Accelerated Rubella Control and Congenital Rubella Syndrome Prevention Strengthen Measles Eradication: The Costa Rican Experience

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1 SUPPLEMENT ARTICLE Accelerated Rubella Control and Congenital Rubella Syndrome Prevention Strengthen Measles Eradication: The Costa Rican Experience Ana Morice, 1 Xinia Carvajal, 1 Mario León, 2 Vicenta Machado, 2 Xiomara Badilla, 2 Susan Reef, 4 Fabio Lievano, 4 Ariel Depetris, 3 and Carlos Castillo-Solórzano 5 1 Ministry of Health, 2 Social Security Administration of Costa Rica, and 3 Pan American Health Organization, San Jose, Costa Rica; 4 Centers for Disease Control and Prevention, Atlanta, Georgia; 5 Pan American Health Organization, Washington, DC In 2000, Costa Rica set a goal for accelerated rubella control and congenital rubella syndrome (CRS) prevention in conjunction with its established measles eradication goal. To achieve this goal, a National Plan of Action for the integration of a measles-rubella (MR) vaccination strategy was implemented. The components of the national plan included conducting a national vaccination campaign with a single dose of MR vaccine for men and women aged years, establishing routine postpartum MR vaccination of all previously unvaccinated women, maintaining high coverage among children with two doses of measles-mumps-rubella vaccine, strengthening the integrated measles and rubella surveillance system, and developing a CRS surveillance system. This report summarizes the results of a successful adult campaign. Targeting MR vaccination appropriately and using the opportunity to strengthen surveillance for rash illness has benefits beyond accelerated rubella control and CRS prevention, including strengthening of the measles eradication program. In Costa Rica, the use of vaccines to prevent disease among children has been a cornerstone of national maternal and child health programs. The National Health System, established in the 1970s, integrates the Ministry of Health (MoH) and the Costa Rican Social Security System (CCSS), to provide health care to all citizens [1]. Vaccines and related supplies have been provided with government funds as part of the World Health Organization Expanded Program on Immunization. Financial and technical support: Pan American Health Organization; CDC. Reprints or correspondence: Dr. Carlos Castillo-Solórzano, rd St. NW, Washington, DC (castilsc@paho.org). The Journal of Infectious Diseases 2003; 187(Suppl 1):S by the Infectious Diseases Society of America. All rights reserved /2003/18710S-0025$15.00 MEASLES VACCINATION AND EPIDEMIOLOGY In 1950, Costa Rica adopted a national strategy to control and eradicate vaccine-preventable diseases. Measles vaccine was introduced in 1967, rubella vaccine in 1972, and measles-rubella (MR) vaccine in 1975 into the childhood program. By 1984 coverage with one dose of MR among 1-year-old children reached about 80%. Use of measles-mumps-rubella (MMR) vaccine started in 1986 [2] and coverage reached 185% that year (figure 1). The epidemiology of measles and rubella remained largely unchanged throughout the 1970s due to low vaccination coverage (!40%). Large measles outbreaks occurred in (nearly 13,000 cases reported) and again in (17000 cases reported). The latter outbreak occurred primarily in densely populated areas, mainly affected children!5 years old (60%; figure 2), and caused 242 deaths. Overall during , S158 JID 2003:187 (Suppl 1) Morice et al.

2 Figure 1. Percentage of 1-year-old children vaccinated with combined measles-rubella vaccine and reported incidence of measles and rubella, Costa Rica, Data from Ministry of Health, Department of Statistics and Epidemiology, Costa Rica. 26,505 measles cases, including 512 measles-associated deaths, were reported. In , a large measles outbreak occurred among preschool-aged children [3]. The last measles outbreak ( ) resulted in 8684 reported cases and 55 deaths: 28% of the cases ( n p 1845, 264/100,000) occurred among school-aged children and 45% occurred among persons aged years ( n p 2914, 246/100,000; figure 3). The shift of measles to older age cohorts led to the introduction of a second dose of MMR in 1992, administered at age 7 years. In October 1991, the MoH adopted the goal of eliminating indigenous measles by achieving and maintaining high vaccine coverage, improving surveillance, and taking aggressive steps to control outbreaks. A national catch-up campaign for children aged 1 14 years was conducted in 1993, followed in 1994, 1997, and 2002 by national follow-up campaigns for children aged 1 4 years (table 1). After 1994, measles cases declined dramatically. However, 2 imported cases from Europe and Peru in 1999 resulted in 2 cases among unvaccinated people (ages, 9 months and 31 years). These were the last confirmed cases of measles in Costa Rica. RUBELLA EPIDEMIOLOGY The epidemiology of rubella in Costa Rica was not well documented before 1990, and thus the magnitude of reported outbreaks during this time was probably underestimated. The largest documented outbreak of rubella in Costa Rica occurred in with 4410 reported cases (144/100,000). During the next two decades, epidemic outbreaks of rubella were reported in (1987: 1557 cases; incidence, 38.5/100,000 population) and in (1999: 1610 cases; incidence, 39.1/ 100,000 population). In the outbreak, 75% of cases were among persons aged years. Incidence was greatest among those years old (85/100,000 population) followed by persons (38/100,000) and years old (29/100,000; figure 3). These findings were substantiated by a seroprevalence survey conducted in 1996, which showed that 37% of women aged years lacked rubella immunity [4]. Immunity was 93% among children!15 years and 46% among persons years old, 66% among those 25 34, and 75% among those 35 45, heightening the concern about the risk of congenital rubella syndrome (CRS). As an immediate response to this outbreak, a subnational vaccination campaign was conducted that targeted adolescent and young adult women in affected districts. There were concerns about the likelihood of CRS; however, no cases were detected by surveillance. Although no CRS cases have been reported to the passive notification system since 1992, 19 cases of CRS should be expected in 1999, assuming a risk of 0.9 cases of CRS in the first trimester of pregnancy by use of birthrates and reported rubella cases. A retrospective study conducted at the National Children s Hospital by analyzing the laboratory database of the hospital s immunology section identified 49 infants!3 months old who were IgM positive for rubella between 1996 and In addition, a study of deafness in [5] evaluated 12,612 first graders in 250 schools nationwide and detected a 2.5% prevalence of deafness. The deficit was bilateral in 86.4% of cases and 70% were moderate to severe. A history of rubella during pregnancy was a leading cause of deafness. It is estimated Costa Rica: Rubella and Measles Control JID 2003:187 (Suppl 1) S159

3 Figure 2. Reported measles and rubella cases by age group, Costa Rica, MR, measles-rubella vaccine; MMR, measles-mumps-rubella vaccine. Data from Ministry of Health, Department of Statistics and Epidemiology, Costa Rica. that babies per 1000 births have sensorineural deafness in Costa Rica. COSTA RICA NATIONAL PLAN OF ACTION, 2000 Based on the epidemiology of measles and rubella since 1970, the results of the 1996 rubella seroprevalence study, and the success in campaigns targeting vaccinations to children through age 14 years, the MoH and the CCSS formulated a National Plan of Action in 2000 for an integrated measles and rubella vaccination strategy [6]. The goal was to eradicate measles, accelerate rubella control, and improve the surveillance system. The plan had five components: (1) a national mass vaccination campaign targeting a single dose of MR to men and women aged years; (2) routine postpartum MR vaccination of all previously unvaccinated women; (3) maintenance of high coverage among children with two doses of MMR; (4) strengthening the integrated measles and rubella surveillance system; and (5) development of a CRS surveillance system. ADULT NATIONAL MR CAMPAIGN The goal of the nationwide adult immunization campaign was to achieve coverage above 95% within a 1-month period (May 2001) in persons 5 39 years old. The target was 42% (1,606,329) of the Costa Rica population [7]. Several important components were identified as key factors: Integration of MoH and CCSS, active participation of the entire national health services network, intersectoral participation of labor and education ministries, and strong social mobilization. To assess the epidemiologic surveillance and the campaign success, a National Commission of Immunization, chaired by the Minister of Health, was established. Social mobilization activities encouraged the participation of political, union, and religious leaders, national personalities, community associations, professional society presidents, educators, artists, entrepreneurs, local nongovernment organizations, and the media. Vaccination approaches varied based on criteria particular to each area such as access to existing services, availability of resources, and previous experience with similar activities. During the first 2 weeks, vaccination was done in areas populated S160 JID 2003:187 (Suppl 1) Morice et al.

4 Table Year, vaccine National measles-rubella campaigns, Costa Rica, Campaign type Target age group, years Targeted Population Vaccinated Coverage 1993, MMR Catch-up ,088,266 1,008,606 93% 1994, MMR Follow-up , ,014 81% 1997, MMR Follow-up , ,118 87% 2001, MR Adults ,665,987 1,635,445 98% 2002, MR Follow-up , ,761 86% NOTE. MMR, measles-mumps-rubella vaccine; MR, measles-rubella vaccine. Source: Directorate of Health Surveillance, Ministry of Health, Costa Rica. by workers and students. In most areas, multiple vaccination locations and times were offered [8]. In rural areas with disperse populations, vaccination began in hard-to-reach areas followed by vaccination in urban areas. Several tactics were used to ensure reaching dispersed population groups such as mobile posts, a call to gather at strategic locations, the use of brigades, houseto-house vaccination, and flexible hours. During weeks 3 and 4, door-to-door vaccination was conducted with maps to identify pockets of unvaccinated persons [9]. Timely progress reports allowed for the quick implementation of corrective measures to ensure the achievement of goals. Local and regional teams obtained daily and weekly information on campaign results. Data were validated by rapid monitoring of vaccination coverage and presented graphically to facilitate decisions regarding corrective measures. A critical component of the campaign was supervision at all levels. This continuous support was critical to ensure that all targeted populations were vaccinated by identifying geographic barriers and other factors that could hinder vaccination. Coverage. Coverage among the target group increased steadily over the 4 weeks from 30% at the end of week 1 to 61%, 80%, and 98% for subsequent weeks. Similar proportions of men (99%) and women (97%) in the target age range were vaccinated. Coverage for all age groups in the target range reached 90%, except for the year age group, which reached 87% [9]. The national vaccination coverage was 98%: Coverage in the provinces was 96% 105%. In 60 cantons (75%), coverage was 195%; in the other 22 cantons, coverage was 80% 95%. For women who were pregnant at the time of the campaign, a postpartum vaccination program was started. By June 2002, coverage in these women had reached 90%. Adverse events and vaccine safety. CCSS staff monitored vaccine safety through the existing national system of surveillance, which also monitored vaccine safety. This system detected 987 adverse events (60/100,000 population) attributed to vaccination [10]. Of these events, 70% were reported by doctors and the rest by nurses or other health professionals. No serious events or deaths were reported. Seven needlestick injuries at the time of vaccine preparation were reported of 11.6 million doses administered. For pregnant women inadvertently vaccinated, follow-up of pregnancy outcome is ongoing. Blood donation. The campaign was expected to decrease the blood supply in Costa Rica because vaccinated persons were not eligible to donate for 1 month after vaccination. The national blood bank observed a 52% decrease in blood donations compared with previous months. To maintain the blood supply, some hospitals targeted awareness and motivational campaigns to persons 40 years old who were not targeted for vaccination. Blood donations from persons 140 years old accounted for 51.1% of donations before the campaign and 95% during and immediately after the campaign. Surveillance. Surveillance of febrile exanthematic diseases is integrated in Costa Rica. It is based on local detection, immediate notification, and investigation of suspected cases of rash and fever. All health services, public and private, must report suspected cases to the regional and central level of health Figure 3. Rate per 100,000 population of reported measles cases during and rubella cases in 1999, Costa Rica. Data from Ministry of Health, Department of Statistics and Epidemiology, Costa Rica. Costa Rica: Rubella and Measles Control JID 2003:187 (Suppl 1) S161

5 and initiate case investigation immediately. A blood sample is collected and sent to the National Reference Laboratory (IN- CIENSA) to be tested for rubella, measles, leptospirosis, dengue, and Hantavirus, depending on epidemiologic and clinical information. During , 3056 blood samples were tested for measles IgM and 3463 for rubella IgM (table 2). Only 4 (0.13%) of 3056 samples tested for measles IgM were confirmed as measles cases; 92 samples with clinical diagnosis of measles were IgM positive for rubella and 40 samples were IgM positive for dengue. Surveillance for measles and rubella in Costa Rica has improved since surveillance protocols were updated, diagnostic capabilities were upgraded to isolate and identify virus, and training programs were developed for staff at the national epidemiologic surveillance center. Table 2. Number of suspected measles and rubella reported cases, number tested, and percentage of confirmed cases tested, Costa Rica, Year No. suspected measles/ rubella cases reported No. blood samples tested for measles/ rubella IgM a Measles confirmed (% tested) Rubella confirmed (% tested) / / (100) 523 (26) / / (3) / / (7) Total 303/ / (100) 580 (17) NOTE. Data source: Inciensa, National Reference Laboratory for Febrile Diseases, Ministry of Health, Costa Rica, Directorate of Health Surveillance. a Some blood samples from patients with rash and fever were tested for measles or rubella regardless of initial diagnosis of measles or rubella. DISCUSSION The epidemiology of rubella and measles in Costa Rica reflects the immunization program implemented over 30 years ago. Because of low coverage of both rubella and measles antigen vaccines in the 1970s and early 1980s, outbreaks continued to occur; however, in the mid-to-late 1980s and early 1990s, a shift in susceptibility to the older age groups was documented. Since the mid-1990s, Costa Rica followed the strategies recommended to eradicate measles. Routine vaccine delivery, including follow-up for defaulters and outreach activities, helped achieve high MMR vaccine coverage. National vaccination campaigns targeting all age cohorts!15 years old, combined with selective subnational and follow-up campaigns after assessment of susceptible age cohorts, led to interruption of endemic transmission of measles. After 1993, measles cases dramatically declined: The last 2 indigenous cases occurred in In contrast to measles, over the last 15 years there have been 3 rubella outbreaks mainly among adults. In the last outbreak in , 75% of the cases were in persons years old. For Costa Rica, the urgency of an adult MR campaign was due to endemic circulation of rubella virus in Costa Rica, increased rubella susceptibility in women of childbearing age, and the high risk of infants born with CRS. The goal of a rubella vaccination program is the prevention of intrauterine rubella infections such as CRS. The premise of a childhood rubella program is to decrease the circulation of the rubella virus, thus indirectly protecting women. To avoid increasing susceptibility in the adult population, childhood vaccination programs should achieve vaccination coverage of 80%; however, in Costa Rica, coverage 180% was not achieved until 12 years after the introduction of rubella-containing vaccine. In Costa Rica, the rubella virus circulation probably did decrease so that persons who would normally be infected (those neither vaccinated nor infected during childhood) remained susceptible at adulthood. Over the last two decades, several countries have introduced vaccination strategies that include childhood programs and the targeting of adolescent girls and/or women of childbearing age [11]. This approach decreases the circulation of rubella virus and protects the high-risk group. To decrease the risk of CRS, Costa Rica conducted the first adult male and female MR campaign in Latin America. When compared with childhood mass campaigns, adult campaigns can be more challenging. The Costa Rica experience reinforced the importance of identifying the target population, implementing social mobilization, ensuring commitment of the political and scientific communities, monitoring of progress during the campaign, and ensuring a nation blood supply. Difficulties associated with targeting an adult population (e.g., high mobility and poor interest in vaccination programs) were taken into consideration for planning purposes. The use of different strategies for rural and urban areas adapted to each particular situation and at different stages of the campaign implementation proved effective. In remote rural areas, activities should begin at the periphery and advance toward the most populated centers. In urban areas, they should begin at places of work and education and end with door-to-door mop up. In areas with immigrants, vaccination teams should be trained to vaccinate all persons in the target age group regardless of nationality or immigration status. Social mobilization activities were important for the success of the campaign. Strategies were directed to the health care workers and the populations. Various innovative activities developed during the campaign encouraged the participation of hospitals, the community, and education and private sectors. In addition, the active participation of health care workers and the involvement of medical societies and others professions proved invaluable. The development and use of progress indicators during the campaign helped in the reformulation of strategies and the achievement of goals. To this end, the availability of timely S162 JID 2003:187 (Suppl 1) Morice et al.

6 partial progress reports was critical to identify and solve problems during the campaign. Sketches mapping coverage by canton and fast monitoring of coverage in convenience samples of dwellings and workplaces complementing the official registry facilitated the identification of unvaccinated groups. To prevent a blood shortage, close collaboration between the national authorities in charge of planning and monitoring of the campaign and blood banks should take place. Donors 140 years old, who were not targeted in the campaign, maintained the blood reserves. Other strategies to prevent blood shortages should be considered during the planning phase of a vaccination campaign for adults including conducting a blood drive before the vaccination campaign to build reserves, selecting a pool of donors to be immunized after the campaign, and offering incentives for blood donation among persons aged years during the campaign. By establishing a goal of accelerated rubella and CRS prevention, Costa Rica strengthened measles eradication. Many of the key components for achieving accelerated rubella control and CRS prevention are key factors for measles elimination (e.g., high routine immunization coverage, nationwide vaccination campaigns targeting all age cohorts!15 years old, and strong epidemiologic surveillance for rash and fever-like illness). Surveillance activities in Costa Rica have demonstrated the lack of measles circulation and the prevalence of rubella in the population and have improved the country s capabilities and documented the epidemiology of diseases such as rubella, dengue, leptospirosis, and parvovirus. The laboratory has been an essential component of the measles eradication program by measuring the success and documenting the absence of disease. However, after years of absence of measles cases, there is the latent risk of missing true cases due to importation from measles-endemic countries. If routine vaccination coverage declines and surveillance activities deteriorate, there is the risk of reintroduction of endemic virus circulation. Countries in the region have experienced this immunization and surveillance fatigue. Costa Rica example, by establishing a goal for accelerated rubella control and CRS prevention, has revitalized surveillance and strengthened epidemiologic surveillance in general. The Costa Rica, experience shows that adopting a goal of accelerated rubella control and CRS prevention, targeting vaccination appropriately, and using the opportunity to strengthen surveillance for rash illness has dual benefits: accelerated rubella control and CRS prevention plus the strengthening of the measles eradication program. The initiative of the Costa Rican Ministry of Health and the CCSS will generate useful knowledge and experience for the development of strategies for accelerated rubella control, CRS prevention, and measles eradication in the Americas. Acknowledgments The Costa Rican initiative is a joint effort of national health institutions represented in the Ministry of Health and the CCSS, specialized agencies, and the international community. We acknowledge the members of the campaign coordinating commission, all persons who helped provide the information presented and whose work was essential to the success of the campaign, and Mary McCauley for editorial support. References 1. Mohs E. Health policies and strategies. In: Muñoz C, Scrimshaw N, eds. The nutrition and health transition of democratic Costa Rica. Boston: International Foundation for Developing Countries, 1995: Morice A, Castillo Solórzano C, Sáenz E, et al. Impact of vaccination on rubella and congenital rubella syndrome in Costa Rica. Panamerican J Public Health (in press). 3. Marranghello B. Measles in Costa Rica: evolution during the XX century. Rev Costarricense Salud Pública 1995; 4: Saénz E, González L, Morice A, Castillo Solorzano C, Depetris A. Rubella seroprevalence in school age children and women in childbearing age. Technical report. San José, Costa Rica: Ministry of Health, Mencher GT, Madriz JJ. Research and expansion of services in the developing world: a Costa Rican experience. J Speech-Language Pathol Audiol 1999; 23: Ministry of Health, Costa Rican Social Security System. Plan to eliminate congenital rubella syndrome and measles eradication. San Jose, Costa Rica: Ministry of Health, Pan American Health Organization. Expanded program on immunization. EPI Newsl 2001; 23: Ministry of Health, Costa Rican Social Security System. Final report of the national immunization campaign against measles and rubella in men and women 15 to 39 years. San Jose, Costa Rica: Ministry of Health, Pan American Health Organization. Expanded program on immunization. EPI Newsl 2001; 23: Centers for Disease Control. Nationwide campaign for vaccination of adults against rubella and measles Costa Rica, MMWR Morb Mortal Wkly Rep 2001; 50: Cutts FT, Robertson SE, Samuel R, Díaz Ortega JL. Control of rubella and congenital rubella syndrome (CRS) in developing countries, part 23: vaccination against rubella. Bull World Health Organ 1997; 75: Costa Rica: Rubella and Measles Control JID 2003:187 (Suppl 1) S163

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