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Global measles vaccine coverage has stagnated at approximately 85% for over a decade. By simplifying vaccine logistics and administration, the measles and rubella microarray patch (MR-MAP) may improve coverage. Clinical trials have demonstrated similar safety and immunogenicity in 9-month-old infants for MR-MAPs compared with syringe-and-needle vaccination. To aid commercialization, we present estimates of MR-MAP demand. We created a spreadsheet-based tool to estimate demand for MR-MAPs using data from 180 WHO countries during 2000–2016. Five immunization scenarios were analyzed: (1a) Supplementary Immunization Activities (SIAs) in Gavi, the Vaccine Alliance (Gavi)-eligible countries and (1b) WHO countries where preventive SIAs are routinely conducted; (2) SIAs and outbreak response immunization in all WHO countries; (3) routine immunization (RI) and SIAs in six high-burden measles countries (the Democratic Republic of the Congo, Ethiopia, India, Indonesia, Nigeria, and Pakistan); (4) RI and SIAs in six high-burden countries and Gavi-eligible countries; and (5) hard-to-reach populations. MR-MAP demand varied greatly across scenarios. Forecasts for 2025–2034 estimate from 137 million doses in hard-to-reach populations (scenario 5) to 2.587 billion doses for RI and SIAs in six high-burden countries and Gavi-eligible countries (scenario 4). When policymakers and manufacturers assess MR-MAP demand, they may consider multiple scenarios to allow for a complete consideration of potential markets and public health needs. [ABSTRACT FROM AUTHOR]

Abstract Introduction Measles is an extremely contagious viral disease that can be prevented through vaccination. It is caused by the measles virus and presents with symptoms such as high fever, cough, runny nose, conjunctivitis, and a distinctive rash. Complications may include pneumonia, diarrhoea, and neurological issues. The disease spreads through respiratory droplets and continues to pose a significant public health challenge, especially in Africa, despite vaccination efforts. Objective This systematic review and meta-analysis aim to estimate the pooled vaccine effectiveness of measles vaccines among African children, providing insights into immunization program success and informing policy decisions on vaccine distribution and resource allocation. Methods Following PRISMA guidelines, search was conducted in databases including PubMed/Medline, Science Direct, HINARI, Cochrane/Wiley library, Europe PMC, and grey literatures like Google Scholar up to March 2024. Cross-sectional studies assessed measles vaccine effectiveness in African children aged nine months and above were included. Data was extracted using JBI extraction tool and entered into microsoft excel and analysed via STATA version 20.1 using random effect model. Results From 5295 identified articles, 18 met the inclusion criteria, encompassing 26,470 children from 13 African countries. The pooled measles vaccine effectiveness was 68.58%, with significant heterogeneity (I2 = 99.66%, p

Abstract Although neutralizing antibody is an established correlate of protection for measles, T cell-mediated responses play at least two critical roles in immunity to measles: first, through provision of ‘help’ enabling robust humoral immune responses; and second, through clearance of measles virus-infected cells. Previously, we identified 13 measles-derived peptides that bound to human leukocyte antigen (HLA) molecules in Priess cells infected with measles virus. In this study, we evaluated the immunogenicity of these peptides in a transgenic mouse model. Our results demonstrated that these peptides induced Th1-biased immune responses at varying levels. Of the 13 peptides, the top four immunogenic peptides were further selected for a viral challenge study in mice. A vaccine based on a combination of these four peptides reduced morbidity and weight loss after viral challenge compared to placebo. Our results emphasize the potential of T cell-mediated, peptide-based vaccines against measles.

Although neutralizing antibody is an established correlate of protection for measles, T cell-mediated responses play at least two critical roles in immunity to measles: first, through provision of 'help' enabling robust humoral immune responses; and second, through clearance of measles virus-infected cells. Previously, we identified 13 measles-derived peptides that bound to human leukocyte antigen (HLA) molecules in Priess cells infected with measles virus. In this study, we evaluated the immunogenicity of these peptides in a transgenic mouse model. Our results demonstrated that these peptides induced Th1-biased immune responses at varying levels. Of the 13 peptides, the top four immunogenic peptides were further selected for a viral challenge study in mice. A vaccine based on a combination of these four peptides reduced morbidity and weight loss after viral challenge compared to placebo. Our results emphasize the potential of T cell-mediated, peptide-based vaccines against measles. [ABSTRACT FROM AUTHOR]

Measles is a highly transmissible systemic viral infection associated with substantial mortality primarily due to secondary infections. Measles induces lifelong immunity to reinfection but loss of immunity to other pathogens. An attenuated live virus vaccine is highly effective, but lapses in delivery have resulted in increasing cases worldwide. Although the primary cause of failure to control measles is failure to vaccinate, waning vaccine-induced immunity and the possible emergence of more virulent virus strains may also contribute. [ABSTRACT FROM AUTHOR]

Introduction: Ethiopia introduced a second dose of measles-containing vaccine (MCV2) in 2019 to provide further protection against measles and further progress toward elimination. However, the sub-optimal coverage of both MCV1 and MCV2 suggest challenges with vaccine uptake. In this qualitative study, we explored barriers to the uptake of MCV2 among caregivers, community leaders, and healthcare workers (HCWs). Method: A qualitative study was conducted between mid-April and mid-May 2021. We selected ten woredas (districts) in the Oromia Region, Ethiopia, stratified by settlement type (urban/rural), MCV1 coverage (high ≥ 80%; low < 80%), and history of measles outbreaks between June 2019 and June 2020. Experiences surrounding barriers to MCV2 uptake were discussed via focus group discussions (FGDs) and in-depth interviews (IDIs) with caregivers of children 12–23 and 24–36 months and key informant interviews (KIIs) with HCWs who administer vaccines and with community leaders. Participants were recruited via snowball sampling. Recorded data were transcribed, translated to English, and analyzed using ATLAS.ti v.09. Results: Forty FGDs and 60 IDIs with caregivers, 60 IDIs with HCWs, and 30 KIIs with community leaders were conducted. Barriers among caregivers included lack of knowledge and awareness about MCV2 and the vaccination schedule, competing priorities, long wait times at health facilities, vaccine unavailability, negative interactions with HCWs, and transportation challenges. At the community level, trusted leaders felt they lacked adequate knowledge about MCV2 to address caretakers' questions and community misconceptions. HCWs felt additional training on MCV2 would prepare them to better respond to caretakers' concerns. Health system barriers identified included the lack of human, material, and financial resources to deliver vaccines and provide immunization outreach services, which caretakers reported as their preferred way of accessing immunization. Conclusions: Barriers to MCV2 uptake occur at multiple levels of immunization service delivery. Strategies to address these barriers include tools to help caretakers track appointments, enhanced community engagement, HCW training to improve provider–client interactions and MCV2 knowledge, and efforts to manage HCW workload. [ABSTRACT FROM AUTHOR]

This study investigated the demographic and clinical characteristics of measles patients who presented to the emergency department, analyzing the relationship with their vaccination status. This single-center and retrospective study included 110 patients with confirmed measles. The patients were categorized based on their clinical outcomes (ambulatory monitoring and inpatient) and vaccination status (≥2 doses vs. <2 doses). We compared demographic and clinical characteristics between these patient groups. Our study included 57 females (51.82%) and 53 males (48.18%), with a mean age of 9.32±10.47 years. Seventy percent of patients were aged ≤10 years. The most common symptoms upon admission were fever (77.27%), fatigue (49.09%), and cough (35.45%). Complications included otitis media (6.36%), pneumonia (2.73%), and seizure (0.91%). Despite no significant differences in hospitalization and severe disease between those who received ≥2 doses of the measles vaccine and those who did not, all hospitalized patients were unvaccinated. Furthermore, 81.8% of complicated measles cases occurred in patients who were not vaccinated with the effective dose. Our study indicates that measles is more severe in unvaccinated patients compared to vaccinated cases. All hospitalizations and most complications were observed in the unvaccinated group. Additionally, most cases were in the pediatric age group. [ABSTRACT FROM AUTHOR]

Objectives: Between 2003 and 2019, three trials (randomised controlled trials [RCTs]) in Guinea-Bissau randomised infants to an early 2-dose measles vaccine (MV) schedule at 4 and 9 months vs standard MV at 9 months. The RCTs produced contradictory mortality results; the effect being beneficial in the 2-dose group in the first but tending to have higher mortality in the last two RCTs. We hypothesised that increased frequency of campaigns with oral polio vaccine (C-OPV) explained the pattern. Methods: We performed per-protocol analysis of individual-level survival data from the three RCTs in Cox proportional hazards models yielding hazard ratios (HR) for the 2-dose vs the 1-dose MV group. We examined whether timing of C-OPVs and early administration of OPV0 (birth to day 14) affected the HRs for 2-dose/1-dose MV. Results: The combined HR(2-dose/1-dose) was 0.79 (95% confidence interval: 0.62-1.00) for children receiving no C-OPV-before-enrolment, but 1.39 (0.97-1.99) for those receiving C-OPV-before-enrolment (homogeneity, P = 0.01). C-OPV-before-enrolment had a beneficial effect in the 1-dose group but tended to have a negative effect in the 2-dose group, especially in females. These effects were amplified further by early administration of OPV0. Conclusion: In the absence of C-OPVs, an early 2-dose MV strategy had beneficial effects on mortality, but frequent C-OPVs may have benefitted the 1-dose group more than the 2-dose MV group, leading to varying results depending on the intensity of C-OPVs.

Abstract Background Ethiopia has made considerable progress toward measles elimination. Despite ongoing efforts, the country remains among those with the highest number of children missing their initial dose of measles vaccine, and the disease continues to be a public health emergency. The barriers within the health system that hinder the first dose of measles immunization have not been thoroughly investigated. This study aims to identify these barriers within the Ethiopian context. Methods Qualitative research, using purposive expert sampling to select key informants from health organizations in Addis Ababa, Ethiopia was employed. We conducted in-depth face-to-face interviews using a semi-structured interview guide. A thematic analysis based on the World Health Organization’s health systems building blocks framework was conducted. Results The study uncovered substantial health system barriers to the uptake of the first dose of the measles vaccine in Ethiopia. These barriers include; restricted availability of immunization services, vaccine stockouts, shortage of cold chain technologies, data inaccuracy resulting from deliberate data falsification or accidental manipulation of data, as well as data incompleteness. Conclusion Our research highlighted significant health system barriers to MCV1 immunization, contributing to unmet EPI targets in Ethiopia. Our results suggest that to accelerate the country towards measles elimination, there is an urgent need to improve the health systems components such as service delivery, information systems, as well as access to vaccine and cold chain technologies.

Measles is a highly contagious viral disease, and hence, sufficient herd immunity is obligatory to prevent infection transmission. Measles is still a cause of considerable disease burden globally, mainly in children. During a national measles outbreak in Israel in 2018–2019, the peak incidence rates occurred in the Jerusalem district. Most measles cases in the Jerusalem district (75.5%, 1702) were observed in children younger than 15 years of age, 49.2% (1109) were in children under 5 years of age, and 18.9% (425) were in infants under 1 year of age. The routine measles vaccination schedule includes two doses at 1 and 6 years of age. Most cases (1828, 81.1%) were unvaccinated (zero measles vaccine doses). These cases comprised the 425 affected infants under 1 year of age, who were ineligible for vaccination, along with the 1403 children over 1 year of age, who were otherwise unvaccinated. This study aimed to describe the epidemiologic and laboratory features of this measles outbreak, and to investigate case ascertainment (laboratory confirmed compared to epidemiologically confirmed cases). The study population included 2254 measles cases notified during the period spanning June 2018 to May 2019 in the Jerusalem district (incidence rate 176 per 10,000 population). Of the 2254 cases, 716 (31.8%) were laboratory confirmed, and 1538 (68.2%) were confirmed as epidemiologically linked. Most laboratory confirmed cases (420, 58.7%) underwent real-time PCR tests. Serological tests (measles IgM and IgG) were used in 189 (26.4%) cases, and a combination of RT-PCR and serology was used in 107 (14.9%) cases. In a multivariate model analysis, the variables significantly associated (after adjustment) with higher odds for laboratory confirmation included month of disease onset (late), additional measles cases in the household (single case), place of medical treatment (hospital; either emergency department, or hospitalization) and vaccination status (at least one prior vaccine dose). The measles outbreak described demonstrates the urgency of addressing vaccination gaps with appropriate outbreak prevention programs. The road to measles elimination needs to be paved with robust public health infrastructure, excellent field epidemiology for outbreak surveillance, investigation, and control, and laboratory proficiency. [ABSTRACT FROM AUTHOR]

B cell transcriptomic signatures hold promise for the early prediction of vaccineinduced humoral immunity and vaccine protective efficacy. We performed a longitudinal study in 232 healthy adult participants before/after a 3rd dose of MMR (MMR3) vaccine. We assessed baseline and early transcriptional patterns in purified B cells and their association with measles-specific humoral immunity after MMR vaccination using two analytical methods ("per gene" linear models and joint analysis). Our study identified distinct early transcriptional signatures/genes following MMR3 that were associated with measles-specific neutralizing antibody titer and/or binding antibody titer. The most significant genes included: the interleukin 20 receptor subunit beta/IL20RB gene (a subunit receptor for IL-24, a cytokine involved in the germinal center B cell maturation/response); the phorbol-12-myristate-13-acetate-induced protein 1/PMAIP1, the brain expressed X-linked 2/BEX2 gene and the B cell Fas apoptotic inhibitory molecule/FAIM, involved in the selection of high-affinity B cell clones and apoptosis/regulation of apoptosis; as well as IL16 (encoding the B lymphocytederived IL-16 ligand of CD4), involved in the crosstalk between B cells, dendritic cells and helper T cells. Significantly enriched pathways included B cell signaling, apoptosis/regulation of apoptosis, metabolic pathways, cell cycle-related pathways, and pathways associated with viral infections, among others. In conclusion, our study identified genes/pathways linked to antigen-induced B cell proliferation, differentiation, apoptosis, and clonal selection, that are associated with, and impact measles virus-specific humoral immunity after MMR vaccination. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Ethiopia has made considerable progress toward measles elimination. Despite ongoing efforts, the country remains among those with the highest number of children missing their initial dose of measles vaccine, and the disease continues to be a public health emergency. The barriers within the health system that hinder the first dose of measles immunization have not been thoroughly investigated. This study aims to identify these barriers within the Ethiopian context. Methods: Qualitative research, using purposive expert sampling to select key informants from health organizations in Addis Ababa, Ethiopia was employed. We conducted in-depth face-to-face interviews using a semi-structured interview guide. A thematic analysis based on the World Health Organization's health systems building blocks framework was conducted. Results: The study uncovered substantial health system barriers to the uptake of the first dose of the measles vaccine in Ethiopia. These barriers include; restricted availability of immunization services, vaccine stockouts, shortage of cold chain technologies, data inaccuracy resulting from deliberate data falsification or accidental manipulation of data, as well as data incompleteness. Conclusion: Our research highlighted significant health system barriers to MCV1 immunization, contributing to unmet EPI targets in Ethiopia. Our results suggest that to accelerate the country towards measles elimination, there is an urgent need to improve the health systems components such as service delivery, information systems, as well as access to vaccine and cold chain technologies. [ABSTRACT FROM AUTHOR]

Information regarding the detection perioid of measles vaccine virus (MeVV) RNA in human nasopharyngeal samples and measles-specific antibodies following measles-mumps-rubella (MMR) vaccination is limited. During contact tracing for a measles outbreak at a hospital in Republic of Korea, 4 out of 206 children vaccinated with MMR underwent real-time RT-PCR assay for measles and measles-specific antibodies test. Measles virus RNA was detected in 2 children, all of which was vaccine virus strain RNA (genotype A). In a healthy 27-month-old boy, MeVV RNA was detected 448 days after MMR vaccination. Measles-specific IgM was positive 1097 days following vaccination in a 4-year-old girl. MeVV RNA and measles-specific IgM were detected for a considerable period following primary MMR vaccination. Physicians should exercise caution when interpreting positive RT-PCR results for MeVV or measles-specific IgM from a child with measles-associated symptoms who has been recently vaccinated against measles.

Global measles vaccine coverage has stagnated at approximately 85% for over a decade. By simplifying vaccine logistics and administration, the measles and rubella microarray patch (MR-MAP) may improve coverage. Clinical trials have demonstrated similar safety and immunogenicity in 9-month-old infants for MR-MAPs compared with syringe-and-needle vaccination. To aid commercialization, we present estimates of MR-MAP demand. We created a spreadsheet-based tool to estimate demand for MR-MAPs using data from 180 WHO countries during 2000–2016. Five immunization scenarios were analyzed: (1a) Supplementary Immunization Activities (SIAs) in Gavi, the Vaccine Alliance (Gavi)-eligible countries and (1b) WHO countries where preventive SIAs are routinely conducted; (2) SIAs and outbreak response immunization in all WHO countries; (3) routine immunization (RI) and SIAs in six high-burden measles countries (the Democratic Republic of the Congo, Ethiopia, India, Indonesia, Nigeria, and Pakistan); (4) RI and SIAs in six high-burden countries and Gavi-eligible countries; and (5) hard-to-reach populations. MR-MAP demand varied greatly across scenarios. Forecasts for 2025–2034 estimate from 137 million doses in hard-to-reach populations (scenario 5) to 2.587 billion doses for RI and SIAs in six high-burden countries and Gavi-eligible countries (scenario 4). When policymakers and manufacturers assess MR-MAP demand, they may consider multiple scenarios to allow for a complete consideration of potential markets and public health needs.

Objective: This study aimed to determine the measles seroprevalence and related factors in healthcare professionals working in units with a high risk of encountering measles cases in Dokuz Eylül University Hospital. Methods: This cross-sectional study was conducted between June 2018 and September 2019. The study population consisted of all healthcare professionals working as specialist doctors, trainee doctors, and nurses in Pediatric hospital, Adult Emergency, Family Medicine, Infectious Diseases, and Clinical Microbiology and Dermatology departments. Healthcare professionals who agreed to participate were interviewed face-to-face, including questions about independent variables such as gender, age, occupation, working unit, and history of disease. The dependent variable was the seropositivity/seronegativity status of the participants, which was determined according to the quantitative anti-Rubella IgG antibody levels measured by the ELISA method from serum samples. P< 0.05 was accepted as statistical significance. Results: During the study period, 326 out of 368 healthcare professionals in the units in question agreed to participate (88.5%). Of the participants, 79 (24.2%) were seronegative and 247 (75.8%) were seropositive. Seronegativity increased with decreasing age (p=0.036) when evaluated according to age groups. Seronegativity was 29.4% in the 20-29 age group, 19.2% in the 30-39 age group, and 10.7% in the 40-49 age group, while all participants aged 50 years and over were seropositive. Seropositivity was not affected by gender (p=0.260), occupation (p=0.364), or department (p=0.129). The study group's median anti-measles IgG antibody level was 654 IU/ml (65-5000 IU/ml). The median antibody level increased with increasing age (p<0.001). Conclusion: In our study, a significant proportion of healthcare professionals at risk for encountering measles were susceptible. [ABSTRACT FROM AUTHOR]

Background The Dengvaxia® (dengue vaccine) controversy has been identified as one of the main reasons for the measles vaccine hesitancy in the Philippines. Our study aimed to identify various issues related to the Dengvaxia® controversy and to link these issues with the social perspective of measles vaccine refusal. Methods Semi-structured interviews and a focus group discussion using ethnography research were conducted with 41 parents and healthcare workers in Pasay City. Using Victor Turner's Social Drama Theory, our study identified existing social issues relating to the different angles of the Dengvaxia® controversy and the measles vaccine hesitancy. Results Misinformation on the failed Dengvaxia® rollout implementation has challenged the fundamental understanding of the importance of immunization programs. Our findings on vaccine hesitancy in the community showed a complex problem with compounded factors, including medical populism, moral panics and other social views. We described how Pasay City's clinic waiting room became a significantly important scenario where individuals often discuss information, concerns and experiences on vaccines and vaccine hesitancy. Conclusion Our study suggests that the Dengvaxia® controversy may reduce the measles vaccination confidence in the Philippines. Lack of transparency played a crucial role in this dilemma, producing a cascading effect on the other vaccines' safety. [ABSTRACT FROM AUTHOR]

B cell transcriptomic signatures hold promise for the early prediction of vaccine-induced humoral immunity and vaccine protective efficacy. We performed a longitudinal study in 232 healthy adult participants before/after a 3rd dose of MMR (MMR3) vaccine. We assessed baseline and early transcriptional patterns in purified B cells and their association with measles-specific humoral immunity after MMR vaccination using two analytical methods (“per gene” linear models and joint analysis). Our study identified distinct early transcriptional signatures/genes following MMR3 that were associated with measles-specific neutralizing antibody titer and/or binding antibody titer. The most significant genes included: the interleukin 20 receptor subunit beta/IL20RB gene (a subunit receptor for IL-24, a cytokine involved in the germinal center B cell maturation/response); the phorbol-12-myristate-13-acetate-induced protein 1/PMAIP1, the brain expressed X-linked 2/BEX2 gene and the B cell Fas apoptotic inhibitory molecule/FAIM, involved in the selection of high-affinity B cell clones and apoptosis/regulation of apoptosis; as well as IL16 (encoding the B lymphocyte-derived IL-16 ligand of CD4), involved in the crosstalk between B cells, dendritic cells and helper T cells. Significantly enriched pathways included B cell signaling, apoptosis/regulation of apoptosis, metabolic pathways, cell cycle-related pathways, and pathways associated with viral infections, among others. In conclusion, our study identified genes/pathways linked to antigen-induced B cell proliferation, differentiation, apoptosis, and clonal selection, that are associated with, and impact measles virus-specific humoral immunity after MMR vaccination.

Abstract Background Malaysia introduced the two dose measles-mumps-rubella (MMR) vaccine in 2004 as part of its measles elimination strategy. However, despite high historical coverage of MCV1 and MCV2, Malaysia continues to report high measles incidence. This study suggests a novel indicator for investigating population immunity against measles in the Malaysian population. Methods We define effective vaccine coverage (EVC) of measles as the proportion of a population vaccinated with measles-containing vaccine (MCV) and effectively protected against measles infection. A quantitative evaluation of EVC throughout the life course of Malaysian birth cohorts was conducted accounting for both vaccine efficacy (VE) and between-dose correlation (BdC). Measles vaccination coverage was sourced from WHO-UNICEF estimates of Malaysia’s routine immunisation coverage and supplementary immunisation activities (SIAs). United Nations World population estimates and projections (UNWPP) provided birth cohort sizes stratified by age and year. A step wise joint Bernoulli distribution was used to proportionate the Malaysian population born between 1982, the first year of Malaysia’s measles vaccination programme, and 2021, into individuals who received zero dose, one dose and multiple doses of MCV. VE estimates by age and doses received are then adopted to derive EVC. A sensitivity analysis was conducted using 1000 random combinations of BdC and VE parameters. Results This study suggests that no birth cohort in the Malaysian population has achieved > 95% population immunity (EVC) conferred through measles vaccination since the measles immunisation programme began in Malaysia. Conclusion The persistence of measles in Malaysia is due to pockets of insufficient vaccination coverage against measles in the population. Monitoring BdC through immunisation surveillance systems may allow for the identification of susceptible subpopulations (primarily zero-dose MCV individuals) and increase the coverage of individuals who are vaccinated with multiple doses of MCV. This study provides a tool for assessment of national-level population immunity of measles conferred through vaccination and does not consider subnational heterogeneity or vaccine waning. This tool can be readily applied to other regions and vaccine-preventable diseases.

Background: Despite the low measles antibody positivity rate among young healthcare workers (HCWs) who have previously received two doses of a measles-containing vaccine (MCV), whether an additional dose of MCV acts as a booster remains unknown. Thus, we aimed to evaluate the immune responses to a third dose of MCV in young HCWs. Methods: Hospital-wide measles seroprevalence was assessed using enzyme-linked immunosorbent assay (ELISA). The immunogenicity of a third dose of MCV was determined in young seronegative HCWs (born between 1986 and 1997) who had previously received a two-dose measles vaccination. Results: A total of 3033 (92.6%) HCWs had anti-measles immunoglobulin G. The lowest seropositivity rate was observed in HCWs aged 20–24 years (87.7%). In this group, HCWs who received a third dose of MCV had higher seropositivity than those who received a second dose (89.5% vs. 75.4%). A third dose of MCV was administered to 18 HCWs who did not have anti-measles IgG despite two doses. Neutralizing antibody titers increased significantly 4 weeks after the third vaccination. Although neutralizing antibody titers decreased 1 year post vaccination, 17 (94.4%) HCWs had medium (121–900 mIU/mL) or high (>900 mIU/mL) levels. Furthermore, the third dose of MCV increased the measles virus-specific T-cell effector function. Conclusions: The third dose of MCV induced a strong immune response against measles in young seronegative HCWs who had previously received a two-dose measles vaccination.

Objectives: Campaigns with measles vaccine (C-MV) are conducted to eradicate measles, but prior studies indicate that MV reduces non-measles mortality and hospital admissions too. We hypothesized that C-MV reduces death/hospital admission by 30%. Methods: Between 2016-2019, we conducted a non-blinded cluster-randomized trial randomizing village clusters in rural Guinea-Bissau to a C-MV targeting children aged 9-59 months. In Cox proportional hazards models, we assessed the effect of C-MV, obtaining hazard ratios (HR) for the composite outcome (death/hospital admission). We also examined potential effect modifiers. Results: Among 18,411 children (9636 in 111 intervention clusters/8775 in 110 control clusters), 379 events occurred (208 intervention/171 control) during a median follow-up period of 22 months. C-MV did not reduce the composite outcome (HR 1.12, 95% confidence interval 0.88-1.41). Mortality among enrolled children (5.3 intervention and 4.6 control, per 1000 person-years) was approximately half the pre-trial mortality rate (11.1 intervention and 8.9 control, per 1000 person-years). Neither planned nor explorative analyses of potential effect modifiers explained the contrasting results to prior studies. Conclusion: C-MV did not reduce overall mortality or hospital admission. This might be explained by changes in disease patterns, baseline differences in health status, and/or modifying effects of other campaigns during follow-up.

Introduction: Ethiopia introduced a second dose of measles-containing vaccine (MCV2) in 2019 to provide further protection against measles and further progress toward elimination. However, the sub-optimal coverage of both MCV1 and MCV2 suggest challenges with vaccine uptake. In this qualitative study, we explored barriers to the uptake of MCV2 among caregivers, community leaders, and healthcare workers (HCWs). Method: A qualitative study was conducted between mid-April and mid-May 2021. We selected ten woredas (districts) in the Oromia Region, Ethiopia, stratified by settlement type (urban/rural), MCV1 coverage (high ≥ 80%; low < 80%), and history of measles outbreaks between June 2019 and June 2020. Experiences surrounding barriers to MCV2 uptake were discussed via focus group discussions (FGDs) and in-depth interviews (IDIs) with caregivers of children 12–23 and 24–36 months and key informant interviews (KIIs) with HCWs who administer vaccines and with community leaders. Participants were recruited via snowball sampling. Recorded data were transcribed, translated to English, and analyzed using ATLAS.ti v.09. Results: Forty FGDs and 60 IDIs with caregivers, 60 IDIs with HCWs, and 30 KIIs with community leaders were conducted. Barriers among caregivers included lack of knowledge and awareness about MCV2 and the vaccination schedule, competing priorities, long wait times at health facilities, vaccine unavailability, negative interactions with HCWs, and transportation challenges. At the community level, trusted leaders felt they lacked adequate knowledge about MCV2 to address caretakers’ questions and community misconceptions. HCWs felt additional training on MCV2 would prepare them to better respond to caretakers’ concerns. Health system barriers identified included the lack of human, material, and financial resources to deliver vaccines and provide immunization outreach services, which caretakers reported as their preferred way of accessing immunization. Conclusions: Barriers to MCV2 uptake occur at multiple levels of immunization service delivery. Strategies to address these barriers include tools to help caretakers track appointments, enhanced community engagement, HCW training to improve provider–client interactions and MCV2 knowledge, and efforts to manage HCW workload.

Background: Malaysia introduced the two dose measles-mumps-rubella (MMR) vaccine in 2004 as part of its measles elimination strategy. However, despite high historical coverage of MCV1 and MCV2, Malaysia continues to report high measles incidence. This study suggests a novel indicator for investigating population immunity against measles in the Malaysian population. Methods: We define effective vaccine coverage (EVC) of measles as the proportion of a population vaccinated with measles-containing vaccine (MCV) and effectively protected against measles infection. A quantitative evaluation of EVC throughout the life course of Malaysian birth cohorts was conducted accounting for both vaccine efficacy (VE) and between-dose correlation (BdC). Measles vaccination coverage was sourced from WHO-UNICEF estimates of Malaysia's routine immunisation coverage and supplementary immunisation activities (SIAs). United Nations World population estimates and projections (UNWPP) provided birth cohort sizes stratified by age and year. A step wise joint Bernoulli distribution was used to proportionate the Malaysian population born between 1982, the first year of Malaysia's measles vaccination programme, and 2021, into individuals who received zero dose, one dose and multiple doses of MCV. VE estimates by age and doses received are then adopted to derive EVC. A sensitivity analysis was conducted using 1000 random combinations of BdC and VE parameters. Results: This study suggests that no birth cohort in the Malaysian population has achieved > 95% population immunity (EVC) conferred through measles vaccination since the measles immunisation programme began in Malaysia. Conclusion: The persistence of measles in Malaysia is due to pockets of insufficient vaccination coverage against measles in the population. Monitoring BdC through immunisation surveillance systems may allow for the identification of susceptible subpopulations (primarily zero-dose MCV individuals) and increase the coverage of individuals who are vaccinated with multiple doses of MCV. This study provides a tool for assessment of national-level population immunity of measles conferred through vaccination and does not consider subnational heterogeneity or vaccine waning. This tool can be readily applied to other regions and vaccine-preventable diseases. [ABSTRACT FROM AUTHOR]

Insufficient adult vaccination coverage rates remain an international challenge. This nationwide study aimed at exploring vaccination coverage and predictors of influenza, pneumococcal, herpes zoster, tetanus, measles, and hepatitis B vaccine uptake, following the recommendations of the National Immunization Program for adults. This was a multicenter, mixed-methods study conducted at 23 primary care units in six different regions of Greece. A pretested questionnaire was administered to three randomly selected adults who visited each practice daily for 30 consecutive working days. Among the 1571 participants, vaccination coverage for influenza in the high-risk groups was 55%, 36% for pneumococcal disease, 12% for herpes zoster (HZ), 21% for tetanus, 33% for measles, and 11% for hepatitis B. Perception of low susceptibility to disease due to good health status, concerns about side-effects and vaccines' efficacy, and mistrust in pharmaceutical companies were among common factors associated with the vaccines uptake. The strongest factor associated with the participants' vaccination status was their doctor's recommendation (odds ratio [95% confidence interval] influenza: 6.06 [4.52–8.14], pneumococcal disease: 15.73 [10.98–22.52], HZ: 17.01 [9.05–31.96], tetanus: 23.93 [16.20–35.35], measles: 33.47 [16.85–66.47], and hepatitis B: 73.92 [17.47–312.74]). Being well-informed about each vaccine was also a predictor of its uptake. Vaccination coverage was suboptimal and especially low in tetanus, HZ, and hepatitis B immunization. Person-centered approach, with provision of appropriate information about vaccines' safety and efficacy, responding to each patient's needs, as well as physicians' strong recommendation for vaccination are considered crucial to advocate against the spread of vaccine misinformation and increase vaccination coverage. [ABSTRACT FROM AUTHOR]

Measles remains a highly contagious and potentially severe infectious disease, necessitating high vaccine coverage. However, misinformation and measles vaccine hesitancy/resistance have posed significant challenges to achieving this goal. The COVID-19 pandemic further exacerbated these challenges, leading to a measles outbreak in Jordan in 2023. This study aimed to investigate the acceptance of the measles rubella (MR) vaccine among parents in Jordan and to identify its associated determinants. This cross-sectional questionnaire-based study was conducted using a previously Arabic-validated version of the Parental Attitudes towards Childhood Vaccines (PACV) survey instrument. Data collection took place in October 2023, and the final study sample comprised a total of 391 parents, with mothers representing 69.8% of the participants (n = 273). The majority of participating parents expressed either resistance (n = 169, 43.2%) or hesitancy (n = 168, 43.0%) towards MR vaccination, while only 54 participants (13.8%) expressed MR vaccine acceptance. Multivariate analysis revealed that trust in vaccine safety/efficacy, behavior, and having fewer offspring were significantly associated with MR vaccine acceptance. The current study revealed a concerning level of MR vaccine hesitancy/resistance among parents in Jordan, which could signal a public health alarm in the country. Urgent and targeted interventions are strongly recommended to address this issue, including mass campaigns aimed at building trust in the MR vaccine's safety/efficacy. Additionally, there is an urgent need for effective public health initiatives to ensure sufficient measles vaccine coverage to prevent future outbreaks of this serious disease. [ABSTRACT FROM AUTHOR]

Despite the low measles antibody positivity rate among young healthcare workers (HCWs) who have previously received two doses of a measles-containing vaccine (MCV), whether an additional dose of MCV acts as a booster remains unknown. Thus, we aimed to evaluate the immune responses to a third dose of MCV in young HCWs. Hospital-wide measles seroprevalence was assessed using enzyme-linked immunosorbent assay (ELISA). The immunogenicity of a third dose of MCV was determined in young seronegative HCWs (born between 1986 and 1997) who had previously received a two-dose measles vaccination. A total of 3033 (92.6%) HCWs had anti-measles immunoglobulin G. The lowest seropositivity rate was observed in HCWs aged 20–24 years (87.7%). In this group, HCWs who received a third dose of MCV had higher seropositivity than those who received a second dose (89.5% vs. 75.4%). A third dose of MCV was administered to 18 HCWs who did not have anti-measles IgG despite two doses. Neutralizing antibody titers increased significantly 4 weeks after the third vaccination. Although neutralizing antibody titers decreased 1 year post vaccination, 17 (94.4%) HCWs had medium (121–900 mIU/mL) or high (>900 mIU/mL) levels. Furthermore, the third dose of MCV increased the measles virus-specific T-cell effector function. The third dose of MCV induced a strong immune response against measles in young seronegative HCWs who had previously received a two-dose measles vaccination. [Display omitted] [ABSTRACT FROM AUTHOR]

• Measles vaccine (MV) may reduce mortality and admissions beyond measles prevention. • For decades, MV has been distributed in campaigns to eliminate measles worldwide. • We assessed an MV campaign's effect in a cluster-randomized trial in Guinea-Bissau. • Mortality was lower than anticipated and MV did not reduce mortality or admissions. • MV's effects may differ by underlying disease patterns and other vaccine campaigns. Campaigns with measles vaccine (C-MV) are conducted to eradicate measles, but prior studies indicate that MV reduces non-measles mortality and hospital admissions too. We hypothesized that C-MV reduces death/hospital admission by 30%. Between 2016-2019, we conducted a non-blinded cluster-randomized trial randomizing village clusters in rural Guinea-Bissau to a C-MV targeting children aged 9-59 months. In Cox proportional hazards models, we assessed the effect of C-MV, obtaining hazard ratios (HR) for the composite outcome (death/hospital admission). We also examined potential effect modifiers. Among 18,411 children (9636 in 111 intervention clusters/8775 in 110 control clusters), 379 events occurred (208 intervention/171 control) during a median follow-up period of 22 months. C-MV did not reduce the composite outcome (HR 1.12, 95% confidence interval 0.88-1.41). Mortality among enrolled children (5.3 intervention and 4.6 control, per 1000 person-years) was approximately half the pre-trial mortality rate (11.1 intervention and 8.9 control, per 1000 person-years). Neither planned nor explorative analyses of potential effect modifiers explained the contrasting results to prior studies. C-MV did not reduce overall mortality or hospital admission. This might be explained by changes in disease patterns, baseline differences in health status, and/or modifying effects of other campaigns during follow-up. [ABSTRACT FROM AUTHOR]

Background: Measles is a highly contagious illness. Sri Lanka (SL) has eliminated the measles in 2019. The country is at risk of importation of measles and there could be vaccine-associated measles like illnesses. Therefore, it is important to investigate patients with fever, rash to differentiate the wild-type from vaccine-type excluding other suspected pathogens to direct infection prevention and control strategies. The objective is to describe the laboratory investigation procedure in an immunocompetent child, developed fever, rash following measles containing vaccine in post-measles eliminated period, SL. Methods: This laboratory based investigation was carried out in National Measles Laboratory, SL. Blood and throat swab were received from a patient with fever, rash, cough and coryza developed at tenth day of receiving the measles containing live-attenuated vaccine. Samples were tested for measles, rubella, and other relevant pathogens according to the laboratory testing algorithm for an immunocompetent child with fever, rash and flu like symptoms. Results: Measles vaccine type A, Edmonston-strain virus was detected after sequencing in throat swab and measles IgM and IgG were positive at sixth-week of illness-onset. In addition, influenza A RNA was detected in throat swab at day-three with detectable parvoB19 IgM in blood sample received at sixth-week of post-onset symptoms. Conclusions: Measles like illness of this immunocompetent child who received measles containing vaccine could be due to measles vaccine-type A or influenza infection. In a measles eliminated, resource-limited setting in SL, there should be a well-defined, testing algorithm to exclude prevalent possible pathogens according to epidemiological and clinical information.

Measles is a highly contagious viral disease, and hence, sufficient herd immunity is obligatory to prevent infection transmission. Measles is still a cause of considerable disease burden globally, mainly in children. During a national measles outbreak in Israel in 2018–2019, the peak incidence rates occurred in the Jerusalem district. Most measles cases in the Jerusalem district (75.5%, 1702) were observed in children younger than 15 years of age, 49.2% (1109) were in children under 5 years of age, and 18.9% (425) were in infants under 1 year of age. The routine measles vaccination schedule includes two doses at 1 and 6 years of age. Most cases (1828, 81.1%) were unvaccinated (zero measles vaccine doses). These cases comprised the 425 affected infants under 1 year of age, who were ineligible for vaccination, along with the 1403 children over 1 year of age, who were otherwise unvaccinated. This study aimed to describe the epidemiologic and laboratory features of this measles outbreak, and to investigate case ascertainment (laboratory confirmed compared to epidemiologically confirmed cases). The study population included 2254 measles cases notified during the period spanning June 2018 to May 2019 in the Jerusalem district (incidence rate 176 per 10,000 population). Of the 2254 cases, 716 (31.8%) were laboratory confirmed, and 1538 (68.2%) were confirmed as epidemiologically linked. Most laboratory confirmed cases (420, 58.7%) underwent real-time PCR tests. Serological tests (measles IgM and IgG) were used in 189 (26.4%) cases, and a combination of RT-PCR and serology was used in 107 (14.9%) cases. In a multivariate model analysis, the variables significantly associated (after adjustment) with higher odds for laboratory confirmation included month of disease onset (late), additional measles cases in the household (single case), place of medical treatment (hospital; either emergency department, or hospitalization) and vaccination status (at least one prior vaccine dose). The measles outbreak described demonstrates the urgency of addressing vaccination gaps with appropriate outbreak prevention programs. The road to measles elimination needs to be paved with robust public health infrastructure, excellent field epidemiology for outbreak surveillance, investigation, and control, and laboratory proficiency.

Healthcare workers are recommended to get vaccinated against measles and varicella. This study aims to describe the implementation process of a measles and varicella vaccination program and report on the reduction in the number of susceptible healthcare workers exposed to measles, varicella, and disseminated herpes zoster at a tertiary hospital. The Consolidated Framework for Implementation Research (CFIR) model was used to describe the vaccination program implemented from October 2015 to September 2018. The number of exposed, reviewed, and susceptible healthcare workers during contact tracing for exposure to (a) measles and (b) varicella and disseminated herpes zoster in 2016, 2017, and 2018 is reported. A total of 6770 (95%) out of 7083 healthcare workers completed their immunization review by 2018. In 2016, 20 (10%) out of 198 healthcare workers exposed to measles were considered susceptible. In 2018, no one was found susceptible out of the 51 staff members exposed to measles (p < 0.01). For exposure to varicella and disseminated herpes zoster, seven (5%) out of 154 exposed healthcare workers were susceptible in 2016. In comparison, only two (1%) out of 377 exposed healthcare workers in 2018 were susceptible (p < 0.01). The vaccination program effectively reduced number of healthcare workers susceptible to measles, varicella, and disseminated zoster. [ABSTRACT FROM AUTHOR]

A large measles outbreak in 2014-2015, linked to Disneyland theme parks, attracted international attention, and led to changes in California vaccine policy. We use dates of symptom onset and known epidemic links for California cases in this outbreak to estimate time-varying transmission in the outbreak, and to estimate generation membership of cases probabilistically. We find that transmission declined significantly during the course of the outbreak (p = 0.012), despite also finding that estimates of transmission rate by day or by generation can overestimate temporal decline. We additionally find that the outbreak size and duration alone are sufficient in this case to distinguish temporal decline from time-invariant transmission (p = 0.014). As use of a single large outbreak can lead to underestimates of immunity, however, we urge caution in interpretation of quantities estimated from this outbreak alone. Further research is needed to distinguish causes of temporal decline in transmission rates.

Accurate and cost-effective identification of areas where co-endemic infections occur would enable public health managers to identify opportunities for implementation of integrated control programs. Dried blood spots collected during cross-sectional lymphatic filariasis surveys in coastal Kenya were used for exploratory integrated detection of IgG antibodies against antigens from several parasitic infections (Wuchereria bancrofti, Schistosoma mansoni, Plasmodium spp., Ascaris lumbricoides, and Strongyloides stercoralis) as well as for detection of responses to immunizing agents used against vaccine-preventable diseases (VPDs) (measles, diphtheria, and tetanus) using a multiplex bead assay (MBA) platform. High heterogeneity was observed in antibody responses by pathogen and antigen across the sentinel sites. Antibody seroprevalence against filarial antigens were generally higher in Ndau Island (P < 0.0001), which also had the highest prevalence of filarial antigenemia compared with other communities. Antibody responses to the Plasmodium species antigens circumsporozoite protein (CSP) and merozoite surface protein-1 (MSP-1)19 were higher in Kilifi and Kwale counties, with Jaribuni community showing higher overall mean seroprevalence (P < 0.0001). Kimorigo community in Taita-Taveta County was the only area where antibody responses against S. mansoni Sm25 recombinant antigen were detected. Seroprevalence rates to Strongyloides antigen NIE ranged between 3% and 26%, and there was high heterogeneity in immune responses against an Ascaris antigen among the study communities. Differences were observed between communities in terms of seroprevalence to VPDs. Seroprotection to tetanus was generally lower in Kwale County than in other counties. This study has demonstrated that MBA holds promise for rapid integrated monitoring of trends of infections of public health importance in endemic areas.

Background: Measles is a highly contagious viral infection that can lead to severe complications. Vaccination has successfully reduced measles cases; however, the immune response to booster doses of the measles vaccine is not fully understood. This follow-up study aimed to investigate the levels of interleukin-8 (IL-8) and IL-17 in the sera of vaccinated subjects after receiving a booster dose of the measles virus. Objectives: This follow-up study evaluated the levels of IL-8 and IL-17 in the sera of volunteers who received a second booster dose of the measles virus vaccine compared to a control group. Materials and Methods: Forty volunteers were included in the study, with 20 volunteers receiving a second booster dose of the vaccine and the remaining volunteers serving as the control group. The levels of IL-8 and IL-17 were measured using the enzyme-linked immunosorbent assay at various time intervals. Results: The results revealed significant differences in IL-8 levels, whereas IL-17 levels showed non-significant differences among the tested subjects at different time intervals (P ≤ 0.05). In the vaccinated group, the mean IL-8 level after one week was 192.04 ± 31.44 pg/mL, whereas it decreased to 30.89 ± 4.44 pg/mL after 7 weeks, showing a significant difference between these two periods. The control group had an IL-8 level of 367.95 ± 32.61 pg/mL. Regarding IL-17, there was no significant difference between the 3-week measurement (415.63 ± 61.12 pg/mL) and the 7-week measurement (848.61 ± 54.29 pg/mL) in the vaccinated group, as well as the control group (819.46 ± 75.33 pg/mL). Conclusions: The findings of this study suggest that the levels of IL-8 decreased, whereas there was variation in IL-17 levels after administering a second booster dose of the measles vaccine compared to normal subjects. These results contribute to our understanding of the immune response following a booster dose of the measles vaccine and highlight potential differences in the immune profile of vaccinated individuals compared to the control group.

Objective: To assess the knowledge of healthcare workers on the measles vaccine and its cold chain management. Method: An institutional-based cross-sectional study was conducted from February 1 to March 30, 2022 in Gondar City Administration public health institutions among 165 healthcare workers. Data were collected using a structured questionnaire. In addition, an on-spot observation checklist was used to assess the availability, status and management of the cold chain. A logistic regression model was used to assess the relationship between the outcome and predictor variables. Crude and adjusted odds ratios were calculated with 95% confidence intervals. Results: Overall, 87 (52.7%; 95% Cl 44.8%-60.5%) of the healthcare workers had unsatisfactory knowledge regarding the measles vaccine and its cold chain management. One hundred thirty-six (82.4%) healthcare workers correctly mentioned the recommended range of temperature (2-8 °C) for measles vaccine storage. Healthcare workers aged 18-29 years (P=0.001) and 30-44 years (P=0.014) were observed as determinants of unsatisfactory knowledge on the measles vaccine and its cold chain management. One hundred and five (63.6%) of the healthcare workers did not correctly mention the type of measles vaccine used in routine immunization. More than one-third (36.4%) of the healthcare workers perceived that the measles vaccine is not safe and could cause measles. Conclusions: More than half of the healthcare workers in the study area had unsatisfactory knowledge on the measles vaccine and its cold chain management. It is necessary to provide technical support and in-service training for healthcare workers to ensure optimal immunization effectiveness.

Abstract Background New strategies to increase measles and rubella vaccine coverage, particularly in low- and middle-income countries, are needed if elimination goals are to be achieved. With this regard, measles and rubella vaccine microneedle patches (MRV-MNP), in which the vaccine is embedded in dissolving microneedles, offer several potential advantages over subcutaneous delivery. These include ease of administration, increased thermostability, an absence of sharps waste, reduced overall costs and pain-free administration. This trial will provide the first clinical trial data on MRV-MNP use and the first clinical vaccine trial of MNP technology in children and infants. Methods This is a phase 1/2, randomized, active-controlled, double-blind, double-dummy, age de-escalation trial. Based on the defined eligibility criteria for the trial, including screening laboratory investigations, 45 adults [18–40 years] followed by 120 toddlers [15–18 months] and 120 infants [9–10 months] will be enrolled in series. To allow double-blinding, participants will receive either the MRV-MNP and a placebo (0.9% sodium chloride) subcutaneous (SC) injection or a placebo MNP and the MRV by SC injection (MRV-SC). Local and systemic adverse event data will be collected for 14 days following study product administration. Safety laboratories will be repeated on day 7 and, in the adult cohort alone, on day 14. Unsolicited adverse events including serious adverse events will be collected until the final study visit for each participant on day 180. Measles and rubella serum neutralizing antibodies will be measured at baseline, on day 42 and on day 180. Cohort progression will be dependent on review of the unblinded safety data by an independent data monitoring committee. Discussion This trial will provide the first clinical data on the use of a MNP to deliver the MRV and the first data on the use of MNPs in a paediatric population. It will guide future product development decisions for what may be a key technology for future measles and rubella elimination. Trial registration Pan-African Clinical Trials Registry 202008836432905 . ClinicalTrials.gov NCT04394689

Ongoing outbreaks of measles threaten its elimination status in the United States. Its resurgence points to lower parental vaccine confidence and local pockets of unvaccinated and undervaccinated individuals. The geographic clustering of hesitancy to MMR indicates the presence of social drivers that shape parental perceptions and decisions on immunization. Through a qualitative systematic review of published literature (n = 115 articles; 7 databases), we determined major themes regarding parental reasons for MMR vaccine hesitancy, social context of MMR vaccine hesitancy, and trustworthy vaccine information sources. Fear of autism was the most cited reason for MMR hesitancy. The social drivers of vaccine hesitancy included primary care/healthcare, education, economy, and government/policy factors. Social factors, such as income and education, exerted a bidirectional influence, which facilitated or hindered vaccine compliance depending on how the social determinant was experienced. Fear of autism was the most cited reason for MMR hesitancy. Vaccine hesitancy to MMR and other childhood vaccines clustered in middle- to high-income areas among mothers with a college-level education or higher who preferred internet/social media narratives over physician-based vaccine information. They had low parental trust, low perceived disease susceptibility, and were skeptical of vaccine safety and benefits. Combating MMR vaccine misinformation and hesitancy requires intersectoral and multifaceted approaches at various socioecological levels to address the social drivers of vaccine behavior. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has severely affected health systems worldwide and raised the issue of vaccine hesitancy. In 2022, the World Health Organization reported an outbreak of measles infection among people over 20 years of age in the European Region. Previous studies found low rates of measles immunization among Italian healthcare workers (HCWs) and medical students. Vaccine hesitancy is a relevant cause of low immunization rate among HCWs and the general population. We aim to evaluate the measles vaccine uptake among medical students of a large teaching hospital, compared to the pre-pandemic period. This is a retrospective observational study, that evaluated the immune status and the vaccine acceptance rate for measles in medical students at the University of Tor Vergata, Rome, who underwent occupational health surveillance from 1 January to 1 December 2022. We also compared the data with the results of a pre-pandemic survey conducted in 2018. Vaccine uptake among unprotected medical students was 59.5%. The data showed no significant difference in vaccine uptake compared with the pre-COVID-19 period. Conversely, the rate of serologically immune subjects to measles increased from 89.66% in 2018 to 97.45% in 2022 as a result of the recent mandatory vaccination policy. Despite efforts to tackle vaccine hesitancy during the COVID-19 pandemic, measles vaccine uptake is still low among young adults starting their medical training, and their compliance with free workplace vaccination offers is suboptimal. Occupational health services should raise awareness among workers and work together to implement strategies to achieve comprehensive measles vaccination coverage among occupational health workers.

BACKGROUND:Depression can impair the immunogenicity of vaccine administration in adults. Whereas many vaccinations are administered in childhood, it is not known whether adolescent or adult onset depression is associated with impairments in the maintenance of protection of childhood vaccines. This study tested the hypothesis that individuals with adolescent or adult onset mood disorders would display compromised immunity to measles, a target of childhood vaccination. METHODS:IgG antibodies to measles were quantified using a solid phase immunoassay in volunteers with bipolar disorder (BD, n = 64, mean age of onset = 16.6 ± 5.6), currently depressed individuals with major depressive disorder (cMDD, n = 85, mean age of onset = 17.9 ± 7.0), remitted individuals with a history of MDD (rMDD, n = 82, mean age of onset = 19.2 ± 8.6), and non-depressed comparison controls (HC, n = 202), all born after the introduction of the measles vaccine in the USA in 1963. RESULTS:Relative to HC, both the cMDD group (p = 0.021, adjusted odds ratios (OR) = 0.47, confidence interval (CI) = 0.24-0.90), and the rMDD group (p = 0.038, adjusted OR = 0.50, CI = 0.26-0.97) were less likely to test seropositive for measles. Compared with unmedicated MDD participants, currently medicated MDD participants had a longer lifetime duration of illness and were less likely to test seropositive for measles. CONCLUSIONS:Individuals with adolescent or adult onset MDD are less likely to test seropositive for measles. Because lower IgG titers are associated with increased risk of measles infection, MDD may increase the risk and severity of infection possibly because of impaired maintenance of vaccine-related protection from measles.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is largely refractory to cancer immunotherapy with PD-1 immune checkpoint blockade (ICB). Oncolytic virotherapy has been shown to synergize with ICB. In this work, we investigated the combination of anti-PD-1 and oncolytic measles vaccine in an immunocompetent transplantable PDAC mouse model. Methods: We characterized tumor-infiltrating T cells by immunohistochemistry, flow cytometry and T cell receptor sequencing. Further, we performed gene expression profiling of tumor samples at baseline, after treatment, and when tumors progressed. Moreover, we analyzed systemic anti-tumor and anti-viral immunity Results: Combination treatment significantly prolonged survival compared to monotherapies. Tumor-infiltrating immune cells were increased after virotherapy. Gene expression profiling revealed a unique, but transient signature of immune activation after combination treatment. However, systemic anti-tumor immunity was induced by virotherapy and remained detectable even when tumors progressed. Anti-PD-1 treatment did not impact anti-viral immunity. Discussion: Our results indicate that combined virotherapy and ICB induces anti-tumor immunity and reshapes the tumor immune environment. However, further refinement of this approach may be required to develop its full potential and achieve durable efficacy. [ABSTRACT FROM AUTHOR]

Objective: To assess the knowledge of healthcare workers on the measles vaccine and its cold chain management. Method: An institutional-based cross-sectional study was conducted from February 1 to March 30, 2022 in Gondar City Administration public health institutions among 165 healthcare workers. Data were collected using a structured questionnaire. In addition, an on-spot observation checklist was used to assess the availability, status and management of the cold chain. A logistic regression model was used to assess the relationship between the outcome and predictor variables. Crude and adjusted odds ratios were calculated with 95% confidence intervals. Results: Overall, 87 (52.7%; 95% CI 44.8%-60.5%) of the healthcare workers had unsatisfactory knowledge regarding the measles vaccine and its cold chain management. One hundred thirty-six (82.4%) healthcare workers correctly mentioned the recommended range of temperature (2-8 °C) for measles vaccine storage. Healthcare workers aged 18-29 years (P=0.001) and 30-44 years (P=0.014) were observed as determinants of unsatisfactory knowledge on the measles vaccine and its cold chain management. One hundred and five (63.6%) of the healthcare workers did not correctly mention the type of measles vaccine used in routine immunization. More than one-third (36.4%) of the healthcare workers perceived that the measles vaccine is not safe and could cause measles. Conclusions: More than half of the healthcare workers in the study area had unsatisfactory knowledge on the measles vaccine and its cold chain management. It is necessary to provide technical support and in-service training for healthcare workers to ensure optimal immunization effectiveness. [ABSTRACT FROM AUTHOR]

Abstract Background Measles is a viral disease and a leading vaccine-preventable childhood killer. More than 95% of measles deaths occur in countries with low incomes and weak health infrastructures. In response to this, Ethiopia prepared a measles elimination strategic plan to achieve by 2020. However, based on the Mini-Ethiopian demographic health survey 2019 the full coverage of immunization is 43% at the country level and it is lowest (20%) in the Afar region where this study was conducted. Therefore, this study aimed to identify the determinants of the measles vaccine dropout rate in Afar regional state which is one of the pastoralist communities in Ethiopia. Methods Community based unmatched case-control study design was used. The study was conducted in Awash district of Afar regional state, Ethiopia from June 1st -30th 2018. Data were collected from a study unit of 12–23 months old children. For this study, a sample of 166 cases and 331controls were selected by simple random sampling methods and the total sample size was 497. Data were collected using a pretested structured questionnaire by health workers using the local language. Data were entered into Epi-info − 7 and analyzed by SPSS version 20 software and logistic regression was used to assess the determinants measles dropout rate. Results A total of 487 children participated in this study with a response rate of 97.9%. More than half of the children were female (53.3%) and 113 (35.2%) children mothers’ were not attended formal education. Mother who had antenatal care ≤ 2 visits [AOR:=5.7(3.2–10.14)], being in the birth order of 1 − 3 [AOR = 4.47(1.63–12.29)], long waiting time > 60 min at nearby health facility for vaccine [AOR = 2.37(1.36–4.15)], households visit by health extension workers [AOR = 2.03(1.12–3.66)], pregnant women not participating with women development army [AOR = 3.5(1.94–6.18)], and poor maternal knowledge on vaccination [AOR = 3.30(1.9–5.73)] were significant determinants with measles vaccination dropout rate. Conclusions Health facility and mother characteristics were the determinants of the measles vaccine dropout rate. Therefore, tracing and strict follow up by the health extension works using home visits and women development army at the pastoralist community is necessary to reach them.

Abstract Background Measles vaccination coverage in Guinea-Bissau is low; fewer than 80% of children are currently measles vaccinated before 12 months of age. The low coverage hampers control of measles. Furthermore, accumulating evidence indicates that measles vaccine has beneficial non-specific effects, strengthening the resistance towards other infections. Thus, even if children are not exposed to measles virus, measles-unvaccinated children may be worse off. To increase vaccination coverage, WHO recommends that contacts with the health system for mild illness are utilised to vaccinate. Currently, in Guinea-Bissau, curative health system contacts are not utilised. Methods Bandim Health Project registers out-patient consultations and admissions at the paediatric ward of the National Hospital in Guinea-Bissau. Measles-unvaccinated children aged 9–59 months consulting for milder illness or being discharged from the paediatric ward will be invited to participate in a randomised trial. Among 5400 children, randomised 1:1 to receive standard measles vaccine or a saline placebo, we will test the hypothesis that providing a measles vaccine at discharge lowers the risk of admission/mortality (composite outcome) during the subsequent 6 months by 25%. All enrolled children are followed through the Bandim Health Project registration system and through telephone follow-up. The first 1000 enrolled children are furthermore followed through interviews on days 2, 4, 7 and 14 after enrolment. Discussion Utilising missed vaccination opportunities can increase vaccination coverage and may improve child health. However, without further evidence for the safety and potential benefits of measles vaccination, these curative contacts are unlikely to be used for vaccination in Guinea-Bissau. Trial registration www.ClinicalTrials.gov NCT04220671 . Registered on 5 January 2020.

• A 2-dose vs 1-dose measles vaccine (MV) schedule was beneficial in the first RCT. • However, in two later RCTs mortality tended to be higher in the 2-dose group. • We examined whether oral polio vaccine campaigns (C-OPV) explained the pattern. • With no C-OPV-before-enrolment, the hazard ratio (HR) was 0.79 (0.62-1.00). • When C-OPV was received before enrolment the HR was 1.39 (0.97-1.99). Between 2003 and 2019, three trials (randomised controlled trials [RCTs]) in Guinea-Bissau randomised infants to an early 2-dose measles vaccine (MV) schedule at 4 and 9 months vs standard MV at 9 months. The RCTs produced contradictory mortality results; the effect being beneficial in the 2-dose group in the first but tending to have higher mortality in the last two RCTs. We hypothesised that increased frequency of campaigns with oral polio vaccine (C-OPV) explained the pattern. We performed per-protocol analysis of individual-level survival data from the three RCTs in Cox proportional hazards models yielding hazard ratios (HR) for the 2-dose vs the 1-dose MV group. We examined whether timing of C-OPVs and early administration of OPV0 (birth to day 14) affected the HRs for 2-dose/1-dose MV. The combined HR(2-dose/1-dose) was 0.79 (95% confidence interval: 0.62-1.00) for children receiving no C-OPV-before-enrolment, but 1.39 (0.97-1.99) for those receiving C-OPV-before-enrolment (homogeneity, P = 0.01). C-OPV-before-enrolment had a beneficial effect in the 1-dose group but tended to have a negative effect in the 2-dose group, especially in females. These effects were amplified further by early administration of OPV0. In the absence of C-OPVs, an early 2-dose MV strategy had beneficial effects on mortality, but frequent C-OPVs may have benefitted the 1-dose group more than the 2-dose MV group, leading to varying results depending on the intensity of C-OPVs. [ABSTRACT FROM AUTHOR]

Measles remains a highly contagious and potentially severe infectious disease, necessitating high vaccine coverage. However, misinformation and measles vaccine hesitancy/resistance have posed significant challenges to achieving this goal. The COVID-19 pandemic further exacerbated these challenges, leading to a measles outbreak in Jordan in 2023. This study aimed to investigate the acceptance of the measles rubella (MR) vaccine among parents in Jordan and to identify its associated determinants. This cross-sectional questionnaire-based study was conducted using a previously Arabic-validated version of the Parental Attitudes towards Childhood Vaccines (PACV) survey instrument. Data collection took place in October 2023, and the final study sample comprised a total of 391 parents, with mothers representing 69.8% of the participants (n = 273). The majority of participating parents expressed either resistance (n = 169, 43.2%) or hesitancy (n = 168, 43.0%) towards MR vaccination, while only 54 participants (13.8%) expressed MR vaccine acceptance. Multivariate analysis revealed that trust in vaccine safety/efficacy, behavior, and having fewer offspring were significantly associated with MR vaccine acceptance. The current study revealed a concerning level of MR vaccine hesitancy/resistance among parents in Jordan, which could signal a public health alarm in the country. Urgent and targeted interventions are strongly recommended to address this issue, including mass campaigns aimed at building trust in the MR vaccine’s safety/efficacy. Additionally, there is an urgent need for effective public health initiatives to ensure sufficient measles vaccine coverage to prevent future outbreaks of this serious disease.

IntroductionPancreatic ductal adenocarcinoma (PDAC) is largely refractory to cancer immunotherapy with PD-1 immune checkpoint blockade (ICB). Oncolytic virotherapy has been shown to synergize with ICB. In this work, we investigated the combination of anti-PD-1 and oncolytic measles vaccine in an immunocompetent transplantable PDAC mouse model.MethodsWe characterized tumor-infiltrating T cells by immunohistochemistry, flow cytometry and T cell receptor sequencing. Further, we performed gene expression profiling of tumor samples at baseline, after treatment, and when tumors progressed. Moreover, we analyzed systemic anti-tumor and anti-viral immunity.ResultsCombination treatment significantly prolonged survival compared to monotherapies. Tumor-infiltrating immune cells were increased after virotherapy. Gene expression profiling revealed a unique, but transient signature of immune activation after combination treatment. However, systemic anti-tumor immunity was induced by virotherapy and remained detectable even when tumors progressed. Anti-PD-1 treatment did not impact anti-viral immunity.DiscussionOur results indicate that combined virotherapy and ICB induces anti-tumor immunity and reshapes the tumor immune environment. However, further refinement of this approach may be required to develop its full potential and achieve durable efficacy.

Background:Substantial heterogeneity in measles outbreak sizes may be due to genotype-specific transmissibility. Using a branching process analysis, we characterize differences in measles transmission by estimating the association between genotype and the reproduction number R among postelimination California measles cases during 2000-2015 (400 cases, 165 outbreaks). Methods:Assuming a negative binomial secondary case distribution, we fit a branching process model to the distribution of outbreak sizes using maximum likelihood and estimated the reproduction number R for a multigenotype model. Results:Genotype B3 is found to be significantly more transmissible than other genotypes (P = .01) with an R of 0.64 (95% confidence interval [CI], .48-.71), while the R for all other genotypes combined is 0.43 (95% CI, .28-.54). This result is robust to excluding the 2014-2015 outbreak linked to Disneyland theme parks (referred to as "outbreak A" for conciseness and clarity) (P = .04) and modeling genotype as a random effect (P = .004 including outbreak A and P = .02 excluding outbreak A). This result was not accounted for by season of introduction, age of index case, or vaccination of the index case. The R for outbreaks with a school-aged index case is 0.69 (95% CI, .52-.78), while the R for outbreaks with a non-school-aged index case is 0.28 (95% CI, .19-.35), but this cannot account for differences between genotypes. Conclusions:Variability in measles transmissibility may have important implications for measles control; the vaccination threshold required for elimination may not be the same for all genotypes or age groups.

BackgroundMeasles is a significant contributor to child mortality in the Democratic Republic of the Congo (DRC), despite routine immunization programs and supplementary immunization activities (SIA). Further, national immunization coverage levels may hide disparities among certain groups of children, making effective measles control even more challenging. This study describes measles vaccination coverage and reporting methods and identifies predictors of vaccination among children participating in the 2013-2014 DRC Demographic and Health Survey (DHS).MethodsWe examined vaccination coverage of 6947 children aged 6-59 months. A multivariate logistic regression model was used to identify predictors of vaccination among children reporting vaccination via dated card in order to identify least reached children. We also assessed spatial distribution of vaccination report type by rural versus urban residence.ResultsUrban children with educated mothers were more likely to be vaccinated (OR = 4.1, 95% CI: 1.6, 10.7) versus children of mothers with no education, as were children in wealthier rural families (OR = 2.9, 95% CI: 1.9, 4.4). At the provincial level, urban areas more frequently reported vaccination via dated card than rural areas.ConclusionsResults indicate that, while the overall coverage level of 70% is too low, socioeconomic and geographic disparities also exist which could make some children even less likely to be vaccinated. Dated records of measles vaccination must be increased, and groups of children with the greatest need should be targeted. As access to routine vaccination services is limited in DRC, identifying and targeting under-reached children should be a strategic means of increasing country-wide effective measles control.

Background The world is set on the eradication of measles. Continuation of the measles vaccine (MV) after eradication could still reduce morbidity because the MV has so-called beneficial nonspecific effects. We evaluated the effect of a "booster" dose of the MV on overall severe morbidity. Methods We conducted a randomized controlled trial among children aged 17.5 to 48 months in Guinea-Bissau, where the MV is recommended only at 9 months of age. At the time of this interim analysis, 3164 children had been allocated 1:1 to a second dose of measles vaccine (MV2) at 18 months of age or to no vaccine. Severe morbidity (a composite outcome of nonaccidental deaths and hospital admissions) rate ratios (SMRRs) were calculated by Cox regression analysis censored for national oral polio vaccine (OPV) campaigns. Results There were no measles cases during the trial period. There were 43 nonaccidental deaths or hospital admissions during follow-up. Severe morbidity was 2.6 per 100 person-years in the MV2 group and 3.6 per 100 person-years among controls; hence, the estimated effect of MV2 on severe morbidity was 28% (SMRR, 0.72; 95% confidence interval [CI],.38–1.38). At 12 months of follow-up, the number needed to treat to prevent 1 severe morbidity event was 137 children. After OPV campaigns, the estimated effect of MV2 was reduced to 9% (SMRR, 0.91; 95% CI,.46–1.81). Conclusions MV2 may reduce nonmeasles severe morbidity by 28% (−38% to 62%), although this did not achieve statistical significance in this study. If significant in higher powered studies, this has major implications for child health, even after measles eradication. Clinical Trials Registration NCT02943681. [ABSTRACT FROM AUTHOR]