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.     

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.     

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.     

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.     

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.     

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.     

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。     

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.     

Age-related changes in the rate of disease transmission: implications for the design of vaccination programmes.

Mathematical models are developed to aid in the investigation of the implications of heterogeneity in contact with infection within a community, on the design of mass vaccination programmes for the control of childhood viral and bacterial infections in developed countries. Analyses are focused on age-dependency in the rate at which individuals acquire infection, the question of ''who acquires infection from whom'', and the implications of genetic variability in susceptibility to infection. Throughout, theoretical predictions are based on parameter estimates obtained from epidemiological studies and are compared with observed temporal trends in disease incidence and age-stratified serological profiles. Analysis of case notification records and serological data suggest that the rate at which individuals acquire many common infections changes from medium to high and then to low levels in the infant, child and teenage plus adult age groups respectively. Such apparent age-dependency in attack rate acts to reduce slightly the predicted levels of herd immunity required for the eradication of infections such as measles, when compared with the predictions of models based on age-independent transmission. The action of maternally derived immunity in prohibiting vaccination in infants, and the broad span of age classes over which vaccination currently takes place in the U.K., however, argue that levels of herd immunity of between 90 and 94% would be required to eliminate measles. Problems surrounding the interpretation of apparent age-related trends in the acquisition of infection and their relevance to the design of vaccination programmes, are discussed in relation to the possible role of genetically based variation in susceptibility to infection and observations on epidemics in ''virgin'' populations. Heterogeneous mixing models provide predictions of changes in serology and disease incidence under the impact of mass vaccination which well mirror observed trends in England and Wales.     

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.     

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.     

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.     

The predicted impact of private sector MMR vaccination on the burden of Congenital Rubella Syndrome

In many developing countries, Measles-Mumps-Rubella (MMR) vaccine is available through the private but not the public sectors, and there is no systematic rubella vaccination among adult women. In this paper, we extend previous modeling studies to demonstrate that in developing countries with a medium-high force of infection (200-400/1000 per year), current levels of private sector MMR coverage (<60%) would lead to increases in the incidence of Congenital Rubella Syndrome (CRS) both among unvaccinated individuals and the general population even when mixing between vaccinated and unvaccinated individuals is fairly minimal. Our findings highlight the need for countries to establish surveillance of trends in susceptibility to rubella and CRS incidence and perhaps introduce rubella vaccination among women of child-bearing age.     

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   

Rubella revisited: where are we on the road to disease elimination in Central Europe?

Rubella is a contagious viral disease with few complications except when contracted by pregnant women. Rubella infection in pregnancy can result in miscarriage, stillbirth or an infant born with congenital rubella syndrome (CRS) which comprises deafness, heart disease, cataracts and other permanent congenital manifestations. Clinical diagnosis of rubella is difficult due to overlapping symptoms with many other diseases and confirmation of rubella is not possible without laboratory testing.Effective vaccination programmes are critical to the elimination of rubella and prevention of CRS. Such programmes have been successful in several countries in Europe and around the world. However, rubella outbreaks still occur due to suboptimal vaccine coverage and in the past 10 years rubella has been reported in Central European countries such as Romania and Poland. Over the past decade the elimination of rubella and prevention of congenital rubella infection in Europe has been a high priority for the WHO European Regional Office. In 2010 the WHO regional committee for Europe renewed its commitment to the elimination of rubella and prevention of CRS with a new target of 2015.This paper examines the current situation for rubella and CRS in Central Europe and describes the different rubella vaccination programmes in the region. The Central European Vaccination Advisory Group (CEVAG) recommends that two doses of measles, mumps and rubella vaccine, MMR, should be given to all children. The first dose should be given between 12 and 15 months of age. The second dose can be given between the ages of 21 months and 13 years with the exact age of administration of the second dose depending on the situation specific to each country. All suspected rubella cases should be laboratory-confirmed and monitoring systems to detect and investigate cases of CRS should be strengthened.     

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.     

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.     

The contagious nature of a vaccine scare: How the introduction of HPV vaccination lifted and eroded MMR vaccination in Denmark

BackgroundHuman papillomavirus (HPV) vaccine coverage was high in Denmark until it plunged following negative media coverage. We examined whether the decline in HPV vaccination undermined uptake of another adolescent vaccine, measles, mumps and rubella (MMR).MethodsThe Danish national health register provided data on uptake of MMR vaccine dose 2 (at age 13) for children born from 1991 to 2003 (n = 827,716). The primary exposure variable comprised three time periods: before HPV vaccine introduction, during high HPV vaccine coverage, and after the drop in HPV vaccine coverage. To examine the effect of HPV vaccination on MMR2 uptake, we estimated MMR2 uptake by age 13 using logistic regression, controlling for gender, birth month, birth year, and maternal education.FindingsMMR2 vaccination coverage was high for both girls and boys (86% and 85%) in 2009. Following the introduction of HPV vaccine for girls in 2009, MMR2 coverage increased for girls even as it decreased for boys (gender gap 4·6 percentage points, 95% CI 4·3 to 4·8). Coverage with MMR2 for girls continued to be high over the following four years, and almost all girls (91%) who received MMR2 vaccination also received HPV1 vaccination within the same week. When negative media coverage led to a decline in HPV vaccination, MMR2 uptake for girls also declined. By 2015, MMR2 coverage for girls and boys had become similar again (80% and 79%). Families with the highest level of maternal education showed the strongest decline in MMR2 coverage for girls.InterpretationConcomitant vaccine provision can increase overall vaccine uptake. However, reduced demand for one vaccine may reduce concomitant vaccination and undermine resiliency of a country’s vaccination program.FundingDrs. Gørtz and Ejrnæs appreciate generous funding from the Novo Nordisk Foundation (grant no. NNF17OC0026542) and from the Danish National Research Foundation through its grant (DNRF-134) to the Center for Economic Behavior and Inequality (CEBI) at the University of Copenhagen.     

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.