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Lowering the age for receiving the first dose of a measles-containing vaccine (MCV1) has been suggested to close the emerging immunity gap in infants. However, tolerability remains one of the main concerns for vaccine-hesitant parents. We conducted a systematic review and meta-analysis of reactogenicity following MCV1 in infants under 12 months of age. We searched EMBASE and PubMed in February 2021. The search was updated in February 2024. With exception of case reports, we included all English-written original studies published >1985 that contained frequency measures on adverse events (AEs) within 56 days following MCV1 in infants <12 months of age. We identified all common AEs and their frequencies and combined these across studies in a meta-analysis. The effect of measles strain and vaccine valency was also evaluated. We included 24 studies for analysis: 18 randomized controlled trials (RCTs), three interventional studies, and three observational studies. Only one RCT was placebo-controlled. Commonly reported AEs were injection site reactions, fever, rash, gastrointestinal symptoms, respiratory tract symptoms, conjunctivitis, and symptoms related to the general condition of the infant. The frequency of any AE was generally <10 %; however, the placebo-controlled trial showed no difference between MCV1 and placebo-injected infants. Edmonston B strains and measles-mumps-rubella-varicella vaccine (MMRV) were associated with a higher rate of high fever >39 °C. Most AEs occurred in <10 % of infants receiving MCV1 at < 12 months of age. The placebo-controlled trial suggested no excess reactogenicity following early MCV. Measles strain and vaccine valency may affect AE risks, but other factors such as socioeconomic status, race, and setting could also explain this finding, as these were not equally distributed between studies. Caution is advised when interpreting findings from studies without a placebo group.

Measles, mumps, rubella and varicella are viral infections which can implicate seriously long-term sequelae of infected individuals or even the unborn child. Vaccines against the individual diseases have long been available. Global measles vaccination is estimated to have prevented more than 20million deaths during 2000–2015. During the same time period, measles incidence decreased from 146 to 36 cases per million populations. Today vaccinations against measles, mumps, rubella and varicella are now carried out mainly with combination vaccines. These are today known as immunogenic and safe. MMRV had similar immunogenicity and overall safety profiles to MMR administered with or without varicella vaccine. This issue provides a review of the different vaccines, mode of administration, catch up immunization and postexposure prophylaxis as well as contraindications and adverse effects of the immunization against measles, mumps, rubella, and varicella. The article presents an overview of important information of preventing these diseases with a focus on the existing combination vaccines.

•Real-world evidence of MMRV clinical protection against varicella is essential.•Data showed effectiveness of two doses MMRV against varicella of any severity of 93%.•Two-dose schedule should be recommended to optimise immunisation programmes worldwide. Priorix-Tetra™ (MMRV GlaxoSmithKline Biologicals’ vaccine) was developed based on the existing measles-mumps-rubella and varicella vaccines. In this study, we aimed to estimate the effectiveness of the combined measles-mumps-rubella-varicella Priorix-Tetra™ vaccine against varicella in real-world conditions. We conducted a post-marketing retrospective case-control study in the Apulia region of Italy in children aged 1–9 years born between January 1, 2008 and December 31, 2016. We assessed the effectiveness against varicella of all grades of severity (including hospitalisation) and against hospitalisation for varicella of a single and two doses of Priorix-Tetra™. Moreover, we also assessed effectiveness of monovalent varicella (monovalent-V) vaccine and any varicella vaccines. Vaccine effectiveness was calculated as (1–OR) x 100. We introduced demographic variables in the model to adjust Vaccine effectiveness (aVE) by potential confounders (sex and year of birth). We recorded 625 varicella cases and matched them with 1,875 controls. Among 625 cases, 198 had received a single MMRV dose, 10 two MMRV doses, 46 a single monovalent-V dose, none two monovalent-V doses; four a monovalent-V as first dose and MMRV as second dose, and one a MMRV as first dose and monovalent-V as second dose; 366 cases were not vaccinated. The aVE against varicella of all grades of severity was 77.0% and 93.0% after a single dose and after two doses of MMRV, respectively. The aVE against varicella of all grades was 72.0% after a single dose of monovalent-V vaccine. The aVE against varicella of all grades of severity was 76.0% after a single dose and 94.0% after two doses of any varicella vaccine. The aVE against varicella hospitalisation was 96% after a single dose of any varicella vaccine. Priorix-Tetra™ showed to be an effective vaccine and the two-dose schedule should be recommended to optimise immunisation programmes. A single dose was able to provide protection against varicella hospitalisation.

•Medical school admission requirements do not match national vaccination guidelines.•Observed increase in requests for quantitative proof-of-immunity serology.•Quantitative serology titers should not be used for asymptomatic screening.•Labs are challenged to support admission requirements with inappropriate testing.•Med school admission requirements should be updated to match national guidelines. To assess the guideline concordance of medical school requirements for students’ proof-of-immunity in the United States (US) and Canada. National guidelines for healthcare worker proof-of-immunity to measles, mumps, rubella, and varicella were compared to admission requirements for 62 US and 17 Canadian medical schools. All surveyed schools accepted at least one recommended form of proof-of-immunity, however, contrary to national guidelines, 16% of surveyed US schools asked for a serologic titer, and only 73–79% US schools accepted vaccination as the sole proof-of-immunity. The requirement of numerical, non-standardized serologic testing highlights an oversight in medical school admissions documentation. The requirement for quantitative values to demonstrate immunity is not practical from a laboratory standpoint, and is not needed to show individual immunity to these vaccine-preventable diseases. Until a more standardized process is adopted, laboratories will need to provide clear documentation and direction for quantitative titer requests.

•Fever and ED risks after measles- or pertussis-containing vaccines are similar in children with and without ASD.•No significant increased risk of fever or ED visits after measles- or pertussis-containing vaccines among children with ASD.•Measles- or pertussis-containing vaccines are safe for both children with and without ASD. To determine whether children aged 4–7 years with a diagnosis of autism spectrum disorders (ASD) were at increased risk of fever, febrile seizures, or emergency department (ED) visits following measles- or pertussis-containing vaccines compared with children without ASD. The study included children born between 1995–2012, aged 4–7 years at vaccination, and members of six healthcare delivery systems within Vaccine Safety Datalink. We conducted self-controlled risk interval analyses comparing rates of outcomes in risk and control intervals within each group defined by ASD status, and then compared outcome rates between children with and without ASD, in risk and control intervals, by estimating difference-in-differences using logistic regressions. The study included 14,947 children with ASD and 1,650,041 children without ASD. After measles- or pertussis-containing vaccination, there were no differences in association between children with and without ASD for fever (ratio of rate ratio for measles-containing vaccine = 1.07, 95% CI 0.58–1.96; for pertussis-containing vaccine = 1.16, 95% CI 0.63–2.15) or ED visits (ratio of rate ratio for measles-containing vaccine = 1.11, 95% CI 0.80–1.54; for pertussis-containing vaccine = 0.87, 95% CI 0.59–1.28). Febrile seizures were rare. Pertussis-containing vaccines were associated with small increased risk of febrile seizures in children without ASD. Children with ASD were not at increased risk for fever or ED visits compared with children without ASD following measles- or pertussis-containing vaccines. These results may provide further reassurance that these vaccines are safe for all children, including those with ASD.

Abstract Background The combined measles, mumps, rubella (MMR) and measles, mumps, rubella, and varicella (MMRV) vaccines are part of Ontario’s routine immunization schedule. Objective To assess adverse events following immunization (AEFIs) reported in Ontario following administration of MMR and MMRV vaccines between 2012 and 2016. Methods Reports of AEFIs were extracted from the provincial surveillance database on May 9, 2017. Events were grouped by provincial surveillance definitions. Reporting rates were calculated using provincial population estimates or net doses distributed as the denominator. A serious AEFI is defined as an AEFI that resulted in an in-patient hospitalization or death. Results Overall, 289 AEFIs were reported following administration of MMR (n=246) or MMRV (n=43) vaccines, for annualized reporting rates of 16.6 and 8.8 reports per 100,000 distributed doses, respectively. The highest age-specific reporting rate was in children aged 1 to 3 years for MMR (7.7 per 100,000 population) and children aged 4 to 9 years for MMRV (0.8 per 100,000 population). Systemic reactions were the most frequently reported event category, while rash was the most frequently reported event for both vaccines. There were 22 serious AEFIs, 19 following MMR and 3 following MMRV (1.3 and 0.6 per 100,000 doses distributed, respectively). Conclusions Our assessment found a low reporting rate of adverse events following MMR and MMRV vaccines in Ontario. No safety concerns were identified. Our findings are consistent with the safety profiles of these vaccines. Continued monitoring of vaccine safety is necessary to maintain timely detection of unusual postvaccine events and public confidence in vaccine safety.

Background PROQUAD ® , a quadrivalent live-attenuated vaccine targeting measles, mumps, rubella, and varicella, is widely used in pediatric immunization programs. While clinical trials and post-marketing studies have established its general safety, real-world evidence from large-scale passive surveillance systems remains limited. Methods We performed a disproportionality analysis of PROQUAD-related adverse events (AEs) reported to the Vaccine Adverse Event Reporting System (VAERS) between 2015 and 2025. Multiple statistical algorithms were applied to detect safety signals, supplemented by stratified analyses across age, sex, severity, and fatal outcomes. Results Among 17,234 reports, the most frequently reported AEs included injection site erythema, swelling, and fever, consistent with established reactogenicity. Several statistically significant signals not listed in the current FDA label were identified, such as febrile convulsion, vaccination failure, cyanosis, and influenza-like illness. These unlabeled events exhibited distinct patterns across age and sex subgroups, with serious and fatal outcomes occurring more frequently in children under three years of age and in medically vulnerable individuals. Most AEs occurred within three days of vaccination, although serious events showed delayed onset profiles. Conclusion This real-world pharmacovigilance analysis confirms the expected safety profile of PROQUAD while revealing additional adverse event signals that merit further clinical investigation and potential regulatory attention. Continued monitoring is essential to inform vaccine safety practices, particularly in pediatric populations with heightened susceptibility.

Background. The effect of age at first dose on the immunogenicity of a 2-dose pediatric schedule of measles-mumps-rubella (MMR) or measles-mumps-rubella-varicella (MMRV) vaccine was assessed in children born to mostly vaccinated mothers. Methods. Immunogenicity data among children given their first measles vaccine dose between 11 and 22 months of age were pooled from 5 randomized controlled trials conducted in Europe and the United States between 2004 and 2010. Measles antibody titers were measured by enzyme-linked immunosorbent assay before and after each dose; geometric mean concentrations (GMCs) and the proportion seronegative (GMC <150 mIU/ML) were derived by age at first dose. Results. Among 5542 children given a first measles vaccine dose at 11, 12, 13–14, and 15–22 months of age, the proportion seronegative decreased from 8.5% to 3.2%, 2.4%, and 1.5%, respectively (P < .001), whereas GMCs increased with older age measles vaccine initiation (P < .001). MMRV induced higher GMCs than MMR (P < .001). First and second dose GMCs were highly correlated (Spearman coefficient = 0.8). Conclusions. As previously noted among infants born to mothers with history of wild-type measles, antibody responses among children born to vaccinated mothers were reduced based on earlier administration of their first measles vaccine dose at ≤12 vs ≥15 months of age. Negative effects of earlier age at first measles vaccine dose persisted after the second dose. The measles elimination goal may require a careful balance between earlier infant protection and the risk of reduced antibody responses and secondary vaccine failure among successive birth cohorts systematically initiated to measles vaccination <15 months of age.

•First dose vaccination with the MMRV vaccine ProQuad® showed a >2-fold risk of FC compared to MMR+V.•This is the first observational study investigating the risk of FC for MMRV vaccine Priorix-Tetra™.•An increased risk of FC similar in magnitude to that of ProQuad® was observed for Priorix-Tetra™.•1 excess FC case per 2747 immunisations with Priorix-Tetra™ compared to MMR/MMR+V.•Our results suggest a class effect for these quadrivalent vaccines. In July 2006, Priorix-Tetra™, a combined measles-mumps-rubella-varicella (MMRV) vaccine, was licensed in Germany. Since a postlicensure study had shown a more than twofold elevated risk of febrile convulsions (FC) after first dose vaccination with the combined MMRV vaccine ProQuad® compared to separately administered MMR and V vaccines (MMR+V), the Paul-Ehrlich-Institute, the German regulatory agency for vaccine licensing and safety, requested a study investigating the risk of FC for Priorix-Tetra™. We performed a matched cohort study based on claims data of more than 17 million insurees in the German Pharmacoepidemiological Research Database. All children born between 01.01.2004 and 31.12.2008 who received a 1st dose of MMRV vaccine were matched to children vaccinated with MMR, MMR+V and MMR or MMR+V (combined group), respectively, by sex, age, month of vaccination and statutory health insurance. The primary outcome was defined as hospitalization with a diagnosis of FC without any alternative plausible cause of FC, e.g. an infection or neurological condition, coded as main discharge diagnosis. The secondary outcome excluded only neurological conditions to provide a more comparable outcome definition to the one used in the ProQuad® study. Numbers needed to harm (NNH), risk ratios and confounder adjusted odds ratios (ORs) with 95% CIs were estimated to compare the exposure groups. In the main risk period 5–12 days after immunization, the adjusted ORs of the primary endpoint for immunization with MMRV vaccine relative to the comparator vaccine indicated in brackets were 4.1 [95% CI 1.3–12.7; MMR], 3.5 [0.7–19.0; MMR+V], and 4.1 [1.5–11.1; MMR and MMR+V]. The corresponding ORs for the secondary outcome were 2.3 [1.4–3.9; MMR], 1.5 [0.8–2.9; MMR+V] and 2.4 [1.5–3.9; MMR and MMR+V]. This study in children younger than 5 years, 90% of them between 11 and 23 months, shows a risk of FC similar in magnitude for Priorix-Tetra™ as has previously been reported for ProQuad® suggesting a class effect for these quadrivalent vaccines.

Background The Ultra-Orthodox Jewish (UO) population has been affected by pertussis, polio, and measles outbreaks. Safed, a deprived, undervaccinated city in Israel’s North, has a large UO population concentrated in specific neighborhoods. We determined whether in Safed UO population concentration was associated with DTP- containing and MMRV1 vaccines coverage, timeliness and drop-out rates. Method For each of Safed’s statistical areas, we estimated UO population based on the proportion of votes for UO political parties in Israel’s 2020 general elections. We determined whether this proportion was associated with timely and delayed MMRV1 and DTP vaccine coverage for children born 2017–2022 using simple linear regression. We compared DTP and MMRV1 coverage and drop-out rates in UO areas (> 50% vote for UO parties) to others, using chi-square tests. Results All eligible 4385 children residing in Safed were included in the MMRV1 and DTP analyses. Vaccine coverage was significantly lower in UO areas compared to non-UO for all doses of DTP and MMRV1 at expected age (-11.8, -15.8, -16.6, -11.8 and − 7.1% points (pp) respectively, P  < 0.005) - and at 36 months old (-0.5, -3.9, -6.2, -9.3 and − 2% points respectively, P  < 0.005). Gaps narrowed more for MMRV1 (from 7.1 to2 pp), than for DTP4 (from 11.8 to9.3 pp). Increasing UO vote was associated with decreased timely coverage for DTP but not MMRV. DTP1-4 drop-out rates were larger in the UO areas than in non-UO areas (26.2% vs. 18%). Conclusions Vaccine coverage was lower in UO neighborhoods, even in a peripheral city where coverage in non-UO areas is already low. Coverage differences between UO and non-UO populations decreased with time for MMRV1 but not DTP. Our findings suggest timeliness should be considered alongside non-vaccination, and vaccination behavior may be vaccine-specific in the UO population.