Description

• A generally self-limited viral infection of children and adults, characterized by a mild, maculopapular rash, lymphadenopathy, and slight fever. Complications in normal, immunocompetent populations are rare. Nonimmune women infected with rubella while pregnant may have devastating fetal effects.
• As many as 50% of all rubella infections are asymptomatic (1),(2).
• 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 most commonly manifests as sensorineural deafness, eye abnormalities, and/or congenital heart disease.
• Exposure during the 1st trimester presents highest risk for development of CRS (2).
• Screening pregnant women for rubella immunity and vaccinating nonimmune women is the most effective strategy to prevent CRS (1),(2),(3).
• Although no case of vaccine-associated CRS has been reported, women should not become pregnant for at least 28 days after vaccination because vaccine-type virus can cross the placenta (4).
• Polymerase chain reaction (PCR) can be used for rapid fetal diagnosis by detection of viral RNA from multiple samples such as amniotic fluid or fetal blood (5).

Epidemiology

• RNA togavirus of genus Rubivirus (1)
• Multiple genotypes have been identified without significant antigenic differences (2),(3).
• A live attenuated vaccine has been available in the United States since 1969. Primary use is to prevent CRS.
• Since 2004, all U.S. cases of rubella have been imported; most cases are inadequately immune travelers.
• Average incubation: 17 days; ranges 12 to 23 days (1).
• Infectious period between 7 days before and 7 days after rash appears
• Transmitted primarily via respiratory droplets
• Most common in late winter and early spring (2)
• Humans are only natural hosts (5).

Incidence

• U.S. incidence: <1/10,000,000 since 2001
• Declared eliminated (no endemic transmission for 12+ months) from the United States in 2004. However, primarily due to disease in international travelers, vaccine avoidance, and lack of routine pediatric care in migrant populations, cases are still reported annually.
• From 2005 to 2015, only 94 cases of rubella and 8 cases of CRS were reported in the United States.
• Still occurs in developing countries with 100,000 cases of CRS reported annually worldwide (1)

Etiology and Pathophysiology

• Virus invades the respiratory epithelium, replicates in nasopharynx and regional lymph nodes, and spreads hematogenously. Infected patients start shedding virus from the nasopharynx 7 days before the rash appears. Shedding lasts 7 or more days after onset of the rash (2).
• Disease typically progresses from a prodromal stage (1 to 5 days) to lymphadenopathy (5 to 10 days) to an exanthematous, maculopapular rash. Petechiae on the soft palate (Forchheimer spots) may precede or accompany the rash. Rash starts on the face and spreads outward to the trunk and extremities, sparing the palms and soles (14 to 17 days after onset of prodromal symptoms). The rash typically lasts an average of 3 days (1),(2).
• Rubella first described by German scientists in the early 1800s as a variant of measles or scarlet fever (2).
• 1964 to 1965: epidemic 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)

Genetics

• Polymorphisms in HLA genes are associated with different rubella antibody levels and with vaccine side effects.
• HLA-DPB1 homozygosity has been associated with higher levels of rubella antibody.
• Arthritis-like joint vaccination side effect has been weakly connected with HLA-DR (3).

Risk Factors

Inadequate immunization, inadequate immunity after prior vaccination, immunodeficiency states, immunosuppressive therapy, crowded living/working conditions, international travel (1),(2)

General Prevention

• Vaccination is the most effective preventive strategy.
• Available combined with mumps, measles, rubella (MMR) or with varicella (MMR-V). Isolated rubella vaccine is not available in the United States.
  • Adults: 1- or 2-dose MMR vaccine schedule is recommended for those born after 1957. When 2 doses are used, each must be ≥28 days apart.
  • Pediatric: A 2-dose MMR vaccine schedule is recommended with the first dose given at ages 12 to 15 months; second dose recommended at 4 to 6 years of age.
  • MMR-V is approved for use in children aged 12 months to 12 years and is the vaccine of choice for the second dose and the first dose at ≥48 months old.
  • Special pediatric cases: In special circumstances (e.g., upcoming international travel), the second dose may be given prior to 4 years of age but no sooner than 28 days since the initial dose.
  • Children 6 to 11 months of age may also receive a single dose prior to international travel but should be revaccinated with a full 2-dose schedule starting at 12 months 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 of infants 6 to 11 months old is recommended.
  • Vaccination 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.
• Contraindications to vaccine: pregnancy, immunodeficiency (except HIV infection without significant immunosuppression), first-degree relative with congenital or genetic immunodeficiency, recent IVIG or blood administration (wait 3 to 11 months to vaccinate; based on product received), 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 (2),(4).
• During outbreaks, serologic screening before vaccination is not recommended because rapid mass vaccination is needed to stop disease spread.
• MMR vaccine is not associated with autism.
• 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.
• Routine rubella antibody (IgG) screening is recommended during pregnancy (4).