Description

• Rubella is a mild viral exanthematous infection of children and adults, generally self-limiting, with rare complications. Nonimmune women who become infected with rubella while pregnant may have devastating fetal effects. Up to 50% of infections may be asymptomatic (1).
• System(s) affected: Hematologic; Nervous; Pulmonary; Exocrine; Ophthalmologic; Skeletal
• Synonym(s): German measles; 3-day measles

• Pregnancy-associated rubella infection may lead to congenital rubella syndrome (CRS) with potentially devastating fetal outcomes.
• CRS is present in 90% of fetuses exposed during the first 11 weeks of gestation and 20% of fetuses exposed by 20 weeks of gestation (2).
• Most effective prevention of CRS is screening pregnant women for rubella immunity and immunizing nonimmune women postpartum (2)[B].
• Women vaccinated against rubella are advised not to become pregnant for 28 days: The vaccine-type virus can cross the placenta. No case of CRS has occurred after inadvertent vaccination, but a risk of 0.5–1.3% cannot be ruled out (2)[C].
• Polymerase chain reaction (PCR)–based method (87–100% sensitive) of detecting viral RNA in amniotic fluid allows rapid diagnosis of fetal infection if performed after 15 weeks gestation; however, recent studies have indicated that fetal blood sampling at the same gestation yielded rubella-specific RNA where amniotic fluid failed (3)[B].

Epidemiology

• A 50–70 nm RNA togavirus of the genus Rubivirus (1)
• 13 genotypes have been identified (4).
• Live attenuated vaccine made first available in the US in 1969
• Since 2004, not endemic in the US. All cases are of imported origin: Travelers with inadequate immunity (1)
• Average incubation: 14 days; range 12–23 days
• Infectious period between 7 days before and 5–7 days after rash onset
• Transmitted by respiratory droplets
• Temporal association: Late winter and early spring
• Only natural host is the human (1)

• US incidence <10/100,000 since 2001
• 5 cases were reported in the US in 2010.
• Still occurs worldwide in developing countries: 100,000 cases of CRS reported annually.

Risk Factors

Inadequate immunization or immunity after prior vaccination, immunodeficiency states, immunosuppressive therapy, crowded living/working conditions, international travel (1)[C]

Genetics
Children with CRS and children with type I diabetes mellitus (DM) share a high frequency of HLA-DR3 histocompatibility Ag and a high prevalence of islet cell Ab.

General Prevention

• Vaccination most effective preventive strategy
• Available combined with measles and mumps (MMR), combined MMR and varicella (MMRV), or as monovalent rubella vaccine
• Rubella vaccine (strain RA 27/3):
  • A 2-dose schedule combined MMR vaccine recommended for those born after 1957. The 1st dose recommended at ages 12–15 months; 2nd dose recommended either at 4–6 or at 11–12 years of age. Children with HIV should receive MMR vaccine at 12 months of age if no contraindications exist. If an outbreak occurs, immediate vaccination for infants 6–11 months old is recommended (2).
  • Recommended for nonimmune people in the following groups: Prepubertal boys and girls, premarital or postpartum women, 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 (1).
• During outbreaks, serologic screening before vaccination is NOT recommended because rapid mass vaccination is necessary to stop the spread of the disease (2)[A].
• Debate about safety of MMR vaccine: Continued studies conducted prove the dissociation of the MMR vaccine with autism (5). Cochrane systematic review stated that it is unlikely to be associated with Crohn disease or ulcerative colitis. It is likely to be associated with benign thrombocytopenic purpura, parotitis, joint and limb complaints, febrile seizures, and aseptic meningitis (mumps).
• Children who receive the MMRV vaccine experience a 2-fold increase in incidence of febrile seizures than those who receive MMR and varicella vaccines separately (5).
• Because the US has adequate vaccination capabilities, antibody screening in prenatal care is recommended by the CDC and the ACOG, and should be reinforced (6)[B].

Pathophysiology

• Virus invades the respiratory epithelium, spreads hematogenously to the lymphatics, where it starts replicating. Once infected, the patient starts shedding the virus from the nasopharynx 3–8 days after inoculation, lasting up to 14 days after the rash starts.
• Progression from prodromal stage (1–5 days), to lymphadenopathy (5–10 days), and finally to a light pink, pruritic, maculopapular rash: Starts on the face and spreads inferiorly to the trunk and extremities, sparing the palms and soles (14–17 days after onset of initial symptoms)
• 90% of fetuses exposed to rubella in the first 11 weeks of gestation (organogenesis) will develop CRS. 20% chance of developing CRS if exposed 12–20 weeks of gestation, and after 20 weeks gestation the risk drops to 2% (2).

Etiology

• German measles first described by German authors in the mid-18th century; thought to be a variant form of either measles or scarlet fever
• In 1815, described in the English literature by Manton; felt to be a separate entity from measles or scarlet fever
• Given the name rubella in 1866 by Veale
• 1962–1965: Global pandemic resulting in an estimated 12.5 million cases in the US, with a devastating 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)
• Live attenuated vaccine (LAV) licensed in the US in 1969 for the purpose of preventing CRS