INTRODUCTION

SUPPLEMENT ARTICLE

The Evidence for the Elimination of Rubella and Congenital Rubella Syndrome in the United States: A Public Health Achievement
Susan E. Reef and Stephen L. Cochi
National Center for Immunization and Respiratory Diseases (proposed), Centers for Disease Control and Prevention, Atlanta, Georgia

Twenty years after Norman Gregg, in 1941, discovered the association between intrauterine rubella and congenital cataracts, a rubella pandemic occurred, with devastating consequences. During the 1962 1965 global pandemic, an estimated 12.5 million rubella cases occurred in the United States, resulting in 2000 cases of encephalitis, 11,250 therapeutic or spontaneous abortions, 2100 neonatal deaths, and 20,000 infants born with congenital rubella syndrome (CRS), a constellation of birth defects that often includes cataracts, heart defects, and deafness [1]. The economic impact of this epidemic in the United States was estimated to be $1.5 billion [1]. The global epidemic spurred the development of rubella vaccines and emphasized the need to develop and implement strategies for using these vaccines to prevent this devastating health burden. In 1969, live attenuated rubella vaccines were licensed in the United States. The goal of the rubella vaccination program was to prevent congenital infections, including CRS. The initial strategy used to achieve the public health goal was to target chilReprints or correspondence: Dr. Susan E. Reef, National Center for Immunization and Respiratory Diseases (proposed), Centers for Disease Control and Prevention, 1600 Clifton Rd. NE, MS A-47, Atlanta, GA 30333 (sreef@cdc.gov). Clinical Infectious Diseases 2006; 43:S1235 This article is in the public domain, and no copyright is claimed. 1058-4838/2006/4309S3-0001

dren between 1 year of age and puberty with 1 dose of rubella-containing vaccine (gure 1) [2]. During the rst 8 years of the program, reported rubella and CRS cases declined by 78% and 66%, respectively. The number of rubella cases declined from 57,686 in 1969 to 12,491 in 1976 [3]. The number of CRS cases declined from 68 reported cases in 1970 to 23 in 1976 [4]. However, in 19771978, there was a resurgence of rubella, mainly among older adolescents and young adults, because the initial vaccination strategy implemented in 1969 targeted children in the rubella vaccination program [5]. This change in the epidemiological prole of rubella prompted a modication of the rubella vaccination program strategy. Several additional groups were targeted, including susceptible postpubertal females, persons in military service, college students, and persons in certain work settings (e.g., health care). In addition, in 1978, the goal of eliminating indigenous measles from the United States was undertaken. The use of combination vaccines, either measles-rubella or measles-mumps-rubella (MMR) vaccine, was encouraged, to increase the rubella and mumps coverage level among children [6]. In 1979, the RA 27/3 rubella vaccine replaced the other rubella vaccines (HPV-77 and Cendehill) in the United States. Because of further declines in rubella and CRS cases after 1978, na-

tional health objectives for rubella and CRS established for 1990 called for reductions in the annual number of rubella cases to !1000 and of CRS cases to !10 [7]. Efforts to increase vaccination coverage of school-age children were successful. For instance, a survey of children entering school (kindergarten or rst grade) in 19801981 showed that 96% had received rubella vaccine. By 1983, the 1990 national health objectives for rubella and CRS had been achieved. With the success in reaching these objectives, in 1989, a goal (Healthy People 2000) was established to eliminate indigenous rubella and CRS in the United States by 2000 [8]. Shortly after the Healthy People 2000 goal was established, another resurgence of rubella occurred in the United States, during 19901991, that mainly affected unvaccinated adults and religious communities that did not accept vaccinations. In response, efforts to ensure high vaccination coverage were intensied; these efforts were part of the Childhood Immunization Initiative that began in 1993 [9]. In 1989, because of continued outbreaks of measles, a policy of 2-dose measles vaccination using the MMR vaccine [10] was implemented, which subsequently resulted in measles elimination in the United States [11]. Because of the recommended use of 2 doses of MMR vaccine, children routinely received a second dose of ru-

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Figure 1. Number of reported cases of rubella and congenital rubella syndrome (CRS), by year, and chronology of rubella vaccination recommendations by the Advisory Committee on Immunization PracticesUnited States, 19662004. *1969: rst ofcial recommendations are published for the use of rubella vaccine; vaccination is recommended for children 1 year of age to puberty. 1978: recommendations for vaccination are expanded to include adolescents and certain adults, particularly females; vaccination is recommended for adolescent or adult females and males in populations in colleges, certain places of employment (e.g., hospitals), and military bases. 1981: recommendations place increased emphasis on vaccination of susceptible persons in training and educational settings (e.g., universities or colleges) and military settings and vaccination of workers in health care settings. 1984: recommendations are published for vaccination of workers in day care centers, schools, colleges, companies, government ofces, and industrial sites; providers are encouraged to conduct prenatal testing and postpartum vaccination of susceptible women; recommendations for vaccination are expanded to include susceptible persons who travel abroad. **1990: recommendations include implementation of a new 2-dose schedule for measles-mumps-rubella vaccine.

bella vaccine. Although, on a theoretical basis, it may have been possible to interrupt rubella virus transmission with a 1-dose schedule, the 1989 2-dose MMR vaccine recommendation was designed to ensure that immunity to all 3 viruses was achieved [12]. Further reductions in numbers of rubella and CRS cases occurred. In the mid-1990s, the epidemiological prole of rubella changed signicantly. Rubella cases, now at or near record-low numbers, occurred mainly among foreign-born Hispanic persons from countries that had not incorporated rubella vaccination into their national program or had just recently implemented routine rubella vaccination programs [13]. In 2000, rubella cases continued to occur among foreign-born Hispanic persons; very few cases occurred among persons born in the United States, because of the high levels of population immunity achieved primarily through the childhood vaccination program and the 30 years of routine use of rubella vaccine [14]. As rubella vacS124 CID 2006:43 (Suppl 3) Reef and Cochi

cination efforts intensied in the countries of the Western Hemisphere, further declines occurred in numbers of rubella and CRS cases in the United States. Between 2000 and 2001, there was a signicant decrease in the number of rubella cases, from 179 to 23. Since 2001, there have been !25 reported rubella cases reported annually [15]. In 2004, an independent panel of internationally recognized experts in public health, infectious diseases, and immunizations reviewed the available data presented in this supplement and unanimously agreed that rubella is no longer endemic in the United States [13]. These data included (1) an epidemiological prole of rubella and CRS that supported elimination of endemic rubella in the United States; (2) a molecular epidemiological prole of rubella and CRS that showed a pattern of virus genotypes consistent with virus originating outside the United States; (3) very high rubella vaccine coverage for the United States; (4) sero-

prevalence data from the National Health and Nutrition Examination Survey that supported very high levels of humoral immunity among residents of the United States; (5) adequacy of rubella and CRS surveillance throughout the United States, including 2 high-risk areas, California and New York City; and (6) international information, including data from Mexico and other countries in the Pan American Health Organization Region of the World Health Organization, that demonstrated the impact of accelerated rubella control during the late 1990s and early 2000s. Several lessons were learned that helped the United States to achieve elimination. For epidemiological proles of rubella and CRS and outbreaks of rubella, it was critical to document where the patients were born. This information assisted us in understanding the risk of susceptibility in foreign-born persons living in the United States. In addition, we were able to work with the patients countries of origin and to target these high-risk populations in the United States for rubella vaccination. Regional elimination of rubella is not an endeavor of a single country or organization; it takes the cooperation and concerted efforts of all countries in the affected geographic area. The number of rubella cases in the United States decreased signicantly after the acceleration of rubella control strategies in Latin America. With the elimination of endemic chains of rubella transmission in the United States, future patterns of rubella will most likely reect global disease epidemiological proles. The United States is, to date, the largest country and geographic area to eliminate rubella. The experiences of the United States and several other countries that have eliminated rubella provide the needed tools on which to build additional efforts to eliminate rubella and CRS in other geographic regions. According to a survey of the member countries in the World Health Organization, the number of countries that have incorporated rubella-containing vaccine into their routine national immunization programs in-

creased from 65 (12% of the birth cohort) in 1996 to 116 (26% of the birth cohort) in 2004. To monitor this public health achievement, the United States will need to continue its vigilance against rubella and CRS. In summary, a major public health milestone has been reached. Rubella, a disease that resulted in many infants being born with congenital birth defects that frequently resulted in lifelong disabilities, is no longer endemic in the United States. We congratulate health professionals in the United States for achieving this success by building strong immunization programs nationwide. In particular, we recognize the thousands of persons in both the public and private sectors, including nurses, doctors, epidemiologists, public health advisors, immunization advocates, and parents, who have participated in ensuring rubella vaccination. Their diligent efforts have resulted in ending endemic rubella virus circulation within the borders of the United States. We dedicate this supplement on rubella and CRS elimination in the United States to them.
Acknowledgments
We thank Mark Papania, for his assistance in the design of the rubella elimination meeting and of studies for the meeting, and Charles LeBaron

and Mary McCauley, for scientic and editorial support, respectively. Financial support. US government. Supplement sponsorship. This article was published as part of a supplement entitled The Evidence for the Elimination of Rubella and Congenital Rubella Syndrome in the United States: A Public Health Achievement, sponsored by the Centers for Disease Control and Prevention. Potential conicts of interest. S.E.R. and S.L.C.: no conicts.

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