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.     

Interpreting serological surveys using mixture models: the seroepidemiology of measles, mumps and rubella in England and Wales at the beginning of the 21st century

A mixture modelling technique is applied to age-specific frequency distributions of quantitative results from serological surveys for measles, mumps and rubella using samples collected across the age range in England and Wales in 2000. In accordance with previous studies the analysis suggests that the antibody response to natural infection is stronger than that produced by vaccination, that vaccine-induced antibody levels wane with time and that levels of vaccine-induced antibody response vary for each virus infection being strongest for rubella and weakest for mumps. The current mumps epidemic in the United Kingdom is focused in cohorts born during 1982-1987 who were too old to have received routine MMR vaccination. In the cohort born in 1981-1985 the model estimates that 7.5% have no evidence of mumps specific IgG and 24.9% have the lowest level of detectable antibody. The similar proportions of mumps antibody in these categories among cohorts with opportunity for 1 or 2 doses of vaccine is a concern, as the degree to which these individuals are protected is unclear. Investigations into the efficacy of two doses of a mumps containing vaccine should be a priority during the current epidemic.     

日照市健康人群麻疹、风疹和流行性腮腺炎抗体水平调查

目的了解日照市健康人群麻疹、风疹、流行性腮腺炎(腮腺炎)抗体水平和自然感染情况。方法 2009年采集日照市开发区1～≥20岁健康人群血清标本245份,采用酶联免疫吸附试验检测麻疹、风疹和腮腺炎抗体。结果麻疹、风疹和腮腺炎抗体分别检测血清245份。麻疹抗体阳性率98.78%,几何平均滴度(GMT)1:1722.13;风疹抗体阳性率60.82%,抗体含量均值为35.30U/ml;腮腺炎抗体阳性率为84.49%,抗体含量均值为62.94U/ml。结论麻疹抗体阳性率显著高于风疹和腮腺炎抗体阳性率,风疹抗体阳性率普遍较低,3～6岁儿童的腮腺炎抗体阳性率显著低于其他健康人群。应加强儿童风疹和腮腺炎疫苗接种,提高接种率。定期开展育龄期妇女风疹疫苗接种工作。     

Masern, Mumps und Röteln in der Schwangerschaft

Measles, mumps and rubella are common childhood diseases. Therefore, frequent and intense contact with children of preschool age may be associated with a higher infection risk for childcare providers. This overview summarizes current knowledge on possible adverse effects of these infections on pregnant women, pregnancy outcome and the fetus. Acute rubella or mumps virus infections are apparently not more severe in pregnant than non-pregnant women. In contrast, measles virus infection in pregnancy is linked to a higher incidence of pneumonitis and hospitalization. Evidence of congenital defects due to fetal infection is only provided in case of rubella virus infection in early pregnancy. Following rubella virus infection in the first trimester an increased fetal loss rate was reported. In 1966, a prospective study showed also a significant association between maternal mumps in the first trimester and an increased risk of abortion. But other investigators could not confirm this association. Measles and rubella but not mumps virus infections are linked to an increased premature birth rate. Occurring in late pregnancy, all three infections can result in birth of an infected infant. But severe disease occurs rarely and is mostly reported for premature infants with early neonatal measles. Preventive measures, aimed to reduce the risk of infection or severe complications for pregnant childcare providers, should consider the individual history of the employee (e.g. previous immunizations or antibody test results), the current epidemiological situation and possible interventions like passive immunization in case of exposure to measles.     

Changes in the prevalence of the measles,rubella, varicella-zoster,and mumps virus antibody titers in Japanese pregnant women

In the present study, immunity against infectious diseases, which are capable of influencing both the mother and fetus during pregnancy and the infant in the postnatal period, were assessed in pregnant women to elucidate the necessity of vaccination during the childbearing age. It was determined that there was a trend of increases in the proportion of patients that had low antibody titers observed at a young age. Overall, after adjusting for age, low antibody titers of measles (≤4 via the neutralization test [NT]), rubella (≤16 via the hemagglutination inhibition [HI]), and varicella and mumps (plus minus or negative on the enzyme-linked immunosorbent assay [EIA]) indicated that the rates of necessity for vaccination against measles, rubella, varicella, and mumps were 27.6%, 16.1%, 3.9%, and 23.8%, respectively. In Japan, acquired immunity for measles, rubella, and mumps was dependent on vaccination, whereas acquired immunity for varicella was dependent on natural infection. We recommend that women be vaccinated after delivery, as these vaccines are live, and thereby, are contraindicated during pregnancy.     

潍坊市健康人群风疹和流行性腮腺炎抗体水平检测

目的了解潍坊市健康人群风疹、流行性腮腺炎（腮腺炎）抗体水平和自然感染情况。方法采集潍坊市高新区1-≥70岁健康人群血清标本843人份,采集血球凝集抑制（Ⅲ）试验检测风疹和腮腺炎抗体。结果检测843份血清中的风疹抗体,抗体阳性率83.51％,几何平均滴度（GMT）为1：93.96。检测843份血清中的腮腺炎抗体,阳性率为71.46％,GMT为1：4.76。结论由于≤5岁儿童风疹感染率为58.64％,腮腺炎感染率为38.58％,建议对≤5岁儿童进行风疹和腮腺炎疫苗查漏补种工作。     

Antibody titers against measles, rubella, mumps and varicella-zoster viruses in medical students]

It is important to identify and immunize susceptible students who have clinical practice to prevent and control hospital infections. The antibody titers to measles, rubella, mumps and varicella viruses were measured in 1,139 students(417 men, 722 women, average age 21.3+/-2.7 yr old)including 510 medical students, 442 nursing students and 187 students of the School of Medical Technology in Kurume University. Antibodies against measles virus were detected by particle agglutination assay(PA), those against rubella virus by hemagglutination inhibition assay(HI), and those against mumps and varicella viruses by enzyme-linked immunosorbent assay(EIA). The serological susceptibilities to measles, rubella, mumps and varicella viruses were 112(9.8%), 112(9.8%), 163(14.3%)and 73(6.4%), respectively. The serological susceptibilities to measles, rubella and mumps viruses in male students were not different from those in female students. The susceptibility to varicella virus in female students was significantly higher than that in male students. After susceptible students were recommended to have vaccinations against each virus, the vaccination rate of the students without antibody was 99.1%. The history of infection and vaccination against the viruses were examined by self-recorded questionnaires in 406 students from all disciplines. The serological susceptibility of students with positive vaccination history was 11.1% for measles, 6.8% for rubella, 18.3% for mumps, and 4.9% for varicella. The serological susceptibility of students with a positive infection history was 5.7% for measles, 3.4% for rubella, 2.9% for mumps, and 4.9% for varicella. In the self-recorded questionnaire, the rate of unknown infection and vaccination histories were 57.5% and 71.6% for measles, 52.5% and 68.4% for rubella, 34.3% and 75.6% for mumps, and 27.1% and 80.5% for varicella, respectively. In conclusion, these data confirm that it is essential to assess immune status against measles, rubella, mumps and varicella in students who have clinical practice in hospital regardless of infection or vaccination history. Accordingly, susceptible students should be vaccinated to prevent those viral infections in hospital.     

Mumps and rubella: a year of enhanced surveillance and laboratory testing

In Victoria (Australia) surveillance for mumps and rubella has historically been passive, with most notified cases clinically diagnosed. In July 2001, the Victorian Department of Human Services implemented an enhanced surveillance system focusing on improved laboratory testing. We tested 85% of notifications and only 9% of all mumps and 27% of rubella notifications were laboratory confirmed. While most notified cases were children who had been clinically diagnosed, we found most laboratory-confirmed cases were in adults. The positive predictive value of the clinical case definition was low: mumps (10%); rubella (22%). These results highlight the value of laboratory confirmation of the diagnosis when mumps and rubella are rare, failure to do so is likely to overestimate disease incidence.     

潍坊市坊子区风疹和流行性腮腺炎抗体水平检测

目的了解潍坊市坊子区健康人群风疹、流行性腮腺炎（腮腺炎）抗体水平和自然感染情况。方法采集潍坊市坊子区1～≥70岁健康人群血清标本843人份,采用血球凝集抑制（HI）试验检测风疹和腮腺炎抗体。结果风疹抗体共检测血清843份,抗体阳性率83．51％,几何平均滴度（GMT）1：93．96。腮腺炎抗体共检测血清834份,抗体阳性率71．46％,GMT1：4．76。结论由于〈5岁儿童风疹感染率为58．64％,腮腺炎感染率为38．58％,建议对≤5岁儿童进行风疹和腮腺炎疫苗查漏补种工作。     

Natural immunity to measles, rubella and mumps among Spanish children in the pre-vaccination era

Prior to the start of mass vaccination campaigns against measles, rubella and mumps, a prevalence study of natural immunity to these diseases was undertaken in a sample of 1700 unvaccinated Spanish children. They were representative of the 3-7 year-old population in terms of age, regional distribution and urban or rural environment. Measles infection prevalence was significantly higher than that for rubella and mumps from 3 (48.3%, 14.2%, 25.5%, respectively) through 7 years of age, (64%, 40.9%, 39%). As a function of age, naturally-acquired immunity increased according to parabolic progressions. In the 3-5 year-old group, rural environment, low socioeconomic status, no school attendance and lack of brothers were associated with statistically lower levels of measles, rubella, or mumps infection. In the 6-7 year-old group, only 12% of the children showed antibodies against the three diseases and 18.7% exhibited triple susceptibility.     

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.     

天津市麻疹风疹及流行性腮腺炎抗体水平分析

目的了解天津市健康人群麻疹、风疹、流行性腮腺炎抗体水平,评价疫苗接种需求。方法2007年3月采集0~57岁健康人群608人份血样品,用ELISA方法定量检测麻疹、风疹、流行性腮腺炎IgG抗体水平。运用直线相关分析抗体阳性率,保护率GMC与疾病发病率之间的关系,P0.05为差异有统计学意义。结果麻疹、风疹和流行性腮腺炎疫苗接种率分别为70.39%、16.78%和12.34%;抗体阳性率分别为91.78%,65.79%和73.52%;抗体几何平均浓度(GMC)分别为2 488.10 IU/L、200.4 IU/ml和759.91 U/ml。麻疹抗体阳性率,保护率与发病率存在明显相关关系(P0.01),而GMC与麻疹发病率没有显著性相关;风疹和流行性腮腺炎抗体阳性率、GMC与发病率无相关关系。结论本次调查显示2007年天津市麻疹人群抗体GMC总体保持在较高水平。风疹、流行性腮腺炎疫苗接种率和抗体水平较低,2剂次的麻腮风疫苗(MMR)纳入免疫规划既有助于消除麻疹,也有利于控制风疹和流行性腮腺炎。     

Changes of the immunological patterns against measles, mumps and rubella. A vaccination programme studied 3 to 7 years after the introduction of a two-dose schedule

A two-dose vaccination programme using a combined measles, mumps and rubella vaccine (MMR) and administration at the ages of 18 months and 12 years was introduced in 1982. The 12-year-old schoolchildren were tested yearly from 1985 to 1989 on serum samples obtained prior to and after vaccination. Each year between 420 and 756 children were tested. The method used for antibody testing was the haemolysis-in-gel (HIG) assay. For measles also the enzyme-linked immunosorbent assay (ELISA) and the neutralization titre (NT) were applied. Only minor variations of the prevaccination immunity to measles were seen during the period 3-7 years after introduction of the programme. The age groups studied had partly been vaccinated against measles earlier. Between 12 and 16% lacked prevaccination immunity. In contrast the immunity to mumps and rubella of the 12-year-old children decreased considerably during the study period. No general vaccination against these diseases had been performed. Thus the susceptibility to mumps increased from 14% in 1985 to 39% in 1989 and to rubella from 41 to 57%. The seroconversion rate of children seronegative for measles was high, i.e. 100% in 1985 and later varied between 96 and 97%. For mumps, the seroconversion rate was lower and varied between 72 and 88%. All sera converted to rubella. During the follow-up period there was a declining incidence of measles, mumps and rubella. The relationship between the vaccination and reduction of disease and natural immunity strongly suggests that the association is causal and that this vaccination policy reduced the transmission of infection.     

Outbreak of measles in medical students and determination of immune status to measles-mumps-rubella viruses

We conducted an investigation after a measles outbreak in medical students to determine the immunity of the medical students, the correlation between history and seropositivity, and measles-mumps-rubella vaccine effectiveness. After a preliminary study done during measles outbreak, a cross-sectional study was planned. Serum samples from 322 medical students were tested by enzyme-linked immunosorbent assay, vaccinated volunteers, then re-tested vaccinees. Histories of measles, mumps and rubella were taken. Of 322 students, seven students (2.2%) were seronegative to measles, 13 (4.0%) to mumps, and 13 (4.0%) to rubella. Historical information revealed 30.4% of sensitivity in measles and 34.3% in mumps, whereas 5.2% in rubella. Among those seronegative on admission and vaccinated, seroconversion rates were 100% (5/5), 90.9% (10/11), 100% (8/8) in measles, mumps and rubella vaccine, respectively. Of 265 vaccinated students parotitis was detected in one female student, arthralgia was observed in three students (1.1%) and myalgia in two (0.7%), and 240 students reported no side effects. We detected the unreliable historical screening and high seroprevalence of measles, mumps and rubella in prevaccine era for mumps and rubella and, safety of MMR vaccination in medical students in Turkey.     

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.     

A random cluster survey and a convenience sample give comparable estimates of immunity to vaccine preventable diseases in children of school age in Victoria,Australia

We compared estimates of the age-specific population immunity to measles, mumps, rubella, hepatitis B and varicella zoster viruses in Victorian school children obtained by a national sero-survey, using a convenience sample of residual sera from diagnostic laboratories throughout Australia, with those from a three-stage random cluster survey. When grouped according to school age (primary or secondary school) there was no significant difference in the estimates of immunity to measles, mumps, hepatitis B or varicella. Compared with the convenience sample, the random cluster survey estimated higher immunity to rubella in samples from both primary (98.7% versus 93.6%, P = 0.002) and secondary school students (98.4% versus 93.2%, P = 0.03). Despite some limitations, this study suggests that the collection of a convenience sample of sera from diagnostic laboratories is an appropriate sampling strategy to provide population immunity data that will inform Australia's current and future immunisation policies.     

Mass vaccination programme aimed at eradicating measles, mumps and rubella in Sweden: vaccination of schoolchildren

In 1982-83, a unique, two-dose programme of immunization with a combined vaccine against measles, mumps and rubella was initiated in Sweden. The first dose was administered at 18 months and the second at 12 years of age. A vaccination study was carried out on 247 12 year old schoolchildren from four schools situated in two urban and two rural areas. In urban areas, 30% of children were found to be susceptible to rubella and 18% to mumps, compared with 55% susceptible to rubella and 31% to mumps in rural areas. The reverse was found for measles, to which 20% of children lacked immunity in urban areas but only 6% in rural areas. Seroconversion was seen in 82% against measles, in 80% against mumps and in 100% against rubella. Follow-up studies of the timing and the virus dosage are also to be carried out.     

Estimating vaccination coverage for the trivalent measles-mumps-rubella vaccine from trivariate serological data

The effectiveness of childhood immunization programs depends on the vaccination coverage actually achieved. Routinely collected coverage data are not always available, and comparability between countries is often compromised because of different data collection methods. In 2000, Gay developed a method to estimate trivalent vaccination coverage from readily available trivariate serological data on the basis of parametric assumptions related to the rate of seroconversion for each vaccine component and probabilities of natural exposure to infection. Gay's work was indirectly published in a paper by Altmann and Altmann, who derived exact solutions for the parameters on the basis of Gay's modeling equations. In this paper, we propose a general likelihood‐based marginal model framework to extend Gay's model by relaxing two of its main assumptions. We use the Bahadur model for trivariate binary data to explicitly account for an association between the disease‐specific exposure probabilities. We fit several correlation structures to measles, mumps, and rubella serology from Belgium and Ireland. For both countries, we estimate a small positive pairwise exposure correlation, which improves the fit to the data. However, the effect on the estimated vaccination coverage and its associated variability is fairly moderate. For both Belgium and Ireland, all models reveal that the vaccination coverage achieved during the first 15 years since the introduction of measles, mumps, and rubella immunization is insufficient to eliminate measles. Copyright © 2012 John Wiley & Sons, Ltd.     

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.     

Prevalence of measles, rubella, mumps, and varicella antibodies among healthcare workers in Japan.

OBJECTIVES: To evaluate the immune status of healthcare workers (HCWs) against measles, rubella, mumps, and varicella in Japan, and to promote an adequate vaccination program among HCWs. SETTING: University of Tokyo Hospital. PARTICIPANTS: Eight hundred seventy-seven HCWs. DESIGN: Serologic screening for measles, rubella, mumps, and varicella was performed on HCWs. Antibodies against measles, rubella, and mumps were detected using hemagglutination inhibition (HI) assay ($4.20 per test). If serum was negative by HI assay, enzyme-linked immunosorbent assay (EIA) was performed ($12.60 per test). Anti-varicella antibodies were detected by EIA only. RESULTS: Among tested HCWs, 98.5%, 90.4%, 85.8%, and 97.2% had immunity to measles, rubella, mumps, and varicella, respectively. All those born before 1970 were seropositive for measles. However, individuals susceptible to rubella, mumps, and varicella were present in all age groups. The sensitivities and negative predictive values of HI assay compared with EIA were 86.6% and 11.3% for measles, 99.1% and 92.2% for rubella, and 47.8% and 24.1% for mumps, respectively. For measles and mumps, prevaccination screening by HI assay in combination with EIA led to significant savings compared with EIA only. In contrast, it was estimated that prevaccination screening using only HI assay would be more economical for rubella. CONCLUSIONS: Aggressive screening and vaccination of susceptible HCWs was essential regardless of age. Prevaccination serologic screening using a combination of HI assay and EIA was more economical for measles and mumps.