Chapter 14: Rubella
Manual for the Surveillance of Vaccine-Preventable Diseases
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Authors: Huong McLean, PhD, MPH; Susan Redd; Emily Abernathy, MS; Joseph Icenogle, PhD, Gregory Wallace, MD, MS, MPH
Rubella is a viral illness caused by a togavirus of the genus Rubivirus and is characterized by
a mild, maculopapular rash. The rubella rash occurs in 50%-80% of rubella-infected persons
and is sometimes misdiagnosed as measles or scarlet fever. Children usually develop few or
no constitutional symptoms, but adults may experience a 1-5-day prodrome of low-grade
fever, headache, malaise, mild coryza, and conjunctivitis. Postauricular, occipital and posterior
cervical lymphadenopathy is characteristic and precedes the rash by 5-10 days. Arthralgia
or arthritis may occur in up to 70% of adult women with rubella. Rare complications include
thrombocytopenic purpura and encephalitis.[1-3] Rubella is transmitted through direct or droplet
contact from nasopharyngeal secretions and has an average incubation period of 17 days
(range: 12-23 days). Persons with rubella are most infectious when rash is erupting, but they
can shed virus from 7 days before to 7 days after rash onset.
When rubella infection occurs during pregnancy, especially during the first trimester, serious
consequences can result. These include miscarriages, fetal deaths/stillbirths, and a constellation
of severe birth defects known as congenital rubella syndrome (CRS). The most common
congenital defects are cataracts, heart defects and hearing impairment. See Chapter 15,
"Congenital Rubella Syndrome," for more details.
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Before the availability of rubella vaccines in the United States, rubella was a common disease
that occurred primarily among young children. Incidence was highest during the spring with
epidemics every 6 to 9 years. The last major epidemic in the United States occurred during
1964-1965, when there was an estimated 12.5 million rubella cases in the United States,
resulting in 2,000 cases of encephalitis, 11,250 therapeutic or spontaneous abortions, 2,100
neonatal deaths, and 20,000 infants born with CRS.
In 1969, live attenuated rubella vaccines were licensed in the United States. The goal of the
rubella vaccination program was and continues to be to prevent congenital infections, including
CRS. Following vaccine licensure, the number of reported cases of rubella in the United States
has declined dramatically to a median of 11 cases annually in 2005-2011 (CDC, unpublished
data). During the 1990s, the incidence of rubella among children younger than 15 years
decreased (from 0.63 per 100,000 population in 1990 to 0.06 1999), whereas the incidence
among adults aged 15 to 44 years increased (from 0.13 per 100,000 in 1990 to 0.24 in 1999).
However, since 2001, the incidence both among persons younger than age 15 years and those
aged 15 to 44 years has been less than 1/10,000,000 population.[8, 9]
During the 1990s and in 2000, rubella outbreaks occurred among members of religious
communities that traditionally refuse vaccination and among adults from countries without a
history of routine rubella vaccination programs.[7, 8] Since 2001, only three rubella outbreaks have
been reported, each with five or fewer cases.
In 2004, an independent panel of internationally recognized experts in public health, infectious
diseases, and immunizations reviewed available data and unanimously agreed that rubella
elimination (i.e., the absence of endemic transmission) was achieved in the United States.
Although rubella has been eliminated in the United States, it continues to be endemic in many
parts of the world. It is estimated more than 100,000 infants are born with CRS annually
worldwide. According to a survey of the member countries in the World Health Organization
(WHO), the number of countries that have incorporated rubella-containing vaccines into their
routine national immunization programs increased from 83 (13% of the birth cohort) in 1996
to 130 countries (40% of the birth cohort) in 2010. As of October 2010, the WHO Region of the
Americas and European Region have established rubella elimination goals for the year 2010 and 2015, respectively; the Western Pacific Region has established targets for accelerated rubella
control and CRS prevention goal (<1 case per 100,000) by 2015; and the Eastern Mediterranean
Region has established a goal of CRS prevention without a target date for countries that have
introduced national rubella vaccination programs. In addition, in 2011, WHO recommended
for all countries that are providing two doses of measles vaccine and have not introduced rubella
vaccine, to consider including rubella-containing vaccine in their immunization program.
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.[11, 13]
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Maintenance of Elimination
The United States has established and achieved the goal of eliminating endemic rubella
transmission and CRS. Elimination of endemic rubella was documented and verified in the
United States in 2004. However, because of international travel and countries without routine
rubella vaccination, imported cases of rubella are likely. To maintain elimination, the United
States should continue to maintain high vaccination rates among children; ensure that women
of childbearing age, particularly women born outside of the United States, are vaccinated; and
maintain sensitive surveillance to detect both rubella and CRS.
Two combination vaccines are licensed and available in the United States to prevent rubella:
MMR vaccine (measles, mumps, and rubella; M-M-R II®, Merck & Co., Inc.) and tetravalent
MMRV vaccine (measles, mumps, rubella, and varicella; ProQuad®, Merck & Co., Inc.).
Monovalent rubella vaccine is no longer available in the United States.
Recommendations for use of rubella-containing vaccines
For prevention of rubella, measles, mumps, rubella (MMR) vaccine is recommended for persons
aged ≥12 months.
Two doses of MMR vaccine are recommended routinely for children with the first dose at
age 12 through 15 months and the second dose at age 4 through 6 years. Because two doses of
combined measles-mumps-rubella (MMR) vaccine are recommended in the current schedule
for measles and mumps vaccination, most children and adolescents now receive two doses of
MMRV vaccine can be used in place of MMR vaccine to implement the two-dose
recommendation for children aged 12 months to 12 years.
Adults born during or after 1957, including those who may be at increased risk for rubella
exposure or transmission, should receive at least one dose of rubella-containing vaccine. These
persons include students attending colleges or other post high school educational institutions,
healthcare personnel, international travelers, and nonpregnant women of childbearing age.
Healthcare providers should routinely assess women of childbearing age for presumptive
evidence of rubella immunity (see below) and vaccinate those who lack acceptable evidence of
immunity and who are not pregnant. Pregnant women who do not have acceptable evidence of
rubella immunity should be vaccinated immediately postpartum.
For unvaccinated healthcare personnel born before 1957 who lack laboratory evidence of
rubella immunity or laboratory confirmation of disease, healthcare facilities should consider
vaccinating personnel with one dose of MMR vaccine.
Presumptive Evidence of Rubella Immunity
Persons who have written documentation of adequate vaccination with at least one dose of live
rubella virus-containing vaccine on or after age 12 months, laboratory evidence of rubella
immunity, laboratory confirmation of disease, or were born before 1957 (except for women
who could become pregnant) have acceptable presumptive evidence of rubella immunity. Birth before 1957 is not acceptable evidence of rubella immunity for women who could become
pregnant. Persons who do not have acceptable presumptive evidence of rubella immunity should
receive one dose of MMR vaccine.
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Case definition for case classification
The following case definition for rubella has been approved by the Council of State and
Territorial Epidemiologists (CSTE) in 2012.
Suspected: Any generalized rash illness of acute onset that does not meet the criteria for
probable or confirmed rubella or any other illness.
Probable: In the absence of a more likely diagnosis, an illness characterized by all of the
- acute onset of generalized maculopapular rash; and
- temperature greater than 99.0° F or 37.2° C, if measured; and
- arthralgia, arthritis, lymphadenopathy, or conjunctivitis; and
- lack of epidemiologic linkage to a laboratory-confirmed case of rubella; and
- noncontributory or no serologic or virologic testing.
Confirmed: A case with or without symptoms who has laboratory evidence of rubella infection
confirmed by one or more of the following:
- isolation of rubella virus; or
- detection of rubella-virus specific nucleic acid by polymerase chain reaction; or
- significant rise between acute-and convalescent-phase titers in serum rubella immunoglobulin
G antibody level by any standard serologic assay; or
- positive serologic test for rubella immunoglobulin M (IgM) antibody*,†
An illness characterized by all of the following:
- acute onset of generalized maculopapular rash; and
- temperature greater than 99.0° F or 37.2° C; and
- arthralgia, arthritis, lymphadenopathy, or conjunctivitis; and
- epidemiologic linkage to a laboratory-confirmed case of rubella.
Epidemiologic classification of internationally-imported and U.S.-acquired
Internationally imported case: An internationally imported case is defined as a case in which
rubella results from exposure to rubella virus outside the United States as evidenced by at least
some of the exposure period (12-23 days before rash onset) occurring outside the United States
and the onset of rash within 23 days of entering the United States and no known exposure to
rubella in the United States during that time. All other cases are considered U.S.-acquired cases.
U.S.-acquired case: A U.S.-acquired case is defined as a case in which the patient had not
been outside the United States during the 23 days before rash onset or was known to have been
exposed to rubella within the United States. U.S.-acquired cases are subclassified into four
mutually exclusive groups:
Import-linked case: Any case in a chain of transmission that is epidemiologically linked to an
internationally imported case.
Imported-virus case: A case for which an epidemiologic link to an internationally imported
case was not identified but for which viral genetic evidence indicates an imported rubella
genotype, i.e., a genotype that is not occurring within the United States in a pattern indicative
of endemic transmission. An endemic genotype is the genotype of any rubella virus that occurs
in an endemic chain of transmission (i.e., ≥12 months). Any genotype that is found repeatedly
in U.S.-acquired cases should be thoroughly investigated as a potential endemic genotype,
especially if the cases are closely related in time or location.
Endemic case: A case for which epidemiological or virological evidence indicates an endemic
chain of transmission. Endemic transmission is defined as a chain of rubella virus transmission
continuous for ≥12 months within the United States.
Unknown source case: A case for which an epidemiological or virological link to importation
or to endemic transmission within the United States cannot be established after a thorough
investigation. These cases must be carefully assessed epidemiologically to assure that they
do not represent a sustained U.S.-acquired chain of transmission or an endemic chain of
transmission within the United States.
Note: Internationally imported, import-linked, and imported-virus cases are considered
collectively to be import-associated cases.
States may also choose to classify cases as "out-of-state-imported" when imported from another
state in the United States. For national reporting, however, cases will be classified as either
internationally imported or U.S.-acquired.
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Clinical diagnosis of rubella is unreliable, therefore, cases must be laboratory confirmed.
Virus detection and serologic testing can be used to confirm acute or recent rubella infection.
Serologic tests can also be used to screen for rubella immunity. For additional information
on laboratory testing for the surveillance of vaccine-preventable diseases, see Chapter 22,
"Laboratory Support for Surveillance of Vaccine-Preventable Diseases."
Virus detection (real-time RT-PCR, RT-PCR)
Rubella virus can be detected from nasal, throat, urine, blood, and cerebrospinal fluid
specimens from persons with rubella (see Appendix 15[2 pages]). The best results come from throat
swabs. Cerebrospinal fluid specimens should be reserved for persons with suspected rubella
encephalitis. Efforts should be made to obtain clinical specimens for virus detection from all
case-patients at the time of the initial investigation. Virus may be detected from 1 week before
to 2 weeks after rash onset. However, maximum viral shedding occurs up to day 4 after rash
Real-time RT-PCR and RT-PCR can be used to detect rubella virus and has been extensively
evaluated for its usefulness in detecting rubella virus in clinical specimens.[17, 18] Clinical
specimens obtained for virus detection and sent to CDC are routinely screened by these
Molecular typing is recommended because it provides important epidemiologic information
to track the epidemiology of rubella in the United States now that rubella virus no longer
continuously circulates in this country. By comparing virus sequences obtained from new
case-patients with other virus sequences, the origin of particular virus types in this country
can be tracked. Furthermore, this information may help in documenting the maintenance
of the elimination of endemic transmission. In addition, genotyping methods are available to
distinguish wild-type rubella virus from vaccine virus.
The serologic tests available for laboratory confirmation of rubella infections and immunity
vary among laboratories. The State health department can provide guidance on available
laboratory services and preferred tests. Enzyme immunoassays (EIA) are the most commonly used and widely available diagnostic test for rubella IgG and IgM antibodies and are sensitive
and relatively easy to perform. EIA is the preferred testing method for IgM, using the capture
technique, although indirect assays are also acceptable.
Latex agglutination (LA) tests appear to be sensitive and specific for screening when performed
by experienced laboratory personnel. Other tests in limited use to detect rubella-specific IgM
include hemagglutination inhibition (HI) and immunofluorescent antibody (IFA) assay.
Detection of IgM antibody
Rubella-specific IgM can usually be detected 4-30 days after onset of illness, and often for
longer. Sera should be collected as early as possible after onset of illness. However, IgM
antibodies may not be detectable before day 5 after rash onset. In case of a rubella IgM-negative
result in specimens taken before day 5, serologic testing should be repeated on a specimen
collected after day 5.
Because rubella incidence is low, a high proportion of IgM-positive tests will likely be false
positive. False-positive serum rubella IgM tests may occur due to the presence of rheumatoid
factors (indicating rheumatologic disease) or cross-reacting IgM, or infection with other
viruses.[20,21] Avidity testing (see below) and detection of wild-type rubella virus can be used to
resolve uncertainties in the serologic evaluation of suspected cases.
Particular care should be taken when rubella IgM is detected in a pregnant woman with no
history of illness or contact with a rubella-like illness. Although this is not recommended,
many pregnant women with no known exposure to rubella are tested for rubella IgM as part
of their prenatal care. If rubella test results are IgM-positive for persons who have no or low
risk of exposure to rubella, additional laboratory evaluation should be conducted. Laboratory
evaluation is similar to that described in the IgM-positive section of Figure 1.
Figure 1. Algorithm for serologic evaluation of pregnant women exposed to rubella
Detection of IgG antibody (significant rise or avidity) for diagnostic testing
To detect a significant rise in rubella-specific IgG concentration, the first serum should be
obtained as soon as possible after onset of illness and the second serum sample should be
collected about 7-21 days after the first specimen. In most rubella cases, rubella IgG is
detectable by 8 days after rash onset. Tests for IgG antibody should be conducted on both
acute-and convalescent-phase specimens at the same time with the same test.
Assays for IgG avidity are useful to distinguish the difference between recent and past rubella
infections. Low avidity is associated with recent primary rubella infection, whereas high avidity
is associated with past infection or reinfection. Avidity tests are not routine tests and should be
performed in reference laboratories. A number of avidity assays have been described.[23, 24]
Detection of IgG antibody to screen for rubella immunity
A single serologic IgG test may be used to determine the rubella immune status of persons
whose history of rubella disease or vaccination is unknown. The presence of serum IgG rubella-specific
antibodies indicates immunity to rubella.
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Importance of Rubella Surveillance
Surveillance data are needed to identify and control rubella virus introductions to prevent
congenital rubella infections and consequent CRS as well as monitor maintenance of disease
Promote awareness of rubella and CRS in the United States
Although only 62 cases of rubella and 4 cases of CRS were reported between 2005 and 2011,
it is likely that not all cases were identified. Efforts should continue to promote physicians’
awareness of the possibility of rubella and CRS. When evaluating patients with suspected
measles who have negative serologic tests for acute measles infection (i.e., negative serum
measles IgM), officials may request additional testing for rubella.
Promote awareness of groups at high risk for rubella infection and CRS birth
Rubella-containing vaccines are not administered routinely in many countries, and in others,
rubella-containing vaccine was only recently added to the childhood immunization schedule.
Thus, many persons born outside the United States or who received childhood immunizations
in other countries may have never received rubella vaccine. Healthcare providers should have
a heightened index of suspicion for rubella and CRS births in persons from countries without a
history of routine rubella vaccination programs or with recently implemented programs.
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Each state and territory has regulations or laws governing the reporting of diseases and
conditions of public health importance. These regulations and laws list the diseases to be
reported and describe those persons or groups who are responsible for reporting, such as
healthcare providers, hospitals, laboratories, schools, daycare and childcare facilities, and other
institutions. Persons reporting should contact the State health department for state-specific
Prompt identification and reporting of suspected, probable, or confirmed cases of rubella is
important to avoid exposure of susceptible pregnant women. Rapid case identification and
investigations are also important so that control measures can be initiated to prevent spread of
Reports of rubella are designated by CSTE as "immediately notifable, urgent" which requires
notification of the CDC within 24 hours. All cases of rubella should be reported by the State
health department to CDC/NCIRD/DVD/Epidemiology Branch (404-639-8253) and to the
National Notifiable Diseases Surveillance System (NNDSS). Reporting should not be delayed
because of incomplete information or laboratory confirmation; following completion of case
investigations, data previously submitted to NNDSS should be updated with the available new
The following data elements are epidemiologically important and should be collected in the
course of a case investigation. Additional information may be collected at the direction of the
state or local health department.
- Demographic information
- Country of birth
- Length of time in United States
- Reporting Source
- Earliest date reported
- Date of illness onset
- Date of rash onset
- Duration of rash
- Arthralgia or arthritis
- Hospitalizations and duration of stay
- Outcome (patient survived or died)
- If female, pregnancy history
- If pregnant, pregnancy status
- Number of weeks gestation at onset of illness
- Prior evidence, date of serologic immunity, or both
- Prior diagnosis and date of rubella
- Number and dates of previous pregnancies and location (e.g., state or country) of these pregnancies
- Pregnancy outcome, when available (e.g., normal infant, termination, CRS)
- Virus isolation
- PCR results
- Vaccine Information
- Number of doses of rubella-containing vaccine received
- Dates of vaccination
- Types of vaccine (rubella, MMR, MMRV)
- If not vaccinated, reason
- Transmission setting (infection acquired at home, healthcare setting, in daycare, school, or workplace)
- Relationship to outbreak (Is case part of an outbreak or is it sporadic?)
- Source of exposure
- Travel history (countries, dates)
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Case Investigation, Contact Investigations, and Outbreak Control
Consider a single case of rubella as a potential outbreak
Because rubella has been eliminated in the United States, health agencies should consider one
case a potential outbreak. Rubella is an infectious disease for which up to 50% of cases are
asymptomatic, and investigation of an apparently isolated case could reveal additional cases.
Confirm a diagnosis of rubella
Clinical diagnosis of rubella is unreliable, therefore, cases must be laboratory confirmed,
especially if the reported cases are not epidemiologically linked to a laboratory-confirmed case.
Laboratory testing should be conducted for all suspected cases of rubella.
Laboratory confirmation of rubella infection may be difficult in pregnant women with unknown
immune status who experience a rash illness or who are exposed to rubella. A serum specimen
should be obtained as soon as possible.
Conduct case investigations and vaccinate contacts without evidence of immunity
Aggressive response to rubella cases may interrupt disease transmission and will increase
vaccination coverage among persons who might otherwise not be protected. The main strategies
are to define populations at risk, to ensure that persons without evidence of immunity are
rapidly vaccinated (or excluded from exposure if a contraindication to vaccination exists) and to
maintain active surveillance to permit modification of control measures if the situation changes.
The goal of rubella case investigation is to identify rubella infections, particularly infection
in pregnant women, and to prevent exposure of susceptible pregnant women, and thereby
prevent cases of CRS. It is essential that exposed pregnant women be identified, evaluated, and
counseled (see section on laboratory evaluation of exposed pregnant women). The Rubella
Surveillance Worksheet[2 pages] may be used as a guideline in conducting a case
investigation. Case investigation and identification of contacts should be conducted for all
suspected cases of rubella.
Cases of rubella occurring within 10 days of rubella vaccination should be investigated, and
specimens should be obtained for virus isolation to determine if the rash is attributable to
vaccine virus or wild virus. Cases in persons vaccinated within 7 days of a rubella-like illness
who are IgM-positive should be classified as confirmed cases of wild-type rubella if they are
epidemiologically linked to a laboratory-confirmed case.
Any direct contact with a patient with rubella during the infectious period (7 days before to
7 days after rash onset) is defined as an exposure. Every effort should be made to identify all
pregnant women who might have been exposed to a patient and evaluate them serologically for
rubella-specific IgM and IgG antibodies. All women of childbearing age who are contacts of a
person with a suspected or confirmed case should have their pregnancy status determined. If
a pregnant woman is infected with rubella, immediate medical consultation is necessary. If a
pregnant woman lacks laboratory evidence of rubella immunity, precautions should be taken to
prevent any type of exposure to persons infected with rubella; these precautions may include
ensuring rubella immunity of household contacts and isolating women from settings where
rubella virus has been identified.
Identify the source of infection
Efforts should be made to identify the source of infection for every confirmed case of rubella.
Case-patients or their caregivers should be asked about contact with other known cases. Since
many rubella cases are asymptomatic, identification of a source will not always be possible.
When no history of contact with a known case can be elicited, opportunities for exposure to
unidentified cases in populations at high risk (e.g., foreign-born persons) should be sought.
Investigating sources of exposure should be directed to the place and time period in which
transmission would have occurred.
Obtain specimens for virus detection
Efforts should be made to obtain clinical specimens (throat swabs and urine) for virus
detection from all case-patients (or from at least some patients in each outbreak) at the time of
the initial investigation.
See Appendix 15[2 pages] for the procedure to follow in collection of specimens.
Conduct laboratory evaluation of exposed pregnant women
Exposed pregnant women should be tested for the presence of rubella IgG and IgM antibodies
as outlined in Figure 1 regardless of symptom history. A blood specimen should be taken as
soon as possible and tested for rubella IgG and IgM antibody and stored for possible retesting.
- If the IgM is positive regardless of the IgG response, this may indicate recent or acute
infection or a false-positive IgM. The next step is testing with a serum collected in 5-10
days. Testing will include IgM, IgG, and avidity (if IgG is present). If the repeat IgM is
positive with low avidity or a significant rise in IgG titers, acute infection is likely. If the
IgM and IgG are positive and the avidity is high, this may indicate either a false-positive
result or a reinfection. Reinfection with rubella occurs more frequently with vaccine-induced
immunity than with natural disease; however, the risk of fetal infection is extremely low.
- If the IgM is negative and the IgG is positive at the time of exposure (the first specimen), this
most likely indicates immunity.
- If the IgM and IgG are negative in the first specimen, a second specimen should be taken
3-4 weeks after exposure and tested concurrently with the first specimen for IgM, IgG, and
avidity (if IgG is present). A negative IgG response with the first specimen and a positive
IgG response with the second specimen indicate that infection has occurred. If the IgG
and IgM remain negative and there are no additional exposures, an IgG-negative result at 4
weeks indicates that infection has not occurred. As long as the exposure to rubella continues,
it is important to continue testing for IgG and IgM responses.
Report the pregnancy outcome for women diagnosed with rubella during pregnancy
All pregnant women infected with rubella during pregnancy should be followed to document
the pregnancy outcome (e.g., normal infant, termination, CRS). Outcomes that are documented
should be reported to CDC.
Conduct enhanced surveillance
Active surveillance for rubella should be maintained for at least two incubation periods (46
days) following rash onset of the last case. Two incubation periods allow for the identification
of transmission from a subclinical case. In addition, surveillance for CRS should be
implemented when confirmed or probable rubella cases are documented in a setting where
pregnant women might have been exposed. Women who contract rubella infection while
pregnant should be monitored for birth outcome, and appropriate testing should be performed
on the infant after birth.
Implement control measures
Control measures should be implemented as soon as at least one case of rubella is confirmed
in a community. In settings where pregnant women may be exposed, control measures
should begin as soon as rubella is suspected and should not be postponed until laboratory confirmation. Patients with rubella should be isolated for 7 days after rash onset. All persons at
risk who cannot readily provide acceptable evidence of rubella immunity should be considered
susceptible and should be vaccinated.
In schools and other educational institutions, exclusion of persons without acceptable evidence
of rubella immunity may limit disease transmission and may help to rapidly raise the vaccination
level in the target population. All persons who have been exempted from rubella vaccination for
medical, religious, or other reasons also should be excluded from attendance. Exclusion should
continue until 23 days after the onset of rash of the last reported case-patient in the outbreak
setting. Unvaccinated persons who receive MMR vaccine as part of the outbreak control may be
immediately readmitted to school provided all persons without documentation of immunity have
In healthcare settings, exposed healthcare personnel without adequate presumptive evidence
of immunity should be excluded from duty beginning 7 days after exposure to rubella and
continuing through either 23 days after last exposure or 7 days after rash appears. Exposed
healthcare personnel who are vaccinated as part of control measures should be excluded
from direct patient care for 23 days after the last exposure to rubella because effectiveness
of postexposure vaccination in preventing rubella infection has not been shown. In addition,
because birth before 1957 does not guarantee rubella immunity, during outbreaks in healthcare
settings, healthcare facilities should recommend one dose of MMR vaccine for unvaccinated
personnel born before 1957 who lack laboratory evidence of rubella immunity or laboratory
confirmation of infection or disease.
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