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.     

Mumps, measles and rubella vaccination: a pragmatic study

The acceptability, adverse effects and uptake of MMR vaccine were assessed in an open pragmatic study. 96.5% of parents chose vaccination with MMR rather than monocomponent measles. Few parents could correctly name a complication of mumps (40.4%), measles (21.7%) or rubella (25.3%). In the three weeks following vaccination, 15.9% of infants had local reactions, 26.4% had rashes, and 30.3% fever. There was no increase in uptake of measles vaccination during the study, but it led to improvements in programme organisation which subsequently boosted coverage.     

Mutual interference on the immune response to yellow fever vaccine and a combined vaccine against measles, mumps and rubella

A randomized trial was conducted to assess the immunogenicity and reactogenicity of yellow fever vaccines (YFV) given either simultaneously in separate injections, or 30 days or more after a combined measles-mumps-rubella (MMR) vaccine. Volunteers were also randomized to YFV produced from 17DD and WHO-17D-213 substrains. The study group comprised 1769 healthy 12-month-old children brought to health care centers in Brasilia for routine vaccination. The reactogenicity was of the type and frequency expected for the vaccines and no severe adverse event was associated to either vaccine. Seroconversion and seropositivity 30 days or more after vaccination against yellow fever was similar across groups defined by YFV substrain. Subjects injected YFV and MMR simultaneously had lower seroconversion rates - 90% for rubella, 70% for yellow fever and 61% for mumps - compared with those vaccinated 30 days apart - 97% for rubella, 87% for yellow fever and 71% for mumps. Seroconversion rates for measles were higher than 98% in both comparison groups. Geometric mean titers for rubella and for yellow fever were approximately three times higher among those who got the vaccines 30 days apart. For measles and mumps antibodies GMTs were similar across groups. MMR's interference in immune response of YFV and YFV's interference in immune response of rubella and mumps components of MMR had never been reported before but are consistent with previous observations from other live vaccines. These results may affect the recommendations regarding primary vaccination with yellow fever vaccine and MMR.     

冻干麻疹-腮腺炎-风疹三联活疫苗免疫安全性及免疫学效果观察

目的 观察卫生部北京生物制品研究所研制的麻疹-腮腺炎-风疹（北京MMR）疫苗的免疫学效果。方法 分别选择10-12岁，2-2.5岁和8-12月龄儿童，接种北京MMR（实验疫苗），并与进口MMR疫苗，麻疹疫苗，腮腺炎疫苗和风疹疫苗（对照疫苗）相比较，开展该疫苗的免疫安全性和免疫原性观察研究。结果 在32名2岁以上较大龄儿童接种北京MMR疫苗无副反应发生后，对104名8-12月龄婴儿接种该疫苗，仅有6.7%和1.9%的儿童分别发生一过性发热（中低反应）和皮疹，无其他不良反应发生，北京MMR疫苗免疫接种后，其麻疹，风疹，腮腺炎HI抗体阳转率分别为100%，100%和85.7%;GMT分别为41，320和6.1，分别与对照疫苗相比，差异多无显著性。结论 北京MMR疫苗具有与目前使用的麻疹疫苗，腮腺炎疫苗，风疹疫苗及进口MMR疫苗相同的免疫安全性和免疫原性，且可以作为麻疹的基础免疫和复种疫苗使用。     

Two doses of MMR vaccine--sufficient to eradicate measles, mumps and rubella?

A review has been done of the available literature on measles, mumps, rubella and vaccines against these diseases. So far, 17 studies on the same virus strains as those in M-M-R II have been published. The rate of seroconversion is practically 100% for rubella, generally more than 90% for measles and between 40 and 100% for mumps. Immediate side effects of vaccination are mild in infants and negligible in schoolchildren. However, the follow-up periods are short. In the only 10-year follow-up published, 14 subjects remained at the end of the period, and the vaccine studied differed from M-M-R II. Large, well-documented studies of MMR vaccination in unselected populations are rare. It must be of crucial importance that the immunity situation is followed up continuously for both vaccinated and non-vaccinated individuals when a mass vaccination programme has been introduced as there will be a risk of outbreaks of diseases mostly among young adults.     

The control of mumps in Israel

Background: Measles–mumps–rubella (MMR) vaccine replaced monovalent measles vaccine in the routine childhood vaccination schedule in Israel in December 1988, primarily to achieve the elimination of the congenital rubella syndrome. In this observational study, we report on changes in reported mumps incidence in Israel from the time of the introduction of MMR vaccine until the end of 1998. Methods: The report is based upon passive national surveillance of mumps incidence, which has been notifiable in Israel since 1977. Results: Reported mumps incidence in Israel is now less than 2% the pre-vaccine incidence. Conclusions: In the decade since the introduction of routine mumps vaccination in 1-year-olds in Israel, mumps control has been achieved. Although small outbreaks occur and may continue to occur in future years, because of undervaccination of children, primary vaccine failure and waning immunity, it can tentatively be said that mumps is no longer a public health problem in Israel.     

国产麻疹流行性腮腺炎风疹联合疫苗初免效果及免疫程序探讨

目的为观察麻疹、流行性腮腺炎(腮腺炎)、风疹联合疫苗(MMR疫苗)的安全性和免疫原性,并探讨其免疫程序.方法选择91名8月龄儿童,接种MMR疫苗,观察接种后局部反应和全身反应,并检测接种后6周血清麻疹、腮腺炎、风疹抗体阳转率和几何平均滴度(GMT).结果91名8月龄儿童接种MMR疫苗后,有8名儿童发生一过性发热,2名儿童发生皮疹,2名儿童发生局部弱反应.麻疹、风疹、腮腺炎血凝抑制(HI)抗体阳转率分别为98.61%、100.00%、74.07%,GMT分别为145.25、1248.71、14.29.结论MMR疫苗对8月龄儿童接种具有较好的安全性和免疫原性,将其初免月龄定为8月龄儿童是可行的.     

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.     

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.     

Rubella susceptibility among pregnant women in North London, 1996-1999

BACKGROUND: Rubella infection and congenital rubella are currently rare in the United Kingdom, although sporadic cases occur, often associated with travel abroad. Uptake of the combined measles, mumps and rubella (MMR) vaccine has declined in recent years, and there is a danger that rubella infection could start to circulate again, with serious implications for susceptible pregnant women. This could be a particular problem in communities where there are relatively high rubella susceptibility rates because of either poor vaccine uptake over several years or the presence of significant numbers of recent immigrants from countries without routine rubella vaccination programmes. METHODS: Routinely collected data on rubella susceptibility in pregnant women in the former North West Thames region were available for 1996-1999. Associations between year of delivery, maternal age, parity and ethnic group, and rubella susceptibility were explored. RESULTS: Overall rubella susceptibility declined significantly from 2.6 per cent to 2.4 per cent between 1996 and 1999. Whereas less than 2 per cent of British-born women were susceptible, overall susceptibility for other women was about 5 per cent. African and Asian women had particularly high susceptibility rates, and patterns of susceptibility by age and parity varied across ethnic groups. CONCLUSIONS: If rubella were to re-establish itself in the United Kingdom, women who had come to Britain in later childhood or adult life would be at higher risk of acquiring infection in pregnancy than indigenous women. Appropriate local and national strategies should be devised to ensure that all such women are offered rubella vaccination at the earliest opportunity.     

A randomised single blind trial of a combined mumps measles rubella vaccine to evaluate serological response and reactions in the UK population

Four hundred and twenty children were randomly assigned to receive either mumps measles rubella (MMR) vaccine (207) or measles vaccine (213) in a single blind study, to investigate the reactogenicity and serology of the MMR vaccine. There was no significant difference between the number of children developing symptoms after MMR vaccination to those developing symptoms after measles vaccination. Both vaccines are associated with a rash, temperature and restlessness five to thirteen days after vaccination. The serological response to measles vaccine was similar in both groups with 92-6% seroconverting with MMR, and 96-8% with measles. Seroconvertion against mumps and rubella with the MMR vaccine was 88% and 96% respectively. This study confirms the safety and efficacy of the MMR vaccine in a UK population.     

Duration of the immune response to MMR vaccine in children of two age-different groups

A combined vaccine against measles, mumps and rubella (MMR) was administered to both a group of children aged 10–12 months simultaneously with booster doses of compulsory diphtheriatetanus toxoids and oral poliovirus vaccine and a group of children aged 15–24 months who had previously received booster doses of the compulsory vaccines.Apart from one subject belonging to the second group who was non responder and one from the same group who did not seroconvert against the mumps virus alone, 5 to 6 weeks after MMR vaccine administration we found protective levels of antibodies against measles, mumps and rubella viruses in all children. The follow up of both groups at 3 years did not reveal difference between the two groups. Protective levels of serum antibodies against measles and mumps were found in the two groups, altough a significant decline of rubella antibodies was shown (p < 0.05).Since the immunogenicity of the vaccines in the two groups did not differ, we recommend that the scientific community reconsider the vaccination schedule until now recommended. In our opinion the MMR vaccine should be administered simultaneously with booster doses of diphtheria-tetanus toxoids and oral poliovirus vaccine at 10–12 months of age because this policy improves parents' compliance, markedly reduces community costs and simplifies routine immunization schedule.     

Vaccine-induced measles virus antibodies after two doses of combined measles, mumps and rubella vaccine: a 12-year follow-up in two cohorts

In Finland, a two-dose vaccination programme against measles, mumps and rubella (MMR) was begun in 1982. The programme with high coverage (97–98%) has eliminated these three diseases from Finland. The aim of the present study was to follow up the kinetics of measles virus antibodies in MMR vaccinated cohorts. We have followed the kinetics of measles virus antibody levels induced by vaccination in the same individuals immunized with their first MMR vaccine in 1982. After 12 years 80% of the original children remained available for sampling. Antibodies to measles virus were measured by haemagglutination inhibition (HI) and plaque reduction neutralization (NT) techniques. The primary dose induced 99.4% seroconversion for measles with a geometric mean HI antibody titre (GMT) of 1/269 (±219), equivalent to 4304 mIU (milli-International Units) ml⁻¹ in group A. The 12-year follow-up specimens showed a measles seropositivity rate of 100% as assayed with the HI and NT tests with a mean HI antibody titre of 1/39 (±54), equivalent to 624 mIU ml⁻¹. The vaccination-induced measles virus antibodies decline in the absence of natural booster infections. It is important to follow how long the protection achieved by the present vaccine programme will last after elimination of indigenous measles.     

Seroprevalence of measles, mumps and rubella antibodies in Luxembourg: results from a national cross-sectional study

A serological prevalence survey was carried out in Luxembourg during 2000-2001 to determine the antibody status of the Luxembourg population against vaccine-preventable infections. Blood samples of children and adolescents were collected prospectively in randomly selected schools. Samples of adults were obtained through volunteer patients of the national health laboratory or of the mandatory pre-nuptial test. Measles, mumps and rubella (MMR) virus antibody concentrations were measured using commercial ELISA tests. Age-standardized prevalence of measles, mumps and rubella virus antibodies was found to be 96.58, 75.40 and 95.69% respectively. Significant age-dependence of serology was observed for all three infections, with study participants born after the introduction of the MMR vaccine experiencing a gradual decline of antibodies following vaccination in childhood. Older study participants who were more likely to have antibodies from natural infection had consistently higher titres than younger individuals. Present vaccination coverage with MMR appears to be sufficient to prevent large local outbreaks of measles and rubella, but probably not mumps.     

Mumps incidence in Israel--impact of MMR vaccine

BACKGROUND: Measles-mumps-rubella (MMR) vaccine replaced measles vaccine in the routine childhood vaccination schedule in Israel in December 1988, primarily to eliminate congenital rubella syndrome. In this observational study, we report on changes in mumps incidence in Israel from the time of the introduction of MMR vaccine until the end of 1991. METHODS: The report is based upon passive surveillance of mumps incidence, which has been notifiable in Israel since 1977. RESULTS: In the three years since the introduction of MMR vaccine, reported mumps incidence has fallen to less than 10% of the pre-vaccine period. CONCLUSIONS: Although this report is based on a relatively short period of observation, it can be tentatively concluded that MMR has led to a reduction in mumps incidence in Israel. It would be imprudent, however, to predict that mumps outbreaks will not occur in the future, and further observation of morbidity data will be needed to determine the magnitude and durability of the observed trend.     

Seroprevalence of Antibodies to Measles, Mumps, and Rubella among Thai Population: Evaluation of Measles/MMR Immunization Programme

Stored serum specimens, from four regions of Thailand, of healthy children attending well baby clinics and of healthy people with acute illnesses visiting outpatient clinics were randomly sampled and tested for IgG antibody to measles, mumps, and rubella (MMR). The immunity patterns of rubella and mumps fitted well with the history of rubella and MMR vaccination, seroprotective rates being over 85% among those aged over seven years. A high proportion of younger children acquired the infection before the age of vaccination. MMR vaccination should preferably be given to children at an earlier age. For measles, 73% seroprotective rates among children, aged 8-14 years, who should have received two doses of measles/MMR vaccine, were lower than expected. This finding was consistent with the age-group reported in outbreaks of measles in Thailand. The apparent ineffectiveness (in relation to measles) of MMR immunization of 1^st grade students warrants further studies.Key words: Antibodies, Immunization, Measles, Measles vaccine, Mumps, MMR vaccine, Rubella, Seroepidemiologic studies, Seroprevalence, Vaccination, Thailand     

Chickenpox: sufficient reasons for the introduction of vaccination

The incidence of chickenpox and its complications is high enough to favour introducing varicella vaccination into the Dutch immunisation programme for children, although current Dutch figures may even underestimate the incidence. Safe and effective MMRV vaccines, in which varicella (V) vaccine is combined with measles, mumps and rubella (MMR), could well replace the MMR vaccine used at present. MMRV vaccines should be administered subcutaneously in two doses. Ten years after the introduction of varicella vaccination in the United States of America, the incidence of complications has decreased impressively. An effect on the incidence of herpes zoster has not (yet) been seen.     

4~6岁儿童接种麻疹-流行性腮腺炎-风疹联合减毒活疫苗加强免疫的免疫原性与安全性研究

目的 探讨4~6岁儿童接种麻疹-流行性腮腺炎-风疹联合减毒活疫苗（MMR）后的加强免疫原性与安全性。方法 分别在山西省、内蒙古自治区以及北京市招募曾有8月龄和18月龄接种过1剂麻疹-风疹联合减毒活疫苗和MMR疫苗免疫史的4~6岁儿童作为研究对象,分为4、5、6岁组,进行MMR疫苗加强免疫研究。接种MMR疫苗前与接种后35~42 d各采集血标本3 ml。在研究期间,主动监测疫苗接种后30 min、1 d、2 d、3 d、4~12 d,以及13~42 d的不良事件。血清采用酶标法检测麻疹、流行性腮腺炎和风疹的IgG抗体。采用方差分析或非参数检验比较研究组间麻疹、腮腺炎和风疹抗体几何平均浓度（GMC）,采用χ²检验或Fisher确切概率法比较组间阳性率和不良事件发生率。结果 共500名完成免后采血儿童纳入免疫原性分析,535名儿童纳入安全性分析。总体不良事件发生率为20.37%,轻度不良事件最多。局部与全身不良事件发生率分别为0.37%和20.00%。局部不良事件的症状以接种部位发红为主,全身不良事件以发热症状为主,其次为咳嗽、皮疹、流涕等。在4~6岁进行1剂MMR疫苗加强免疫后,麻疹抗体、腮腺炎抗体与风疹抗体阳性率均在99%以上,3组间阳性率差异无统计学意义。3组间仅腮腺炎抗体GMC差异有统计学意义（P=0.042）,麻疹与风疹抗体相关结果均无差异。免前阴性者的麻疹、腮腺炎及风疹抗体GMC均低于免前阳性者。结论 在4~6岁儿童中进行MMR疫苗的加强免疫,具有良好的免疫原性与安全性,在4~6岁之间的加强免疫效果相近。     

麻疹-流行性腮腺炎-风疹联合减毒活疫苗流行性腮腺炎组份免疫效果观察

目的对麻疹-流行性腮腺炎（流腮）-风疹联合减毒活疫苗（Measles,Mumps and Rubella Combined Atteruated Live Vaccine,MMR）中,流腮组份的免疫效果进行观察评价。方法对接种MMR后,流腮组份免疫学效果进行分析评价,并追踪观察记录2年内受种人群及本地人群中流腮发病情况。结果接种MMR前,流腮抗体几何平均滴度（Geometric Mean Titer,GMT）为1∶6.87,免疫后GMT为1∶26.35,免疫后GMT是免疫前GMT的3.8倍,免疫前、后GMT差异有统计学意义（Z=-6.22,P〈0.001）。免疫前、后流腮抗体阳性率分别为64.63%、95.12%,差异有统计学意义（χ2=23.71,P〈0.001）。免疫前、后流腮抗体阴性者与阳性者GMT和免疫前相比差异均有统计学意义（Z=-4.40,P〈0.001;Z=-4.84,P〈0.001）。免疫前流腮抗体阴性者与阳性者接种MMR后,免疫成功率分别为86.21%、54.72%,差异有统计学意义（χ2=8.266,P=0.004）。对受种人群及本地人群进行为期2年的流腮发病追踪观察,在受种人群中未发现流腮病例报告。结论在3-6岁儿童中接种MMR,对于预防流腮效果良好,产生的保护效果至少能维持2年。     

Antibodies to measles,mumps, and rubella virus in Thai children after two-dose vaccination at 9 months and 2.5 years: A longitudinal study

IntroductionThailand changed the schedule of childhood measles–mumps–rubella (MMR) vaccination in 2014, moving the second dose from the age of 6 years to 2.5 years. There are currently no data on antibody responses to the MMR vaccine since this recommendation.Material and methodsWe investigated antibody responses in a cohort of children who received two doses of MMR vaccine at the ages of 9 months and 2.5 years that was originally established to evaluate antibody levels to Bordetella pertussis antigens (ClinicalTrials.gov no. NCT02408926). Infants were born to mothers who previously received tetanus–diphtheria–acellular pertussis vaccine at 27–36 weeks of gestation. Anti-measles, -mumps, and -rubella virus IgG levels were measured at birth (cord blood) and the ages of 2 and 7 months (before the first MMR vaccination); 18 and 24 months (9 and 15 months, respectively, after the first dose); and 36 months (6 months after the second dose) using commercially available enzyme-linked immunosorbent assay kits.ResultsAt 7 months of age, 96.2%, 99.6%, and 98.8% of infants had no protection against measles, mumps, and rubella, respectively. Levels of antibody against all three antigens increased significantly after the first but not the second dose. At 6 months after two-dose vaccination, 97.4%, 84.8%, and 78.7% of children remained seroprotected against measles, mumps, and rubella, respectively.ConclusionsMaternally derived antibodies to measles, mumps, and rubella virus disappeared by the age of 7 months in Thai children. Two-dose MMR vaccination at 9 months and 2.5 years of age induced robust immune responses against these viruses.