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.     

Response of Children to Inactivated Measles Vaccine Prepared in Bovine Renal Cell Culture

Formalin-inactivated, alum-adsorbed measles vaccine was readily prepared from virus grown in calf kidney cell culture infected with the Sugiyama strain of measles virus which had been adapted to this cell culture. The vaccine induced no side reaction of any consequence in vaccinated children, but demonstrated antigenic capacity in children as well as guinea pigs, comparable to that of currently used killed measles vaccines prepared from virus grown in monkey kidney or chick embryo tissue cultures. The host system employed for the preparation of this vaccine has an advantage over monkey kidney or chick embryo tissue cultures which are currently used for manufacture of killed measles vaccine. Bovine kidneys are much easier to obtain and cultivate. Of importance is the fact that calf kidneys are practically free of latent virus, whereas monkey kidneys and chick embryos frequently harbor latent viruses.     

The measles epidemic in Calgary 1969-70: the protective effect of vaccination for the individual and the community

Twenty per cent of the city''s population of 375,000 had had live measles vaccination as pre-school children in the preceding four years. Protection rates for killed-live vaccine schedule (Edmonston) and live vaccine only (Schwarz) were approximately 66%, not diminishing in four years; the rates for killed vaccine only (three doses) were similar for 18 months, diminishing later. As the numbers who have acquired immunity by contracting the disease fall by 10 percentage points, numbers immunized by live vaccines must rise by 15 percentage points to maintain an equivalent balance of immune and susceptible subjects.     

An in-host model of acute infection: measles as a case study

The epidemiology of acute infections is strongly influenced by the immune status of individuals. In-host models can provide quantitative predictions of immune status and can thus offer valuable insights into the factors that influence transmission between individuals and the effectiveness of vaccination protocols with respect to individual immunity. Here we develop an in-host model of measles infection. The model explicitly considers the effects of immune system memory and CD8 T-cells, which are key to measles clearance. The model is used to determine the effects of waning immunity through vaccination and infection, the effects of booster exposures or vaccines on the level of immunity, and the immune system characteristics that result in measles transmission (R(0)>1) even if an individual has no apparent clinical symptoms. We find that the level of immune system CD8 T-cells at the time of exposure to measles determines whether an individual will experience a measles infection or simply a boost in immunity. We also find that the infected cell dynamics are a good indicator of measles transmission and the degree of symptoms that will be experienced. Our results indicate that the degree of immunity in adults is independent of the source of exposure in early childhood, be it vaccine or natural infection.     

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)     

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.     

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.     

Epidemic of mumps in a partially immune population.

The incidence of mumps in vaccinated and nonvaccinated schoolchildren was studied after a recent epidemic. Information was collected by telephone interviews with the parents and a review of the physicians'' records. The vaccine appeared to be effective, for the incidence of mumps in the 145 vaccinated children--5.5%, or 8 cases--was significantly less (P less than 0.001) than the incidence in the 350 children considered susceptible to infection--21.7%, or 76 cases. The percentage of children who had been immunized decreased with increasing age, and acquisition of immunity through natural infection had the reverse trend; thus, the proportions of children susceptible to infection in each age group were about the same, and the age-specific attack rates were similar. Although the mothers were accurate in indicating absence of vaccination, they incorrectly indicated vaccination of their children 43.0% of the time; this error in reporting could influence vaccine administration in older children. Our findings suggest that mumps vaccination may substitute for natural illness in immunizing populations, and that more extensive use of the vaccine over a broader age range is required to prevent similar epidemics in the future.     

Think globally,act locally: the role of local demographics and vaccination coverage in the dynamic response of measles infection to control

The global reduction of the burden of morbidity and mortality owing to measles has been a major triumph of public health. However, the continued persistence of measles infection probably not only reflects local variation in progress towards vaccination target goals, but may also reflect local variation in dynamic processes of transmission, susceptible replenishment through births and stochastic local extinction. Dynamic models predict that vaccination should increase the mean age of infection and increase inter-annual variability in incidence. Through a comparative approach, we assess national-level patterns in the mean age of infection and measles persistence. We find that while the classic predictions do hold in general, the impact of vaccination on the age distribution of cases and stochastic fadeout are mediated by local birth rate. Thus, broad-scale vaccine coverage goals are unlikely to have the same impact on the interruption of measles transmission in all demographic settings. Indeed, these results suggest that the achievement of further measles reduction or elimination goals is likely to require programmatic and vaccine coverage goals that are tailored to local demographic conditions.     

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.     

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.     

Application of a live attenuated varicella vaccine to hospitalized children and its protective effect on spread of varicella infection.

Twenty-three hospitalized children with no history of varicella or no detectable complement fixing (CF) antibody, were vaccinated with a live attenuated varicella vaccine (Oka strain) immediately after the occurrence of a case of varicella in a children's ward of hospital. These children suffered from the nephrotic syndrome, nephritis, purulent meningitis, hepatitis etc., and 12 of them were receiving steroid therapy. An antibody response was noticed in all the vaccinated children, with mild fever in 6 and a mild rash in 2 of 6. It was uncertain whether these reactions were due to vaccinatin or to naturally acquired infection modified by vaccination. No other clinical reactions or abnormalities of the blood or urine were detected. Thus the spread of varicella infection was prevented, with the exception of one severe case in an unvaccinated patient. In another trial, 16 children with renal diseases were also vaccinated. All the children showed an immune response with no clinical reactions and no abnormalities in blood and urine examinations. Thus live varicella vaccine (Oka strain) can be used safely and effectively for hospitalized children, and its effectiveness in preventing spread of varicella infection was confirmed.     

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).     

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.     

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.     

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.     

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.     

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.     

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.     

Negative seroconversion and circulating interferon in children vaccinated with live measles vaccine

In none of the examined children, regardless of whether they manifested negative (17 children) or positive (25 children) seroconversion after vaccination with live measles vaccine, interferon activity could be demonstrated in the serum (starting with 1:4 dilution) withdrawn at the time of the vaccine administration.