Pathogenesis and Pathology Neonatal, childhood, and adult infections occur through the mucosa of the upper respiratory tract. Rubella has an incubation period of about 12 days or longer. Initial viral replication probably occurs in the respiratory tract followed by multiplication in the cervical lymph nodes. Viremia develops after 7–9 days and lasts until the appearance of antibody on about day 13–15. The development of antibody coincides with the appearance of the rash, suggesting an immunologic basis for the rash. After the rash appears, the virus remains detect able only in the nasopharynx, where it may persist for several weeks (Figure 1). In 20–50% of cases, the primary infection is subclinical.

Fig1. Natural history of primary rubella infection: virus production and antibody responses. CF, complement fixation; HI, hemagglutination inhibition.

Clinical Findings

Rubella usually begins with malaise, low-grade fever, and a morbilliform rash appearing on the same day. The rash starts on the face, extends over the trunk and extremities, and rarely lasts more than 3 days. No feature of the rash is pathognomonic for rubella. Unless an epidemic occurs, the disease is difficult to diagnose clinically because the rash caused by other viruses (eg, enteroviruses) is similar.

Transient arthralgia and arthritis are commonly seen in adults, especially women. Despite certain similarities, rubella arthritis is not etiologically related to rheumatoid arthritis. Unusual complications include thrombocytopenic purpura and encephalitis. Virus can rarely persist in the immunologically priviledged intraocular site and in immunocompromised individuals.

Immunity

Rubella antibodies appear in the serum of patients as the rash fades and the antibody titer rises rapidly over the next 1–3 weeks. Much of the initial antibody consists of IgM antibodies, which generally do not persist beyond 6 weeks after the illness. IgM rubella antibodies found in a single serum sample obtained 2 weeks after the rash give evidence of recent rubella infection. IgG rubella antibodies usually persist for life.

One attack of the disease confers lifelong immunity because only one antigenic type of the virus exists. Because of the nondescript nature of the rash, a history of “rubella” is not a reliable index of immunity. Immune mothers transfer antibodies to their offspring, who are then protected for 4–6 months.

Laboratory Diagnosis

Clinical diagnosis of rubella is unreliable because many viral infections produce symptoms similar to those of rubella. Certain diagnosis rests on specific laboratory studies (isolation of virus, detection of viral RNA, or evidence of seroconversion).

A. Nucleic Acid Detection

RT-PCR can be used to detect rubella virus nucleic acid directly in clinical samples or in cell cultures used for virus isolation. Molecular typing can identify virus subtypes and genotypes and is useful in surveillance studies. Throat swabs are appropriate samples for molecular typing.

B. Isolation and Identification of Virus

Nasopharyngeal or throat swabs taken 6 days before and after onset of rash are a good source of rubella virus. Various cell lines of monkey or rabbit origin may be used. Rubella produces a rather inconspicuous cytopathic effect in most of the cell lines. Using cells cultured in shell vials, viral antigens can be detected by immunofluorescence 3–4 days postinoculation.

C. Serology

The HI test is a standard serologic test for rubella. However, serum must be pretreated to remove nonspecific inhibitors before testing. ELISA tests are preferred because serum pretreatment is not required and they can be adapted to detect specific IgM.

Detection of IgG is evidence of immunity because there is only one serotype of rubella virus. To accurately confirm a recent rubella infection (critically important in the case of a pregnant woman), either a rise in antibody titer must be demonstrated between two serum samples taken at least 10 days apart or rubella-specific IgM must be detected in a single specimen.

Epidemiology Rubella is worldwide in distribution. Infection occurs throughout the year with a peak incidence in the spring. Epidemics occur every 6–10 years, with explosive pandemics every 20–25 years. Infection is transmitted by the respiratory route, but rubella is not as contagious as measles.

A worldwide rubella epidemic occurred from 1962 to 1965. There were more than 12 million cases in the United States, resulting in 2000 cases of encephalitis, more than 11,000 fetal deaths, 2000 neonatal deaths, and 20,000 infants born with congenital rubella syndrome. The economic impact of this epidemic in the United States was estimated at $1.5 billion. The use of rubella vaccine eliminated both epidemic and endemic rubella in the United States by 2005. A program is underway to also eliminate rubella and rubella congenital syndrome from Central and South America.

Treatment, Prevention, and Control

Rubella is a mild, self-limited illness, and no specific treatment is indicated.

Laboratory-proven rubella in the first 3–4 months of pregnancy is almost uniformly associated with fetal infection. Intravenous immune globulin injected into the mother does not protect the fetus against rubella infection because it is usually not given early enough to prevent viremia.

Attenuated live rubella vaccines have been available since 1969. The vaccine is available as a single antigen or combined with measles and mumps vaccine. The primary purpose of rubella vaccination is to prevent congenital rubella infections. The vaccine virus multiplies in the body and is shed in small amounts, but it does not spread to contacts. Vaccinated children pose no threat to mothers who are susceptible and pregnant. In contrast, nonimmunized children can bring home wild virus and spread it to susceptible family contacts. The vaccine induces lifelong immunity in at least 95% of recipients.

The vaccine is safe and causes few side effects in children. In adults, the only significant side effects are transient arthralgia and arthritis in about one-fourth of vaccinated women.

Vaccination in the United States decreased the incidence of rubella from about 70,000 cases in 1969 to fewer than 10 in 2004, cases that occurred predominantly among persons born outside the United States. The virus was subsequently declared eliminated from the United States. Cost–benefit studies in both developed and developing countries have shown that the benefits of rubella vaccination outweigh the costs.

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مواضيع ذات صلة

Congenital Rubella Syndrome

Hendra Virus and Nipah Virus Infections

Measles (Rubeola) Virus Infections

Rhabdoviruses

Retroviruses

Reoviruses

Poxviruses

Role of Biomarkers in COVID-19

Mumps Virus Infections

Human Metapneumovirus Infections

Respiratory Syncytial Virus Infections

Parainfluenza Virus Infections