Counsel of State and Territorial Epidemiologists (CSTE) Case Definition Classifications of Rubella (1):

• Clinical Case Definition:
  • Acute onset of generalized maculopapular rash
  • Temperature >99°F (37.2°C), if measured
  • Arthralgia or arthritis, lymphadenopathy or conjunctivitis
• Laboratory criteria for diagnosis:
  • Isolation of virus from: Throat or nasal swabs, serum, CSF, urine, or cataracts if removed from infected infant
  • 4-fold rise in acute- and convalescent-phase titers of serum IgG Ab
  • Positive serologic test for IgM Ab
  • PCR positive for virus

History

• Most cases of postnatal rubella are due to inadequately immunized travelers returning from endemic areas.
• Rubella can spread quickly among persons residing in close quarters.
• Postnatal rubella: Low-grade fever, sore throat, nausea, anorexia, arthritis, arthralgia, malaise. 50% may be asymptomatic.
• CRS: Parental concerns about hearing or vision impairment, jaundice, or developmental delay
• Deafness could be the only manifestation and not be noticed until second year of life (2).

Physical Exam

• Postnatal rubella: Low-grade fever, lymphadenopathy (postauricular, occipital, posterior cervical), exanthem (mild, pink, discrete 1–4 mm maculopapular), soft palate petechiae (Forchheimer sign) (20%)
• CRS: Microcephaly, large anterior fontanelle, sensorineural hearing loss (58%), cataracts, glaucoma, microphthalmia, pigmentary retinopathy, purpuric (“blueberry muffin”) skin lesions, murmur (50%) consistent with PDA or PPAS, hepatosplenomegaly with jaundice, cryptorchidism, inguinal hernia, radiolucent bone disease

Diagnostic Tests and Interpretation

Lab

• Because 50% of cases are subclinical, laboratory testing is the only way to confirm the diagnosis (1).
• Detection of wild-type virus is considered the gold standard (1).
• Enzyme immunoassay (EIA): Preferred testing for IgM antibodies, which may not be detectable before 5 days after the onset of rash (1)
• Hemagglutination inhibition (HAI) test: Was once the standard. A 4-fold increase of IgG Ab levels from acute to convalescent phase is diagnostic for recent infection (1).
• Latex agglutination (LA) test: Appears to be sensitive and specific, but dependent on experienced lab personnel (1)
• Immunofluorescent antibody (IFA) assay: Used for detection of IgG and IgM Ab to the virus (1)
• Avidity test: Not routine and should be performed in reference labs. Purpose: Distinguish between recent and past infections (1).
• Serum collection should be performed within 7–10 days after the onset of the illness. When testing for IgM, repeat collection may be necessary if the sample was taken before day 5. When testing for seroconversion, a second sample for IgG testing should be collected 2–3 weeks after the first specimen (acute to convalescent phase). In most cases, IgG is detectable 8 days after rash onset (1).
• The virus may be isolated from 1 week prior to 2 weeks after the rash onset. Maximal viral shedding occurs up to day 4 after rash onset. Best results yielded from throat swabs (1).
• Viral genotyping by RT-PCR is performed to help determine the country of origin for epidemiology. For typing, throat swabs should be collected 4 days after the rash onset and sent directly to the CDC (1).
• In general, viral cultures of CSF are only reserved for suspected cases of CRS or rubella encephalitis (1).
• If a pregnant female is exposed, amniotic fluid for PCR or fetal blood may be obtained at 15 weeks gestation for viral detection. Placental biopsy may be done at 12 weeks, but is performed less often. If positive, the parents should be offered genetic counseling (1).
• As the incidence of rubella decreases, the PPV of IgM results decreases. False positives can occur in patients with parvovirus B19, mononucleosis, and positive rheumatoid factor (1).
• After re-exposure, a person with a low level of Ab from past infection or vaccination may experience an acute, small rise in Ab levels. This is not associated with a high incidence of contagion to others or of fetal risk (1).

• Reporting: State dependent. Samples should be sent to the CDC for genotyping. Cases of CRS, report to the National Congenital Rubella Syndrome Registry (1,2).
• Infants with CRS may shed virus up to 1 year. Place on contact isolation during all admissions until their first birthday, unless they have 2 negative throat cultures and urine specimens a month apart once they are 3 months old (2).

• Pink, discrete, maculopapular rash that begins on the face and spreads down
• Congenital cataracts
• Purpuric lesions in the neonate (“blueberry muffin” baby)
• Congenital hearing loss

Differential Diagnosis

• Postnatal rubella:
  • Measles virus (rubeola)
  • Scarlet fever
  • Infectious mononucleosis
  • Erythema infectiosum (parvo B19/Fifth disease)
  • Roseola infantum (i.e., exanthem subitum)
  • Toxoplasmosis
  • Drug eruptions
  • Other exanthematous enteroviral infections
• Congenital rubella:
  • Measles
  • Parvo B19
  • Human herpesvirus 6
  • Other exanthematous entero- or arboviruses