Immunological effectiveness of a booster inoculation against measles in children remaining seronegative after vaccination

Booster immunization against measles with a highly immunogenic vaccine leads to the development of prolonged postvaccinal immunity lasting at least 6-7 years (the term of observation) in the groups of children found to be seronegative after the titration of their blood sera with 1 hemagglutinating unit (HAU) of the antigen. The booster immunization of children in whose blood sera the minimal concentrations of antibodies can be determined in the presence of 1 HAU of the antigen (seronegative in the presence of 4 HAU) is less effective. The serological checks of immunized children entering preschool institutions and the primary grades at schools and the subsequent booster immunization of children found to be seronegative will lead to a further decrease in measles morbidity.     

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.     

Immunostructure of school-age children inoculated against measles

The mass serological survey of school children immunized against measles was carried out by means of the hemagglutination inhibition test. As a result, 20.4% of these school children were found to be seronegative, and in 9.5% of them even the minimum concentration of measles antihemagglutinins (when titrated with 1 hemagglutinating unit of the antigen) was not detected. The accumulation of a considerable seronegative (measles-susceptible) stratum among children of school age occurred due to the low immunogenic potency of some batches of live measles vaccine, used for immunization in 1973, as well as due to the formerly practiced immunization of children under 1 year of age. A direct and close dependence of focal measles morbidity among immunized children having had contacts with the source of infection on the number of children among them, found to be seronegative after titration with 1 hemagglutination unit of measles antigen, was established.     

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 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)     

The use of the cluster selection method for assessing the status of immunity to controlled infections (measles, diphtheria and tetanus)]

The use of the method of cluster selection in mass serological examination makes it possible to obtain statistically significant results with very low expenditures. The coincidence of the results on the number of seronegative children, obtained by the method of cluster selection, with the results of mass serological examination of all children aged 6-7 years in the district (children found to be seronegative to measles constituted 5.5% and 5.0% respectively) is indicative of the statistical significance of the method used in this investigation. The results obtained by the method of cluster selection indicate that the level of protection among the children of the district was high both with respect to measles (94.5 +/- 1.8%) and tetanus (96.5 +/- 1.7%); with respect to diphtheria, the immune stratum was found to be less (91.1 +/- 2.3%). These data may be helpful in working out scientifically substantiated administrative decisions contributing to an increase in the effectiveness of planned mass immunization.     

Immunological effectiveness of secondary revaccination against tetanus performed at prolonged intervals

After primary immunization with adsorbed DPT vaccine antitetanus immunity was retained for 9-10 years in 90.6-98.4% of children covered by this study. The second booster immunization of children against tetanus with adsorbed DT toxoid with reduced antigen content, made at an interval prolonged to 7-10 years under the conditions of lower antitoxic immunity, ensured a high level of intense antitetanus immunity. These data point to the possibility of prolonging the interval between booster immunizations to 9-10 years and reducing the number of injections and antigenic load.     

Duration of immunity in children who received a primary complex of inoculations with ADT-M anatoxin and an assessment of postponed secondary revaccination against diphtheria and tetanus (the results of an epidemiologic trial)

The prolonged observations of the immunological effectiveness of adsorbed diphtheria-tetanus toxoid with reduced antigen content in children who had received the primary course of immunization with this preparation showed that the preparation induced the development of prolonged and intensive immunity to both infections. In 2-3 years after the first booster immunization the protective level of diphtheria antitoxin was registered in 89.9% and that of tetanus antitoxin, in 99% of children. 6 years later the level of immunity remained practically unchanged: the titers of diphtheria antitoxin above the protection level were determined in 92% and those of tetanus antitoxin, in 97% of children. These data made it possible to increase intervals between booster immunizations to 6-7 years in children of this category. The results of the epidemiological trial made to find out the possibility of a change in the timing of the second booster immunization confirmed the expediency of postponing booster immunization from 6 and 11 years to 9 and 16 years of age.     

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.     

Study of combined vaccination against yellow fever and measles in infants from six to nine months

A study has been carried out in the Ivory Coast to assess the efficacy of a combined vaccine against yellow fever and measles relative to that of each vaccine administered separately. Healthy children aged six to nine months were recruited and divided into two age groups: less than seven months (group I) and more than eight months (group II). In each group, they were randomly assigned to receive either yellow fever vaccine only (A), measles vaccine only (B), or the combined vaccine (C). The serological responses to measles and yellow fever were assessed in 219 initially seronegative children 45 days after immunization. More than 90% of the children developed yellow fever haemagglutination inhibiting antibodies. Neither age nor combination with measles vaccine influenced the responses to yellow fever vaccine. Measles haemagglutinational inhibiting antibodies were found in 97% of the children and the seroconversion rate was influenced neither by age nor by combination with yellow fever vaccine. Younger infants had lower titres of measles antibody. No particular adverse reactions were notified during the follow up. This study shows that combined yellow fever and measles vaccines are immunogenic in infants from the age of six months. Controlling yellow fever in endemic areas and the prevention of measles in young infants may greatly benefit by this combination.     

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.     

Immunological effectiveness of a 2d revaccination against diphtheria performed at intervals extended up to 7-10 years

The present article deals with the data on the duration of antidiphtheria immunity, induced by the primary cycle of immunization with adsorbed DPT vaccine, with the aim of considering the problems of optimizing the immunization schedule for children. The prolongation of the interval before the second booster immunization to 7-10 years produces no negative influence on the effectiveness of immunization. Besides, the study has shown that after the main complex of immunizations with adsorbed DPT vaccine protective immunity to diphtheria is retained in 90.3-96.8% of children covered by this study for 9-10 years. These data point to high immunological effectiveness of adsorbed DPT vaccine and to the possibility of prolonging the intervals between booster immunizations to 10 years, as well as decreasing the number of booster immunizations in the immunization schedule for children.     

Hepatitis B vaccine: prospects for duration of immunity

The duration of hepatitis B vaccine-induced immunity was studied in a group of 54 seronegative health professionals who received plasma-derived hepatitis B vaccine (Merck's Heptavax) in 1978 and 1979. Five to seven years later, 52 vaccinees received a booster dose of yeast recombinant hepatitis B vaccine (Merck's Recombivax). Of 54 vaccinees, 47 (87 percent) had a favorable anti-HBs response (greater than 10 S/N RIA units) and 7 (13 percent) had low (2.1-10 S/N) or undetectable levels (less than 2.1 S/N) one year after primary immunization. After five to seven years, the anti-HBs values had declined to undetectable levels in 25 percent and to low levels in 23 percent. A booster dose of vaccine induced an anamnestic response in 90 percent of vaccinees by two weeks. The results of this study indicate that persons who respond favorably to primary immunization may be protected for at least seven years.     

Epidemiologic effectiveness of mass revaccination against measles

The data on the epidemiological effectiveness of the mass booster immunization of students of high schools, as well as professional and technical schools, against measles are presented. Booster immunization is considered to be a highly effective antiepidemic measure aimed at decreasing morbidity rate in measles.     

Effectiveness of measles immunoprophylaxis and the criteria for assessing its possible elimination

The study of measles morbidity in Donetsk Province in 1960-1984 and the study of antimeasles immunity in different groups of the population have shown that the problem of the liquidation of measles cannot be solved by immunizing the population in a single administration of the vaccine. To enhance the effectiveness of the immunoprophylaxis of measles and its influence on the epidemic process, a number of problems must be solved with the aim to improve the quality of the vaccine, especially its thermal stability, to establish the possibility of shifting the beginning of immunization from 15-17 months to 12 months of age, to increase the coverage of children with immunization against measles by decreasing the number of groundless exemptions from immunization and by immunizing children in risk groups according to individual schedules and dosage, to carry out selectively the booster immunization of persons who have lost their postvaccinal immunity, as revealed by laboratory test, or in whom such loss may be supposed, to introduce the objective method (indirect hemagglutination test) for controlling the state of immunity among different groups of the population into laboratory practice at sanitary and epidemiological stations. As to the possibility of the liquidation of measles, the statement of this problem is correct, but for its solution a complex of additional prophylactic and epidemic-control measures should be taken.     

克拉玛依市2008年麻疹监测与控制情况分析

分析克拉玛依市麻疹流行状况及预防控制措施,为消除麻疹提供依据。采用描述流行病学分析方法,对2008年克拉玛依市麻疹资料进行分析。结果显示,克拉玛依市2008年麻疹发病率为38.83/10万(138/355381),呈高度散发,较2007年有所上升。发病高峰在3～5月,发病数占全年的83.33%。年龄分布大年龄组高于小年龄组,>20岁年龄组病例占50.00%,<1岁病例占18.84%;流动人口发病占51.11%。应切实提高麻疹常规免疫接种率和做好入托、入学儿童查验预防接种证工作,加强麻疹监测,提高实验室确诊病例的比例。     

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.     

Transplacental measles immunity in infants in the 1st year of life]

A total of 187 parturients (66 with a history of measles and 121 immunized with live measles vaccine, or LMV, in childhood) and their 187 newborn infants, as well as 195 children aged up to 1 year, were examined. Antimeasles antibodies in blood sera were detected in the hemagglutination inhibition test. In all mothers with a history of measles and in their newborn infants antimeasles antibodies in different titers were detected. In mothers, formerly immunized with LMV, antimeasles antibodies were absent in 5.8% and in their newborn infants, in 6.6% of the examinees. Among children aged up to 1 year, born of formerly immunized mothers, more rapid disappearance of passive antimeasles immunity was observed. In cases of contact with measles, the serological examinations of all children born of mothers immunized with LMV should be carried out in order to protect seronegative children by passive or active immunization.     

Use of the leukocyte adherence inhibition reaction for assessing the effectiveness of vaccination against measles

The reaction of the inhibition of leukocyte adhesion to a glass slide under the action of measles antigen may be used for the evaluation of the activity of antigen-specific T-lymphocytes in the process of immunization against measles and recommended, along with serological studies, for finding out persons susceptible to measles among vaccinees. The immunological effect of booster immunizations against measles can be evaluated by the degree of the inhibition of leukocyte agglutination to a glass slide.     

国产甲型肝炎灭活疫苗用于儿童免疫效果研究

为了探讨国产甲型肝炎灭活疫苗在儿童中应用的免疫效果,选择2～15岁抗-HAV阴性健康易感儿童91名作为接种对象,采用0、6程序接种国产甲型肝炎灭活疫苗250U／剂,观察免疫后的局部反应和全身反应,并于全程免疫后一个月检测抗-HAV阳转率和抗体GMT。结果91例观察对象在初免和加强免疫后均未见即时副反应,只在8～72小时内出现轻微的一过性局部和全身反应。全程免疫后一个月抗-HAV阳转率为100％。抗体GMT为14 407mIU／ml。国产甲肝灭活疫苗在儿童中应用具有良好的安全性和免疫原性,采用0、6个月程序可获得高滴度抗体。