childhood immunizations [113,114]. However, if routine injectable or nasally administered live attenuated vaccines (ie, MMR, varicella, live attenuated influenza) are not administered at the same clinic visit, they should be separated by ≥28 days [46]. Administration at <28 days may impair the immune response to one of the vaccines [115-117]. If MMR and yellow fever vaccine (which is not routine) are not administered at the same clinic visit, they should be separated by ≥30 days [118]. (See "Immunizations for travel", section on 'Dosing and administration'.)

Live attenuated oral vaccines (eg, rotavirus vaccine, oral typhoid vaccine) can be administered at the same time as or at any interval before or after other live vaccines (table 7) [46].

ADVERSE EFFECTS — Adverse reactions to measles, mumps, and rubella combination vaccines (MMR or measles-mumps-rubella vaccine [MMRV]) occur more frequently with the first than with the second dose [119,120]. The rates of most adverse effects are similar whether the child receives MMRV or MMR and varicella vaccine at the same visit [50]. Adverse effects include:

●Fever (>39.4°C) develops in 5 to 15 percent of recipients, usually within 6 to 12 days after immunization [50].

●Transient rashes also occur in approximately 5 percent of recipients [50].

The combination of fever and rash after MMR immunization generally is attributed to measles vaccine virus but may be due to wild-type measles or other viral illnesses [121]; virologic studies may be warranted in children with potential exposure to wild-type measles (eg, international travel, contact with immigrants).

●Transient lymphadenopathy occurs in 5 percent of children and 20 percent of adults [1].

●Joint complaints (secondary to the rubella component of the vaccine) may occur 7 to 21 days after immunization [122]. Joint pain, usually of small peripheral joints, has been reported in 0.5 percent of young children and arthralgia and transient arthritis in 25 and 10 percent of postpubertal females, respectively.

●Hypersensitivity reactions are usually minor (wheal and flare, or urticaria) and have been attributed to trace amounts of neomycin or gelatin but not to egg antigens, since MMR does not contain significant amounts of egg white cross-reacting proteins [50,123,124]. (See "Allergic reactions to vaccines".)

●Although the risk of development of immune thrombocytopenia (ITP) in the six weeks after vaccination is increased [89,125,126], vaccine-associated ITP is rare.

In a systematic review of nine studies, the estimated risk of ITP after MMR vaccine (1 in 40,000 cases) was lower than the incidence of ITP after natural measles, mumps, or rubella infection (1 in 20,000 cases ) [2] and similar to the incidence of ITP in children. In another systematic review, thrombocytopenia resolved within six months in 93 percent of cases, and severe bleeding manifestations were rare [127]. MMR vaccination was not associated with recurrence of thrombocytopenia in children with ITP (either MMR-associated or nonvaccine-associated). (See "Immune thrombocytopenia (ITP) in children: Clinical features and diagnosis", section on 'Epidemiology'.)

●MMR or MMRV is associated with an increased risk of febrile seizures within 6 to 14 days of immunization. In a systematic review of observational studies, the estimated attributable risk was one febrile seizure for every 1150 to 1700 doses of vaccine [2]. In a meta-analysis of two large cohort studies [128,129], the rate of febrile seizures between one and two weeks after MMR-containing immunization was 3.2 times (95% CI 2.9-3.5 times) the rate in unvaccinated children [2]. Post-MMR febrile seizures may be associated with increased risk of recurrent febrile seizure but do not appear to be associated with increased risk of nonfebrile seizures or epilepsy [128,129]. (See "Clinical features and evaluation of febrile seizures".)

●MMR does not appear to be associated with encephalopathy or encephalitis. In a meta-analysis of two observational studies including more than one million children, no association was detected between MMR immunization and encephalopathy or encephalitis (rate ratio 0.90, 95% CI 0.50-1.61) [2].

LACK OF ASSOCIATION WITH AUTISM SPECTRUM DISORDER — Multiple studies have failed to demonstrate an association between measles, mumps, and rubella vaccination with autism spectrum disorder (ASD) or chronic diseases. However, there is an association between congenital rubella syndrome and ASD, highlighting a potential role for rubella immunization in the prevention of ASD [130]. (See "Autism spectrum disorder and chronic disease: No evidence for vaccines or thimerosal as a contributing factor".)

RESOURCES — Resources related to measles, mumps, and rubella immunization in infants and children include:

●The Advisory Committee on Immunization Practices measles, mumps, and rubella recommendations

●Vaccine information statements for measles, mumps, and rubella vaccine and measles, mumps, rubella, and varicella vaccine

●The World Health Organization position papers for measles, mumps, and rubella [59-61]

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Immunizations in children and adolescents" and "Society guideline links: Measles, mumps, and rubella vaccination".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)

●Basics topics (see "Patient education: Measles (The Basics)" and "Patient education: Mumps (The Basics)" and "Patient education: Rubella (The Basics)" and "Patient education: Vaccines for babies and children age 0 to 6 years (The Basics)" and "Patient education: Vaccines for children age 7 to 18 years (The Basics)")

●Beyond the Basics topics (see "Patient education: Why does my child need vaccines? (Beyond the Basics)" and "Patient education: Vaccines for infants and children age 0 to 6 years (Beyond the Basics)" and "Patient education: Vaccines for children age 7 to 18 years (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Measles, mumps, and rubella disease – Measles, mumps, and rubella infections may have serious complications (eg, encephalitis, orchitis and oophoritis, congenital rubella syndrome). (See 'Measles, mumps, and rubella disease' above.)

●Vaccine effectiveness – Introduction of routine measles, mumps, and rubella immunization in the United States reduced the numbers of cases of measles, mumps, and rubella infections (figure 1A-C). Measles vaccine is >95 percent effective, and mumps vaccine is >85 percent effective after two doses; rubella vaccine is approximately 90 percent effective after one dose. (See 'Vaccine effectiveness' above.)

●Indications and schedules in the United States

•Routine immunization – For susceptible children ≥12 months, we recommend routine measles, mumps, and rubella vaccination (Grade 1A). These diseases may have serious complications, and the vaccines are safe and effective.

The routine schedule measles-mumps-rubella vaccine (MMR) or measles-mumps-rubella-varicella virus vaccine (MMRV) consists of two doses: the first at age 12 through 15 months and the second at age 4 through 6 years. (See 'Routine immunization' above.)

•Catch-up immunization – Catch-up MMR immunization (table 3) is necessary for children whose immunization status is unknown or who lack appropriate evidence of immunity (table 2). (See 'Catch-up immunization' above.)

•Other indications – Other indications for routine or early MMR immunization include international travel, outbreaks, and measles postexposure prophylaxis. (See 'International travel and outbreaks' above and 'Measles postexposure prophylaxis' above.)

●Indications and schedules in other countries – MMR immunization schedules for other countries are available through the European Center for Disease Prevention and Control [62] or the World Health Organization [63]. (See 'Other countries' above.)

●Administration

•Contraindications – The table summarizes contraindications to MMR and MMRV (table 4). (See 'Contraindications' above.)

•Special circumstances – The table summarizes circumstances that may affect the timing of routine immunization (table 8). (See 'Special circumstances' above.)

•Choice between MMR and MMRV (algorithm 1):

-When administering the first dose to a child <48 months old or any dose of vaccine to a child who has a personal or family history of seizures, we suggest separate MMR and varicella vaccines (Grade 2C). MMRV is a reasonable alternative for children without a personal/family history of seizures if the caregivers wish to avoid an extra injection.

-When administering the vaccine to a child ≥48 months old, we suggest MMRV (Grade 2C). (See 'Choice between MMR and MMRV' above.)

•Route and dose – All forms of MMR, including MMRV, can be administered subcutaneously. Some formulations are also approved for intramuscular administration. Refer to local product information. MMR and MMRV are usually administered in the upper outer triceps for children ≥12 months of age and the lateral thigh for infants <12 months of age. The dose is 0.5 mL. (See 'Administration' above.)

●Adverse effects – Adverse effects of MMR and MMRV are more common with the first than the second dose. They include fever, rash, lymphadenopathy, joint complaints, hypersensitivity reactions, immune thrombocytopenia, and seizures. (See 'Adverse effects' above.)

Multiple studies have failed to demonstrate an association between MMR and autism spectrum disorder (ASD) or other chronic diseases. (See "Autism spectrum disorder and chronic disease: No evidence for vaccines or thimerosal as a contributing factor".)