> Table of Contents > Measles, German (Rubella)
Measles, German (Rubella)
Mark B. Stephens, MD, MS, FAAFP, CAPT, MC, USN
image BASICS
DESCRIPTION
  • A mild, generally self-limited exanthematous viral infection of children and adults, with rare complications. Nonimmune women who become infected with rubella while pregnant may have devastating fetal effects. Up to 50% of rubella infections may be asymptomatic (1,2)[A].
  • System(s) affected: hematologic; nervous; pulmonary; exocrine; ophthalmologic; skeletal
  • Synonym(s): German measles; 3-day measles
Pregnancy Considerations
  • Pregnancy-associated rubella infection may lead to congenital rubella syndrome (CRS) with potentially devastating fetal outcomes.
  • CRS is present in up to 90% of fetuses exposed during the 1st trimester (2)[A].
  • Screening pregnant women for rubella immunity and vaccinating nonimmune women is the most effective means to prevent CRS (2)[A].
  • Although no case of vaccine-associated CRS has been reported, women should not become pregnant for at least 28 days after vaccination because the vaccine-type virus can cross the placenta (2)[A].
  • Polymerase chain reaction (PCR) detection of viral RNA in amniotic fluid and fetal blood sampling allow for rapid diagnosis of fetal infection after 15 weeks' gestation (3)[B].
EPIDEMIOLOGY
  • 50- to 70-nm RNA togavirus of genus Rubivirus (1)[A]
  • 13 genotypes have been identified (4)[A].
  • Live attenuated vaccine available in United States. since 1969—primarily to prevent CRS
  • Since 2004, all cases of rubella in United States have been imported, typically in travelers with inadequate immunity (1)[A].
  • Average incubation: 14 days; range 12 to 23 days
  • Infectious period between 7 days before and 5 to 7 days after rash onset
  • Transmitted by respiratory droplets
  • Most common in late winter and early spring
  • Humans are only natural hosts (1)[A].
Incidence
  • U.S. incidence: <10/100,000 since 2001
  • From 2004 to 2012, six cases of CRS reported in United States (5).
  • Still occurs worldwide in developing countries: 100,000 cases of CRS annually worldwide
ETIOLOGY AND PATHOPHYSIOLOGY
  • Virus invades the respiratory epithelium, replicates in nasopharynx and regional lymph nodes, and spreads hematogenously. Infected patients shed virus from the nasopharynx 3 to 8 days after inoculation. Shedding lasts 7 or more days after onset of rash.
  • Disease progresses from a prodromal stage (1 to 5 days) to lymphadenopathy (5 to 10 days) and finally to an exanthematous, pruritic, and maculopapular rash. Rash starts on the face and spreads to the trunk and extremities, sparing the palms and soles (14 to 17 days after onset of initial symptoms).
  • Rubella first described by German scientists in the early 1800's as a variant of measles or scarlet fever
  • 1962 to 1965: global pandemic resulting in an estimated 12.5 million cases in the United States, with 2,000 cases of encephalitis; 11,250 cases of therapeutic or spontaneous abortions; 2,100 neonatal deaths; and 20,000 infants born with CRS (1)[A]
Genetics
Children with CRS and children with type 1 diabetes share a high frequency of HLA-DR3 histocompatibility Ag and a high prevalence of islet cell Ab.
RISK FACTORS
Inadequate immunization, inadequate immunity after prior vaccination, immunodeficiency states, immunosuppressive therapy, crowded living/working conditions, international travel (1)[A]
GENERAL PREVENTION
  • Vaccination is the most effective preventive strategy.
  • Available combined with measles and mumps (MMR) or with varicella (MMR-V). Single rubella vaccine is not available in the United States.
    • A 2-dose schedule combined MMR vaccine recommended for those born after 1957. The 1st dose recommended at ages 12 to 15 months; 2nd dose recommended either at 4 to 6 years or at 11 to 12 years of age. Children with HIV should receive MMR vaccine at 12 months of age if no contraindications exist. In the event of an outbreak, immediate vaccination for infants 6 to 11 months old is recommended (2)[A].
    • Vaccine is recommended for nonimmune people in the following groups: prepubertal boys and girls, all women of reproductive age, college students, daycare personnel, health care workers, and military personnel.
  • Contraindicated: pregnancy, immunodeficiency (except HIV infection), within 3 months of IVIG or blood administration, severe febrile illness, or hypersensitivity to vaccine components. Patients who receive rubella vaccine do not transmit rubella to others, although the virus can be isolated from the pharynx. Breastfeeding is not a contraindication to vaccination (1)[A].
  • During outbreaks, serologic screening before vaccination is NOT recommended because rapid mass vaccination is necessary to stop disease spread (2)[A].
  • The MMR vaccine is not associated with autism (6)[A],(7)[B].
  • Children who receive the MMR-V vaccine have a 2-fold increase in risk of febrile seizures compared with those who receive MMR and varicella vaccines separately (7)[B].
  • Routine rubella antibody screening is recommended during pregnancy by the CDC and ACOG (6)[A].
image DIAGNOSIS
Council of State and Territorial Epidemiologists (CSTE) Case Definition Classifications of Rubella (1)[A]
  • Clinical case definition
    • Acute onset of pink, coalescent macules on the face spreading to the trunk and extremities, becoming discrete macules then fading in previously affected areas
    • Temperature >99°F (37.2°C; if measured)
    • Arthralgia or arthritis, lymphadenopathy, or conjunctivitis
  • Laboratory criteria for diagnosis
    • Isolation of virus from throat or nasopharynx, serum, CSF, urine, or cataracts (postmortem)
    • 4-fold rise in acute- and convalescent-phase titers of serum IgG Ab
    • Positive serologic test for IgM Ab
    • PCR positive for virus
PHYSICAL EXAM
  • Postnatal rubella: low-grade fever, lymphadenopathy (posterior auricular, occipital, posterior cervical), exanthem (mild, pink, discrete 1- to 4-mm maculopapular rash), soft palate petechiae (Forchheimer sign) (20%) (1)[A]
  • CRS: microcephaly, large anterior fontanelle, sensorineural hearing loss (58%), cataracts, glaucoma, microphthalmia, pigmentary retinopathy, purpuric (“blueberry muffin”) skin lesions, murmur (50%) consistent with patent ductus arteriosus (PDA), hepatosplenomegaly, jaundice, cryptorchidism, inguinal hernia, radiolucent bone disease (2)[A]
DIFFERENTIAL DIAGNOSIS
  • Postnatal rubella
    • Measles virus (rubeola)
    • Scarlet fever (strep A)
    • Infectious mononucleosis
    • Erythema infectiosum (parvovirus B19)
    • Roseola infantum (i.e., exanthem subitum)
    • Toxoplasmosis
    • Drug eruptions
    • Other exanthematous enteroviral infections
  • Congenital rubella
    • Measles
    • Parvovirus B19
    • Human herpesvirus 6
    • Other exanthematous entero- or arboviruses
DIAGNOSTIC TESTS & INTERPRETATION
  • Because 50% of cases are subclinical, laboratory testing is best to confirm the diagnosis (1,2)[A].
  • Detection of wild-type virus is gold standard (1)[A].
  • Enzyme immunoassay (EIA): preferred testing for IgM antibodies, which may not be detectable before 5 days after the onset of rash (1)[A]
  • Hemagglutination inhibition (HAI) test: A 4-fold increase of IgG Ab levels from acute to convalescent phase is diagnostic for recent infection (1)[A].
  • Latex agglutination (LA) test: sensitive and specific but dependent on experience of lab personnel (1)[A]
  • P.645

  • Immunofluorescent antibody (IFA) assay: used for detection of viral IgG and IgM Ab (1)[A]
  • Avidity test: not routinely used. Should only be performed in reference labs. Used to distinguish between recent and past infections (1)[A]
  • Serum collection should be performed within 7 to 10 days after illness onset. When testing for IgM, repeat collection may be necessary if the sample was taken before day 5. When testing for seroconversion, a 2nd IgG sample should be collected 2 to 3 weeks after the first (acute to convalescent phase). In most cases, IgG is detectable 8 days after rash onset (1)[A].
  • Virus may be isolated from 1 week prior to 2 weeks after the onset of rash. Maximal viral shedding occurs up to day 4 after rash onset. Best results are from throat swabs (1)[A].
  • Epidemiologically, viral genotyping by reverse transcription (RT)-PCR helps determine the country of origin. Throat swabs should be collected 4 days after the rash onset and sent to the CDC (1)[A].
  • Viral cultures of CSF are reserved for suspected cases of CRS or rubella encephalitis (1)[A].
  • If a pregnant female is exposed, amniotic fluid PCR or fetal blood sampling may be done at 15 weeks' gestation for viral detection. Placental biopsy (less common) may be done at 12 weeks' gestation. If positive, offer genetic counseling (1)[A].
  • As the incidence of rubella decreases, the positive predictive value (PPV) of IgM results decreases. False-positive findings occur in patients with parvovirus B19, mononucleosis, and positive rheumatoid factor (1)[A].
  • After reexposure, a person with a low level of Ab from past infection or prior vaccination may experience an acute, small rise in Ab levels. This is not associated with a high incidence of contagious to others or of fetal risk (1)[A].
Follow-Up Tests & Special Considerations
  • Reporting: state-dependent. Samples should be sent to the CDC for genotyping. Cases of CRS are reported to the National Congenital Rubella Syndrome Registry (1,2)[A].
  • Infants with CRS may shed virus up to 1 year. Observe contact isolation during all hospitalizations until child turns 1 year old (unless child has two negative throat cultures and urine specimens a month apart after 3 months of age) (2)[A].
image TREATMENT
  • Supportive for mild cases
  • Isolate patients for 5 to 7 days after rash onset.
  • Postnatal rubella: mild and self-limited; treat symptomatically. Hospitalize for complications: idiopathic thrombocytopenic purpura (ITP) or encephalitis (1)[A].
  • CRS: supportive care unless neurologic or hemorrhagic complications develop; phototherapy may be indicated for jaundice; multidisciplinary management of long-term complications (2)[A]
MEDICATION
No specific therapy available for mild cases.
First Line
  • Age- and dose-appropriate antipyretics
  • NSAIDs can be used for arthritis and arthralgias in adults and infants age >6 months.
  • IVIG can be given for severe thrombocytopenia— most cases, however, are self-limited.
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
  • Individuals immune to rubella through natural infection or vaccine may be reinfected when reexposed; such infection is usually asymptomatic and detectable only by serology. Those who have received the vaccine have lower measurable IgG levels than those who had the natural disease.
  • In CRS, it is important to detect auditory and visual impairment early (2)[A].
  • 2/3 of internationally adopted children have no written record of immunizations (4)[A].
PATIENT EDUCATION
http://www.cdc.gov/rubella/
PROGNOSIS
  • Postnatal rubella: Complete recovery is typical.
  • CRS
    • Varied and unpredictable spectrum, ranging from stillbirth to normal infancy/childhood (1,2)[A]
    • Detectable levels of IgG persist for years and then may decline (does not drop at the expected 2-fold dilution/month). By age 5 years, 20% have no detectable antibody (2)[A].
    • IgM may not be detectable until 1 month after birth and may persist for 6 to 12 months (2)[A].
    • Overall mortality (up to 10%) is greatest during first 6 months.
    • 70% of encephalitis cases develop residual neurologic defects, including autistic syndrome.
    • Prognosis is excellent if only minor congenital defects are present.
REFERENCES
1. Centers for Disease Control and Prevention. Chapter 14—rubella. In: McLean H, Redd S, Abernathy E, et al, eds. Manual for the Surveillance of Vaccine-Preventable Diseases. 5th ed. Atlanta, GA: Centers for Disease Control and Prevention; 2014. http://www.cdc.gov/vaccines/pubs/surv-manual/chpt14-rubella.html. Accessed January 21, 2016.
2. Centers for Disease Control and Prevention. Chapter 15—congenital rubella syndrome. In: McLean H, Redd S, Abernathy E, et al, eds. Manual for Surveillance of Vaccine-Preventable Diseases. 5th ed. Atlanta, GA: Centers for Disease Control and Prevention; 2014. http://www.cdc.gov/vaccines/pubs/surv-manual/chpt15-crs.html. Accessed January 21, 2016.
3. Tang JW, Aarons E, Hesketh LM, et al. Prenatal diagnosis of congenital rubella infection in the second trimester of pregnancy. Prenat Diagn. 2003;23(6):509-512.
4. Abernathy ES, Hubschen JM, Muller CP, et al. Status of global virologic surveillance for rubella viruses. J Infect Dis. 2011;204(Suppl 1):S524-S532.
5. Centers for Disease Control and Prevention. Three cases of congenital rubella syndrome in the postelimination era—Maryland, Alabama, and Illinois, 2012. MMWR Morb Mortal Wkly Rep. 2013;62(12):226-229.
6. McLean HQ, Fiebelkorn AP, Temte JL, et al. Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2013;62(RR-04):1-34.
7. Lai J, Fay KE, Bocchini JA. Update on childhood and adolescent immunizations: selected review of US recommendations and literature: part 2. Curr Opin Pediatr. 2011;23(4):470-481.
Additional Reading
&NA;
  • Centers for Disease Control and Prevention. Rubella. In: Atkinson W, Wolfe C, Hamborsky J, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 13th ed. Atlanta, GA: Centers for Disease Control and Prevention; 2012.www.cdc.gov/vaccines/pubs/pinkbook/rubella.html. Accessed January 21, 2016.
  • Mongua-Rodriguez N, Díaz-Ortega JL, García-García L, et al. A systematic review of rubella vaccination strategies implemented in the Americas: impact on the incidence and seroprevalence rates of rubella and congenital rubella syndrome. Vaccine. 2013;31(17):2145-2151.
  • Walling A. Measles, mumps, and rubella in pregnant women. Am Fam Physician. 2006;73(5):907-908.
Codes
&NA;
ICD10
  • B06.9 Rubella without complication
  • B06.00 Rubella with neurological complication, unspecified
  • P35.0 Congenital rubella syndrome
Clinical Pearls
&NA;
  • Rubella is typically a self-limited viral exanthematous infection of children and adults.
  • Nonimmune women who are infected with rubella while pregnant may have devastating fetal effects (CRS).