Search Results (201)

Avian influenza viruses (AIVs) pose a significant zoonotic threat, with the emerging H3N8 subtype raising increasing concern due to sporadic human infections. Current strategies for risk assessment of novel AIVs primarily rely on genetic surveillance and isolated case reports, which provide limited insight into their cross-species transmission potential. However, these approaches may overlook critical phenotypic determinants, such as pathogenicity, transmissibility, and environmental persistence, that directly influence zoonotic risk. This study investigates the evolutionary relationships, receptor-binding properties, replication dynamics, pathogenicity in mice, transmission efficiency in guinea pigs, and environmental persistence of three H3N8 strains isolated from a live poultry market. All three H3N8 strains bound exclusively to α-2,3 sialic acid receptor and achieved 100% transmissibility among guinea pigs through direct contact. Notably, the environment-origin strain A09 exhibited an indirect contact transmission efficiency of 33.3%. The findings reveal strain-specific differences, with A09 displaying enhanced pathogenicity, broader transmission routes, and greater environmental persistence compared with A05 and A01. This perspective underscores the value of integrated profiling from genotype to phenotype combined with multi-route transmission and environmental persistence analyses to delineate the adaptive roadmap of H3N8 from avian to mammalian hosts and to assess its emerging infection risk. Future directions for surveillance and intervention were also discussed, highlighting their potential to strengthen preparedness against zoonotic influenza threats. Full article

Reticuloendotheliosis virus (REV) has multiple transmission routes and can induce severe immunosuppression upon infection. Three application scenarios were set up to explore transfer factor’s (TF’s) potential in controlling REV. These scenarios involved using TF in chicks infected with REV during incubation, in 1-day-old chicks post-infection, and in chicks prior to REV infection. The application value of TF in controlling REV was evaluated based on various indices, including weight gain, organ development, and virus replication. The results all indicate that the use of TF could effectively alleviate the developmental delay, hepatomegaly, and thymic atrophy caused by REV infection through different routes, as well as significantly reduce the mortality rate. It could also effectively inhibit REV replication in vivo and cloacal virus shedding. Notably, TF had apparent advantages in inhibiting cloacal virus shedding through the egg in the chicks infected with REV. The functions of TF are dose-dependent, where increasing the dose or frequency of use is beneficial for enhancing its effect. This study observed the role of TF in controlling REV infection under different application scenarios, providing necessary auxiliary means to reduce the harm of REV infection. Full article

Alphaviruses are transmitted by Aedes mosquitoes and cause large-scale epidemics worldwide. Chikungunya virus (CHIKV) infection can cause febrile seizures known as chikungunya fever (CHIKF), which ultimately leads to severe joint pain and myalgia. While a vaccine has recently been introduced against CHIKV, at present, no anti-viral drug is available. CHIKV, like other alphaviruses, has a short 6K protein capable of forming an ion channel. Blocking this ion channel with drugs can therefore serve as a potential way to curtail CHIKV infection. To that end, we screened a repurposed drug library using three bacteria-based channel assays to detect blockers against 6K viroporin, yielding several hits. Interestingly, several of the blockers were able to inhibit the 6K protein from the similar Eastern equine encephalitis virus (EEEV), while others were not, pointing to structural specificity which may be explained by modeling studies. In conclusion, our study provides a starting point for developing a new route to potentially inhibit CHIKV. Full article

The changing structure of modern cities intensifies anthropopressure, resulting in the need to create plans for the protection of biodiversity in cities. This can be achieved by establishing lawns and flower strips along the streets and maintaining parks and squares in cities, creating green infrastructure and contributing to sustainable urban development. However, this vegetation also requires protection that is safe for the environment and city residents. Entomopathogenic fungi (EPF) are among the most well-known and effective microorganisms that infect plant pests and conduct the disease process leading to their death. The aim of the study was to conduct a comparative analysis of the generic composition of EPF and determine the density of their colony-forming units (CFUs) in soils from flower strips and lawns located along the main communication routes of the city of Siedlce (Poland). Soil samples collected from two sites and two habitats (a flower strip and a lawn directly adjacent to it)—Site No. 1, Wyszyńskiego Street; Site No. 2, Jagiełły Street—in the spring and autumn of 2021/2022 and 2024. At each site within the habitat, three zones (repeats) were designated, spaced approximately 10–15 m apart. Approximately six samples were collected from each replication, and then a mixed sample was prepared. Four genera of EPF were found in the soil samples: Beauveria, Metarhizium, Cordyceps, and Akanthomyces. The location, habitat type, and season had a significant effect on the diversity of individual genera of fungi and the density of colony-forming units (CFUs) in the studied soils. The dominant types of EPF, forming the most CFUs in the soils from the studied flower strips and the adjacent lawns, were Metarhizium spp. and Beauveria spp. It was found that EPF occurred in higher densities in the soil from the studied habitats (flower strips and lawns) in autumn than in spring. Both of these semi-natural habitats constitute forms of urban greenery that increase biodiversity and provide valuable ecosystem services that support sustainable urban development. Full article

Background: Hansen’s disease or leprosy is one of the 21 neglected tropical diseases (NTDs). In Ecuador, leprosy is considered eliminated as a public health problem; however, new cases are reported annually. Additionally, Mycobacterium leprae infection was detected in nine-banded armadillos across the country, suggesting a potential zoonotic reservoir. This literature review aims to provide an updated overview of the epidemiological situation of leprosy in Ecuador, identify knowledge gaps, and outline research priorities to support the development of a comprehensive national strategy for achieving zero autochthonous cases. Methods: This article analyses the current situation of leprosy in Ecuador based on international and national publications. A retrospective literature search using five international, regional, and national publications on leprosy published between 1954 and 2024 (70 years) with no restriction on language or publication date, was performed. Findings: Our review identified 28 publications with the earliest article dating back to 1954. Of these, 14 were published in international journals, 15 (53.6%) were in Spanish. Four nationwide studies documented leprosy cases across Ecuador’s three continental regions (Coast, Andes, and Amazon) with a predominance in the tropical coast. No cases have been reported from the Galápagos Islands. From 1983, Ecuador started multi-drug therapy. Data from the Ministry of Public Health (MoH) system identified 1539 incident cases, showing a significant decline in new cases from 2000 to 2024, with no cases in children. New cases detection rate by 100,000 inhabitants was 0.51 in 2019 according to the World Health Organization (WHO). No study has genotyped the Mycobacterium spp. in human cases, other animal species, or environment. According to the MoH, multibacillary leprosy accounts for 78.95% of diagnosed cases, with confirmation based on Ziehl–Neelsen staining and histopathology. No survey has assessed disabilities, knowledge, attitudes, and practices (KAP) or stigma related to leprosy. Research is needed on transmission routes, Mycobacterium genotyping, genetic susceptibility, and antibiotic resistance. BCG vaccination coverage fell to 75.3% in 2021. Cases are currently diagnosed and treated on an outpatient basis in large hospitals. Conclusions: This comprehensive review highlights persistent gaps in leprosy research and critical information, despite seven decades of documented cases in Ecuador. The disease is still endemic across the country, particularly at subnational level in the subtropics and tropics of the Pacific coast and the Amazon. There is a need for nationwide epidemiological research on reservoirs and the environment applying the One Health concept. Increased laboratory facilities and readily available official data are required to improve our understanding of leprosy in Ecuador. Strengthening community-level efforts is essential for Ecuador to meet the targets of the “WHO’s Towards Zero Leprosy: Strategy 2021–2030.” Full article

Human brucellosis is a zoonotic, bacterial infection caused by the intracellular, Gram-negative Brucella spp., which is common globally but rare in the United Kingdom, with approximately 20 imported cases per annum following travel to countries with high endemicity. Transmission typically occurs via the ingestion of infected animal products, including unpasteurised dairy products. Human-to-human transmission is rare, and routes include postpartum vertical transmission through breastfeeding. We report here on a familial cluster of three cases within a single UK-based Kurdish household of four, including a 11-month-old infant infected through the consumption of breast milk. Four months prior to presentation, the family had travelled together to northern Iraq for a 5-week holiday and all consumed local dairy products except for the children, including the 11-month-old, who was exclusively breastfed at the time. All three patients, including one adult male with complicated brucellosis, had a favourable outcome with medical therapy.: Brucellosis is an important differential diagnosis in returning travellers and specialist advice should be obtained early to prevent sequelae. It is also important for active case-finding, especially in family units with shared exposure. Paediatricians and adult physicians who may manage brucellosis should consider the possibility of vertical transmission in breastfeeding mothers. Full article

Canine leishmaniosis (CanL), caused by Leishmania infantum, is a major zoonotic disease primarily transmitted by sand flies. Unlike in adult dogs, the clinical course of CanL in puppies remains poorly characterized, regardless of the transmission pathway (i.e., vertical transmission or vector exposure). This study presents the first systematic literature review (SLR) focused on juvenile CanL, alongside an atypical clinical case report. A PRISMA-compliant search across four databases identified three eligible studies describing CanL in puppies (≤9 months, according to the current canine life stage guidelines). The case involves a 4.5-month-old puppy adopted from southern Italy with papulo-nodular skin lesions and generalized lymphadenomegaly as well as a mild normocytic normochromic anemia and increased C-reactive protein. L. infantum infection was confirmed by serology, polymerase chain reaction (PCR), and cytology. The SLR suggests that dermatological lesions and/or lymphadenomegaly, whether associated with laboratory abnormalities, represent the most common clinical manifestations of CanL in puppies. In the presented case, the coexistence of systemic dissemination signs and papulo-nodular skin lesions, typically associated with vector-borne transmission, suggests the possibility of a dual route of infection by L. infantum. Juvenile CanL should be considered in differential diagnoses and supported by thorough diagnostic evaluation and appropriate follow-up protocols. Full article

Hemotrophic mycoplasmas (HMs) are cell wall-less, small and uncultivable pathogens, which can cause infections in pigs with no to severe clinical signs and can contribute to significant economic losses in the pig industry. In addition to the known mechanical transmission routes of HMs (e.g., via blood-contaminated instruments or lesions from ranking fights), transmission to pigs by arthropod vectors such as Stomoxys calcitrans is being discussed. To date, there is scant available data concerning the transmission of HMs by stable flies. The objective of this study is to gain more data concerning the occurrence of HMs in Stomoxys calcitrans. Therefore, quantitative real-time PCR was conducted on different stable fly samples (surface washings and whole flies). We found Mycoplasma (M.) suis in 5.2% of crushed flies and 4.2% of fly wash solutions, and M. parvum was detected in 5.2% of flies and 9.4% of fly wash solutions. ‘Candidatus (Ca.) M. haemosuis’ was not detected in any sample. The mean bacterial loads were 2.0 × 10² M. suis/fly, 9.3 × 10² M. suis/fly wash solution and, for M. parvum, 2.4 × 10³ M. parvum/fly and 2.1 × 10³ M. parvum/fly wash solution. This molecular occurrence of porcine HMs in blood-sucking flies and reasonable bacterial loads in the two- to three-digit range demonstrate that these flies serve as mechanical vectors in stables and are, therefore, of epidemiological importance. Full article

Nocardia, an easily missed but potentially fatal opportunistic pathogen, can lead to serious infections like lung and brain abscesses. Intranasal inoculation (IN) is the traditional approach for constructing a Nocardia-induced pneumonia mice model, while it usually only results in limited local bacterial infection in the lungs. To comprehensively assess infection dynamics across distinct pulmonary inoculation routes in mice models, this study compared the pathogenicity of three different Nocardia farcinica pneumonia models established via IN, intratracheal aerosolization (ITA), and intratracheal instillation (ITI). C57BL/6J mice were infected with N. farcinica through IN, ITA and ITI with comparative analyses of bacterial distribution in lungs, survival rate, weight, bacterial load, inflammatory cytokines, histopathological characteristics and transcriptome differences. The findings suggest that ITA N. farcinica infections caused severer clinical symptoms, higher mortality, pulmonary bacterial load, levels of inflammatory cytokines in bronchoalveolar lavage fluid, and more significant histopathological damage to lungs than IN and ITI. Furthermore, ITA resulted in better lung bacterial distribution and delivery efficiency than ITI and IN. Transcriptome analysis of lungs from N. farcinica infected mice via IN, ITA and ITI revealed significant differential gene expression, whereas ITA route resulted in a larger fold change. ITA provides a more consistent and severe model of N. farcinica pneumonia in mice than IN and ITI, which can make the bacteria more evenly distributed in the lungs, leading to more severe pathological damage and higher mortality rates. In conclusion, ITA is an optimal route for developing animal models of N. farcinica pneumonia infections. Full article

Background: Non-cholera Vibrio species are rare waterborne pathogens that can cause severe infections. Among these, few cases of Vibrio metschnikovii infections have been reported, especially in the gastrointestinal tract, with no cardiac tissue involvement as a result. Following the PRISMA checklist, we conducted a literature review, and thirteen articles for twenty-two cases overall were included: seven cases of sepsis (in three cases, the echocardiographic results were negative), seven cases of pneumonia, two skin infections, eleven cases of diarrhoea, and a gastroenteritis outbreak. This report documents the expanding clinical spectrum and the role played by V. metschnikovii in infective endocarditis. Case report: A 28-year-old male patient was referred to the cardiac surgery unit for urgent mitral valve replacement due to suspicion of infective endocarditis. Microbiological tests yielded negative results. Following recovery and discharge with antimicrobial therapy for 6 weeks, the patient experienced prosthesis detachment, necessitating re-hospitalisation for an emergency valve replacement. Vibrio metschnikovii was identified on the prosthesis valve through PCR and successfully treated with ciprofloxacin. However, a spontaneous rupture of the ascending thoracic aorta led to a neurological injury. Discussion: This case represents the first case of valve infection caused by Vibrio metschnikovii, characterised by diagnostic and therapeutic challenges and the involvement of the great vessels. Also considered in this case, for a disease with a median age of 58 years (11–83) and a male-to-female ratio of 2.2, were one male neonate and six cases for whom neither sex nor age was indicated. Excluding gastrointestinal cases, the septic forms are associated with high morbidity, although the single case described involved a young and healthy subject. Risk factors for the pathogen or predisposing/pathological conditions for endocarditis did not emerge. The routes and the time of infection could not be determined, deepening the possibility of occupational exposure via the patient’s position as a boat worker. Poor sensitivity to third-generation cephalosporins has been reported in the literature: the absence of an antibiogram does not allow for a comparison, although resolution was achieved with ciprofloxacin. Conclusion: The rising global incidence of non-cholera Vibrio infections, driven by environmental changes, calls for urgent research into the factors behind their pathogenicity and infection routes. Diagnostic complexities have emerged together with clinical severity. Full article

During 2022, AIDS claimed a life every minute and about 9.2 million HIV-infected people were not on treatment. In addition, a person living with HIV is estimated to be 20–30 times more susceptible to developing active tuberculosis. Every year, 130,000 infants are newly infected, with vertical transmission being the main cause of pediatric HIV infection. Thus, the development of an effective, safe, and accessible vaccine for neonates and/or adults is an urgent need to prevent or control HIV infection or progression to AIDS. An effective HIV vaccine should induce long-lasting mucosal immunity, broadly neutralizing antibodies, innate immunity, and robust stimulation of CD4+ and CD8+ T-cell responses. Recombinant BCG is a promising live-attenuated bacterial vaccine vector because of its capacity to stimulate T-cell immunity. As a slow-growing microorganism, it provides prolonged low-level antigenic exposure upon infecting macrophages and APCs, potentially stimulating both effector and memory T-cell responses. BCG is considered safe and is currently administered to 80% of infants in countries where it is part of the national immunization program. Additionally, BCG offers several benefits as a live vaccine vehicle since it is cost-effective, easy to mass-produce, and heat stable. It is also well-suited for newborns, as maternal antibodies do not interfere with its efficacy. Furthermore, BCG has a strong safety profile, having been administered to over three billion people as a TB vaccine. In this review, we provide an extensive summary of the literature relating to immunogenicity studies in animal models performed since 2011. Moreover, we provide a comprehensive analysis of the key factors influencing the design of recombinant BCG as a live vaccine vehicle: (i) expression vectors; (ii) selection of HIV immunogen; (iii) promoters to regulate gene expression; (iv) BCG strain and BCG codon optimization; (v) genetic plasmid stability; (vi) influence of preexisting immunity, route, and dose immunization; and (vii) safety profile. Full article

Plasmodione is a potent early antiplasmodial compound. A metabolic study on mice treated with plasmodione revealed that 6-hydroxy–plasmodione was the main metabolite eliminated in the urine of treated mice. To block the metabolic pathway in the host, the introduction of fluorine at C-6 of the 3-benzylmenadione core was applied and showed potent antiplasmodial activity similar to that of the plasmodione analogue in vitro. In this work, a library of 38 6-fluoro-3-benzylmenadione analogues (a series) was constructed by incorporating structurally diverse groups in place of the 4-(trifluoromethyl) substituent present in the antiplasmodial plasmodione, via three synthetic routes. All new compounds were tested against the P. falciparum NF54 strain and for cytotoxicity with the rat L6 line. With a fluorine atom at C-6, A-a-21 was revealed to be the only compound from the a series, superior to the 6-H- analogue from the b series, with an IC₅₀ value of 70 nM versus 200 nM. Then, five other fluorine-based 3-benzylmenadiones, in which the fluorine was introduced in various positions of the 3-benzylmenadione core, were synthetized to assist our understanding of the impact of fluorine on antiplasmodial potencies in vitro; in particular, the aim here was to compare the effects of human serum and P. berghei species in these drug screens. This was also conducted in vivo with the P. berghei-infected mouse model. In the P. berghei species assay, PD and the 4′-fluoro-3′-trifluoromethyl-benzylmenadione A-b-9 exhibited a similar antiplasmodial behavior toward P. falciparum versus P. berghei. In the human serum versus Albumax assays, only the 6-fluoro–plasmodione showed a lower shift factor between Albumax assays and human serum conditions, suggesting a lower protein binding for the 6-F-PD compared to plasmodione or A-b-9. In vivo, 6-fluoro–plasmodione proved to be the most potent 3-benzylmenadione, reducing parasitemia by 50% after oral administration at 50 mg/kg. Full article

Neurological symptoms involving the central nervous system (CNS) and peripheral nervous system (PNS) are common complications of acute COVID-19 as well as post-COVID conditions. Most research into these neurological sequalae focuses on the CNS, disregarding the PNS. Guinea pigs were previously shown to be useful models of disease during the SARS-CoV-1 epidemic. However, their suitability for studying SARS-CoV-2 has not been experimentally demonstrated. To assess the suitability of guinea pigs as models for SARS-CoV-2 infection and the impact of SARS-CoV-2 infection on the PNS, and to determine routes of CNS invasion through the PNS, we intranasally infected wild-type Dunkin-Hartley guinea pigs with ancestral SARS-CoV-2 USA-WA1/2020. We assessed PNS sensory neurons (trigeminal ganglia, dorsal root ganglia), autonomic neurons (superior cervical ganglia), brain regions (olfactory bulb, brainstem, cerebellum, cortex, hippocampus), lungs, and blood for viral RNA (RT-qPCR), protein (immunostaining), and infectious virus (plaque assay) at three- and six-days post infection. We show that guinea pigs, which have previously been used as a model of SARS-CoV-1 pulmonary disease, are not susceptible to intranasal infection with ancestral SARS-CoV-2, and are not useful models in assessing neurological impacts of infection with SARS-CoV-2 isolates from the early pandemic. Full article

Cyvirus cyprinidallo2 (CyHV-2) is the causative agent of herpesviral hematopoietic necrosis in several economically important farmed freshwater fish species of the genus Carassius. Despite several CyHV-2 strains being isolated and fully sequenced, there is a lack of detailed characterization and consistent information on strains that exhibit high virulence in adult goldfish through viral challenge by immersion, particularly in the context of European strains and host populations. Strains that can cause highly virulent disease via this inoculation route are much more compatible with experimental designs that are representative of natural infection; thus, their utilization provides greater biological relevance. Consequently, in this study, we isolated three novel strains of CyHV-2 (designated NL-1, NL-2, and NL-3), originating from outbreaks in The Netherlands. Full-length genome sequencing and phylogenetic analyses revealed that these newly isolated strains are distinct from known strains and from each other. Significant differences were observed between the strains, in terms of in vitro growth kinetics, with NL-2 exhibiting stable passaging and superior fitness in vitro. Importantly, the challenge of adult Shubunkin goldfish with the NL-2 strain via immersion (2000 PFU/mL) induced an average mortality of ~40%, while parallel experiments with the CyHV-2 reference strain ST-J1 resulted in no mortality. Taken together, this study represents the characterization of a new CyHV-2 in vivo infection model, much more compatible with experimental designs that are required to be representative of natural infection. This model will be extremely useful in many aspects of CyHV-2 research in the future. Importantly, the genetic and phenotypic characterization performed in this study generates hypotheses on the potential roles of CyHV-2 genes in adaptation of the virus in vitro or in vivo. Full article

Infectious bronchitis virus (IBV) of the GI-23 lineage, which first emerged in the Middle East in the late 1990s, has since spread worldwide. The factors driving its expansion, whether human involvement, wild bird migration, or the virus’s biological traits, are still unclear. This study aimed to trace the genome evolution of GI-23 IBV in chickens and its adaptability to quails, which are susceptible to both gamma- and deltacoronaviruses. Thirty specific-pathogen-free (SPF) birds, aged between two and three weeks, were used. Initially, three birds were inoculated with the G052/2016 IBV via the oculo-nasal route. On the third day post-infection (dpi), oropharyngeal swabs were collected from the whole group, pooled, and subsequently used to infect three next birds. This process was repeated nine more times during consecutive IBV passages (P-I–P-X), and eventually, virus sequencing was performed using Next-Generation Sequencing (NGS). The obtained results showed that quails were not susceptible to the IBV GI-23 lineage, as the virus RNA was detected in low amounts only during the first passage (QP-I) with no further detections in later rounds of IBV passaging. In chickens, only mild diarrhea symptoms appeared in a few individuals. The NGS analysis identified sixty-two single nucleotide variants (SNVs), thirty of which caused amino acid changes, twenty-eight were synonymous, and one SNV introduced a stop codon. Three SNVs were found in untranslated regions. However, none of these SNVs lasted beyond seven passages, with forty-four being unique SNVs. The Shannon entropy values measured during passages varied for pol1a, pol1b, S, 5a, 5b, and N genes, with overall genome complexity peaking at CP-VI and CP-X. The highest complexity was observed in the pol1a (CP-X) and S genes (CP-IV, CP-VI, CP-VIII, and CP-X). Along with the S gene that was under positive selection, eight codons in pol1a were also positively selected. These findings suggest that even in an adapted host, IBV variability does not stabilize without immune pressure, indicating continuous molecular changes within its genome. Full article