Congenital Rubella Syndrome Surveillance Research Articles

Rubella Diagnostic Issues in Canada

With the success of the rubella vaccination program, a goal for the elimination of rubella and congenital rubella syndrome (CRS) by 2010 has been established. To monitor the progress toward elimination, surveillance is critical. The laboratory plays an important role in both diagnostics and surveillance for rubella and CRS. In the elimination phase, there are particular issues and challenges that are important to consider when undertaking rubella diagnostics and surveillance activities. Although immunoglobulin (Ig) M serological testing is the primary diagnostic test used to confirm acute rubella infection, additional tests, such as paired IgG serological testing, molecular detection of rubella virus, and rubella IgG avidity testing need to be considered for confirming cases, depending on the clinical and epidemiologic context of a particular suspected rubella case.

Elimination of Rubella and Congenital Rubella Syndrome in the Americas

In 2003, the Pan American Health Organization (PAHO) adopted a resolution calling for rubella and congenital rubella syndrome (CRS) elimination in the Americas by the year 2010. To accomplish this goal, PAHO advanced a rubella and CRS elimination strategy including introduction of rubella-containing vaccines into routine vaccination programs accompanied by high immunization coverage, interruption of rubella transmission through mass vaccination of adolescents and adults, and strengthened surveillance for rubella and CRS. The rubella elimination strategies were aligned with the successful measles elimination strategies. By the end of 2009, all countries routinely vaccinated children against rubella, an estimated 450 million people had been vaccinated against measles and rubella in supplementary immunization activities, and rubella transmission had been interrupted. This article describes how the region eliminated rubella and CRS.

Status of Rubella and Congenital Rubella Syndrome Surveillance, 2005–2009, the World Health Organization European Region

The World Health Organization European Region has a goal for rubella elimination and congenital rubella syndrome (CRS) prevention. Although all Member States recommend a rubella-containing vaccine in their national immunization programs, rubella and CRS continue to occur, and surveillance quality varies throughout the region. To describe the status of regional rubella and CRS surveillance and assess progress toward elimination, we reviewed surveillance practices by surveying all 53 Member States and analyzed rubella and CRS surveillance data during 2005-2009. Overall, 41 (91%) of 45 responding Member States have nationwide rubella surveillance, and 39 (87%) have nationwide CRS surveillance. During 2005-2009, rubella cases reported in the region decreased by 94% from 206,359 cases to 11,623 cases. The greatest decrease (99%) was observed in newly independent states of the former Soviet Union. In the rest of the region, high rubella incidence was observed in Poland, Romania, Italy, and San Marino during 2005-2008 and in Poland, Bosnia and Herzegovina, and Austria in 2009. A total of 68 CRS cases were reported during 2005-2009. As the foundation to achieving and verifying rubella elimination, high-quality rubella and CRS surveillance needs to be implemented and sustained in all Member States.

The Epidemiology of Rubella Disease in Ethiopia: Data From the Measles Case-Based Surveillance System

Rubella is usually a mild rash illness. However, when a woman contracts rubella early in pregnancy, serious consequences may occur, including birth defects known as congenital rubella syndrome (CRS). Information is limited on the epidemiology of rubella and CRS in Ethiopia. Rubella cases reported through the measles case-based surveillance system during 2004-2009 were analyzed. A total of 8212 samples were tested for rubella immunoglobulin (Ig) M, and 992 (12.1%) of these specimens had test results that were positive for rubella IgM. The age distribution of patients with rubella-positive cases ranged from 3 months to 44 years. The majority (94.7%) of the cases were in individuals <15 years of age. The proportion of positive specimens from urban areas (19.4%) was higher than that from rural areas (11.6%). Rubella is endemic in Ethiopia and mainly occurs among children and young adolescents. To better understand the burden of rubella and CRS, and to develop a national strategy for rubella control in Ethiopia, CRS surveillance will need to be established, and appropriate studies need to be conducted.

Progress Toward Measles and Rubella Elimination in Egypt

Measles and rubella were common infectious diseases in Egypt during the prevaccine era. Monovalent measles vaccine was introduced in 1977, and measles vaccination coverage increased from <50% to >90% from 1980 to 1999; however, measles outbreaks continued to occur at 2- to 4-year intervals during this period. After the introduction of a second routine dose of measles vaccine as a combined measles-mumps-rubella (MMR) vaccine in 1999 and the implementation of measles immunization campaigns targeting 6- to 16-year-old children during 2000-2003, reported measles cases dramatically decreased by 2003. In 2002, Egypt established a goal to eliminate measles and rubella and to prevent congenital rubella syndrome (CRS) by 2010. Large-scale rubella and measles outbreaks in 2005-2007, however, led to a revision of the plan of action to achieve the 2010 goals. A nation-wide measles-rubella immunization campaign, targeting children, adolescents, and young adults 2-20 years old, was conducted in 2 phases during 2008-2009 and achieved coverage >95%. With the decrease to record low levels of cases of measles and rubella in 2009 and 2010, Egypt should achieve measles and rubella elimination in the near future, but high coverage(>95%) with 2 doses of measles-rubella vaccine needs to be maintained, measles-rubella surveillance strengthened, and CRS surveillance developed.

Developing Rubella Vaccination Policy in Nepal—Results From Rubella Surveillance and Seroprevalence and Congenital Rubella Syndrome Studies

The Government of Nepal is interested in preventing congenital rubella syndrome (CRS). Surveillance data were analyzed and studies conducted to assess the burden of rubella and CRS and aid in developing a rubella vaccination strategy. (1) Analysis of rubella cases reported through measles surveillance, 2004-2009; (2) in 2008, rubella seroprevalence among women 15 to 39 years of age was evaluated; and (3) in 2009, children attending a school for the deaf were examined for ocular defects associated with CRS. From 2004-2009, there were 3,710 confirmed rubella cases and more than 95% of these cases were less than 15 years of age. Of 2,224 women of childbearing age (WCBA) tested for anti-rubella IgG, 2,020 (90.8%) were seropositive. Using a catalytic infection model, approximately 1,426 infants were born with CRS (192/100,000 live births) in 2008. Among 243 students attending a school for the deaf, 18 (7.4%) met the clinical criteria for CRS. Rubella and CRS were documented as significant public health problems in Nepal. A comprehensive approach is necessary, including introducing rubella vaccine in the routine program, assuring immunity among WCBA, strengthening routine immunization, integrating rubella surveillance with measles case-based surveillance, and establishing CRS surveillance.

Outbreak of rubella after mass vaccination of children and adult women: challenges for rubella elimination strategies

To describe rubella outbreaks and control strategies in the Brazilian state of Rio Grande do Sul before rubella elimination. We analyzed rubella and congenital rubella syndrome surveillance data for the state of Rio Grande do Sul and calculated age- and gender-specific incidence of confirmed rubella cases in 2007. We obtained data on measles-rubella doses administered during the outbreak from the state immunization program and reviewed the timing of suspect case notification and implementation of control measures. Of 2,842 confirmed rubella cases reported to the state health department in 2007, 2,145 (75.5%) were in males (39.5 cases per 100,000 population) and 697 (24.5%) were in females (12.3 per 100,000 population). Incidence among 15- to 39-year-olds was 1.8 to 5.5 times higher in males than in females. Rubella genotype 2B was detected in nasopharyngeal specimens from 13 patients from multiple chains of transmission. Eight children were born with congenital rubella syndrome (5.9 cases per 100 000 births in 2008). Delayed notification of initial cases hampered early control efforts, resulting in outbreak spread throughout the state. Rubella transmission was interrupted after mass vaccination of adult men and women as part of a national vaccination campaign. Routine vaccination strategies and mass vaccination of adolescents and adults for accelerated rubella control and elimination should target men and women.

Primary investigation of 31 infants with suspected congenital rubella syndrome in Sudan

Between 2005 and 2006, clinical specimens were collected from 31 infants with suspected congenital rubella syndrome (CRS) who presented at six hospitals in Khartoum, Sudan. Eleven (35.5%) were laboratory confirmed as CRS cases by testing for anti-rubella IgM, IgG and viral genome. For the first time in Sudan, the rubella virus genome was directly detected in clinical specimens of six CRS cases and two viruses were isolated in cell culture. Phylogenetic analysis suggested that three genotypes of rubella virus (RV; 1E, 2B and 1G) were co-circulating in Sudan. The study introduced the methodology for CRS confirmation and surveillance in Sudan and provides preliminary data.

Congenital rubella syndrome: pattern and presentation in a southern Nigerian tertiary hospital

Congenital rubella syndrome (CRS) resulting from maternal rubella infection can result in miscarriages, still birth and rubella infection of the infant. The aim of this study was to evaluate the pattern and presentation of CRS over an 8-year period as seen in the University of Port-Harcourt Teaching Hospital (UPTH), Nigeria. The medical records of all cases of CRS presenting to the Pediatric Department of UPTH from January 2000 to December 2007 were reviewed. There were 16 394 babies delivered in UPTH from January 2000 to December 2007. Of these babies, 19 were clinically diagnosed as having CRS, but none had laboratory confirmation. They had a mean age of 5.1 +/-3.2 months (range: 1-11 months). Seventy-five percent of their mothers had presumed rubella infection during the first trimester of pregnancy. Cataract was noticed to be the most prominent systemic manifestation in 18 of the 19 babies. Other common manifestations included hearing impairment (n=14), microcephaly (n=13), patent ductus arteriosus (n=11), and low birth weight (n=10). A surge was observed in the number of babies with CRS from 2004 to 2007; however, this was not statistically significant (chi (2)=8.68, P=0.28). Unfortunately, long-term outcome of the 19 babies was not available. CRS is commonly diagnosed at our center. Thus, mounting effective surveillance for CRS and considering the inclusion of rubella vaccine in Nigeria are of extreme importance.

Progress Toward Elimination of Rubella and Congenital Rubella Syndrome—the Americas, 2003-2008

In 2003, the Pan American Health Organization (PAHO) adopted a resolution calling for rubella and congenital rubella syndrome (CRS) elimination in the Americas by the year 2010. Elimination was defined as the interruption of endemic rubella virus transmission in all countries of North America, Central America, South America, and the Caribbean for more than 12 months and no occurrence of CRS cases attributed to endemic transmission. To accomplish this goal, PAHO developed a rubella and CRS elimination strategy (3) to 1) introduce rubella-containing vaccine (RCV) into routine vaccination programs of all countries for children aged 12 months and reach >/=95% coverage in all municipalities, 2) conduct a one-time mass campaign among adolescents and adults and periodic follow-up campaigns among children aged <5 years, and 3) integrate rubella surveillance with measles surveillance and initiate CRS surveillance. During 1998-2006, confirmed rubella cases decreased 98% (from 135,947 to 2,998) in the Americas. However, in 2007, rubella outbreaks with a total of 13,014 cases occurred in three countries (Argentina, Brazil, and Chile), primarily in males not included in previous vaccination campaigns. This report summarizes overall progress toward reaching the 2010 goal of eliminating rubella and CRS. With completion of campaigns in Argentina, Brazil, and Haiti, all countries will have implemented the recommended PAHO strategy by the end of 2008, with the expectation of reaching the 2010 rubella and CRS elimination goal.

Use of low birth weight as selecting criterion for the routine surveillance of congenital anomalies of infectious origin.

Introduction: Surveillance of congenital anomalies receives importance in the world-wide context of eradicating the congenital rubella syndrome. Objective: To identify the congenital anomalies and to consider the low birth weight a criterion to test IgM for the complex TORCH. Methodology: Surveillance of the congenital specific and non specific anomalies of the congenital rubella syndrome(CRS) and low birth weight in ten hospitals. It was considered as case, everything new born with some congenital anomaly or low weight for the gestational age. Serum tests for rubella, toxoplasmosis, citomegalovirus, herpes and parvovirus were practiced. For the negative cases cariotype was performed. Results: A total of 840 cases were selected, 669 by low weight for the gestational age, 52 by anomalies not related to CRS, 52; by anomalies that could be related to the CRS, 105. The most frequent anomalies were congenital heart diseases, 5.1%; hepatosplenomegalies, 3.9%; and microcephalies, 1.2%. There were confirmatory IgM titles for rubella in 0.5% of cases; toxoplasmosis 1.4%; citomegalovirus 1.5%; parvovirus 1.2%; herpes 0.5%; and positive test for congenital syphilis, 3.7%. In total there were 8.8% positive results for any congenital infectious disease. The relative risk for low birth weight having IgM positive rubella was RR = 2.83 (IC: 1.26:6.36-0.95). Discussion and conclusions: The surveillance for CRS, through the monitoring of febrile in the first year and by the presence of some specific congenital anomalies, could be improved in sensitivity by means of the routine monitoring of congenital anomalies, with the inclusion of low birth weight, like a selecting criterion to study the infectious agents.

Impacto da vacinação contra rubéola na ocorrência da síndrome da rubéola congênita

OBJETIVO: A vacinação rotineira contra a rubéola foi implementada na Paraíba, nordeste brasileiro, através de uma campanha de catch-up direcionada a crianças com idades entre 1 e 11 anos em 1998. Uma campanha entre as mulheres em idade reprodutiva foi realizada em 2001. Descrevemos a epidemiologia da rubéola e da síndrome da rubéola congênita (SRC) no estado da Paraíba entre 1999 e 2005. MÉTODOS: Foram analisados os dados de vigilância da rubéola e da SRC entre 1999 e 2005. Os casos suspeitos de rubéola foram confirmados por exames laboratoriais, vínculo epidemiológico ou por critério clínico. Foram utilizadas as definições internacionais padrão de SRC. RESULTADOS: Dos 5.924 casos suspeitos de rubéola entre 1999 e 2005, 1.266 (21%) foram confirmados, 766 (61%) deles através dos exames laboratoriais. Durante uma epidemia de rubéola em 2000 (18,8/100.000), a incidência entre os indivíduos com idades entre 14 e 19 anos (42/100.000) quadruplicou em relação a crianças com idades entre 1 e 13 anos (intervalo de confiança de 95% = 3,2-5,1). A incidência geral da rubéola foi de 0,9/100.000 em 2005. Dos 177 casos suspeitos de SRC entre 1999 e 2005, 167 (94%) foram testados para a presença de IgM. Dos 14 (8%) casos de SRC confirmados laboratorialmente, 12 (86%) haviam nascido em 2001, com uma incidência de 0,2/100.000 crianças menores de 1 ano nesse ano. CONCLUSÕES: A campanha de vacinação contra a rubéola em 1998 não foi suficiente para prevenir um surto entre adultos jovens em 2000, com uma alta incidência de SRC em 2001. Entre 2002 e 2005, as incidências de rubéola e de SRC diminuíram; entretanto, a alta cobertura da vacina e a vigilância de alta qualidade são importantes para que se atinja a erradicação da SRC até 2010.

Impact of rubella vaccination strategy on the occurrence of congenital rubella syndrome

Routine rubella vaccination was introduced in Paraíba, northeastern Brazil, through a catch-up campaign targeting children aged 1-11 years, in 1998. A campaign among women of childbearing age was conducted in 2001. We describe the epidemiology of rubella and congenital rubella syndrome (CRS) in the state of Paraíba between 1999 and 2005. Rubella and CRS surveillance data for the 1999-2005 period were analyzed. Suspected cases of rubella were confirmed by laboratory findings, epidemiological link, or clinical data. International standardized CRS definitions were used. Of 5,924 suspected cases of rubella between 1999 and 2005, 1,266 (21%) were confirmed, 766 (61%) by laboratory findings. During a rubella epidemic in 2000 (18.8/100,000), the incidence among individuals aged 14-19 years (42/100,000) had a fourfold increase relative to children aged 1-13 years (95% confidence interval = 3.2-5.1). The overall rubella incidence was 0.9/100,000 in 2005. Of 177 suspected cases of CRS between 1999 and 2005, 167 (94%) were tested for IgM. Of 14 (8%) laboratory confirmed cases of CRS, 12 (86%) were born in 2001, with an incidence of 0.2/100,000 children aged less than 1 year. The 1998 rubella vaccination campaign was insufficient to prevent an outbreak among young adults in 2000, with a high CRS incidence in 2001. Between 2002 and 2005 the incidence of rubella and CRS decreased; however, high routine vaccination coverage and high-quality surveillance remain critically important to achieve CRS elimination by 2010.

Seroprevalence of rubella among Jordanian women of childbearing age

This study was conducted to assess immunity (seroprevalence) to rubella among Jordanian women of childbearing age. A multistage cluster sampling was used to recruit 1125 women of childbearing age (15–49 year) from the 12 Governorates of Jordan. Anti-rubella antibody titers were measured using enzyme-linked immunoassays. The overall immunity rate to rubella among women in childbearing age was 90.9% (CI: 88.8–92.9). However, the immunity rate was significantly lower in younger women aged 15–19 years (83%) compared to the whole cohort ( P ≤ 0.001) which means potential increased risk for congenital rubella syndrome (CRS). Immunity rates did not differ between regions and between urban and rural areas. Since the main priority is to decrease CRS among relatively susceptible cohorts, we recommend modifying the existing Expanded Program on Immunization with inclusion of a second dose of rubella vaccine at school entry (6 years of age) to decrease circulation of the virus among susceptible young females. We also recommend yearly catch-up school vaccination of young females entering the 10th grade for the next 10 years. Strengthening of rubella and CRS surveillance programs is also recommended in parallel with pre-marriage counseling regarding rubella and CRS for young females.

Scenario of the twins with suspected congenital rubella syndrome (CRS) in Yangon, Myanmar

Rubella is a common cause of childhood rash and fever. Congenital rubella syndrome (CRS) can lead to deafness, heart disease, cataracts, and a variety of other permanent manifestations. In order to identify the disease burden of rubella infection, CRS surveillance among infants in Yangon was conducted for two consecutive years from December 2000 to December 2002, as a WHO-funded study. Among the 13 participating hospitals, the Special Care Baby Unit of the Central Women‘s Hospital in Yangon reported 17 infants with suspected CRS. Interestingly, three sets of twins with suspected CRS were reported. One ml of blood was collected from each infant after obtaining informed consent, then tested for the presence of rubella antibody (Immunoglobulin M and G) by the ELISA method, and for the presence of rubella viral RNA by the RT-PCR method. Furthermore, nucleotide sequencing and genotype identification of samples from two cases with positive rubella RNA were performed. All 3 sets of twins were IgM negative. However, rubella RNA was detected by RT-PCR in twin 1A who showed no obvious clinical signs, and in twin 2B who had patent ductus arteriosus, splenomegaly and hepatomegaly. Nucleotide sequences of PCR positive cases revealed genotype Ia sequences. Twin 2B was identified as having deafness of the left ear on audiometry assessment conducted at 5 years and 4 months of age. Both twins of twin set-2 were IgG positive at age 12 days, but turned out to be negative by the age of 9 months. Both twins of twin set-3 presented with splenomegaly and died before 2 months of age, probably due to other infections. Our findings revealed the different scenario of twins with suspected CRS. It is expected to serve as a valuable addition to the medical literature as there were very few reports on twins with CRS.

Evaluation of a commercial rubella IgM assay for use on oral fluid samples for diagnosis and surveillance of congenital rubella syndrome and postnatal rubella

Background Clinical diagnosis (surveillance) of rubella is unreliable and laboratory confirmation is essential. Detection of virus specific IgM in serum is the most commonly used method. However, the use of serum necessitates the drawing of blood, either through venipuncture or finger/heel prick, which can be difficult in young babies. Oral fluid samples have proved useful as an alternative, less invasive sample for virus specific IgM detection however until recently no commercial rubella IgM tests were available, restricting the usefulness of this approach. Objectives To evaluate the performance of the Microimmune Rubella IgM capture EIA using oral fluid samples from outbreaks as well as in cases of suspected congenital rubella syndrome (CRS). Study design Paired serum and oral fluids were collected from cases during a rubella outbreak in three provinces in Turkey. Matched serum and oral fluid samples were collected from children with suspected CRS in an active surveillance programme at the Aravind Eye Hospital in South India. Serum samples were collected as part of the measles surveillance programme in Ethiopia. Results On serum samples the sensitivity and specificity of the Microimmune Rubella IgM capture EIA compared to Behring Enzygnost rubella IgM test was 96.9% (62/64; 95% CI 94.2–100%) and 100% (53/53; 95% CI 93.2–100%). On oral fluids compared to matched Behring results on serum the sensitivity was 95.5% (42/44; 95% CI 84.5–99.4%). The sensitivity and specificity of Microimmune Rubella IgM capture EIA on oral fluids from suspected CRS cases compared to serum results using Behring Enzygnost IgM assay was 100% (95% CI 84.5–100%) and 100% (95% CI 95.8–100.0%) respectively. Conclusion Microimmune Rubella IgM capture EIA has adequate performance for diagnosis and surveillance of rubella in outbreak using either serum or oral fluid specimens.

Seroprevalence of rubella antibodies among antenatal patients in the Western Cape.

To determine the seroprevalence of rubella virus infection among antenatal patients aged between 15 and 45 years in the Western Cape province of South Africa, in order to provide data to determine the need for vaccination to protect women of childbearing age. A cross-sectional study. Setting. Virology laboratory, Groote Schuur Hospital, National Health Laboratory Service (NHLS), South Africa. One thousand two hundred provincial serum specimens from participants in the 2003 Department of Health antenatal HIV/syphilis serosurvey were selected from the 4 districts of the Western Cape. The specimens were age-stratified and screened qualitatively for rubella immunoglobulin G (IgG) antibodies by means of a commercial immunoassay during October 2004. Within the Western Cape a total of 95.3% of women in the 15-24-year age group, 97.5% in the 25-34-year group and 98% in the 35-45-year age group were immune to rubella. There was no statistically significant difference in the rate of rubella susceptibility between the 4 districts tested. The study is an important step in addressing the seroprevalence of rubella infection in women of childbearing age in South Africa. Further information is needed on rubella seroprevalence from the other provinces in South Africa as well as formal implementation of rubella and congenital rubella syndrome surveillance to determine the feasibility of routine rubella immunisation.

Síndrome de rubéola congénita en Costa Rica: importancia de reforzar la vigilancia activa

To identify cases of congenital rubella syndrome (CRS) and their form of presentation in children aged < 3 months in the National Children's Hospital of Costa Rica between 1996 and 2000. Between 1996 and 2000, patients aged 1 day to 3 months with positive IgM serology for rubella, identified by means of the computerized database of the National Children's Hospital Laboratory, were selected. Their corresponding medical records were reviewed and the characteristics of these patients were analyzed. Sixty-six children with positive serology were identified, of which 49 had a complete medical record that allowed review. Of these, 29 (60 %) were boys. The mean age at which IgM serology was requested was 33 days. The principal manifestations leading to serology were hepatosplenomegaly, microcephaly and multiple congenital anomalies. The initial diagnosis was TORCH infection. Of the 49 patients, 45 were classified as CRS and four as infection with rubella. The present study highlights the need to increase active surveillance of CRS. Greater vigilance in applying the criteria for clinical diagnosis is required to allow an adequate degree of suspicion and early reporting of cases.

Monitoring congenital rubella embryopathy

Currently, all developed countries include rubella vaccination in their immunization programs, targeting the complete elimination of congenital rubella syndrome (CRS). In the underdeveloped world, where this severely disabling condition still exists, only a few countries have implemented vaccination policies, and almost no data on their effectiveness or on prevalence rates are available. The aims of the present work were to search for the best phenotype to be used as a sentinel for CRS in a large series of malformed newborns and to propose a CRS surveillance system, based only on clinical data. A total of 43 infants diagnosed as having CRS were obtained from 19,184 multimalformed infants, ascertained by the Latin-American Collaborative Study of Congenital Malformations, World Health Organization (WHO) Collaborating Centre for the Prevention of Birth Defects (ECLAMC), over 3,883,165 consecutive births, between 1982 and 2003. They were distributed by country and the most frequent birth defects were identified. From the 19,184 multimalformed infants, all cases presenting the birth defects identified were selected. The sensitivity, specificity, and likelihood ratio (LR) in detecting CRS were determined for these birth defects, alone and in combination. The sample size of multimalformed infants required to detect different levels of increase in the rate of CRS was determined for three sentinel phenotypes. The rate of CRS was highest in Brazil. Based on the best possible combination of sensitivity, specificity, and LR, the dyad comprising eye anomalies and congenital heart defects was shown to be the most appropriate sentinel, with the lowest sample size required, to detect CRS in neonates. A surveillance system for CRS, based on clinical data in newborns, is being proposed, in an attempt to monitor ongoing vaccination policies, aimed at eliminating CRS in developing countries.

Surveillance of congenital rubella syndrome in Japan, 1978–2002: effect of revision of the immunization law

Infection of rubella virus at the early stages of pregnancy in women who are not immune to rubella often induces congenital anomalies in infants, namely congenital rubella syndrome (CRS). This paper is the first comprehensive report of CRS cases in Japan, compiled from a questionnaire to major hospitals, reports to journals and academic meetings, and cases for virus/virus genome verification submitted to the National Institute of Infectious Diseases. CRS incidence in Japan was determined to be 0.2–8.1 cases/100,000 live births per year in epidemic years and 0.1–0.7 in non-epidemic years, respectively. In the last 4 years, the number of CRS cases remarkably decreased to one–three cases per year. This decrease is thought to be because the immunization law was revised in 1994 for changing the focus of rubella immunization from junior high school girls to infants of both sexes.