Elsevier

The Lancet

Volume 363, Issue 9415, 3 April 2004, Pages 1127-1137
The Lancet

Seminar
Rubella

https://doi.org/10.1016/S0140-6736(04)15897-2Get rights and content

Summary

Maternal rubella is now rare in many developed countries that have rubella vaccination programmes. However, in many developing countries congenital rubella syndrome (CRS) remains a major cause of developmental anomalies, particularly blindness and deafness. WHO have provided recommendations for prevention of CRS, and, encouragingly, the number of countries introducing rubella vaccination programmes has risen. However, declining uptake rates due to concerns about the measles-mumps-rubella vaccine in the UK, and increasing numbers of cases in some European countries coupled with poor uptake rates might jeopardise this progress. Surveillance of postnatally and congenitally acquired infection is an essential component of CRS prevention since rubella is difficult to diagnose on clinical grounds alone. Laboratory differentiation of rubella from other rash-causing infections, such as measles, parvovirus B19, human herpesvirus 6, and enteroviruses in developed countries, and various endemic arboviruses is essential. Reverse transcriptase PCR and sequencing for diagnosis and molecular epidemiological investigation and detection of rubella-specific IgG and IgM salivary antibody responses in oral fluid are now available.

Section snippets

Pathogenesis

Infection is acquired via inhalation of aerosol, and the virus infects cells in the upper-respiratory tract, after which cell entry occurs by receptor-mediated endocytosis. Rubella spreads and replicates in the lymphoid tissue of the nasopharynx and upper-respiratory tract, after which a viraemia leads to systemic infection, involving many organs, including the placenta.

Infected people excrete high concentrations of rubella in nasopharyngeal secretions. Thus, vaccinees may excrete more than 105

Pathogenesis

Fetal damage is multifactorial, resulting from a combination of rubella-virus-induced cellular damage and the effect of the virus on dividing cells. Placental infection occurs during maternal viraemia, resulting in focally distributed areas of necrosis in the epithelium of chorionic villae and in the endothelial cells of its capillaries.31 These cells seem to be desquamated into the lumen of vessels, suggesting that rubella virus is transported into the fetal circulation as infected endothelial

Postnatally acquired infection

Various techniques have been used to assess immunity by detecting rubella-specific IgG from naturally acquired or vaccine-induced infection. In the past, tests to detect rubella-specific neutralising antibodies, haemagglutination-inhibition antibodies or single radial haemolysis were widely used.74 However, laboratories now generally use commercially available enzyme immunoassay for IgG and IgM detection.75, 76 In Britian a national standard serum is available and an antibody concentration of

Vaccination

Rubella vaccination makes CRS a preventable disease. Live attenuated rubella vaccines were first licensed in the 1960s (panel). RA27/3, which is grown in human diploid cells, is now used in most of the world, although China and Japan use similar locally developed live attenuated vaccines. Immune responses to rubella vaccine closely resemble those of naturally acquired infection. More than 95% of recipients older than 11 months seroconvert and antibody responses are detectable for more than 21

Epidemiology, immunisation, and surveillance

Immunisation programmes have already had a major impact on the epidemiology of rubella in many developed and several developing countries. In some countries in Europe, in the USA, and Australasia, CRS is now very rare, and countries using two doses of the MMR vaccine, such as the USA, have interrupted indigenous transmission of rubella virus.104

There is now an impetus to extend vaccination programmes to the developing world. A review of published work sponsored by WHO in 1996 showed that in 45

Future issues

The indigenous circulation of rubella has been interrupted and CRS cases have been virtually eliminated in the USA and several European countries. These achievements indicate that the goal of rubella elimination and CRS control is largely dependent on the establishment of vaccination programmes. Elimination programmes should be supported by appropriate surveillance including molecular epidemiological studies to establish links between cases and outbreaks and provide useful evidence about the

Search strategy and selection criteria

We did a computerised and manual search on PubMed of published work to identify studies, with particular focus on original reports published in the past 10 years. Selection criteria included a judgment about importance of studies and their relevance to the well-informed general medical doctor. Keywords used were “CRS”, “congenital rubella syndrome”, “immunisation”, “vaccination”, “MMR”, “rubella”, “rubella virus”, “rubella diagnosis”, and “rubella epidemiology”.

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