What is rubella?

Rubella is an acute viral infection characterized by rash, fever, and lymphadenopathy (as well as many other manifestations) in adults and children. Rubella can resemble a mild case of measles. Rubella is known as “German measles” because it was first clinically distinguished from measles (rubeola) in Germany in the mid-eighteenth century.

What is the causative agent of rubella?

Rubella is caused by rubella virus which belongs to togavirus family and Rubivirus genus. Rubella virus does not require a vector for transmission. The rubella virion is approximately 60 nm (nanometer) in size and composed of an inner RNA and protein that is surrounded by a lipid-containing envelope with glycoprotein spikes. The structural proteins associated with rubella virus are E1 and E2 (envelope glycoproteins) and C or the capsid protein that surrounds the RNA. Only one serotype of rubella virus has been identified (which has made rubella vaccine very effective and easy to prepare).

How long is incubation period of rubella?

Incubation period of rubella is generally 18 days with a range of 12-23 days.

How rubella is transmitted?

Both subclinical and symptomatic rubella is contagious, although less than measles. Rubella is transmitted by droplets shed in respiratory secretions, infects the respiratory tract and then the bloodstream. Rubella virus is shed during prodromal phase of the illness (when there is fever and malaise) and shedding from the pharynx can continue for approximately 1 week. Infants with congenital rubella may excrete rubella virus from the respiratory tract and in the urine until the age of 2 years, despite high titers of specific neutralizing antibodies. Persons who are recently vaccinated do not transmit the vaccine virus to others.

Global problem of rubella:

According to WHO (World Health Organization) more than half of the countries rubella vaccine in their national programs by 2003, but rubella is still endemic in many areas around the world. During the pre vaccination time rubella was most common in the spring and most often affected school-age children. A major epidemic used to occur every 6 to 9 years as only 80 to 90% of adults were immune to rubella. During prevaccination time rubella used to be a major health problem with more than 12 million cases of postnatal rubella infection and more than 20,000 cases of the congenital rubella syndrome in the United States alone in year 1964–1965 (before rubella vaccine was developed in 1969). At present in the United States only a handful of cases of rubella are reported in CDC and a few cases of congenital rubella syndrome among immigrants.

Pathogenesis of rubella:

Rubella is a self limiting disease and consequently little study was done about the pathology and pathogenesis of rubella as it is not a serious disease. Rash in rubella is imminologically mediated and coincide with the development of specific antibodies. Viremia is present about a week before rash appear and last only few days after onset of rash. How rubella virus cause organ and cell damage in congenital rubella is also not well understood. Congenital rubella may cause organ and cell damage by mitotic arrest of cells, tissue necrosis without inflammation, and chromosomal damage.

What are the clinical manifestations of rubella?

Rubella acquired after birth has extremely mild clinical presentation or may be subclinical infection. In adults rubella can be more severe disease, with a brief episode of prodrome symptoms like malaise, fever, and anorexia. Posterior auricular, cervical, and suboccipital lymphadenopathy, fever and rash are seen in adults with rubella. The rash (generally lasts for 3–5 days) is maculopapular, which begins on the face and spreads down the body. There may be mild cold and conjunctivitis. Forschheimer spots (present in other diseases also), which is a petechial enanthem on the soft palate may be present. Fever if occurs, generally occurs in the early phase of rubella.

What are the complications of rubella?

Complications of rubella if acquired after birth are uncommon. Bacterial superinfection may occur rarely. Arthritis involving joints of fingers, wrists, and/or knees may occur almost exclusively in women. Arthritis as a complication of rubella if occurs, generally starts at the time of appearance of rash and may take several weeks to resolve. Rubella virus can be isolated from joint fluid during acute rubella arthritis and from peripheral blood in chronic rubella arthritis. Encephalitis (five times lower than that of encephalitis following measles) may occur after infection with rubella virus both in children as well as adults and it is commoner in adults, with high mortality of 20-50%. Hemorrhage can occur approximately 1 in 3,000 cases of rubella, due to thrombocytopenia and damage to the blood vessels. If hemorrhage occurs in the eye or the brain it may have long-term consequences. Rarely there may be hepatitis.

What is congenital rubella?

Maternal infection with rubella virus in early pregnancy can cause infection of the fetus with rubella virus which results in congenital rubella. The classic signs of congenital rubella are cataract, heart disease, deafness, and number of other defects. The gestational age at which infection occurs is the most important factor in determining the severity and symptoms of congenital rubella. Maternal infection during the first trimester leads to fetal infection in approximately 50% of cases (more common and severe fetal malformation with involvement of more organ systems). Maternal infection in the second trimester leads to fetal infection in approximately 33% (one third) of cases with less severe fetal malformations. For example, a fetus infected in the fourth week of gestation may develop many problems in compare to a fetus infected later in the twentieth week, which may have only isolated deafness as symptom of congenital rubella.

The transient symptoms of congenital rubella seen only at birth which disappear afterwards are cloudy cornea, hepatitis, bony abnormalities, enlarged liver and spleen, hemolytic anemia, jaundice, pneumonia, meningoencephalitis, lymphadenopathy, low birth weight etc.

The permanent signs and symptoms of congenital rubella are cataract, glaucoma, myopia, retinopathy, congenital heart disease (patent ductus arteriosus, pulmonic stenosis etc.), deafness, autism, mental retardation, behavioral disorders, cryptorchidism, microcephaly, brain degeneration, diabetes mellitus, inguinal hernia, precocious puberty, spastic diplegia, thyroid problems etc.

How rubella is diagnosed?

Diagnosis of rubella on clinical ground may be difficult as many other diseases may mimic same clinical features as rubella. The diseases which can cause similar clinical manifestation as rubella are toxoplasmosis, scarlet fever, measles, erythema infectiosum or fifth disease due to parvovirus B19, and enteroviral infection.

Commonly used laboratory technique for diagnosis of rubella is ELISA (enzyme-linked immunosorbent assay) for IgG and IgM antibodies against rubella virus. Acute rubella is diagnosed by demonstration of a fourfold or greater rise in the titer of IgG antibodies or by the detection of rubella-specific IgM antibodies in one serum specimen. But there may be false-negative and false-positive IgM reactions sometimes.

Isolation of rubella virus in cell cultures of throat samples, urine, or other secretions is difficult as well as expensive. Polymerase chain reaction (PCR) is also sometimes used for diagnosis of rubella. Both of these techniques are useful when congenital rubella is suspected. Congenital rubella can also be diagnosed by demonstration of IgM antibodies in at least one serum sample, and/or the documentation of persistence of rubella antibodies in serum beyond 1 year of age or a rising antibody titer anytime during infancy in an unimmunized child.

Routine laboratory tests generally demonstrate leukopenia and atypical lymphocytes.

How rubella is treated?

Rubella is a self limiting disease and no specific treatment is required. Fever, arthralgia, and arthritis are the common symptoms and symptomatic treatment is generally given in rubella.

How to prevent rubella?

Rubella can be prevented by rubella vaccine, a live attenuated vaccine in use since 1969, which cause seroconversion in more then 95% of recipients. The vaccine was developed to prevent congenital rubella and that there would be little circulating wild-type virus. After the universal use of rubella vaccine the clinical cases of rubella came down drastically to less then 2% of prevaccination time. The present vaccination strategy for rubella is to use it with measles and mumps as measles-mumps-rubella (MMR) vaccine all infants at 12–15 months of age and to administer a second booster dose in early childhood. Due to universal use of MMR vaccine the incidence of congenital rubella is extremely low at present (e.g. in the United Stares approximately only 10 cases of congenital rubella occurs annually)

Rubella vaccine can be given to anyone though to be susceptible to rubella and it is important that all hospital workers of either sex be immune to rubella so that nosocomial (hospital acquired) transmission is avoided.

Rubella vaccine may sometime cause arthralgia or arthritis, (generally in young women) and very rarely, rubella vaccination can result in chronic arthritis but, even in frank arthritis in vaccinees are generally self-limited, which subsides in approximately one week. Rubella vaccine is contraindicated in pregnant women and it is advisable not become pregnant at least for 3 months after receiving rubella vaccine, although there is no clear evidence that rubella vaccine in pregnant women can cause congenital rubella syndrome, as was seen in the United Stares in a study by CDC, where more then 400 pregnant women were studied who inadvertently received rubella vaccine during pregnancy and who carried their infants to term. In the study it was concluded that vaccine-type rubella virus does not cause the congenital rubella syndrome at all or if it does, it does so at an incidence too low to be detected.

Rubella vaccine is not recommended in immunosuppressed individuals, but it can be given and is given to children infected with HIV. In immunocompromized individuals the rubella vaccine does not cause any adverse effects.

The rubella antibody is not detectable years after immunization, but protection against infection continues, possibly due to cell-mediated immunity, as evident from the fact that there has been little change in the prevalence of immunity to rubella among women of childbearing age (at approximately 80% before vaccination period and after universal vaccination against rubella), the incidence of congenital rubella is extremely low. The vaccine currently licensed and used in the United States (RA 27/3) is more immunogenic with regard to the stimulation of secretory immunity than previously licensed vaccines.