Search Results (422)

Integrins and other cell adhesion molecules play a critical role in the migration and homing of leukocytes. This study investigates whether metastatic tumor cells can exploit leukocyte-like rolling and arrest mechanisms during early vascular steps of metastatic dissemination. B16 melanoma cell adhesion to activated bEnd.3 endothelial monolayers or immobilized VCAM-1 were analyzed under defined shear flow using a parallel-plate chamber. Function-blocking antibodies, divalent cation modulation, pertussis toxin, and low-temperature conditions were used as classical controls. B16-BL6 melanoma cells exhibited robust VLA-4-dependent rolling and arrest on activated endothelial monolayers and on immobilized VCAM-1 under physiological shear stresses (0.7–2 dyn/cm²), independent of chemokine-related Gαi signaling. These findings identify a chemokine-independent mechanism of VLA-4-mediated vascular capture by melanoma cells under shear flow, providing a potential mechanistic basis for early steps in metastatic dissemination. Full article

Objective: Influenza and pertussis vaccines are recommended during pregnancy; however, uptake remains insufficient in many European countries, increasing the risk of preventable infections. Recent recommendations for maternal respiratory syncytial virus vaccination have been endorsed by scientific societies. This study evaluated maternal vaccination coverage, knowledge, attitudes, and factors influencing vaccine uptake among Lithuanian women. Methods: A retrospective cross-sectional online survey was conducted between 4 and 14 November 2025 in Lithuania among women aged 18–55 years with at least one previous pregnancy. The questionnaire contained 29 questions on sociodemographic characteristics, obstetric history, vaccination history, attitudes, and informational sources influencing decisions. Internal reliability was confirmed (Cronbach’s α = 0.83). Descriptive statistics were used to summarize the data. Associations between categorical variables were assessed using the Chi-square test or exact tests (Fisher’s exact or Fisher–Freeman–Halton). Binary and multivariable logistic regression analyses were performed to evaluate factors associated with self-reported vaccination uptake and the relationship between influenza and pertussis vaccination. Odds ratios with 95% confidence intervals were calculated. Statistical significance was set at p < 0.05. Results: A total of 241 women participated. Self-reported vaccination coverage during pregnancy was 28.7% for influenza, 43.8% for tetanus–diphtheria–pertussis, and 4.2% for respiratory syncytial virus. Physician’s recommendation was the strongest predictor: women advised to vaccinate were 17.0 times more likely to receive influenza, 16.5 times more likely to receive pertussis, while RSV vaccination occurred almost exclusively among women who reported receiving a physician’s recommendation. Higher uptake was associated with younger maternal age and university education. Reasons for declining vaccination were avoidance of medical interventions and concerns about safety or side effects. Conclusions: Maternal vaccination coverage in Lithuania remains low despite public funding and national recommendations. Strengthening provider communication, improving information strategies, and integrating vaccination counseling into routine antenatal care may increase uptake and enhance maternal and neonatal protection. Full article

Background: Molecular diagnostics may detect several respiratory pathogens simultaneously with rapid turnaround times. The aim of this study was to determine the frequency and distribution of respiratory pathogens among symptomatic outpatients. Methods: All outpatients presented for testing due to suspected acute respiratory infection between 1 January and 31 December 2024 to the Teaching Institute for Public Health of Split-Dalmatia County, Croatia, and multiplex real-time PCRs for 13 respiratory pathogens were included. Results: Out of 15,437 analyzed panels, 8878 (57.5%) were positive. Single-pathogen infections dominated (82.6%), while co-infections were recorded in 17.4% of panels; therefore, a total of 10,546 individual pathogens were detected, which were mostly viruses (87.0%). The following distribution of pathogens was observed: rhinovirus/enterovirus in 38.9% of positive results, influenza A virus in 14.5%, SARS-CoV-2 in 9.5%, parainfluenza virus in 7.9%, respiratory syncytial virus in 7.3%, Mycoplasma pneumoniae in 4.9%, Bordetella pertussis in 4.6%, human metapneumovirus in 4.2%, adenovirus in 3.4%, Chlamydia pneumoniae in 3.4%, influenza B virus in 1.3%, Bordetella parapertussis in 0.1% and Legionella pneumophila had one positive result. The first trimester of the year had the highest number of positive test panels (47.0%). Conclusions: Our study demonstrates a predominance of viral pathogens across all age groups and seasons, further supporting guideline-based practice and highlighting the importance of confirming bacterial infection before initiating antibiotic therapy. This insight into the post-pandemic circulation of respiratory pathogens may help inform public health strategies, including improved surveillance, anticipation of seasonal outbreaks, and targeted interventions, thereby supporting future pandemic preparedness and mitigation efforts. Full article

Background: Pemphigus diseases are rare autoimmune blistering disorders mediated by pathogenic autoantibodies directed mainly against desmoglein 1 and desmoglein 3. Although most cases are considered idiopathic, external triggers that can disrupt immune tolerance have been described. Vaccination has been discussed as a potential precipitating factor in autoimmune skin diseases. However, the relationship between vaccination and the induction of pemphigus-related autoantibodies has not been comprehensively summarized. Methods: We conducted a narrative review of all available studies published in the last 25 years identified through medical databases, excluding studies on COVID-19 vaccinations. Reports describing either new-onset pemphigus or exacerbation of preexisting pemphigus with a temporal association to vaccination were included. Clinical characteristics, vaccine type, latency period, direct immunofluorescence findings, and ELISA results for desmoglein autoantibodies were analyzed. In addition, we present our own clinical-laboratory experience illustrating this issue. Results: The current evidence consists predominantly of case reports and small case series. Published cases describe pemphigus vulgaris and pemphigus foliaceus occurring after vaccinations against influenza, hepatitis B, tetanus, diphtheria, pertussis, rabies, and other routinely administered immunizations. The latency period most often ranged from several days to a few weeks. Immunopathological findings were consistent with classical pemphigus diseases, including intercellular IgG deposits in the epidermis and circulating autoantibodies against desmoglein 1 and/or desmoglein 3. Our patient was a 78-year-old woman who developed cutaneous form of pemphigus vulgaris, diagnosed with direct immunofluorescence (DIF) and multiplex ELISA, 10 days after diphtheria–tetanus–pertussis vaccination. The patient had a positive family history of autoimmune blistering disease, namely mucous membrane pemphigoid. Conclusions: Based on the currently available evidence, a direct causal relationship between vaccination and pemphigus diseases cannot be established. Nevertheless, accumulated clinical and serological observations suggest that vaccination may act as a triggering factor in genetically or immunologically predisposed individuals, possibly by amplifying pre-existing subclinical autoreactive immune responses. Further population-based and mechanistic studies are required to clarify this association, while the overall benefits of vaccination remain substantial. Full article

Background: Pertussis and influenza immunization during pregnancy protects both mother and infant through transplacental transfer of antibodies. However, global vaccination coverage among pregnant women remains suboptimal. Aim: This systematic review aimed to assess influenza and pertussis vaccination coverage during pregnancy and identify determinants influencing vaccine uptake. Methods: A systematic search of MEDLINE, SCOPUS, and grey literature was conducted for studies published between 2000 and 2023. Studies reporting actual vaccination rates for influenza and/or pertussis among pregnant women were included, while those assessing only willingness were excluded. Studies on H1N1 pandemic vaccination in pregnant women were excluded to avoid bias, as awareness levels during the pandemic differed from routine influenza vaccination. Determinants of vaccine acceptance were recorded. Study quality was evaluated using the Newcastle–Ottawa Scale. Results: Of 3251 identified records, 78 studies on influenza (N₁ = 287,124 participants) and 51 on pertussis (N₂ = 172,801) met inclusion criteria after removing overlapping populations. Most influenza studies (55/78) reported vaccination coverage below 50%. A key determinant of influenza vaccination uptake was physician recommendation, while maternal attitudes, parity, and previous influenza vaccination also had a significant impact. For pertussis, vaccination coverage was primarily driven by physician recommendation, with parity and maternal perceptions of vaccine safety and effectiveness further influencing uptake. Regarding quality assessment, 52.5% of influenza studies and 37.5% of pertussis studies scored above 6 on the Newcastle–Ottawa Scale. Conclusions: Maternal vaccination coverage for influenza and pertussis remains inadequate worldwide and is shaped by national strategies, healthcare provider practices, and maternal perceptions. Addressing vaccine hesitancy and improving awareness are essential to increase uptake. Full article

Background: Liberia modernized vaccination data systems in 2023–2025 by piloting a District Health Information System (DHIS2)-based Digital Vaccination Registry (Electronic Immunization Registry, EIR) to address the limitations of paper-based workflows and of a proprietary COVID-19 electronic platform (offline gaps, lack of unique identifiers, performance issues and cost). Objective: To assess a pilot platform by evaluating training, registry use and device management, utility for routine immunization, vaccine logistics and Adverse Events Following Immunization (AEFI) data, and routine immunization data quality in the DHIS2 mobile application compared with paper registers. Methods: Using the Public Health Informatics Institute’s Collaborative Requirements Development Methodology, stakeholders defined requirements, trained users and implemented a pilot. Mixed methods were used; a mini data audit was performed, and qualitative data were collected across 19 facilities in Montserrado, Gbarpolu and Grand Bassa. Seventy-eight health workers were trained to use the DHIS2 mobile application. Results: The future state design replaces paper aggregation steps with real-time mobile entry to a national registry and dashboard. Dual entry persisted during high-volume periods. The mini data audit found discrepancies between facility paper registers and DHIS2-EIR entries for child enrollment data and, Bacillus Calmette Guérin and Diphtheria–Pertussis–Tetanus dose administration records Participants attributed these discrepancies to internet and device problems and challenges navigating the system. Participants requested a training manual, improved connectivity at point of service, integration with supportive supervision, additional staff and system features (field to record hospital number, automated next visit date, and vaccination status prompts). Conclusions: Lessons from the pilot will inform country-wide implementation, including planned linkage with electronic birth and death registration to enable a unique child identifier and reduce manual errors and delays. Full article

Background: Despite its high vaccination coverage, pertussis remains a public health concern due to waning vaccine-induced immunity and the emergence of pertactin (Prn)-negative strains. Nevertheless, anti-Prn antibodies and memory B cells elicited by vaccinations may contribute to long-term immunity and protection against Prn-positive strains. While most vaccination studies focus on serum antibodies, data on memory B cells remain limited. Methods: In this study, we implemented a flow cytometry-based approach to characterize Prn-specific B-cell fluctuations following Tdap booster vaccination in five healthy adults. Total and Prn- and tetanus toxoid fragment C (TTC)-specific plasma cells and memory B cells were analyzed at baseline and at 7, 14, 21, and 90 days post-vaccination using Prn Klickmers^® and TTC tetramers. Following this, cellular responses were correlated with antigen-specific serum IgG and IgA levels. Results: Prn-specific and TTC-specific memory B cells increased on days 14 and 7 post-vaccination, respectively, accompanied by a phenotypic shift from IgMD+ to IgG+ cells. Clear expansions of total as well as Prn- and TTC-specific plasma cells occurred on day 7. These plasma cells primarily comprised IgG+, but an increase in Prn-specific IgA+ plasma cells was also observed. The numbers of Prn-specific IgG+ memory B cells on day 7 post-vaccination correlated weakly with serum anti-Prn IgG levels at later time points. Conclusion: To our knowledge, this is the first study to use flow cytometry to evaluate Prn-specific B-cell responses and report their fluctuations over time following vaccination. These findings support the potential of this method to complement serological assays and improve our understanding of vaccine-induced immunity. Full article

Pertussis, caused by Bordetella pertussis, remains a public health concern despite long-standing vaccination programs. After a marked decline during the COVID-19 pandemic, a resurgence was observed in Europe and Italy, with a sharp increase in 2024. This study describes pertussis epidemiological trends in the Tuscany Region (Italy) from 2019 to 2024 to identify high-risk groups and inform prevention strategies. A retrospective population-based analysis was conducted using cases reported to the national surveillance system (PREMAL). Incidence rates were calculated using ISTAT population data, and demographic, temporal, and clinical characteristics were analyzed. Overall, 669 cases were reported (mean annual incidence rate: 3.03/100,000 (IC 95% 2.47–3.59; period incidence rate: 18.2/100,000 (IC 95% 16.81–19.56)), with 89% occurring in 2024 (16.34/100,000 (IC 95% 15.03–17.65)). No sex differences were observed, and most cases were reported in Central Tuscany (64%). Children under 15 years accounted for 87% of cases. The highest incidence was observed among 10–14-year-olds, while infants < 1 year, particularly those under 4 months, showed the highest burden in narrower age strata. Hospitalizations occurred in 12.6% of cases, decreasing substantially in 2024. The 2024 resurgence likely reflects waning immunity, disruptions to routine vaccinations during the pandemic, and reduced pathogen circulation in previous years due to containment and isolation measures related to the pandemic. Strengthening surveillance and improving booster and maternal vaccination coverage are essential to protect vulnerable populations. Full article

Pertussis toxin (PTx) is a major virulence factor of Bordetella pertussis and an AB5-type exotoxin that disrupts host signaling. Its enzymatic A subunit ADP-ribosylates the α-subunit of inhibitory G proteins (Gα_i), preventing them from mediating receptor-induced inhibition of adenylyl cyclase (AC). This leads to unrestrained cAMP accumulation in host cells, a canonical mechanism underlying many pertussis disease manifestations. PTx works in concert with the bacterium’s adenylate cyclase toxin (ACT) to subvert immune defenses and establish infection. Interestingly, PTx exerts both cAMP-dependent and cAMP-independent effects. In addition to the well-known cAMP-mediated pathway, PTx’s B oligomer can engage host cell surface receptors to trigger signaling cascades independent of the A subunit’s catalytic activity. Such B oligomer-mediated pathways modulate cellular responses in the absence of ADP-ribosylation. This review provides a comprehensive analysis of PTx’s dual functionality, distinguishing its G_i protein-dependent elevation of cAMP from the noncanonical activities of the B oligomer. It also highlights how disruption of constitutive G_i signaling and the interplay between PTx and ACT shape host–pathogen interaction in pertussis pathogenesis. Full article

Background/Objectives: Healthcare workers (HCWs) have a crucial role in addressing vaccine hesitancy in ethnic minority populations as they are a trusted source of information. The aim of this systematic review is to synthesise and evaluate behaviour change techniques (BCTs) and strategies in interventions aimed at HCWs to promote vaccine uptake among ethnic minority populations. Methods: The literature was systematically searched in peer-reviewed databases and the grey literature. Studies were included if they reported interventions for respiratory and routinely recommended vaccine-preventable diseases which were delivered by HCWs to increase vaccine uptake in ethnic minority groups. Interventions were coded using the Behaviour Change Wheel (BCW) and BCT Taxonomy. Results: From 7250 records identified, 14 studies were included in the review. Vaccines targeted by interventions included influenza, pneumococcal disease, pertussis, tetanus, diphtheria, meningitis and hepatitis B. Seven BCW intervention types, six policy options and 22 BCTs were identified. Main intervention types used were persuasion, enablement and education. Effective interventions had multi-components and were tailored to specific populations. Staff training to improve vaccine recommendation and dialogue with patients, and prompts/cues were associated with positive effects, but there was no strong evidence to recommend one specific intervention strategy over another as effectiveness was linked to a multitude of BCTs and intervention types. Conclusions: Several strategies aimed at HCWs can be used and tailored to increase vaccine uptake among ethnic minority communities; however, this does not address all issues related to low vaccine uptake. While HCWs are necessary, without system-level enablement, they cannot fully address barriers to vaccine uptake. Full article

Objective: To investigate how the high-altitude environment modifies severe pertussis in young infants and analyze its pathophysiological mechanisms and clinical management implications. Methods: Clinical data of two young infants with severe pertussis residing at 3650 m were retrospectively analyzed, including presentation, laboratory findings, pathogen detection, treatment, and outcomes. A literature review explored synergistic interactions between high-altitude factors and pertussis pathophysiology. Results: Case 1 had macrolide-resistant Bordetella pertussis (MRBP, 23S rRNA A2047G) with peak WBC 52.25 × 10⁹/L, and received cefoperazone-sulbactam, piperacillin-tazobactam and azithromycin, and was successfully treated with trimethoprim-sulfamethoxazole combined with exchange transfusion. Case 2 had Bordetella pertussis confirmed by PCR with peak WBC 36.55 × 10⁹/L, receiving cefoperazone-sulbactam and azithromycin, and recovered. Both developed respiratory failure requiring non-invasive ventilation and survived without pulmonary hypertension. High-altitude stressors—hypoxia, enhanced pulmonary vascular reactivity, and hypercoagulability—synergize with pertussis-induced hyperleukocytosis as a “dual hit,” accelerating cardiopulmonary deterioration and elevating thrombotic risks. Conclusions: High altitude is an independent risk modifier in infantile pertussis, demanding heightened vigilance and proactive interventions: early non-invasive ventilation, prophylactic anticoagulation, and timely exchange transfusion before pulmonary hypertension develops. This is the first high-altitude case series that provides essential insights for clinicians in similar environments globally, guiding early recognition and proactive management strategies to improve outcomes in this vulnerable population. Full article

Objectives: The study’s objective was to assess ten diphtheria–tetanus–pertussis (DTP) vaccination program indicators globally and in World Health Organization (WHO) regions in 2024, and compare the values in 2024 and 2019. Methods: Global and regional values for routine DTP vaccination performance indicators were assessed in 2024. Means and percentages in 2024 and 2019 were compared using the t-test and Chi-square test, respectively, considering p < 0.05 as statistically significant. High-priority countries for DTP vaccination coverage increase were identified in each WHO region based on the indicators assessed in this study. Results: The global mean vaccination coverage for DTP1, DTP3 and three DTP doses were 90.7%, 86.6% and 72.8%, respectively, in 2024. Eight of the ten indicators assessed in this study worsened and two improved globally from 2019 to 2024. The differences between 2019 and 2024 were statistically significant for the three-dose DTP coverage decrease in the European WHO region (88.1% vs. 82.5%, p < 0.05), and the decrease in the global percentage of countries with ≥90% three-dose coverage (34% vs. 21%, OR = 0.52, 95% CI: 0.33–0.81, p < 0.005). This study identified 27 (13.8%) high-priority countries for DTP vaccination coverage increase due to DTP1 coverage lower than 80%; 47 (24.1%) countries due to DTP3 coverage lower than 80%; and 48 (24.6%) countries due to three-dose coverage lower than 60%. Conclusions: Global and regional DTP vaccination performance indicators in 2024 did not recover to pre-pandemic levels, although the differences between 2024 and 2019 were statistically significant only for two regional indicators. Full article

Background: In 2019, pneumonia caused 740,180 deaths in children under five years of age, representing 22% of global mortality in this age group. During the COVID-19 pandemic, public health interventions markedly reduced the circulation of most respiratory viruses other than SARS-CoV-2, leading to significant post-pandemic shifts in respiratory pathogen epidemiology. This study aimed to characterize the epidemiology, clinical features, and risk factors associated with respiratory viruses and bacteria causing pneumonia in Mexican children during the late pandemic and post pandemic periods. Methods: Children younger than 14 years with pneumonia were recruited from seven hospitals in Mexico. Demographic and clinical data were collected, and nasopharyngeal swabs were analyzed using a multiplex PCR panel detecting 19 viruses and 7 bacteria. Univariate, bivariate, and logistic regression analyses were performed (SPSS v25). Results: A total of 1715 children were included: 704 during the pandemic (2021–2023) and 1011 post-pandemic (2023–2025). Co-infections (72% vs. 65%, p < 0.001), virus–virus co-infections (25% vs. 11%, p < 0.001), and single viral infections (20% vs. 15%, p = 0.007) were more frequent during the pandemic. Pathogen detection was high in both periods, though negative samples increased post-pandemic (5.4% vs. 15%, p < 0.001). During the pandemic, the 5 most frequently detected pathogens were rhinovirus (66%), RSV A and B (38%), Streptococcus pneumoniae (30%), Haemophilus influenzae (28%), human metapneumovirus (13%). In the post-pandemic period, the 5 most frequently detected pathogens were rhinovirus (52%), Haemophilus influenzae (36%), Streptococcus pneumoniae (35%), RSV A and B (28%), metapneumovirus (11%). Rhinovirus and RSV predominated during the pandemic, whereas Haemophilus influenzae, Streptococcus pneumoniae, parainfluenza viruses, Bordetella pertussis, and Mycoplasma pneumoniae significantly increased post-pandemic. Conclusions: Pediatric pneumonia epidemiology shifted from a predominantly viral profile during the pandemic to increased bacterial detections and virus–bacteria co-infections post-pandemic, alongside re-emergence of typical RSV and influenza seasonality. Higher mean age and rhinovirus as the most frequent pathogen persist after the pandemic. Sustained molecular surveillance and reinforced vaccination programs remain essential in the post-pandemic era. Full article

Global cancer incidence reached 20 million new cases across 185 countries in 2022, with approximately 10 million cancer-related deaths annually. Among adults with solid tumors and hematological malignancies, infections are a major contributor to morbidity and mortality, with respiratory infections playing a particularly significant role. These infections not only reduce life expectancy but can also delay cancer therapy, negatively affect treatment outcomes, and increase healthcare costs. In recent years, the burden of respiratory infections in this population has been driven by influenza virus, SARS-CoV-2, respiratory syncytial virus, Streptococcus pneumoniae, and Bordetella pertussis. Effective vaccines are available for all these pathogens and are recommended for adults with cancer, yet vaccination uptake remains suboptimal despite their heightened vulnerability. This review provides practical guidance for healthcare professionals on vaccinating adults with cancer against respiratory infections, summarizing key information to help clinicians address vaccination-related complacency, confidence, and convenience. Evidence from studies in both the general population and cancer patients consistently shows that vaccination benefits outweigh potential risks, with adverse event rates comparable to those seen in individuals without cancer. Early vaccination is encouraged, as there is limited justification for delaying immunization even when immune responses may be reduced. Vaccine dosing aligns with recommendations for the general population, with important exceptions. Live attenuated vaccines should be avoided because of the risk of replication and disease in immunocompromised patients, and selected groups may require booster doses to achieve adequate protection. Notably, cancer immunotherapy does not appear to impair vaccine-induced immune responses. Full article

Background: Administering several separate childhood vaccines can reduce adherence to immunization schedules due to missed appointments and the burden of repeated injections. A hexavalent formulation targeting diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type B, and poliovirus offers a practical approach to improve compliance and streamline immunization. Methods: Toxicity testing was performed in Wistar rats and New Zealand White rabbits (60 rats and 30 rabbits). Animals were distributed into three groups: hexavalent vaccine + low-dose sIPV, hexavalent vaccine + high-dose sIPV, and control. Each animal received a 0.5 mL intramuscular injection at weeks 0, 4, 8, and 12. Clinical observations were conducted throughout the study. Serum samples were collected one day before each injection and at the endpoint, while liver tissue was collected at the endpoint. ALT and AST concentrations were analyzed using an automated analyzer, and hepatic morphology was evaluated microscopically. Results: No abnormal clinical signs related to vaccination were observed. ALT concentrations showed no significant differences (p > 0.05). AST differences (p < 0.05) were detected between the high-dose group and the control on day 27 in female rabbits and on day 83 in female rats; however, all values remained within normal physiological limits. Histopathological examination revealed no irreversible hepatic lesions, including hydropic degeneration, portal inflammation, focal necrosis, or connective tissue proliferation, and no significant differences were noted (p > 0.05). Conclusions: Repeated administration of the hexavalent vaccine candidate at low and high doses produced no toxicological effects in animal models, supporting its safety for further clinical development. Full article