Search Results (342)

Background/Objectives: Rabies is a fatal zoonotic disease caused by the rabies virus (RABV), and effective therapeutic treatments are currently lacking. Vaccination remains the primary strategy for rabies control. The Semliki Forest virus-rabies virus glycoprotein (SFV-RVG), a virus-like vesicle rabies vaccine combining Semliki Forest virus replicase and rabies glycoprotein, has shown potential as a promising vaccine candidate. This study aimed to optimize the production of SFV-RVG and evaluate adjuvant formulations to improve its immunogenicity in both mice and dogs. Methods: SFV-RVG production was optimized by determining the optimal multiplicity of infection (MOI) at 0.03 and cell density at 1 × 10⁶–1.3 × 10⁶ cells/mL, followed by scaling up the process in bioreactors. Eleven adjuvant formulations were tested in mice and dogs to assess their effects on immunogenicity. Cytokine analysis and antibody responses were measured, including IFN-γ, IL-4, IgG2a/IgG1 ratios, and neutralizing antibody titers. Results: The optimized SFV-RVG production was successfully scaled up, and M103 adjuvant induced rapid early antibody titers in mice. In dogs, GEL02 led to the highest neutralizing antibody levels, exceeding 40 IU/mL by 28 days post-immunization. Cytokine analysis indicated that both M103 and GEL02 significantly enhanced IFN-γ and IL-4 expression, balancing the Th1/Th2 immune response. SFV-RVG with GEL02 demonstrated stronger immunogenicity than a commercial vaccine, and challenge studies confirmed robust protection against lethal RABV in mice. Conclusions: This study establishes GEL02 as a superior adjuvant for rabies vaccines and provides a scalable SFV-RVG production process. These findings highlight SFV-RVG with GEL02 as a promising rabies vaccine candidate for dogs, offering significant potential for rabies control. Full article

Background: Healthcare-associated infections represent a significant public health problem, with a major impact on patient safety and quality of care. Nursing students play a central role in implementing infection prevention and control measures, yet the existing literature highlights gaps in their preparedness. Objective: To investigate nursing students’ knowledge of healthcare-associated infections, providing a comprehensive understanding of their level of awareness and identifying potential gaps that could guide improvements in nursing education. Methods: A systematic review was conducted by PRISMA guidelines. Searches were performed in PubMed, CINAHL Complete, APA PsycArticles, and APA PsycInfo, using predefined keywords and inclusion criteria. Twenty-two studies met the eligibility requirements. The articles were assessed for methodological quality using validated appraisal tools. Results: Across the included studies, nursing students demonstrated good knowledge of certain infection prevention measures, particularly standard precautions and hand hygiene. However, significant theoretical gaps were identified, especially regarding epidemiology, transmission mechanisms, and risk factors for healthcare-associated infections. Knowledge tended to improve with academic progression, clinical experience, and the use of active, contextualized teaching strategies. A consistent gap between theoretical understanding and practical application was observed. Conclusions: Nursing curricula should systematically integrate theory and practice, ensure alignment with validated international guidelines, and adopt active, practice-oriented teaching approaches. Strengthening these areas could improve nursing students’ infection prevention competencies, thereby enhancing patient safety and quality of care. Full article

Primary hip and knee arthroplasties are common surgeries in the U.S., with periprosthetic joint infection (PJI) being the leading cause of implant revision. Systemic antibiotics often fail to achieve sufficient local concentrations, driving interest in localized drug delivery. Titanium (Ti) implants modified with titania nanotubes (TNTs) provide an increased surface area for drug loading and controlled release. Previous studies have shown that gentamicin-loaded TNTs inhibit Staphylococcus aureus growth in vitro without compromising osteoblast viability. This study investigated the effect of gentamicin–chitosan (GC)-coated TNT implants in a murine model, hypothesizing a positive impact on osseointegration. Titanium alloy (Ti6Al4V) wires were anodized to form TNTs and then coated with gentamicin–chitosan (GC) via electrophoretic deposition. Implants (Bare, TNT, TNT+GC; n = 30) were inserted bilaterally into femoral canals of C57BL/6J mice. After > 1 month, osseointegration was assessed by histological point counting, scanning electron microscopy (SEM)-based areal analysis, and mechanical pull-out testing. ANOVA was used to identify differences between groups, and linear regression was applied to account for harvest time, bone contact area, and anatomical section. Bone area fraction (BAF) around the implant measured by the SEM–areal method was significantly higher around TNT+GC (18.4% ± 1.1) and TNT (16.5% ± 1.4) versus Bare (9.0% ± 2.3) (p < 0.0028) implants. The maximum fixation strength was higher for TNT (0.878 ± 0.175 N/mm²) and TNT+GC (0.853 ± 0.215N/mm²) when compared to bare implants 0.316 ± 0.082 N/mm²) (p = 0.048 and p = 0.050, respectively). No significant differences appeared between TNT and TNT+GC. These findings indicate that GC coatings on TNT implants do not impair osseointegration and may even enhance bone–implant integration. Such coatings may therefore provide dual benefits, offering antibacterial protection while improving bone fixation, making them a promising strategy for PJI prevention. Further long-term studies are needed to confirm durability and clinical translation. Full article

Infection with oncogenic human papillomavirus (HPV) remains a leading cause of cervical cancer and other HPV-related diseases. This situation persists despite the availability of effective prophylactic vaccines. While global vaccination programs have significantly reduced the incidence of HPV in adolescents and young adults, many women presenting with HPV infection or squamous intraepithelial lesions (SIL) were not covered by primary prevention. This review was performed with the aim of evaluating the impact of administering the 9-valent HPV vaccine in adult women who are HPV-positive or have histologically confirmed cervical precancerous lesions. Following the PRISMA 2020 guidelines, a search was performed in the MEDLINE, Scopus, and Cochrane Library databases. A total of 653 studies were retrieved, of which 7 studies, including 19,414 women, met the inclusion criteria. According to the literature, vaccination was linked to significant reductions in persistent HPV infection, progression of SIL, and recurrence of high-grade lesions after surgical removal. Complete HPV remission was achieved in up to 72.4% of vaccinated women, compared to 45.7% among unvaccinated controls. Vaccination after conization lowered the recurrence risk of CIN2+ lesions by 87%, with benefits seen regardless of timing. The most significant effect was observed when vaccine administration was performed before the surgical procedure. Furthermore, HPV vaccination notably enhanced viral clearance and decreased the likelihood of repeated surgical interventions. Despite differences in study design and follow-up definitions, the overall evidence supports additional vaccination in HPV-positive adult women as an effective measure to reduce recurrence and promote viral remission. These findings emphasize the need for clear guidelines and wider access to HPV vaccination for adult populations. Full article

Legionella is an environmental bacterium capable of causing severe respiratory infections, with outbreaks posing significant public health challenges in developed countries. Understanding public awareness of Legionella transmission, risk perception, and preventive behaviors is crucial for reducing exposure and guiding health education strategies. This study aimed to evaluate the Portuguese population’s knowledge of Legionella infections and their readiness to adopt preventive measures. A structured questionnaire was developed and administered to 239 participants aged 18–76 years across Portugal, collecting socio-demographic data and assessing literacy through statements organized into domains related to Legionella risk, control measures, and public health impact. The results indicate that participants possess moderate to high awareness of Legionella severity, transmission routes, and preventive strategies, yet gaps remain in understanding key risk factors, optimal water system maintenance, and the influence of temperature on bacterial growth. Age, educational attainment, and occupational status were associated with differences in self-assessed literacy levels. Artificial neural network models were applied to classify literacy levels, achieving a near 90% accuracy and demonstrating higher confidence in low and moderate categories. These findings provide insights for designing tailored educational programs, improving public health communication, and enhancing preventive behaviors to reduce Legionella infection risks. Full article

Chicken infectious anemia virus (CIAV) causes immunosuppression in poultry, leading to substantial global economic losses through both vertical and horizontal transmission. Since 2014, frequent outbreaks have been reported in southern China; however, the epidemiology of CIAV in Guangdong Province remains poorly defined. Between July 2018 and March 2022, we collected 105 tissue samples and 786 serum samples from poultry in nine cities. PCR/qPCR assays targeting the VP1 gene confirmed CIAV infection, and positive tissues inoculated into MSB1 cells yielded four isolates (GDHZ1, GDHZ2, GDJM, GDLF). Phylogenetic analysis demonstrated that GDHZ1, GDJM, and GDLF clustered within clade A1, whereas GDHZ2 belonged to clade A2. All isolates shared glutamine (Q) at position 394, together with virulence-associated amino acid signatures (75V, 89T, 125L, 139K, 141Q, 144E). Serological testing indicated a high prevalence, with 627 of 786 samples positive (79.77%). The relatively low proportion of virus-positive tissues and successful isolations may reflect viral tropism or limitations in detection sensitivity. These findings enhance understanding of CIAV molecular epidemiology in Guangdong and provide evidence to inform surveillance, vaccination strategies, and control measures. Full article

Bovine Viral Diarrhea Virus (BVDV) is a globally important cattle pathogen causing substantial economic losses. In Kazakhstan, BVDV’s epidemiological status remains poorly characterized due to the absence of systematic surveillance. We carried out a cross-sectional study of cattle herds across Kazakhstan, using ELISA to detect anti-BVDV antibodies and RT-PCR to identify active infections. Positive samples underwent sequencing for phylogenetic analysis of circulating strains. Additionally, a standard reference serum panel was developed to measure virus neutralization titers (ND₅₀) and to evaluate cross-neutralization with Border Disease virus (BDV). Antibodies against BVDV were prevalent, with seropositivity ranging from 28.89% to 96.13% across surveyed regions. Active BVDV infection was confirmed by RT-PCR in 17 animals. Phylogenetic analysis with 2 samples from Mangystau region classified the virus as BVDV2 genotype. The reference serum panel exhibited high neutralizing titers ND₅₀ up to 1:286 against the local BVDV-1 isolate. Notably, these sera also neutralized BDV, albeit at lower titers ND₅₀ 1:45. These findings provide crucial baseline epidemiological data and enhanced diagnostic tools for BVDV in Kazakhstan. They highlight the need for improved surveillance and will inform strategic control measures against this economically significant cattle disease. Full article

Background: While rhinoviruses (RVs) typically cause mild respiratory infections, their persistence during the SARS-CoV-2 pandemic, particularly in Hong Kong’s strict zero-coronavirus disease 2019 policy, revealed unexpected epidemiological patterns. Two distinct RV surges emerged despite stringent public health measures, suggesting unique transmission advantages among circulating strains. We hypothesised that RV persistence during pandemic restrictions reflected strain-specific adaptations in respiratory tract replication efficiency and/or immune evasion. Methods: We analysed RV genotypes and conducted blinded clinical severity assessment for 96 paediatric hospitalisations during 2020–2021 outbreaks, compared with 180 age- and sex-matched control subjects from the corresponding weeks in pre-pandemic years (2018–2019). RV isolates from 2020 to 2021 outbreaks were characterised for their replication competence and transcriptomic responses in primary human nasal epithelial cell (HNEC) and environmental stability assays, using RV-A16 and RV-A1B as controls. Result: Minor group genotypes RV-A47 and RV-A49 were overrepresented during these two outbreaks. RV-A49 exhibited comparable replication efficiency to RV-A16 but induced significantly stronger transcriptomic responses, notably enhanced TNF and IL-1 signalling, in HNECs, alongside robust replication competence. Our data also suggests the association of RV-A49 with tachypnoea in 2021, particularly in younger males, though limited by a small sample size and single-centre design. Conclusion: The predominance of RV-A49 in hospitalised children during the SARS-CoV-2 pandemic potentially driven by its replication competence in HNECs and its capacity to enhanced inflammatory responses. The result is hypothesis-generating, warranting further studies with historical strains and broader populations to confirm strain-specific severity. Full article

Background: Lower respiratory tract infections (LRTIs) are one of the leading causes of mortality. Pharmacist-led interventions can enhance adherence to antibiotics; the present study aims to determine adherence to the antibiotics prescribed for LRTIs and related factors. Methods: An individual randomized controlled trial was conducted with 1:1 (intervention = 205, control = 205) participants aged >18 years. The primary outcomes included adherence to therapy at weeks 1 and 2, awareness of antibiotic use, and appropriate discontinuation as prescribed. The secondary outcome measures were the overall clinical outcomes of the therapy and the effectiveness of educational interventions assessed at the final week 7 (overall assessment checked and treatment was not continued). The data were analyzed using different statistical methods, including descriptive statistics for data summarization, and inferential techniques were used. Results: Finally, 187 patients remained in the intervention group, and a total (n = 18) lost to follow-up. The awareness was significantly increased through pharmacist-led interventions (n = 106, 56.7%; p = 0.01), along with the factors leading to antibiotic resistance knowledge. Overall, adherence to antibacterial therapy for the LRTIs has improved (p ≤ 0.01), and a significant correlation exists between overall MMAS-8 mean scores and other demographic factors; interventions improved [0.441–2.151] with adherence (post-intervention). Higher adherence was found (p ≤ 0.05) among the participants in the intervention group compared to the control group and with (OR: 1.050; CI: 0.150–1.024) demographics (education, p = 0.05). Conclusions: Overall, the intervention group showed better awareness, understanding, and attitudes about antibiotics, and their adherence to antibiotic therapy improved significantly, along with the overall clinical outcomes. Full article

The current studies examined very early events associated with activation and initiation of a human immune response after sham exposure or exposure to influenza virus (IAV) versus respiratory syncytial virus (RSV), focusing on the function of a critical accessory cell for lymphocyte responses. Calcium mobilization by monocytes/macrophages was rapid and marked in response to exposure to IAV but was muted in response to RSV. Monocytes/macrophages exposed to IAV showed markedly enhanced expression of Cox-2 mRNA measured soon after exposure, whereas exposure to RSV resulted in reduced expression (relative to control cells). In contrast, expression of the constitutively expressed 2.8 kb Cox-1 mRNA was relatively constant. The 72/74 kDa/pl 7.5 protein doublet (product of the Cox-2 gene) was identified in lysates of IAV-exposed monocytes/macrophages but not RSV-exposed monocytes/macrophages. The results demonstrate that human monocytes/macrophages show reduced responses to RSV, similar to previously demonstrated effects of RSV on lymphocyte responses. This relative lack of early responses may contribute substantially to the ability of RSV to re-infect individuals. Full article

Candida infections pose a significant health threat, and conventional antifungal drugs like nystatin are limited due to poor solubility, skin permeability, and frequent dosage requirements. Nystatin effectively targets Candida species by disrupting cell membranes, but formulation issues hinder clinical use. Lipid-based vesicular carriers, or novasomes, provide controlled, prolonged drug release and enhanced skin penetration. This study focuses on developing nystatin-loaded novasomal gels as an advanced drug delivery system to enhance therapeutic efficacy, bioavailability, and patient compliance. The formulation was prepared using a modified ethanol injection technique, combining stearic acid, oleic acid, Span 60, cholesterol, and Carbopol to produce a stable transdermal gel. Comprehensive in vitro characterization using FTIR, SEM, XRD, and thermal analysis confirmed the chemical compatibility, morphological uniformity, and physical stability of the nystatin-loaded novasomal gel. Entrapment efficiency differed significantly among the formulations (p < 0.05), with F7 achieving the highest value (80%). All formulations maintained pH levels within the skin-friendly range of 5.5 to 7.0. Viscosity measurements, ranging from 3900 ± 110 to 4510 ± 105 cP, confirmed their appropriate consistency for dermal use. Rheological analysis showed a dominant elastic response, as indicated by storage modulus values consistently higher than the loss modulus. Particle size ranged from 4143 to 9570 nm, while PDI values remained below 0.3, reflecting uniform particle distribution. Zeta potential values were strongly negative, supporting physical stability. XRD studies indicated reduced crystallinity of nystatin within the formulations, while FTIR confirmed drug-excipient compatibility. SEM images showed spherical particles within the micrometer range. In vitro release studies demonstrated sustained drug release over 12 h, with F6 releasing the highest amount. The novasomal gel formulations-maintained stability for 30 days, with no notable alterations in pH, viscosity, or entrapment efficiency. Antifungal evaluation showed a larger inhibition zone (23 ± 2 mm) compared with the plain drug solution (15 ± 1.6 mm), while the MIC value was reduced (4.57 µg/mL), indicating greater potency. Skin irritation assessment in rats revealed only minor, temporary erythema, and the calculated Primary Irritation Index (0.22) confirmed a non-irritant profile. These findings suggest that the developed novasomal gel offers a promising approach for enhancing the treatment of fungal infections by enabling prolonged drug release, minimizing dosing frequency, and improving patient compliance. Full article

Colistin resistance, driven by chromosomal mutations and the spread of plasmid-mediated MCR genes, has emerged as a critical challenge in combating multidrug-resistant Gram-negative bacteria. This resistance compromises the efficacy of colistin, leading to higher treatment failure rates, prolonged hospitalizations, and increased mortality. Recent studies have highlighted key mechanisms, including lipid A modifications, that enable bacteria to evade colistin’s effects. The global spread of MCR genes exacerbates the issue, underlining the need for improved diagnostics and rapid detection of resistant strains to prevent adverse patient outcomes. To combat this growing threat, a multifaceted approach is essential, involving enhanced antimicrobial stewardship, stricter infection control measures, and continued research into alternative therapies and diagnostic methods. Collaborative efforts from researchers, healthcare providers, policymakers, and the pharmaceutical industry are crucial to preserving colistin’s effectiveness and mitigating the broader impact on public health. Full article

A spatiotemporal transmission epidemic model is proposed based on human mobility, spatial factors of population migration across multiple regions, individual protection, and government quarantine measures. First, the model’s basic reproduction number and disease-free equilibrium are derived, and the relationship between the basic reproduction number in a single region and that across multiple regions is explored. Second, the global asymptotic stability of both the disease-free equilibrium and the endemic equilibrium is proved by constructing a Lyapunov function. The impact of population migration on the spread of the virus is revealed by numerical simulations, and the global sensitivity of the model parameters is analyzed for a single region. Finally, a protection isolation strategy based on the optimal path is proposed. The experimental results indicate that increasing the isolation rate, improving the treatment rate, enhancing personal protection, and reducing the infection rate can effectively prevent and control the spread of the epidemic. Population migration accelerates the spread of the virus from high-infected areas to low-infected areas, aggravating the epidemic situation. However, effective public health measures in low-infected areas can prevent transmission and reduce the basic reproduction number. Furthermore, if the inflow migration rate exceeds the outflow rate, the number of infected individuals in the region increases. Full article

Ehrlichiosis and anaplasmosis are endemic to tropical and subtropical regions and pose significant zoonotic threats to both human and animal health. This study aimed to detect anti-Ehrlichia canis, anti-Borrelia burgdorferi, and anti-Anaplasma antibodies in dogs from the rural–urban area of Huamanga, Ayacucho. The cross-sectional survey was conducted at the Facultad de Ciencias Biológicas of the Universidad Nacional de San Cristóbal de Huamanga between May and August 2023. Samples were collected via venipuncture, and antibody detection was performed using the immunochromatographic assay Anigen Rapid CaniV-4 kit. Frequencies, percentages, and statistical analyses were conducted using the SPSS^® software package. A total of 107 samples from dogs in the Covadonga Human Settlement were analyzed, comprising 64 (59.8%) males and 43 (40.2%) females. The majority (78.5%) were from mixed-breed dogs, while other dogs breed included Schnauzers, Pekingese, and Pitbulls. Thirty positive samples were identified, with antibodies against Ehrlichia canis (15.9%), Anaplasma phagocytophilum/Anaplasma platys (3.7%), mixed infections of Ehrlichia canis and Anaplasma phagocytophilum/Anaplasma platys (6.5%), and Ehrlichia canis/Borrelia burgdorferi (1.9%) detected, as well as an association between vector exposure and the presence of Ehrlichia canis antibodies. These findings underscore the urgent need for the implementation of integrated control strategies and enhanced surveillance programs targeting tick-borne diseases in high-risk areas, along with targeted educational campaigns to promote responsible pet ownership and preventive measures. Full article

Healthcare professionals (HCPs) working in paediatric settings are routinely exposed to respiratory pathogens, increasing their risk of asymptomatic colonisation by meningitis-associated bacteria. This study is the first to assess oropharyngeal and nasopharyngeal carriage of major bacterial meningitis pathogens among paediatric HCPs in Benin, and to identify associated risk factors. A cross-sectional analytical study was conducted in nine hospitals between 1 September 2023 and 30 September 2024. Data collection involved a structured questionnaire and paired oropharyngeal and nasopharyngeal swabs. Culture-based identification and antimicrobial susceptibility testing were performed according to CA-SFM guidelines. By culture method, Streptococcus pneumoniae was the most frequently isolated pathogen, mainly from oropharyngeal samples (47.5%). Most of these strains exhibited multidrug resistance. In nasopharyngeal samples analysed by real-time PCR, detection rates for S. pneumoniae were markedly higher (24.4%) compared to culture (5.0%), highlighting the limited sensitivity of conventional methods in detecting asymptomatic carriage. Pneumococcal colonisation was significantly associated with recent respiratory tract infections, and residence in high-risk areas (p < 0.05). These findings underscore the need for enhanced molecular surveillance, along with strengthened infection control measures and targeted vaccination strategies, to mitigate the risk of horizontal transmission in paediatric wards. Full article