A measles and rubella vaccine microneedle patch in The Gambia: a phase 1/2, double-blind, double-dummy, randomised, active-controlled, age de-escalation trial.

BACKGROUND: Microneedle patches (MNPs) have been ranked as the highest global priority innovation for overcoming immunisation barriers in low-income and middle-income countries. This trial aimed to provide the first data on the tolerability, safety, and immunogenicity of a measles and rubella vaccine (MRV)-MNP in children. METHODS: This single-centre, phase 1/2, double-blind, double-dummy, randomised, active-controlled, age de-escalation trial was conducted in The Gambia. To be eligible, all participants had to be healthy according to prespecified criteria, aged 18-40 years for the adult cohort, 15-18 months for toddlers, or 9-10 months for infants, and to be available for visits throughout the follow-up period. The three age cohorts were randomly assigned in a 2:1 ratio (adults) or 1:1 ratio (toddlers and infants) to receive either an MRV-MNP (Micron Biomedical, Atlanta, GA, USA) and a placebo (0·9% sodium chloride) subcutaneous injection, or a placebo-MNP and an MRV subcutaneous injection (MRV-SC; Serum Institute of India, Pune, India). Unmasked staff ransomly assigned the participants using an online application, and they prepared visually identical preparations of the MRV-MNP or placebo-MNP and MRV-SC or placebo-SC, but were not involved in collecting endpoint data. Staff administering the study interventions, participants, parents, and study staff assessing trial endpoints were masked to treatment allocation. The safety population consists of all vaccinated participants, and analysis was conducted according to route of MRV administration, irrespective of subsequent protocol deviations. The immunogenicity population consisted of all vaccinated participants who had a baseline and day 42 visit result available, and who had no protocol deviations considered to substantially affect the immunogenicity endpoints. Solicited local and systemic adverse events were collected for 14 days following vaccination. Unsolicited adverse events were collected to day 180. Age de-escalation between cohorts was based on the review of the safety data to day 14 by an independent data monitoring committee. Serum neutralising antibodies to measles and rubella were measured at baseline, day 42, and day 180. Analysis was descriptive and included safety events, seroprotection and seroconversion rates, and geometric mean antibody concentrations. The trial was registered with the Pan African Clinical Trials Registry PACTR202008836432905, and is complete. FINDINGS: Recruitment took place between May 18, 2021, and May 27, 2022. 45 adults, 120 toddlers, and 120 infants were randomly allocated and vaccinated. There were no safety concerns in the first 14 days following vaccination in either adults or toddlers, and age de-escalation proceeded accordingly. In infants, 93% (52/56; 95% CI 83·0-97·2) seroconverted to measles and 100% (58/58; 93·8-100) seroconverted to rubella following MRV-MNP administration, while 90% (52/58; 79·2-95·2) and 100% (59/59; 93·9-100) seroconverted to measles and rubella respectively, following MRV-SC. Induration at the MRV-MNP application site was the most frequent local reaction occurring in 46 (77%) of 60 toddlers and 39 (65%) of 60 infants. Related unsolicited adverse events, most commonly discolouration at the application site, were reported in 35 (58%) of 60 toddlers and 57 (95%) of 60 infants that had received the MRV-MNP. All local reactions were mild. There were no related severe or serious adverse events. INTERPRETATION: The safety and immunogenicity data support the accelerated development of the MRV-MNP. FUNDING: Bill & Melinda Gates Foundation.

Rubella in Poland in 2021. / Rózyczka w Polsce w 2021 roku.

INTRODUCTION: Rubella is a viral infectious disease, and humans are the only reservoir of the virus. In 2020, all WHO member countries conducted epidemiological surveillance for rubella, and almost all (99%) had access to rubella testing at laboratories operating under the WHO Global Measles and Rubella Laboratory Network. OBJECTIVES: The aim of this study was to evaluate epidemiological indicators of rubella in Poland in 2021 compared to previous years, taking into account the impact of the COVID-19 pandemic. MATERIAL AND METHODS: The assessment of the epidemiological situation was based on a review of data from the bulletin , "Infectious Diseases and Poisons in Poland in 2021" (5), and the assessment of the immunization status of the population was based on data from the bulletin , "Immunization in Poland in 2021" (6). Classification of cases was made based on the definition used in the 2021 surveillance (7). Data from the epidemiological surveillance system "EpiBase" were also used. RESULTS: In 2021, 50 cases of rubella were registered, 48 fewer than in 2020 (98 cases). There was also a decrease in incidence to 0.13 per 100,000, compared to 0.26 per 100,000 in 2020. The highest incidence, regardless of gender and residential environment, was recorded in the 0-4 age group (1.23 per 100 thousand). No cases of congenital rubella syndrome were reported in 2021. CONCLUSIONS: In 2021, there was a decrease in the number of rubella cases in Poland, which could be a result of the COVID-19 pandemic and the introduced restrictions. In addition, rubella was registered 99% on the basis of clinical diagnoses, without the required laboratory confirmation, which means that other rash diseases could be registered as rubella.

A case of congenital rubella syndrome and epidemiology of related cases in China, 2014-2023.

Rubella is a major cause of congenital defects, and the presence of rubella infection in a pregnant woman may lead to fetal death or congenital defects known as congenital rubella syndrome(CRS). Since China has not yet established a national CRS surveillance system, the true incidence cannot be determined. To understand the disease burden and epidemiological characteristics of CRS cases in China, the article reports the first case of CRS in Quzhou, China, and conducts a retrospective analysis of related cases that have been reported in China over the past decade. Because the availability of rubella-containing vaccines (RCV) was not widespread in China before 2008, women of childbearing age born before 2008 are generally unvaccinated against RCV. Due to the lack of routine CRS monitoring and screening, CRS is underreported in China. Vaccination of nonimmune women of childbearing age with RCV and establishing a sensitive and timely case-based CRS surveillance system can accelerate the elimination of rubella and CRS.

Age-specific prevalence of IgG against measles/rubella and the impact of routine and supplementary immunization activities: A multistage random cluster sampling study with mathematical modelling.

BACKGROUND: Vietnam continues to have measles and rubella outbreaks following supplementary immunization activities (SIA) and routine immunization despite both having high reported coverage. To evaluate immunization activities, age-specific immunity against measles and rubella, and the number of averted Congenital Rubella Syndrome (CRS) cases, must be estimated. METHODS: Dried blood spots were collected from 2091 randomly selected individuals aged 1-39 years. Measles and rubella virus-specific immunoglobulin G (IgG) were measured by enzyme immunoassay. Results were considered positive at ≥120 mIU/mL for measles and ≥10 IU/mL for rubella. The number of CRS cases averted by immunization since 2014 were estimated using mathematical modelling. RESULTS: Overall IgG seroprevalence was 99.7% (95%CI: 99.2-99.9) for measles and 83.6% (95%CI: 79.3-87.1) for rubella. Rubella IgG seroprevalence was higher among age groups targeted in the SIA than in non-targeted young adults (95.4% [95%CI: 92.9-97.0] vs 72.4% [95%CI: 63.1-80.1]; P < 0.001). The estimated number of CRS cases averted in 2019 by immunization activities since 2014 ranged from 126 (95%CI: 0-460) to 883 (95%CI: 0-2271) depending on the assumed postvaccination reduction in the force of infection. CONCLUSIONS: The results suggest the SIA was effective, while young adults born before 1998 who remain unprotected for rubella require further vaccination.

Identifying the population susceptible to rubella in Japan, 2020: Fine-scale risk mapping.

BACKGROUND: Rubella remains a public health challenge in Japan, impeding the attainment of herd immunity. Despite vaccination efforts since 1976, persistent outbreaks reveal a susceptibility gap in male adults born before 1995. Seroepidemiological surveys are pivotal in evaluating population immunity and identifying at-risk groups. METHODS: This study aims to pinpoint high-risk areas for potential rubella outbreaks in Japan by merging seroepidemiological data from 2020 with population census information. Various data sources, including spatial demographic data, reported rubella and congenital rubella syndrome (CRS) cases, and traveler lodging statistics, were employed. Geospatial information for Japan's 230,300 small geographic areas was analyzed, and HI (hemagglutination inhibition) titers were examined by age and sex. Seroconversion was defined as an HI titer ≥ 1:32 or 1:16, indicating protective immunity. Geospatial maps illustrated the distribution of susceptible individuals per square kilometer, emphasizing high-risk urban areas like Tokyo and Osaka. Demographic shifts in the working-age population were assessed. RESULTS: Susceptible individuals cluster in densely populated urban centers, persisting despite demographic changes. The study highlights areas at risk of increased susceptibility, particularly with an HI titer cut-off of 1:16. Foreign travelers pose potential rubella importation risks as travel volume to Japan rises. To prevent epidemics and congenital rubella syndrome burden, achieving and sustaining herd immunity in high-risk areas is crucial. CONCLUSIONS: This study offers a comprehensive assessment of vulnerability in densely populated Japanese regions. Integrating population statistics with seroepidemiological data enhances our understanding of population immunity, guiding resource allocation for supplementary vaccination planning. To avert rubella epidemics, high-risk locations must bolster indirect protection through herd immunity, ultimately preventing congenital rubella syndrome.

Post-campaign coverage evaluation of a measles and rubella supplementary immunization activity in five districts in India, 2019-2020.

BACKGROUND: In alignment with the Measles and Rubella (MR) Strategic Elimination plan, India conducted a mass measles and rubella vaccination campaign across the country between 2017 and 2020 to provide a dose of MR containing vaccine to all children aged 9 months to 15 years. We estimated campaign vaccination coverage in five districts in India and assessed campaign awareness and factors associated with vaccination during the campaign to better understand reasons for not receiving the dose. METHODS AND FINDINGS: Community-based cross-sectional serosurveys were conducted in five districts of India among children aged 9 months to 15 years after the vaccination campaign. Campaign coverage was estimated based on home-based immunization record or caregiver recall. Campaign coverage was stratified by child- and household-level risk factors and descriptive analyses were performed to assess reasons for not receiving the campaign dose. Three thousand three hundred and fifty-seven children aged 9 months to 15 years at the time of the campaign were enrolled. Campaign coverage among children aged 9 months to 5 years documented or by recall ranged from 74.2% in Kanpur Nagar District to 90.4% in Dibrugarh District, Assam. Similar coverage was observed for older children. Caregiver awareness of the campaign varied from 88.3% in Hoshiarpur District, Punjab to 97.6% in Dibrugarh District, Assam, although 8% of children whose caregivers were aware of the campaign were not vaccinated during the campaign. Failure to receive the campaign dose was associated with urban settings, low maternal education, and lack of school attendance although the associations varied by district. CONCLUSION: Awareness of the MR vaccination campaign was high; however, campaign coverage varied by district and did not reach the elimination target of 95% coverage in any of the districts studied. Areas with lower coverage among younger children must be prioritized by strengthening the routine immunization programme and implementing strategies to identify and reach under-vaccinated children.

Is vaccination against measles, mumps, and rubella associated with reduced rates of antibiotic treatments among children below the age of 2 years? Nationwide register-based study from Denmark, Finland, Norway, and Sweden.

OBJECTIVES: Previous studies have shown that vaccination against measles, mumps, and rubella (MMR) may have beneficial non-specific effects, reducing the risk of infections not targeted by the vaccine. We investigated if MMR vaccine given after the third dose of diphtheria-tetanus-acellular pertussis vaccine (DTaP3), was associated with reduced rates of antibiotic treatments. METHODS: Register-based cohort study following children from the age of recommended MMR vaccination until age 2 years. We included 831,287 children born in Denmark, Finland, Norway, and Sweden who had received DTaP3 but not yet MMR vaccine. Cox proportional hazards regression with age as the underlying timescale and vaccination status as a time-varying exposure was used to estimate covariate-adjusted Hazard Ratios (aHRs) and inverse probability of treatment weighted (IPTW) HRs of antibiotic treatments. Summary estimates were calculated using random-effects meta-analysis. RESULTS: Compared with only having received DTaP3, receipt of MMR vaccine after DTaP3 was associated with reduced rates of antibiotic treatments in all countries: the aHR was 0.92 (0.91-0.93) in Denmark, 0.92 (0.90-0.94) in Finland, 0.84 (0.82-0.85) in Norway, and 0.87 (0.85-0.90) in Sweden, yielding a summary estimate of 0.89 (0.85-0.93). A stronger beneficial association was seen in a negative control exposure analysis comparing children vaccinated with DTaP3 vs two doses of DTaP. CONCLUSIONS: Across the Nordic countries, receipt of MMR vaccine after DTaP3 was associated with an 11% lower rate of antibiotic treatments. The negative control analysis suggests that the findings are affected by residual confounding. Findings suggest that potential non-specific effects of MMR vaccine are of limited clinical and public health importance for the milder infections treated out-of-hospital in the Nordic setting.

A paired measles-rubella catch-up campaign in Sichuan China to stop an outbreak and strengthen local immunization programs.

BACKGROUND: China has been working towards measles elimination, but in 2017, measles outbreaks occurred in Ganzi and Aba prefectures of Sichuan province, representing 95% of all provincial cases and jeopardizing measles elimination. METHODS: During March and April 2017, high-performing prefectures were paired with outbreak and other interested counties to jointly conduct a measles-rubella (MR) catch-up campaign, build population immunity, and strengthen the counties' programs. RESULTS: House-to-house search identified 88,383 children in Ganzi that lacked MCV vaccination; 85,144 (96.34%) were vaccinated. Search identified 33,683 children in Aba who were not vaccinated against measles; 33,074 (98.19%) were vaccinated. The supporting prefectures helped install Immunization Information Systems and enroll unvaccinated children into the immunization program.The outbreak ended within a month and incidence has remained low for the subsequent six years. CONCLUSION: A paired catch-up campaign represents an effective model of using measles elimination strategies to strengthen local immunization programs for long-term program effectiveness.

Implications of Measles Inclusion by Commercial Syndromic Polymerase Chain Reaction Panels - United States, May 2022-April 2023.

Syndromic polymerase chain reaction (PCR) panels are used to test for pathogens that can cause rash illnesses, including measles. Rash illnesses have infectious and noninfectious causes, and approximately 5% of persons experience a rash 7-10 days after receipt of a measles, mumps, and rubella (MMR) vaccine. MMR vaccine includes live attenuated measles virus, which is detectable by PCR tests. No evidence exists of person-to-person transmission of measles vaccine virus, and illness does not typically result among immunocompetent persons. During September 2022-January 2023, the Tennessee Department of Health received two reports of measles detected by syndromic PCR panels. Both reports involved children (aged 1 and 6 years) without known risk factors for measles, who were evaluated for rash that occurred 11-13 days after routine MMR vaccination. After public health responses in Tennessee determined that both PCR panels had detected measles vaccine virus, six state health departments collaborated to assess the frequency and characteristics of persons receiving a positive measles PCR panel test result in the United States. Information was retrospectively collected from a commercial laboratory testing for measles in syndromic multiplex PCR panels. During May 2022-April 2023, among 1,548 syndromic PCR panels, 17 (1.1%) returned positive test results for measles virus. Among 14 persons who received a positive test result and for whom vaccination and case investigation information were available, all had received MMR vaccine a median of 12 days before specimen collection, and none had known risk factors for acquiring measles. All positive PCR results were attributed to detection of measles vaccine virus. Increased awareness among health care providers about potential measles detection by PCR after vaccination is needed. Any detection of measles virus by syndromic PCR testing should be immediately reported to public health agencies, which can use measles vaccination history and assessment of risk factors to determine the appropriate public health response. If a person recently received MMR vaccine and has no risk factors for acquiring measles, additional public health response is likely unnecessary.

A review of potential use cases for measles-rubella, measles-mumps-rubella, and typhoid-conjugate vaccines presented on microarray patches.

As an innovative vaccine delivery technology, vaccine microarray patches could have a meaningful impact on routine immunization coverage in low- and middle-income countries, and vaccine deployment during epidemics and pandemics. This review of the potential use cases for a subset of vaccine microarray patches in various stages of clinical development, including measles-rubella, measles-mumps-rubella, and typhoid conjugate, highlights the breadth of their applicability to support immunization service delivery and their potential scope of utilization within national immunization programs. Definition and assessment of the use cases for this novel vaccine presentation provide important insights for vaccine developers and policymakers into the strengths of the public health and commercial value propositions, and the preparatory requirements for public health systems for the future rollout of vaccine microarray patches. An in-depth understanding of use cases for vaccine microarray patches serves as a foundational input to overcoming the remaining technical, regulatory, and financial challenges. Additional efforts will help to realize the potential of vaccine microarray patches as part of the global effort to improve the coverage and equity of national immunization programs.

Measles vaccination - An underestimated prevention measure: Analyzing a fatal case in Hildesheim, Germany.

Measles and rubella are targeted for elimination in the WHO region Europe. To reach the elimination goal, vaccination coverage of 95% must be achieved and sustained, the genotype information has to be provided for 80% of all outbreaks and transmission chains of a certain variant must not be detected for >12 months. The latter information is collected at Germany's National Reference Center Measles, Mumps, Rubella (NRC MMR). We describe here an outbreak of measles occurring in Hildesheim. The outbreak comprised 43 cases and lasted 14 weeks. Surprisingly, a high number of vaccination failures was observed since 11 cases had received two doses of the MMR vaccine and 4 additional cases were vaccinated once. A 33-year-old woman passed away during the outbreak. She was the mother of 5 children between 4 and 16 years of age. Two schoolchildren contracted measles and passed it on to the rest of the family. Due to delivery bottlenecks, the vaccination of the mother was delayed. She developed measles-like symptoms 3 days after vaccination and was found dead on the morning of day 8 after vaccination. A post-mortem examination was done to identify the cause of death. Moreover, molecular characterization of the virus was performed to analyze whether she was infected by the wildtype virus circulating at that time in Hildesheim or whether the vaccine may have been a concomitant and aggravating feature of her death. The result showed that the samples taken from her at the time of death and during necropsy contained the wildtype measles virus variant corresponding to MVs/Gir Somnath.IND/42.16 (WHO Seq-ID D8-4683) that fueled the Hildesheim outbreak and circulated in Germany from March 2018 to March 2020. The vaccine virus was not detected. Moreover, two aspects uncovered by the post-mortem examination were remarkable; the woman died from giant cell pneumonia, which is a complication seen in immune-suppressed individuals and she was actively using cannabis. THC is known to influence the immune system, but literature reports describing the effects are limited.

Neutralizing antibody titers against D8 genotype and persistence of measles humoral and cell-mediated immunity eight years after the first dose of measles, mumps, and rubella vaccine in Brazilian children.

OBJECTIVE: Assess the level of measles vaccine-induced neutralizing antibodies against the D8 genotype and the persistence of humoral and cell-mediated immunity in children who received their first dose of the measles, mumps, and rubella vaccine eight years previously. METHODS: Measles-specific IgG and neutralizing antibodies were determined in serum using ELISA and plaque reduction neutralization test, respectively. Cellular response was evaluated from peripheral blood mononuclear cells (PBMC). IFN-γ-secreting cells, memory B and T cells, and immunological mediators were assayed by ELISpot, flow cytometry, and multiplex liquid microarray assay, respectively. RESULTS: Antibody concentrations declined over time; however, the vaccine-induced neutralizing antibodies' effect against D8 and vaccinal genotypes persisted. PBMC stimulated with the vaccine virus exhibited specific IFN- γ-measles-secreting responses in most participants. Participants with high levels of neutralizing antibodies showed a higher proportion of activated B cells compared to participants with low levels of neutralizing antibodies, while proportions of memory CD4+ and CD8+ T cells were similar between these groups. PBMC supernatant cytokine levels showed a significant difference between stimulated and non-stimulated conditions for IL-2, TNF-α, IL-10, and CXCL10. CONCLUSION: Despite the decline in antibody concentrations over time, the participants still demonstrated neutralizing capacity against the measles D8 genotype five to eight years after the second dose of the measles, mumps, and rubella vaccine. Additionally, most of the enrolled children exhibited cell-mediated immunity responses to measles virus stimulation.

Trend of measles-rubella vaccination coverage and impact on measles epidemiology in the Savannah Region, Ghana; 2018-2022: A secondary data analysis.

INTRODUCTION: Ghana witnessed an outbreak of measles in 2022 following the COVID-19 pandemic, and Savannah Region was among the regions severely impacted. The objective of this study was to conduct trend analysis of measles case incidence and measles-rubella (MR) vaccination coverage in the Savannah Region to identify gaps and propose remedial actions to mitigate future outbreaks of vaccine preventable diseases (VPDs). METHODS: Analysis of measles surveillance and measles-rubella vaccination data for 2018-2022 was conducted to assess relationship between immunization coverage and measles case incidence. Data were extracted from the District Health Information Management System (DHIMS) platform and loaded into Microsoft Excel 16.0 spreadsheet for analysis. Coverages for first (MR1) and second (MR2) doses of measles-rubella vaccination, dropout rates, and measles incidence (per 100,000) were calculated. RESULTS: The coverage trend for both vaccine doses followed similar trajectories, increasing from 2018 to a peak in 2019, and declining sequentially thereafter to the lowest (for the study period) in 2022. Generally, MR1/MR2 dropout rate was high across all districts during the entire study period. The regional incidence of confirmed measles rose sharply from less than 1/1,000,000 in 2018-2021 to 94 in 2022. Wide variations in vaccination coverage and dropout rates were observed among the districts. There was moderate to fairly strong negative correlation between MR vaccination coverage and measles case incidence. CONCLUSIONS: The MR vaccination coverage in the Savannah Region declined probably due to pre-existing weaknesses in the immunization programme accentuated by impact of the COVID-19 pandemic. The lowered population immunity likely contributed to occurrence of the measles outbreak in 2022. Pragmatic actions are needed to catch-up on missed children, restore coverage to pre-pandemic levels, and strengthen the immunization programme as part of global efforts towards achieving the Immunization Agenda 2030 (IA2030) trajectory.

Immunity Rates of Live Viral Vaccines in Pediatric Renal Transplant Candidates: A Single-Center Experience.

OBJECTIVES: Solid-organ transplant recipients are at an increased risk of severe infections due to their immunosuppressed state. Despite the recommendation of routine screening and vaccination before transplant to mitigate this danger, vaccination rates in these patients are still below desirable levels. We aimed to investigate the prevalence of positive antibody rates for measles, mumps, rubella, and varicella among children who are candidates for renal transplant. MATERIALS AND METHODS: This retrospective study was conducted at a single center and included 144 pediatric kidney transplant patients for the past 7 years. We reviewed the medical records of all participants to evaluate their serologic status for measles, mumps, rubella, and varicella viruses before kidney transplant. RESULTS: In this study, 144 pediatric kidney transplant candidates (mean age 11.5 years, 56.9% male) were enrolled, and the most frequent causes of the chronic renal disease were congenital anomalies of the kidney and urinary tract and glomerular diseases (32.6%). Seropositivity rates for measles, mumps, rubella, and varicella were 59.0%, 31.9%, 46.5%, and 43.6%, respectively, and all patients who tested negative for antibodies were vaccinated before transplant. Younger age at transplant (OR = 0.909, 95% CI = 0.840-0.923; P = .017) and congenital anomalies of the kidney and urinary tract (OR = 3.46, 95% CI = 1.1548-7.735; P = .002) were significantly associated with increased measles seropositivity, although no significant associations were observed for the other viruses. CONCLUSIONS: We observed lower seropositivity rates for measles, mumps, rubella, and varicella in pediatric kidney transplant patients versus healthy children and other previous studies. It is essential to address these suboptimal rates to protect the health of these vulnerable patients. Future research should focus on targeted interventions to improve vaccination rates and outcomes in this population.

Live-attenuated vaccination for measles, mumps, and rubella in pediatric liver transplantation.

BACKGROUND: Infections are a serious short- and long-term problem after pediatric organ transplantation. In immunocompromised patients, they can lead to transplant rejection or a severe course with a sometimes fatal outcome. Vaccination is an appropriate means of reducing morbidity and mortality caused by vaccine-preventable diseases. Unfortunately, due to the disease or its course, it is not always possible to establish adequate vaccine protection against live-attenuated viral vaccines (LAVVs) prior to transplantation. LAVVs such as measles, mumps, and rubella (MMR) are still contraindicated in solid organ transplant recipients receiving immunosuppressive therapy (IST), thus creating a dilemma. AIM: This review discusses whether, when, and how live-attenuated MMR vaccines can be administered effectively and safely to pediatric liver transplant recipients based on the available data. MATERIAL AND METHODS: We searched PubMed for literature on live-attenuated MMR vaccination in pediatric liver transplantation (LT). RESULTS: Nine prospective observational studies and three retrospective case series were identified in which at least 833 doses of measles vaccine were administered to 716 liver transplant children receiving IST. In these selected patients, MMR vaccination was well tolerated and no serious adverse reactions to the vaccine were observed. In addition, an immune response to the vaccine was demonstrated in patients receiving IST. CONCLUSION: Due to inadequate vaccine protection in this high-risk group, maximum efforts must be made to ensure full immunization. MMR vaccination could also be considered for unprotected patients after LT receiving IST following an individual risk assessment, as severe harm from live vaccines after liver transplantation has been reported only very rarely. To this end, it is important to establish standardized and simple criteria for the selection of suitable patients and the administration of the MMR vaccine to ensure safe use.

Progress Toward Rubella and Congenital Rubella Syndrome Elimination - Worldwide, 2012-2022.

Rubella virus is a leading cause of vaccine-preventable birth defects. Infection during pregnancy can result in miscarriage, fetal death, stillbirth, or a constellation of birth defects, including cataracts, deafness, heart defects, and developmental delay, known as congenital rubella syndrome (CRS). A single dose of rubella-containing vaccine can provide lifelong protection against rubella. The Global Vaccine Action Plan 2011-2020 included a target to achieve elimination of rubella in at least five of the six World Health Organization (WHO) regions by 2020, and rubella elimination is a critical goal of the Immunization Agenda 2030. This report updates a previous report and describes progress toward rubella and CRS elimination during 2012-2022. During 2012-2022, among 194 WHO countries, the number that included rubella-containing vaccine (RCV) in their immunization schedules increased from 132 (68%) to 175 (90%) and the percentage of the world's infants vaccinated against rubella increased from 40% to 68%. Reported rubella cases declined 81%, from 93,816 in 2012 to 17,407 in 2022. Verification of rubella elimination was achieved in 98 (51%) of 194 countries by 2022, an increase from 84 (43%) countries in 2019. Despite significant progress in the introduction of RCV into routine immunization programs worldwide, approximately 25 million infants annually still do not have access to RCV. Nevertheless, even in complex settings, the increasing number of countries that have achieved and sustained rubella elimination demonstrates progress toward global rubella elimination.

Effectiveness of the combined MMRV Priorix-Tetra™ vaccine against varicella in a large Italian region: A case-control study.

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.