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.     

Immunogenic activity of temperature sensitive mutation of herpes simplex virus type-1 in mono- and polyvalent conditions with different attenuated strains of virus. II. Analysis of humoral immunologic response induced by mutants of temperature sensitive herpes simplex type-1 virus in polyvalent systems

The ability of mutant ts HSV-1 on 45 passage to induction of IgG antibody response in the presence of other attenuated viral strain, like measles, mumps, rubella was evaluated, and the effect of mutant ts HSV-1 on humoral immunity induced by attenuated measles and mumps strains was also tested. The obtained results clearly indicated that even immunization with other RNA virus strains had no effect on IgG antibody response to mutant ts HSV-1. Significant differences were observed in IgG antibody responses to mumps and measles between groups of guinea pigs immunized with these viruses alone or together with other viruses. This was especially observed in the case of mumps virus. It clearly shows that change of virus concentration rates in polyvalent schema of immunization is needed.     

潍坊市健康人群麻疹、风疹、流行性腮腺炎抗体水平调查

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

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.     

Evidence of local antibody response against Alloiococcus otitidis in the middle ear cavity of children with otitis media

Alloiococcus otitidis is a recently discovered bacterium frequently associated with otitis media. However, no study is available as to whether A. otitidis has a pathogenic role and induces local immune response in the middle ear as a true pathogen. Whole bacterial sonicate of A. otitidis was separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and transferred to a nitrocellulose membrane. Then, Western blot analysis was performed with supernatant of the middle ear effusions from children with A. otitidis-positive otitis media. SDS-PAGE of the bacterial sonicate showed several protein bands, designated A1-A11. Western blot analysis revealed the presence of IgG, secretory IgA, IgG2, and IgM against A. otitidis in the middle ear effusions. Absorption of the specimens with sonicates of other major middle ear pathogens did not alter the reactivity of antibodies against the alloiococcal antigens. The results suggest that specific local immune response against A. otitidis is induced during middle ear infection of the organism as a true pathogen. A5, A6 or A11 is expected to be a main antigenic determinant. This is the first report to show evidence of local antibody response against A. otitidis and to disclose antigenic components of A. otitidis.     

国产腮腺炎和进口麻风腮疫苗免后腮腺炎HI抗体比较

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

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.     

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

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

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)     

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

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

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

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

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

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

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

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

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.     

Role of the pro-inflammatory cytokines tumor necrosis factor-alpha,interleukin-1 beta,interleukin-6 and interleukin-8 in the pathogenesis of the otitis media with effusion

Inflammation in the middle ear mucosa, caused usually by bacterial and viral pathogens, is the primary event in the middle ear predisposing the development of otitis media with effusion (OME). Numerous inflammatory mediators have been identified in OME. However, cytokines play a central role as initiators, mediators and regulators of middle ear inflammation and subsequent molecular-pathological processes in middle ear tissues, leading to histopathological changes in the middle ear cavity and the pathogenesis of OME. In this article, we aim to present an overview of current research developments in the pro-inflammatory cytokine involvement in the aetiology of otitis media with effusion.     

麻疹、腮腺炎、风疹三联减毒活疫苗的安全性和免疫原性研究

为了评价国产麻疹、腮腺炎、风疹三联减毒活疫苗(MMR)的安全性和免疫原性,按整体随机抽样原则,以进口同类疫苗和国产各单价疫苗作为对照,开展现场临床观察;比较不同疫苗组免疫后的反应率、抗体阳转率、保护率及几何平均滴度(GMT)。试验组与对照组接种后,除了试验疫苗的中、强发热反应率高于进口对照疫苗的发热反应率(8.60%与2.00%)外,未见其它有显著差异的不良反应。试验组麻疹免后抗体阳转率高于进口对照疫苗(99.5%与94.6%),麻疹抗体GMT也高于单价麻疹对照疫苗的GMT;试验疫苗与进口MMR疫苗的风疹抗体阳转率、腮腺炎抗体阳转率相比,均无显著性差异。实验研究结果显示,试验MMR疫苗与进口MMR疫苗具有相似的临床反应及良好的免疫原性。     

Immunization

Vaccines have eliminated or substantially reduced the incidence in Canada of smallpox, poliomyelitis, measles, mumps, rubella, diphtheria, tetanus and pertussis. The Canadian Medical Association (CMA) advocates a single immunization schedule, complete for all age groups and diseases where immunization is indicated and available. CMA has endorsed in principle (1984), the second edition of the Guide to Immunization for Canadians compiled by the National Advisory Committee on Immunization and requested that it be disseminated to all practising physicians in Canada. CMA also firmly endorses the concept of a readily accessible nationwide method of recording immunization status. In keeping with the World Health Organization''s commitment to global control of measles, CMA (1981) supports and encourages mandatory vaccination against measles for children. The association advocates a much more aggressive and sustained public education program to promote public awareness and acceptance of immunization.     

Role of Toll-like receptor 4 in innate immune responses in a mouse model of acute otitis media

Nontypeable Haemophilus influenzae (NTHi) is considered a major pathogen underlying middle ear infection. This study characterized the role of Toll-like receptor 4 in the innate immune responses to acute otitis media induced by NTHi in mice. We used C3H/HeJ mice, which have nonfunctional Toll-like receptor 4, and normal wild-type C3H/HeN mice. NTHi were injected into the tympanic bulla, and middle ear effusions and tissues were collected. In C3H/HeN mice, the severity of acute otitis media decreased promptly with a significant reduction in bacterial recovery from middle ear effusions 48 h after injection. In contrast, all C3H/HeJ mice had otitis media at all time points examined, and increasing bacterial counts from middle ear effusions were detected in C3H/HeJ mice 72 h after injection. Expression of intracellular adhesion molecule-1 by the middle ear mucosa paralleled the number of polymorphonuclear cells in the middle ear in both strains. The findings of transmission electron microscopy revealed that phagocytosis and phagosome maturation of polymorphonuclear cells was impaired in C3H/HeJ mice. Our findings indicate that Toll-like receptor 4 plays a part in the early accumulation and functional promotion of polymorphonuclear cells in the middle ear for eradicating NTHi infection.     

Lower Transplacental Antibody Transport for Measles,Mumps, Rubella and Varicella Zoster in Very Preterm Infants

Background

Maternal antibodies, transported over the placenta during pregnancy, contribute to the protection of infants from infectious diseases during the first months of life. In term infants, this protection does not last until the first recommended measles-mumps-rubella vaccination at 14 months in the Netherlands, while these viruses still circulate. The aim of the study was to investigate the antibody concentration against measles, mumps, rubella and varicella (MMRV) in mothers and preterm infants or healthy term infants at birth.

Methods

Antibody concentrations specific for MMRV were measured in cord blood samples from preterm (gestational age <32 weeks and/or birth weight <1500 g) and term infants, and matched maternal serum samples, using a fluorescent bead-based multiplex immune-assay.

Results

Due to lower placental transfer ratios of antibodies against MMRV in 96 preterm infants (range 0.75–0.87) compared to 42 term infants (range 1.39–1.65), the preterm infants showed 1.7–2.5 times lower geometric mean concentrations at birth compared to term infants. Maternal antibody concentration is the most important determinant of infant antibody concentration against MMRV.

Conclusions

Preterm infants benefit to a lesser extent from maternal antibodies against measles, mumps, rubella and varicella than term infants, posing them even earlier at risk for infectious diseases caused by these still circulating viruses.     

Bacterial otitis media: current vaccine development strategies

Otitis media is the most common reason for children less than 5 years of age to visit a medical practitioner. Whilst the disease rarely results in death, there is significant associated morbidity. The most common complication is loss of hearing at a critical stage of the development of speech, language and cognitive abilities in children. The cause and pathogenesis of otitis media is multifactorial. Among the contributing factors, the single most important are viral and bacterial infections. Infection with respiratory syncytial virus, influenza viruses, para-influenza viruses, enteroviruses and adenovirus are most commonly associated with acute and chronic otitis media. Streptococcus pneumoniae, non-typeable Haemophilus influenzae and Moraxella catarrhalis are the most commonly isolated bacteria from the middle ears of children with otitis media. Treatment of otitis media has largely relied on the administration of antimicrobials and surgical intervention. However, attention has recently focused on the development of a vaccine. For a vaccine to be effective against bacterial otitis media, it must, at the very least, contain antigens that induce a protective immune response in the middle ear against the three most common infecting bacteria. Whilst over the past decade there has been significant progress in the development of vaccines against invasive S. pneumoniae disease, these vaccines are less efficacious for otitis media. The search for candidate vaccine antigens for non-typeable H. influenzae are well advanced whilst less progress has been made for M. catarrhalis. No human studies have been conducted for non-typeable H. influenzae or M. catarrhalis and the concept of a tribacterial vaccine remains to be tested in animal models. Only when vaccine antigens are determined and an understanding of the immune responses induced in the middle ear by infection and immunization is gained will the formulation of a tribacterial vaccine against otitis media be possible.