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Rubella virus is the only member of the Rubrivirus genus of the Togavirus family.

Rubella (which means "little red" and is also known as German measles) was originally though to be a variant ofmeasles. It is a mild disease in children and adults, but can cause devastating problems if it infects the fetus,especially if infection is in the first few weeks of pregnancy.

THE VIRUS

Rubella virus (figure 1) is the only member of the Rubivirus genus of the Togavirus family. Unlike mostTogaviruses it is NOT arthropod-borne, but is acquired via the respiratory route. It is an enveloped (toga=cloak),non-segmented, positive sense, RNA virus and replicates in the cytoplasm. Its nucleocapsid has icosahedralsymmetry (figure 2).There is only one major antigenic type.

PATHOGENESIS AND DISEASETable 1 - CLINCAL ASPECTS OF RUBELLA

Site ofreplication of

virus

Symptoms Notes

Respiratorytract

Minor symptoms although virus is shed (Mildsore throat, coryza, cough)

Patient is infectious 5 daysbefore to 3 days after symptoms

Skin

Rash

Rash of rubella on skin of child's back.

Distribution is similar to that of measles but the lesionsare less intensely red. CDC

Infant with congenital rubella and"blueberry muffin" skin lesions. Lesions are sites ofextramedullary hematopoiesis and can be associated withseveral different congenital viral infections andhematologic diseases. CDC

This infant has the rash of congenitalrubella (German measles). These infants are at great riskfor severe mental retardation, deafness, blindness(atrophic eyes, cataracts and chorioretinitis) as well ascongenital heart disease and other abnormalities. Thisdisease has been nearly eradicated in the United States asthe result of routine rubella vaccine use, whereas in earlieryears as many as 20,000 infants were severely affected in

Often short-lived, atypical;immunopathology (Ag-Abcomplexes)

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a given year. From Amer. Acad. Pediatrics

Congenital rubella with hemorrhagic

lesions in the skin. From Amer. Acad. Pediatrics

Face of adult with rubella. CDC/Barbara Riceber2@cdc.gov

Lymph nodes lymphadenopathyCommoner in posterior triangleof neck or behind ear

Joints mild arthralgia, arthritisImmunopathology (circulatingimmune complexes)

Placent/fetus

PlacentitisFetal damage

Baby born with rubella: Thickening of

the lens of the eye that causes blindness (cataracts) CDC

Congenital rubella

Adapted from Mims et al. Medical Microbiology, 1993, Mosby.

CHILDREN AND ADULTSMan is the only host. Rubella virus is spread via an aerosol route and occurs throughout the world.

The initial site of infection is the upper respiratory tract. The virus replicates locally (in the epithelium, lymphnodes) leading to viremia and spread to other tissues. As a result the disease symptoms develop.

Rash (if it occurs) (table 1) starts after an incubation period of approximately 2 weeks (12 to 23 days) from theinitial infection. There is probably an immunological basis for the rash (since it occurs as antibody titers rise).

The patient is infectious from about 1 week before onset of rash to about 1 week after (figure 3). There is usuallyno prodrome in young children but in older children and adults disease results in low grade fever, rash, sore throatand lymphoadenopathy. Maculopapularrash begins on the face and lasts from 12 hours to 5days. Someindividuals (especially adults and especially women) get arthralgia and sometimes arthritis which usually clears upin a few weeks.

RecoveryT-cell immunity plays an important role in recovery. IgM may persist for up to a year. There are also IgG, IgA

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responses.

Complications

Complications are extremely rarely (1 in 6000 cases). Rubella encephalopathy (headache, vomiting, stiff neck,lethargy, convulsions) may occur about 6 days after rash. It usually lasts only a few days and most patientsrecover (no sequelae). If death occurs, it is within few days of onset of symptoms.

Other rare complications include orchitis, neuritis and panencephalitis.

FETUSThe risk to a fetus is highest in the first few weeks of pregnancy and then declines in terms of both frequency andseverity, although there is still some risk in second trimester. The virus infects the placenta and then spreads tothe fetus. In an outbreak of rubella in the United States in the mid 1960's, there were over 12 million cases ofrubella and 20,000 cases of congenital rubella syndrome. If non-immune mothers are infected in the first trimester,up to 80% of neonates may have sequelae.

The sequelae of congenital rubella syndrome are:

y Hearing loss. This is the most common sequella of congenital rubella infection especially when thelatter occurs after four months of pregnancy.

y Congenital heart defects such as ductus arteriosis and othersy Neurologic problems (psychomotor retardation, mental retardation, microcephaly)y Ophthalmic problems (cataract, glaucoma, retinopathy, microphthalmia - table 1)y intrauterine growth retardationy Thrombocytopenia purpura (table 1)y Hepatomegalyy Splenomegaly

There may also be variety of other problems including bone lesions, pneumonitis etc..

In most cases, there is neural involvement - lethargy, irritability, motor tone problems, mental retardation, motordisabilities, abnormal posture, neurosensory hearing loss.

Virus from congenital infections persists after birth. Those with congenital infections can infect others after birthfor a year or more. Virus occurs in naso-pharyngeal secretions, urine and feces. Later on, patients with congenitalrubella syndrome may develop additional complications including diabetes mellitus (up to 20%), thyroiddysfunction, growth hormone deficiency, ocular complications.

Progressive rubella panencephalitis

This is an extremely rare slow virus disease. It usually develops in the teens with death within 8 years. Most often itis associated with congenital rubella and may be associated with childhood rubella.

DIAGNOSIS OF RUBELLAMany (possibly 50%) infections are apparently subclinical and many infections go unrecognized, even if symptoms

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develop (rash is not always present).

Infections with many other agents give similar symptoms to rubella (e.g. infection with human parvovirus, certainarboviruses, many of the enterovirus group of picornaviruses, some adenoviruses, EBV, scarlet fever, toxic drugreactions).

Serological tests, RT-PCR or isolation of virus (immunofluorescence) are needed to confirm infection of individual.

EPIDEMIOLOGYMan is the only host and rubella occurs world wide. Periodic epidemics occur in an unvaccinated population.Natural infection protects for life (there is a single serotype).

PREVENTION

A live vaccine (attenuated strain) is available. The vaccine virus is grown in human diploid fibroblasts. Since there

is only one serotype, a univalent attenuated vaccine can provide lifelong immunity. The vaccine strain does notspread to family members.

It is important that women are vaccinated prior to their first pregnancy. United States recommendations are forchildhood vaccination to prevent epidemics, combined with vaccination of susceptible, non-pregnant adolescentand adult females. The vaccine is contraindicated for pregnant women, but when unwittingly used, no problemshave been seen. If the patient is pregnant and seronegative, the pregnancy should be monitored carefully and thepatient vaccinated postpartum.

TREATMENTThere is no specific treatment. Supportive care should be used.