Toxoplasma gondii (T. gondii) is a globally prevalent parasite that poses significant medical and veterinary challenges. Although current therapies such as pyrimethamine and sulfadiazine are effective, they often cause severe adverse effects, including myelosuppression, highlighting the need for safer and more effective alternatives. In this study, we evaluated the immunostimulatory and antiparasitic activities of three traditional herbal extracts, Stellaria dichotoma L. var. lanceolata Bge. (LDS), Stellaria aquaatic (SA) and Gypsophila oldhamiana (GO), in a murine model of T. gondii infection. To investigate mechanisms, bone marrow-derived dendritic cells (BMDCs) were treated in vitro. For the in vivo model, C57BL/6 mice received oral extracts (100 mg/kg/day) for 13 days, starting six days prior to intraperitoneal challenge with T. gondii (ME49). Parasite burden and splenic immune profiles were analyzed at 7 days post-infection to assess acute-phase containment. The findings of this study show that in vitro, GO extract promoted the maturation of BMDCs, significantly increasing CD11c+CD11blo mature dendritic cell subset and the expression of costimulatory molecules (CD40/CD80). Notably, GO simultaneously upregulated PD-L1 and PD-L2 on DCs, indicating a balanced Th1 response that prevents excessive immunopathology through checkpoint regulation while preserving strong effector functions. In vivo, GO-treated mice exhibited significantly lower splenic parasite loads than those in the control, LDS, or SA groups. GO significantly increased the frequency of IL-12-producing MHC II⁺ DCs and conventional DC type 1 (cDC1). This activation expanded IFN-γ -producing CD8⁺ and double-negative T cells, while NK cell responses were lower. Therefore, our findings show that GO extract limits acute T. gondii infection by modulating the DC-IL-12-CD8⁺ T cell axis. This study provides a modern immunological basis for the traditional use of Yinchaihu and highlights GO as a promising plant-based candidate for preventing and maintaining immunological balance during intracellular parasitic challenges.
Although veterinary vaccines against West Nile virus (WNV) have been developed, no approved human vaccine is currently available, highlighting the need for scalable and safer WNV vaccine candidates. In this study, a recombinant WNV subunit nanoparticle vaccine was developed by displaying the envelope protein domain III (ED3) on a cholera toxin B subunit (CTB) pentameric scaffold. The resulting recombinant protein comprising CTB-ED3 was expressed predominantly as soluble nanoparticles in Escherichia coli. Immunized mice produced strong humoral responses with balanced IgG1/IgG2a ratios, and some constructs achieved neutralizing titres comparable to those elicited by formalin-inactivated WNV. Importantly, no cross-reactivity with other flaviviruses was observed, alleviating potential concerns about ADE. These findings demonstrate that CTB-ED3 is assembled into multimeric nanoparticles in bacteria, offering a cost-effective, scalable, and biosafe platform for developing subunit nanoparticle vaccines against WNV and potentially other flaviviruses.
Ticks of the genus Ixodes are major vectors of pathogens of medical and veterinary importance, including the causative agents of Lyme borreliosis. While much is known about tick immune responses during feeding, the molecular mechanisms that enable pathogen persistence during the off-host period remain poorly understood. Here, we investigated the gut immune landscape of questing Ixodes ricinus females naturally infected with members of the Borrelia burgdorferi sensu lato species complex. Transcriptional profiling of gut tissues revealed sustained upregulation of the NF-κB transcription factor dorsal and redox-associated genes in Borrelia-infected individuals, whereas other selected immune signalling pathway genes and antimicrobial peptides remained unchanged. Correlation analyses further indicated that Borrelia load was positively associated with gene expression levels, while redox genes were strongly co-regulated, indicating a coordinated control of oxidative homeostasis. These findings point to a targeted immune response that supports gut homeostasis rather than triggering broad antimicrobial activity. However, the limited number of Borrelia-positive questing ticks analyzed in this study highlights the need for further investigations with larger sample sizes, multiple developmental stages, and additional infection experiments to validate and expand these findings.
Colistin is a last-resort antimicrobial in human and veterinary medicine, yet it remains unclear whether prolonged exposure can drive collateral resistance beyond polymyxins. Here, we used a spatial experimental-evolution platform, the Microbial Evolution and Growth Arena (MEGA)-plate, to examine adaptation of Escherichia coli ATCC 25922 to stepwise colistin selection in three independent runs. Endpoint isolates from all three runs (n = 3 isolates per exposure zone) were phenotyped, whereas one randomly selected representative isolate per exposure zone (0× , 1× , 10× , 100× , and 1000×) was sequenced because MIC profiles were identical across runs. Colistin MIC increased from 0.5 to 64 μg/mL across the selection gradient, while MICs for the other tested agents remained unchanged. Across the sequenced representatives, no plasmid-mediated colistin resistance determinants were detected and the overall set of CARD strict hits remained unchanged. Comparative genomics identified only limited coding changes with potential relevance to envelope-associated adaptation, notably an ftsI missense variant in the 100× and 1000× representatives and an ompC synonymous variant of uncertain functional significance in the 1× representative. Relative to the untreated representative, exposed isolates differed by only a small number of baseline-unique high-confidence annotated coding variants. These data support a compound-restricted phenotypic response in this single-strain model under the conditions tested. However, because genomic sampling was limited to one endpoint representative per exposure zone and no transcriptomic or functional assays were performed, broader regulatory adaptation or efflux-related responses cannot be excluded.
Effective disinfection is critical for controlling pathogenic and opportunistic microorganisms in livestock environments. Didecyldimethylammonium chloride (DDAC), a quaternary ammonium compound, is widely used due to its strong antimicrobial properties; however, improving its efficacy without increasing toxicity remains a key challenge. This study aimed to evaluate the antimicrobial activity of DDAC in combination with fatty alcohol ethoxylate (FAEO8) and to assess the toxicological safety of the resulting complex preparation. The antimicrobial activity of DDAC, FAEO8, and DDAC-FAEO8 was evaluated against Staphylococcus aureus, Escherichia coli, and Salmonella Typhimurium using minimum inhibitory concentration (MIC) determination, inhibition zone diameter assays, scanning electron microscopy, potassium ion (K+) leakage analysis, and membrane potential assays. Toxicological evaluation included acute and sub-acute oral toxicity studies in rats and dermal irritation/corrosion tests in rabbits, conducted in accordance with international and national guidelines. The DDAC-FAEO8 complex exhibited significantly enhanced antimicrobial activity compared to DDAC alone, with MIC reductions of 44.4%, 30.8%, and 26.7% against S. aureus, E. coli, and S. Typhimurium, respectively. At concentrations ≥2× MIC, the complex inhibited >99% of microbial growth and demonstrated prolonged bacteriostatic effects. Microscopic analysis revealed pronounced structural damage and cell lysis, while K+ leakage and membrane depolarization assays confirmed disruption of bacterial membrane integrity. FAEO8 alone showed no bactericidal activity but did contribute to changes in membrane permeability. Toxicological assessment indicated that the complex preparation was non-lethal at doses up to 2000 mg/kg, with no significant pathological alterations observed. Subacute exposure showed minimal physiological changes, and dermal testing confirmed that the diluted formulation (40 mg/mL) was non-corrosive, with only mild, reversible irritation. The combination of DDAC with FAEO8 enhances antimicrobial efficacy through membrane disruption mechanisms while maintaining low toxicity. This additive interaction highlights the potential of DDAC-FAEO8 as an effective and safe disinfectant for veterinary applications.
Canine mammary tumors (CMTs) are the most prevalent neoplasms in intact female dogs, accounting for up to 50% of all neoplasms, with malignancy rates ranging from 50% to 89%. Human breast cancer (HBC) remains a leading cause of cancer morbidity and mortality worldwide. Both diseases exhibit remarkable biological and molecular similarity, making the domestic dog an excellent spontaneous model for studying HBC. CMTs and HBC share histopathological features. They also have comparable classification systems, including hormone receptor-based subtypes (luminal A, luminal B, HER2-positive) and the triple-negative subtype, as well as dysregulation of pathways such as PI3K/AKT and Wnt/β-catenin. Furthermore, they share several risk factors and environmental determinants. In contrast to rodent models, dogs offer natural genetic variation and comparable environmental exposures, enabling more physiological studies of cancer development. This review focuses on genomic instability, specifically microsatellite instability (MSI) and loss of heterozygosity (LOH), as an important driver of neoplastic growth in both species. MSI results from DNA mismatch repair defects, whereas LOH indicates tumor suppressor gene inactivation. Emerging evidence shows that these alterations occur in CMTs just as they do in HBC. Investigating MSI and LOH in dogs can uncover common molecular mechanisms, identify reliable biomarkers, and reveal novel therapeutic targets. Ultimately, this comparative approach reinforces the "One Health" concept, bridging veterinary and human medicine to improve cancer outcomes for both species.
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Neurological complications such as anosmia are among the most frequent and persistent symptoms of COVID-19; yet, the mechanisms linking SARS-CoV-2 infection to sensory neuronal injury remain unclear. We demonstrate that SARS-CoV-2 directly infects olfactory sensory neurons through ACE2 upregulation and stimulates basal stem cell proliferation, as shown in human iPSC-derived sensory neurons and validated in golden Syrian hamsters. Exposure to live viruses or its S1 spike protein induces TRPV1 channel redistribution from the nucleus to the plasma membrane, resulting in axonal degeneration. Single-nucleus RNA sequencing reveals activation of exocytosis and transmembrane transport pathways with disruption of axonal guidance networks. Pharmacological inhibition of TRPV1 with capsazepine mitigates neuronal injury and preserves axonal integrity. These findings identify TRPV1 activation as a central mediator of SARS-CoV-2-induced neurodegeneration in the olfactory epithelium and suggest that TRPV1 antagonism offers a promising therapeutic avenue for treating COVID-19-related anosmia.
Antimicrobial resistance (AMR) is a global health concern, yet the extent of resistant genes and microbial exchange between humans and livestock in low- and middle-income countries remains underexplored. Vietnam, an AMR hotspot, was studied using shotgun metagenomic sequencing of paired faecal samples from pigs and caretakers across 50 small-scale farms. Results revealed 10,270 antimicrobial resistance genes (ARGs) representing 550 unique types, including clinically relevant mcr, blaOXA-58, and optrA genes. Pigs showed higher total AMR abundance, while workers harboured richer resistomes. Approximately 52% (288/550) of ARGs were shared between hosts, dominated by aminoglycoside, β-lactam, and tetracycline resistance genes, often co-located with mobile genetic elements, indicating horizontal transfer potential. Closely related Escherichia coli strains were identified in both hosts, consistent with strain sharing or exposure to common sources beyond individual farms. These findings highlight the human-pig interface as an important setting for shared AMR signatures and support the need for integrated One Health surveillance and antimicrobial stewardship.
Bovine viral diarrhea virus (BVDV) causes persistent infection and immunosuppression, yet whether it hijacks host immunometabolism to facilitate replication remains unclear. Using untargeted metabolomics in bovine turbinate (BT) cells, we found that BVDV infection significantly elevated xanthurenic acid within the tryptophan-kynurenine (Trp-Kyn) pathway. BVDV persistently upregulated indoleamine 2,3-dioxygenase 1 (IDO1), resulting in decreased extracellular tryptophan and increased kynurenine levels. Supplementation with L-tryptophan or IDO1 inhibition suppressed viral replication, whereas L-kynurenine promoted it. Rescue of viral replication by L-kynurenine in IDO1-silenced cells confirmed that IDO1 promotes BVDV proliferation through downstream kynurenine generation. Mechanistically, IDO1 inhibition enhanced STAT1 phosphorylation and upregulated ISG15, MX1, and OAS1 expression. A negative feedback loop was identified between IFN-γ/STAT1 signaling and the IDO1-kynurenine axis. Furthermore, L-kynurenine activated the aryl hydrocarbon receptor (AhR) target gene CYP1A1, and the AhR antagonist CH-223191 partially reversed its pro-viral effects. In conclusion, BVDV hijacks the IDO1-dependent Trp-Kyn metabolic axis to limit interferon-STAT1 antiviral signaling, while AhR-related signaling may act as a possible partial downstream branch contributing to a pro-viral intracellular environment.
Vibrio europaeus is an important pathogen in shellfish aquaculture, yet its genomic diversity remains poorly understood. Here, we present the first comprehensive analysis of the V. europaeus pangenome, integrating genomic data from all strains available to date (n=39) sequenced specifically for this study. These were isolated from different aquaculture facilities (shellfish hatcheries) associated with mass mollusc mortalities from different geographical locations, years and host species. Our findings revealed an open pangenome with 61% of the genes associated with the accessory genome that contribute to environmental and host adaptations. Phylogenomic analyses of the core-genome (39% of the pangenome size) allowed us to evaluate the evolutionary history and intraspecific diversity of V. europaeus and revealed that Spanish strains displayed a much lower genetic variability than French, Chilean or American strains, probably due to a monophyletic radiation event. Functional annotation of core and accessory genes revealed the key virulence factors of the species, while it also disclosed that these are located mainly in the core genes. The high number of anti-phage defence systems encoded in the accessory genome explained almost all the variability of the species. The results provide important insights into the evolutionary history and ecological versatility of V. europaeus, with potential implications for diagnostics, epidemiological surveillance and disease management strategies in aquaculture.
H5 clade 2.3.4.4b high pathogenicity avian influenza viruses (HPAIVs) have caused unprecedented mortality in marine wildlife. However, host determinants of susceptibility to influenza A virus (IAV) infection remain poorly understood. IAVs adapted to different hosts show distinct binding preferences for different kinds of sialic acid (Sia) receptors on cell surfaces. Human‑adapted IAVs preferentially bind Sia α2,6-linked glycans, while avian‑adapted viruses prefer Sia α2,3-linked glycans. We characterized the distribution of α2,6- and α2,3-linked Sia, and fucosylated or sulfated Siaα2,3 across respiratory, intestinal, and neural tissues from stranded marine animals, including two South American sea lions (Otaria flavescens), a Burmeister's porpoise (Phocoena spinipinnis), and a Magellanic penguin (Spheniscus magellanicus). We also compared binding patterns of recombinant hemagglutinins (rHAs) derived from a classical H5 clade 1 virus and contemporary clade 2.3.4.4b viruses in the same tissues. We detected widespread expression of Sia receptors and H5 rHA binding in bronchial and alveolar epithelium (including air capillaries of the penguin) of the lung, enterocytes and goblet cells of intestinal villi, and the meninges and vascular endothelium of neural tissues, with species‑ and tissue‑specific patterns. These findings indicate that marine mammals and penguins possess receptor landscapes compatible with infection by both classical and contemporary H5 HPAIVs. Further investigation is necessary to determine how receptor distribution relates to productive replication, respiratory or fecal shedding, and cross-species transmission risk, particularly given the pronounced neurotropism and peracute disease course associated with clade 2.3.4.4b viruses.
The indiscriminate use of fungicides in agricultural crops is considered one of the most important causes of antifungal resistance. Hence, it is our interest to contribute to the knowledge of antifungal resistance, within the framework of One Health. The results will be useful to define appropriate policies in the use of these drugs both in the clinical area and in agriculture. Thus, the susceptibility patterns of 187 Aspergillus spp. (A. flavus [n = 46], A. fumigatus [n = 8], A. insuetus [n = 1]; A. niger [n = 85], A. tamarii [n = 34] and Aspergillus section Versicolores [n = 13]), isolated from coffee beans from the Los Santos coffee-growing region in Costa Rica, were evaluated for amphotericin B (AMB), itraconazole (ITZ) and voriconazole (VRC); using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution M38 guideline. The mean minimal inhibitory concentration (MIC) for AMB was 2.77 ± 3.19 μg mL-1, 0.29 ± 0.26 μg mL-1 for ITZ, and 1.14 ± 2.68 μg mL-1 for VRZ. Based on the CLSI guidelines, 15.2% of A. flavus, 75.0% of A. fumigatus and 3.5% of the A. niger were classified as non-wild type for AMB; 4.3% of the A. flavus/oryzae and 25.0% of the A. fumigatus were classified as non-wild type for VRC. ITZ presented the lowest MIC distribution, and the isolates were classified as wild-type strains. The results show a high susceptibility to ITZ, moderate to VRC (treatment of choice for invasive aspergillosis) and low susceptibility to AMB.
Anaplasma marginale and Anaplasma ovis are tick-borne obligate intracellular bacteria causing anaplasmosis in cattle and small ruminants, respectively, with considerable economic losses worldwide. Given the favorable ecological conditions for tick survival and the limitation of data on Anaplasma spp. in local tick populations in northwestern Iran, this study aimed to molecular and phylogenetic analysis of A. ovis and A. marginale in Ixodidae infesting livestock in northwestern Iran. In this cross-sectional study, a total of 780 ixodid ticks were collected from livestock across 198 herds in 11 counties of Ardabil Province during 2025. Ticks were morphologically identified and grouped into pools based on species and host type. Genomic DNA was extracted using a commercial kit and molecular detection of A. ovis and A. marginale was performed using PCR assays targeting the 16 S rRNA and groEL genes. Positive samples were submitted for Sanger sequencing to confirm the identity of Anaplasma spp., phylogenetic analysis was conducted using reference sequences from GenBank (NCBI) using MEGA software (version 12). Statistical analyses were conducted using SPSS (version 25), and associations between categorical variables were assessed using Fisher's exact test (p < 0.05). Eight tick species belonging to three genera were identified. Among the hosts, sheep exhibited the highest infestation rate (49.3%). Hyalomma anatolicum anatolicum was the most prevalent species (25.3%) and was present in all sampled counties. Tick distribution varied significantly among host species (p = 0.003) and geographic locations (p = 0.002). PCR analysis detected A. ovis DNA in 16.6% (4/24) and A. marginale DNA in 8.3% (2/24) of tick pools. Positive pools were primarily associated with Rhipicephalus spp. and Dermacentor marginatus. According to the results of the statistical analysis a significant association was found between tick species and host type (χ² = 13.87, p = 0.0031), with Hyalomma anatolicum anatolicum more prevalent in sheep (p = 0.001). Tick abundance varied across counties (χ² = 16.42, p = 0.002), with highest densities in Nir, Khalkhal, and Kowsar (χ² = 14.21, p = 0.0028). No significant association was observed between Anaplasma positivity and tick species (p = 0.21) or host type (p = 0.09). The detection of A. ovis and A. marginale DNA in ixodid tick pools indicates their circulation in Ardabil Province. However, due to pooled sampling and the limited number of positive samples, the infection rate at the individual tick level could not be determined. These findings also highlight the importance of a One Health approach, considering the interconnected roles of animal health, tick vectors, and the environment in the transmission and control of tick-borne diseases.
During Mycobacterium tuberculosis (Mtb) infection, infected alveolar macrophages (AMs) initially up-regulate a nuclear factor erythroid 2-related factor 2 (NRF2)-regulated cell-protective program, which is detrimental to host control and impedes AM activation, including MHC II expression. MHC II is critical for CD4+ T cell activation and host immunity during Mtb infection. We hypothesized that NRF2 regulates the MHC II pathway and AM antigen presentation to T cells. We found that NRF2 inhibits MHC II, but not MHC I, specifically in AMs, following Mtb infection in vitro and in vivo. NRF2 dampens Ciita and H2-Ab1 gene expression in uninfected AMs, and MHC II inhibition by NRF2 is retained following innate stimuli and IFNγ exposure. NRF2 expression in Mtb-infected AMs impedes their ability to activate ESAT6-specific CD4+ T cells. Thus, although NRF2 expression enhances cell-protective functions, it has the unexpected consequence of limiting innate-adaptive crosstalk, which can impair CD4+ T cell activation and host immunity during Mtb infection.
Synanthropic rodents cohabiting with the human and livestock are potential reservoirs for several zoonotic pathogens, which include Leptospira spp, Yersinia spp, Salmonella and Toxoplasma spp. In view of the higher incidence of leptospirosis in human and animals, this study was carried out to analyse the role of rodents and shrews in the transmission of pathogenic Leptospira spp in Puducherry, India. The rodents/shrews were trapped at 15 randomly selected sites in Puducherry, using Sherman traps between July to December 2022. The DNA from the blood and kidney of the rodents was extracted individually. The presence of pathogenic Leptospira spp in the rodent DNA sample was screened by Real-time PCR, targeting the lipl32 gene. Further secY gene was amplified and analysed to identify the pathogenic Leptospira spp. Five kidney DNA samples ( Rattus rattus = 1 and Suncus murinus = 4) were tested positive for Leptospira sp by Real time PCR. The BLAST, phylogeny and sequence alignment studies of secY gene indicated the circulation Leptospira borgpetersenii in the synanthropic rodents. We first report, that the Suncus murinus , the Asian house shrew, has also been found harbouring the pathogenic Leptospira sp. The shrews and the black rat harbouring the pathogenic Leptospira sp in our study indicates that they are one among the key environmental determinants for Leptospirosis transmission to human and animals in Puducherry.
Interferon regulator factor 3 (IRF3) inhibition is a shared strategy of many virally encoded proteins to effectively block the induction of interferon signaling. Although rotavirus nonstructural protein 1 (NSP1) is known to target IRF3 for proteasomal degradation, the exact molecular mechanism remains unclear. Here, we found that rotavirus NSP1 contains a BC box motif that mediates interaction with the Elongin BC complex. Either siRNA knockdown or CRISPR knockout of TCEB2, which encodes Elongin B, substantially prevented IRF3 degradation by NSP1. Recombinant rotaviruses that encode NSP1 with BC box mutations failed to degrade IRF3, induced elevated interferon responses, and were attenuated in interferon-competent cells in vitro and in vivo. NSP1 protein was significantly less stable in infected cells in the absence of Elongin B. Importantly, Elongin BC was required for the stability of additional BC box-containing viral antagonists, including pestiviral N proteases and human adenovirus E4orf6, indicating that Elongin BC functions not only as an adaptor for host protein degradation but also as a broadly exploited stabilizing factor for viral innate immune antagonists. This knowledge of virus co-opting of the host ubiquitin ligase machinery may instruct the development of broad-spectrum antiviral therapeutics.
Oropouche virus (OROV; Orthobunyavirus) is an emerging arbovirus endemic to South America and the Caribbean, with imported cases in European countries, including Spain. Although primarily transmitted by biting midges (Culicoides spp.), OROV has been detected in several mosquito species, raising concerns about potential establishment in nonendemic regions. European populations of Aedes albopictus, and Culex pipiens, as well as the invasive Aedes aegypti, represent relevant models for assessing vector competence. Here, we evaluated the vector competence of Spanish Cx. pipiens biotype molestus, Spanish Ae. albopictus, and Ae. aegypti (Liverpool strain), for the 2024 OROV outbreak strain. Female mosquitoes were orally exposed to infectious blood meals and maintained under controlled insectary conditions at 27 °C. In addition, an additional group received a second noninfectious blood meal. The survival of the mosquitoes was monitored, and infection, dissemination, and transmission rates were assessed at 7, 14, and 21 days post infection. Vertical transmission of the virus to the progenies was also analyzed. Overall, Ae. albopictus exhibited low infection rates, with occasional dissemination and transmission events. Aedes aegypti and Cx. pipiens biotype molestus showed infection and occasional dissemination, but no evidence of transmission. A second noninfectious blood meal did not significantly affect infection, dissemination, or transmission rates in any species. Viral loads in bodies and legs were low and did not differ significantly between species, time points, or feeding regimens. Survival was not affected by infection or blood-feeding regime. We did not find vertical transmission of OROV to the progenies. Regardless of virus dissemination in mosquitoes, our study indicates a poor vector competence of Spanish Ae. albopictus and no evidence of transmission under the conditions tested in Ae. aegypti and Cx. pipiens biotype molestus for the circulating OROV strain. These findings suggest a low risk for local OROV establishment in Spain, although continuous surveillance and research are warranted to monitor potential vector-virus adaptation.
Scabies is a neglected tropical disease with substantial public health impact, especially in resource-limited countries like Ghana. Worldwide, more than 300 million people are affected by scabies. In Ghana, scabies outbreaks have been occurring frequently, especially among school-going children. This study assessed scabies burden, diagnostic accuracy, and the effect of ivermectin-based Mass Drug Administration (MDA) on scabies prevalence in the Sefwi Wiawso Municipality of the Western North Region of Ghana. A total of 341 participants were recruited at health facilities within the Municipality between October 2022 and October 2023. Scabies was diagnosed using the 2020 The International Alliance for the Control of Scabies (IACS) consensus criteria, and demographic data were collected. Health facility diagnoses were compared with study findings, and the relationship between MDA intake and scabies occurrence was also assessed. There was equal representation of both males (N = 172) and females (N = 169) with the mean ages of recruited male and female participants being 23.49 ± 14.26 years and 25.28 ± 13.68, respectively. IACS consensus criteria assessment of all participants showed 83% had clinical scabies and 10% had suspected scabies. Participants with basic education (JHS and primary) were disproportionately more likely to be diagnosed with either clinical or suspected scabies (p = 0.006). Ivermectin MDA intake was significantly associated with scabies diagnosis (p = 0,001). Study participants who had received at least 3 rounds of ivermectin MDA over the years were less likely to be diagnosed with either clinical (18.73%) or suspected (14.71%) scabies (p = 0.009). Study participants who reported more than 3 skin condition symptoms were significantly more likely to be diagnosed with clinical scabies (89.4%) compared to suspected scabies (64.71%) (p < 0.001). Clinical and suspected scabies were also only correctly diagnosed in 43.82% and 14.71% of participants, respectively, prior to training of health workers on the IACS consensus criteria tool (p < 0.001). Scabies is often overlooked in health facilities in Ghana, highlighting the need for better diagnostic capacity. The observed reduction in scabies burden with ivermectin MDA supports its use in integrated control programs for neglected tropical diseases.
Marek's disease virus (MDV) is a highly immunosuppressive alphaherpesvirus. However, whether and how MDV exploits extracellular vesicles (EVs) to evade host immunity, particularly the critical type I interferon (IFN-I) response, remains unknown. We hypothesized that MDV reprograms the EV microRNA (miRNA) cargo to facilitate its escape from the IFN-I-mediated antiviral state. Small RNA (sRNA) sequencing was conducted to profile and compare the expression patterns of EV miRNAs in chicken embryo fibroblast (DF-1) cells under four conditions: control, MDV infection, chicken interferon-alpha (chIFN-α) treatment and MDV-chIFN-α co-treatment. Integrative bioinformatic analyzes were employed to identify key differentially expressed miRNAs (DEMs) and predict their target genes within the IFN-I signaling network. MDV infection and chIFN-α treatment induced fundamentally distinct EV miRNA profiles. Strikingly, MDV infection counteracted the specific EV miRNA signature triggered by chIFN-α. We identified 65 key DEMs with the potential to cooperatively target multiple nodes of the IFN-I pathway. Among these, gga-miR-20a-5p and gga-miR-148a-3p were experimentally validated to directly target the 3' untranslated regions of the key innate immune sensors cGAS and TLR3, respectively, leading to a significant suppression of downstream IFN-I signaling activation. This study identifies dysregulated EV miRNAs during MDV-interferon antagonism, validating their direct targeting of innate immune sensors. These findings provide new insights into viral pathogenesis and pinpoint specific miRNA-target axes as potential avenues for antiviral intervention.