Swedish experience of two dose vaccination programme aiming at eliminating measles,mumps, and rubella.

In 1982 a two dose regimen was introduced in Sweden for the combined vaccination against measles, mumps, and rubella of children aged 18 months and 12 years. Since 1977 about half of the preschool children were vaccinated against measles annually, and since 1974 about 80% of 12 year old girls were vaccinated against rubella. During the period 1982 to 1985 90-93% of the eligible age cohorts of 18 month old children and 88-91% of the 12 year old children were immunised with the new combined vaccine. A study in 1982 of about 140 18 month old children who were nearly all seronegative before vaccination showed that 96%, 92%, and 99% seroconverted against measles, mumps, and rubella, respectively. A second study was carried out in 1983 of 247 12 year old children, of whom 11% lacked antibodies to measles, 27% to mumps, and 45% to rubella. This showed seroconversion in 82% and 80% against measles and mumps, respectively, and all children seroconverted against rubella. In the latest study in 1985 of 496 12 year olds 9% and 13% were seronegative against measles and mumps before vaccination, and 41% against rubella. Of these, 88% seroconverted to measles and 80% to mumps, and all converted to rubella when sera were tested by the haemolysis in gel method. After a neutralisation test against measles as well all children showed immunity to the disease. A low incidence of measles and declining figures for mumps and rubella were reported in 1984 to 1986. An outbreak of rubella during 1985 affected mainly boys in age cohorts in which only the girls had been vaccinated during the 1970s.     

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.     

Revaccination of children during school-based measles outbreaks: potential impact of a new policy recommendation.

OBJECTIVE: To evaluate the potential impact of revaccination on measles outbreak control during school-based epidemics. DESIGN: Retrospective cohort study. SETTING: Thirty-two public elementary and high schools in 14 communities on the west island of Montreal. PARTICIPANTS: All 19,439 children attending these schools during the 1989 measles epidemic in Quebec. INTERVENTION: After notification of a case children with provider-verified records of vaccination on or after their first birthday were identified; the remaining children were vaccinated or excluded from school. OUTCOME MEASURE: Clinical or confirmed measles cases not prevented by this intervention that could have been prevented had revaccination been included during the outbreak. RESULTS: Of the 88 measles cases (74 confirmed) proof of one adequate vaccination was present in 48 (55%). Intervention generally occurred within 5 school days after case notification. The nonpreventable cases involved 75 children who had measles onset before the intervention and 11 (7 vaccinated) who had onset within 8 days after the intervention. The two remaining cases occurred 20 and 25 days after the intervention among nonvaccinated students who refused to be vaccinated. Except for these two cases measles was eliminated at every school. Application of the new Canadian guidelines for measles outbreak control would have required the administration of at least 10,000 additional doses during the outbreak to students vaccinated before 1980; implementation of the new US guidelines would have required the administration of 16,629 additional doses to children previously vaccinated only once. Well-enforced provincial regulations ensuring vaccination of every student upon school entry might have prevented 38 (43%) of the cases. The US recommendation of two routine doses of vaccine before school entry might have prevented 86 (98%) of the cases. However, revaccination during the outbreak would not have prevented a single additional case. CONCLUSION: Revaccination of previously vaccinated students during a measles outbreak would have been costly and of little benefit.     

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.     

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.     

Reduced childhood mortality after standard measles vaccination at 4-8 months compared with 9-11 months of age.

OBJECTIVE--To evaluate the impact on mortality of standard Schwarz measles immunisation before 9 months of age. DESIGN--Children vaccinated in 1980-3 at 4-5, 6-8, and 9-11 months of age were followed to migration, death, or the age of 5 years. SETTING--One urban district and nine villages in two rural areas of Guinea-Bissau. SUBJECT--307 children vaccinated at 4-8 months and 256 at 9-11 months. MAIN OUTCOME MEASURES--Mortality from 9 months to 5 years of age for children immunised at 4-5, 6-8, and 9-11 months. RESULTS--Mortality was significantly lower in children vaccinated at 6-8 months than at 9-11 months (mortality ratio = 0.63, (95% confidence interval 0.41 to 0.97), p = 0.047). As vaccination was provided in semiannual or annual campaigns it is unlikely that age at vaccination reflected a selection bias. The trend was the same in all three study areas. Improved survival after early immunisation was not related to better protection against measles infection. With a Cox multivariate regression model to adjust for age, sex, season at risk, season at birth, measles infection, and region, children vaccinated at 4-8 months had a mortality ratio of 0.61 (0.40 to 0.92, p = 0.020) compared with children vaccinated at 9-11 months. Reimmunised children tended to have lower mortality than children who received only one vaccine (0.59 (0.28 to 1.27, p = 0.176)). CONCLUSION--Standard measles vaccination before 9 months is not associated with higher childhood mortality than is the currently recommended strategy of immunising from 9 months, and it may reduce mortality. This has implications for measles immunisation strategy in developing countries.     

Effect of Measles Vaccination on Incidence of Measles in the Community

A study of the effect of measles vaccination on the incidence of the disease in eight separate areas of England and Wales was begun in 1966. It showed an inverse association between the proportion of children vaccinated and the incidence of measles in the area in the following year, but measles epidemics occurred in several of the areas in subsequent years, despite continuing vaccinations.Measles vaccination was introduced on a large scale in Britain in 1968. Analysis of the notification and vaccination statistics shows that the vaccination of about 10% of the child population (under 15 years) in 1968 sufficed to “replace” the measles epidemic which had been expected in the period October 1968 to September 1969 by a low incidence of the disease, typical of that in previous “interepidemic” years. Further, the effect of the vaccinations was to prevent the development of natural measles in susceptible unvaccinated children as well as in the vaccinated subjects. Thus the number of immune subjects in the community was increased by the vaccinations, but as a result there was a reduction in the number of subjects who acquired immunity from natural measles. These opposed results can therefore explain why vaccination may be effective in the community for only a year or two, though vaccination protects the individual for much longer.It is estimated that a continuing vaccination rate of 40 to 50% of the children born each year would be necessary to replace the regular biennial measles epidemics in Britain by a continuous endemic incidence, and might perhaps lead to the disappearance of the disease without a further major epidemic, but that a continuing vaccination rate of 80 to 90% of children born each year would then be necessary to prevent its reintroduction. The long-term control of measles by vaccination will thus probably prove more difficult than for any other infectious disease.     

The duration and strength of postvaccinal measles immunity

A prolonged immunoepidemiological follow-up of a large group of children immunized against measles revealed a high epidemiological efficacy of a single vaccination. Cases of measles were registered only among those vaccinees in whose blood sera no specific hemagglutinins were detectable by titration with 4 hemagglutinating units of measles antigen prior to the disease. The study showed that groups of children seronegative with respect to measles appeared, as a rule, after unsatisfactory immunization and not due to loss of postvaccinal immunity with time. Properly immunized children in whom the formation of antimeasles antibodies had occurred in response to the injection of live measles vaccine retained postvaccinal immunity for more that 15 years (the term of observation).     

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.     

Altered Reactivity to Measles Virus in Previously Vaccinated Children

In children vaccinated with killed measles vaccine, exposure to natural rubeola within two to four years can result in a clinical syndrome of altered measles reactivity.During a small epidemic of measles in Edmonton, Alberta, 51 children who had received their last killed measles vaccination 27 to 45 months before, were admitted to hospital with this syndrome.The syndrome consists of a prodromal cough and high fever followed by a maculopapular rash appearing on the extremities and progressing centrally. Pulmonary consolidations with or without pleural effusions were evident, but these cleared rapidly in four or five days. Initial WBC and ESR values suggested a bacterial etiology, but no pathogens could be isolated.Complement fixation titres for rubeola are present in acute and convalescent sera and indicate a definite measles infection.Previous killed measles vaccination excites a delayed hypersensitivity which is activated by the natural measles infection to account for this syndrome.It is recommended that killed measles vaccine be no longer used in routine vaccinations.     

Evaluation of the eight-year period of compulsory measles vaccination in the Czech Socialist Republic (CSR)

The object of the study is the evaluation of a more than 8-year period of compulsory vaccination against measles in the CSR. So far, a total of 1,850,000 children have been vaccinated. A pronounced decrease has been achieved in morbidity while mortality and lethality reached zero values as early as in 1973. Changes occur in the epidemiological characteristic of measles manifested primarily by the shift of the age distribution of notified cases into older age groups, by continuous prolongation of interepidemic intervals and by gradual disappearances of typical seasonal incidence. Regular immunological surveys have become the most efficient tools in epidemiological surveillance of this infection and in monitoring the vaccination programme. The results of immunological surveys indeed led to the introduction in 1975 of so-called second vaccination compulsory for children starting the first year of school attendance. Up to the present, a total of 24,000 cases of measles have been recorded in children vaccinated earlier, i.e., 1.5% of the total of vaccinated children. It can be expected that measles as a mass disease will be eliminated from the territory of the CSR in the next few years.     

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)     

Immunization with Live Measles Virus Vaccine

One hundred and fifty children who had no measurable serum measles antibody were vaccinated with live measles virus. All showed post-vaccinal serum antibody levels generally considered sufficient to prevent measles.One hundred and thirty-nine (93%) of the infants and children demonstrated one or more symptoms following vaccination. In view of their generally mild and limited nature, and of the protection subsequently afforded, this procedure would seem to be a real advance in preventive medicine.     

Effectiveness of revaccination against measles]

The authors studied the efficacy of measles revaccination in children in whose serum no specific antihemagglutinins were revealed in titration with 1 GAE antigen (the first group) and having no specific antibodies in titration with 4 GAE antigen (the second group). Investigations demonstrated that children in whose blood serum no measles antibodies were revealed in the presence of 1 GAE antigen were subject of vaccination. Repeated vaccination used at present in persons who produced minimal antibody concentrations in response to vaccination is not recommended.     

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.     

Protective immunity in macaques vaccinated with a modified vaccinia virus Ankara-based measles virus vaccine in the presence of passively acquired antibodies

Recombinant modified vaccinia virus Ankara (MVA), encoding the measles virus (MV) fusion (F) and hemagglutinin (H) (MVA-FH) glycoproteins, was evaluated in an MV vaccination-challenge model with macaques. Animals were vaccinated twice in the absence or presence of passively transferred MV-neutralizing macaque antibodies and challenged 1 year later intratracheally with wild-type MV. After the second vaccination with MVA-FH, all the animals developed MV-neutralizing antibodies and MV-specific T-cell responses. Although MVA-FH was slightly less effective in inducing MV-neutralizing antibodies in the absence of passively transferred antibodies than the currently used live attenuated vaccine, it proved to be more effective in the presence of such antibodies. All vaccinated animals were effectively protected from the challenge infection. These data suggest that MVA-FH should be further tested as an alternative to the current vaccine for infants with maternally acquired MV-neutralizing antibodies and for adults with waning vaccine-induced immunity.     

An epidemiologic and immunologic study of measles under conditions of massive immunization against that infection]

Massive measles immunization in Riga led to a marked reduction of measles incidence and to a change of the principal regularities of the epidemic process in this infection. Among those who contracted the disease there was an increase in the percentage of schoolchildren; affection with measles of children attending creches and kindergartens and the intensity of the spread of the infection in them diminished. Selective examination of the immunological efficacy of the living measles vaccine prepared of the (see article) and applied in 1967--1972 demonstrated the presence of specific stimulation of the antibody formation in about 90% of the persons vaccinated. The intensity of humoral immunity in the persons vaccinated did not diminish with the advance of time after the vaccination, and 6--7 years after the vaccination over 90% of the vaccinated individuals were reliably protected from measles. The presence of numerous negative results in carrying out the vaccinations in individual institutions is apparently attributed chiefly to disturbances of the storage regimen of transportation and of the use of the vaccine.     

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.     

Delays in the primary vaccination of children.

The results of a population-based survey of 170 children''s vaccination records were used to calculate the cumulative distributions of the ages (in months) at which each dose of vaccine had been received. Considerable delays in the administration of measles-mumps-rubella (MMR) vaccine and of the fourth dose of diphtheria-pertussis-tetanus vaccine were observed, particularly in children vaccinated by private physicians rather than at public health clinics. The delay before MMR vaccination causes concern because of the frequency of measles in children aged 1 to 2 years, particularly those attending day-care centres, and the fragility of the herd immunity against this disease. Physicians should follow up patients who have missed appointments for MMR vaccination if a voluntary measles control program is to succeed.     

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.