Effectiveness of "Priorix" Against Measles and Mumps Diseases in Children Born After 2004 in the United Kingdom: A Retrospective Case-control Study Using the Clinical Practice Research Datalink GOLD Database.

BACKGROUND: Evidence on vaccine effectiveness (VE) may encourage vaccination and help fight the reemergence of measles and mumps in Europe. However, limited data exist on real-life effectiveness of individual measles, mumps and rubella (MMR) vaccines. This study evaluated VE of GSK's MMR vaccine ("Priorix") against measles and mumps. METHODS: This retrospective, case-control study used UK data from the Clinical Practice Research Datalink GOLD linked to the Hospital Episode Statistics database to identify children 1-13 years old diagnosed with measles or mumps from January 2006 to December 2018. Cases were matched to controls according to birth month/year and practice region. Cases were identified using clinical codes (without laboratory confirmation). "Priorix" exposure was identified using vaccine batch identifiers. Children exposed to other MMR vaccines were excluded. Adjusted VE was estimated for ≥1 vaccine dose in all children, and for 1 dose and ≥2 doses in children ≥4 years at diagnosis. RESULTS: Overall, 299 measles cases matched with 1196 controls (87.6% <4 years old), and 243 mumps cases matched with 970 controls (74.2% <4 years old) were considered. VE for ≥1 dose in all children was 78.0% (97.5% confidence interval: 67.2%-85.3%) for measles and 66.7% (48.1%-78.6%) for mumps. In children ≥4 years old, VE after 1 dose was 74.6% (-21.7% to 94.7%) for measles and 82.3% (32.7%-95.3%) for mumps, and VE after ≥2 doses was 94.4% (79.7%-98.5%) for measles and 86.5% (64.0%-94.9%) for mumps. CONCLUSIONS: "Priorix" is effective in preventing measles and mumps in real-life settings.

Safety of measles-containing vaccines in post-marketing surveillance in Anhui, China.

The safety of measles vaccination is of great interest and importance to public health practice and the general society. We have analyzed the adverse events following immunization (AEFIs) of currently used measles-containing vaccines (including live attenuated measles vaccine, live attenuated measles and rubella combined vaccine, live attenuated measles and mumps combined vaccine, live attenuated Measles, Mumps and Rubella Combined Vaccine) in Anhui Province, China. From 2009 to 2014, 9.9 million doses of measles-containing vaccines were administrated and 1893 AEFIs were found (191.4 per million doses), of which, 33 serious AEFIs (3.3 per million vaccine doses) were reported. 59.4% (1124 cases) were male cases, and 85.1% (1611 cases) occurred in persons aged < 1 year. 93.3% (1766 cases) occurred at the first dose of vaccination and 95.9% (1815 cases) were found within 3 days after vaccination. This study presents up-to-date data and suggests that the measles-containing vaccines used in Anhui Province of China are safe.

EpiReview: Measles in NSW, 2002-2011.

Measles has been eliminated in NSW for more than a decade; however outbreaks associated with international travel do occur. This EpiReview describes the epidemiology of measles in NSW from 2002-2011. A total of 281 cases of measles were notified during the period, an average annual notification rate of 0.41 notifications per 100 000 population (range: 0.06-1.25). There were 139 hospitalisations recorded with a measles diagnosis in the 10-year reporting period, corresponding to a rate of 0.20 hospitalisations per 100 000 population. Of the 80 measles virus specimens genotyped, five genotypes were identified: D9 (38%), D8 (24%), D4 (16%), D5 (14%) with H1 identified less frequently (9%). No single genotype was associated with local transmission across successive years. To sustain good measles control, children should be vaccinated against measles on time through routine childhood immunisation, and all young adults who travel internationally should be vaccinated. Clinician awareness remains important in the early identification and control of measles to avoid further transmission during outbreaks and to enable the timely implementation of public health measures.

Identifying optimal risk windows for self-controlled case series studies of vaccine safety.

In vaccine safety studies, subjects are considered at increased risk for adverse events for a period of time after vaccination known as risk window. To our knowledge, risk windows for vaccine safety studies have tended to be pre-defined and not to use information from the current study. Inaccurate specification of the risk window can result in either including the true control period in the risk window or including some of the risk window in the control period, which can introduce bias. We propose a data-based approach for identifying the optimal risk windows for self-controlled case series studies of vaccine safety. The approach involves fitting conditional Poisson regression models to obtain incidence rate ratio estimates for different risk window lengths. For a specified risk window length (L), the average time at risk, T(L), is calculated. When the specified risk window is shorter than the true, the incidence rate ratio decreases with 1/T(L) increasing but there is no explicit relationship. When the specified risk window is longer than the true, the incidence rate ratio increases linearly with 1/T(L) increasing. Theoretically, the risk window with the maximum incidence ratio is the optimal risk window. Because of sparse data problem, we recommend using both the maximum incidence rate ratio and the linear relationship when the specified risk window is longer than the true to identify the optimal risk windows. Both simulation studies and vaccine safety data applications show that our proposed approach is effective in identifying medium and long-risk windows.

The establishment of a highly sensitive ELISA for detecting bovine serum albumin (BSA) based on a specific pair of monoclonal antibodies (mAb) and its application in vaccine quality control.

A highly sensitive sandwich enzyme-linked immunosorbent assay (ELISA) for quantifying BSA was established, based on two mAbs that recognize different epitopes on a BSA molecule. Our ELISA system was used to detect BSA concentrations in several vaccines, such as the MMR (measles, mumps and rubella) vaccine, hepatitis A vaccine, and hepatitis B vaccine. Moreover, we compared the mAb ELISA and the present pAb ELISA by detecting BSA standards and bovine serum samples. The results showed that our ELISA system was in good accordance with the pAb ELISA system. A pair of mAbs (FMU-BSA NO.6 and FMU-BSA NO.11) from 11 murine hybridomas secreting BSA-specific mAbs was selected for the development of the sandwich ELISA. The detection limit of this quantitative assay reaches 0.38 µg/L, which is 10-fold more sensitive than those previously reported. The quantitative range of BSA concentration is from 0.5 to 40 µg/L, which is comparable to the currently used polyclonal antibody (pAb) ELISA. Intra-assay and inter-assay coefficient variations are both lower than 10% at the three concentrations used (10, 20, and 40 µg/L). Thus, the mAb sandwich ELISA developed herein may provide a stable, precise, and highly sensitive method for quantifying BSA, which is very useful in the quality control of some vaccines.

Antibody induced by immunization with the Jeryl Lynn mumps vaccine strain effectively neutralizes a heterologous wild-type mumps virus associated with a large outbreak.

Recent mumps outbreaks in older vaccinated populations were caused primarily by genotype G viruses, which are phylogenetically distinct from the genotype A vaccine strains used in the countries affected by the outbreaks. This finding suggests that genotype A vaccine strains could have reduced efficacy against heterologous mumps viruses. The remote history of vaccination also suggests that waning immunity could have contributed to susceptibility. To examine these issues, we obtained consecutive serum samples from children at different intervals after vaccination and assayed the ability of these samples to neutralize the genotype A Jeryl Lynn mumps virus vaccine strain and a genotype G wild-type virus obtained during the mumps outbreak that occurred in the United States in 2006. Although the geometric mean neutralizing antibody titers against the genotype G virus were approximately one-half the titers measured against the vaccine strain, and although titers to both viruses decreased with time after vaccination, antibody induced by immunization with the Jeryl Lynn mumps vaccine strain effectively neutralized the outbreak-associated virus at all time points tested.

Comparison of the safety and immunogenicity of a refrigerator-stable versus a frozen formulation of ProQuad (measles, mumps, rubella, and varicella virus vaccine live).

OBJECTIVE: A refrigerator-stable formulation of ProQuad has been developed to expand the utility of ProQuad to areas in which maintenance of a frozen cold chain (-15 degrees C or colder) during storage and transport may not be feasible. The objective of this study was to demonstrate that the immunogenicity and safety profiles of a refrigerator-stable formulation of ProQuad are similar to the recently licensed frozen formulation. METHODS: In this double-blind, randomized, multicenter study, healthy 12- to 23-month-old children with negative vaccination and clinical histories for measles, mumps, rubella, varicella, and zoster were vaccinated with either the refrigerator-stable formulation of ProQuad (N = 1006) or the frozen formulation of ProQuad (N = 513). Patients were followed for 42 days after vaccination for adverse experiences. Immunogenicity was evaluated 6 weeks after vaccination. RESULTS: The refrigerator-stable formulation of ProQuad was generally well tolerated. The incidence of adverse experiences was similar between groups. No vaccine-related serious adverse experiences were reported. For both groups, the response rate was > or = 97.7% for measles, mumps, and rubella, and the percentage of patients with a varicella zoster virus antibody titer of > or = 5 U/mL glycoprotein antigen-based enzyme-linked immunosorbent assay after vaccination was > or = 88.8%. The geometric mean titers for all antigens were numerically slightly higher in patients who received the refrigerator-stable formulation. CONCLUSIONS: The refrigerator-stable formulation of ProQuad is generally well tolerated, highly immunogenic, and noninferior in terms of postvaccination antibody responses. This refrigerator-stable formulation may improve ease of vaccine administration, increase use of the vaccine throughout the world because of its improved storage conditions, and replace the frozen formulation of ProQuad or any dose of M-M-RII and Varivax in routine practice.

The safety and immunogenicity of a quadrivalent measles, mumps, rubella and varicella vaccine in healthy children: a study of manufacturing consistency and persistence of antibody.

BACKGROUND: This clinical trial was conducted to demonstrate that each of 3 consistency lots of a combined measles, mumps, rubella and varicella vaccine (MMRV) would be well tolerated, induce clinically acceptable and similar immune responses to each antigen and induce immune responses similar to measles, mumps and rubella vaccine (MMR) administered concomitantly with varicella vaccine (V). An additional objective was to evaluate the persistence of antibodies 1 year postvaccination. METHODS: Study participants 12 to 23 months of age received a single injection of either one of 3 consistency lots of MMRV or MMR + V administered at separate injection sites. RESULTS: A total of 3,928 healthy children were enrolled at study sites in the United States and Canada. Immune responses to measles, mumps, rubella and varicella in children immunized with each of 3 lots of MMRV were similar and the combined response to all 3 lots was comparable to that of the control group. The 1-year antibody persistence rates for measles, mumps, rubella and varicella viruses were each greater than 95% and comparable among the recipients of the 3 consistency lots of MMRV and the control group. All vaccines were generally well tolerated during the 42 days after vaccination and the overall incidence of adverse experiences was comparable between recipients of MMRV and MMR + V. Rates of fever (temperature >or=38.9 degrees C oral equivalent or tactile) were greater in recipients of MMRV than in recipients of MMR + V (39.1% versus 33.1%, P = 0.001). Fevers were transient and there was no difference in the incidence of febrile seizures. CONCLUSIONS: MMRV was generally well tolerated and had comparable immunogenicity and overall safety profiles to MMR + V administered concomitantly. Long-term persistence of antibodies after receipt of MMRV is expected based on similar antibody titers against all 4 antigens 1 year postvaccination compared with recipients of MMR and V.

Comparative efficacy of Rubini, Jeryl-Lynn and Urabe mumps vaccine in an Asian population.

OBJECTIVE: The comparative efficacy of the three mumps vaccine strains (Jeryl-Lynn, Urabe and Rubini) was conducted in an Asian population from data arising from an epidemiological investigation of seven institutional outbreaks of mumps in Singapore. METHODS: Demographic information (gender, age, ethnic group), clinical presentation and vaccination history (date and place of mumps vaccination, type of mumps vaccine received) of all children who attended the six childcare centres and one primary school where outbreaks of 20 or more cases of mumps occurred in 1999 were collected. The attack rate of the unvaccinated group and the attack rates of the vaccine groups (for each vaccine strain) were determined and the vaccine efficacy of the three vaccines calculated. RESULTS: The vaccine efficacy of the Jeryl-Lynn strain, Urabe strain and Rubini strain mumps vaccine were 80.7, 54.4 and -55.3%, respectively. CONCLUSION: Rubini strain mumps vaccine conferred no protection and has since been deregistered in Singapore.

Informing education policy on MMR: balancing individual freedoms and collective responsibilities for the promotion of public health.

The recent decrease in public confidence in the measles, mumps and rubella vaccine has important implications for individuals and public health. This article presents moral arguments relating to conflicts between individual autonomy and collective responsibilities in vaccination decisions with a view to informing and advising health professionals and improving the effectiveness of education policies in avoiding resurgence of endemic measles. Lower population immunity, due to falling uptake, is hastening the need for greater public awareness of the consequences for the population. Vaccination refusals go hand in hand with responsibilities owed to future generations and society in not knowingly contributing to preventable harms. Issues such as parents' rights are considered and balanced against: collective responsibilities for public health; permissibility of 'free-riding'; conflicting duties of health professionals; and possible enforcement of vaccination. It is suggested that the arguments may form a persuasive tool for the practice of health professionals involved in informing and supporting parents' vaccination decisions.

Measles and the importance of maintaining vaccination levels.

Measles is caused by the paramyxovirus which spreads through airborne droplets. The disease has an incubation period of between six and 19 days. People with measles are usually infectious for one to two days before the rash appears but the total period during which an individual is infectious is not known.

Seroprevalence of measles, mumps and rubella antibodies in Luxembourg: results from a national cross-sectional study.

A serological prevalence survey was carried out in Luxembourg during 2000-2001 to determine the antibody status of the Luxembourg population against vaccine-preventable infections. Blood samples of children and adolescents were collected prospectively in randomly selected schools. Samples of adults were obtained through volunteer patients of the national health laboratory or of the mandatory pre-nuptial test. Measles, mumps and rubella (MMR) virus antibody concentrations were measured using commercial ELISA tests. Age-standardized prevalence of measles, mumps and rubella virus antibodies was found to be 96.58, 75.40 and 95.69% respectively. Significant age-dependence of serology was observed for all three infections, with study participants born after the introduction of the MMR vaccine experiencing a gradual decline of antibodies following vaccination in childhood. Older study participants who were more likely to have antibodies from natural infection had consistently higher titres than younger individuals. Present vaccination coverage with MMR appears to be sufficient to prevent large local outbreaks of measles and rubella, but probably not mumps.

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.

Mumps: immune status of adults and epidemiology as a necessary background for choice of vaccination strategy in Jordan.

The prevalence of antibodies against mumps in 333 students at Jordan University was assessed using the ELISA technique. Most of the students (93.7%) were seropositive for mumps. About 50% of unvaccinated students and students vaccinated using the optional single-dose MMR vaccine had mumps. The incidence rate of mumps in different age groups and sexes, the geographic distribution and the seasonality of mumps infection prior to the adoption of compulsory MMR vaccination were investigated during the period from 1988 to 2000. Mumps occurred in all age groups in both sexes and the incidence rate was higher in children aged 5-14 years than in adults. There was a higher frequency in winter and spring with epidemic peaks in 1988, 1993 and 2000. Southern Jordan had the highest incidence rate due to low vaccination coverage by the private clinics. The data support the introduction of compulsory MMR vaccination in Jordan for all susceptible individuals. Evaluation of the effectiveness of the compulsory single-dose vaccine and, based on the outcome, a second dose of this vaccine is also recommended in order to achieve and maintain a high level of immunization.

[Vaccination offers good protection against measles, mumps and rubella. To refuse vaccination would seriously threaten our good immunity status]. / Vaccination mot mässling, påssjuka och röda hund har god skyddseffekt. Att avstå från att vaccinera skulle allvarlight hota vårt goda immunitetsläge.

Since vaccination against measles, rubella and mumps (MMR) was introduced in Sweden in 1982 for children at 1.5 and 12 years of age these diseases have almost completely disappeared. Severe side effects have been rare. Threats against the continued protection from these diseases include a lessening inclination on the part of parents to vaccinate their children, a weakening of the vaccine-induced immunological response with time, and possibly also genetic changes in strains of circulating wild type virus. By law physicians are bound to report diagnosed cases as well as new or severe side effects. Continuous laboratory analysis of antibodies and circulating viruses is also necessary.