The decline in congenital rubella syndrome in Western Australia: an impact of the school girl vaccination program?

Rubella vaccination became available in 1970 in Australia. In Western Australia (WA), a school girl vaccination program was well established by 1971. Mothers under 26 years of age in 1983 would have been eligible for this program and they constitute 40 per cent of WA births. Data on Congenital Rubella Syndrome (CRS) cases were obtained for years of birth 1968-83 inclusive to ascertain if there had been an impact of the program on the CRS rate. Epidemics of rubella occurred in 1970-71, 1974, and 1979-80. The CRS rate has fallen steadily; it did not rise during the 1979-80 epidemic and was less than one in each year after 1977. All CRS cases born since 1974 were to mothers too old to have been eligible for the program. The data suggest that the vaccination program is effective, but this cannot be proven until data become available on pregnancy terminations.     

Congenital rubella syndrome (CRS) in Vietnam 2011–2012—CRS epidemic after rubella epidemic in 2010–2011

BackgroundRubella is endemic in Vietnam with epidemics occurring every 4–5 years. In 2011, Vietnam experienced the large nationwide rubella epidemic. During the rubella epidemic, many infants born with congenital rubella syndrome (CRS) were identified and reported from the neonatal units or cardiology departments of the national hospitals. To understand the burden of CRS, National Expanded Program on Immunization (NEPI) established sentinel CRS surveillance system.MethodThree national paediatric hospitals in Hanoi and Ho Chi Minh City (HCMC) were selected as CRS sentinel surveillance sites. Blood specimens from the infants were collected for rubella specific IgM and ELISA testing was performed at the national measles and rubella laboratory.ResultsFrom January 2011 to December 2012, 424 infants with suspected CRS were identified and reported. Among them 406 (96%) had specimens obtained, 284 (70%) cases were IgM positive including 279 laboratory confirmed CRS and 5 Congenital Rubella Infection (CRI). 13 cases were clinically confirmed and 127 (30%) were discarded. Total 292 infants were confirmed as CRS. Of the 292 infants with CRS, 69% of mothers had a history of “fever and rash” during pregnancy, of which 85% was in the first trimester. The most common clinical defects were congenital heart disease and cataract(s). However, 81.9% of the infants had a combination of major and minor signs and symptoms. Low birth weight in full term infants with confirmed CRS was observed in 114 infants (39%).ConclusionsThe newly established CRS sentinel surveillance system documented the significant burden of CRS in Vietnam and provided evidence to the policy makers for the introduction of rubella containing vaccine (RCV) into Vietnam. This report highlights the importance of countries with rubella epidemic to establish CRS surveillance rapidly in order to support the introduction of RCV into the routine Expanded Programme on Immunization (EPI) immunization.     

Incidence of congenital rubella syndrome in Japan (1965-1985). A nationwide survey of the number of deaf children with history of maternal rubella attending special schools for the deaf in Japan

Accurate congenital rubella syndrome surveillance in Japan is of great interest because of the hypothesis that the Japanese rubella virus was less virulent than the strains prevalent in Europe and the Americas 20 years ago. A nationwide survey of deaf children with a history of maternal rubella in special schools for the deaf in Japan yielded a total of 365 deaf school children with congenital rubella syndrome born between 1963 and 1982. The overall average prevalence was 0.31 case per 100,000 population, and the incidence was 0.1-6.1 cases per 100,000 annual live births in Japan. If one considers the decrease in the number of deaf children attending special schools for the deaf because of the recent adoption of the policy of integrating deaf children into ordinary schools, the number of cases of congenital rubella syndrome might actually be much greater than that revealed by this survey and much greater than the 88 cases previously reported in Japan. Among the 365 cases who had deafness, 8.2% were found to have cataract (with and without congenital heart disease), and 11.0% were found to be complicated by congenital heart disease (but without cataract).     

Epidemiological profile and progress toward rubella elimination in China. 10 years after nationwide introduction of rubella vaccine

BackgroundRubella-containing vaccine (RCV) became available in China in 1993 and was introduced nationwide into the Expanded Immunization Program (EPI) in 2008. We evaluated implementation and impact of RCV from 2 years prior to nationwide introduction through the 10 years after nationwide introduction.MethodsWe analyzed RCV lot-release (doses distributed) data, 1- and 2-dose RCV coverage, and rubella data from China’s nationwide disease surveillance system to describe the current status and changes in rubella epidemiology between 2005 and 2017.ResultsWhile the vaccine was included into the routine immunization program in 2008, its full implementation required 4 years due to sporadic vaccine supply constraints. RCV1 and RCV2 coverage increased from 51.5% and 39.0% in 2008 to >95% during 2012 through 2016. From 2005 to 2017, the annual incidences (per million) of rubella ranged from 91.09 in 2008 down to 1.16 in 2017; reductions occurred in all age groups. The proportion of cases among individuals ≥20 years old increased from 0.97% in 2005 to 31.2% in 2017. In the better-developed eastern China, most cases were among adults; in central and western China, most cases were among children or adolescents.ConclusionsThe marked decrease rubella was a result of inclusion of RCVs into EPI targeting children less than 2 years of age and achieving high level of 2-dose coverage. Rubella was reduced in absolute terms, and its epidemiology was changed to older cases with substantial inter-province variation. Ensuring full vaccination of school children and identifying strategies to reach adults with measles and rubella combined vaccines will be important to hasten elimination of rubella and prevent CRS outbreaks.     

Clinical manifestations of congenital rubella syndrome: A review of our experience in Vietnam

Rubella vaccination programs have dramatically reduced the incidence of rubella and congenital rubella syndrome (CRS) in developed countries. However, CRS prevalence is still rising in developing countries where rubella-containing vaccines (RCV) are not included in the immunization program and even in some countries where a part of the population lacks immunity to rubella despite the presence of RCV in the regular immunization program. This review aimed to summarize the clinical features of CRS using data from our studies conducted between 2011 and 2015 in Vietnam, wherein we examined clinical manifestations in Vietnamese children with CRS who were born after the large rubella outbreak of 2011; a series of studies dealing with CRS in North America and Europe after the 1960s epidemic; and those from countries before introduction of RCVs.This review shows that children with CRS have a variety of disabilities such as hearing, visual, developmental, behavioral, cardiac, and endocrine impairments, which have variable severity and may appear in different combinations. Some of these impairments can appear or worsen later in the lives of these children.Physicians should thus complete pediatric, cardiac, auditory, ophthalmologic, and neurologic examinations along with laboratory diagnostic testing soon after birth. These assessments should be repeated during follow-up if congenital rubella infection is suspected in a neonate. Timely intervention for cardiac defects can be lifesaving. Early introduction and continuation of speech, occupational, physical, and behavior therapies and training with appropriate medical interventions by a multidisciplinary team approach are required to maximize quality of life.     

Therapeutic abortions following rubella infection in pregnancy: the potential impact on the incidence of congenital rubella syndrome

In 1977, a large rubella outbreak occurred in Hawaii. Because attack rates were high among women of childbearing age, we conducted extensive surveillance efforts to detect both pregnancies complicated by rubella and cases of congenital rubella syndrome (CRS). Initial surveillance included a survey of physicians and hospitals, review of fetal death and birth certificates, and cord blood screening for rubella-specific IgM of infants born following the epidemic. Two years after the outbreak, the medical community was again surveyed to identify affected children who were missed initially. No case of CRS was identified either shortly after the outbreak or in the ensuing two years. In addition, none of the 5,605 cord serum samples obtained was found to contain rubella-specific IgM antibody. Through active surveillance, we received 12 reports of rubella in pregnant women, of whom 11 elected to terminate their pregnancies. The extensive use of therapeutic abortion by exposed women may have prevented the birth of infants with CRS. Surveillance for rubella-related abortions is an important component in assessing the health impact of rubella in a community.     

Elimination of rubella and congenital rubella syndrome--United States, 1969-2004

In October 2004, CDC convened an independent panel of internationally recognized authorities on public health, infectious disease, and immunization to assess progress toward elimination of rubella and congenital rubella syndrome (CRS) in the United States, a national health objective for 2010. Since rubella vaccine licensure in 1969, substantial declines in rubella and CRS have occurred, and the absence of endemic transmission in the United States is supported by recent data: 1) fewer than 25 reported rubella cases each year since 2001, 2) at least 95% vaccination coverage among school-aged children, 3) estimated 91% population immunity, 4) adequate surveillance to detect rubella outbreaks, and 5) a pattern of virus genotypes consistent with virus originating in other parts of the world. Given the available data, panel members concluded unanimously that rubella is no longer endemic in the United States. This report summarizes the history and accomplishments of the rubella vaccination program in the United States and the Western Hemisphere and the challenges posed by rubella for the future.     

Molecular surveillance of rubella virus in Beijing,China during 2010–2021: Progress and challenges in rubella elimination

Rubella is listed by the World Health Organization (WHO) as a disease that needs to be eliminated worldwide. The aim of this study was to understand the progress and challenges towards rubella elimination in Beijing, China, by analyzing molecular surveillance data combined with immunization and surveillance strategies as well as epidemiological data. With high immunization coverage under the 3-dose policy (8 months, 18 months, and 6 years) and supplementary immunization activities for the floating population, rubella incidence showed a downward trend since 2010, despite two epidemics that occurred in 2014–2015 and 2019. The reported rubella cases were generally concentrated in the age group of 15–34 years. Although citywide surveillance for congenital rubella syndrome (CRS) has been carried out since 2016, only one case has been confirmed by laboratory testing. Furthermore, molecular surveillance data showed that rubella viruses (RVs) circulating in Beijing during 2010–2020 were evidently heterogeneous; the domestic lineage 1E-L1 and multiple imported lineages, including 2B-L1, 1E-L2, and 2B-L2c, were identified in the last decade. Meanwhile, two lineage-related switches were determined, including the displacement of lineage 1E-L1 with lineage 2B-L1 around 2014 and the transition between lineage 2B-L1 and lineage 1E-L2 and 2B-L2c in 2018–2019. This RV transmission pattern was similar to that observed across the country, whereas lineages 1E-L1 and 2B-L2c were prevalent in Beijing for a shorter period. Overall, these results indicate the need to maintain routine immunization with rubella-containing vaccines, promote regular supplementary immunization activities, and enhance rubella and CRS surveillance even in order to accelerate rubella elimination in Beijing. Further, the existing immunization strategies must be optimized to further close the immunity gap.     

Control of rubella and congenital rubella syndrome (CRS) in developing countries, Part 1: Burden of disease from CRS.

Congenital rubella syndrome (CRS) can lead to deafness, heart disease, and cataracts, and a variety of other permanent manifestations. In developing countries, the burden of CRS has been assessed as follows: by surveillance of CRS; by surveillance of acquired rubella; by age-stratified serosurveys; and by serosurveys documenting the rubella susceptibility of women of childbearing age. During rubella outbreaks, rates of CRS per 1000 live births were at least 1.7 in Israel, 1.7 in Jamaica, 0.7 in Oman, 2.2 in Panama, 1.5 in Singapore, 0.9 in Sri Lanka, and 0.6 in Trinidad and Tobago. These rates are similar to those reported from industrialized countries during the pre-vaccine era. Special studies of CRS have been reported from all WHO regions. Rubella surveillance data show that epidemics occur every 4-7 years, similar to the situation in Europe during the pre-vaccination era. In developing countries, the estimated average age at infection varies from 2-3 years to 8 years. For 45 developing countries we identified serosurveys of women of childbearing age that had enrolled > or = 100 individuals. The proportion of women who remained susceptible to rubella (e.g. seronegative) was < 10% in 13 countries. 10-24% in 20 countries, and > or = 25% in 12 countries. Discussed are methods to improve the surveillance of rubella and CRS in developing countries.     

Progress toward control of rubella and prevention of congenital rubella syndrome --- worldwide, 2009

Rubella usually is a mild, febrile rash illness in children and adults; however, infection early in a woman's pregnancy, particularly during the first 16 weeks, can result in miscarriage, fetal death, or an infant born with birth defects (i.e., congenital rubella syndrome [CRS]). In 2000, the World Health Organization (WHO) published the first rubella vaccine position paper to guide introduction of rubella-containing vaccine (RCV) in national childhood immunization schedules. As of December 2009, a total of 130 WHO member states have introduced RCV, a 57% increase from 83 member states in 1996. In addition, goals to eliminate rubella and CRS have been established in the WHO Region of the Americas (by 2010) and the WHO European Region (by 2015), and the WHO Western Pacific Region has established targets for accelerated rubella control and CRS prevention by 2015. During 2009, a total of 121,344 rubella cases were reported from 167 member states to WHO, an 82% decrease from 670,894 cases reported in 2000 from 102 member states. This report summarizes reported rubella and CRS cases globally and progress toward global introduction and use of RCV.     

Strategies to eradicate rubella in the English-speaking Caribbean

OBJECTIVE: This report presents the strategies used to eradicate rubella in the Caribbean region and the challenges faced by that effort. METHODS: Using the surveillance system for measles cases that was instituted in all countries in the Caribbean Community (CARICOM), 12 countries confirmed cases of rubella between 1992 and 1996. Rubella infections occurred in epidemic proportions in 6 countries during that period. RESULTS: On the basis of the rubella prevalence data, rubella-congenital rubella syndrome (CRS) cost-benefit analysis, and cost-effectiveness of the mass campaign, the Council for Human and Social Development of CARICOM resolved, on April 21, 1998, that every effort would be made to eradicate rubella, as well as to prevent the occurrence of new cases of CRS by the end of 2000. Using the Pan American Health Organization's template for measles eradication, CARICOM proposed and implemented the main strategies for rubella and CRS eradication, and rubella mass campaigns were conducted in 18 countries. The target population, which included males and females (aged 20-40 years), was approximately 2.2 million. CONCLUSION: The major challenges for rubella eradication are attaining high vaccine coverage in the adult population and maintaining an effective surveillance system able to detect rubella activity.     

Development of the Rubella Vaccine and Vaccination Strategy in Japan

The development of the rubella vaccine and vaccination strategy in Japan was unique. Five rubella vaccines used in Japan were licensed, and the rubella vaccination program to schoolgirls was started in 1977. The measles-mumps-rubella vaccination to children, which was started in 1989, was terminated in 1993 due to the adverse effect of aseptic meningitis. In 1994, rubella vaccination to children, using the monovalent rubella vaccine, was restarted. Then, a new vaccination program, vaccinating twice by using the combined measles and rubella vaccine, was started in 2006. The increase in the rate of vaccination leads us to hope for the “Elimination of Rubella and Congenital Rubella Syndrome in 2012”.     

Surveillance of congenital rubella and rubella infections in pregnancy in EU/EEA countries, 2012: Current status and future perspective to monitor elimination

IntroductionRubella elimination and congenital rubella syndrome (CRS) prevention are targets for achievement by 2015 in the WHO-EURO Region. This paper describes the existing surveillance systems for CRS and rubella in pregnancy in order to critically interpret the findings in relation to the 2012 WHO-EURO surveillance guidelines.MethodsIn 2012 we conducted a survey to collect information on surveillance of CRS and rubella in pregnancy in 29 EU/EEA countries. Questionnaires explored the characteristics of the surveillance systems, case definition, epidemiological investigation and follow-up of cases, reference laboratories and types of tests performed.ResultsTwenty-eight countries had surveillance systems for CRS, mostly nationwide, mandatory, passive and case-based; 23 collected information on the origin of the infection; 11 reported asymptomatic infections; 6 required zero-reporting. Case definitions varied among countries, although 24 used the EU definition. Laboratories reported cases in 18 countries. Twenty countries collected information on pregnancy within the rubella surveillance system and 5 had specific surveillance for rubella in pregnancy. Two countries did not monitor outcomes of suspected infections in pregnancy; infants with CRS were monitored in all the remaining countries; asymptomatic infected infants in 15; stillbirths and fetal deaths in 13; therapeutic and spontaneous abortions in 8 and 7. Twenty-seven countries had a national reference laboratory for CRS and rubella in pregnancy; genotyping was performed in 15.DiscussionThe current surveillance systems allow adequate CRS monitoring in EU. Further efforts are needed to improve their quality, including uniform case definitions, collection of information on the origin of infection, and promotion of reporting from laboratories. Follow-up of pregnant women with suspected infection should be strengthened because it is an entry point for CRS, including detection of fetal deaths, stillbirths and abortions. Laboratory capacity for confirming congenital rubella infections and infections in pregnancy is good in EU, however the use of genotyping should be encouraged.     

A rubella vaccination program for women entering the U.S. Army

A voluntary rubella vaccination program for female basic trainees was initiated on April 21, 1975, at Fort Jackson, S.C. A total of 29,852 women were tested for rubella titers between April 21, 1975, and December 31, 1977, and 6,167 were found to be nonimmune. An average of 53 percent of the susceptible women were vaccinated. The best results were obtained from August 1 to December 31, 1977, when 67 percent of the susceptible women were vaccinated. During this period, blood specimens for rubella titer and for pregnancy testing were obtained simultaneously. This procedure reduced the number of referrals to the Obstetrics-Gynecology Clinic, as well as the amount of training time lost when pregnancy testing and rubella titer testing were done on separate days. Despite the vaccination program, however, rubella epidemics occurred among female trainees at Fort Jackson in 1975, 1976, and 1977. A significant number of women are still susceptible to rubella. To reduce morbidity and the risk of congenital rubella syndrome, rubella titer testing and immunization of susceptibles should be considered for women-especially where they can be screened, counseled, and vaccinated en masse.     

A systematic review of rubella vaccination strategies implemented in the Americas: impact on the incidence and seroprevalence rates of rubella and congenital rubella syndrome

Objective

To evaluate the impact of rubella vaccination strategies on the rates of acquired rubella and congenital rubella syndrome in the Americas.

Methods

We conducted a systematic review of the literature (MEDLINE, PubMed, EMBASE, Cochrane Library, Artemisa Database, LILACS Database, Evidence Portal, VHL-PAHO Portal, Scielo, and Grey-Literature sources) that was published from 1969–2010. We included studies on rubella incidence and seroprevalence rates that were associated with rubella vaccination. The quality of the studies was evaluated according to international guidelines.

Results

A total of 14 studies were identified: 2 clinical trials, 2 cohort studies, 3 transversal studies, 5 ecological studies, and 2 mathematical models. Childhood vaccination reduced the incidence of rubella by 23.6% to 99.6%, increased the occurrence of epidemic cycles in Argentina and in the United States, and shifted the illness to susceptible adults. Vaccination strategies that focused on women and children in Brazil were associated with a 5.5-fold greater incidence of rubella in men leading to new outbreaks and CRS. A combined vaccination strategy with a universal approach that included routine vaccination for boys, girls, women, and men in Mexico and in Costa Rica reduced the incidence of rubella by more than 98% and led to absence of CRS since 2008. A medium and a low risk of bias were found in 3 and 4 articles, respectively.

Conclusion

The results of this review demonstrate that the combined vaccination strategy with a universal approach was the most effective strategy as evidenced by a drastic reduction in the number of cases and the interruption of endemic transmission of rubella in the Americas.     

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.     

Public Health Implications of Rubella Antibody Levels in California

Rubella hemaggluttination inhibition (HI) antibody determinations were performed in 1977 on a sample of California school children and in 1977-1979 on young women who were about to be married or who were pregnant. Among the pupils, 66 per cent reported prior rubella immunization; immunization history was more common in younger pupils. Seventy-seven per cent had detectable antibody, with little trend of greater seropositivity at older ages. Over 86 per cent of those with a written record of immunization had detectable antibody. There was no consistent indication of loss of seropositivity with increasing time since immunization. Children immunized at 12-14 months of age tended to have a lower seropositivity rate than those immunized at older ages. Among young women, the prevalence of detectable antibody was 80-83 per cent. Comparison with data obtained in 1968-1969 indicates that rubella immunization has had a marked impact on antibody levels in children but less impact on levels in teenagers and adults. The pool of rubella-susceptibles entering secondary schools will probably not decrease soon, so that rubella outbreaks may continue in high school and college-age populations. Ultimately, school entry immunization requirements should drastically curtail disease activity. In the interim, programs to immunize teenagers and young adult females must be strengthened. (Am J Public Health 1982; 72:167-172.)     

妊娠早期妇女原发风疹感染率的研究

Rubella virus is the common agent of prenatal infection. Congenital malformation rate is very high among pregnant women who are infected rubella primarily during the first trimester of pregnancy. Sera were taken from 10412 early pregnant women in 4 cities and 4 countries of 6 Provinces in 4 districts of China from April 1990 to October 1991 for detection of special IgM antibodies against rubella with Capture-EIA test. The results showed that the primary infection rate was 0.318% of those women without clinical symptoms of rubella during their early pregnant period. A high infection rate of 1.477% was found in those women with clinical symptoms, 4.7 times the former rate. The total infection rate of 10,412 women was 0.461%. By this rate at least some 40 thousand CRS infants will be born each year in China. This figure is more than the sum of patients suffering from poliomyelitis and Japanese encephalitis, and much more than the number disabled from these two infectious diseases. Some suggestions to prevent CRS were put forward in this paper.     

An epidemiological assessment towards elimination of rubella and congenital rubella syndrome in Singapore

ObjectiveIn line with regional and global goals for the elimination of rubella and congenital rubella syndrome (CRS), we reviewed the epidemiological situation in Singapore, based on surveillance reports on rubella and CRS, national immunization coverage and seroprevalence surveys. The aim of our review was to identify current gaps and steps taken to achieve the targets set by the World Health Organization (WHO) Western Pacific Regional Office (WPRO).MethodsEpidemiological data on clinical and laboratory-confirmed rubella cases, including CRS, notified to the Communicable Diseases Division, Ministry of Health, Singapore, from 2003 to 2013 were collated and analyzed. Vaccination coverage against rubella was obtained from the National Immunization Registry and School Health Services of the Health Promotion Board. The changing prevalence of rubella was determined from periodic serological surveys.FindingsThe incidence of indigenous rubella cases per million population decreased from 37.2 in 2008 to 7.6 in 2013 and there had been no indigenous case of CRS in 2012 and 2013. Therapeutic abortions performed due to rubella infections had become uncommon. The annual measles, mumps, and rubella (MMR) vaccination coverage in childhood population remained high ranging from 93% to 96%. The overall susceptibility to rubella in women aged 18–44 years had reduced significantly from 15.8% in 2004 to 11.0% in 2010. The prevalence of IgG antibody against rubella among Singapore children aged 1–17 years was maintained at 87.3% in 2008–2010.ConclusionAll available data indicated that Singapore has made good progress towards the elimination of rubella and CRS. It has attained the targets set by the WHO WPRO for 2015. In preparation for verification of rubella elimination, an enhanced surveillance system has been implemented to ensure that all reported cases are laboratory confirmed, and genotyping of rubella virus strains isolated is carried out to provide evidence for interruption of endemic transmission.