INFECTIOUS DISEASE

TURKISH

VIROLOGY - CHAPTER   FIFTEEN  

RUBELLA (GERMAN MEASLES) VIRUS  

Dr Margaret Hunt 
Professor Emerita
University of South Carolina School of Medicine

En Español

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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 because it was first described in Germany) was originally though to be a variant of measles. It is a mild disease and often goes unnoticed in children and adults, but can cause devastating problems if it infects the fetus, especially if infection occurs during 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 3 Rubella pathogenesis

Man is the only host. Rubella virus is spread via an aerosol route and occurs throughout most of the world although endemic rubella, like measles, has been eliminated in North America.

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 (less than 101F, 38.3C)

• rash (starts on the face and spreads over the body)

• sore throat

• 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.

In about half of all rubella infections there are no noticeable symptoms.

Recovery
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.

Child operated on at age 3 days to correct congenital glaucoma, due to a case of congenital rubella. Note that the baby’s left eye also displayed the cloudiness associated with a congenital rubella cataract, and can be compared to the normal appearance of the right eye.
CDC/ Dr. Andre J. Lebrun

Congenital rubella cataract.
CDC/ Dr. Andre J. Lebrum

Rubella cases in the United States CDC

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 devastating sequelae. However, as the result of an excellent vaccine, there have been no cases of congenital rubella syndrome in the United States in recent years.

The sequelae of congenital rubella syndrome are:

• Hearing loss. This is the most common sequela of congenital rubella infection (58% of patients) especially when the latter occurs after four months of pregnancy.

• Ophthalmic problems (congenital cataract, glaucoma, retinopathy, microphthalmia - table 1). These occur in about 43% of patients.

• Congenital heart defects including, among others, pulmonary artery stenosis and patent ductus arteriosis. The Ductus arteriosis is a short blood vessel through which blood going to the fetal heart (through the pulmonary artery) is shunted away from the lungs to the aorta. It usually closes at or shortly after birth and blood passes freely to the lungs. If however, it remains open (patent ductus arteriosis), blood flow is reversed and blood from the aorta goes to the pulmonary artery and recirculates to the lungs. It then requires surgical ligation. These occur in about half of patients.

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

• Intrauterine growth retardation

• Thrombocytopenia purpura (table 1)

• Hepatomegaly

• Splenomegaly

Hearing loss, ophthalmic abnormalities and congenital heart disease are the classic triad of congenital rubella.

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, Epstein-Barr virus, scarlet fever, toxic drug reactions).

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

EPIDEMIOLOGY

Man is the only host and rubella occurs in many countries of the world. Periodic epidemics occur in an unvaccinated population; however, natural infection protects for life because there is a single serotype.

United States
Rubella was a very common disease in children prior to the introduction of a very effective live attenuated vaccine. There were period epidemics every six to nine years in the spring months with the last being in 1964/1965 during which there were (CDC figures):

• 12.5 million cases of rubella

• 2,000 cases of encephalitis

• 11,250 therapeutic or spontaneous abortions

• 2,100 neonatal deaths

• 20,000 infants born with congenital rubella syndrome

The median number of cases in the United States in the period 2005-2010 was just 11 per year.

Incidence of Rubella in the United States
	1990	1999	2004 to present
Children under 15	6.3 per million	0.6 per million	0.1 per million
Adults (15 to 44 years)	1.3 per million	2.4 per million	0.1 per million

In 1965, the incidence of rubella disease in the United States was approximately 64,500 cases per million population.

Almost all the sporadic cases in recent years have been imported or  linked to importation. In 2014, an expert panel concluded that there was no evidence of endemic rubella transmission through 2011 and therefore endemic rubella had been eliminated from the United States.

Global Epidemiology

Approximately 100,000 children are born around the world each year with congenital rubella syndrome.

 

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. Normally it is given as part of a trivalent inoculation (mumps, measles and rubella vaccine).

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.

To maintain elimination of rubella, it is important that all children receive the vaccine unless there are specific contraindications.

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

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This page last changed on Monday, October 31, 2016
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