Search Results (2,465)

African swine fever (ASF) needs to be controlled, and prevention of the spread of African swine fever virus (ASFV) is dependent on enhanced surveillance and early disease detection. Commercial swine operations, especially in North America, Europe, and Asia, are characterized by comparatively large numbers of pigs, and sampling individual pigs, which represents the main strategy for current ASF surveillance, can be both costly and labor intensive. A study performed in Ghana was designed to estimate the diagnostic sensitivity of pen-based aggregate oral fluid testing for ASFV in infected pigs in a pen of 30 animals and to evaluate its utility as a tool to support surveillance of ASF in the US. This study was performed in three phases: (i) virus (Ghana ASFV24) amplification in a target host species to generate the challenge inoculum; (ii) titration of the inoculum (10% spleen homogenate) in target host species to determine the minimum dose inducing acute ASF in pigs with survival up to 5–6 days post-inoculation (dpi); and (iii) the main study, involving 186 pigs, consisting of 6 replicates of 30 pigs per pen and one seeder pig inoculated with wildtype ASFV (highly virulent genotype II) per pen. Daily sampling of aggregate oral fluids, uncoagulated blood, oropharyngeal swabs, fecal and water nipple swabs, and recording of rectal temperatures and clinical observations was carried out. The seeder pigs were each inoculated intramuscularly with 0.5 mL of the 10% spleen homogenate, which induced the desired clinical course of ASF in the pigs, with survival of up to 6 dpi. ASFV DNA was detected in the seeder pigs as early as 1 dpi and 2 dpi in the blood and oropharyngeal swabs, respectively. Transmission of ASFV from the seeder pigs to the contact pig population was detected via positive amplification of ASFV DNA in aggregate oral fluid samples at 3 days post-contact (dpc) in 4 out of 6 pens, and in all 6 pens, at 4 dpc. Testing of oropharyngeal swabs and blood samples from individual pigs revealed a variable number of ASFV-positive pigs between 3 and 5 dpc, with detection of 100% positivity between 6 and 18 dpc, the study endpoint. These findings demonstrate the potential utility of aggregate oral fluid sampling for sensitive and early detection of ASFV incursion into naïve swine herds. It also demonstrates that testing of environmental samples from the premises could further enhance overall ASF early detection and surveillance strategies. Full article

Scrofuloderma, a cutaneous manifestation of tuberculosis, is a rare but clinically significant form of mycobacterial infection. It typically results from the local spread of Mycobacterium tuberculosis from an infected lymph node or bone area to the overlying skin. This disease is mainly characterized by chronic granulomatous inflammation, leading to skin ulcers and abscesses. Due to its nonspecific clinical presentation, scrofuloderma can mimic various dermatological conditions, making its diagnosis particularly challenging. This case report presents the clinical course of a patient who was positive for the Human Immunodeficiency Virus (HIV) with a diagnosis of scrofuloderma, managed at a tertiary healthcare center, with follow-up before and after treatment. A literature review was also made, highlighting the importance of maintaining a high index of clinical suspicion and utilizing appropriate diagnostic methods to ensure timely diagnosis. Full article

Background: It is still challenging to develop effective vaccines against tumorigenic human gammaherpesviruses such as Epstein–Barr virus (EBV). A major obstacle is the lack of a small animal model that reproduces the natural infection course of human gammaherpesviruses to allow for proper assessment of vaccine efficacy. Murine gammaherpesvirus 68 (MHV68) is a natural pathogen of wild rodents and laboratory mice and therefore can be used as a surrogate for human gammaherpesviruses to evaluate vaccination strategies. Methods: In this study, two mRNA vaccine candidates were generated, one encoding a fusion protein of the MHV68 gH with the gL (gHgL-mRNA) and the other expressing the MHV68 gB protein (gB-mRNA). The immunogenicity and protective efficacy of the mRNA vaccine candidates were evaluated in a mouse model of MHV68 infection. Results: The gHgL-mRNA but not the gB-mRNA candidate vaccine was able to induce neutralizing antibodies in mice, whereas both vaccines could elicit antigen-specific T-cell responses. Following MHV68 intranasal inoculation, complete blocking of the establishment of viral latency was observed in some mice immunized with individual gHgL-mRNA or gB-mRNA vaccines. Notably, co-immunization with the two mRNA vaccines appeared to be more effective than individual vaccines, achieving sterile immunity in 50% of the vaccinated mice. Conclusions: This study demonstrates that immunization with mRNA platform-based subunit vaccines is indeed capable of preventing MHV68 latent infection, thus validating a safe and efficacious vaccination strategy that may be applicable to human gammaherpesviruses. Full article

Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a heterogeneous group of small-vessel vasculitides, characterized by the presence of antibodies binding to myeloperoxidase (MPO) and proteinase-3 (PR3) found in neutrophil granules. Apart from being the target of ANCA, neutrophils actively contribute to the vicious cycle of inflammation and vascular damage in AAV. On the other hand, platelets have recently been recognized as essential for thrombosis and as inflammatory effectors that collaborate with neutrophils, reinforcing the generation of reactive oxygen species (ROS) and the formation of neutrophil extracellular traps (NETs) in those diseases. Neutrophils exhibit morphological and functional heterogeneity in AAV, reflecting the complexity of their contribution to disease pathogenesis. Since long-term immunosuppression may be related to serious infections and malignancies, there is an urgent need for reliable biomarkers of disease activity to optimize the management of AAV. This review summarizes the current understanding of the role of neutrophils and platelets in the pathogenesis of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), focusing on their crosstalk, and highlights the potential for identifying novel biomarkers relevant for predicting the disease course and its relapses. Full article

Background: Perioperative care is an integral part of the procedure of a surgical operation, with strictly defined rules. The need to upgrade and improve some individual long-term processes aims at optimal patient care and the provision of high-level health services. Therefore, preoperative care is drawn up with new data resulting from the evolution of technology to upgrade the procedures that need improvement. According to the international literature, a factor considered to be of major importance is high preoperative anxiety and its effects on the patient’s postoperative course. High preoperative anxiety is postoperatively responsible for prolonged hospital stays, increased postoperative pain, decreased effect of anesthetic agents, increased amounts of analgesics, delayed healing of surgical wounds, and increased risk of infections. The use of Virtual Reality technology appears as a new method of managing preoperative anxiety. Objective: This study investigates the effect and effectiveness of Virtual Reality (VR) technology in managing preoperative anxiety in adult patients. Methods: A literature review was performed on 193 articles, published between 2017 and 2024, sourced from the scientific databases PubMed and Cochrane, as well as the trial registry ClinicalTrials, with a screening and exclusion process to meet the criterion of investigating VR technology’s effectiveness in managing preoperative anxiety in adult patients. This systematic review was conducted under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. Results: Out of the 193 articles, 29 were selected. All articles examined the efficacy of VR in adult patients (≥18) undergoing various types of surgery. The studies represent a total of 2.354 participants from 15 countries. There are two types of VR applications: distraction therapy and patient education. From the studies, 14 (48%) used the distraction VR intervention, 14 (48%) used the training VR intervention, and 1 (4%) used both VR interventions, using a range of validated anxiety scales such as the STAI, VAS-A, APAIS, and HADS. Among the 29 studies reviewed, 25 (86%) demonstrated statistically significant reductions in preoperative anxiety levels following the implementation of VR interventions. VR technology appears to manage preoperative anxiety effectively. It is a non-invasive and non-pharmacological intervention with minimal side effects. Conclusions: Based on the review, the management of preoperative anxiety with VR technology shows good levels of effectiveness. Further investigation of the efficacy by more studies and randomized controlled trials, with a larger patient population, is recommended to establish and universally apply VR technology in the preoperative care process as an effective method of managing preoperative anxiety. Full article

Background: Periprosthetic joint infections (PJIs) are considered as one of the most serious complications after total joint arthroplasty. Aim of this study was to evaluate the prevalence of PJI caused by difficult-to-treat (DTT) pathogens as well as PJIs with a superinfection with a DTT pathogen in the course of the infection and assess the risk factors leading to this emergence. Methods: Data of 169 consecutive patients with a PJI was analyzed in this retrospective observational single-center study, and cases were categorized into PJIs with initial DTT pathogens, PJIs with DTT pathogen superinfection, non-DTT PJIs, and PJIs with superinfection. Recorded parameters comprised age, gender, side, body mass index (BMI), preoperative anticoagulation, and serum level of C-reactive protein (CRP) at admission, as well as preoperative patient status using the ASA (American Society of Anesthesiologists) score and the age-adjusted form of the Charlson comorbidity index (CCI). Furthermore, the infecting microorganism and the type of infection as well as the chosen operative treatment regime, duration of the antibiotics interval, and the outcome were recorded. Results: In total, 46.2% of cases were DTT PJIs, and 30.8% of them were superinfections. Elevated serum CRP levels at admission (≥92.1 mg/L) were linked to a nearly 7-fold increased likelihood of a DTT PJI (OR 6.981, CI [1.367–35.63], p = 0.001), compared to patients with a non-DTT PJI. Hip joint involvement was also associated with a 3.5-fold higher risk compared to knee joints (OR 3.478, CI [0.361–33.538], p = 0.0225). Furthermore, patients undergoing ≥3 revision surgeries demonstrated a significantly 1.3-fold increased risk of developing a DTT superinfection (OR 1.288, CI [1.100–1.508], p < 0.0001). Chronic PJIs were similarly associated with a markedly 3.5-fold higher likelihood of superinfection by DTT pathogens (OR 3.449, CI [1.159–10.262], p = 0.0387). Remaining parameters did not significantly affect the rate of a DTT PJI or a PJI with DTT superinfection. Conclusions: These findings underscore the importance of early identification of high-risk patients and highlight the need for tailored preventive and therapeutic strategies in managing DTT PJIs. Full article

Introduction: Respiratory Syncytial Virus (RSV) infection causes seasonal respiratory illness in both children and adults, with increasing recognition of its impact in older adults with chronic comorbidities. This study aimed to characterize adult patients hospitalized with RSV infection in Switzerland and identify comorbidities linked to poor outcomes. Methods: Adults hospitalized with RSV infection between May 2022 and April 2024 at a Swiss public teaching hospital were included in this retrospective observational study. To assess the association between comorbidities and patient outcomes, separate multivariable regression analyses for each comorbidity, adjusted for age and sex, were performed. The primary composite endpoint was ’severe course’ (in-hospital death or intensive care unit (ICU) admission), secondary endpoints included in-hospital death, ICU admission, and length of stay. Results: Among 136 included patients (mean age 78, 38% male), 98% had comorbidities, most commonly cardiovascular (75.7%), respiratory (51%), and chronic kidney disease (CKD) (36.7%). Further, 18.4% experienced a severe course. The ICU admission rate was 14.0%, in-hospital mortality 6.6%, and the median hospital stay of survivors was 6 days (IQR 4–10). CKD was significantly associated with severe course (OR 2.64, p = 0.045) and in-hospital mortality (OR 11.6, p = 0.025), while immunosuppression predicted ICU admission (OR 5.7, p = 0.018). Length of stay was not linked to any comorbidities. Conclusions: In this cohort of hospitalized adults, mainly elderly individuals with chronic comorbidities were tested positive for RSV. CKD and immunosuppression were associated with severe course. Prevention strategies, including RSV vaccination, should prioritize these high-risk populations. Full article

Staphylococcus aureus frequently causes intramammary infections in dairy cows (bovine mastitis), which impair animal welfare, milk yield, and food safety. This study determined the prevalence and genetic diversity of S. aureus in bulk tank milk (BTM) samples from community-based Alpine dairy pastures in Tyrol, a major milk-producing region in Austria. Throughout the 2023 Alpine season (May–September), 60.3% (94/156) of BTM samples tested positive for S. aureus at least once over the course of up to four samplings. A total of 140 isolates collected from the 94 S. aureus-positive community-based Alpine dairy pastures revealed 33 distinct spa types, with t2953 (n = 33), t529 (n = 12), t267 (n = 11), and t024 (n = 10) being the most common. Selected isolates representing the different spa types were characterised by DNA microarray-based genotyping, multi-locus sequence typing (MLST), and antimicrobial susceptibility testing. Isolates with spa types associated with bovine-adapted CC8 (CC8bov/GTB) were identified as the most common subtype, being detected in BTM samples from 35.3% (55/156) of the pastures. This emphasises the high prevalence of this subtype in dairy herds across European Alpine countries. Other common bovine-associated subtypes were also detected, including CC97, CC151, and CC479. While antimicrobial resistance was rare, enterotoxin-producing genes were detected in all CC8bov-associated spa types. Overall, these findings underscore the importance of rigorous hygiene practices in dairy farming, particularly in community-based Alpine dairy pastures, where the risk of transmission is particularly high. It also emphasises the need for continued surveillance and subtyping to improve animal health, ensure food safety, and promote sustainable milk production. Full article

With the rise in immunocompromised individuals and patients with immune-related comorbidities such as COVID-19, the rate of fungal infections is growing. This increase, along with the current plateau in antifungal drug development, has made understanding the pathogenesis and dissemination of these organisms more pertinent than ever. The mouse model of fungal infection, while informative on a basic scientific level, has severe limitations in terms of translation to the human disease. Here we present data supporting the implementation of the human cerebral organoid model, which is generated from human embryonic stem cells and accurately recapitulates relevant brain cell types and structures, to study fungal infection and dissemination to the central nervous system (CNS). This approach provides direct insight into the relevant pathogenesis of specific fungal organisms in human tissues where in vivo models are impossible. With this model system we assessed the specific brain tropisms and cellular effects of fungal pathogens known to cross the blood–brain barrier (BBB), such as Cryptococcus neoformans. We determined the effects of this fungal pathogen on the overall gross morphology, cellular architecture, and cytokine release from these model organoids. Furthermore, we demonstrated that C. neoformans penetrates and invades the organoid tissue and remains present throughout the course of infection. These results demonstrate the utility of this new model to the field and highlight the potential for this system to elucidate fungal pathogenesis to develop new therapeutic strategies to prevent and treat the disseminated stages of fungal diseases such as cryptococcal meningitis. Full article

Determining the optimal duration of antibiotic therapy for infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) is a critical challenge in clinical medicine, balancing therapeutic efficacy against the risks of adverse effects and antimicrobial resistance. This narrative review synthesises current evidence and guidelines regarding antibiotic duration for MDR-GNB infections, emphasising bloodstream infections (BSI), hospital-acquired and ventilator-associated pneumonia (HAP/VAP), complicated urinary tract infections (cUTIs), and intra-abdominal infections (IAIs). Despite robust evidence supporting shorter courses (3–7 days) in uncomplicated infections caused by more susceptible pathogens, data guiding optimal therapy duration for MDR-GNB remain limited, particularly concerning carbapenem-resistant Enterobacterales (CRE), difficult-to-treat Pseudomonas aeruginosa (DTR-Pa), and carbapenem-resistant Acinetobacter baumannii (CRAB). Current guidelines from major societies, including IDSA and ESCMID, provide explicit antimicrobial selection advice but notably lack detailed recommendations on the duration of therapy. Existing studies demonstrate non-inferiority of shorter versus longer antibiotic courses in specific clinical contexts but frequently exclude critically ill patients or those infected with non-fermenting MDR pathogens. Individualised duration decisions must integrate clinical response, patient immunologic status, infection severity, source control adequacy, and pharmacologic considerations. Significant knowledge gaps persist, underscoring the urgent need for targeted research, particularly randomised controlled trials assessing optimal antibiotic duration for the most challenging MDR-GNB infections. Clinicians must navigate considerable uncertainty, relying on nuanced judgement and close monitoring to achieve successful outcomes while advancing antimicrobial stewardship goals. Full article

Feline superficial non-healing corneal ulcers are persistent lesions requiring individualized treatment to reduce recurrence. This retrospective study evaluated 136 affected eyes (113 nonrecurrent; 23 recurrent) to identify clinical and treatment-related factors associated with recurrence. Recurrent ulcers were more common in older cats (7.2 ± 4.3 vs. 5.1 ± 4.6 years; p = 0.026). Domestic Shorthairs were the most frequently affected breed (50%), and central ulcer location predominated in both groups. Recurrent cases required more intensive management, with 16.9% needing ≥ 2 treatment courses, compared to 83% of nonrecurrent cases resolving after a single course. Healing time following corneal debridement was longer in recurrent cases (32.3 ± 34.4 vs. 25.5 ± 23.1 days; p = 0.272), and corneal sequestrum occurred more frequently (13.0% vs. 10.6%; p = 0.735). Corneal debridement was the primary treatment modality. Systemic medications were more often used in recurrent cases, notably oral lysine (47.8% vs. 26.5%; p = 0.049) and famciclovir (17.4% vs. 2.6%; p = 0.016). Recurrent cases also showed significantly higher rates of concurrent viral (p < 0.001) and bacterial/fungal infections (p = 0.027). In conclusion, recurrent superficial non-healing corneal ulcers were associated with age and systemic illness, emphasizing the need for early diagnosis and management of underlying conditions. Full article

Sepsis causes millions of deaths each year. Rapid, targeted therapy can reduce mortality rates. Both bacterial and viral pathogens can trigger sepsis, but the utility of commonly used inflammatory markers for differentiation remains controversial. Moreover, little is known about the time courses of alternative inflammatory parameters. The aim of this prospective, two-center observational study was to investigate the differences in the course of soluble Neuropilin-1 (sNRP-1) levels between bacterial and viral sepsis over a 7-day period. To be included, adult patients had to meet the SEPSIS-3 criteria and be diagnosed with either a bacterial or viral pathogen. Immunosuppressed patients were excluded. While IL-6, PCT, and CRP levels decreased consistently over time, sNRP-1 levels remained elevated in the bacterial group throughout the entire ICU stay. PCT (p < 0.001) and CRP (p = 0.016) levels were significantly associated with the course of sNRP-1. The AUC of sNRP-1 was 0.777 for discriminating between bacterial and viral infections on day 1. sNRP-1 remained stable and significantly higher in bacterial than in viral infections. Furthermore, the AUC values for discrimination ranged from acceptable to good, depending on the day of the ICU stay. sNRP-1 may serve as a potential tool to differentiate between bacterial and viral pathogens in sepsis. Full article

Background/Objectives: Neutropenia is a common adverse effect of oral valganciclovir (VGCV) treatment in infants with congenital cytomegalovirus infection (CCMVI), with an estimated prevalence of 20%. However, its clinical course and associated factors, including the influence of VGCV dosage, remain inadequately characterized. Methods: We conducted a single-center retrospective cohort study of infants treated with VGCV for symptomatic congenital CMV infection (CCMVI) at the Kobe University Hospital between 1 April 2009 and 31 March 2017. Detailed descriptive analyses of neutropenia were performed, and factors associated with its onset were explored using univariable logistic regression analyses. Results: A total of 31 patients were included, and neutropenia occurred in 35% of them during the 6-week treatment period. Its occurrence was observed throughout the treatment course, with no substantial difference in incidence between the 16 mg/kg/day and 32 mg/kg/day dosing groups. Neutropenia was more likely to occur in infants with shorter gestational age. Conclusions: Neutropenia occurred in 35% of patients during 6 weeks of VGCV treatment, irrespective of dosage, and was more common in those with shorter gestational age. Full article

Machupo virus (MACV), a member of the Arenaviridae family and causative agent of Bolivian hemorrhagic fever, results in lethality rates of 25–35% in humans. Mice lacking the signal transducer and activator of transcription 1 (STAT-1^−/−) have previously been shown to succumb to MACV infection within 7–8 days via the intraperitoneal route. Despite these reports, we observed partial lethality in STAT-1^−/− mice following challenge with wild-type MACV. Serial sampling studies to evaluate the temporal progression of infection and pathologic changes after challenge revealed a two-phase disease course. The first phase was characterized by viral load and pathological lesions in the spleen, liver, and kidney followed by a second, lethal phase, defined by high viral titers and inflammation in the brain and spinal cord resulting in neurological manifestations and subsequent mortality. Tissue adaptation in the brains of challenged STAT-1^−/− mice resulted in a fully lethal model in STAT-1^−/− mice (mouse-adapted; maMACV). A similar two-phase disease course was observed following maMACV challenge, but more rapid dissemination of the virus to the brain and overall pathology in this region was observed. The outcome of these studies is a lethal small rodent model of MACV that recapitulates many aspects of human disease. Full article

Trichophyton indotineae is emerging globally from its origin in India, presenting with a terbinafine resistance and causing significant clinical burden. We report herein the first four confirmed cases of T. indotineae dermatophytoses in Malaysia, which were diagnosed based on the microscopic examination of skin scrapings using potassium hydroxide (KOH) wet mount, followed by confirmation via culture and Internal Transcribed Spacer (ITS1) sequencing. In contrast to conventional Trichophyton infections, T. indotineae dermatophytoses demonstrate extensive cutaneous involvement and marked inflammation with erythematous lesions. All cases exhibited a chronic course lasting more than three months, with evidence of person-to-person transmission. Although one patient reported a travel to Singapore, three had no recent travel history, suggesting possible local transmission. The isolates produced characteristic white, cottony colonies with radial mycelial growth on Mycosel agar after incubation at 30 °C for four days. Three patients responded well to oral itraconazole (200 mg daily), with reduced inflammation and erythematous lesions observed two weeks after treatment initiation. The occurrence of T. indotineae particularly among patients without a travel history, suggests a potential endemic establishment. This fungal pathogen warrants consideration in cases of extensive or recalcitrant dermatophytoses. Further investigations into the diagnostic methods, antifungal susceptibility profiles, and epidemiological risk factors of Malaysian strains are warranted to enhance clinical management and inform public health interventions. Full article