Rubella

Clinical Description

Identification

For most people, rubella is a mild febrile viral disease with a diffuse punctate and maculopapular rash. Clinically, rubella is indistinguishable from febrile rash illness due to measles, dengue, parvovirus B19, human herpesvirus 6, Coxsackie virus, Echovirus, adenovirus or scarlet fever. Children usually present few or no constitutional symptoms, but adults may experience a 1–5 day prodrome of low-grade fever, headache, malaise, mild coryza and conjunctivitis. Post-auricular, occipital and posterior cervical lymphadenopathy is the most characteristic clinical feature, and precedes the rash by 5–10 days. Leukopenia is common and thrombocytopenia can occur, but hemorrhagic manifestations are rare. Arthralgia and, less commonly, arthritis complicate a substantial proportion of infections, particularly among adult females. Encephalitis is seen in 1:6 000 cases, and occurs with a higher frequency in adults. Up to 50% of rubella infections are subclinical.

For surveillance purposes, the WHO-recommended case definition of a suspected rubella case is any person with fever, non-vesicular (maculopapular) rash and adenopathy (cervical, sub-occipital or post-auricular). Laboratory diagnosis of rubella is required, since clinical diagnosis is often inaccurate. Laboratory confirmation is usually based on a positive rubella-specific IgM ELISA test on a blood specimen obtained within 28 days after the rash onset. An epidemiologically confirmed rubella case is a patient with suspected rubella with an epidemiological link to a laboratory-confirmed case. Other methods for rubella diagnosis include paired serum specimens that show seroconversion, or at least a 4-fold rise in rubella-specific IgG antibody titer, positive rubella PCR test, and virus isolation; PCR and virus isolation may be only available in higher-level reference laboratories.

Rubella is important because of its ability to produce anomalies in the developing fetus. Congenital rubella syndrome (CRS) occurs in up to 90% of infants born to women who are infected with rubella during the first 10 weeks of pregnancy; defects are rare when maternal infection occurs after the 20th week of gestation. Congenital malformations and fetal death may occur following inapparent maternal rubella.

Fetuses infected early are at greatest risk of intrauterine death, spontaneous abortion and congenital malformations of major organ systems. These include single or combined defects such as hearing impairment, cataracts, microphthalmia, congenital glaucoma, microcephaly, meningoencephalitis, developmental delay, patent ductus arteriosus, atrial or ventricular septal defects, purpura, hepatosplenomegaly, jaundice, and radiolucent bone disease. Moderate and severe CRS is usually recognizable at birth; mild CRS with only slight cardiac involvement or hearing impairment may not be detected for months or even years after birth. Insulin-dependent diabetes mellitus is recognized as a frequent late manifestation of CRS.

Infectious Agents

Rubella virus (family Togaviridae; genus Rubivirus).
 


Diagnosis

Laboratory confirmation of CRS in an infant is based on a positive rubella-specific IgM ELISA test on a blood specimen; the persistence of a rubella-specific IgG antibody titer in a blood specimen beyond the time expected from passive transfer of maternal IgG antibody; isolation of the virus from a throat swab or urine specimen; or detection of rubella virus by PCR. Almost all infants with CRS have a positive rubella IgM test in the first 3 months of life, and >30% remain positive during the second 6 months of life. Rubella virus has been isolated from throat and urine specimens of infants with CRS, and from cataract surgery aspirates in children up to 3.
 


Epidemiology

Mode of Transmission

Contact with nasopharyngeal secretions of infected people. Infection is by droplet spread or direct contact with patients. Infants with CRS shed large quantities of virus in their pharyngeal secretions and urine, and serve as a source of infection to their contacts.

Incubation Period

From 14–17 days with a range of 14–21 days.

Period of Communicability

For about 1 week before and at least 4 days after onset of rash; highly communicable. Infants with CRS may shed virus for months after birth.

Reservoir

Humans.

Susceptibility

Immunity is usually permanent after natural infection, and thought to be long-term, probably lifelong, after immunization; but persistent immunity may require contact with endemic cases. Infants born to immune mothers are ordinarily protected for 6–9 months, depending on the amount of maternal antibodies acquired transplacentally.

Occurrence

In the absence of generalized immunization, rubella occurred worldwide at endemic levels with epidemics every 5–9 years. Large rubella epidemics resulted in very high levels of morbidity: for example, the USA epidemic in 1964–1965 led to an estimated 12.5 million cases of rubella, over 20 000 cases of CRS, and 11 000 fetal deaths; the incidence of CRS during endemic periods was 0.1–0.2 per 1 000 live births, and 1–4 per 1 000 live births during epidemics. In countries where rubella vaccine has not been introduced, rubella remains endemic. In 1999, an estimated minimum of 100 000 CRS cases occurred each year in developing countries.

As of end-2006, 123 countries/territories (64% of the world total) regularly use rubella vaccine in their national immunization programs, with the highest coverage in the Americas (97% of countries), Europe (96%), the Eastern Mediterranean region (71%), and the Western Pacific (67%). Of these 123 countries, 107 include 2 doses in the routine schedule, and nine provide a 3rd dose during adolescence. In many countries, sustained high levels of rubella immunization have drastically reduced or practically eliminated rubella and CRS.


Prevention and Control

Rubella control is needed primarily to prevent defects in the offspring of women who acquire the disease during pregnancy.

1)    Preventive measures:

a)    Educate the general public on modes of transmission, and stress the need for rubella immunization. Health care providers must be aware of the risks caused by rubella in pregnancy.

b)    WHO recommends use of the vaccine in all countries where control or elimination of CRS is considered a public health priority. The primary purpose of rubella vaccination is to prevent the occurrence of congenital rubella infection, including CRS. This can be done using combined vaccines (MR or MMR), and current efforts in global measles control should be used as an opportunity to pursue control of rubella. Two approaches are recommended to prevent the occurrence of CRS:

i)    Prevention of CRS only, through immunization of adolescent girls or women of childbearing age.


ii)     Elimination of rubella as well as CRS, through universal immunization of infants and ensuring immunity in women of childbearing age. For increased impact men should also be vaccinated.

c)    To achieve rubella and CRS elimination rapidly, countries may wish to conduct mass campaigns in adults, both male and female. Decisions on which approach is taken should be based on level of susceptibility in women of childbearing age, burden of disease due to CRS, strength of the basic immunization program as indicated by routine measles vaccine coverage, infrastructure, and resources for child and adult immunization programs. Following well-designed and well-implemented programs, rubella and CRS have almost disappeared from many countries. Two regions—the Americas and Europe—have adopted a goal of rubella elimination.

A policy of rubella vaccination of adults is unlikely to alter rubella transmission dynamics, and in practice is difficult to implement with high coverage rates. Inadequately implemented childhood vaccination may run the risk of increasing the number of susceptibles among women—and the possibility of increased numbers of cases of CRS—until immunized child cohorts become adults. Consequently, it is essential that childhood rubella vaccination programs achieve and maintain high levels of coverage (estimated at above 80% to be effective) to decrease the incidence of rubella on a long-term basis.

A single dose of live, attenuated rubella virus vaccine elicits a significant and long-lasting antibody response in about 95%–100% of susceptible individuals aged 9 months or older. Rubella vaccines are cold-chain dependent, and should be protected from light. Several rubella vaccines are available as single antigen, measles-rubella (MR), measles-mumps-rubella (MMR), or measles-mumps-rubella-varicella (MMRV) vaccines. Most of the currently licensed vaccines are based on the live attenuated RA27/3 strain of rubella virus; other live attenuated rubella virus strains are used in China and Japan.

Following the introduction of large-scale rubella vaccination, coverage should be measured periodically by age and locality. In addition, surveillance is needed for rubella and CRS. If resources permit, longitudinal serological surveillance can be used to monitor the impact of the immunization program, especially through assessing rubella IgG antibody in serum samples from women attending antenatal clinics.

Rubella vaccine should be avoided in pregnancy because of the theoretical—but never demonstrated—teratogenic risk. No CRS occurred in more than 2 000 susceptible pregnant women who were unknowingly pregnant and received RA 27/3 rubella vaccine in early pregnancy. If pregnancy is being planned, however, an interval of one month should be observed after rubella immunization. Receipt of rubella vaccine during pregnancy is not an indication for abortion.

Rubella vaccine should not be given to anyone with an immunodeficiency or who receives immunosuppressive therapy. Asymptomatic HIV-infected persons can be immunized.

d)    In case of infection with wild rubella virus early in pregnancy, culturally appropriate counseling should be provided. Abortion may be considered in those countries where this is an option.


e)    Intramuscular Immune Globulin (IG) given in a dose of 20 mL within 72 hours of rubella exposure may decrease clinical disease, viral shedding and the rate of viremia in exposed susceptible persons. IG may be considered for a susceptible pregnant woman exposed to the disease who would not be in a position to consider abortion. The absence of clinical signs in a pregnant woman who has received IG does not guarantee that fetal infection has been prevented. Infants with congenital rubella have been born to mothers who were given IG shortly after exposure.

2)    Control of patient, contacts and the immediate environment:

a)    Report to local health authority: In countries where rubella eradication is a goal, all cases of rubella and of CRS should be reported. In many countries, reporting is obligatory, Class 3. Early reporting of suspected cases permits early establishment of control measures.

b)    Isolation: In hospitals, patients suspected of having rubella should be managed under contact isolation precautions; attempts should be made to prevent exposure of non-immune pregnant women. Exclude children from school and adults from work for 7 days after onset of rash. Infants with CRS may shed virus for prolonged periods of time. All persons having contact with infants with CRS should be immune to rubella (naturally or through immunization); contact between these infants and pregnant women should be avoided. In hospitals, contact isolation precautions should be applied to infants under 12 months with CRS, unless urine and pharyngeal virus cultures are negative for rubella virus.

c)    Concurrent disinfection: Not applicable.

d)    Quarantine: Not applicable.

e)    Immunization of contacts: Immunization of contacts will not necessarily prevent infection or illness. Passive immunization with IG is not indicated.

f)    Investigation of contacts and source of infection: Identify pregnant female contacts, especially those in the first trimester. Such contacts should be tested serologically for susceptibility or early infection (IgM antibody), and advised accordingly.

g)    Specific treatment: None.

3)    Epidemic measures:

a)    Prompt reporting of all confirmed and suspected cases; the country's established goal for rubella control/elimination will dictate the level of investigation required. During an outbreak, a limited number (5–10) of suspect cases (see definition earlier) should be investigated with laboratory tests to confirm that disease is due to rubella.

b)    The medical community and general public should be informed about rubella epidemics in order to identify and protect susceptible pregnant women. Active surveillance for infants with CRS should be carried out until 9 months after the last reported rubella case.

4)    Disaster implications:

None.

5)    International measures:

None.

Source: Heymann (Ed.). (2008). Control of Communicable Diseases Manual, 19th edition. Washington, DC: American Public Health Association.
 


Available Vaccines

WHO-Prequalified Rubella Vaccines

 

Common Disease Taxonomy: