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



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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 and was called “third disease”. 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, Hess postulated a viral 

etiology based on his work with monkeys. Hiro and Tosaka 

in 1938 confirmed the viral etiology by passing the disease 

to children using filtered nasal washings from persons with 

acute cases.  

Following a widespread epidemic of rubella infection in 

1940, Norman Gregg, an Australian ophthalmologist, 

reported in 1941 the occurrence of congenital cataracts 

among 78 infants born following maternal rubella infection 

in early pregnancy. This was the first published recognition 

of congenital rubella syndrome (CRS). Rubella virus was first 

isolated in 1962 by Parkman and Weller. The first rubella 

vaccines were licensed in 1969.  



Rubella Virus 

Rubella virus is classified as a togavirus, genus Rubivirus.  

It is most closely related to group A arboviruses, such as  

eastern and western equine encephalitis viruses. It is an  

enveloped RNA virus, with a single antigenic type that does  

not cross-react with other members of the togavirus group.  

Rubella virus is relatively unstable and is inactivated by lipid  

solvents, trypsin, formalin, ultraviolet light, low pH, heat,  

and amantadine.    

Pathogenesis 

Following respiratory transmission of rubella virus, 

replication of the virus is thought to occur in the 

nasopharynx and regional lymph nodes. A viremia occurs 5 

to 7 days after exposure with spread of the virus throughout 

the body. Transplacental infection of the fetus occurs during 

viremia. Fetal damage occurs through destruction of cells as 

well as mitotic arrest.  



Clinical Features 

Acquired Rubella 

The 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 children, 

rash is usually the first manifestation and a prodrome is 

rare. In older children and adults, there is often a 1 to 5 day 

prodrome with low-grade fever, malaise, lymphadenopathy, 

and upper respiratory symptoms preceding the rash. The 

rash of rubella is maculopapular and occurs 14 to 17 days 

Rubella 

From Latin meaning 

“little red” 

Discovered in 18th century 

–thought to be variant 

of measles 

First described as 

distinct clinical entity in 

German literature 

Congenital rubella syndrome 

(CRS) described by Gregg 

in 1941 


Rubella virus first isolated in 

1962 by Parkman and Weller 



Rubella Virus 

Togavirus 

RNA virus 

One antigenic type 

Inactivated by lipid solvents, 

trypsin, formalin, ultraviolet 

light, low pH, heat, and 

amantadine 



Rubella Pathogenesis 

Respiratory transmission 

of virus 

Replication in nasopharynx 

and regional lymph nodes 

Viremia 5 to 7 days after 

exposure with spread 

throughout body 

Transplacental infection of 

fetus during viremia 

Centers for Disease Control and Prevention 

Epidemiology and Prevention of Vaccine-Preventable Diseases, 13th Edition 

April, 2015 


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Rubella Clinical Features 

Incubation period 14 days  

(range 12 to 23 days) 

Prodrome is rare in children 

Prodrome of low-grade fever in 

adults 


Maculopapular rash 14 to 17 

days after exposure 

Lymphadenopathy occurs 

before rash and lasts for 

several weeks 

Rubella Complications 

Arthralgia or arthritis (adult 

female) – up to 70% 

Arthralgia or arthritis 

(children) – rare 

Encephalitis  - 1/6000 cases 

Hemorraghic manifestations 

(e.g. thrombocytopenic  

purpura) 1/3000

Orchitis, neuritis, progressive 

panencephalitis – rare 

Epidemic Rubella – United States, 

1964-1965 

12.5 million rubella cases 

20,000 CRS cases 

Estimated cost more than  

$840 million

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 

measles rash and does not coalesce. The rash is often more 

prominent after a hot shower or bath. Lymphadenopathy 

may begin a week before the rash and last several weeks. 

Postauricular, posterior cervical, and suboccipital nodes are 

commonly involved. 

Arthralgia and arthritis occur so frequently in adults that 

they are considered by many to be an integral part of 

the illness rather than a complication. Other symptoms 

of rubella include conjunctivitis, testalgia, or orchitis. 

Forschheimer spots may be noted on the soft palate but are 

not diagnostic for rubella. 

Complications 

Complications of rubella are not common, but they 

generally occur more often in adults than in children.  

Arthralgia or arthritis may occur in up to 70% of adult 

women who contract rubella, but it is rare in children and 

adult males. Fingers, wrists, and knees are often affected. 

Joint symptoms tend to occur about the same time or 

shortly after appearance of the rash and may last for up to 1 

month; chronic arthritis is rare.  

Encephalitis occurs in one in 6,000 cases, more frequently 

in adults (especially in females) than in children. Mortality 

estimates vary from 0 to 50%.  

Hemorrhagic manifestations occur in approximately one per 

3,000 cases, occurring more often in children than in adults. 

These manifestations may be secondary to low platelets and 

vascular damage, with thrombocytopenic purpura being the 

most common manifestation. Gastrointestinal, cerebral, or 

intrarenal hemorrhage may occur. Effects may last from days 

to months, and most patients recover.  

Additional complications include orchitis, neuritis, and a 

rare late syndrome of progressive panencephalitis.  

Congenital Rubella Syndrome 

Prevention of CRS is the main objective of rubella 

vaccination programs in the United States.  

A rubella epidemic in the United States in 1964–1965 

resulted in 12.5 million cases of rubella infection and 

about 20,000 newborns with CRS. The estimated cost of 

the epidemic was $840 million. This does not include the 

emotional toll on the families involved. 



Rubella

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Infection with rubella virus is most severe in early gestation. 

The virus may affect all organs and cause a variety of 

congenital defects. Infection may lead to fetal death, 

spontaneous abortion, or preterm delivery. The severity of 

the effects of rubella virus on the fetus depends largely on 

the time of gestation at which infection occurs. As many as 

85% of infants infected in the first trimester of pregnancy 

will be found to be affected if followed after birth. While 

fetal infection may occur throughout pregnancy, defects are 

rare when infection occurs after the 20th week of gestation. 

The overall risk of defects during the third trimester is 

probably no greater than that associated with uncompli­

cated pregnancies.  

Congenital infection with rubella virus can affect virtually 

all organ systems. Deafness is the most common and often 

the sole manifestation of congenital rubella infection, 

especially after the fourth month of gestation. Eye defects, 

including cataracts, glaucoma, retinopathy, and microph­

thalmia may occur. Cardiac defects such as patent ductus 

arteriosus, ventricular septal defect, pulmonic stenosis, and 

coarctation of the aorta are possible. Neurologic abnormali­

ties, including microcephaly and mental retardation, and 

other abnormalities, including bone lesions, splenomegaly, 

hepatitis, and thrombocytopenia with purpura may occur.  

Manifestations of CRS may be delayed from 2 to 4 years. 

Diabetes mellitus appearing in later childhood occurs 

frequently in children with CRS. In addition, progressive 

encephalopathy resembling subacute sclerosing panencepha­

litis has been observed in some older children with CRS. 

Children with CRS have a higher than expected incidence of 

autism. 

Infants with CRS may have low titers by hemagglutination 

inhibition (HI) but may have high titers of neutralizing 

antibody that may persist for years. Reinfection may occur. 

Impaired cell-mediated immunity has been demonstrated in 

some children with CRS.  



Laboratory Diagnosis 

Many rash illnesses can mimic rubella infection, and as 

many as 50% of rubella infections may be subclinical. The 

only reliable evidence of acute rubella infection is a positive 

viral culture for rubella or detection of rubella virus by 

polymerase chain reaction (PCR), the presence of rubella-

specific IgM antibody, or demonstration of a significant rise 

in IgG antibody from paired acute- and convalescent-phase 

sera. 

Rubella virus can be isolated from nasal, blood, throat, 



urine and cerebrospinal fluid specimens from rubella and 

CRS patients. Virus may be isolated from the pharynx 1 week 



Congenital Rubella Syndrome 

Infection may affect all organs 

May lead to fetal death or 

premature delivery 

Severity of damage to fetus 

depends on gestational age 

Up to 85% of infants affected 

if infected during first trimester 

Deafness 

Eye defects 

Cardiac defects 

Microcephaly 

Mental retardation 

Bone alterations 

Liver and spleen damage 

Rubella Laboratory Diagnosis 

Isolation of rubella virus 

from clinical specimen (e.g., 

nasopharynx, urine) 

Serologic tests available vary 

among laboratories 

Positive serologic test for 

rubella IgM antibody 

Significant rise in rubella 

IgG by any standard 

serologic assay (e.g., enzyme 

immunoassay) 



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peak in late winter 

and spring 

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7 days before 5 to 7 days 



after rash onset 

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Reservoir 



human 

Transmission 

respiratory (Subclinical 

cases may transmit) 

Temporal pattern 

Communicability 

Infants with CRS may shed 

virus for up to a year 



Rubella Epidemiology 

before and until 2 weeks after rash onset. Although isolation 

of the virus is diagnostic of rubella infection, viral cultures 

are labor intensive, and therefore not done in many labora­

tories; they are generally not used for routine diagnosis of 

rubella. Viral isolation is an extremely valuable epidemiologic 

tool and should be attempted for all suspected cases of 

rubella or CRS. Information about rubella virus isolation can 

be found on the CDC website at www.cdc.gov/rubella/lab/ 

lab-protocols.htm.  

Serology is the most common method of confirming the 

diagnosis of rubella. Acute rubella infection can be serologi­

cally confirmed by a significant rise in rubella antibody titer 

in acute- and convalescent-phase serum specimens or by the 

presence of serum rubella IgM. Serum should be collected 

as early as possible (within 7–10 days) after onset of illness, 

and again 14–21 days (minimum of 7) days later.  

False-positive serum rubella IgM tests have occurred 

in persons with parvovirus infections, with a positive 

heterophile test for infectious mononucleosis, or with a 

positive rheumatoid factor. 

The serologic tests available for laboratory confirmation of 

rubella infections vary among laboratories. The state health 

department can provide guidance on available laboratory 

services and preferred tests. 

Enzyme-linked immunosorbent assay (ELISA) is sensitive, 

widely available, and relatively easy to perform. It can 

also be modified to measure IgM antibodies. Most of the 

diagnostic testing done for rubella antibodies uses some 

variation of ELISA.  



Epidemiology 

Occurrence 

Rubella occurs worldwide. For information about the clinical 

case definition, clinical classification and epidemiologic 

classification of rubella and congenital rubella syndrome see 

www.cdc.gov/vaccines/pubs/surv-manual/default.htm. 

Reservoir 

Rubella is a human disease. There is no known animal 

reservoir. Although infants with CRS may shed rubella virus 

for an extended period, a true carrier state has not been 

described. 

Transmission 

Rubella is spread from person to person via droplets shed 

from the respiratory secretions of infected persons. There is 

no evidence of insect transmission.  



Rubella

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Rubella - United States,  

1966-2011

Rubella  CRS 

70000 

60000 

70 

60

50000 

50

40000 

40 

30000 

30 

20000 

20 

10 



CR

S

 C

ase



R

ub

el

la 

C

ase



10000 



1966  1970  1975  1980  1985  1990  1995  2000  2005  2010 

Source: National Notifiable Disease Surveillance System, CDC 

80 

Rubella may be transmitted by persons with subclinical 

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

infections).  



Temporal Pattern 

In temperate areas, incidence is usually highest in late winter 

and early spring. 

Communicability 

Rubella is only moderately contagious. The disease is most 

contagious when the rash first appears, but virus may be 

shed from 7 days before to 5–7 days or more 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. 

Secular Trends in the United States 

Rubella and congenital rubella syndrome became nationally  

notifiable diseases in 1966. The largest annual total of cases 

of rubella in the United States was in 1969, when 57,686 

cases were reported (58 cases per 100,000 population).  

Following vaccine licensure in 1969, rubella incidence 

declined rapidly. By 1983, fewer than 1,000 cases per year 

were reported (less than 0.5 cases per 100,000 population). 

A moderate resurgence of rubella occurred in 1990–1991, 

primarily due to outbreaks in California (1990) and among 

the Amish in Pennsylvania (1991). In 2003, a record low 

annual total of seven cases was reported. In October 2004, 

CDC convened an independent expert panel to review 

available rubella and CRS data. After a careful review, 

the panel unanimously agreed that rubella was no longer 

endemic in the United States. The number of reported cases 

of rubella in the United States remains low with a median of 

11 cases annually in 2005-2011. 



Rubella - United States, 

1980-2011 



500 

1000 

1500 

2000 

2500 

3000 

3500 

4000 

4500 

1980  1985  1990  1995  2000  2005  2010 

R

ub

el

la 

C

ase







10 

15 

20 

25 

30 

35 

40 

CR

S

 C

ase



Rubella  CRS 

Source: National Notifiable Disease Surveillance System, CDC 

Until recently, there was no predominant age group for 

rubella cases. During 1982 through 1992, approximately 

30% of cases occurred in children younger than 5 years, 30% 

occurred in children 5 through 14 years, and 30% occurred 

in persons 15 through 39 years. Adults 40 years of age and 

older typically accounted for less than 10% of cases. Since 

2004 when endemic rubella was declared eliminated in the 

U.S., persons 20-49 years of age have accounted for 60 

percent of the cases (median age 32 years). 

Most reported rubella in the United States in the mid-1990s 

has occurred among Hispanic young adults who were born 

in areas where rubella vaccine is routinely not given. In 1998, 


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Rubella and CRS 

in the United States 

Most reported rubella in the 

U.S. in the mid-1990s has 

occurred among foreign-born 

Hispanic young adults 

Indigenous transmission of 

rubella determined to have 

ended in 2004 

In 2010 PAHO announced 

region of the Americas 

achieved rubella and CRS 

elimination goal 

Latin America nations and Mexico began major rubella 

control efforts, which resulted in a marked decrease in the 

number of rubella cases. 

CRS surveillance is maintained through the National 

Congenital Rubella Registry, which is managed by the 

National Center for Immunization and Respiratory Diseases. 

The largest annual total of reported CRS cases to the 

registry was in 1970 (67 cases). An average of 2-3 CRS 

cases were reported annually during 1998-2012. Although 

reported rubella activity has consistently and significantly 

decreased since vaccine has been used in the United States, 

the incidence of CRS has paralleled the decrease in rubella 

cases only since the mid-1970s. The decline in CRS since 

the mid-1970s was due to an increased effort to vaccinate 

susceptible adolescents and young adults, especially women. 

Rubella outbreaks are almost always followed by an increase 

in CRS. 

Rubella outbreaks in California and Pennsylvania in 

1990–1991 resulted in 25 cases of CRS in 1990 and 

33 cases in 1991.  From 2004-2012, a total of 6 CRS 

cases were reported in the U.S., 5 of which where the 

mother was likely infected while in Asia or Africa. In 2010, 

the Pan American Health Organization (PAHO) announced 

that the Region of the Americas had achieved the rubella 

and CRS elimination goals set in 2003 based on surveillance 

data. Although regional documentation of elimination is 

ongoing, an expert panel unanimously agreed in December 

2011 that rubella elimination has been maintained in the 

United States. 

Rubella Vaccine 

Three rubella vaccines were licensed in the United States in 

1969: HPV-77:DE-5 Meruvax (duck embryo), HPV-77:DK-12 

Rubelogen (dog kidney), and GMK-3:RK53 Cendevax (rabbit 

kidney) strains. HPV-77:DK-12 was later removed from the 

market because there was a higher rate of joint complaints 

following vaccination with this strain. In 1979, the RA 27/3 

(human diploid fibroblast) strain (Meruvax-II, Merck) was 

licensed and all other strains were discontinued.  

Rubella Vaccine 

Vaccine 


Trade Name 

Licensure  Discontinued 

HPV-77:DE5 

Meruvax 


1969 

1979 


HPV-77:DK12 

Rubelogen 

1969 

1979 


GMK-3:RK53 

Cendevax 

1969 

1979 


RA 27/3* 

Meruvax II 

1979 

Still in use 



*Only vaccine currently licensed in U.S. 

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Characteristics 

The RA 27/3 rubella vaccine is a live attenuated virus. It was 

first isolated in 1965 at the Wistar Institute from a rubella-

infected aborted fetus. The virus was attenuated by 25–30 

passages in tissue culture, using human diploid fibroblasts. 

It does not contain duck, chicken or egg protein. 

Vaccine virus is not communicable except in the setting of 

breastfeeding (see Contraindications Section), even though 

virus may be cultured from the nasopharynx of vaccinees.  

Rubella vaccine is available combined with measles and 

mumps vaccines as MMR, or combined with mumps, 

measles, and varicella vaccine as MMRV (ProQuad). The 

Advisory Committee on Immunization Practices (ACIP) 

recommends that combined measles-mumps-rubella vaccine 

(MMR) be used when any of the individual components is 

indicated. Single-antigen rubella vaccine is not available in 

the U.S. 

MMR and MMRV are supplied as a lyophylized (freeze-dried) 

powder and are reconstituted with sterile, preservative-free 

water. The vaccines contains a small amount of human 

albumin, neomycin, sorbitol, and gelatin. 

Immunogenicity and Vaccine Efficacy  

RA 27/3 rubella vaccine is safe and more immunogenic 

than rubella vaccines used previously. In clinical trials, 95% 

or more of vaccinees aged 12 months and older developed 

serologic evidence of rubella immunity after a single dose. 

More than 90% of vaccinated persons have protection 

against both clinical rubella and viremia for at least 15 years. 

Follow-up studies indicate that one dose of vaccine confers 

long-term, probably lifelong, protection. Seroconversion 

rates are similar for single-antigen rubella vaccine, MMR, 

and MMRV. 

Several reports indicate that viremic reinfection following 

exposure may occur in vaccinated persons who have low 

levels of detectable antibody. The frequency and conse­

quences of this phenomenon are unknown, but it is believed 

to be uncommon. Rarely, clinical reinfection and fetal 

infection have been reported among women with vaccine-

induced immunity. Rare cases of CRS have occurred among 

infants born to women who had documented serologic 

evidence of rubella immunity before they became pregnant. 



Vaccination Schedule and Use 

At least one dose of rubella-containing vaccine, as 

combination MMR (or MMRV) vaccine, is routinely 

recommended for all children 12 months of age or older. 

MMRV is approved for ages 12 months through 12 

Rubella Vaccine 

Composition 

live virus (RA 27/3 strain) 

Efficacy 

95% or more 

Duration of Immunity 

lifelong 

Schedule 

at least 1 dose 

Should be administered with 

measles and mumps as MMR 

or with measles, mumps and 

varicella as MMRV 


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Rubella Vaccine (MMR) 

Indications 

All infants 12 months of age 

and older 

Susceptible adolescents and 

adults without documented 

evidence of rubella immunity 

Emphasis on nonpregnant 

women of childbearing 

age, particularly those born 

outside the U.S. 

Emphasis on males and 

females in college, places 

of employment, and health 

care settings 

years (that is, until the 13th birthday) and should not be 

adminstered to persons 13 years or older. All persons born 

during or after 1957 should have documentation of at least 

one dose of MMR. The first dose of MMR should be given 

on or after the first birthday. Any dose of rubella-containing 

vaccine given before 12 months of age should not be 

counted as part of the series. Children vaccinated with 

rubella-containing vaccine before 12 months of age should 

be revaccinated when the child is at least 12 months of age. 

A second dose of MMR is recommended to produce 

immunity to measles and mumps in those who failed to 

respond to the first dose. Data indicate that almost all 

persons who do not respond to the measles component of 

the first dose will respond to a second dose of MMR. Few 

data on the immune response to the rubella and mumps 

components of a second dose of MMR are available. 

However, most persons who do not respond to the rubella 

or mumps component of the first MMR dose would be 

expected to respond to the second dose. The second dose is 

not generally considered a booster dose because a primary 

immune response to the first dose provides long-term 

protection. Although a second dose of vaccine may increase 

antibody titers in some persons who responded to the first 

dose, available data indicate that these increased antibody 

titers are not sustained. The combined MMR vaccine is 

recommended for both doses to ensure immunity to all 

three viruses.  

The second dose of MMR vaccine should routinely be given 

at age 4 through 6 years, before a child enters kindergarten 

or first grade. The recommended health visit at age 11 

or 12 years can serve as a catch-up opportunity to verify 

vaccination status and administer MMR vaccine to those 

children who have not yet received two doses of MMR 

(with the first dose administered no earlier than the first 

birthday). The second dose of MMR may be administered 

as soon as 1 month (i.e., minimum of 28 days) after the 

first dose. The minimum interval between doses of MMRV is 

3 months. 

All older children not previously immunized should receive 

at least one dose of rubella vaccine as MMR or MMRV if 12 

years of age or younger. 

Adults born in 1957 or later who do not have a medical 

contraindication should receive at least one dose of MMR 

vaccine unless they have documentation of vaccination 

with at least one dose of measles-, mumps-, and rubella-

containing vaccine or other acceptable evidence of immunity 

to these three diseases. Some adults at high risk of measles 

and mumps exposure may require a second dose. This 

second dose should be administered as combined MMR 


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vaccine (see Measles chapter for details). Efforts should 

be made to identify and vaccinate susceptible adolescents 

and adults, particularly women of childbearing age who 

are not pregnant. Particular emphasis should be placed on 

vaccinating both males and females in colleges, places of 

employment, and healthcare settings. 

Only doses of vaccine with written documentation of the 

date of receipt should be accepted as valid. Self-reported 

doses or a parental report of vaccination is not considered 

adequate documentation. A healthcare provider should 

not provide an immunization record for a patient unless 

that healthcare provider has administered the vaccine or 

has seen a record that documents vaccination. Persons 

who lack adequate documentation of vaccination or other 

acceptable evidence of immunity should be vaccinated. 

Vaccination status and receipt of all vaccinations should be 

documented in the patient’s permanent medical record and 

in a vaccination record held by the individual.  

For the first dose of measles, mumps, rubella, and varicella 

vaccines at age 12 through 47 months, either MMR vaccine 

and varicella vaccine or MMRV vaccine may be used. 

Providers who are considering administering MMRV vaccine 

should discuss the benefits and risks of both vaccination 

options with the parents or caregivers. Unless the parent or 

caregiver expresses a preference for MMRV vaccine, CDC 

recommends that MMR vaccine and varicella 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 (15 months through 12 years) and for 

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

vaccine generally is preferred over separate injections of 

its equivalent component vaccines (i.e., MMR vaccine and 

varicella vaccine). 

Rubella Immunity 

Persons generally can be considered immune to rubella if 

they have documentation of vaccination with at least one 

dose of MMR (or MMRV) or other live rubella-containing 

vaccine administered on or after their first birthday, have 

serologic evidence of rubella immunity, or were born before 

1957. Persons who have an “equivocal” serologic test result 

should be considered rubella-susceptible. Although only one 

dose of rubella-containing vaccine is required as acceptable 

evidence of immunity to rubella, children should receive two 

doses of MMR vaccine according to the routine childhood 

vaccination schedule. 

Birth before 1957 provides only presumptive evidence of 

rubella immunity; it does not guarantee that a person is 

immune to rubella. Because rubella can occur in some 

Rubella Immunity 

Documentation of one dose 

of rubella-containing vaccine 

on or after the first birthday 

Serologic evidence 

of immunity 

Birth before 1957 (except 

women of childbearing age) 

Birth before 1957 is not 

acceptable evidence of rubella

immunity for women who 

might become pregnant 

 

Only serology or documented 



vaccination should be 

accepted 



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MMR Vaccine Contraindications 

and Precautions 

History of anaphylactic 

reactions to neomycin 

History of severe allergic 

reaction to any component of 

the vaccine 

Pregnancy 

Immunosuppression 

Moderate or severe 

acute illness 

Recent blood product 

Personal or family (i.e., sibling 

or parent) history of seizures 

of any etiology (MMRV only) 

unvaccinated persons born before 1957 and because 

congenital rubella and congenital rubella syndrome can 

occur in the offspring of women infected with rubella during 

pregnancy, birth before 1957 is not acceptable evidence of 

rubella immunity for women who might become pregnant. 

Only a positive serologic test for rubella antibody or docu­

mentation of appropriate vaccination should be accepted 

for women who may become pregnant. 

Healthcare personnel born before 1957 also should not be 

presumed to be immune. Medical facilities should consider 

recommending at least one dose of MMR vaccine to unvac­

cinated healthcare personnel born before 1957 who do 

not have laboratory evidence of rubella immunity. Rubella 

vaccination or laboratory evidence of rubella immunity 

is particularly important for healthcare personnel who 

could become pregnant, including those born before 1957. 

This recommendation is based on serologic studies which 

indicate that among hospital personnel born before 1957, 

5% to 9% had no detectable measles antibody. 

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 because their reagents 

and procedures are strictly standardized. 

Serologic screening need not be done before vaccinating 

for measles and rubella unless the medical facility considers 

it cost-effective. Serologic testing is appropriate only if 

tracking systems are used to ensure that tested persons who 

are identified as susceptible are subsequently vaccinated 

in a timely manner. If the return and timely vaccination of 

those screened cannot be assured, vaccination should be 

done without prior testing. Serologic testing for immunity 

to measles and rubella is not necessary for persons 

documented to be appropriately vaccinated or who have 

other acceptable evidence of immunity.  

Neither rubella vaccine nor immune globulin is effective 

for postexposure prophylaxis of rubella. Vaccination after 

exposure is not harmful and may possibly avert later disease. 

Contraindications and Precautions 

to Vaccination 

Contraindications for MMR and MMRV vaccines include 

history of anaphylactic reactions to neomycin, history of 

severe allergic reaction to any component of the vaccine, 

and immunosuppression. Women known to be pregnant or 

attempting to become pregnant should not receive rubella 



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20

vaccine. Although there is no evidence that rubella vaccine 

virus causes fetal damage, pregnancy should be avoided for 

4 weeks (28 days) after rubella or MMR vaccination.  

Persons with immunodeficiency or immunosuppression, 

resulting from leukemia, lymphoma, generalized malignancy, 

immune deficiency disease, or immunosuppressive therapy 

should not be vaccinated. However, treatment with 

low-dose (less than 2 mg/kg/day), alternate-day, topical, or 

aerosolized steroid preparations is not a contraindication 

to rubella vaccination. Persons whose immunosuppressive 

therapy with steroids has been discontinued for 1 month 

(3 months for chemotherapy) may be vaccinated. Rubella 

vaccine should be considered for persons with asymptomatic 

or mildly symptomatic HIV infection. See Measles chapter 

for additional details on vaccination of immunosuppressed 

persons, including those with human immunodeficiency 

virus infection. 

Persons with moderate or severe acute illness should not be 

vaccinated until the illness has improved. Minor illness (e.g., 

otitis media, mild upper respiratory infections), concurrent 

antibiotic therapy, and exposure or recovery from other 

illnesses are not contraindications to rubella vaccination. 

Receipt of antibody-containing blood products (e.g., 

immune globulin, whole blood or packed red blood 

cells, intravenous immune globulin) may interfere with 

seroconversion to rubella vaccine. Vaccine should be given 

2 weeks before, or deferred for at least 3 months following 

administration of an antibody-containing blood product. If 

rubella vaccine is given as combined MMR, a longer delay 

may be necessary before vaccination. For more information, 

see Chapter 2, General Recommendations on Immunization. 

Previous administration of human anti-Rho(D) immune 

globulin (RhoGam) does not generally interfere with an 

immune response to rubella vaccine and is not a contra­

indication to postpartum vaccination. However, women 

who have received anti-Rho immune globulin should be 

serologically tested 6–8 weeks after vaccination to ensure 

that seroconversion has occurred. 

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

of seizures of any etiology is a precaution for MMRV 

vaccination. Studies suggest that children who have a 

personal or family history of febrile seizures or family 

history of epilepsy are at increased risk for febrile seizures 

compared with children without such histories. Children 

with a personal or family history of seizures of any etiology 

generally should be vaccinated with MMR vaccine and 

varicella vaccine (for the first dose) because the risks for 

using MMRV vaccine in this group of children generally 

outweigh the benefits. 



336 

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●  

●  


●  

●  


●  

●  


●  

●  


●  

●  


●  

●  


●  

●  


●  

MMR Adverse Events 

Fever 


Rash 

Chronic arthralgias 

Chronic arthritis 

Transient peripheral 

neuritic complaints 

Recurrent joint symptoms 

Collagen disease 

MMR Adverse Reactions 

Fever 


Lymphadenopathy 

Arthralgia – associated with 

rubella component 

Arthritis- associated with 

rubella component 

Pain, paresthesia – begins 

1-3 weeks after vaccination, 

persist for 1 day to three 

weeks, and rarely recurs 

Rubella Vaccine Arthropathy 

Acute arthralgia in about 25% 

of vaccinated, susceptible 

adult women 

Acute arthritis-like signs and 

symptoms occurs in about 

10% of recipients 

Rare reports of chronic or 

persistent symptoms 

Although vaccine virus may be isolated from the pharynx, 

vaccinees do not transmit rubella to others, except 

occasionally in the case of the vaccinated breastfeeding 

woman. In this situation, the infant may be infected, 

presumably through breast milk, and may develop a mild 

rash illness, but serious effects have not been reported. 

Infants infected through breastfeeding have been shown to 

respond normally to rubella vaccination at 12–15 months 

of age. Breastfeeding is not a contraindication to rubella 

vaccination and does not alter rubella vaccination recom­

mendations. 



Adverse Events Following Vaccination 

Rubella vaccine is very safe. Most adverse events reported 

following MMR vaccination (such as fever and rash) are 

attributable to the measles component. Data from studies in 

the United States and experience from other countries using 

the RA 27/3 strain rubella vaccine have not supported an 

association between the vaccine and chronic arthritis. The 

Institute of Medicine found that evidence was inadequate 

to accept or reject a causal relationship between MMR 

vaccine and chronic arthralgia or arthritis in women. Rarely, 

transient peripheral neuritic complaints, such as paresthesias 

and pain in the arms and legs, have been reported. One 

study among 958 seronegative immunized and 932 sero­

negative unimmunized women aged 15–39 years found no 

association between rubella vaccination and development of 

recurrent joint symptoms, neuropathy, or collagen disease. 



Adverse Reactions Following Vaccination 

The most common complaints following rubella vaccination 

are fever, lymphadenopathy, and arthralgia. These reactions 

only occur in susceptible persons and are more common in 

adults, especially in women. 

Joint symptoms, such as arthralgia (joint pain) and arthritis 

(joint redness and/or swelling), are associated with the 

rubella component of MMR. Arthralgia and transient 

arthritis occur more frequently in susceptible adults than 

in children and more frequently in susceptible women 

than in men. Acute arthralgia or arthritis is rare following 

vaccination of children with RA 27/3 vaccine. By contrast, 

approximately 25% of susceptible postpubertal females 

develop acute arthralgia following RA 27/3 vaccination, 

and approximately 10% have been reported to have acute 

arthritis-like signs and symptoms.  

When acute joint symptoms occur, or when pain or 

paresthesias not associated with joints occur, the symptoms 



Rubella

337 


20

● 

● 



● 

Vaccination in Pregnancy Study 

1971-1989 

● 

● 



● 

● 

321 women vaccinated 



324 live births 

No observed CRS 

Maximum theoretical risk of 

1.6%, based on confidence 

limits (1.2% for all types of 

rubella vaccine) 

generally begin 1–3 weeks after vaccination, persist for 1 

day to 3 weeks, and rarely recur. Adults with acute joint 

symptoms following rubella vaccination rarely have had to 

disrupt work activities.  

The ACIP continues to recommend the vaccination of all 

adult women who do not have evidence of rubella immunity. 

See the Measles and Varicella chapters for information 

about adverse reactions following MMRV vaccine. 



Rubella Vaccination of Women 

of Childbearing Age 

Women who are pregnant or who intend to become 

pregnant within 4 weeks should not receive rubella vaccine. 

ACIP recommends that vaccine providers ask a woman if 

she is pregnant or likely to become pregnant in the next 

4 weeks. Those who are pregnant or intend to become 

pregnant should not be vaccinated. All other women 

should be vaccinated after being informed of the theoretical 

risks of vaccination during pregnancy and the importance 

of not becoming pregnant during the 4 weeks following 

vaccination. ACIP does not recommend routine pregnancy 

screening of women before rubella vaccination.  

If a pregnant woman is inadvertently vaccinated or if 

she becomes pregnant within 4 weeks after vaccination, 

she should be counseled about the concern for the fetus 

(see below), but MMR vaccination during pregnancy 

should not ordinarily be a reason to consider termination 

of the pregnancy.  

When rubella vaccine was licensed, concern existed about 

women being inadvertently vaccinated while they were 

pregnant or shortly before conception. This concern came 

from the known teratogenicity of the wild-virus strain. To 

determine whether CRS would occur in infants of such 

mothers, CDC maintained a registry from 1971 to 1989 of 

women vaccinated during pregnancy. This was called the 

Vaccine in Pregnancy (VIP) Registry.  

Although subclinical fetal infection has been detected 

serologically in approximately 1%–2% of infants born to 

susceptible vaccinees, regardless of the vaccine strain, 

the data collected by CDC in the VIP Registry showed no 

evidence of CRS occurring in offspring of the 321 susceptible 

women who received rubella vaccine and who continued 

pregnancy to term. The observed risk of vaccine-induced 

malformation was 0%, with a maximum theoretical risk of 

1.6%, based on 95% confidence limits (1.2% for all types 

of rubella vaccine). Since the risk of the vaccine to the 

fetus appears to be extremely low, if it exists at all, routine 

Vaccination of Women of 

Childbearing Age 

Ask if pregnant or likely to 

become so in next 4 weeks 

Exclude those who say “yes” 

For others 

 explain theoretical risks 



 vaccinate 



338 

Rubella

  20


termination of pregnancy is not recommended. Individual 

counseling for these women is recommended. As of April 30, 

1989, CDC discontinued the VIP registry. 

The ACIP continues to state that because of the small 

theoretical risk to the fetus of a vaccinated woman, pregnant 

women should not be vaccinated. 



Vaccine Storage and Handling 

MMR vaccine can be stored either in the freezer or the 

refrigerator and should be protected from light at all times. 

MMRV vaccine should be stored frozen between -58°F and 

+5°F (-50°C to -15°C).  When MMR vaccine is stored in the 

freezer, the temperature should be the same as that required 

for MMRV, between -58°F and +5°F (-50°C to -15°C).  

Storing MMR in the freezer with MMRV may help prevent 

inadvertent storage of MMRV in the refrigerator. 

Manufacturer package inserts contain additional 

information and can be found at http://www.fda.gov/ 

BiologicsBloodVaccines/Vaccines/ApprovedProducts/ 

ucm093830.htm.  For complete information on best 

practices and recommendations please refer to CDC’s 

Vaccine Storage and Handling Toolkit, http://www.cdc.gov/ 

vaccines/recs/storage/toolkit/storage-handling-toolkit.pdf. 



Strategies to Decrease Rubella and CRS 

Vaccination of Susceptible Postpubertal Females  

Elimination of indigenous rubella and CRS can be 

maintained by continuing efforts to vaccinate susceptible 

adolescents and young adults of childbearing age, particu­

larly those born outside the United States. These efforts 

should include vaccinating in family planning clinics, 

sexually transmitted disease (STD) clinics, and as part of 

routine gynecologic care; maximizing use of premarital 

serology results; emphasizing immunization for college 

students; vaccinating women postpartum and postabor­

tion; immunizing prison staff and, when possible, prison 

inmates, especially women inmates; offering vaccination to 

at-risk women through the special supplemental program 

for Women, Infants and Children (WIC); and implementing 

vaccination programs in the workplace, particularly those 

employing persons born outside the United States. 



Hospital Rubella Programs 

Emphasis should be placed on vaccinating susceptible 

hospital personnel, both male and female (e.g., volunteers, 

trainees, nurses, physicians.) Ideally, all hospital employees 

should be immune. It is important to note that screening 

programs alone are not adequate. Vaccination of susceptible 

staff must follow.  


Rubella

339 


20

Acknowledgement 

The editors thank Drs. Greg Wallace, and Zaney Leroy, CDC 

for their assistance in updating this chapter. 

Selected References 

American Academy of Pediatrics. Rubella. In: Pickering L, 

Baker C, Kimberlin D, Long S, eds. Red Book: 2009 Report of 

the Committee on Infectious Diseases

. 28th ed. Elk Grove Village, 

IL: American Academy of Pediatrics, 2009:579–84. 

CDC. Measles, mumps, and rubella—vaccine use and 

strategies for elimination of measles, rubella, and congenital 

rubella syndrome and control of mumps. Recommendations 

of the Advisory Committee on Immunization Practices 

(ACIP). MMWR 1998;47(No. RR-8):1–57. 

CDC. Immunization of health-care personnel. 

Recommendations of the Advisory Committee on 

Immunization Practices (ACIP). MMWR 2011;60(RR-7):1­

45. 


CDC. Control and prevention of rubella: evaluation and 

management of suspected outbreaks, rubella in pregnant 

women, and surveillance for congenital rubella syndrome. 

MMWR 

2001;50(No. RR-12):1–30.  

CDC. Rubella vaccination during pregnancy—United States, 

1971–1988. MMWR 1989;38:289–93. 

CDC. Notice to readers. Revised ACIP recommendations 

for avoiding pregnancy after receiving rubella-containing 

vaccine. MMWR 2001;50:1117. 

CDC. Use of combination measles, mumps, rubella, 

and varicella vaccine: recommendations of the Advisory 

Committee on Immunization Practices (ACIP). MMWR 

2010;59(No. RR-3):1–12. 

Frenkel LM, Nielsen K, Garakian A, et al. A search for 

persistent rubella virus infection in persons with chronic 

symptoms after rubella and rubella immunization and in 

patients with juvenile rheumatoid arthritis. Clin Infect Dis 

1996;22:287–94. 

Mellinger AK, Cragan JD, Atkinson WL, et al. High incidence 

of congenital rubella syndrome after a rubella outbreak. 



Pediatr Infect Dis J

 1995;14:573–78. 

Orenstein WA, Hadler S, Wharton M. Trends in vaccine-

preventable diseases. Semin Pediatr Infect Dis 1997;8:23–33. 

Reef SE, Frey TK, Theall K, et al. The changing epidemiology 

of rubella in the 1990s. JAMA 2002;287:464–72. 



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Institute of Medicine. 2012. Adverse Events of Vaccines: 

Evidence and Causality. Washington D.C. : The National 



Academies Press. 


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