Rubella

Etiology

Rubella virus is a member of the family Togaviridae and is the only species of the genus Rubivirus. It is a single-stranded RNA virus with a lipid envelope and 3 structural proteins, including a nucleocapsid protein that is associated with the nucleus and 2 glycoproteins, E1 and E2, that are associated with the envelope. The virus is sensitive to heat, ultraviolet light, and extremes of pH but is relatively stable at cold temperatures. Humans are the only known host.

Epidemiology

In the prevaccine era, rubella appeared to occur in major epidemics every 6-9 yr, with smaller peaks interspersed every 3-4 yr, and was most common in preschool-age and school-age children. During the rubella epidemic of 1964-1965 there were an estimated 12.5 million cases of rubella associated with 2,000 cases of encephalitis, more than 13,000 abortions or perinatal deaths, and 20,000 cases of CRS. Following introduction of the rubella vaccine in 1969, the incidence of rubella fell 78% and CRS cases fell 69% by 1976 ( Fig. 274.1 ). Further decline in rubella and CRS cases occurred when certain at-risk populations were added to those for whom rubella immunization is indicated, including adolescents and college students. After years of decline, a resurgence of rubella and CRS cases occurred during 1989-1991 in association with the epidemic of measles during that period (see Fig. 274.1 ). Subsequently, a 2-dose recommendation for rubella vaccine was implemented and resulted in a decrease in incidence of rubella from 0.45 per 100,000 population in 1990 to 0.1 per 100,000 population in 1999 and a corresponding decrease of CRS, with an average of 6 infants with CRS reported annually from 1992 to 2004. Mothers of these infants tended to be young, Hispanic, or foreign born. The number of reported cases of rubella continued to decline through the 1990s and the 1st decade of this century.

The endemic spread of rubella was declared eliminated in the United States in 2004 and eliminated in the Americas in 2015. However, cases of rubella continue to be imported into the United States from countries where it remains endemic, with more than 100,000 cases of CRS annually worldwide. From 2004 to 2016 there were 101 cases of rubella and 11 cases of CRS reported in the United States, all of which were imported cases of unknown source. Three of the CRS cases were acquired in Africa. Worldwide in 2016, 22,106 cases of rubella and 358 cases of CRS were reported, demonstrating that the elimination of rubella internationally has not been achieved and highlighting that continued vigilance and maintenance of high levels of immunity in the United States are necessary.

Pathology

Little information is available on the pathologic findings in rubella occurring postnatally. The few reported studies of biopsy or autopsy material from cases of rubella revealed only nonspecific findings of lymphoreticular inflammation and mononuclear perivascular and meningeal infiltration. The pathologic findings for CRS are often severe and may involve nearly every organ system ( Table 274.1 ).

Pathogenesis

The viral mechanisms for cell injury and death in postnatal or congenital rubella are not well understood. Following infection, the virus replicates in the respiratory epithelium and then spreads to regional lymph nodes ( Fig. 274.2 ). Viremia ensues and is most intense from 10 to 17 days after infection. Viral shedding from the nasopharynx begins approximately 10 days after infection and may be detected up to 2 wk following onset of the rash. The period of highest communicability is from 5 days before to 6 days after the appearance of the rash.

Congenital infection occurs during maternal viremia. After infecting the placenta, the virus spreads through the vascular system of the developing fetus and may infect any fetal organ. The most important risk factor for severe congenital defects is the stage of gestation at the time of infection. Maternal infection during the first 8 wk of gestation results in the most severe and widespread defects. The risk for congenital defects has been estimated at 90% for maternal infection before 11 wk of gestation, 33% at 11-12 wk, 11% at 13-14 wk, and 24% at 15-16 wk. Defects occurring after 16 wk of gestation are uncommon, even if fetal infection occurs.

Causes of cellular and tissue damage in the infected fetus may include tissue necrosis due to vascular insufficiency, reduced cellular multiplication time, chromosomal breaks, and production of a protein inhibitor causing mitotic arrests in certain cell types. The most distinctive feature of congenital rubella is chronicity. Once the fetus is infected early in gestation, the virus persists in fetal tissue until well beyond delivery. Persistence suggests the possibility of ongoing tissue damage and reactivation, most notably in the brain.

Clinical Manifestations

Postnatal infection with rubella is a mild disease not easily discernible from other viral infections, especially in children. Following an incubation period of 14-21 days, a prodrome consisting of low-grade fever, sore throat, red eyes with or without eye pain, headache, malaise, anorexia, and lymphadenopathy begins. Suboccipital, postauricular, and anterior cervical lymph nodes are most prominent. In children, the 1st manifestation of rubella is usually the rash, which is variable and not distinctive. It begins on the face and neck as small, irregular pink macules that coalesce, and it spreads centrifugally to involve the torso and extremities, where it tends to occur as discrete macules ( Fig. 274.3 ). About the time of onset of the rash, examination of the oropharynx may reveal tiny, rose-colored lesions ( Forchheimer spots ) or petechial hemorrhages on the soft palate. The rash fades from the face as it extends to the rest of the body so that the whole body may not be involved at any one time. The duration of the rash is generally 3 days, and it usually resolves without desquamation. Subclinical infections are common, and 25–40% of children may not have a rash. Teenagers and adults tend to be more symptomatic and have systemic manifestations, with up to 70% of females demonstrating arthralgias and arthritis.