Search Results (6,829)

To prevent the spread of antibiotic resistance, bacteriophages have gradually become the most promising alternative to antibiotics for treating bacterial infectious diseases. In this study, using E. coli DC1 as the host strain, we isolated a bacteriophage named Escherichia coli phage XJA18 from farm sewage. We conducted morphological identification, host range determination, biological characteristic analysis, genomic feature analysis, and evaluation of in vitro and in vivo antibacterial effects. Electron microscopy revealed that phage XJA18 belongs to the class Caudoviricetes, with an icosahedral head and a non-contractile long tail. Whole-genome sequencing revealed that the phage has dsDNA with a length of 50,572 bp, with a GC content of 45.33%. The genome does not contain any antibiotic resistance genes or virulence genes, indicating good safety. XJA18 showed lytic activity against 24% of clinically isolated E. coli strains. The optimal multiplicity of infection (MOI) was 0.001, with a latent period of 10 min, a burst period of 30 min, and a burst size of 2.22 × 10² PFU/cell. It remained stable at 4–50 °C and pH 4–12. In vitro antibacterial results revealed that XJA18 had the most pronounced initial bacterial growth suppression at MOI = 0.001 during the first 4 h. In vivo experiments demonstrated that both prophylactic and therapeutic administration of XJA18 could protect against E. coli infection, significantly reducing inflammatory cytokine levels and bacterial loads in the livers and spleens of mice (p < 0.001), significantly increasing body weight (p < 0.05), and reducing histopathological damage to the colon, liver, and lungs. In summary, phage XJA18 can effectively inhibit E. coli and is safe and stable. These characteristics indicate that phage XJA18 has great potential as a novel biological agent to replace antibiotics for treating bacterial infectious diarrhea in calves. Full article

Human papillomavirus (HPV) is one of the most widespread sexually transmitted infections globally, whose persistent infection plays a major role in causing cervical cancer. Vaccination is therefore a key prevention strategy. Using a gender-stratified dynamic transmission model tailored to a Tunisian case, we investigate the impact of bivalent HPV vaccination. The proposed model accounts for partial cross-immunity and captures both direct and indirect effects of female-only vaccination. We derive the basic reproduction number and the corresponding herd immunity threshold, and a global sensitivity analysis shows that vaccine coverage, efficacy, and cross-protection are strong drivers of transmission reduction. Their combined effects on disease spread are quantified by varying these parameters across biologically relevant ranges. An optimal control problem was formulated and analyzed using Pontryagin’s Maximum Principle to minimize persistent infections and cancer cases while limiting vaccination effort. Three vaccination scenarios are compared: an ideal case with full vaccine availability and two resource-constrained cases with respective maximum coverage rates of $100\%$ and $80\%$. The numerical simulations revealed that the optimal strategy under unconstrained conditions can achieve significant suppression of infection, persistence, and cancer. Under constrained effort, the optimal control still achieves substantial reductions in disease burden, with minor differences in dynamics and speed of immunity buildup. Our results highlight the effectiveness of female-only HPV vaccination in providing both direct and indirect protection. They also emphasize the importance of sustained coverage in constrained settings. Full article

Variegated squirrel bornavirus 1 (VSBV-1) is a recently identified zoonotic virus associated with fatal encephalitis in humans. A literature search in electronic databases such as PubMed, Web of Science, Scopus, and Google Scholar was performed using the following search terms: “VSBV-1”, “orthobornavirus”, “squirrel”, “zoonotic encephalitis”, and “mammalian bornavirus”, to identify peer-reviewed literature relevant to the veterinary and zoonotic aspects of VSBV-1. This narrative review summarizes the current knowledge on VSBV-1 with emphasis on veterinary aspects, including taxonomy, epidemiology, clinical presentation, diagnostics, hypothetical transmission routes, surveillance strategies, and proposed biosecurity measures. However, evidence regarding virus shedding, natural reservoirs, distribution, and transmission pathways is presently absent. VSBV-1 may persist undetected in infected squirrels due to the absence of clinical signs and limited surveillance efforts. Large-scale epidemiological studies have not yet been performed. Given the limited understanding of viral epidemiology and the severe course of zoonotic infection, a precautionary approach is warranted. Structured surveillance, control of animal movements, and occupational protection are essential to limit both viral spread and the risk of zoonotic infection. Future research should focus on identifying natural reservoirs, virus distribution in captive squirrel populations, transmission pathways, and improving diagnostic tools. Full article

In early 2020, a respiratory virus swept across the world. The World Health Organization (WHO) confirmed pandemic status and the virus was identified as a coronavirus with superlative transmission properties. Using work from the 1950s, the WHO declared that the virus was transmitted through respiratory ‘droplets’, which were expelled by infected persons through coughing/sneezing. These would fall to the ground within 1–2 m. Scientists investigating viral transmission questioned this premise because recent work had shown that viruses populate the smallest respiratory particles, remaining airborne for much longer than larger ‘droplets’ and capable of spreading throughout the indoor environment. Advice such as handwashing, surface disinfection and social distancing was not as important as face masks and adequate indoor ventilation. People needed to know that poor ventilation constituted the highest risk for contracting the virus. Instead, homes and surfaces were disinfected and social distancing was maintained in community settings. The scientists formed a consortium named Group 36 in order to contest the WHO over airborne transmission but they could not present definitive evidence in the short term to reverse initial guidance. This account details the evolution of understanding of COVID-19 transmission and the role of Group 36 and others in challenging WHO-based policies based on dated physical science. Full article

Weather conditions, especially temperature, rainfall, and humidity, affect the transmission and spread of West Nile virus (WNV). This study investigated the effects of weather patterns on WNV activity in Croatia using climatological, equine seroprevalence, and human case data collected in two endemic continental Croatian regions with high WNV activity from 2015 to 2024. Overall equine WNV IgG prevalence was significantly higher in East Croatia (30.34%) than in Central Croatia (10.90%) and increased over time in both regions with a similar temporal pattern, indicating a shared upward trend in viral circulation. Higher equine seroprevalence was observed in areas with confirmed recent equine infections (IgM positive) within the same transmission season. In addition, human cases and recent equine infections were significantly associated with higher equine seroprevalence in the following season, with increases of 4% and 7%, respectively. In contrast to precipitation and humidity, temperature was significantly associated with human WNV cases, whereas no comparable effect was found in horses. Temperatures in February, April, May, and October emerged as key predictors, and the model including mean April and May temperatures showed the best predictive performance for human WNV cases, further supported by analysis of the epidemic year 2018. However, when 2018 was excluded, the effects of temperature remained significant only for May and July, with increased May temperatures emerging as the most important predictor of WNV activity in the upcoming transmission season. Full article

Understanding the heterogeneous spread of tuberculosis (TB), particularly multidrug-resistant (MDR) forms and the role of subclinical infection, is critical for achieving the WHO End TB strategy. This study develops a novel compartmental model that explicitly incorporates incipient and subclinical TB together with MDR forms, and links them to case detection and treatment pathways. The key innovation lies in integrating a sensitivity-based identifiability analysis with a Bayesian MCMC framework to quantify parameter uncertainty and correlations directly from regional surveillance data. Applied to five high-burden regions of the Russian Federation (2009–2020), the approach reveals strong heterogeneity in epidemic drivers: wide credible intervals for contagiousness, the rate of progression to bacterio-positive (BE+) states, and detection rates. The probabilistic forecasts up to 2025 are validated against 2021–2023 data. The region-specific differences in these correlated parameters dictate transmission dynamics, and improving detection of BE+ cases is the most effective lever for control. Full article

Background/Objectives: Individuals with limitations in their daily activities use assistive technology (AT), which helps them restore body structures and functions. During the pandemic, to prevent the spread of infection, health policies have disrupted the traditional delivery mode of AT service, and the lack of preparedness for contingency measures has further caused AT service disruptions, making the continuity of AT services a major challenge. This study explores the critical success factors (CSFs) for preventing AT service interruptions in the post-pandemic era and supporting decision-makers in responding rapidly to similar infectious disease pandemics in the future, while ensuring delivery of high-quality AT services. Methods: A systematic literature review was conducted, and then, the multicriteria decision-making (MCDM) model, combined with a decision-making trial and evaluation laboratory (DEMATEL) and an analytic network process (ANP), was applied to stratify complex problems in a structured manner, thereby constructing a multicriteria decision analysis structure for identifying the CSFs for avoiding AT service interruptions in the post-pandemic era. Results: The study results revealed that the three most influential direct factors are improving the providers’ telemedicine capabilities, enhancing access to digital AT service support, and establishing a digital AT ecosystem. Indirect factors include addressing resource shortages. Conclusions: To avoid repeating past mistakes during future pandemics involving similar infectious diseases, strengthening the telemedicine capabilities of medical staff and ensuring a complete AT service delivery system are the most essential priorities. Full article

Background: An outbreak of Marburg virus in Jinka Town, Southern Ethiopia, has raised significant concern regarding the potential spreading of disease throughout the country. Healthcare workers play a crucial role in early prevention and control of such an outbreak. However, the knowledge, attitudes, and preparedness of healthcare workers regarding Marburg virus disease have not been assessed yet, despite these factors being critical for early prevention and control of an outbreak. This study aimed to assess the knowledge, attitude, and preparedness regarding Marburg virus disease among healthcare workers in Awi Zone public hospitals, northwest Ethiopia, in 2026. Methods: An institutional-based cross-sectional study was conducted among healthcare workers in Awi Zone public hospitals from 26 December 2025 to 10 January 2026. A simple random sampling technique was used to select 394 participants. The data were collected using a pre-tested, structured self-administered questionnaire. The data were entered into Epi-data version 4.6 and analyzed using SPSS version 25. Results: A total of 394 healthcare workers participated in this study. The mean age of the participants was 32.9 ± 4.87 years. The study revealed that 47.7% (95% CI: 42.78–52.62%) and 61.2% (95% CI: 56.4–66%) of participants had good knowledge and a positive attitude towards Marburg virus disease, respectively. However, only 20.3% (95% CI: 16.34–24.26%) demonstrated good preparedness for the Marburg virus outbreak. Conclusions: The study revealed that the majority of healthcare workers had positive attitudes and suboptimal knowledge but critically low preparedness regarding Marburg virus disease prevention and control in Awi Zone public hospitals, northwest Ethiopia. Hence, healthcare workers who are frontline staff for outbreak prevention and control, Awi zone health departments and hospital administrators should be provided with targeted training preparation, training for implementing emergency preparedness plans, and essential infection prevention protocols to improve readiness for a potential outbreak. Full article

Erysiphe corylacearum, a newly emerging pathogen of hazelnut (Corylus avellana L.), has rapidly spread across Europe, causing severe outbreaks and threatening the sustainability of hazelnut production. This study investigated the biochemical and morphological traits associated with cultivar susceptibility to E. corylacearum. Eight cultivars representing a range of resistance levels were analyzed for leaf phenolic composition and trichome density. A total of 22 phenolic compounds were identified, with myricetin-3-O-rhamnoside, 1,7-bis-(4-hydroxyphenyl)-4,6-heptadien-3-one-hexoside, hirsutenone-hexoside, and quercetin-3-O-rhamnoside as dominant metabolites; however, no correlation was found between constitutive phenolic content/profile and disease resistance. In contrast, leaf trichome density showed a strong negative association with susceptibility, suggesting that denser trichomes act as a physical barrier to infection. Our results indicate that trichome density is a key morphological trait conferring resistance to E. corylacearum and could serve as a practical marker for breeding and selection of more resistant hazelnut cultivars. Full article

Entomopathogenic fungi are vital components of integrated pest management; however, environmental temperature is one of the key factors that limits their individual-level virulence, population-level transmission dynamics, and field efficacy. In this study, we isolated an indigenous fungal strain from a naturally infected Zeugodacus cucurbitae cadaver, and evaluated its biological characteristics, virulence, and horizontal transmission efficiency against Z. cucurbitae across 20–35 °C. A temperature-driven Susceptible–Infected–Removed (SIR) epidemiological model was developed to simulate infection dynamics and predict its epizootic potential. Morphological and molecular (ITS) analyses identified the isolate as Beauveria bassiana, designated as strain WZS5. WZS5 exhibited notable thermotolerance. At 30 °C, the strain displayed a short median germination time (7.7 h), high sporulation yield (1.1 × 10⁸ conidia mL⁻¹), and fast radial growth (4.8 mm d⁻¹). Additionally, it showed substantial virulence with a median lethal concentration (LC₅₀) of 1.32 × 10⁷ conidia mL⁻¹ and a median lethal time (LT₅₀) of 5.28 days at a concentration of 1.0 × 10⁸ conidia mL⁻¹. Baseline biological activity was maintained even at 35 °C. At 30 °C, horizontal transmission was effective, yielding a cadaver sporulation rate of approximately 70.0%, a 4.0-day sporulation lag, and viable F₁ conidia (88.6% germination). The SIR model adequately captured these dynamics (r = 0.919), predicting potential epizootic spread at 30 °C with a basic reproduction number (R₀) of 1.90. This predictive framework quantifies temperature thresholds for fungal epizootics, providing valuable ecological insights for managing Z. cucurbitae in tropical and subtropical regions. Full article

Background/Objectives: Acinetobacter baumannii is a critical opportunistic pathogen causing severe healthcare-associated infections, particularly in intensive care units. The global dissemination of carbapenem-resistant A. baumannii (CRAB) and its environmental persistence necessitate continuous genomic surveillance to monitor high-risk clones. Methods: We conducted whole-genome sequencing (WGS), core genome multi-locus sequence typing (cgMLST), and phylogenomic analyses on 26 CRAB isolates collected at the National Institute for Infectious Diseases (INMI) “Lazzaro Spallanzani” IRCCS (September 2023–September 2024). Antimicrobial resistance determinants, virulence-related genes, and capsular (KL) and lipooligosaccharide outer core (OCL) loci were characterized by interrogation of comprehensive bioinformatic pipelines. Results: All CRAB isolates displayed an extensively drug-resistant (XDR) phenotype, with a shared resistance pattern to carbapenems, aminoglycosides, fluoroquinolones, fosfomycin, and sulfonamides, while being susceptible only to colistin and cefiderocol. The carbapenemase gene bla_OXA-23 was detected in all CRAB isolates, together with clone-specific bla_OXA-51-like variants. For all isolates, the resistome profile fully matched the observed resistance phenotype. All isolates belonged to the International Clonal Lineage II (ICL II), Pasteur Sequence Type (ST) 2, and Oxford ST369, ST208, and ST455. Integration of cgMLST data with phylogenomic analyses and genome-based classification of KL and OCL loci revealed five distinct clusters, each one including nearly identical isolates, indicating both intra-hospital dissemination and possible inter-hospital transmission. Virulome profiling revealed heterogeneous repertoires of virulence-associated genes, resulting in cluster-specific patterns, while patristic analysis identified phylogenetic clusters linking the study isolates to other Italian and other European lineages. Conclusions: This study underscores the complex genomic landscape of CRAB in our setting, driven by the circulation of different ICL II clonal types, and reinforces the urgency of integrated genomic surveillance and robust antimicrobial stewardship to mitigate the spread of high-risk XDR A. baumannii clones. Full article

Zika virus (ZIKV) remains a significant global public health threat due to its association with severe neurological and ocular abnormalities, including microcephaly and congenital glaucoma in infants. Viruses often exploit host metabolic programs, such as energy and lipid metabolism, to support their replication. However, how ZIKV-driven metabolic reprogramming affects the anterior segment of the eye, especially trabecular meshwork (TM) cells, remains poorly defined. In this study, we investigated the roles of AMP-activated protein kinase (AMPK) signaling, fatty acid (FA) metabolism, and lipid droplet (LD) biogenesis in ZIKV-induced ocular pathogenesis using primary human TM cells and an IFNAR1-deficient mouse model. ZIKV infection triggered time-dependent activation of the LKB1-AMPK-ACC signaling axis and significantly increased LD accumulation. Pharmacological activation of AMPK suppressed viral replication, whereas its inhibition enhanced infection, highlighting an antiviral role for AMPK signaling. In contrast, ZIKV promoted LD biogenesis, and inhibition of DGAT1 reduced both LD formation and viral replication, indicating a proviral role for LDs. Modulation of FA metabolism further revealed differential effects on ZIKV infection: saturated FA (palmitate) enhanced viral replication, whereas inhibition of FA oxidation with etomoxir reduced infection. Conversely, unsaturated FAs (oleate and linoleate) suppressed viral replication, in part by impairing viral binding and entry. Collectively, these findings show that ZIKV reshapes host metabolic pathways in TM by differentially engaging AMPK signaling, FA metabolism, and LD biogenesis to promote viral replication and spread in ocular tissue. Targeting these metabolic pathways may offer promising therapeutic avenues for preventing and/or treating ZIKV-associated ocular complications. Full article

Extracellular vesicles (EVs) can disseminate replication-competent viral genomes complexed with selected host proteins, enabling stealth cell-to-cell transfer within lipid membrane-enclosed bubbles. In addition to complementing free-virion spread, EV-associated genomes can be protected from neutralizing antibodies and persist under conditions in which classical virion production decreases. Here, we propose a route-resolved framework in which interconnected cellular secretory pathways, including endoplasmic reticulum (ER) remodeling, multivesicular body (MVB) biogenesis, secretory autophagy, and plasma-membrane budding, jointly generate EV heterogeneity and create discrete opportunities for the capture, protection, and export of infectious cargo. We highlight reticulon-3 (RTN3), an ER-shaping protein, as an upstream regulator that can couple infection-induced ER microdomains to endosomal docking and to autophagy-linked trafficking decisions that bias intermediates toward secretion rather than degradation. Supporting this view, transmission electron microscopy of dengue virus-infected cells reveals extensive vesicular remodeling, including irregular MVBs adjacent to the plasma membrane and autophagosome-like double-membrane structures, consistent with altered vesicular routing following RTN3 perturbation. Collectively, these route-resolved, spatially organized spatio-organelle changes support a pathomechanistic model in which RTN3-mediated ER remodeling reshapes ER-endosome-autophagy trafficking interfaces, creating regulated decision points that can be leveraged to stratify infectious EV subsets (with infectivity-linked single-vesicle and quantitative proteomics approaches) and to inform host-directed strategies that curb non-lytic viral dissemination. Full article

The 2022 highly pathogenic avian influenza (HPAI) outbreak of H5N1 clade 2.3.4.4b was one of the major avian influenza outbreaks, leading to multiple spillover events infecting domestic and wild bird flocks, as well as mammals. The sustained spread was a result of viral circulation in wild birds across migratory flyways in North America. Pennsylvania has a significant poultry population that supports both retail and live bird markets. The state also features migratory bird stopovers on the Atlantic flyway, increasing exposure to HPAI infections. This study investigates clinical presentation and sequence data from H5N1 clade 2.3.4.4b viruses during the 2022 outbreak in Pennsylvania. Eight different H5N1 clade 2.3.4.4b genotypes were detected (A1, B1.1, B1.2, B1.3, B2.2, B3.3, B3.5, and one minor genotype) during the first year. The earliest detection was genotype A1, a fully Eurasian virus, in commercial poultry in April 2022. All other genotypes identified were reassortants of A1 with North American avian influenza gene segments (denoted with “B”). Genotype B3.3 was a rare genotype prior to the initial spillover into the live bird market system, but remained predominant among backyard flocks in Pennsylvania and surrounding states until September 2023. Genotype B3.3 has not been detected in migratory waterfowl since, suggesting the genotype has waned and is no longer in circulation. This study sheds light on the genotype diversity of H5N1 during the 2022 outbreak in Pennsylvania poultry, contributing to the understanding of virus evolution and its potential impacts. Full article

Wheat streak mosaic (WSM), historically attributed to wheat streak mosaic virus (WSMV) and transmitted by the wheat curl mite (WCM; Aceria tosichella), remains a major cause of yield loss in the Texas High Plains. In recent years, Triticum mosaic virus (TriMV), also transmitted by WCM, has emerged as an increasingly important component of the WSM disease complex. Under field conditions, TriMV is most frequently detected in mixed infections with WSMV. Management of WSM relies primarily on resistant cultivars carrying genes such as Wsm1 or Wsm2. Although synergistic interactions between WSMV and TriMV have been documented under controlled conditions, their dynamics during natural field infections—particularly during the latent phase between initial infection and symptom development—remain poorly understood. Moreover, the extent to which host genotype influences virus–virus interactions and vector acquisition dynamics in the field has not been fully resolved. Replicated field trials conducted over two growing seasons were used to quantify temporal accumulation patterns and relative ratios of WSMV and TriMV in susceptible (TAM 304) and resistant cultivars differing in resistance source (BT [Wsm1] and Joe [Wsm2]) under natural disease spread. WSMV remained the predominant virus in mixed infections across cultivars, sampling times, and disease stages. However, as plants aged and entered senescence, WSMV titers declined more rapidly than TriMV titers, resulting in a progressive reduction in the WSMV-to-TriMV ratio. From early infection through disease development, the Wsm1 cultivar (BT) consistently supported significantly lower TriMV accumulation than the Wsm2 cultivar (Joe), providing a mechanistic explanation for the comparatively stronger disease suppression associated with WSM. Mites feeding on BT also acquired lower TriMV titers. Although viral concentrations in wheat tissue were strongly correlated with those detected in feeding mites, substantial differences in plant-level WSMV-to-TriMV ratios among cultivars were not mirrored within the vector. These findings indicate that while host resistance regulates absolute virus accumulation, vector-associated factors may influence the relative proportions of viruses detected following acquisition, with important implications for WSM epidemiology and resistance deployment in field systems. Full article