MMR vaccine uptake rates: a data validation study

As part of our investigation into the decrease in the measles, mumps and rubella (MMR) vaccine uptake rates, we validated MMR vaccination records of all children born between 01/09/1998 and 31/08/1999 in our area (North Cheshire, South Cheshire, and Wirral). A significant number of children had received their MMR vaccine but were not recorded as such by the Child Health Computer System (CHCS). Reported COVER (cover of vaccination evaluated rapidly) data uptake (combined) for North Cheshire, South Cheshire, and Wirral Health Authorities for the period covered by the data validation study was 90.5%, the corrected uptake following the validation was 92.6%, 2.1% higher than the reported coverage. If the coverage data were to continue to form part of the NHS indicators of PCT performance, action by all PCTs to improve accuracy of immunisation data would be highly desirable. Electronic transfer of information from practices to the CHCS and between CHCSs, i.e. across boundaries, could improve data accuracy.     

Outbreak of aseptic meningitis and mumps after mass vaccination with MMR vaccine using the Leningrad-Zagreb mumps strain.

Data from routine surveillance during two mass immunisation campaigns (MIC) with Measles-mumps-rubella (MMR)vaccine using Leningrad-Zagreb mumps strain in two states in Brazil were analysed to estimate the risk of vaccine-related meningitis and mumps. Increase in the incidence of the two diseases was observed in both states, 3 weeks after the vaccination campaigns. The estimated number of doses applied per one case of vaccine-related meningitis ranged from 6199 (95% CI: 4854-8058) to 19,247 (95% CI: 12,648-29,513) depending on the diagnostic criteria used and state. It was 300 doses (95% CI: 286-317) for each case of mumps. The implications for vaccination policy are discussed.     

Infection with wild-type mumps virus in army recruits temporally associated with MMR vaccine

Four cases of mumps were reported among 180 army recruits who had received MMR vaccine 16 days earlier. Mumps serology, salivary mumps IgM and PCR tests for the SH gene were performed on the 4 cases and on 5 control recruits who remained well. PCR products were sequenced and the sequences compared to those of wild type and vaccine strains of mumps. Further salivary mumps IgM tests were performed on the remaining 171 recruits. Mumps infection was confirmed in the 4 cases but not in the 5 controls. The controls had serological evidence of prior immunity. The SH gene sequence found in the 4 cases was wild type. Saliva tests identified 2 additional recruits with mumps IgM, one of whom had presented with suspected mumps 2 days before the MMR vaccine was given. Thus 6 (5 symptomatic and 1 asymptomatic) cases of mumps in army recruits recently receiving MMR vaccine were not due to the vaccine but to coincidental infection with wild-type mumps virus. The probable index case was revealed by salivary mumps IgM tests. This study highlights the importance of appropriate investigation of illness associated with MMR vaccination.     

一起流行性腮腺炎暴发中的疫苗效率评估

流行性腮腺炎(流腮)暴发疫情中对疫苗效率(VE)的评估,国外已有较多的研究报道^[1],而我国类似报道相对较少.2012年3-6月四川省阆中市某幼儿园发生一起流腮暴发疫情,发病儿童绝大多数属免疫覆盖人群,为此本研究通过此次疫情评估腮腺炎疫苗效率. 1.对象与方法:本文病例定义为2012年1月1日至6月22日该幼儿园儿童与老师出现单侧或双侧腮腺和(或)其他唾液腺肿胀、疼痛持续>2d且排除其他原因者.     

Successful seroresponses to measles and rubella following aerosolized Triviraten vaccine,but poor response to aerosolized mumps (Rubini) component: Comparisons with injected MMR

Seroresponses to measles, rubella and mumps were evaluated following the injection of MMR II and injection or aerosol administration of Triviraten in young adults. Response to aerosolized Rubini mumps strain was a focus of interest, given robust responses to aerosolized mumps vaccine (Leningrad-Zagreb strain) in a prior study using aerosolized MMR vaccine. The aerosolized Edmonston-Zagreb (EZ) measles vaccine was significantly more immunogenic than injected EZ vaccine, and comparable to results following injected Moraten measles vaccine having twice the dosage. Responses to rubella were comparable in the three MMR study groups. Aerosolized Rubini vaccine was very highly and unexpectedly less immunogenic than either injected Rubini or Jeryl-Lyn strains. The high attenuation of Rubini vaccine appears to have limited its affinity for respiratory tract receptors, which may underlie its lack of clinical effectiveness.     

MMR vaccine effectiveness in an outbreak that involved day-care and primary schools

Objective

In 2006, a large measles outbreak occurred in Catalonia (Spain), where the immunization schedule included two doses of MMR vaccine at 15 months and 4 years. The aim of this study was to investigate the vaccine effectiveness (VE) of MMR in children attending day-care and pre-school centres and to estimate the number of cases that would have been avoided by administering the first dose of MMR at 12 months.

Methods

A retrospective cohort study was carried out between October 2006 and January 2007 in day-care and pre-school centres with confirmed measles cases. VE was calculated in children aged ≥15 months without previous measles infection. Cases avoided by advancing the first dose of MMR to 12 months were estimated by calculating the basic and effective reproduction number in centres where transmission outside the class was observed.

Results

Fifteen centres and 1394 children were included. There were 77 confirmed cases (attack rate = 5.5%). Vaccination coverage of the 1121 children aged ≥15 months was 91.6% and VE was 96% (95%CI 89-98%).There were 33 (41%) cases in the 81 children aged 12-14 months. Advancing the first dose to 12 months would have prevented 74 cases (91.5%) and lowered the attack rate from 41% to 8.6%.

Conclusions

Over 90% of cases in children aged 12-14 months would have been avoided by MMR administration at 12 rather than 15 months. We strongly recommend advancing the first dose of MMR to 12 months in order to reduce the risk of measles outbreaks.     

Mumps and mumps vaccine: a global review

Mumps is an acute infectious disease caused by a paramyxovirus. Although the disease is usually mild, up to 10% of patients can develop aseptic meningitis; a less common but more serious complication is encephalitis, which can result in death or disability. Permanent deafness, orchitis, and pancreatitis are other untoward effects of mumps. Based on data reported to WHO up to April 1998, mumps vaccine is routinely used by national immunization programmes in 82 countries/areas: 23 (92%) of 25 developed countries, 19 (86%) of 22 countries with economies in transition (mainly the Newly Independent States of the former Soviet Union), and 40 (24%) of 168 developing countries. Countries that have achieved high coverage have shown a rapid decline in mumps morbidity. Furthermore, in many of these countries, mumps-associated encephalitis and deafness have nearly vanished. This review considers the disease burden due to mumps; summarizes studies on the immunogenicity, efficacy, and safety of different strains of mumps vaccine; and highlights lessons learned about implementing mumps immunization in different countries. Countries already using mumps vaccine should monitor immunization coverage and establish routine mumps surveillance with investigation of outbreaks. Where mumps is targeted for elimination, countries need to add a second dose of mumps vaccine for children, keeping in mind that the disease may still occur in susceptible adults.     

Evidence and policymaking: The introduction of MMR vaccine in the Netherlands

Based on a case-study of the introduction of measles-mumps-rubella (MMR) vaccine in the Netherlands two decades ago, using documentary and archival sources, this paper examines the way evidence is used in policymaking. Starting from the question of ‘what counts as evidence’, two central claims are developed. First, the decision to introduce MMR was not one but a series of decisions going back at least seven years, over the course of which the significance attached to various forms of evidence changed. Second, results of international studies were coming gradually to be of greater significance than evidence gathered from within the Netherlands itself. These developments had, and continue to have, major consequences for national scientific competences.     

Concomitant administration of live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) and measles,mumps, rubella (MMR) vaccine: Randomized study in toddlers in Taiwan

Background

Japanese encephalitis (JE) is the most important cause of viral encephalitis in Asia.

Methods

In this randomized, open-label, multicenter trial in 550 children aged 12 to 18 months in Taiwan, children received one dose of JE-CV and one dose of MMR vaccine. Vaccines were either administered separately 6 weeks apart (Groups ‘JE-CV’ and ‘MMR’, named after which vaccine was given first), or concomitantly (Group ‘Co-Ad’). JE neutralizing antibody titers were assessed using PRNT₅₀. MMR antibody levels were determined by ELISA.

Results

All groups had low seroprotection/seropositivity rates (<10%) before vaccination for all antigens. Forty two days after vaccination, on either Study Day 42 or 84, seroconversion rates for all antigens were high in all groups, irrespective of the order of vaccinations. Seroconversion for JE ranged from 96.9% in Group Co-Ad on D42 to 100% in Group MMR. Non-inferiority was demonstrated for all analyses as the lower bound of the 95% CI of the difference in seroconversion rates between groups was above the pre-defined limit of −10.0%. The immune responses remained high for all antigens and well above the level of protection 12 months after vaccination in all groups. There were no safety concerns.

Conclusions

JE-CV is safe and induces a strong protective immune response which persists over 1 year when co-administered with MMR vaccine.     

Factors influencing MMR vaccination decisions following a mumps outbreak on a university campus

Following a number of mumps outbreaks in universities and colleges, the UK Health Protection Agency has suggested that it is appropriate to consider offering the MMR vaccine in these settings. However, little is known about the factors associated with uptake of the MMR jab or perceptions of risks/benefits of the vaccine among higher education students. The current study focused on a sample of students offered the MMR vaccine following an outbreak of mumps on a university campus. Perceptions of risks/benefits of the vaccine varied considerably and students were unlikely to have the jab when perceived risks of immunising were equivalent to perceived risks of not immunising. Results suggest that public health interventions should address students' attitudes towards the vaccine, perceptions of peer expectations, and perceptions of barriers to uptake.     

The case test-negative design for studies of the effectiveness of influenza vaccine

Background

A modification to the case–control study design has become popular to assess vaccine effectiveness (VE) against viral infections. Subjects with symptomatic illness seeking medical care are tested by a highly specific polymerase chain reaction (PCR) assay for the detection of the infection of interest. Cases are subjects testing positive for the virus; those testing negative represent the comparison group. Influenza and rotavirus VE studies using this design are often termed “test-negative case-control” studies, but this design has not been formally described or evaluated. We explicitly state several assumptions of the design and examine the conditions under which VE estimates derived with it are valid and unbiased.

Methods

We derived mathematical expressions for VE estimators obtained using this design and examined their statistical properties. We used simulation methods to test the validity of the estimators and illustrate their performance using an influenza VE study as an example.

Results

Because the marginal ratio of cases to non-cases is unknown during enrollment, this design is not a traditional case-control study; we suggest the name “case test-negative” design. Under sets of increasingly general assumptions, we found that the case test-negative design can provide unbiased VE estimates. However, differences in health care-seeking behavior among cases and non-cases by vaccine status, strong viral interference, or modification of the probability of symptomatic illness by vaccine status can bias VE estimates.

Conclusions

Vaccine effectiveness estimates derived from case test-negative studies are valid and unbiased under a wide range of assumptions. However, if vaccinated cases are less severely ill and seek care less frequently than unvaccinated cases, then an appropriate adjustment for illness severity is required to avoid bias in effectiveness estimates. Viral interference will lead to a non-trivial bias in the vaccine effectiveness estimate from case test-negative studies only when incidence of influenza is extremely high and duration of transient non-specific immunity is long.     

Parents' attitude towards the second dose of measles, mumps and rubella vaccine: a case-control study

In response to media scares and subsequent falls in measles, mumps and rubella (MMR) vaccine uptake, a case-control study was conducted to identify factors associated with non-uptake of the second dose of the vaccine in children resident in North Wales. Subjects were selected from parents of children scheduled for the second dose between October and December 1997. Postal questionnaires were used to compare knowledge, attitudes and practice of non-acceptors (cases) and acceptors (controls). Of non-acceptors, 92.1% (95% CI 82.2-97.5%) stated that they would allow another child to have at least one dose of MMR, and 39.2% (95% CI 25.8-53.9%) both doses of MMR vaccine. Non-acceptors were more likely to report having obtained information from newspapers/television (OR 2.04, 95% CI 1.03-4.02) or from the general practitioner (OR 2.02, 95% CI 1.07-3.86) and to report having 'a lot' or 'some' influence from newspapers/television (OR 3.52, 95% CI 1.57-7.86). The 'combination of three vaccines in one jab' was identified as a worry by 55.1% (95% CI 40.2-69.3%) of non-acceptors and 38.5% (95% CI 30.6-46.9%) of acceptors. On this evidence, catch-up campaigns would be an effective way of increasing coverage; also health professionals need tools to enable them to communicate effectively in the face of ongoing scares.     

Measles,mumps, and rubella antibody patterns of persistence and rate of decline following the second dose of the MMR vaccine

BackgroundAntibodies to measles, mumps, and rubella decline 3% per year on average, and have a high degree of individual variation. Yet, individual variations and differences across antigens are not well understood. To better understand potential implications on individual and population susceptibility, we reanalyzed longitudinal data to identify patterns of seropositivity and persistence.MethodsChildren vaccinated with the second dose of measles, mumps, rubella vaccine (MMR2) at 4–6 years of age were followed up to 12 years post-vaccination. The rates of antibody decline were assessed using regression models, accounting for differences between and within subjects.ResultsMost of the 302 participants were seropositive throughout follow-up (96% measles, 88% mumps, 79% rubella). The rate of antibody decline was associated with MMR2 response and baseline titer for measles and age at first dose of MMR (MMR1) for rubella. No demographic or clinical factors were associated with mumps rate of decline. One month post-MMR2, geometric mean titer (GMT) to measles was high (3892 mIU/mL), but declined on average 9.7% per year among those with the same baseline titer and <2-fold increase post-MMR2. Subjects with ≥2-fold experienced a slower decline (≤7.4%). GMT to rubella was 149 one month post-MMR2, declining 2.6% and 5.9% per year among those who received MMR1 at 12–15 months and >15 months, respectively. GMT to mumps one month post-MMR2 was 151, declining 9.2% per year. Only 14% of subjects had the same persistence trends for all antigens.ConclusionsThe rate of antibody decay varied substantially among individuals and the 3 antigen groups. A fast rate of decline coupled with high variation was observed for mumps, yet no predictors were identified. Future research should focus on better understanding waning titers to mumps and its impacts on community protection and individual susceptibility, in light of recent outbreaks in vaccinated populations.     

Communicating science to the public: MMR vaccine and autism

Media attention and consequent public concerns about vaccine safety followed publication of a small case-series of children who developed autism after receipt of the measles-mumps-rubella (MMR) vaccine. Many well-controlled studies performed subsequently found no evidence that MMR vaccine causes autism. However, despite these studies, some parents remain concerned that the MMR vaccine is not safe. We will discuss the origins of the hypothesis that the MMR vaccine causes autism, studies performed to test the hypothesis, how these studies have been communicated to the public, and some suggested strategies for how this communication can be improved.     

Statistical analysis of MMR vaccine adverse events on aseptic meningitis using the case cross-over design

Vaccination is quite effective in reducing the incidence of disease. However, it may cause some adverse events. For example, one of the adverse events of measles-mumps-rubella(MMR) vaccination is the occurrence of aseptic meningitis. Since the vaccination rate is usually quite high, it is not plausible to use popular study designs such as cohort or case-control studies. We considered a case cross-over design to investigate the association between MMR vaccination and aseptic meningitis in Korean children. We used the Cochran-Mantel-Haenszel(CMH) approach, and obtained a Mantel-Haenszel odds ratio estimator as a measure of association. However, the validity of case cross-over design or the CMH approach in vaccine adverse studies has not been fully investigated. In this paper, through Monte Carlo simulation studies, we show the appropriateness of the case cross-over design and the CMH approach. We also discuss alternative approaches such as Poisson regression using offset and a simple uniformity test. In conclusion, the case cross-over design seems useful to investigate the association between vaccination and occurrence of acute adverse events.