Rubella Virus

Diagnosis

Indications for Testing

• Prenatal screening for evidence of immunity (presence of maternal antibodies)
• Typical symptoms  in unvaccinated patient – rash, fever, headache, pink eye, malaise, lymphadenopathy, cough, rhinitis

Criteria for Diagnosis

• World Health Organization (WHO) case definition for congenital rubella syndrome (CRS)
  • Suspected case – any infant <1 year in whom a health worker suspects CRS
    • Infant presents with heart disease and/or suspicion of deafness and/or ≥1 of the following eye signs – white pupil (cataract), diminished vision, pendular movement of the eyes (nystagmus), squint, smaller eye ball (microphthalmos), or larger eye ball (congenital glaucoma)
    • Infant’s mother has a history of suspected or confirmed rubella during pregnancy, even when the infant shows no signs of CRS
  • Clinically confirmed case – an infant in whom a qualified physician detects 2 of the complications in section A or 1 from section A and 1 from section B
    • Section A – cataracts, congenital glaucoma, congenital heart disease, hearing impairment, pigmentary retinopathy
    • Section B – purpura, splenomegaly, microcephaly, developmental delay, meningoencephalitis, radiolucent bone disease, jaundice with onset within 24 hours of birth
  • Laboratory-confirmed case – infant with rubella IgM antibody who has clinically confirmed CRS
  • Congenital rubella infection – infant with rubella IgM antibody who does not have clinically confirmed CRS
• Rubella/German measles case definition (CDC, 2013)

Laboratory Testing

• CDC manual for surveillance of rubella​
• Rubella laboratory testing (CDC, 2016)
• Serology
  • Appearance of clinical symptoms is associated with appearance of both IgG and IgM antibodies
    • IgM antibodies
      • Detectable a few days after onset of symptoms
      • Peak 7-10 days later
    • May consider fetal IgM serology if fetal infection suspected
  • Prenatal screening – test women before pregnancy to confirm presence of IgG antibodies indicating previous infection and immunity
  • Serologic testing for rubella and CRS in low prevalence setting
• Polymerase chain reaction (PCR)
  • Usually throat or urine samples
  • Amniotic fluid when fetus is at least 2 weeks of age to identify fetal infection
• Congenital – see CDC testing recommendations

Differential Diagnosis

• Measles virus
• Parvovirus B19
• Human herpesvirus 6 (HHV6)
• West Nile virus
• Enterovirus
• Dengue fever virus

Background

Epidemiology

• Incidence – <10 cases per year in the U.S. (all contracted outside the country since 2012)
  • CRS – <2/100,000 births
• Age – usually children who are unvaccinated
• Transmission
  • Via droplets, aerosol particles – close contact required

Organism

• Rubella, an RNA virus, is a member of the Togaviridae family
• Virus infects cells in the upper respiratory tract and replicates in the lymphoid system; virus then spreads to other organs

Clinical Presentation

• Transmission can occur up to 7 days before and 7 days after onset of rash
• In children and adults, infection usually results in mild, exanthematous disease
  • Adults are more likely to experience prodromal phase – fever, headache, sore throat, cough, conjunctivitis
  • Rare complications – arthralgias and arthritis, thrombocytopenia, hemorrhage, and encephalitis
• In pregnant women, particularly during first trimester, infection can result in fetal death or congenital abnormalities
  • Disease can be asymptomatic
  • Congenital abnormalities include
    • Ophthalmologic – cataracts, glaucoma, iris hypoplasia, retinopathy
    • Otorhinolaryngologic – sensorineural or central deafness
    • Cardiac – patent ductus arteriosus, pulmonary stenosis, pulmonary arterial hypoplasias, myocarditis
    • Central nervous system – developmental delay with central nervous system calcifications, microcephaly
    • Dermatologic – petechia, purpura
  • 10-20% of newborns infected in utero will die during the first year of life
  • Because complications in utero are so severe, diagnosis during first trimester may result in decision to terminate pregnancy
  • Delayed manifestations
    • Insulin-dependent diabetes mellitus
    • Panencephalitis (rare)
    • Thyroid dysfunction
    • Behavioral disorders

Prevention

• Vaccination programs have resulted in marked decrease in infections
  • Estimated >95% of children in U.S. are vaccinated (recommended between ages 12-15 months)
  • Vaccine is live, attenuated virus and contraindicated in pregnant women