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.     

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.     

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.     

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.     

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.     

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.     

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).     

A long-term follow-up study on the efficacy of further attenuated live measles vaccine, Biken CAM vaccine

Antibody persistence was measured in 39 children in an open community 12-13 years after immunization against measles with further attenuated live vaccine, Biken CAM. Serum samples of the children taken every two or three years after vaccination had higher, lower, or the same HI antibody titers as those in samples taken 6 weeks after vaccination. These differences reflected a decrease in the titer in some children and subclinical natural reinfection in others. However, all the children still retained detectable antibody in 12 or 13 years after vaccination, indicating long-term persistence of immunity after immunization with Biken CAM vaccine. For evaluation of the protective efficacy of the vaccine, matched controls were studied during the same period. Serological examination revealed that 97.5% of the controls were infected with measles and contracted the disease. In contrast, none of the vaccinees developed clinical infection after close contact with measles patients.     

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.     

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 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)     

Decline in measles mortality: nutrition,age at infection,or exposure?

The mortality from measles was studied in an urban area of Guinea-Bissau one year before and five years after the introduction of a vaccination programme. The years after the introduction of immunisation saw a decline in mortality among unvaccinated children with measles. This decline occurred despite a lower age at infection and an increasing prevalence of malnourished children. State of nutrition (weight for age) did not affect the outcome of measles infection. The incidence of isolated cases, however, increased in the period after the introduction of measles vaccination. As mortality was lower among these cases, diminished clustering explained some of the reduction in mortality. Comparison between the urban district and a rural area inhabited by the same ethnic group showed a lower age at infection, less clustering of cases, and lower case fatality ratios in the urban area.Endemic transmission of measles in urban districts leads to less clustering of cases, which may help explain the usually lower case fatality ratios in these areas. As measles vaccination increases herd immunity and diminishes clustering of cases, it may reduce mortality even among unvaccinated children who contract the disease.     

Economic effectiveness of using a live measles vaccine in an agricultural area of the Ukrainian SSR

Economic effectiveness of vaccination against measles in an agricultural region of the Ukrainian SSR has been studied. At the period preceding vaccination expenses for each measles patient in the country were three times as low as those in towns. At the period of vaccination a considerable decrease in expenses covering the payment of sick-leave certificates given to mothers taking care of their sick children, in losses connected with absenteeism, in expenses for gamma globulin prophylaxis and the hospital treatment and outpatient servicing of measles patients was observed due to the sharp drop of the total morbidity rate and the increased number of school children among measles patients. In urban and rural areas the equalization of expenses for each patient occurred. In spite of increased expenses for each measles patient, the considerable economy of sums spent for controlling measles was achieved: about 70,000 rubles per annum.     

Are we protected? Imported measles - on the way to eradication

In accordance with the 2015 regional goal for measles and rubella elimination of the WHO European Region, only a few imported cases have been documented of both diseases in Hungary for years.This paper presents a case of a Hungarian woman, born in 1975, who received measles vaccination at age of 12 months and later at age of 11 years, according to her certificate of vaccination. In 2009, after arriving home from a vacation in Ireland, she developed acute measles infection with clinical symptoms. It was confirmed by the detection of measles specific IgM, IgA and IgG antibodies, and by detection of viral nucleic acid from throat swab in virus transport medium.Additionally, an outbreak occurred in December of 2011 among a family emigrated from Romania to Hungary. No new measles cases were diagnosed among the contact persons of neither the young Hungarian woman returning from Ireland, nor the family emigrated from Romania. This observation refers to the effectiveness of the Hungarian vaccination program.     

Immunoepidemiological observations on the duration of post-vaccinal immunity in children vaccinated against measles

In the course of 4 years the authors carried out an immunological and epidemiological observation over 4719 children which attended creches, kindergartens and schools, and were vaccinated with live measles vaccines L-16 and ASC in 1967--1972. A stable persistence of immunity was revealed in the majority of children vaccinated against measles which responded to the vaccination by the formation of humoral antibodies. Among these groups an insignificant number of persons with the appearance of measles sensitivity was noted during the observation period. The quality of the preparation, conditions of its storage, use, and different errors during the vaccination influenced the efficacy of the vaccination. Children immunized with the low-immunogenic series of the vaccine whose blood sera failed to display any specific antibodies in the reaction with 1 AU of the antigen, as a rule, were the ones that contracted the disease.     

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.     

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.     

Recurring measles epidemic in Vietnam 2005-2009: implication for strengthened control strategies

Background: Measles remains a serious vaccine preventable cause of mortality in developing nations. Vietnam is aiming to achieve the level of immunity required to eliminate measles by maintaining a high coverage of routine first vaccinations in infants, routine second vaccinations at school entry and supplementary local campaigns in high-risk areas. Regular outbreaks of measles are reported, during 2005-2009.Methods: National measles case-based surveillance data collected during 2005-June 2009 was analyzed to assess the epidemiological trend and risk factors associated with measles outbreak in Vietnam.Results: Of the 36,282 measles suspected cases reported nationwide, only 7,086 cases were confirmed through laboratory examination. Although cyclical outbreaks occurred between 2005 and 2009, there was no definite trend in measles outbreaks during these periods. Overall, 2438 of measles confirmed cases were among children ≤5 years and 3068 cases were among people ≥16 years. The distribution with respect to gender skewed towards male (3667 cases) significant difference was not observed (P= 0.1693). Unsurprisingly, 4493 of the confirmed cases had no history of vaccination (X² <0.01). The northern and highland regions were identified as the main endemic foci and the spatial distribution changed with time. The occurrence of cases, in a considerable proportion of vaccinated population, is not only a reflection of the high vaccination coverage in Vietnam but also portrays a possibility of less than 100% vaccine efficacy. More so, in order to prevent measles in adults, high-risk groups must be identified and catch-up for selected groups selected.Conclusions: This study therefore reinforces the need for continued improvement of surveillance system and to probe into the possible role of changes in age-distribution of cases if the effective control of measles is to be achieved.     

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.