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J. Pediatr. (Rio J.) vol.83 no.5 Porto Alegre Sept./Oct. 2007
Rubella vaccination strategy
Alan R. Hinman
MD, MPH. Task Force for Child Survival and Development, Decatur, Georgia, USA
When rubella vaccines were introduced in 1969 they were initially used only in industrialized countries. Two major strategies were used to prevent the occurrence of congenital rubella syndrome (CRS). In the United States, the strategy aimed to interrupt rubella virus circulation among young children, thereby reducing the possibility of exposure of a susceptible pregnant woman. This was accomplished by mass vaccination of children aged 1-12 (over the course of 1-3 years) followed by universal vaccination of children as they reached 1 year of age. In the United Kingdom (UK), the approach was to provide individual protection to girls as they entered the childbearing age and this involved vaccinating girls (only) at 12-14 years of age.
The U.S. approach greatly reduced the overall incidence of rubella and CRS and eliminated the prior 6-9 year epidemic cycle of the disease, but sporadic cases of CRS continued with transmission among young adults. In the UK, there was little change in the secular trend of rubella occurrence and there were sizeable epidemics with substantial increases in the number of cases of CRS, although fewer than in the pre-vaccine era. Thus, both approaches had some success, but neither had optimum impact. Reviewing the experience, in 1983, we concluded that the first priority of rubella vaccination programs should be to vaccinate women of childbearing age. The second priority should be to interrupt transmission of rubella (by vaccinating children). This "complete" strategy should lead to maximal prevention of CRS.1
The UK added rubella vaccine to its routine childhood immunization schedule in 1988 (as measles-mumps-rubella [MMR] vaccine) and conducted a large-scale campaign using measles-rubella (MR) vaccine in 1994.2 There has been a significant reduction in both rubella and CRS. In the United States, greater emphasis has been placed on immunizing women of childbearing age. Rubella is no longer an endemic disease in the United States. 3
There was a rapid evolution of rubella vaccination strategies in the Americas in the late 1980s and early 1990s. The lead was taken by the countries of the English-speaking Caribbean. As part of their measles elimination activities, many countries included rubella vaccine. There were two major components to the strategy: mass vaccination of males and females 1-40 years of age with MR or MMR and addition of rubella vaccine into the routine childhood immunization schedule. The result was that both measles and rubella were eliminated as indigenous diseases in the English-speaking Caribbean. 4
Notwithstanding the progress in the Caribbean, in 1998, we concluded that it was premature to establish a hemispheric goal of rubella elimination while acknowledging it could be a logical development as progress continued with elimination of measles. We did recommend initiation of surveillance of CRS (and rubella) throughout the Americas and incorporation of rubella vaccine (as MR or MMR) into childhood vaccination programs, both as part of routine childhood immunization at 12-15 months and as part of the follow-up measles campaigns reaching all children 1-4 years of age every 4 years. Over the course of several years this would prevent epidemic rubella among children, although it would not have an immediate effect on transmission of rubella among adults or on the occurrence of CRS. We also recommended that all countries should adopt one of three additional steps: mass vaccination of females 5-39 years of age, mass vaccination of both males and females 5-39 years of age, or vaccination of women of childbearing age. When a hemispheric goal of elimination was established, countries would need to fill in any of the steps that were not previously carried out. 5 Rubella surveillance was integrated with measles surveillance.
A 2000 meeting at the World Health Organization recommended two approaches for CRS prevention - prevention of CRS only (through immunization of adolescent girls and/or women of childbearing age), and elimination of rubella as well as CRS (through universal vaccination of infants with or without mass campaigns, surveillance, and assuring immunity in women of childbearing age). The meeting also recommended that countries which currently included rubella in their childhood immunization program should ensure that women of childbearing age are immune and should move toward rubella elimination. 6
The Pan American Health Organization (PAHO) recommended that "countries ready to accelerate rubella control and/or CRS prevention should rapidly introduce a rubella-containing vaccine into the adult population in addition to routine childhood vaccination. In order to accelerate CRS prevention, countries are advised to conduct a one-time mass vaccination campaign that targets all females aged 5-39 years with rubella-containing vaccines. With this strategy, the number of CRS cases drops significantly, but as men remain susceptible, the virus continues to circulate. However, for countries that seek an accelerated rubella control strategy, a one-time mass campaign (with a measles and rubella-containing vaccine) is recommended for both males and females aged 5-39 years. This strategy will interrupt rubella virus transmission." 7 Brazil and Chile targeted their campaigns to women only, while campaigns in Costa Rica and Honduras included men and women.8
Reflecting continuing progress in Western Hemisphere measles elimination and growing interest in the use of rubella vaccine, in September 2003, PAHO's Directing Council approved a resolution calling for Member States to eliminate rubella and CRS by the year 2010. 9
The magnitude of rubella as a public health problem in Brazil became apparent as Brazil implemented its measles elimination plan. Between 1993 and 1996, nearly 50% of suspected cases in which measles was ruled out were subsequently diagnosed as rubella. As part of measles elimination activities, children aged 1-11 years were vaccinated with the MR vaccine. Nonetheless, outbreaks of rubella were reported in several states between 1998 and 2000 and in many of them the highest proportion of cases occurred in adolescents and young adults. In response, a two-phase program of mass vaccination of women was carried out. Each state established the target group and the date. The most common target was women 12-39 years of age. Thirteen states carried out campaigns in adult women in November 2001 and the other 11 states carried out campaigns between June and July, 2002. In total, 27 million women were targeted.10
The article by Lanzieri et al. in this issue describes the progressive control of rubella and CRS in the state of Paraíba, Brazil.11 It also reflects the need to take a comprehensive approach in order to assure interruption of rubella transmission and elimination of CRS. Vaccination of all children aged 1-11 years in a mass campaign in 1998 followed by the introduction of the MMR vaccine into the routine childhood immunization schedule had a significant impact on transmission of rubella among children but did not prevent the occurrence of outbreaks of rubella in adolescents and young adults, as seen in 2000 in Paraíba. Had it been feasible to carry out mass vaccination of women at the time of the childhood campaign, the outbreak probably could have been prevented. However, in a country the size of Brazil, that would have presented enormous challenges in financing, planning and implementation. Vaccinating adult men as well as women (as done in most other countries in Latin America) would have virtually ensured there would be no continuing transmission of rubella among adults but also would have added another 25 million persons (or more) to be vaccinated, with concomitant additional cost and complexity.
There are two other items of note in Lanzieri's investigation. The first is the high proportion of suspected cases of CRS who had laboratory investigation (167/171 = 97.7%). This was the result of active surveillance that was implemented in the referral maternity hospital in the state capital in Paraíba and is to be contrasted with a lower proportion in a neighboring state that did not have active surveillance (2/45 = 4.4%).12 Effective surveillance is critical to assess interruption of rubella transmission. The second item of note is the fact that only half of the CRS cases had hearing impairment identified, lower than typically reported. This may reflect the often subtle manifestations of CRS.
I believe the main message to take from the experience in Paraíba (and Brazil) is that in a five-year period rubella and CRS have been nearly eliminated from a large and populous country. This is an important achievement and, with the experience in the rest of the Americas, should serve as a stimulus to the rest of the world to take action to prevent and eliminate congenital rubella infection.
I am grateful for the useful comments of Tatiana Lanzieri, Rebecca Prevots, and Susan Reef on drafts of this manuscript.
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11. Lanzieri TM, Pinto D, Prevots DR. Impact of rubella vaccination strategy on the occurrence of congenital rubella syndrome. J Pediatr (Rio J). 2007;83:415-21.
12. Lanzieri TM, Parise MS, Siqueira MM, Fortaleza BM, Segatto TC, Prevots DR. Incidence, clinical features and estimated costs of congenital rubella syndrome following a large rubella outbreak in Recife, Brazil, 1999-2000. Pediatr Infect Dis J 2004;23:1116-22.