Vaccination against measles, mumps and rubella (MMR): a comparison between the antibody responses at the ages of 18 months and 12 years and between different methods of antibody titration

In connection with the introduction of the trivalent vaccine against measles, mumps and rubella at 18 months and 12 years of age, an evaluation of the seroconversion and booster effects in the two age-groups was carried out. This also comprised different laboratory-test methods appropriate for follow-up studies after large-scale, vaccination studies. The measles, mumps and rubella antibodies were measured by the haemolysis-in-gel (HIG) method. Measles antibodies were also measured by the haemagglutination-inhibition (HI) test. Borderline values or samples negative to measles or mumps were also tested by the serum-neutralization (SN) test. All but four of 150 18-month-old children lacked antibodies against measles by the HI test and one of these by the HIG method. Against mumps, 99% were seronegative in the HIG test and 97% in the SN test and two against rubella prior to vaccination. Among 247 schoolchildren, 60 (24%) lacked antibodies in the HI test and 28 (11%) of these also in the HIG test. Sixty-six schoolchildren (25%) were negative to mumps and 45% to rubella prior to vaccination. The seroconversion rate for the 18-month-old children was 96% against measles, 93% against mumps and 99% against rubella. The figure for the schoolchildren was 82% against measles, 80% against mumps and 100% against rubella. On comparing the titre levels in seroconverting children, the measles-antibody levels were found to be lower among older children, compared with younger, while the opposite was true for rubella.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immune response to the mumps component of the MMR vaccine in the routine of immunisation services in the Brazilian National Immunisation Program

A non-controlled longitudinal study was conducted to evaluate the combined vaccine against measles, mumps and rubella (MMR) immunogenicity in 150 children vaccinated in the routine of three health units in the city of Rio de Janeiro, Brazil, 2008-2009, without other vaccines administered during the period from 30 days before to 30 days after vaccination. A previous study conducted in Brazil in 2007, in 1,769 children ranging from 12-15 months of age vaccinated against yellow fever and MMR simultaneously or at intervals of 30 days or more between doses, had shown low seroconversion for mumps regardless of the interval between administration of the two vaccines. The current study showed 89.5% (95% confidence interval: 83.3; 94.0) seroconversion rate for mumps. All children seroconverted for measles and rubella. After revaccination, high antibody titres and seroconversion rates were achieved against mumps. The results of this study and others suggest that two MMR doses confer optimal immunoresponses for all three antigens and the possible need for additional doses should be studied taking into account not only serological, but also epidemiological data, as there is no serological correlate of protection for mumps.     

Seroprevalence of measles-, mumps- and rubella-specific IgG antibodies in german children and adolescents and predictors for seronegativity

We have undertaken a seroprevalence study with more than 13,000 children, who had been included in the German KIGGS survey, a representative sample of children and adolescents 0-17 years of age. The IgG titres against measles, mumps and rubella were determined in 1 to 17 year olds While 88.8% of the children were MMR-vaccinated at least once, 76.8% of children aged 1 to 17 years showed prevalence of antibodies to MMR. The highest seronegativity was seen with respect to mumps. Gender differences were most pronounced with regard to rubella IgG titres: girls aged 14 to 17 years were best protected, although seronegativity in 6.8% of this vulnerable group still shows the need of improvement. Search for predictors of missing seroprevalence identified young age to be the most important predictor. Children living in the former West and children born outside of Germany had a higher risk of lacking protection against measles and rubella, while children with a migration background but born in Germany were less often seronegative to measles antibodies than their German contemporaries. An association of seronegativity and early vaccination was seen for measles but not for mumps and rubella. A high maternal educational level was associated with seronegativity to measles and rubella. In vaccinated children, seronegativity was highest for mumps and lowest for rubella. For mumps, high differences were observed for seronegativity after one-dose and two-dose vaccination, respectively. Seronegativity increases as time since last vaccination passes thus indicating significant waning effects for all three components of MMR.     

Evaluation of live trivalent vaccine of measles AIK-C strain, mumps Hoshino strain and rubella Takahashi strain, by virus-specific interferon-gamma production and antibody response

A trivalent measles-mumps-rubella live virus vaccine, containing measles AIK-C strain, mumps Hoshino strain, and rubella Takahashi strain, was evaluated in 229 children, aged 1 to 5 years. The vaccine induced a high seroconversion rate: 221 (98.7%) out of 224 subjects initially seronegative for measles virus, 167 (93.3%) out of 179 initially seronegative for mumps virus, and 212 (99.1%) out of 214 initially seronegative for rubella virus. It also induced a sufficient cellular immunity against each of the three viruses in over 90% of the subjects, as judged by virus-specific interferon-gamma (IFN-gamma) production. Virus-specific IFN-gamma production was observed 10 days after vaccination by stimulation with measles virus and rubella virus and 14 days after vaccination by stimulation with mumps virus. Mumps-virus-specific IFN-gamma production was observed in 7 out of 12 recipients without seroconversion for mumps virus. And measles-virus-specific IFN-gamma production was demonstrated in one out of three recipients without seroconversion for measles virus. A significant correlation was observed between the serum antibody and IFN-gamma production six weeks after vaccination for measles virus (r = 0.201, P less than 0.01) and for mumps virus (r = 0.174, P less than 0.05) but not for rubella virus (r = -0.045, P less than 0.05). The incidence of febrile reactions of greater than or equal to 37.5 C was quite low, 14.4%, and that of greater than or equal to 39 C occurred in only 1.3% of the recipients. These results suggested that the trivalent vaccine induced sufficient humoral and cellular immunity and yet resulted in no more untoward reaction than observed from the measles vaccine alone.     

Surveillance of antibody to measles,mumps, and rubella by age.

Before the introduction of measles, mumps, and rubella vaccine a survey was carried out to measure antibody prevalence to the three viruses by age. A total of 8716 samples of serum collected by five public health laboratories in different parts of England during 1986-7 were tested. Despite the current measles vaccination programme 60% of children aged 1-2 years did not have measles antibody and over 80% did not have antibodies to mumps and rubella. In the 3-4 year age group 17% of the children were susceptible to measles, 55% to mumps, and 73% to rubella. The results suggest that vaccinating children early in the second year of life will be necessary to eliminate the three diseases. The survey provides baseline data for continuing surveillance of the immediate and long term effects of the new vaccination strategy.     

Vaccination coverage in hard to reach Roma children in Slovenia

The results of the retrospective analysis of data on vaccination coverage in the preschool-aged and school-aged Roma children (436 preschool and 551 schoolchildren) in three geographical regions of Slovenia were analyzed to establish the differences concerning coverage for specific vaccinations: poliomyelitis, diphtheria, tetanus, pertussis, measles, mumps and rubella between the two generation. The data were obtained from health records, immunization records (Vaccination booklet) and National Computerized Immunization System (CEPI 2000). Vaccination coverage was calculated by comparing the number of children eligible for immunization with the number of vaccinated children. This article performs the log-rank statistical test, also known as the Mantel-Haenszel test. Log rang test is comparing survival curves for two generations. Preschool-aged Roma children showed higher vaccination coverage than the school-aged Roma generation. There was no significance difference in the generations of preschool aged and school aged Roma children fully vaccinated against poliomyelitis, diphtheria, tetanus and pertussis. Rubella vaccination was significantly lower in the school aged Roma generation. Only 33% of school aged Roma population received two doses of measles, mumps and rubella vaccine. Vaccination coverage of preschool Roma children in Slovenia against poliomyelitis, diphtheria, tetanus, pertussis and MMR (measles, mumps, rubella) were significantly lower then the national vaccination coverage for preschool aged Slovenia children. Many joint efforts will have to be made to improve the vaccination coverage in Roma communities.     

Protection of mumps in children with various underlying diseases: application of a live attenuated mumps and trivalent measles-rubella-mumps (MRM) vaccines in these children

A live attenuated mumps and trivalent measles-rubella-mumps (MRM) vaccines have been applied to 887 and 148 children with various underlying diseases at the vaccine clinic of Osaka University Hospital between 1975 and 1985, respectively. Clinical reactions after mumps vaccination occurred in only 7 children (0.8%) and those after MRM vaccination in 28 children (19%), but their underlying diseases were not deteriorated by either vaccination. Clinical follow up study revealed that 2 of the 430 children immunized with mumps vaccine had contracted the disease during 7 year period and 2 of the 123 children immunized with MRM vaccine had contracted clinical mumps or rubella during 3 year period. The seroconversion rates after mumps vaccination were 70% and 61% by the hemagglutination inhibition (HI) test and neutralization (NT) test, respectively, while 94% by the fluorescent antibody to membrane antigen (FAMA) test. Those after MRM vaccination were 87% for measles, 96% for rubella by the HI test and 89% for mumps by the FAMA test. Serological follow up study revealed that antibodies elicited by mumps vaccination were sustained without substantial decline for at least 7 years. These results suggest that a live attenuated mumps and MRM vaccines are safe and effective in children with various underlying diseases.     

Factors affecting uptake of measles,mumps, and rubella immunisation.

OBJECTIVE--To study factors affecting uptake of measles, mumps, and rubella immunisation. DESIGN--Cohort study using data from computerised child health systems. SETTING--10 health districts in North East Thames and North West Thames regions. SUBJECTS--7841 children born in January to March 1990 and resident in the districts up till the end of October 1991. MAIN OUTCOME MEASURES--Overall uptake of measles, mumps, and rubella immunisation, variation of uptake among groups of children, and odds ratio of being vaccinated against measles, mumps, and rubella. RESULTS--The overall uptake rate of measles, mumps, and rubella immunisation for the study cohort in the 10 districts was 82%. Wide variation was identified among children with different demographic characteristics. Lower uptake was associated with absent or incomplete primary immunisation, including omission of pertussis vaccine. Other factors affecting uptake included the type of resident district, birth order, where registered for immunisation (general practitioner or clinic), and one parent family status. CONCLUSIONS--Many districts have difficulties in meeting the 90% target for measles, mumps, and rubella immunisation, mainly because of the characteristics of their local population. To increase overall coverage, the health service should target families with adverse factors, especially those whose children have missed previous immunisations.     

Multiple sclerosis and common viral infections in Iceland

Sero-epidemiological studies on a few common virus infections, including measles, rubella, mumps and varicella-zoster, were carried out on patients with multiple sclerosis (MS) and controls matched for age, sex, and residences since birth. The frequency of antibodies against measles was significantly higher in the MS patients. Where measles preceded the onset of MS, the time interval varied from 3 to 32 years. In two cases, known MS patients contracted measles 9 and 3 years after their onset of MS. Furthermore, three MS patients were vaccinated against measles as adults. Two of these took part in a WHO measles vaccine trial in 1962, 18 and 6 years after the onset of MS. Both of them were seronegative prior to vaccination.     

Methods for screening the naturally acquired and vaccine-induced immunity to the measles virus

Since the measles, mumps and rubella (MMR) vaccine was introduced into Sweden in 1982, a yearly evaluation of the immunity patterns and sero-conversion rates in 12-year-old children has been carried out. Since 1977, about half of the pre-school children have been vaccinated against measles. This study includes two study groups. (1) 145 selected pre- and post-vaccination samples tested by the haemolysis-in-gel (HIG) technique and the neutralization test (NT). The selection was made from 1298 12-year-old schoolchildren in 1986 and 1987, whose pre-vaccination sera had shown negative or borderline reactions to the HIG technique. (2) Consecutive pre- and post-vaccination samples obtained from 190 vaccinees in 1988 and 1989. These samples were studied by an enzyme-linked, immunosorbent assay (ELISA) and compared to the NT. The NT and the HIG tests yielded congruent results in early post-vaccination sera from children susceptible to measles prior to vaccination. In late post-vaccination samples, the NT and the HIG tests were discordant, up to 25% of the NT-positive samples being negative by the HIG technique. In no instance did the ELISA produce discrepant results, compared with those of the NT. With both this assays significantly lower antibody levels were detected in late post-vaccination sera (8-11 years) compared to early post-vaccination samples (P less than 0.001) or to sera obtained after natural infection.     

Recent mumps outbreaks in vaccinated populations: no evidence of immune escape

Recently, numerous large-scale mumps outbreaks have occurred in vaccinated populations. Clinical isolates sequenced from these outbreaks have invariably been of genotypes distinct from those of vaccine viruses, raising concern that certain mumps virus strains may escape vaccine-induced immunity. To investigate this concern, sera obtained from children 6 weeks after receipt of measles, mumps, and rubella (MMR) vaccine were tested for the ability to neutralize a carefully selected group of genetically diverse mumps virus strains. Although the geometric mean neutralizing antibody titer of the sera was lower against some virus strains than others, all viruses were readily neutralized, arguing against immune escape.     

潍坊市健康人群麻疹、风疹、流行性腮腺炎抗体水平调查

目的了解潍坊市健康人群麻疹、风疹、流行性腮腺炎血清抗体水平,为消除麻疹、控制风疹及腮腺炎疫情提供依据。方法 2011年8月,采集昌乐、潍城2个县区<2、2～5、5～8、8～11、11～15、15～20、20～40、>40岁健康人群血标本,应用酶联免疫吸附试验检测麻疹、风疹、腮腺炎IgG抗体。结果检测总数320人,其中昌乐县健康人群的麻疹抗体阳性率为98.75%、潍城为96.25%;风疹抗体阳性率昌乐县健康人群为89.38%、潍城区为91.88%。昌乐、潍城两地区健康人群麻疹、风疹的抗体阳性率差异均无统计学意义(χ2=1.15、0.59,P>0.05);昌乐县健康人群腮腺炎抗体阳性率为84.38%、潍城区健康人群为66.25%,两者差异有统计学意义(χ2=14.14,P<0.01);8组不同年龄健康人群的麻疹抗体阳性率为92.50%～100%,风疹抗体阳性率为87.50%～92.50%,腮腺炎抗体阳性率为67.50%～85.00%,各年龄组间均无统计学意义(χ2=13.49、1.58、5.23,P>0.05)。结论潍坊市麻疹抗体阳性率较高,风疹、腮腺炎抗体阳性率相对偏低,今后须要积极开展学龄儿童麻腮风三联疫苗的查漏补种工作。     

Immunity to rubella in women of childbearing age in the United Kingdom.

In the first three years of a surveillance scheme for susceptibility to rubella in women aged 15-44 the results of over 1.3 million serological tests were collected by 80 laboratories throughout the United Kingdom. Seventy eight per cent of the results, or an average of 340,000 a year, were from pregnant women, so that just under half of all pregnant women in the United Kingdom were reported on. Eighteen per cent of results were from women tested before vaccination and the remainder were from diagnostic and other tests. Pregnant women showed an overall downward trend in susceptibility to rubella (from 4.2% at the beginning of 1984 to 3.0% at the end of 1986), and a similar decline was seen in the two other categories. Regional data showed a significant negative correlation between the proportion of pregnant women aged 15-19 who were susceptible to the virus and rate of uptake of vaccine in 14 year old schoolgirls. Women aged 25-29 were least susceptible. This form of laboratory surveillance is feasible and representative; it should be continued to monitor the effect of introducing the measles, mumps, and rubella vaccine.     

A randomised double-blind clinical trial of two yellow fever vaccines prepared with substrains 17DD and 17D-213/77 in children nine-23 months old

This randomised, double-blind, multicentre study with children nine-23 months old evaluated the immunogenicity of yellow fever (YF) vaccines prepared with substrains 17DD and 17D-213/77. YF antibodies were tittered before and 30 or more days after vaccination. Seropositivity and seroconversion were analysed according to the maternal serological status and the collaborating centre. A total of 1,966 children were randomised in the municipalities of the states of Mato Grosso do Sul, Minas Gerais and São Paulo and blood samples were collected from 1,714 mothers. Seropositivity was observed in 78.6% of mothers and 8.9% of children before vaccination. After vaccination, seropositivity rates of 81.9% and 83.2%, seroconversion rates of 84.8% and 85.8% and rates of a four-fold increase over the pre-vaccination titre of 77.6% and 81.8% were observed in the 17D-213/77 and 17DD subgroups, respectively. There was no association with maternal immunity. Among children aged 12 months or older, the seroconversion rates of 69% were associated with concomitant vaccination against measles, mumps and rubella. The data were not conclusive regarding the interference of maternal immunity in the immune response to the YF vaccine, but they suggest interference from other vaccines. The failures in seroconversion after vaccination support the recommendation of a booster dose in children within 10 years of the first dose.     

国产腮腺炎和进口麻风腮疫苗免后腮腺炎HI抗体比较

报道了用国产流行腮腺炎减毒活疫苗和美国产麻－风－腮减毒活疫苗接种８～９岁小学生后,采血进行ＨＩ抗体测定比较,其抗体阳转率均在８０％左右,ＧＭＴ为７．３５～１０．０３,说明两种疫苗均有较好的免疫应答     

Analysis of a measles epidemic; possible role of vaccine failures.

A measles epidemic occurred in the Greensville (Ont.) Unit schools during January and February 1975. There were 47 cases of measles in 403 students: 26 (55%) of the children had a history of being vaccinated and 18 (38%) had not been vaccinated. Among children known to have been vaccinated at less than 1 year of age 7 of 13 contracted measles, while among the 48 children who had not been vaccinated 18 contracted measles. The attack rate among vaccinees increased with increasing time since vaccination. The observations of this study as well as those of similar studies suggest that vaccine failures contributed to the genesis of the epidemic. It is recommended that all children initially vaccinated at less than 1 year of age should be revaccinated with live attenuated measles virus vaccine.     

Measles outbreak in 31 schools: risk factors for vaccine failure and evaluation of a selective revaccination strategy.

OBJECTIVE: To examine the risk factors for measles vaccine failure and to evaluate the effectiveness of a selective revaccination strategy during a measles outbreak. DESIGN: Matched case-control study. SETTING: Thirty-one schools in Mississauga, Ont. SUBJECTS: Eighty-seven previously vaccinated school-aged children with measles that met the Advisory Committee on Epidemiology''s clinical case definition for measles. Two previously vaccinated control subjects were randomly selected for each case subject from the same homeroom class. INTERVENTIONS: All susceptible contacts were vaccinated, and contacts who had been vaccinated before Jan. 1, 1980, were revaccinated. When two or more cases occurred in a school all children vaccinated before 1980 were revaccinated. MAIN OUTCOME MEASURES: Risk of measles associated with age at vaccination, time since vaccination, vaccination before 1980 and revaccination. RESULTS: Subjects vaccinated before 12 months of age were at greater risk of measles than those vaccinated later (adjusted odds ratio [OR] 7.7, 95% confidence interval [CI] 1.6 to 38.3; p = 0.01). Those vaccinated between 12 and 14 months of age were at no greater risk than those vaccinated at 15 months or over. Subjects vaccinated before 1980 were at greater risk than those vaccinated after 1980 (adjusted OR 14.5, 95% CI 1.5 to 135.6). Time since vaccination was not a risk factor. Revaccination was effective in reducing the risk of measles in both subjects vaccinated before 1980 and those vaccinated after 1980 (adjusted OR reduced to 0.6 [95% CI 0.1 to 5.3] and 0.3 [95% CI 0.13 to 2.6] respectively). However, only 18 cases were estimated to have been prevented by this strategy. CONCLUSIONS: Adherence to routine measles vaccination for all eligible children is important in ensuring appropriate coverage with a single dose. The selective revaccination strategy''s high labour intensiveness and low measles prevention rate during the outbreak bring into question the effectiveness of such a strategy.     

Methods for screening the naturally acquired and vaccine-induced immunity to the mumps virus

Since the introduction of the measles, mumps and rubella (MMR) vaccine in Sweden in 1982, a yearly evaluation of the immunity pattern and seroconversion rate of 12-year-old children has been carried out. To be able to realize large-scale, follow-up studies, techniques have to be used which are not too labour-intensive and time-consuming but are sensitive enough to detect past immunity and post-vaccination titres. We report tests with haemolysis-in-gel (HIG) technique and an enzyme-linked, immunosorbent assay (ELISA) compared with neutralization (NT) for the detection of mumps antibodies. This study comprises 226 paired serum samples obtained between 1985 and 1989. One hundred and forty-one of the paired samples had been selected because they had given negative or borderline readings, using HIG technique. The remaining samples were consecutive pre- and post-vaccination sera obtained in 1989 from 85 vaccinees from one area in Sweden. HIG technique gave both false positive and false negative readings, compared with NT as also the false positive sera were detected. Non-inactivated sera could not be used in the NT test against mumps virus, owing to unspecific NT reactions. No differences between non-inactivated and inactivated sera by NT were seen, as against other paramyxoviruses. Cross-reactivity between mumps and parainfluenzae in NT tests was not demonstrated. The ELISA test proved more reliable and specific than HIG and was more sensitive than NT. Some post-vaccination sera from vaccinees who failed to seroconvert by NT contained high levels of mumps antibody detectable by the ELISA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Studies on live rubella vaccine. V. Quantitative aspects of interference between rubella, measles and mumps viruses in their trivalent vaccine

Rubella vaccine combined with measles and mumps vaccines was administered in a single injection to children of 1 to 5 years of age. All three vaccines were serologically effective, and the clinical reactions caused by measles vaccine were considerably alleviated, when 6 x 10(3) PFU of rubella and 10(4) TCD50 per dose of mumps vaccines were combined with 5 x 10(4) TCD50 of measles vaccine. When a larger amount of mumps vaccine (3 x 10(5) TCD50/dose) was used, it caused interference with the rubella and measles viruses, i.e., the antibody response to rubella virus became poor and the incidence of clinical reactions to measles virus decreased. On the other hand, when 5 x 10(5) TCD50/dose of measles vaccine was combined with 10(4) TCD50/dose of mumps vaccine, the clinical reactions to measles virus were decreased but were almost the same as those induced by this vaccine alone.     

Measles morbidity among children inoculated against this infection

In the serological survey of 2009 children immunized against measles 285 children (14.2%) were found to be seronegative to this infection in the hemagglutination inhibition test with 4 hemagglutinating units of the antigen. Among 1724 immunized children showing positive response to vaccination and placed under dynamic observation for 11 years, 2 cases of measles were registered. At the same time, in the dynamic observation of 111 seronegative children 66 measles cases (59.5%) were registered during the above period, while among 169 children, also seronegative, but receiving booster immunization against measles, morbidity rate was only 1.2%. In some vaccinees the decrease of postvaccinal immunity to seronegative values was observed, but such decrease had no essential influence on the morbidity level among the vaccines. The increase of measles morbidity among schoolchildren immunized against this infection was due not to the decrease of their postvaccinal immunity, but to their concentration in schools and to their more intensive contacts with the sources of infection in comparison with children of preschool age.