Rubella

Rubella is a viral infection, also known as German measles. Rubella is serious only if it affects a nonimmune woman in the early months of pregnancy, when there is a risk that the virus will cause severe birth defects (known as congenital rubella syndrome) in the fetus.

Transmission and symptoms

The rubella virus is spread through mother-to-baby transmission and from person to person in airborne droplets; it has an incubation period of two to three weeks. Infection usually occurs in children between the ages of six and 12 and is almost invariably mild. The first symptoms may be a slight fever, malaise, and enlarged lymph nodes at the back of the neck. A rash then appears on the face, spreads to the trunk and limbs, and disappears within about three days. In adolescents and adults the symptoms may be more marked, such as a headache before the rash appears and a more pronounced fever. The virus may be transmitted from about a week before the rash appears until a few days after its onset. An unborn baby is at risk if the mother is infected during the first four months of pregnancy. The earlier the infection occurs, the more likely the infant is to be affected and the more serious the resulting abnormalities tend to be. The most common abnormalities are deaf- ness , congenital heart disease , learning difficulties , cataract , purpura , cerebral palsy , and bone abnormalities. About one in five affected babies dies in early infancy.

Diagnosis and treatment

Rubella is easily confused with other viral infections, scarlet fever , and drug reactions, which may produce similar symptoms. Rubella can be positively diagnosed only by laboratory isolation of the virus, for example from a throat swab or by tests to look for antibodies (proteins manufactured by the immune system) to the virus in the blood. There is no specific treatment. Paracetamol can be given to reduce fever. Treatment of congenital rubella syndrome depends on the defects present.

Prevention

The rubella vaccine provides long-lasting immunity to the disease; it is now given in the MMR vaccine to babies aged 12 to 15 months, with a booster at school entry. Rubella infection also confers immunity. Any woman who is planning a pregnancy should have her rubella status checked. If she is not immune, she should be vaccinated immediately. If a nonimmune pregnant woman comes into contact with a person who has rubella, passive immunization by immunoglobulin injection may help to prevent infection of the fetus.

Detailed technical article about rubella.

Topics covered:

  • Essentials
  • Introduction
  • Aetiology
  • Epidemiology
  • Postnatally acquired infection
  • Congenital infection
  • Management of rubella-like illness during pregnancy
  • Prevention Likely developments
  • Further reading

Essentials

Rubella is caused by an enveloped RNA virus, for which humans are the only known host. Transmission is by airborne droplet spread, with infection seen predominantly in spring and early summer in temperate zones.

Postnatally acquired infection—presents after incubation of 14 to 21 days with rash (maculopapular, usually beginning on the face before spreading to the trunk and extremeties), lymphadenopathy (suboccipital and posterior cervical), and mild fever. Sore throat, coryza, cough, conjunctivitis, and arthralgia may be seen. The illness is usually mild. Management is symptomatic.

Rubella in pregnancy—in the first 10 weeks of gestation this is associated with a 90% risk of congenital fetal abnormalities, most typically comprising sensorineural hearing loss, alone or combined with cataracts and/or cardiac anomalies. Clinical diagnosis is unreliable, hence rapid investigation is essential when a woman develops a rubella-like illness in the first 16 weeks of pregnancy, comprising (1) testing of maternal serum for rubella IgG and IgM antibodies; and sometimes (2) amniotic fluid and/or fetal blood testing; and (3) ultrasonography to detect fetal defects. If a fetus is infected, termination of pregnancy is considered.

Prevention—live attenuated rubella vaccines provide protection to about 95% vaccinees and are usually given in combination with measles (MR) or measles and mumps (MMR) vaccines. Vaccination of >80% of children is required to prevent circulation of rubella virus. Health care workers and women of childbearing age whose rubella status is unknown (including recent immigrants) should also be targeted for MMR vaccination. Immunization of pregnant women is contraindicated, but women found to be susceptible at antenatal testing should be offered MMR vaccination after delivery.

Introduction

Rubella is a mild exanthematous disease of little clinical significance. However, infection in early pregnancy may result in multiple congenital abnormalities, often referred to as ‘congenital rubella syndrome’. As a result of the widespread use of rubella vaccine, congenital rubella syndrome is now rare in many countries.

Aetiology

Rubella is caused by rubella virus, an enveloped RNA virus, which is classified in its own genus Rubivirus within the family Togaviridae. There are no major antigenic differences among rubella virus isolates, although at least seven genotypes have been described.

Epidemiology

Humans are the only known host for rubella virus. In temperate zones the infection is seen predominantly in spring and early summer. Before the introduction of rubella vaccine, rubella was endemic in virtually all countries. Epidemics were superimposed on the endemic infection every 4 to 9 years and pandemics every 10 to 30 years. In most populations, in the absence of a mass immunization programme, 10 to 20% of women are still susceptible to rubella infection when they reach child-bearing age. A review by the World Health Organization in 2000 estimated that more than 100 000 infants were born with congenital rubella syndrome each year in developing countries.

Postnatally acquired infection

The rash usually begins on the face and spreads to the trunk and then the extremities; the pink maculopapular lesions are initially discrete but later tend to coalesce. The suboccipital and posterior cervical lymph nodes are characteristically enlarged. Mild fever, sore throat, coryza, cough, and conjunctivitis may be present; symptoms are usually mild and last 3 to 7 days. There may be a prodrome with malaise and fever, especially in adults. There is no specific treatment.

Transient arthralgia with or without arthritis occurs in up to 70% of postpubertal women, but is less common in men and children. Less common complications include thrombocytopenia with or without purpura, postinfectious encephalitis, transverse myelitis, and rarely the Guillain–Barré syndrome. When rubella is acquired in early pregnancy congenital infection may occur (see below).

Rubella is clinically indistinguishable from several other infections and 20 to 50% of infections are subclinical. Therefore, a history of clinically diagnosed rubella infection is unreliable.

The incubation period is 14 to 21 days. The exact mode of transmission is uncertain but airborne spread by the respiratory route is likely and close contact is usually necessary for transmission. Individuals are most infectious just before the onset of symptoms, and the infectious period lasts from about a week before to a week after the rash appears. Infection usually produces lifelong immunity; however, when rubella is circulating reinfection may occur and is usually asymptomatic.

Congenital infection

Risk to the fetus

The possible consequences of rubella in pregnancy are the birth of an infant with congenital rubella infection with or without congenital defects, the birth of a normal infant, or spontaneous abortion. Infection before conception is not a risk to the fetus. Spontaneous abortion may occur when rubella is acquired early in pregnancy. When maternal infection occurs during the first 10 weeks of pregnancy the rate of fetal infection is about 90%; it then declines until the last few weeks of pregnancy when the rate rises again. Virtually all of those infected during the first 10 weeks of pregnancy are likely to have congenital defects, but the risk declines over the next 6 weeks. After 16 weeks’ gestation even sensorineural hearing loss and growth retardation are rare, and no abnormalities have been demonstrated following serologically confirmed maternal infection after 18 weeks’ gestation. Most prospective studies of the risk to the fetus have been carried out on women with symptoms, but asymptomatic primary infection is thought to carry a similar risk.

Following maternal reinfection in pregnancy the risk of transmission to the fetus is probably less than 10% and the risk of damage less than 5%, although it may be higher following symptomatic reinfection.

Clinical features

Congenital rubella is typically associated with cataracts, cardiac anomalies, and sensorineural hearing loss, and the term congenital rubella syndrome (CRS) refers to this classic triad of defects. The teratogenic effects may result in a wide range of defects (Bullet list 1 below), but sensorineural hearing loss alone or combined with other abnormalities is most common. Severe multiple problems are more likely when infection occurs early in pregnancy.

Some defects, particularly sensorineural hearing loss, may not develop or become apparent until late infancy or childhood. Other reported late-onset problems include diabetes mellitus, thyroid dysfunction, autism, and other behavioural and psychiatric disorders. A rare progressive rubella panencephalitis has also been reported.

Laboratory diagnosis

The diagnosis of congenital rubella infection is relatively easy if suspected early, but more difficult to confirm after 3 months of age. The presence of rubella IgM antibody in early infancy is virtually diagnostic of congenital infection because acquired infection is rare at this age. Using sensitive assays, rubella IgM may be detected in 85% of infected infants at 3 to 6 months and about 30% at 6 to 12 months of age. The presence of IgG antibody alone is not diagnostic since it is likely to indicate passively transferred maternal antibody, but persistence of IgG between 6 and 12 months is strongly suggestive of congenital infection. When abnormalities present late, a presumptive diagnosis can be made based on a compatible clinical picture and the presence or persistence of rubella IgG antibodies in a young child who has not yet been vaccinated.

Congenital infection can also be diagnosed by detection of virus during the first months of life when it can be isolated or detected by polymerase chain reaction from a variety of specimens including nasopharyngeal swabs, urine, oral fluid, and conjunctival fluid. Congenitally infected infants shed large amounts of virus from the oropharynx and may be a source of infection for many months; viral shedding occasionally persists for more than a year.

Management of rubella-like illness during pregnancy

Appropriate management of a rash illness in pregnancy will depend on the local epidemiology of rubella. Routine antenatal rubella testing is not designed to identify rubella infection in pregnancy, and specific diagnostic investigations are needed. Pregnant women with a rubella-like rash should be investigated simultaneously for rubella and parvovirus B19, since they are clinically indistinguishable, and even women previously reported to be immune should be investigated in case of laboratory error. Blood should be tested for rubella IgG and IgM antibodies. Rising IgG or detectable IgM antibody indicates recent infection; a positive IgM result alone should be confirmed with a second serum sample. Pregnant women who are susceptible or of unknown rubella antibody status and are in contact with a rubella-like illness should also be investigated as rapidly as possible. The detection of rubella IgM in a woman without a rash or history of contact should be interpreted with caution as rubella IgM may persist for some months or even years after infection or vaccination, or the IgM may be due to cross-reaction with autoantibodies or other viral IgM antibodies. Investigations must be done in consultation with a virologist who should be aware of the date and type of contact, stage of pregnancy, and history of previous immunization and testing. Prenatal diagnosis of congenital infection using amniotic fluid and/or fetal blood may sometimes be indicated. Ultrasound examination may detect such defects as microcephaly, dystrophic calcification, cataracts, microphthalmos, hepatosplenomegaly, and intrauterine growth restriction.

Bullet list 1 Most common defects associated with congenital rubella

Classic triad

  • Deafness
    • Sensorineural
    • Central auditory
  • Abnormalities of the cardiovascular system
    • Patent ductus arteriosus
    • Pulmonary stenosis
    • Pulmonary arterial hypoplasia
  • Abnormalities of the eye
    • Retinopathy
    • Cataracts
    • Microphthalmos
    • Iris hypoplasia

Other defects

  • Growth retardation
  • Microcephaly
  • Mental retardation
  • Speech defects

Other signs in the neonatal period and infancy

Low birthweight

  • Hepatosplenomegaly
  • Jaundice
  • Meningoencephalitis
  • Rash
  • Thrombocytopenia with or without purpura
  • Adenopathies
  • Bony radiolucencies
  • Hypogammaglobulinaemia
  • Pneumonitis

Prevention

Rubella can be prevented by live attenuated rubella vaccines. The RA27/3 strain is commonly used and this produces antibodies in about 95% of recipients; protection is probably lifelong in most vaccinees. Rubella vaccine is usually combined with measles (MR) or measles and mumps (MMR) vaccines.

In children, rubella vaccine causes few side effects. Low-grade fever and rash are occasionally reported, and transient arthralgia has been seen in about 3% of vaccinees; there have also been rare reports of myositis and vasculitis. Joint symptoms are more common in adult women, affecting up to 60% of vaccinees, but are transient and less severe than following naturally acquired rubella.

When rubella vaccines were first licensed in the late 1960s, universal childhood vaccination was implemented in the United States of America with the aim of eliminating rubella. A different strategy was pursued elsewhere, and the selective programmes established in Australia and some European countries targeted prepubertal girls and women of child-bearing age. This provided individual protection while allowing the continued circulation of wild virus and the acquisition of natural immunity by the majority of individuals. When the combined MMR vaccine became available, many countries with high vaccine uptake moved to a universal offer of MMR vaccine for children in the second year of life, usually with a second dose offered preschool or later.

The MMR vaccine was introduced into the United Kingdom schedule in 1988, and uptake by the age of 24 months reached 92% between 1992 and 1996. The schoolgirl programme was discontinued in 1996 and replaced by the offer of a second MMR for four-year-olds. Uptake of MMR subsequently declined to a low point of 80% in 2003, because of unfounded concerns about safety; however, by 2005 there were signs of recovery and uptake increased to over 85% by 2008. Antenatal screening continues. Although the circulation of rubella virus has dropped to very low levels since the introduction of MMR, prolonged periods of low vaccine uptake may lead to outbreaks of rubella in the future, putting susceptible pregnant women at risk.

Use of rubella-containing vaccines has led to the elimination of rubella in the United States of America and Scandinavian countries, although outbreaks have occurred in the United States of America due to importations of rubella virus. Similarly, in the United Kingdom there have been dramatic declines in the numbers of susceptible pregnant women, rubella-associated terminations, and children born with congenital rubella syndrome. Less than five congenitally infected infants were reported on average each year between 1990 and 1999, compared with about 50 per year in the 1970s. Between 2000 and 2008 fewer than 15 cases were identified, and in about half of these the infant’s mother acquired infection abroad. Termination of pregnancy associated with rubella disease or contact is also now a rare occurrence.

The World Health Organization has recommended that all countries undertaking measles elimination should consider the introduction of MR or MMR vaccine in order to eliminate rubella as well. By 2005, rubella vaccine was used by 117 of 214 countries, with particularly good progress seen in the Americas. In 1997 the Pan American Health Organization recommended a regional initiative to eliminate rubella and congenital rubella syndrome, and by 2004 all countries in the region, except Haiti, had incorporated rubella vaccine into their routine vaccination programmes leading to a significant fall in cases of rubella and congenital rubella syndrome. The World Health Organization European Region established a goal of reducing congenital rubella syndrome cases to less than 1 per 100 000 births by 2010. The strategy to be adopted in any country seeking to control congenital rubella by vaccination must depend on the projected uptake of vaccination and the long-term prospects for continuing the programme. An important element should be the immunization of susceptible health personnel, particularly those in contact with pregnant women. It is also important to target women who have emigrated from countries without rubella vaccination programmes, as they are more likely to be susceptible than women born in countries with well-established vaccination programmes.

Vaccination in pregnancy

There have been persistent concerns that the vaccine virus might be teratogenic if given during pregnancy. Although vaccinees cannot infect other susceptible individuals, the virus can cross the placenta. Data from studies of children born to several hundred women inadvertently vaccinated up to 3 months before conception or during pregnancy show less than 3% with serological evidence of congenital infection, and no reported case of abnormalities attributable to congenital rubella. At least 80 of these infants were born to women vaccinated in the month of conception, probably the period of greatest vulnerability. These data suggest that the likely maximum theoretical risk of rubella-associated abnormalities is less than 5%.

Likely developments

  • Elimination of rubella by further countries
  • Introduction of rubella vaccine in additional countries worldwide
  • Use of mathematical models to guide rubella vaccination strategies in different countries
  • Use of genotyping to track the source of rubella outbreaks as countries approach elimination of rubella virus
  • Development of techniques for the diagnosis of congenital rubella syndrome after the age of 3 months

Further reading

Top

Banatvala JE, Brown DWG (2004). Rubella. Lancet, 363, 1127–37.

Banatvala JE, Peckham C (eds) (2007). Rubella viruses. Perspectives in medical virology, vol. 15. Elsevier, London.

Best JM, Cooray S, Banatvala JE (2005). Rubella. In: Mahy BWJ, ter Meulen V (eds) Topley and Wilson’s microbiology and microbial infections, 10th edition, pp. 959–92. Hodder Arnold, London.

Cooper LZ, Alford CA (2006). Rubella. In: Remington JS, et al. (eds) Infectious diseases of the fetus and newborn infant, 6th edition, pp. 894–926. Elsevier, Saunders, Philadelphia.

Department of Health (2006). Rubella. In: Immunisation against Infectious Disease—‘The Green Book’.

Morgan-Capner P, Crowcroft NS; PHLS Joint Working Party of the Advisory Committees of Virology and Vaccines and Immunisation (2002). Guidelines on the management of, and exposure to, rash illness in pregnancy (including consideration of relevant antibody screening programmes in pregnancy). Commun Dis Public Health, 5, 59–71.

Robertson SE, et al. (2003). Rubella and congenital rubella syndrome: global update. Pan Am J Public Health, 14, 306–15.