Search Results (613)

Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant brain tumors, necessitating novel therapeutic approaches. Oncolytic treatments, particularly oncolytic viruses (OVs), have emerged as promising candidates by selectively infecting and lysing tumor cells while stimulating anti-tumor immunity. Various virus-based therapies are under investigation, including genetically engineered herpes simplex virus (HSV), adenovirus, poliovirus, reovirus, vaccinia virus, measles virus, and Newcastle disease virus, each exploiting unique tumor-selective mechanisms. While some, such as HSV-based therapies including G207 and Delytact^TM, have demonstrated clinical progress, significant challenges persist, including immune evasion, heterogeneity in patient response, and delivery barriers due to the blood–brain barrier. Moreover, combination strategies integrating OVs with immune checkpoint inhibitors, chemotherapy, and radiation are promising but require further clinical validation. Non-viral oncolytic approaches, such as tumor-targeting bacteria and synthetic peptides, remain underexplored. This review highlights current advancements while addressing critical gaps in the literature, including the need for optimized delivery methods, better biomarker-based patient stratification, and a deeper understanding of GBM’s immunosuppressive microenvironment. Future research should focus on enhancing OV specificity, engineering viruses to deliver therapeutic genes, and integrating OVs with precision medicine strategies. By identifying these gaps, this review provides a framework for advancing oncolytic therapies in GBM treatment. Full article

Background/Objectives: Medical and nursing students, as future healthcare professionals, influence public trust and vaccine acceptance. Knowledge gaps or misconceptions regarding immunization may undermine their confidence and effectiveness in addressing vaccine hesitancy. This study explores perceptions and attitudes toward childhood vaccination among Bulgarian healthcare students and factors shaping these outcomes. Methods: A cross-sectional survey was conducted in 2024, using an online self-administered questionnaire completed by 374 medical and nursing students. Descriptive statistics were used to analyze vaccine-related responses, comparing attitudes between healthcare programs and education years. Binomial logistic regression was applied to identify predictors of support for mandatory vaccination, first considering demographic and academic variables, and then adding students’ beliefs and common misconceptions. Results: Medical students showed more positive attitudes toward vaccination than nursing students, with 96.8% of medical students versus 89.4% of nursing students believing vaccines are effective (p = 0.005). Students in advanced years demonstrated stronger belief in vaccine effectiveness (p = 0.038). Additionally, misbeliefs about the measles vaccine causing autism decreased significantly, with most students in higher years rejecting this misconception (p = 0.009). Logistic regression revealed that belief in following the vaccine schedule (OR = 22.71; p < 0.001) and confidence in vaccine effectiveness (OR = 10.20; p < 0.001) were the strongest predictors of support for mandatory vaccination, with attitudinal factors explaining over half of the variance. Conclusions: Healthcare students’ attitudes about vaccination influence public health outcomes, as their perspectives reflect experience and beliefs. Targeted vaccine education helps address misconceptions and improve vaccination rates. Full article

The ability to study mature neuronal cells ex vivo is complicated by their non-dividing nature and difficulty in obtaining large numbers of primary cells from organisms. Thus, numerous transformed progenitor models have been developed that can be routinely cultured, then scaled, and differentiated to mature neurons. In this paper, we present a new method for differentiating one such model, the Lund human mesencephalic (LUHMES) dopaminergic neurons. This method is two days faster than some established protocols, results in nearly five times greater numbers of mature neurons, and involves fewer handling steps that could introduce technical variability. Moreover, it overcomes the problem of cell aggregate formation that commonly impedes high-resolution imaging, cell dissociation, and downstream analysis. While recently established for herpes simplex virus type 1, we demonstrate that LUHMES neurons can facilitate studies of other herpesviruses, as well as RNA viruses associated with childhood encephalitis and hemorrhagic fever. This protocol provides an improvement in the generation of large-scale neuronal cultures, which may be readily applicable to other neuronal 2D cell culture models and provides a system for studying neurotrophic viruses. We named this method the Streamlined Protocol for Enhanced Expansion and Differentiation Yield, or SPEEDY, method. Full article

Young children are particularly vulnerable to measles infections. Investigating the gap between the waning of maternal antibodies and onset of vaccination-induced immunity via seroprevalence studies can be hampered by recruiting enough young-aged participants. We present measles IgG-antibody results from 2148 patients aged 0 to 2 years, who were hospitalized with acute aseptic meningitis or encephalitis in Lower Saxony or Bremen. Measles serology was performed for differential diagnostics clarification of neurotropic pathogens, during syndromic surveillance between 2006 and 2024. At birth, 79% of children presented with measles IgG-antibodies, but only 30% of three-month-old patients and 11% of five-month-olds. From 0 to 10 months, seropositivity declined monthly by 8%. Over 95% of children aged six to 11 months were unprotected. From 11 months onwards, measles seroprevalence increased, reaching 80–90% towards the end of the second year of life. Our results indicate an absence of maternal measles IgG antibodies after nine months of age and that vaccination starts around 11 months of age; however, not all children had received vaccination by their second birthday. These findings confirm the current recommendation to advance first measles vaccination to nine months in high-exposure settings and support efforts to increase vaccination rates in small children and young adults. Full article

Background: Despite ongoing global elimination efforts, measles remains a persistent public health threat. Methods: This retrospective observational study examines trends in crude measles incidence and vaccination coverage from 1948 to 2024 in the northern region of Serbia—Autonomous Province of Vojvodina (AP Vojvodina)—which accounts for 26.9% of the national population. This study further explores measles vaccination coverage across the province’s seven districts, along with the number of reported measles cases, age distribution, and vaccination status of affected individuals from 2000 to 2024. Data were obtained from official annual immunization records maintained by public health institutions within the framework of Serbia’s national mandatory immunization program. Results: A notable resurgence of measles occurred in Serbia during 2017–2018, following a decline in vaccination coverage. In AP Vojvodina, outbreaks were recorded in 2007, 2014–2015, and 2017–2018, predominantly affecting unvaccinated children and adults aged 20–39 years. Since 2019, the measles incidence has significantly declined. During the 2018 outbreak, the highest incidence was observed among children aged 1–4 years (40.6 per 100,000), followed by infants under 1 year (17.3 per 100,000) and adults aged 20–39 years (12.5 per 100,000). An analysis of the data from 2000 to 2024 revealed substantial age- and dose-related differences in measles incidence, particularly among unvaccinated individuals, those who had received one or two doses of a measles-containing vaccine (MCV), and those with unknown vaccination status. During the 2017–2018 epidemic, unvaccinated children under 1 year and those aged 1–4 years were the most affected. A marked increase in cases among single-dose recipients was noted in 2018, especially in adults aged 20–39 years (9.5%) and those ≥40 years (13.5%). A considerable proportion of measles cases in these age groups had unknown vaccination status: 33.1% among individuals aged 20–39 years and 18.2% among those aged ≥ 40 years. Epidemiological investigation linked the 2007 and 2014–2015 outbreaks in AP Vojvodina to importations from Bosnia and Herzegovina. No specific source was identified for the 2017–2018 outbreak, suggesting possible endemic transmission. Conclusions: These findings underscore the impact of fluctuating vaccination coverage on measles resurgence. Sustaining high two-dose MCV coverage, strengthening routine immunization programs, enhancing surveillance systems, and ensuring timely outbreak preparedness are critical measures for achieving effective measles control. Full article

Background/Objectives: Measles, mumps, and rubella (MMR) continue to pose a significant public health challenge due to insufficient immunization coverage. This study aimed to provide the first seroprevalence data against MMR and to explore self-reported immunity among future healthcare workers (HCWs) in Serbia, including women of childbearing age. Methods: We included 1296 future health care workers (HCWs) aged 19 to 29, born in Serbia. All HCWs supplied a blood sample for serology and filled in a questionnaire. Antibodies were measured using an enzyme immunoassay against measles, mumps, and rubella (MMR). Results: Anti-measles, -mumps, and -rubella seronegativity rates were 25.6%, 26.5%, and 4.4%, respectively, among future HCWs in Serbia. The mumps seronegativity rate was significantly higher in the oldest (27–29-year) age group, accompanied by significantly lower anti-mumps IgG GMCs in the same age group compared to younger participants (p = 0.035 and p < 0.001, respectively). Anti-mumps seronegativity also increased significantly across birth cohorts, from the youngest to the oldest (p = 0.004). Furthermore, anti-mumps IgG antibody GMCs were significantly higher among females, those who attended nursery/kindergarten, and unvaccinated individuals (p = 0.050, p = 0.020, and p = 0.005, respectively). Finally, older age and unvaccinated status were identified as independent factors associated with anti-measles and anti-mumps seronegativity among future HCWs in Serbia. Conclusions: The cross-sectional seroprevalence data revealed insufficient seroprotection in this population of particular importance, i.e., future HCWs, and women of childbearing age. These results strongly support the national recommendations for the mandatory vaccination of these populations. Identified immunity gaps should be closed promptly by strategic, targeted serologic screening, followed by vaccination of those lacking MMR antibodies. Full article

Between 2018 and 2019, Israel experienced one of its largest measles outbreaks in recent decades, with over 4300 reported cases and more than 100 documented importation events. Despite high national vaccination coverage, the prolonged nature of the outbreak posed a risk to the country’s measles elimination status. Traditional epidemiological investigations and genotyping based on the N450 region lacked sufficient resolution to differentiate between sustained local transmission and multiple independent introductions. To address this, we performed whole-genome sequencing on 123 measles virus samples representing both imported and locally acquired cases from diverse geographic regions. Phylogenetic analysis revealed multiple, distinct transmission chains, several of which could be linked to separate importation events. The MF non-coding region (MF-NCR) not only showed the highest genetic variability, but also contained many of the phylogenetic cluster-defining mutations, though informative changes were found throughout the whole genome. These findings demonstrate the value of whole-genome sequencing in resolving complex transmission dynamics and highlight the importance of integrating genomic epidemiology into routine measles surveillance. Such integration can enhance outbreak investigations and better inform public health responses to protect elimination status. Full article

Background/Objectives: Maintaining high childhood vaccination coverage is essential to prevent outbreaks of vaccine-preventable diseases. In Italy, Law No. 119/2017 introduced mandatory childhood immunizations, leading to significant improvements. However, the COVID-19 pandemic disrupted routine services, potentially jeopardizing these gains. This study aimed to evaluate national and regional trends in vaccine coverage across three phases: post-mandate (2015–2016 vs. 2017–2019), pandemic (2017–2019 vs. 2020–2021), and post-pandemic recovery (2020–2021 vs. 2022–2023). Methods: National and regional administrative data on vaccination coverage at 24 months of age were obtained from the Italian Ministry of Health. Temporal trends were analyzed using Joinpoint regression to estimate annual percent changes (APCs), and absolute changes in coverage (Δ) were calculated across defined periods. Pearson correlation coefficients were used to assess associations between baseline coverage and subsequent changes. Results: After the 2017 mandate, coverage increased significantly for varicella (APC = +28.6%), MenB (+22.6%), and measles (+3.4%). Regionally, varicella coverage rose by up to +58.4% in Emilia-Romagna and measles by +11.1% in Campania. During the pandemic, coverage declined for polio (−2.4% in the South) and measles (−6.2% in Abruzzo), while MenB increased in regions with lower initial uptake (r = −0.918, p < 0.001). Post-pandemic, coverage rebounded, with varicella improving by +20.1% in central regions and measles by +13.9% in Abruzzo. A strong inverse correlation between baseline coverage and improvement was observed for varicella across all periods (r from −0.877 to −0.915). Conclusions: Mandatory vaccination policies led to substantial coverage improvements, and despite the disruption caused by the pandemic, recovery trends were observed for most vaccines. The consistent association between low baseline coverage and stronger gains highlights the resilience of the system, but also the ongoing need for regionally tailored strategies to reduce geographic disparities and ensure equitable immunization across Italy. Full article

Background: Immunization coverage in Nigeria is low, with many children missing out on important lifesaving vaccines. To enable a better understanding of contextual factors towards increasing uptake, we piloted a Decentralized Immunization Monitoring (DIM) approach in the Kumbotso local government area (LGA) of Kano state, Nigeria, to identify wards with low vaccination rates and understand why this is happening. The findings were used to improve routine immunization (RI) programs and reduce the number of unvaccinated children and children yet to receive their first dose of diphtheria–pertussis–tetanus (DPT) vaccine, referred to as Zero-Dose children (ZD). Methods: This study adopted a cross-sectional design approach using the Behavioural and Social Drivers of Vaccination (BeSD) framework and the Lot Quality Assurance Sampling (LQAS). The study population comprised caregivers of children aged 0–11 months and 12–23 months across the 11 wards in Kumbotso District, Kano State, Nigeria, using a segmentation sampling approach. The study covered 209 settlements selected using probability proportionate to size (PPS) sampling from the wards. Univariate and bivariate analyses were performed to show patterns and relations across variables. Results: Out of 418 caregivers surveyed, 98.1% were female. Delayed vaccination was experienced by 21.9% of children aged 4.5–11 months, while the prevalence of ZD was estimated at 26.8% amongst the older cohort (12–23 months). A total of 71.4% of the delayed group and 89.1% of the ZD group remained unvaccinated. Caregiver education, rural residence, and home births correlated with delayed/ZD status (p < 0.05). Logistic regression associated higher caregiver education with reduced delayed vaccination odds (OR:0.34, p < 0.001) and urban residence with lower ZD odds (OR:1.89, p = 0.036). The antigen coverages of BCG (81.5%), DPT3 (63.6%), and measles 1 (59.7%) all surpassed the national dropout thresholds. Kumbotso, Unguwar Rimi, and Kureken Sani wards were all identified as underperforming and therefore targeted for intervention. Negative vaccine perceptions (50% delayed, 53.6% ZD) and distrust in health workers (46.4% delayed, 48.2% ZD) were significant barriers, though the caregiver intent to vaccinate was protective (OR: 0.27, p < 0.001). The cost of accessing immunization services appeared to have a minor effect on coverage, as the majority of caregivers of delayed and ZD children reported spending less than 200 Naira (equivalent to USD 0.15) on transport. Conclusions: This pilot study highlighted the utility of LQAS and BeSD in identifying low-performing wards, barriers, and routine immunization gaps. Barriers included low caregiver education, rural residence, and negative vaccine perceptions/safety. Caregiver education and urban residence were protective factors against delayed and ZD vaccination, suggesting social and systemic barriers, particularly in rural and less educated populations. Antigen-specific coverage showed disparities, with dropouts for multi-dose vaccines exceeding the national thresholds of 10%. Targeted measures addressing education, trust, and systemic issues are needed. Findings emphasize decentralized monitoring, community engagement, and context-specific strategies to reduce ZD children and ensure equitable vaccination in Nigeria. Full article

Background/Objectives: A resurgence of measles has been observed in Europe and worldwide since 2023. The aim of this article is to describe characteristics of cases reported to the Italian national measles surveillance system and discuss reasons for the outbreak and its public health relevance. Methods: We analyzed measles cases reported to the Italian national measles surveillance system with a symptom onset from August 2023 to January 2025. Results: Overall, 1164 cases were reported, of which 1065 (91.5%) were laboratory confirmed. The median age was 30 years, but the highest incidence was in children under one year of age. Transmission occurred mainly in families and nosocomial settings. Multiple importations occurred during 2023, which initially led to localized outbreaks with limited spread but was subsequently followed by increasing local transmission in 2024. Conclusions: These findings suggest lingering immunity gaps in children and adults in Italy, highlighting the potential severity of measles and the ease with which measles crosses country borders. Besides improving routine immunization coverage, targeted vaccination opportunities should be provided to susceptible population groups. Communication activities are also needed to increase awareness about disease severity, especially among young adults. In view of the upcoming travel season, travel clinics should encourage persons without evidence of measles immunity to be vaccinated before any international travel. Full article

Background/Objectives: In the Republic of Serbia, measles vaccination was first introduced in 1971, while combined vaccination (measles, mumps, rubella) was made mandatory in 1996 as part of the national vaccination program. Reported prevalence values for 2023 were <0.75 cases per 100K population for measles, 0.09 cases per 100K for mumps, and no cases of rubella. Methods: This cross-sectional study was performed in May, 2024 as part of the project “Herd Immunity to Vaccine-Preventable and Other Relevant Infections in the Belgradian Population.” It focused on assessing herd immunity to measles, mumps and rubella (MMR) among residents insofar as these remain a public concern despite the availability of vaccines. A total of 2533 subjects were distributed across nine age groups, covering those aged 1–70⁺ years and various professional groups residing in Belgrade. Participants were stratified by age and activity. Upon obtaining individual information by online questionnaire and receiving a signed statement of informed consent, blood samples were obtained for IgG antibody testing (ELISA) to determine MMR serological status. The results were compared to national and international immunization standards to evaluate herd immunity levels. Results: Our results indicate varying levels of immunity for each virus, with specific demographic groups showing different immunity levels. Total measles seroprevalence during this study was 74.7%, with significant variation across all age groups. While high seropositivity was observed in both children (90.7%) and elder age groups (98.4%), middle-aged individuals in the age group 30–49 years showed significantly lower IgG levels. Between 2021 and 2023, there were no registered cases of rubella detected in Serbia, which indicates a high level of immunity. This was confirmed here with consistently high IgG levels across all age groups, with an average seropositivity of 94.8%. Average mumps seropositivity across all age groups was 85.1%. The lowest value was in the young child (1–5 years) age group (76.1%); the highest was in the elderly group (92.6%). Conclusions: The current findings suggest that the Belgradian population has strong overall immunity to MMR, yet with some concerns regarding measles immunity in middle-aged adults, suggesting a potential need for catch-up vaccinations. While rubella status indicates strong herd immunity and minimal risk of outbreaks, mumps immunity in some groups (children, middle-aged adults) is below the protective threshold. While it is still sufficient to prevent widespread transmission, it should be closely observed. To our knowledge, this study is the first of its kind to provide data about MMR seroprevalence in Belgrade. Findings indicate the need for constant surveillance and revaccination of vulnerable/seronegative groups. Full article

Measles is a highly contagious viral disease and remains a global health challenge despite the availability of effective vaccines. Although many regions have successfully eliminated measles, outbreaks continue to occur owing to vaccine hesitancy, inadequate coverage, and imported cases. Differences in epidemiology, vaccination policies, and immunity assessment influence measles control across countries. This paper compares measles epidemiology, vaccination policies, and immunity assessment approaches in the United States and Japan. Data were obtained from surveillance reports, national immunization programs, and peer-reviewed literature. The introduction of the measles vaccine led to substantial reductions in incidence. The United States eliminated measles in 2000 but continues to experience outbreaks due to vaccine hesitancy and imported cases. Japan implemented a two-dose policy in 2006, reducing case numbers; however, sporadic outbreaks among adults persist. In the United States, immunity is primarily assessed using documented vaccination history, whereas in Japan, enzyme immunoassay is commonly used to evaluate immunity status. Despite progress in measles elimination, achieving high vaccination coverage and addressing vaccine hesitancy remain critical challenges. Variations in immunity assessment methods impact surveillance accuracy and outbreak control. Strengthening international collaboration, standardizing assessment protocols, and enhancing public health education are crucial for sustained measles elimination. Full article

Immunization coverage is a key public health indicator reflecting healthcare accessibility and socio-economic conditions. This study employs Principal Component Analysis (PCA) to construct composite development scores and analyze their relationship with immunization coverage for measles and diphtheria-tetanus-pertussis (DTP) vaccines across 195 countries (2000–2021). The analysis comprises a training period (2000–2015) for score development and a test period (2016–2021) for validation. Variables were selected based on correlation with immunization coverage and standardized before PCA extraction. PC1, the principal component explaining the largest variance, was identified as a key indicator of development disparities. Findings reveal that higher PC1 scores (lower socio-economic development) are associated with reduced immunization rates, while lower PC1 scores (higher socio-economic development) correspond to greater coverage, a trend consistent across both periods. Geospatial analysis highlights stark disparities, particularly in sub-Saharan Africa and South Asia, whereas North America, Europe, and East Asia maintain significantly higher coverage. These results provide policy-relevant insights, demonstrating the utility of PCA-derived scores for resource allocation and targeted interventions. Full article

Background: Newly arrived migrants are at increased risk for vaccine-preventable and communicable diseases due to low immunization coverage, poor access to healthcare, and challenging migration trajectories. This study describes the implementation and outcomes of a one-stop public health intervention focused on serological screening and accelerated vaccination in recently arrived migrants in Galicia, Spain. Methods: We conducted a cross-sectional descriptive study in July and August 2024 involving 335 adult migrants from sub-Saharan Africa with irregular administrative status and asylum applications. A centralized mobile health unit provided point-of-care screening for immunity against measles, mumps, rubella, varicella, and hepatitis A, alongside testing for active infections, including hepatitis B and syphilis. Sociodemographic and clinical data were collected, and individuals were offered vaccination according to an accelerated immunization schedule. Results: Of 336 migrant adults invited to participate in the study, only 1 individual declined to participate (participation rate: 99.7%). Therefore, 335 migrants were assessed. A significant proportion of participants were susceptible to at least one vaccine-preventable disease, particularly hepatitis B (36.4%, 95% CI 31.3–41.6), measles (22.7%, 95% CI 18.2–27.2), and varicella (16.4%, 95% CI 12.5–20.4). Active infections were detected in 12.9% (95% CI 9.3–16.4) of individuals, including hepatitis B (9.9%, 95% CI 6.7–13.0) and syphilis (3.0%, 95% CI 1.2–4.8). The intervention allowed for timely vaccination and linkage to care, minimizing dependence on passive healthcare access. Conclusions: This study highlights substantial immunization gaps and the presence of undiagnosed infections in vulnerable migrant populations. Centralized and culturally adapted screening programs, combined with accelerated vaccination strategies, are feasible and effective. These findings support the integration of structured protocols into national health systems to ensure equity, reduce transmission risk, and align with WHO and ECDC public health frameworks. Full article

Cutaneous warts caused by human papillomavirus (HPV) are among the most common dermatological conditions, affecting the quality of life of numerous people. Although they are widespread, effective and reliable treatment alternatives are limited, emphasizing the necessity for novel treatment options. Intralesional immunotherapy has emerged as a promising alternative, aiming to stimulate the host immune response to achieve the clearance of both treated and distant lesions. This review explores the immunopathogenesis of cutaneous warts and provides an in-depth analysis of intralesional therapies including measles–mumps–rubella (MMR) vaccine, purified protein derivative (PPD), Bacillus Calmette–Guérin (BCG), Candida antigen, Mycobacterium w vaccine (MWV), vitamin D3, and autoinoculation. We provide a comprehensive analysis of the most promising modalities, highlighting their mechanism of action, outcomes, advantages, and limitations. Although initial data indicate that intralesional immunotherapy offers advantageous efficacy and tolerability, there is a lack of standardized treatment protocols and randomized controlled trials to endorse its broad application. Nevertheless, considering its potential to address local and distant lesions with minimal adverse effects, intralesional immunotherapy may represent a transformative approach to managing cutaneous warts. Full article