Rubella is a contagious viral illness, which, prior to vaccination, was responsible for a significant number of fetal losses and congenital abnormalities. The reported number of rubella cases in the U.S. is low enough that the CDC considers it eliminated in 2004.
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
- Suspected case – any infant <1 year in whom a health worker suspects 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
- IgM antibodies
- 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
- Appearance of clinical symptoms is associated with appearance of both IgG and IgM antibodies
- 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
ARUP Laboratory Tests
Aid in diagnosis of suspected rubella infection
If test results are equivocal, repeat testing in 10-14 days
Semi-Quantitative Chemiluminescent Immunoassay
Determine seroreactivity of women of childbearing age or provide evidence of vaccination/past infection
Semi-quantitative Chemiluminescent Immunoassay
Not recommended as a stand-alone test
Panel that combines rubella IgG and IgM antibodies is preferred
Semi-Quantitative Chemiluminescent Immunoassay
Not recommended for diagnosing congenital infections in newborns; tests should be selected individually to target the most likely infectious agents
May be used in pregnant women to assess past exposure or immunization to Toxoplasma, rubella, cytomegalovirus (CMV), and herpes simplex virus (HSV)
Semi-Quantitative Chemiluminescent Immunoassay
Not recommended for diagnosing congenital infections in newborns; tests should be selected individually to target the most likely infectious agents
Semi-Quantitative Chemiluminescent Immunoassay/Semi-Quantitative Enzyme-Linked Immunosorbent Assay
References
CDC - Manual for the Surveillance of Vaccine-Preventable Diseases - Chapters
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Manual for the surveillance of vaccine-preventable diseases. [Updated: Jun 2020; Accessed: Mar 2021]
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Centers for Disease Control and Prevention (CDC). Recommendations from an ad hoc Meeting of the WHO Measles and Rubella Laboratory Network (LabNet) on use of alternative diagnostic samples for measles and rubella surveillance. MMWR Morb Mortal Wkly Rep. 2008;57(24):657-660.
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Neu N, Duchon J, Zachariah P. TORCH infections. Clin Perinatol. 2015;42(1):77-103.
CDC - Adult Immunization Schedule
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Recommended adult immunization schedule for ages 19 years or older, United States, 2020. [Last reviewed: Feb 2022; Accessed: Jun 2022]
CDC - Recommended Immunization Schedules for Children and Adolescents Aged 18 Years or Younger
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Advisory Committee on Immunization Practices recommended immunization schedule for children and adolescents aged 18 years or younger – United States, 2019. [Last reviewed: Feb 2019; Accessed: Jun 2022]
Medical Experts
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