The Eradication of Rubella

During 1963 to 1964, a pandemic of rubella swept across Europe and the United States, leaving in its wake at least 20,000 affected infants in this country alone.¹ During the epidemic an expanded congenital rubella syndrome (CRS) was described, involving not only the classic triad of cataracts, cardiac abnormalities, and deafness, but also encephalitis, wasting, hepatitis, pneumonia, endocrinopathies, and other sequelae. This disaster supervened just after the first isolation of rubella virus in cell culture and stimulated efforts to develop a vaccine, which were successful by the end of the decade.

The initial strategy of vaccination of infants was only partly successful because transmission continued among adults.² An alternative strategy focusing on vaccination of schoolgirls failed to provide sufficient population immunity.³ Consequently, current policy in the United States, and in most European countries,⁴ is to vaccinate all infants against rubella using measles-mumps-rubella (MMR) and then to revaccinate either at school entry or at adolescence. This policy is supplemented by targeted vaccination of seronegative women, in particular those who have just delivered an infant, to prevent rubella in a future pregnancy.⁵

The success of current policies in countries using the rubella vaccine has been considerable. In Finland, a systematic 2-dose MMR policy completely eliminated both rubella and CRS from the country.⁶ In the United Kingdom, MMR vaccination controlled rubella in children and their mothers, but an epidemic in 1996 showed that men were susceptible.⁷

In the United States, transmission of indigenous rubella may have been interrupted at least once, and the source of rubella outbreaks now is from infected persons from countries where rubella is not included in routine immunization or just recently introduced schedules or administered in mass campaigns.⁸ Unvaccinated persons arrive in the United States mainly from Latin American countries and thus the outbreaks occur mainly in Latino communities, often in young men. When rubella outbreaks occur in adults, CRS follows.⁹ A review of CRS from 1985 to 1996 reported that 44% of cases were in Latino infants.⁸ Opportunities to vaccinate against rubella had been neglected in 52% of women who gave birth to affected infants.⁸

The CRS is still an important cause of birth defects and disabilities in developing countries. An extensive review by Cutts et al¹⁰ showed convincingly that CRS occurs on all continents and in persons of all races and socioeconomic levels. Seroprevalence studies have demonstrated that women in many developing countries have low seroimmunity to rubella, particularly in rural areas and islands.¹¹

Fortunately, as was the case previously with poliomyelitis and measles, the Pan American Health Organization has recognized the rubella problem and has taken action. Laboratory testing of suspected measles cases during 1996 and 1997 in several Latin American countries revealed that at least one third were actually rubella. Armed with that information, and bearing in mind that both MMR and measles-rubella vaccines are widely available, the Pan American Health Organization now advises countries in the Americas to use combined vaccines in routine vaccination and in mass campaigns against measles. This policy takes advantage of an opportunity that may not come again, for if measles vaccination eliminates measles, it may no longer be cost-effective to use mass catch-up campaigns for rubella control. Recently, the governments of the English-speaking Caribbean nations have decided to add rubella to measles elimination efforts. An international task force sponsored by numerous organizations¹² concluded that eradication of rubella should be possible for many reasons.

First, rubella is an infection of humans only. The only reservoirs are CRS cases, who may excrete virus for many months, so when CRS cases are reduced,¹³ reservoirs disappear.

Second, the RA 27/3 rubella vaccine is highly immunogenic and protective. Seroconversion is usually greater than 97%, and protection against rubella has been recorded as 95% or higher after a single dose of the vaccine.^{1 ,14} Although reinfection can occur, bearing a child with CRS after reinfection during pregnancy is rare. The vaccine is well tolerated in children. Although women can develop arthralgias and arthritis following vaccination, the latter resolves within weeks. The previously advanced idea that joint symptoms may become chronic has not been supported by recent data.¹⁵

Third, rubella vaccine is available in combination with measles or with measles and mumps vaccines at relatively low prices outside of the United States and should be affordable except in the poorest countries. Rubella vaccination already has been applied in some developing countries, such as Brazil, with subsequent reduction in CRS.^{16 - 17}

Fourth, the measles and rubella vaccines can be administered at age 9 months, in conformity with the Expanded Programme of Immunisation calendar, without compromising the immunogenicity of either component.¹⁸

To monitor the effects of an eradication campaign, better surveillance of rubella and CRS is necessary. Rash disease is ubiquitous and often unreported, and one cannot expect to identify all cases of rubella, particularly as infection without rash is common.¹⁹ Nevertheless, IgM testing for rubella from serum or even saliva is now practical, and efforts have begun to apply these tests to the diagnosis of epidemic or sporadic illnesses with rash.²⁰ The easiest clinical indicator of CRS to detect would be the combination of congenital cataracts and congenital heart disease.^{19 ,21} If all infants with this combination of signs were tested for virological or serological evidence of rubella infection, the true incidence of severe CRS could be approximated. Hearing tests in infants, now practical and simple to perform, would be required to improve case ascertainment.

With a surveillance system for CRS in place (or at least being organized), rubella vaccination could be administered routinely to infants, preferably with a second dose administered later in childhood, as part of a plan to eradicate rubella. For reasons of cost-effectiveness, this effort should be launched using a combination vaccine in the context of a simultaneous effort to eradicate measles.

Unfortunately, universal vaccination of infants without associated vaccination of adults is not likely to eradicate rubella until many cohorts have been accumulated. There is also a theoretical risk that women will be less exposed to the wild virus as a result of infant vaccination and therefore more susceptible to infections leading to CRS.²² However, although the US experience with infant-only vaccination showed a relative shift upward in the age of rubella, it did not show an increase in the absolute incidence of the disease in adults nor were there more CRS cases.² Thus, the risk remains theoretical.

An earlier effect could be expected if vaccination of adolescent girls and women were also undertaken. In this regard, there are several options depending on the desired rapidity of effect and the finances available. The most effective option would be mass vaccination of both men and women up to age 40 years. A second option is a vaccination campaign involving only women younger than 40 years, and the third option is vaccination of girls, adolescent girls, and young women between the ages of 5 and 20 years, as suggested by Hinman et al.²³ The campaign would need to be done only once, but it should be supplemented by routine postpartum vaccination of women to protect future pregnancies. These options are much more cost-effective if chosen in the context of campaigns against measles that use combined vaccines.

The eradication of CRS and rubella is feasible. Rubella vaccine should be included in routine immunization programs of more countries. Aside from routine vaccination of infants, efforts to strengthen routine postpartum vaccination of susceptible women are needed. In addition, adolescents of both sexes and young men should be included in rubella vaccination strategies. Rubella is vulnerable to eradication. The tools to achieve eradication are available and if used properly, thousands of future infants will be saved from disability or premature death.