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.     

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.     

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.     

Rubella and congenital rubella syndrome: global update.

Worldwide, it is estimated that there are more than 100.000 infants born with congenital rubella syndrome (CRS) each year. In 1998, standard case definitions for surveillance of CRS and rubella were developed by the World Health Organization (WHO). In 2001, 123 countries/territories reported a total of 836.356 rubella cases. In the future more countries are expected to report on rubella as a global measles/rubella laboratory network is further developed under the coordination of WHO. Operational research is being conducted to improve rubella surveillance. This includes projects on initiating CRS surveillance, comparative studies on diagnostic laboratory methods, and molecular epidemiology research to expand the global understanding of patterns of rubella virus circulation. In 1996 a WHO survey found that 78 od 214 reporting countries/territories (36%) were using rubella vaccine in their routine immunization services. By the en of 2002 a total of 124 of the 214 counties/territories (58%) were using rubella vaccine. Rubella vaccine use varies by stage of economic development: 100% for industrialized countries, 71% for countries with economies in transition, and 48% for developing countries. A safe effective rubella vaccine is available, and there are proven vaccination strategies for preventing rubella and CRS. A WHO position paper provides guidance on programmatic aspects of rubella vaccine introduction. The introduction of rubella vaccine is cost-effective and cost-beneficial but requires ongoing strengthening of routine immunization services and surveillance systems.     

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.     

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.     

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.     

2010-2014年哈尔滨市先天风疹综合征监测分析

目的 分析2010-2014年哈尔滨市先天风疹综合征（CRS）的监测结果。方法 采用描述流行病学方法,对监测的CRS病例进行分析,并对监测指标进行评价。结果 2010-2014年,哈尔滨市共报告CRS疑似病例611例,诊断为CRS的37例,发病率在6.88/10万~15.23/10万之间,年平均发病率为10.05/10万活产儿童;临床表现主要为先天性心脏病、听力损失和眼部疾病,患儿母亲均无明确风疹疫苗接种史;实验室诊断病例感染风疹病毒的时间集中在孕4~6周。结论 我市CRS发病率仍在较高水平。应继续加强疫苗接种,开展育龄期妇女血清抗体水平监测,继续开展CRS病例监测,为制定CRS防控策略提供依据。     

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.     

Safety profile of rubella vaccine administered to pregnant women: A systematic review of pregnancy related adverse events following immunisation,including congenital rubella syndrome and congenital rubella infection in the foetus or infant

BackgroundData on the safety of inadvertent rubella vaccination in pregnancy is important for rubella vaccination programs aimed at preventing congenital rubella syndrome.MethodsThe association between monovalent rubella or combination vaccinations in or shortly before pregnancy and potential harm to the foetus was examined by conducting a systematic review and meta-analysis using fixed effect methods and simulation.ResultsFour cohort studies of inadvertently vaccinated and unvaccinated women were found, 15 cohorts of pregnant women who were rubella susceptible at time of inadvertent vaccination and 9 cohort studies with no information on susceptibility and case series. No case of vaccine associated congenital rubella syndrome (CRS) was identified. Cohort studies with an unvaccinated comparison group were limited in number and size, and based on these only a theoretical additional risk of 6 or more cases of CRS per 1000 vaccinated women (0% observed, upper 95% CI 0.6%) could be excluded. Based on cohorts of vaccinated rubella susceptible pregnant women a maximum theoretical risk of 1 CRS case in 1008 vaccinated women (0% observed, upper 95% CI 0.099%) was estimated. Asymptomatic rubella vaccine virus infection of the neonate was also noted (fixed effects estimate of risk overall 1.74%, 95% CI 1.21, 2.28).ConclusionThere is no evidence that CRS is caused by rubella-containing vaccines but transplacental vaccine virus infection can occur. CRS is effectively prevented by vaccination, thus the risk/benefit balance is unequivocally in favour of vaccination. The data confirm previous recommendations that inadvertent vaccination during pregnancy is not an indication for termination of pregnancy.     

Prevention of Congenital Rubella Syndrome--What Makes Sense in 2006?

This review summarizes the practical aspects of rubella immunizationprograms in both developed and developing countries. Routineuse of rubella vaccine is gradually resulting in the eliminationof endemic rubella and congenital rubella syndrome (CRS) inthe developed world, and routine use of vaccine in young childrenis now being implemented in many developing countries. However,such programs must achieve high immunization rates or be supplementedby the immunization of seronegative women of childbearing ageto prevent a paradoxical increase in CRS as the burden of illnessis shifted to an older age group. There are many successfulprenatal screening programs for rubella immunity in developedcountries, but screening prior to pregnancy could theoreticallyprevent even more cases of CRS. Enzyme-linked immunosorbentassay is the most commonly used laboratory test for screening,but the protective titer remains to be established. The needfor reimmunization of women who serorevert or who remain seronegativefollowing rubella vaccine has not been established. Surveillancefor rubella cases and for CRS is vital in assessment of theongoing success of rubella immunization programs. antibodies, viral • immunization programs • rubella • rubella syndrome, congenital • rubella vaccine • rubella virus     

山东省风疹流行现状分析

为了解风疹发病现况 ,进一步做好控制风疹和先天性风疹综合征 (CRS)工作 ,对近年来山东省风疹流行现状进行了分析。结果显示 :自 1995年山东省推广风疹疫苗免疫接种以来 ,风疹发病得到了有效控制。但部分地区风疹疫苗免疫接种存在漏洞 ,风疹仍在局部地区以爆发形式呈小规模周期性流行。 1999年全省共报告风疹 114例 ,2 0 0 0年报告 2 13例 ,2 0 0 0年比 1999年上升 86 84 % ;高峰季节为春季 ,病例主要集中于学龄儿童 ,1999年 7岁发病最高 ,2 0 0 0年为 10～ 12岁。免疫史分析发现 ,山东省风疹发病主要与风疹疫苗实际接种率不高有关。因此 ,今后应加强风疹疫苗的常规免疫接种 ,以降低风疹和CRS的发生 ,提高麻疹监测工作的质量。     

Inferring rubella outbreak risk from seroprevalence data in Belgium

Rubella is usually a mild disease for which infections often pass by unnoticed. In approximately 50% of the cases, there are no or only few clinical symptoms. However, rubella contracted during early pregnancy could lead to spontaneous abortion, to central nervous system defects, or to one of a range of other serious and debilitating conditions in a newborn such as the congenital rubella syndrome. Before the introduction of mass vaccination, rubella was a common childhood infection occurring all over the world. However, since the introduction of rubella antigen-containing vaccines, the incidence of rubella has declined dramatically in high-income countries. Recent large-scale mumps outbreaks, one of the components in the combined measles-mumps-rubella vaccine, occurring in countries throughout Europe with high vaccination coverage, provide evidence of pathogen-specific waning of vaccine-induced immunity and primary vaccine failure. In addition, recent measles outbreaks affecting populations with suboptimal vaccination coverages stress the importance of maintaining high vaccination coverages. In this paper, we focus on the assessment of rubella outbreak risk using a previously developed method to identify geographic regions of high outbreak potential. The methodology relies on 2006 rubella seroprevalence data and vaccination coverage data from Belgium and information on primary and secondary vaccine failure obtained from extensive literature reviews. We estimated the rubella outbreak risk in Belgium to be low, however maintaining high levels of immunisation and surveillance are of utmost importance to avoid future outbreaks.     

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.     

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。     

Mass Measles Rubella Immunization Campaign: Bhutan Experience

Background:

Bhutan has attained universal child immunization since 1991. Since then, immunization coverage is maintained at high level through routine immunization, periodic National Immunization Days, and mop up campaigns. Despite high immunization coverage, every year, significant numbers of clinically suspected measles cases were reported.

Objective:

To assess the cause of continuing high “suspected measles cases” and take appropriate public health measures.

Materials and Methods:

Febrile rash outbreaks occurred in several districts in 2003. These episodes were investigated. Simultaneously, a retrospective data search revealed evidence of congenital rubella syndrome (CRS) in the country.

Results:

Thirty five percent of the tested samples were positive for rubella but none for measles. There were evidences of the presence of CRS. This was discussed in the annual health conference 2004, amongst health policy makers and district heads who recommended that a possibility of inclusion of rubella as an antigen be looked into. A nationwide measles and rubella immunization campaign was conducted in 2006 followed by introduction of rubella vaccine in the immunization schedule.

Conclusion:

Febrile rash can be caused by a host of viral infections. Following universal measles immunization, it is pertinent that febrile rash be looked in the light of rubella infections. Following the introduction of rubella vaccination in the national immunization schedule, there has been significant reduction of febrile rash episodes, cases of rubella, and congenital rubella syndrome.     

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.     

Rubella seroprevalence among primary and pre- primary school pupils at Moi's Bridge location, Uasin Gishu District, Kenya

Background  

Rubella is an infectious and generally mild childhood viral disease. The disease is of public health importance because infection acquired during early pregnancy often results in foetal abnormalities that are classified as congenital rubella syndrome (CRS). The burden of rubella infection in most developing countries in not well documented because of limited epidemiological data. However, availability of an effective vaccine has made it necessary to have all the countries with no routine vaccination schedule to evaluate the burden of disease in order to make informed decisions on rubella vaccination and strategy. To address this gap we conducted a study to determine age-specific rubella seroprevalence rates and related risk factors among primary and pre-primary school children in Uasin Gishu district, Moi's Bridge location of Kenya.