The seroepidemiology of rubella in western Europe

Most of the countries in western Europe have now implemented mass infant rubella immunization programmes, instead of or in addition to selective vaccination in order to achieve the elimination of congenital rubella syndrome. The European countries Denmark, England and Wales, Finland, France, Germany, Italy and the Netherlands undertook large, national serological surveys collecting several thousand serum specimens during 1994-8. Antibodies against rubella virus were detected by a variety of enzyme immuno-assays. Comparability of the assay results was achieved by a standardized methodology. The age- and sex-stratified serological results were related to the schedules, coverage of rubella vaccination and the incidence in these countries. The results show widely differing levels of immunity to rubella both in the general population and in the specific age groups of males and females. A low rate (< 5%) of susceptibles in childhood and adolescents of both sexes was obtained only in Finland and the Netherlands. Countries such as Italy with only moderate coverage for the infant immunization programme currently have both high susceptibility levels in the general population and in the at-risk population. The likelihood is of continued epidemics of rubella with cases of congenital rubella syndrome. The continued implementation of selective vaccination will help to offset the impact of this ongoing transmission and to protect women on reaching childbearing age.     

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.     

Modelling forces of infection for measles, mumps and rubella

Serological data from 8870 persons collected prior to the introduction of measles, mumps and rubella (MMR) vaccine in the UK are used to describe the rate at which individuals acquire infection by these diseases at different ages. A parsimonious model is developed and fitted under various interpretations of the data, particularly concerning the probability of lifelong susceptibility to infection. It is shown that, while the force of infection curves are relatively robust in their general features, they exhibit considerable sensitivity in matters of important detail. This is true in particular of the values taken by the force of infection in older age groups. As a result, estimates of the average age at infection are highly sensitive to these interpretations. This in turn may limit the accuracy of predictions from mathematical models based on these parameters, in particular regarding the level of immunization required for eradication of disease.     

Incidence of congenital rubella syndrome in 19 regions of Europe in 1980–1986

Twenty-five cases of congenital rubella syndrome were recorded in 1,458,126 live births in 19 EUROCAT birth defects registries from 1980 to 1986. During the study period, the incidence declined steadily from 3.50 to 0.41 per 100,000 births. Rubella infection occurred in 12 multiparous women indicating failure in immunization programme.Corresponding author.     

Modelling BSE trend over time in Europe,a risk assessment perspective

BSE is a zoonotic disease that caused the emergence of variant Creuzfeldt-Jakob disease in the mid 1990s. The trend of the BSE epidemic in seven European countries was assessed and compared, using Age-Period-Cohort and Reproduction Ratio modelling applied to surveillance data 2001–2007. A strong decline in BSE risk was observed for all countries that applied control measures during the 1990s, starting at different points in time in the different countries. Results were compared with the type and date of the BSE control measures implemented between 1990 and 2001 in each country. Results show that a ban on the feeding of meat and bone meal (MBM) to cattle alone was not sufficient to eliminate BSE. The fading out of the epidemic started shortly after the complementary measures targeted at controlling the risk in MBM. Given the long incubation period, it is still too early to estimate the additional effect of the ban on the feeding of animal protein to all farm animals that started in 2001. These results provide new insights in the risk assessment of BSE for cattle and Humans, which will especially be useful in the context of possible relaxing BSE surveillance and control measures.     

The pre-vaccination epidemiology of measles, mumps and rubella in Europe: implications for modelling studies

Data on the pre-vaccination patterns of infection for measles, mumps and rubella are collated from a number of European countries in order to compare the epidemiology of the three viruses. Key epidemiological parameters, such as the age-specific force of infection and the basic reproduction number (R0) are estimated from case notification or serological data using standard techniques. A method is described to compare force of infection estimates derived from serological data. Analysis suggests that the pre-vaccination patterns of measles and mumps infection in the different countries were similar. In contrast, the epidemiology of rubella was highly variable between countries. This suggests that it may be acceptable to use parameter values estimated from other countries to model measles and mumps transmission, but that this approach to modelling rubella transmission requires more caution. Estimates of R0 depend on underlying mixing assumptions. Constraints were placed on R0 estimates by utilising knowledge of likely mixing patterns. The estimates for R0 were highest for measles, intermediate for mumps, and generally lowest for rubella. Analysis of within- and between-age-group transmission rates suggested that mumps transmission tends to be more concentrated within young children than the other two viruses. The implications for the design of immunization programmes are that mumps may be the easiest to control via infant immunization since it is predominantly transmitted between the very young and the variability in rubella epidemiology requires that careful consideration of the possible effects of vaccination options should be made using local data when planning rubella immunization programmes.     

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.     

Seroepidemiology of rubella in Bahrain

Although the Ministry of Health of the State of Bahrain has set priorities for vaccination against a number of communicable diseases including the six target diseases of the Expanded Program of Immunization, no such policy for rubella immunization exists. The incidence of rubella in Bahrain is not precisely known nor is the magnitude of the problem of Congenital Rubella Syndrome. A survey of schoolchildren and primigravidae attending antenatal clinics was undertaken in Bahrain to determine the level of natural immunity against rubella in these groups, which we hope would help us in formulating a vaccination policy. We have found that 67.8% of the 6-7 year old children are susceptible to rubella and that by the age of 18 years susceptibility drops to 10.4%. The decrease in susceptibility was significant until the age of 14 years after which the change became minimal. Efforts should ideally be focused on immunizing all susceptible females before they get married. However, at present, it would be more economical to vaccinate all girls premaritally than to screen and vaccinate those susceptible. When a cheaper screening test for assessing immunity against rubella becomes available, a policy of premarital and post-partum screening followed by vaccination of susceptibles should be put into practice.     

Radial haemolysis for the detection of rubella antibody in acute postnatal rubella.

One hundred and forty-eight sera from 101 cases of acute postnatal rubella were examined by the radial haemolysis (RH) technique currently recommended by the Public Health Laboratory Service of the United Kingdom. In 75 cases the date of onset of rash was known. No sera were RH positive until the third day after the onset of rash and one serum was still negative at 9 days. By 10 days all sera gave a zone of at least 10 mm. The antibody response detected by RH appears later than that detected by haemagglutination inhibition (HI). Thirty-nine of the 101 cases could be diagnosed by seroconversion or a significant rise in titre using the HI test (diagnosis of the remainder depending upon rubella-specific IgM tests). Using the RH test this figure rises to 48 but in ten of these cases reliance on RH would have meant a delay in diagnosis. The results also indicate that many more sera would need to be tested for rubella-specific IgM if the RH test was used instead of the HI test for evaluating possible cases and contacts of rubella.     

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.     

Accelerated rubella control and the prevention of congenital rubella syndrome]

Congenital rubella syndrome (CRS) is associated with substantial morbidity and mortality and with high costs. Today, as a result of improved vaccination and epidemiological surveillance efforts directed at eradicating measles from the Western Hemisphere, there has been a notable increase in the ability to detect, prevent, and control rubella and CRS. The importance of these measures is undeniable, and this piece examines the components that are essential in moving ahead to reduce these major public health problems in Latin America and the Caribbean. One step in that direction would be to integrate the surveillance of measles with that of rubella and CRS.     

Economic analyses of rubella and rubella vaccines: a global review

OBJECTIVE: To investigate whether the incorporation of rubella vaccine into immunization programmes in developing countries is economically justified. METHODS: A MEDLINE search was conducted for articles published between 1970 and 2000 that dealt with economic analyses of rubella and rubella-containing vaccines. The Eastern Mediterranean, South-East Asia, and Africa regional Index Medicus databases and the LILACS database for Latin America and the Caribbean were also searched. FINDINGS: For developed countries, five cost- benefit analyses of rubella vaccine and five of measles-mumps-rubella vaccine as well as two cost-effectiveness analyses were found. For developing countries, five cost analyses and five cost-benefit analyses were found. All the cost-benefit analyses had a benefit:cost ratio greater than 1 and the cost-effectiveness studies indicated that rubella immunization was a cost-effective means of reducing the impact of congenital rubella syndrome. However, the methodologies were not standardized. CONCLUSION: The data support the inclusion of rubella vaccine in the immunization programmes of both developing and developed countries and indicate economic benefits comparable to those associated with hepatitis B vaccine and Haemophilus influenzae type b vaccine. More studies should be carried out on costs for care and immunization using standardized methodologies and locally obtained information.