Quantitative investigations of different vaccination policies for the control of congenital rubella syndrome (CRS) in the United Kingdom.

The paper examines predictions of the impact of various one-, two- and three-stage vaccination policies on the incidence of congenital rubella syndrome (CRS) in the United Kingdom with the aid of a mathematical model of the transmission dynamics of rubella virus. Parameter estimates for the model are derived from either serological data or case notifications, and special attention is given to the significance of age-related changes in the rate of exposure to rubella infection and heterogeneous mixing between age groups. Where possible, model predictions are compared with observed epidemiological trends. The principal conclusion of the analyses is that benefit is to be gained in the UK, both in the short and long term, by the introduction of a multiple-stage vaccination policy involving high levels of vaccination coverage of young male and female children (at around two years of age) and teenage girls (between the ages of 10-15 years), plus continued surveillance and vaccination of adult women in the child-bearing age classes. Model predictions suggest that to reduce the incidence of CRS in future years, below the level generated by a continuation of the current UK policy (the vaccination of teenage girls), would require high rates of vaccination (greater than 60%) of both boys and girls at around two years of age. Numerical studies also suggest that uniform vaccination coverage levels of greater than 80-85% of young male and female children could, in the long term (40 years or more), eradicate rubella virus from the population. The robustness of these conclusions with respect to the accuracy of parameter estimates and various assumptions concerning the pattern of age-related change in exposure to infections and ''who acquires infection from whom'' is discussed.     

Policies for immunization against rubella in European countries

In 1986 a survey on immunization policies against rubella was conducted in 17 European countries. A questionnaire was sent to each Ministry of Health and selected practitioners, requesting information on official policy for vaccination against rubella, level of policy decision, immunization strategy, target groups, current recommendations for vaccination, measures taken to facilitate vaccine uptake, vaccine strains used and legislation concerning abortion.A policy for the prevention of congenital rubella is explicitly defined in 16 countries (in 12 at a national level, in 3 at a regional level and in one at both levels). In Greece only, no official policy has been defined, although the practice is to vaccinate infants over 15 months of age and girls by 9–11 years of age. There are 3 countries maintaining the selective strategy of vaccinating teenage girls, but in 8 countries this strategy changed to a mass vaccination of young infants. In 5 other countries an approach combining both mass immunization and selective vaccination is adopted. This situation of different strategies between countries in Europe could have a deleterious effect for young migrants or travelling pregnant women and could reduce the effectiveness of programmes for prevention of congenital rubella syndrome. Harmonization of immunization policies and of recommendations for vaccine administration is advisable. The mass vaccination of all young children combined with systematic revaccination either of all children or of teenage girls is probably the most effective approach for elimination of congenital rubella syndrome in Europe.Corresponding author.     

Modelling rubella in Europe

The prevention of congenital rubella syndrome (CRS), as a complication of rubella infection during pregnancy, is the main aim of rubella vaccination programmes. However, as vaccination of infants leads to an increase in the average age at which those who were not immunized become infected, certain rubella vaccination programmes can lead to an increase in the incidence of CRS. In this paper we use a mathematical model of the transmission dynamics of rubella virus to investigate the likely impact of different vaccination policies in Europe. The model was able to capture pre- and post-vaccination patterns of infection and prevalence of serological markers under a wide variety of scenarios, suggesting that the model structure and parameter estimates were appropriate. Analytical and numerical results suggest that endemic circulation of rubella is unlikely in Finland, the United Kingdom, The Netherlands, and perhaps Denmark, provided vaccine coverage is uniform across geographical and social groups. In Italy and Germany vaccine coverage in infancy has not been sufficient to interrupt rubella transmission, and continued epidemics of CRS seem probable. It seems unlikely that the immunization programmes in these countries are doing more harm than good, but this may be partly as a result of selective immunization of schoolgirls. Indeed, in both these countries, selective vaccination of schoolgirls with inadequate vaccination histories is likely to be an important mechanism by which CRS incidence is suppressed (unlike the other countries, which have had sufficiently high infant coverage rates to withdraw this option). Reducing inequalities in the uptake of rubella vaccine may bring greater health benefits than increasing the mean level of coverage.     

Control of rubella and congenital rubella syndrome (CRS) in developing countries, Part 2: Vaccination against rubella.

In 1995-96 we conducted a review of rubella immunization strategies. Worldwide, 78 countries (more than one-third) reported a national policy of using rubella vaccine. This was closely related to country economic status. Based on the United Nations country classification, rubella vaccine is used in 92% of industrialized countries, 36% of those with economies-in-transition, and 28% of developing countries. Cases of congenital rubella syndrome (CRS) may be prevented as follows: by providing direct protection to women and/or schoolgirls (a selective vaccination strategy); by vaccinating boys and girls to provide indirect protection by reducing the transmission of rubella virus (a childhood vaccination strategy); or by a combination of these approaches (a combined strategy). A combined strategy was most commonly reported (60% of countries); seven countries (9%) reported a selective strategy; and 24 countries (31%) reported only childhood immunization. Experience has shown that it is essential to include vaccination of women of childbearing age in any rubella control strategy. Childhood vaccination alone may pose a risk of an increase in CRS cases. Although many countries have introduced rubella vaccine, few report any data on the impact of vaccination. Countries using rubella vaccine need to establish surveillance for rubella and CRS and monitor coverage in each of the target groups.     

Rötelsituation in Deutschland Ergebnisse der seroepidemiologischen Überwachung von 1990 bis 1998

The present situation regarding rubella is reflected in seroprevalence studies performed between 1990 and 1998. By selective immunisation of girls and young women (the female population >13 years of age) it was possible to a wide extent to close immunity gaps in young adults which occurred in the pre-vaccination era. In 1998 in the cohort of the 18–30-year-old population only 0.8–3% of the women were seronegative for rubella, compared to 5–13% of the men. Differences regarding immunity between old and new federal Länder are no longer existent, although vaccination against rubella was only introduced in the new Länder after the reunification. Above all, a potential risk for pregnant women without protection against rubella is conferred by the high percentage of pre-school children without rubella immunity. This is due to the delay in starting to vaccinate small children, but also to a lower acceptance of the combined vaccination. Compared to countries like Finland, Sweden or the United States, which have almost achieved the elimination of congenital rubella syndrome (CRS), in Germany a considerable number of individuals remain susceptible to this infection. Continuous endemic virus circulation endangers the main target group of rubella vaccination, i. e. women in the early stages of pregnancy. Only when MMR vaccination rates of more than 90% are achieved in small children in the course of their second year of life, there will be a real chance in Germany to eradicate not only measles, but also the CRS over the next 10 years.     

Sero-epidemiology of rubella in the urban population of Addis Ababa, Ethiopia

We conducted a community-based cluster sample survey of rubella sero-epidemiology in Addis Ababa, Ethiopia in 1994. Among 4666 individuals for whom complete data were available, rubella antibody prevalence was 91% (95% confidence interval: 90, 92). On multivariable analysis, seroprevalence was lower among individuals who were resident in Addis Ababa for 1 year or less. Approx. 50% seroprevalence was attained by age 4 years, and the estimated average age at infection was 5.2 years. The highest age-specific force of infection was estimated to occur in 5- to 9-year-olds. The early age at infection corresponded with a low estimated incidence of congenital rubella syndrome (CRS) of 0.3 per 1000 live births, equivalent to nine cases of CRS in 1994. The predicted critical level of immunity for elimination of rubella via vaccination was 85-91%, requiring 89-96% coverage with a vaccine of 95% effectiveness. Unless very high coverage of rubella vaccine could be guaranteed, the introduction of childhood vaccination could increase the incidence of CRS in Addis Ababa.     

Models of strategies for control of rubella and congenital rubella syndrome—A 40 year experience from Australia

We investigated the impact of vaccination on rubella epidemiology in Australia, using a mathematical model fitted to Australian serosurvey data and incorporating pre-vaccination European estimates of rubella transmissibility. Mass infant measles–mumps–rubella (MMR) vaccination produced a 99% reduction in both rubella and congenital rubella syndrome (CRS) incidence by 2010 compared to the pre-vaccination era (1960–70). The model is consistent with reductions in CRS based on surveillance of congenital hearing impairment. Model simulations suggest that selective schoolgirl vaccination (1971–88) was associated with a 90% reduction in CRS incidence, but only a 1–4% reduction in rubella incidence. Our model predicted that these reductions in rubella were much less vulnerable to reductions in MMR vaccine coverage than for measles. In the future, a less than 15% decrease in MMR vaccine coverage is estimated to have minimal impact before 2060, but a 20% reduction may result in a 7-fold increase in rubella incidence, with the effective reproductive number R rising from 0.28 to 0.78 by 2060. The 99% reduction in both rubella and CRS incidence and low effective reproductive number (R ≤ 0.28) we documented after 2010 are consistent with Australia having achieved rubella elimination.     

Modelling the incidence of congenital rubella syndrome in developing countries

BACKGROUND: As of 1997, less than one-third of developing countries included rubella vaccine in their national immunization programme. In countries that have achieved high coverage of measles vaccine, an ideal opportunity exists to include control of rubella and congenital rubella syndrome (CRS) in enhanced measles control activities. Data on the burden of congenital rubella syndrome are important to guide rubella vaccination policies. METHODS: We reviewed the literature to identify studies of rubella antibody prevalence in developing countries that were conducted on populations with no major selection bias, prior to wide-scale rubella vaccination in the country. We used a simple catalytic model to describe the age-specific prevalence of susceptibility to rubella virus infection in given populations. Estimates of the incidence of infection among pregnant women were calculated using expressions for the average prevalence of susceptibility to infection and the incidence of infection during gestation. To estimate the number of cases of CRS, we assumed an overall risk of 65% after infection in the first 16 weeks of pregnancy and zero risk thereafter. These estimates were derived for each country for which data were available, then for each World Health Organization region, excluding Europe. RESULTS: The estimated mean incidence of CRS per 100,000 live births was lowest in the Eastern Mediterranean region (77.4, range 0-212) and highest in the Americas (175, range 0-598). The mean of the estimates of the total number of cases of CRS in developing countries in 1996 was approximately 110,000. The range was, however, very wide, from as few as 14,000 to as many as 308,000 cases. CONCLUSIONS: Congenital rubella syndrome is an under-recognized public health problem in many developing countries. There is an urgent need for collection of appropriate data to estimate the cost-effectiveness of a potential global rubella control programme.     

Rubella in the Russian Federation: epidemiological features and control measures to prevent the congenital rubella syndrome

A review of the epidemiology of clinical rubella in the Perm region of the Russian Federation from 1979-97 showed that the incidence was about 220 cases per 100,000 population. Congenital rubella syndrome (CRS) accounted for 15% of birth defects and for about 3.5 cases of CRS per 1000 live births per year. Surveys of the seroepidemiology of rubella infection revealed that the susceptibility rate among pregnant women (i.e. rubella virus antibody haemagglutination-inhibition (HAI) assay titres < 10) was 16.5%. As serum rubella antibody HAI titres > or = 10 both prevented infection in pregnant women and protected their foetuses, serological testing has been introduced into the routine antenatal services. Pre-existing rubella antibodies were found not to interfere with the immune response to vaccination, so selective immunization was provided to girls approaching puberty and to women of childbearing age. A programme of epidemiological surveillance is being developed to define tactics for the widescale introduction of rubella vaccination.     

Newsprint media representations of the introduction of the HPV vaccination programme for cervical cancer prevention in the UK (2005–2008)

In September 2008, the human papillomavirus (HPV) immunisation programme was introduced in the UK for schoolgirls aged between 12 and 18 years of age. The vaccine shows high efficacy in preventing infection against HPV types 16 and 18 responsible for 70% of cervical cancer. However, to be most effective, the vaccine needs to be administered before exposure to the viruses and therefore, ideally, before young people become sexually active. The introduction of any new vaccine, and perhaps particularly one given to young teenage girls to prevent a sexually transmitted cancer-causing virus, has the potential to attract a great deal of media attention. This paper reports on content analysis of 344 articles published between January 2005 and December 2008 in 15 UK newspapers. It includes both manifest and latent analysis to examine newsprint media coverage of the introduction of the HPV vaccination programme and its role in HPV advocacy. We concluded that the newspapers were generally positive towards the new HPV vaccination and that over the 4 years period the newsworthiness of the HPV vaccination programme increased. In 2008 two events dominated coverage, firstly, the introduction of the HPV programme in September 2008 and secondly, in August 2008 the diagnosis on camera of cervical cancer given to Jade Goody, a 27 year old mother of two, who gained fame and notoriety in the UK through her participation in several reality television shows.     

Predicting the dynamic effects of rubella vaccination programmes

In the Netherlands, prepubertal girls have been vaccinated against rubella since 1974 (the UK strategy). Recently the Dutch Health Council advocated the introduction of an elimination strategy: vaccination of 1- and 9-year-old children. Dynamic effects of both strategies are studied using deterministic and stochastic models. Estimates of several epidemiological parameters are given. All computations and simulations were performed using as much field data as possible. Under the old strategy a new equilibrium is expected around the years 1995 to 2000; the new strategy is estimated to eliminate rubella (CRS) in large parts of the population 3 to 5 years after its initiation. Possible consequences of the new strategy on a cluster of people who refuse vaccination are investigated.     

山东省实施儿童风疹疫苗免疫后风疹发病年龄变化趋势的分析

目的分析山东省自1995年开始实施儿童风疹疫苗免疫后风疹发病年龄的变化趋势。方法对1999—2004年通过麻疹疫情专报系统得到的风疹疫情资料以及风疹疫苗接种情况进行分析。结果1999—2004年山东省风疹年平均报告发病率为0．59／10万，多为暴发（占总病例数的81．17％）；发病主要集中在7～15岁学龄儿童（77．77％），7岁以下发病较少（占7．93％），发病年龄中位数分别为10．37岁、11．66岁、11．41岁、12．81岁、14．28岁和13．96岁，发病高峰年龄逐年后移，成人发病有所增加；学龄前儿童风疹疫苗基础免疫估算接种率约为60％，学龄儿童约为20％。结论风疹发病年龄后移，将威胁育龄期妇女，增加发生先天性风疹综合征的危险性；应在继续做好儿童风疹免疫的同时，积极开展育龄期妇女风疹抗体筛查及疫苗接种工作。     

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相似文献   

Estimating the burden of rubella virus infection and congenital rubella syndrome through a rubella immunity assessment among pregnant women in the Democratic Republic of the Congo: Potential impact on vaccination policy

BackgroundRubella-containing vaccines (RCV) are not yet part of the Democratic Republic of the Congo’s (DRC) vaccination program; however RCV introduction is planned before 2020. Because documentation of DRC’s historical burden of rubella virus infection and congenital rubella syndrome (CRS) has been minimal, estimates of the burden of rubella virus infection and of CRS would help inform the country’s strategy for RCV introduction.MethodsA rubella antibody seroprevalence assessment was conducted using serum collected during 2008–2009 from 1605 pregnant women aged 15–46 years attending 7 antenatal care sites in 3 of DRC’s provinces. Estimates of age- and site-specific rubella antibody seroprevalence, population, and fertility rates were used in catalytic models to estimate the incidence of CRS per 100,000 live births and the number of CRS cases born in 2013 in DRC.ResultsOverall 84% (95% CI 82, 86) of the women tested were estimated to be rubella antibody seropositive. The association between age and estimated antibody seroprevalence, adjusting for study site, was not significant (p = 0.10). Differences in overall estimated seroprevalence by study site were observed indicating variation by geographical area (p ⩽ 0.03 for all). Estimated seroprevalence was similar for women declaring residence in urban (84%) versus rural (83%) settings (p = 0.67). In 2013 for DRC nationally, the estimated incidence of CRS was 69/100,000 live births (95% CI 0, 186), corresponding to 2886 infants (95% CI 342, 6395) born with CRS.ConclusionsIn the 3 provinces, rubella virus transmission is endemic, and most viral exposure and seroconversion occurs before age 15 years. However, approximately 10–20% of the women were susceptible to rubella virus infection and thus at risk for having an infant with CRS. This analysis can guide plans for introduction of RCV in DRC. Per World Health Organization recommendations, introduction of RCV should be accompanied by a campaign targeting all children 9 months to 14 years of age as well as vaccination of women of child bearing age through routine services.     

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.     

Prevalence of antibodies against rubella virus in The Netherlands 9 years after changing from selective to mass vaccination

A two-dose mass vaccination programme with a combined vaccine against measles, mumps and rubella (MMR) was adopted in the Netherlands in 1987, replacing the selective schoolgirl vaccination strategy introduced in 1974. To obtain insight into the effect of mass vaccination and the population's immunity, the antibody levels against rubella were studied in the general Dutch population and in religious groups refusing vaccination. In the national sample, we observed a high prevalence (96.5%) for rubella antibodies in vaccinated cohorts as well as in the older unvaccinated cohorts. No indications of rapidly waning immunity after vaccination were found. There are indications of low virus circulation in the last few years. The very high seroprevalence in women at childbearing age is consistent with the few reported cases of congenital rubella syndrome (CRS) at present. However, individuals in the age group of 1-9 years who are not vaccinated for religious or other reasons have a considerably lower seroprevalence and thus there is a potential risk of a CRS outbreak in the future.     

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.     

Epidemiology of rubella and congenital rubella syndrome in Japan before 1989

Epidemiological studies of rubella and congenital rubella syndrome (CRS) in Japan have been conducted since the first nationwide rubella epidemic of 1965–1969 and subsequent epidemics of 1975–1977, 1982, 1987–1988, and 1992–1993. Rubella was non-endemic in Japan before the 1975–1977 epidemic, and endemic thereafter. Japan started a selective rubella vaccination program for junior high school girls in 1977, and universal rubella vaccination of children of both sexes in 1989. No nationwide rubella epidemics have occurred since 1994.Only three children with CRS were reported in Japan before 1964; however, many children with CRS were identified in 1965 when a rubella epidemic struck Okinawa, which has many the United States military bases. After the 1965–1969 and 1975–1977 rubella epidemics on the Japanese mainland, small numbers of children with CRS were identified (hospital survey). These findings led to the hypothesis that, compared to U.S. rubella virus strains, Japanese strains of rubella virus are less teratogenic. This hypothesis strongly affected the development of rubella vaccines in Japan. However, retrospective seroepidemiological studies attributed the CRS in many children in Okinawa to the high rate of rubella infection in pregnant women. According to the survey conducted at special schools for the deaf, 83, 232, 77, and 167 children were born with CRS on the Japanese mainland respectively after the 1965–1969, 1975–1977, 1982, and 1987–1988 nationwide rubella epidemics, suggesting that the incidence of CRS in Japan is in fact comparable to that in the U.S. and Europe.Rubella epidemics in children have been effectively prevented since 1994. However, a rubella outbreak among adult males and CRS occurred between 2012 and 2014.     

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.     

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.