Dr. Margaret Hunt 

   Revised October 2006

READING: Murray et al., Microbiology, 3rd Ed., Chapter 59 pp. 499-502

VIROLOGY - CHAPTER   FIFTEEN  

RUBELLA (GERMAN MEASLES) VIRUS  

TEACHING OBJECTIVES

Brief review of structure and properties of rubella virus. Discussion of viral pathogenesis and disease, epidemiology, prevention and treatment.

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 of measles. 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 most Togaviruses 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 icosahedral symmetry (figure 2).
There is only one major antigenic type.

Figure 2 Structure of rubella virus

Figure 3 Rubella pathogenesis

Man 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, lymph nodes) 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 the initial 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 usually no prodrome in young children but in older children and adults disease results in low grade fever, rash, sore throat and lymphoadenopathy.  Maculopapular rash begins on the face and lasts from 12 hours to 5days. Some individuals (especially adults and especially women) get arthralgia and sometimes arthritis which usually clears up in a few weeks.

T-cell immunity plays an important role in recovery. IgM may persist for up to a year. There are also IgG, IgA 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 patients recover (no sequelae). If death occurs, it is within few days of onset of symptoms.

Other rare complications include orchitis, neuritis and panencephalitis.

The risk to a fetus is highest in the first few weeks of pregnancy and then declines in terms of both frequency and severity, although there is still some risk in second trimester. The virus infects the placenta and then spreads to the fetus. In an outbreak of rubella in the United States in the mid 1960's, there were over 12 million cases of rubella 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:

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

• Congenital heart defects such as ductus arteriosis and others

• Neurologic problems (psychomotor retardation, mental retardation, microcephaly)

• Ophthalmic problems (cataract, glaucoma, retinopathy, microphthalmia - table 1)

• intrauterine growth retardation

• Thrombocytopenia purpura (table 1)

• Hepatomegaly

• 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, motor disabilities, abnormal posture, neurosensory hearing loss.

Virus from congenital infections persists after birth. Those with congenital infections can infect others after birth for a year or more. Virus occurs in naso-pharyngeal secretions, urine and feces. Later on, patients with congenital rubella syndrome may develop additional complications including diabetes mellitus (up to 20%), thyroid dysfunction, 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 it is associated with congenital rubella and may be associated with childhood rubella.

Many (possibly 50%) infections are apparently subclinical and many infections go unrecognized, even if symptoms develop (rash is not always present).

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

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

Man 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 not spread to family members.

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

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

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