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The name rubella is derived from Latin, meaning “little red.” 

Rubella was initially considered to be a variant of measles or 

scarlet fever. It was not until 1814 that it was first described 

as a separate disease in the German medical literature, hence 

the common name “German measles.” In 1914, Alfred F. Hess 

postulated a viral etiology based on his work with monkeys. 

Following a widespread epidemic of rubella infection 

in 1940, Norman Gregg, an Australian ophthalmologist, 

reported in 1941 the occurrence of congenital cataracts 

among infants born following maternal rubella. This 

was the first published recognition of congenital rubella 

syndrome (CRS). Rubella virus was first isolated in 1962 by 

two independent groups, Paul D. Parkman and colleagues 

and Thomas H. Weller and Franklin A. Neva. The first rubella 

vaccines were licensed in 1969. In 1971, a combined measles, 

mumps, and rubella (MMR) vaccine was licensed for use in 

the United States. In 2005, a combination measles, mumps, 

rubella, and varicella (MMRV) vaccine was licensed.

Rubella Virus 

Rubella virus is the sole member of the genus Rubivirus, 

in the family Matonaviridae. It is an enveloped virus with 

a single-stranded RNA of positive polarity and has a single 

antigenic type. 

Pathogenesis 

Following respiratory transmission, the virus replicates in 

the nasopharynx and regional lymph nodes. In a pregnant 

woman, placental infection occurs during viremia and may 

lead to transplacental fetal infection. Fetal damage occurs 

through destruction of cells, as well as disruption of cell 

division. Fetal infection often results in a persistent infection 

typically leading to hearing impairment and ocular and 

cardiovascular abnormalities. 

Clinical Features 

Acquired Rubella 

The average incubation period of rubella is 14 days, with a 

range of 12 to 23 days. Symptoms are often mild, and up to 

50% of infections may be subclinical or inapparent. In young 

children, rash is usually the first symptom. In older children and 

adults, there may be a 1- to 5-day prodrome with low-grade 

fever, malaise, lymphadenopathy, and upper respiratory 

symptoms preceding the rash. Lymphadenopathy may begin 

a week before the rash and last several weeks. The rubella rash 

Tatiana Lanzieri, MD; Penina Haber, MPH; Joseph P. Icenogle, PhD, MS; and Manisha Patel, MD, MS

Rubella Pathogenesis

● Respiratory transmission of virus

● Replication in nasopharynx and

regional lymph nodes

● Possible transplacental infection

of fetus during viremia

■ Hearing impairment and

ocular and cardiovascular

abnormalities may result

Rubella Clinical Features

● Incubation period 14 days

(range, 12 to 23 days)

● Rash first symptom in

young children

● Prodrome with low-grade fever,

malaise, lymphadenopathy, and

upper respiratory symptoms

before rash in older children

and adults

● Maculopapular rash 14 to 17

days after exposure

● Arthralgia common in

adult women

Rubella Virus

● Rubivirus

● RNA virus

● One antigenic type

Rubella

● Initially thought to be variant of

measles or scarlet fever

● First described as distinct

disease in German literature in

1814 (hence “German measles”)

● Congenital rubella syndrome

(CRS) first described 1941

● Rubella virus isolated in 1962

https://www.cdc.gov/vaccines/pubs/pinkbook/rubella.html Aug 2021
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is maculopapular and occurs 14 to 17 days after exposure. The 

rash usually occurs initially on the face and then progresses 

from head to foot. It lasts about 3 days and is occasionally 

pruritic. The rash is fainter than a measles rash, does not 

coalesce, and is often more prominent after a hot shower or 

bath. Postauricular, posterior cervical, and suboccipital nodes 

may be involved. 

Arthralgia (joint pain) and arthritis are rare in children and adult 

males but occur frequently in adult women. Joint symptoms 

tend to occur at about the same time or shortly after the 

rash appears and may last for up to 1 month. Fingers, wrists, 

and knees are often affected. Chronic arthritis is rare. Other 

symptoms of rubella include conjunctivitis, testalgia, or orchitis. 

Small, red (Forschheimer) spots may be noted on the soft palate 

but are not diagnostic for rubella.

Complications 

Complications of rubella are rare. Hemorrhagic manifestations 

occur in approximately 1 per 3,000 cases. These manifestations 

may be secondary to low platelets and vascular damage, 

with thrombocytopenic purpura being the most common. 

Gastrointestinal, cerebral, or intrarenal hemorrhage may also 

occur. Effects may last from days to months, and most patients 

recover. Encephalitis occurs in 1 in 6,000 cases and may be fatal. 

Additional rare complications include granulomas in persons 

with primary immune deficiencies, orchitis, neuritis, and a late 

syndrome of progressive panencephalitis. 

Congenital Rubella Syndrome (CRS)

Prevention of congenital rubella syndrome (CRS) is the main 

objective of rubella vaccination programs. 

Infection with rubella virus is most consequential in early 

gestation and can lead to miscarriages, stillbirths, and severe 

birth defects in infants. The risk of CRS is highest when a 

woman acquires rubella during the first 12 weeks of gestation. 

Congenital infection with rubella virus can affect many organ 

systems. Congenital rubella syndrome includes a constellation 

of birth defects, such as deafness, eye abnormalities (cataracts, 

glaucoma, retinopathy, microphthalmia), and congenital 

heart disease. 

Laboratory Testing

Many rash illnesses can mimic rubella infection, so clinical 

diagnosis is unreliable. Acute or recent rubella infection can be 

confirmed by detection of rubella virus by polymerase chain 

reaction (PCR), a significant rise in rubella specific immune 

globulin (Ig)G antibody from paired acute- and convalescentphase sera, or the presence of rubella-specific IgM antibody. 

Rubella Complications

● Encephalitis 1 in 6000 cases

● Hemorrhagic manifestations

(e.g., thrombocytopenic

purpura) 1 in 3000 cases

● Other rare complications—

granulomas, orchitis, neuritis,

progressive panencephalitis

Congenital Rubella Syndrome (CRS)

● Prevention of CRS is the

main objective of rubella

vaccination programs

● May lead to miscarriages,

stillbirths, and birth defects

● Birth defects may include

deafness, eye abnormalities,

and congenital heart disease
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The optimal time for serum collection for IgM detection is 

5 days after onset of symptoms (fever and rash). If serum is 

collected less than 5 days after onset and is IgM negative, a 

second sample is necessary to confirm or rule out rubella 

using IgM detection. 

In persons with rubella infection, the virus may be detected in 

nasal, throat, urine, blood, and cerebrospinal fluid specimens 

up to 10 days after rash onset (most successful within 3 days). 

In infants with suspected CRS, nasopharyngeal swabs and/or 

urine should be collected as close to birth as possible. If CRS 

is confirmed, infants should be screened for viral shedding 

monthly after the age of 3 months until two consecutive 

negative tests are obtained. Viral shedding may be detected 

for up to one year. 

Epidemiology 

Occurrence 

Rubella used to be a worldwide infection. Endemic rubella and 

CRS were eliminated in the United States in 2004, and in the 

region of the Americas in 2009. 

Reservoir 

Rubella is a human disease. There is no known animal reservoir 

and no evidence of insect transmission. Infants with CRS may 

shed rubella virus for an extended period. 

Transmission 

Rubella is spread from person-to-person via direct contact 

or droplets shed from the respiratory secretions of infected 

persons. Rubella may be transmitted by persons with subclinical 

or asymptomatic cases (up to 50% of all rubella virus infections). 

Temporal Pattern 

Since rubella elimination in the United States, sporadic cases of 

rubella have been imported or linked to an imported case, with 

no temporal pattern.

Communicability 

Rubella is most contagious when the rash first appears, but virus 

may be shed from 7 days before to 7 days after rash onset.

Infants with CRS shed large quantities of virus from body 

secretions for up to 1 year and can therefore transmit rubella to 

persons caring for them who are susceptible to the disease. 

Rubella Epidemiology

● Reservoir

■ Human

● Transmission 

■ Person-to-person via droplets

● Temporal pattern

■ No known temporal pattern

● Communicability

■ 7 days before to 7 days after 

rash onset

■ Infants with CRS may shed 

virus for up to a year 
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Secular Trends in the United States 

Rubella and congenital rubella syndrome became nationally 

notifiable diseases in 1966. Following vaccine introduction 

in 1969, rubella incidence declined dramatically. Rubella 

outbreaks continued to occur among adolescents and 

young adults and in settings where unvaccinated adults 

gathered. National recommendations to vaccinate susceptible 

postpubertal females, adolescents, persons in military service, 

college students, and persons in certain work settings, as well 

as increased rubella vaccination efforts in the Region of the 

Americas, led to further declines in rubella and CRS cases. In 

2004, endemic rubella was declared eliminated in the United 

States, with fewer than 10 cases reported annually and less than 

one CRS case per year. Since 2012, all rubella cases reported 

in the United States had evidence the patients were infected 

outside the United States. In most CRS cases reported since 

1998, the mother was born outside the United States. Among 

nine CRS cases reported in the United States between 2004 and 

2014, all were import-associated or from unknown sources.

Among children born during 2016–2017, 90.7% received 

measles, mumps, and rubella-containing vaccine by age 24 

months; this was not statistically significantly different from the 

coverage of 90.3% for children born during 2014–2015. 

Rubella Vaccines 

In 1971, a combined measles, mumps, and rubella (MMR) 

vaccine was licensed for use in the United States, and the 

current rubella vaccine component (RA27/3) was licensed in 

1979. In 2005, a combination measles, mumps, rubella, and 

varicella (MMRV) vaccine was licensed. 

Rubella vaccine is available as measles, mumps, and rubella 

vaccine (MMR [MMR-II]) and measles, mumps, rubella, and 

varicella vaccine (MMRV [ProQuad]). Both MMR and MMRV 

vaccine contain live, attenuated viruses. Single-antigen rubella 

vaccine is not available in the United States. The Advisory 

Committee on Immunization Practices (ACIP) recommends that 

MMR or MMRV vaccine be used when any of the individual 

components is indicated. 

Characteristics 

MMR vaccine is a lyophilized preparation of measles virus 

vaccine live, an attenuated line of measles virus, derived from 

Enders’ attenuated Edmonston strain and propagated in chick 

embryo cell culture; mumps virus vaccine live, the Jeryl Lynn 

strain of mumps virus propagated in chick embryo cell culture; 

and rubella virus vaccine live, the Wistar RA 27/3 strain of live 

attenuated rubella virus propagated in WI-38 human diploid 

lung fibroblasts. MMRV vaccine contains measles, mumps, and 

rubella virus of equal titer and identical to those in the MMR 

Rubella Vaccines

● MMR (MMR-II)

● MMRV (ProQuad)

Rubella Vaccine Characteristics

● Live, attenuated vaccine

● Available as lyophilized powder 

and reconstituted with sterile, 

preservative-free water

● Administered by subcutaneous 

injection

● Contains gelatin

● Contains neomycin

Rubella Secular Trends 

in the United States

● Following vaccine introduction, 

incidence declined dramatically

● Postvaccine outbreaks led to 

recommendations to vaccinate 

susceptible populations, further 

decreasing rubella and CRS

● In 2004, endemic rubella 

declared eliminated in the 

United States (fewer than 10 

cases rubella and 1 case CRS 

per year)

● Since 2012, all rubella 

cases imported
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vaccine. The titer of Oka varicella zoster virus is higher in MMRV 

vaccine than in single-antigen varicella vaccine, a minimum of 

9,772 plaque-forming units (PFU) versus 1,350 PFU, respectively. 

MMR and MMRV vaccines are supplied as a lyophilized 

(freeze-dried) powder and are reconstituted with sterile, 

preservative-free water. Both vaccines contain gelatin. MMR and 

MMRV vaccines are administered by the subcutaneous route. 

Each dose of MMR and MMRV vaccine contains neomycin as an 

antibiotic. It contains no adjuvant or preservative. 

Vaccination Schedule and Use

MMR vaccine or MMRV vaccine can be used to implement 

the vaccination recommendations for prevention of measles, 

mumps, and rubella. MMR vaccine is licensed for use in persons 

age 12 months or older. MMRV vaccine is licensed for use in 

persons age 12 months through 12 years; MMRV vaccine should 

not be administered to persons age 13 years or older. 

Two doses of MMR vaccine, separated by at least 4 weeks, are 

routinely recommended for children age 12 months or older. 

Dose 1 of MMR vaccine should be given at age 12 through 

15 months. A second dose of MMR vaccine is recommended 

based on previous observations of the failure of some to 

generate an immune response to measles following dose 1. 

Dose 2 is routinely given at age 4 through 6 years, before a 

child enters kindergarten or first grade. All students entering 

school should receive 2 doses of MMR vaccine (with the 

first dose administered at age 12 months or older) before 

enrollment. Dose 2 of MMR vaccine may be administered as 

soon as 4 weeks after dose 1. 

The minimum interval between doses of MMRV vaccine is 

3 months, although when dose 2 is administered 4 weeks 

following dose 1, it can be considered valid. For the first dose 

of measles, mumps, rubella, and varicella vaccines at age 12 

through 47 months, either separate MMR and varicella (VAR) 

vaccines, or MMRV vaccine, may be used. However, the risk of 

febrile seizures is about twice as high for children receiving 

MMRV vaccine versus separate MMR and VAR vaccines. Providers 

who are considering administering MMRV should discuss the 

benefits and risks of both vaccination options with the parents. 

Unless the parent or caregiver expresses a preference for MMRV, 

separate MMR vaccine and VAR vaccine should be administered 

for the first dose in this age group. For the second dose of 

measles, mumps, rubella, and varicella vaccines at any age and 

for the first dose at age 48 months or older, the use of MMRV 

generally is preferred over separate injections of its equivalent 

component vaccines (i.e., MMR vaccine and VAR vaccine). 

Rubella Vaccination Schedule

● 2 dose series at age 12 through 

15 months and at age 4 

through 6 years

● Minimum age for dose 1 is 12 

months

● Minimum interval from dose 1 

to 2 is 4 weeks for MMR and 3 

months for MMRV (although a 

4-week interval is valid)

● Discuss risks and benefits of 

MMRV versus separate MMR 

and VAR 

■ Separate MMR and VAR 

vaccines preferred for dose 

1 in ages 12 through 47 

months

■ MMRV preferred for dose 2 

and dose 1 at age 48 months 

or older
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Vaccination of Adults

Adults born in 1957 or later should receive at least 1 dose of 

MMR vaccine unless they have documentation of vaccination 

with at least 1 dose of measles, mumps, and rubella-containing 

vaccine or other acceptable presumptive evidence of immunity 

to these three diseases. Except for health care personnel, who 

should have documented immunity, birth before 1957 generally 

can be considered acceptable evidence of immunity to measles, 

mumps, and rubella. 

Colleges and other post-high-school educational institutions 

are potential high-risk areas for measles, mumps, and rubella 

transmission because of large concentrations of persons. 

Prematriculation vaccination requirements for measles 

immunity have been shown to significantly decrease the 

risk of measles outbreaks on college campuses where such 

requirements are implemented and enforced. All students 

entering colleges, universities, technical and vocational 

schools, and other institutions for post-high-school education 

should receive 2 doses of MMR vaccine or have other 

acceptable evidence of measles, mumps, and rubella 

immunity before entry.

For unvaccinated health care personnel born before 1957 

who lack laboratory evidence of measles, mumps, or rubella 

immunity or laboratory confirmation of disease, health care 

facilities should have policies that offer 2 doses of MMR vaccine 

at the appropriate interval for measles and mumps and 1 dose 

of MMR vaccine for rubella, respectively. Health care facilities 

should also have policies for such personnel that recommend 2 

doses of MMR vaccine during an outbreak of measles or mumps 

and 1 dose during an outbreak of rubella. This recommendation 

is based on serologic studies indicating that among hospital 

personnel born before 1957, 5% to 10% had no detectable 

measles, mumps, or rubella antibody. Adequate vaccination 

for health care personnel born during or after 1957 consists of 

at least 1 dose of MMR for rubella, and 2 appropriately spaced 

MMR doses for measles and mumps.

Elimination of indigenous rubella and CRS can be maintained 

by continuing efforts to vaccinate susceptible adolescents 

and women of childbearing age, particularly those born 

outside the United States. These efforts should include 

vaccinating in family planning clinics and sexually transmitted 

disease (STD) clinics, and as part of routine gynecologic care. 

Efforts should also be made to maximize use of premarital 

serology results when such tests assess rubella immunity; 

emphasize vaccination for college students; vaccinate women 

postpartum and postabortion; immunize female prison staff 

and, when possible, female prison inmates; offer vaccination 

to at-risk women through the special supplemental program 

MMR Vaccination of Adults

● Certain persons without 

acceptable presumptive 

immunity:

■ At least 1 dose MMR for 

unvaccinated adults

■ 2 doses MMR for students 

entering colleges, universities, 

technical and vocational 

schools, and other post-highschool educational institutions

■ 2 doses MMR for measles and 

mumps and at least 1 dose 

MMR for rubella for healthcare 

personnel

● Healthcare personnel during an 

outbreak

■ 2 doses MMR for measles or 

mumps outbreak and 1 dose 

MMR for rubella outbreak
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for Women, Infants, and Children (WIC); and implement 

vaccination programs in certain workplaces, particularly those 

employing persons born outside the United States. 

Revaccination

Measles-, mumps-, or rubella- virus-containing vaccine 

administered prior to age 12 months (e.g., for international 

travel) should not be counted as part of the 2-dose series. 

Children vaccinated before age 12 months should be 

revaccinated with 2 doses of appropriately spaced MMR or 

MMRV vaccine, the first dose administered when the child is 

age 12 through 15 months (12 months if the child remains in 

an area where disease risk is high) and the second dose at least 

4 weeks later.

Persons who experienced perinatal HIV infection who may have 

received MMR vaccine prior to the establishment of effective 

combined antiretroviral therapy (cART), should be revaccinated 

with 2 appropriately spaced doses of MMR (i.e., the dose does 

not count) unless they have other acceptable current evidence 

of immunity. MMR series should be administered once effective 

cART has been established for at least 6 months and there is no 

evidence of severe immunosuppression.

Rubella Immunity 

Generally, persons can be considered immune to rubella 

if they were born before 1957, have serologic evidence of 

rubella immunity (equivocal test results should be considered 

negative), or laboratory confirmation of disease, or have 

documentation of adequate vaccination for rubella. Birth before 

1957 provides only presumptive evidence of rubella immunity; 

it does not guarantee that a person is immune to rubella. Birth 

before 1957 is not acceptable evidence of rubella immunity for 

women who could become pregnant.

Clinical diagnosis of rubella is unreliable and should not 

be considered in assessing immune status. Because many 

rash illnesses may mimic rubella infection and many rubella 

infections are unrecognized, the only reliable evidence of 

previous rubella infection is the presence of serum rubella IgG 

antibody. Laboratories that regularly perform antibody testing 

are generally the most reliable. 

Immunogenicity and Vaccine Efficacy 

At least 95% of vaccinated persons age 12 months or older 

develop serologic evidence of rubella immunity after a single 

dose, and more than 90% have protection against clinical 

rubella for at least 15 years. Follow-up studies indicate that 1 

dose of vaccine confers long-term, probably lifelong, protection. 

Seroconversion rates are similar for MMR and MMRV vaccines. 

Rubella Immunity

● Born before 1957

■ Not acceptable evidence 

for women who could 

become pregnant

● Serologic evidence of rubella 

immunity (equivocal tests are 

considered negative)

● Laboratory confirmation of 

disease

● Documentation of adequate 

vaccination for rubella

Rubella Vaccine Efficacy 

● 95% develop immunity after a 

single dose

● 1 dose confers long-term, 

probably lifelong, protection
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Although titers to rubella wane in the years after vaccination, 

there is no evidence that this leads to significant susceptibility 

to clinical rubella or CRS. Clinical rubella and CRS-affected 

pregnancies are extremely rare in vaccinated persons the 

United States. 

Contraindications and Precautions 

to Vaccination 

As with other vaccines, a history of a severe allergic reaction 

(anaphylaxis) to a vaccine component or following a prior dose 

is a contraindication to further doses. Moderate or severe 

acute illness (with or without fever) in a patient is considered a 

precaution to vaccination, although persons with minor illness 

may be vaccinated. 

MMR and MMRV vaccines both contain minute amounts of 

neomycin and gelatin. Persons with alpha-gal allergy may 

wish to consult their physician before receiving a vaccine that 

contains gelatin.

Severe immunocompromise (e.g., from hematologic and solid 

tumors, receipt of chemotherapy, congenital immunodeficiency, 

long-term immunosuppressive therapy or patients with 

HIV infection who are severely immunocompromised) is a 

contraindication for MMR and MMRV vaccination. If the person’s 

level of immunocompetence is uncertain, the decision to 

vaccinate should be made by the health care provider that 

prescribed the immunosuppressive medication for those 

patients whom immunocompromise is due to medication. 

Patients who have not received chemotherapy for at least 3 

months, whose disease remains in remission, and who have 

restored immunocompetence, may receive MMR or MMRV 

vaccine. Healthy, susceptible close contacts of severely 

immunocompromised persons should be vaccinated. 

Persons receiving systemic high-dose corticosteroid therapy 

(2 milligrams per kilogram of body weight or more per day or 

20 milligrams or more per day of prednisone) for 14 days or 

more should not receive MMR or MMRV vaccine because of 

concern about vaccine safety. MMR or MMRV should not be 

administered for at least 1 month after cessation of systemic 

high-dose corticosteroid therapy. Although persons receiving 

high doses of systemic corticosteroids daily or on alternate 

days for less than 14 days generally can receive MMR or MMRV 

immediately after cessation of treatment, some experts prefer 

waiting until 2 weeks after completion of therapy.

Available data indicate that vaccination with MMR has not 

been associated with severe or unusual adverse reactions in 

HIV-infected persons who are not severely immunosuppressed, 

although antibody responses have been variable. MMR 

Rubella Vaccine Contraindications

● Contraindication

■ Severe allergic reaction 

to vaccine component or 

following a prior dose

■ Severe immunocompromise

■ Systemic high-dose 

corticosteroid therapy for 14 

days or more

■ HIV infection, regardless of 

immunocompetence status*

■ Family history of 

congenital or heredity 

immunodeficiency in firstdegree relatives

■ Pregnancy

*MMRV only
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vaccine is recommended for susceptible HIV-infected 

persons age 12 months or older with no evidence of current 

severe immunosuppression (“no evidence of current severe 

immunosuppression” is defined as CD4 percentages greater 

than or equal to 15% for 6 months or longer for persons age 5 

years or younger; and CD4 percentages greater than or equal to 

15% and CD4 count greater than or equal to 200 cells/mm3 for 

6 months or longer for persons older than age 5 years). MMR 

vaccine is not recommended for HIV-infected persons with 

evidence of severe immunosuppression. 

MMRV is not approved for and should not be administered to a 

person known to be infected with HIV.

A family history of congenital or hereditary immunodeficiency 

in first-degree relatives (e.g., parents and siblings) is a 

contraindication for MMR or MMRV vaccine, unless the immune 

competence of the potential vaccine recipient has been 

substantiated clinically or verified by a laboratory.

A history of thrombocytopenic purpura or thrombocytopenia 

is a precaution for MMR and MMRV vaccine. Such persons 

may be at increased risk for developing clinically significant 

thrombocytopenia after MMR or MMRV vaccination. 

Receipt of specific antiviral drugs (e.g., acyclovir, famciclovir, 

or valacyclovir) 24 hours before vaccination is a precaution for 

MMRV vaccine due to the varicella component. These drugs 

should be avoided for 14 days after vaccination.

Simultaneous use of aspirin or aspirin-containing products is a 

precaution for MMRV vaccine due to the varicella component. 

The manufacturer recommends that vaccine recipients avoid 

the use of salicylates for 6 weeks after receiving MMRV vaccine 

because of the association between aspirin use and Reye 

syndrome following chickenpox. 

A personal or family (i.e., sibling or parent) history of seizures 

of any etiology is a precaution for MMRV vaccine but not MMR. 

Children with a personal or family history of seizures of any 

etiology should ideally be vaccinated with separate MMR and 

VAR vaccines because the risks for using MMRV vaccine in this 

group of children generally outweigh the benefits.

MMR vaccine may be administered to egg-allergic persons 

without prior routine skin testing or the use of special protocols.

Spacing Considerations

The effect of the administration of antibody-containing blood 

products (e.g., immune globulin, whole blood or packed 

red blood cells, or intravenous immune globulin) on the 

response to MMR or MMRV vaccine is unknown. Because of the 

potential inhibition of the response to vaccination by passively 

Rubella Vaccine Precautions

● Precaution

■ Moderate or severe acute 

illness

■ Alpha-gal allergy (consult 

with physician)

■ Receipt of antibodycontaining blood products 

(wait 3 to 11 months 

to vaccinate)

■ History of thrombocytopenic 

purpura or thrombocytopenia

■ Need for tuberculin skin 

testing or interferon-gamma 

release assay testing

■ Simultaneous use of aspirin 

or aspirin-containing 

products*

■ Personal or family history of 

seizures of any etiology*

■ Receipt of specific antiviral 

drugs 24 hours before 

vaccination*

*MMRV only
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transferred antibodies, neither MMR vaccine nor MMRV 

vaccine (nor VAR vaccine) should be administered for 3 to 11 

months after receipt of antibody-containing blood products. 

The interval between the antibody-containing blood product 

and receipt of MMR or MMRV vaccine is determined by the 

type of product administered. Antibody-containing products 

should not be given for 2 weeks following vaccination unless 

the benefits exceed those of the vaccine. In such cases, vaccine 

recipients should either be revaccinated later at the appropriate 

intervals (ranging 3 to 11 months) or tested for immunity and 

revaccinated if seronegative.

Need for tuberculin skin testing or interferon-gamma release 

assay (IGRA) testing is a precaution for MMR and MMRV 

vaccine. Measles vaccine (and possibly mumps, rubella, and 

varicella vaccines) may transiently suppress the response 

to tuberculin skin test (TST) in a person infected with 

Mycobacterium tuberculosis. TST and measles-containing 

vaccine may be administered at the same visit if necessary. 

Simultaneously administering TST and measles-containing 

vaccine does not interfere with reading the TST result at 

48 to 72 hours and ensures that the person has received 

measles vaccine. If the measles-containing vaccine has been 

administered recently, TST screening should be delayed for at 

least 4 weeks after vaccination.

Receipt of specific antiviral drugs (e.g., acyclovir, famciclovir, 

or valacyclovir) 24 hours before vaccination is a precaution for 

MMRV vaccine due to the varicella component. These drugs 

should be avoided for 14 days after vaccination.

Vaccination in Pregnancy

Pregnancy is a contraindication for MMR or MMRV vaccine. 

Pregnancy should be avoided for 4 weeks following MMR or 

MMRV vaccine. Close contact with a pregnant woman is not a 

contraindication to MMR or MMRV vaccination of the contact.

If a pregnant woman inadvertently receives MMR or MMRV 

vaccine, termination of pregnancy is not recommended because 

the risk to the fetus appears to be extremely low. Instead, 

individual counseling for these women is recommended. Data 

from 321 susceptible women who received rubella vaccine 

showed no evidence of CRS in offspring. Studies conducted 

in six Latin American countries showed a negligible or absent 

risk for CRS after administration of rubella vaccine shortly 

before or during pregnancy. Of the 1,980 susceptible pregnant 

women followed, 70 (3.6%) of the infants had congenital rubella 

infection, but none had congenital defects associated with CRS.
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Vaccine Safety 

Studies have shown MMR and MMRV vaccines are safe and welltolerated. The National Academy of Medicine, formerly called 

the Institute of Medicine, reviewed the evidence between MMR 

vaccination and certain adverse events. The experts determined 

that evidence supports a causal relation between MMR 

vaccination and anaphylaxis, febrile seizures, thrombocytopenic 

purpura, transient arthralgia, and measles inclusion body 

encephalitis in persons with demonstrated immunodeficiencies.

Most adverse events reported following MMR vaccination 

(such as fever and rash) are attributable to the measles 

component. After MMR vaccination, 5% to 15% of susceptible 

persons develop a temperature of 103°F (39.4°C) or higher, 

usually occurring 7 to 12 days after vaccination and generally 

lasting 1 or 2 days. Most persons with fever do not have other 

symptoms. MMR vaccine is associated with a very small risk 

of febrile seizures; approximately one case for every 3,000 to 

4,000 doses of MMR vaccine administered. The febrile seizures 

typically occur 6 to 14 days after vaccination and do not appear 

to be associated with any long-term sequelae. Children with a 

personal or family history of febrile seizures or family history of 

epilepsy might be at increased risk for febrile seizures after MMR 

vaccination.

Allergic reactions following the administration of MMR 

vaccine are rare. Most of these are minor and consist of a 

wheal and flare or urticaria at the injection site. Immediate, 

anaphylactic reactions to MMR vaccine occur in 1.8 to 14.4 

cases per million doses. 

Arthralgias and other joint symptoms are reported in up to 25% 

of adult women following MMR vaccine and are associated with 

the rubella component. Transient lymphadenopathy sometimes 

occurs following receipt of MMR or other rubella-containing 

vaccine, and parotitis has been reported rarely (less than 1%) 

following receipt of MMR or other mumps-containing vaccine. 

Rarely, MMR vaccine may cause thrombocytopenia within 

two months after vaccination. The clinical course of these 

cases is usually transient and benign, although hemorrhage 

occurs rarely. Based on case reports, the risk for MMR vaccineassociated thrombocytopenia may be higher for persons who 

have previously had immune thrombocytopenic purpura, 

particularly for those who had thrombocytopenic purpura after 

an earlier dose of MMR vaccine.

Measles inclusion body encephalitis has been documented after 

measles vaccination in persons with immune deficiencies. The 

illness is also known to occur within 1 year after initial infection 

with wild-type measles virus and has a high death rate. In 

the cases after MMR vaccination, the time from vaccination to 

Rubella Vaccine Safety 

MMR

● Fever of 103°F (39.4°C) or 

higher

■ 5%–15%

● Rash

■ 5%

● Febrile seizures

■ 1 in every 3,000 to 4,000 

doses

● Anaphylactic reactions

■ 1.8 to 14.4 cases per million 

doses

● Arthralgias and other joint 

symptoms

■ 25% (adult women)

MMRV

● Fever of 102°F or higher

■ 21.5%

● Febrile seizures

■ 1 additional per 2,300 

to 2,600 children age 12 

through 23 months
312

Rubella

 20

development of measles inclusion body encephalitis was 4–9 

months, consistent with development of measles inclusion body 

encephalitis after infection with wild-type measles virus. 

In MMRV vaccine prelicensure studies conducted among 

children age 12 to 23 months, fever (reported as abnormal or 

elevated greater than or equal to 102°F oral equivalent) was 

observed 5 to 12 days after vaccination in 21.5% of MMRV 

vaccine recipients compared with 14.9% of MMR vaccine and 

VAR vaccine recipients. Two postlicensure studies indicated that 

one additional febrile seizure per 2,300 to 2,600 children age 

12 through 23 months occurred 5 to 12 days after the first dose 

of MMRV vaccine, compared with children who had received 

the first dose of MMR vaccine and VAR vaccine administered as 

separate injections at the same visit. Data from postlicensure 

studies do not suggest that this increased risk exists for children 

age 4 to 6 years receiving the second dose of MMRV vaccine.

Multiple studies, as well as a National Academy of Medicine 

Vaccine Safety Review, refute a causal relationship between 

autism and MMR vaccine or between inflammatory bowel 

disease and MMR vaccine. 

Vaccine Storage and Handling 

For MMR-II and Proquad storage and handling specifics, refer 

to the manufacturer. For complete information on storage and 

handling best practices and recommendations, please refer to 

CDC’s Vaccine Storage and Handling Toolkit, https://www.cdc.

gov/vaccines/hcp/admin/storage/toolkit/storage-handlingtoolkit.pdf.

Surveillance and Reporting for Rubella 

Rubella and congenital rubella syndrome became nationally 

notifiable diseases in 1966. For information on guidance for state 

and local health department staff who are involved in surveillance 

activities for vaccine-preventable diseases, please consult the 

Manual for the Surveillance of Vaccine-Preventable Diseases, 

www.cdc.gov/vaccines/pubs/surv-manual/chapters.html. 
Rubella

313

20

Acknowledgements

The editors would like to acknowledge Zaney Leroy, 

Ginger Redmon, and Greg Wallace for their contributions 

to this chapter.

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NOTES