Latest publications

Nat Commun. 2025 Jul 10;16(1):6374. doi: 10.1038/s41467-025-61687-0.

ABSTRACT

Soil-transmitted helminths (STHs) are intestinal parasites that affect over a billion people worldwide. STH control relies on microscopy-based diagnostics to monitor parasite prevalence and enable post-treatment surveillance; however, molecular diagnostics are rapidly being developed due to increased sensitivity, particularly in low-STH-prevalence settings. The genetic diversity of helminths and its potential impact on molecular diagnostics remain unclear. Using low-coverage genome sequencing, we assess the genetics of STHs within worm, faecal, and purified egg samples from 27 countries, identifying differences in the genetic connectivity and diversity of STH-positive samples across regions and cryptic diversity between closely related human- and pig-infective species. We define substantial copy number and sequence variants in current diagnostic target regions and validate the impact of genetic variation on qPCR diagnostics using in vitro assays. Our study provides insights into the diversity and genomic epidemiology of STHs, highlighting both the challenges and opportunities for developing molecular diagnostics needed to support STH control efforts.

PMID:40640199 | DOI:10.1038/s41467-025-61687-0

Nature. 2025 Jul 9. doi: 10.1038/s41586-025-09192-8. Online ahead of print.

ABSTRACT

Infectious diseases have had devastating effects on human populations throughout history, but important questions about their origins and past dynamics remain1. To create an archaeogenetic-based spatiotemporal map of human pathogens, we screened shotgun-sequencing data from 1,313 ancient humans covering 37,000 years of Eurasian history. We demonstrate the widespread presence of ancient bacterial, viral and parasite DNA, identifying 5,486 individual hits against 492 species from 136 genera. Among those hits, 3,384 involve known human pathogens2, many of which had not previously been identified in ancient human remains. Grouping the ancient microbial species according to their likely reservoir and type of transmission, we find that most groups are identified throughout the entire sampling period. Zoonotic pathogens are only detected from around 6,500 years ago, peaking roughly 5,000 years ago, coinciding with the widespread domestication of livestock3. Our findings provide direct evidence that this lifestyle change resulted in an increased infectious disease burden. They also indicate that the spread of these pathogens increased substantially during subsequent millennia, coinciding with the pastoralist migrations from the Eurasian Steppe4,5.

PMID:40634616 | DOI:10.1038/s41586-025-09192-8

Mol Ecol Resour. 2025 Jul 9:e70005. doi: 10.1111/1755-0998.70005. Online ahead of print.

ABSTRACT

New approaches are urgently needed to enrich rare or low-abundant DNA in complex samples. Soil-transmitted helminths (STHs) inhabit heterogeneous environments, including the gastrointestinal tract of their host as adults and are excreted as eggs and larvae in faeces, complicating our understanding of their biology and the use of genetic tools for species monitoring and population tracking. We have developed a hybridisation capture approach to enrich mitochondrial genome sequences of two STH species, the roundworm Ascaris lumbricoides and whipworm Trichuris trichiura, from extracted DNA from faecal material and worm specimens. Employing ~1000 targeted probes, we achieved > 6000 and > 12,000 fold enrichment for A. lumbricoides and T. trichiura, respectively, relative to direct whole genome shotgun (WGS) sequencing. Sequencing coverage was highly concordant with probe targets and correlated with the number of eggs per gram (EPG) of parasites present, from which DNA from as few as 336 EPG for Ascaris and 48 EPG for Trichuris were efficiently captured and sufficient to provide effective mitochondrial genome data. Finally, allele frequencies were highly concordant between WGS and hybridisation capture, suggesting little genetic information is lost with additional sample processing required for enrichment. Our hybridisation capture design and approach enable sensitive and flexible STH mitochondrial genome sampling from faecal DNA extracts and pave the way for broader hybridisation capture-based genome-wide applications and molecular epidemiology studies of STHs.

PMID:40631469 | DOI:10.1111/1755-0998.70005

Vet Res. 2025 Jul 7;56(1):139. doi: 10.1186/s13567-025-01574-0.

ABSTRACT

Streptococcus uberis is a causative pathogen of bovine mastitis with high genetic diversity. Rhamnose-rich polysaccharides (RPS) are abundant surface structures covalently anchored to peptidoglycan and represent promising vaccine candidates for several streptococcal pathogens. It was previously reported that the RPS of S. uberis strain 233 is composed of a repeating → 2)-α-L-Rhap-(1 → 3)-α-L-Rhap-(1 → disaccharide backbone decorated with α-D-Glcp side-chains. In this study, we identified a hitherto unknown glycerol phosphate (GroP) modification at the 6-OH of the Glc residue in S. uberis 233 RPS using nuclear magnetic resonance analysis. Comparative genomic analysis of 592 S. uberis genomes revealed significant diversity in the RPS biosynthesis gene cluster with six major RPS genotypes. RPS genotypes 1-4, representing 97.5% of the analyzed strains, all contained the rhamnan backbone biosynthesis genes shared between several streptococcal species, as well as a putative GroP transferase gene. Using rhamnan-reactive immune serum, we further demonstrated that rhamnan is a conserved and accessible glycan motif in S. uberis RPS genotype 1 and 2 strains, but this motif is inferred to be shielded by side-chains in genotype 4 strains. Importantly, experiments with sera from cattle, challenged intramammarily with S. uberis, revealed that the rhamnan backbone of S. uberis RPS is an immunogenic glycan motif and remained accessible to bovine IgG antibodies in the presence of single residue RPS side-chains. Overall, this study suggests that S. uberis RPS are modified with GroP and reports that RPS in most strains contain a conserved, immunogenic and antibody accessible rhamnan glycan motif.

PMID:40624561 | DOI:10.1186/s13567-025-01574-0

Front Vet Sci. 2025 Jun 20;12:1583988. doi: 10.3389/fvets.2025.1583988. eCollection 2025.

ABSTRACT

Cerebrospinal fluid (CSF) analysis is a common diagnostic tool in the investigation of neurological presentations. Whether its routine use after every brain magnetic resonance imaging (MRI) is warranted is debated amongst clinicians, and its usefulness after a normal MRI has not yet been examined. To investigate whether CSF analysis affected the final diagnosis in dogs and cats with suspected intracranial disease in the presence of unremarkable magnetic resonance imaging (MRI), clinical, imaging and laboratory records of dogs and cats with suspected intracranial disease, unremarkable MRI and CSF analysis were reviewed in this multi-center retrospective study. Of 593 animals, (533 dogs and 60 cats), 17 dogs (3%) had abnormal CSF, nine of these demonstrating pleocytosis (with or without elevated microprotein) and eight showing hyperproteinorrachia alone. In only five of these dogs (0.8% of the total cohort) was the final diagnosis and/or treatment meaningfully affected by CSF findings: three diagnosed with inflammatory brain conditions and two had undetermined diagnoses, with corticosteroids initiated following abnormal CSF results. No cats in this population had an abnormal CSF. All dogs with a diagnosis based on abnormal CSF results had an abnormal neurological examination. In this population, CSF analysis was unlikely to reveal an undiagnosed intracranial condition following an unremarkable brain MRI, particularly in dogs presenting with a normal neurological examination. In dogs presenting with an abnormal neurological examination or a high suspicion of inflammatory disease, CSF evaluation following normal MRI is more likely to be diagnostically valuable.

PMID:40621502 | PMC:PMC12226868 | DOI:10.3389/fvets.2025.1583988

Nat Commun. 2025 Jul 4;16(1):6067. doi: 10.1038/s41467-025-60248-9.

ABSTRACT

Food-grade titanium dioxide (fgTiO2) is a bio-persistent particle under intense regulatory scrutiny. Yet paradoxically, the only known cell reservoirs for fgTiO2 are graveyard intestinal pigment cells which are metabolically and immunologically quiescent. Here we identify immunocompetent cell targets of fgTiO2 in humans, most notably in the subepithelial dome region of intestinal Peyer's patches. Using multimodal microscopies with single-particle detection and per-cell / vesicle image analysis we achieve correlative dosimetry, quantitatively recapitulating human cellular exposures in the ileum of mice fed a fgTiO2-containing diet. Epithelial microfold cells selectively funnel fgTiO2 into LysoMac and LysoDC cells with ensuing accumulation. Notwithstanding, proximity extension analyses for 92 protein targets reveal no measureable perturbation of cell signalling pathways. When chased with oral ΔaroA-Salmonella, pro-inflammatory signalling is confirmed, but no augmentation by fgTiO2 is revealed despite marked same-cell loading. Interestingly, Salmonella causes the fgTiO2-recipient cells to migrate within the patch and, sporadically, to be identified in the lamina propria, thereby fully recreating the intestinal tissue distribution of fgTiO2 in humans. Immunocompetent cells that accumulate fgTiO2 in vivo are now identified and we demonstrate a mouse model that finally enables human-relevant risk assessments of ingested, bio-persistent (nano)particles.

PMID:40615368 | DOI:10.1038/s41467-025-60248-9

J Vet Intern Med. 2025 Jul-Aug;39(4):e70182. doi: 10.1111/jvim.70182.

ABSTRACT

BACKGROUND: Humans with peripheral vestibular disorders can suppress nystagmus through visual fixation, a capability often compromised in those with central vestibular disorders. Bedside tests that exploit this difference can aid neurolocalization in humans. These tests remain unexplored in veterinary medicine.

HYPOTHESIS: Removal of visual input will reveal or enhance nystagmus in animals with peripheral vestibular disease, while animals with central vestibular disease would show little change.

ANIMALS: Twenty-one dogs and cats with peripheral vestibular lesions and 16 with central vestibular lesions. Diagnosis was confirmed by MRI.

METHODS: A prospective study was conducted using a modified penlight-cover test. Because animals cannot be easily instructed to fixate on a visual target, removal of visual input was used as a substitute for eliminating visual fixation, based on the assumption that visual fixation also occurs spontaneously. A 0.5-W LED penlight was shined into one eye while covering the other to eliminate visual input. Nystagmus beat frequency (BF) and subjective evaluation of slow phase velocity (SPV) were recorded before and during penlight application.

RESULTS: In animals with peripheral lesions, BF increased in 33% and SPV in 24% of cases after removal of visual input. Among those with central lesions, only one of 16 showed an increase in BF, and none exhibited an increase in SPV.

CONCLUSIONS: When used alongside the neurological examination, the modified penlight-cover test, could raise suspicion of a peripheral vestibular lesion if it reveals increased BF or SPV.

PMID:40577055 | DOI:10.1111/jvim.70182

Neurosurg Rev. 2025 Jun 27;48(1):530. doi: 10.1007/s10143-025-03677-w.

ABSTRACT

Neuro-oncological surgery necessitates a careful balance between maximising tumour resection whilst minimising damage to healthy brain parenchyma. Tubular retractors represent an emerging tool proposed to facilitate in the optimisation of this onco-functional balance. The objective was to evaluate the evidence regarding tubular retractors in neuro-oncological surgery. A systematic review and meta-analysis was performed. Studies reporting on surgical outcomes of tubular retractors in adult neuro-oncological cases were eligible. Medline, Embase, Cochrane Library, ClinicalTrials.gov, and ICTRP were searched to 14th July 2024. Duplicate title/abstract screening, data extraction, and risk of bias assessments were conducted. Prevalence of gross total resection (GTR) and complications were calculated using random effects models. 49 studies were included in the final analysis with a total of 684 patients. Combined pooled prevalence for GTR was 76% (95% CI: 67-85%), whilst for complications was 14% (95% CI: 8-20%). GTR rate by tumour histology was: 52% for gliomas (95% CI: 41-62%), 80% for metastases (95% CI: 65-92%), and 100% for colloid cysts (95% CI: 99-100%). Complication rate by tumour histology was: 16% for gliomas (95% CI: 5-30%), 12% for metastases (95% CI: 1-28%), and 16% for colloid cysts (95% CI: 8-24%). There was no significant difference between tubular retractor brands and GTR or complication rate (p > 0.05). Despite the mounting interest regarding the utility of tubular retractors in neuro-oncological surgery, the current evidence remains largely in the form of case series. Prospective studies with greater sample sizes, longer follow-up, and direct comparison to conventional retraction are now needed.

PMID:40576849 | DOI:10.1007/s10143-025-03677-w

Nat Microbiol. 2025 Jun 20. doi: 10.1038/s41564-025-02035-2. Online ahead of print.

ABSTRACT

Numerous important environments harbour low levels of microbial biomass, including certain human tissues, the atmosphere, plant seeds, treated drinking water, hyper-arid soils and the deep subsurface, with some environments lacking resident microbes altogether. These low microbial biomass environments pose unique challenges for standard DNA-based sequencing approaches, as the inevitability of contamination from external sources becomes a critical concern when working near the limits of detection. Likewise, lower-biomass samples can be disproportionately impacted by cross-contamination and practices suitable for handling higher-biomass samples may produce misleading results when applied to lower microbial biomass samples. This Consensus Statement outlines strategies to reduce contamination and cross-contamination, focusing on marker gene and metagenomic analyses. We also provide minimal standards for reporting contamination information and removal workflows. Considerations must be made at every study stage, from sample collection and handling through data analysis and reporting to reduce and identify contaminants. We urge researchers to adopt these recommendations when designing, implementing and reporting microbiome studies, especially those conducted in low-biomass systems.

PMID:40542287 | DOI:10.1038/s41564-025-02035-2

Microb Genom. 2025 Jun;11(6). doi: 10.1099/mgen.0.001426.

NO ABSTRACT

PMID:40531181 | DOI:10.1099/mgen.0.001426

PLoS Pathog. 2025 Jun 9;21(6):e1013227. doi: 10.1371/journal.ppat.1013227. Online ahead of print.

ABSTRACT

Influenza A viruses (IAVs) are prime examples of emerging viruses in humans and animals. IAV circulation in domestic animals poses a pandemic risk as it provides new opportunities for zoonotic infections. The recent emergence of H5N1 IAV in cows and subsequent spread over multiple states within the USA, together with reports of spillover infections in humans, cats and mice highlight this issue. The horse is a domestic animal in which an avian-origin IAV lineage has been circulating for >60 years. In 2018/19, a Florida Clade 1 (FC1) virus triggered one of the largest epizootics recorded in the UK, which led to the replacement of the Equine Influenza Virus (EIV) Florida Clade 2 (FC2) lineage that had been circulating in the country since 2003. We integrated geographical, epidemiological, and virus genetic data to determine the virological and ecological factors leading to this epizootic. By combining newly-sequenced EIV complete genomes derived from UK outbreaks with existing genomic and epidemiological information, we reconstructed the nationwide viral spread and analysed the global evolution of EIV. We show that there was a single EIV FC1 introduction from the USA into Europe, and multiple independent virus introductions from Europe to the UK. At the UK level, three English regions (East, West Midlands, and North-West) were the main sources of virus during the epizootic, and the number of affected premises together with the number of horses in the local area were found as key predictors of viral spread within the country. At the global level, phylogeographic analysis evidenced a source-sink model for intercontinental EIV migration, with a source population evolving in the USA and directly or indirectly seeding viral lineages into sink populations in other continents. Our results provide insight on the underlying factors that influence IAV spread in domestic animals.

PMID:40489557 | DOI:10.1371/journal.ppat.1013227

bioRxiv [Preprint]. 2025 May 24:2025.05.24.655922. doi: 10.1101/2025.05.24.655922.

ABSTRACT

Ornithobacterium hominis is a recently described Gram-negative bacterium that colonises the human nasopharynx and may be associated with poor upper respiratory tract health. Here, we describe the isolation of O. hominis from samples collected from a South African birth cohort, creating the first archive of cultured strains of the species from Africa. Sequenced genomes from this archive reveal that South African O. hominis is more similar to Australian strains than those from Southeast Asia, and that it may share genes with other members of the microbiome that are relevant for virulence, colonisation, and antibiotic resistance. Leveraging existing microbiome data from the cohort, O. hominis was found to be closely associated with bacterial co-colonisers that are rare in non-carrier individuals, including Suttonella, Helcococcus, Moraxella spp., and Gracilibacteria. Their collective acquisition has a significant impact on the diversity of nasopharyngeal communities that contain O. hominis. Individuals who have not yet acquired O. hominis have a higher abundance of Moraxella (particularly M. lincolnii) than individuals who never acquire O. hominis, suggesting that this could be a precursor state for successful colonisation. Finally, a novel co-coloniser species, Helcococcus ekapensis, was successfully isolated and sequenced.

PMID:40475515 | PMC:PMC12139837 | DOI:10.1101/2025.05.24.655922

PLOS Glob Public Health. 2025 Jun 6;5(6):e0004675. doi: 10.1371/journal.pgph.0004675. eCollection 2025.

ABSTRACT

This study examines the use and translation of epidemiological modelling by policy and decision makers in response to the COVID-19 outbreak. Prior to COVID-19, there was little readiness for global health systems, and many science-policy networks were assembled ad-hoc. Moreover, in the field of epidemiological modelling, one with significant sudden influence, there is still no international guidance or standard of practice on how modelled evidence should guide policy during major health crises. Here we use a multi-country case study on the use of epidemiological modelling in emergency COVID-19 response, to examine the effective integration of crisis science and policy in different countries. We investigated COVID-19 modelling-policy systems and practices in 13 countries, spanning all six UN geographic regions. Data collection took the form of expert interviews with a range of national policy/ decision makers, scientific advisors, and modellers. We examined the current use of epidemiological modelling, introduced a classification framework for outbreak modelling and policy on which best practice can be structured, and provided preliminary recommendations for future practice. Full analysis and interpretation of the breadth of interview responses is presented, providing evidence for the current and future use of modelling in disease outbreaks. We found that interviewees in countries with a similar size and type of modelling infrastructure, and similar level of government interaction with modelling reported similar experiences and recommendations on using modelling in outbreak response. From this, we introduced a helpful grouping of country experience upon which a tailored future best practice could be structured. We concluded the article by outlining context-specific activities that modellers and policy actors could consider implementing in their own countries. This article serves as a first evidence base for the current use of modelling in a recent major health crisis and provides a robust framework for developing epidemiological modelling-to-policy best practice.

PMID:40478854 | DOI:10.1371/journal.pgph.0004675

Vet Clin Pathol. 2025 Jun 6. doi: 10.1111/vcp.70029. Online ahead of print.

ABSTRACT

BACKGROUND: Neutrophil cell population data (CPD), including fluorescent light intensity (NE-SFL) and side scatter (NE-SSC), are promising inflammatory markers in human sepsis but remain unexplored in dogs and cats.

OBJECTIVES: Determine the diagnostic utility of NE-SSC and NE-SFL for detecting systemic inflammation in dogs and cats.

METHODS: Dogs and cats with archived CPD, blood films, and acute phase protein (APP) measurements were included. Increased C-reactive protein (CRP) in dogs and Serum Amyloid A (SAA) in cats were considered indicative of systemic inflammation. CPD was compared with APPs, white cell count (WCC), neutrophil count, band neutrophil count, and toxic change grade. Optimal cut-offs and associated sensitivities and specificities were calculated using ROC curve analysis. Correlations were assessed using Spearman's coefficient.

RESULTS: NE-SFL and NE-SSC were significantly increased in dogs and cats with systemic inflammation. The area under the curve (AUC) of NE-SFL was higher than that of NE-SSC, WCC, and band neutrophil count in both dogs (0.82) and cats (0.77). The optimal NE-SFL cut-off for detecting systemic inflammation was > 41.7 ch in dogs (sensitivity 80%; specificity 66%) and > 37.4 ch in cats (sensitivity 75%; specificity 67%). NE-SFL was positively correlated with APPs, WCC, neutrophil count, and band neutrophil count in both species. NE-SSC was positively correlated with APPs in both species and, in dogs, also with WCC, neutrophil count, and band neutrophil count.

CONCLUSION: CPD, particularly NE-SFL, is a promising marker of inflammation in dogs and cats and could be especially useful when APP quantification or blood smear examination are unavailable.

PMID:40476643 | DOI:10.1111/vcp.70029

Emerg Microbes Infect. 2025 Jun 6:2511132. doi: 10.1080/22221751.2025.2511132. Online ahead of print.

ABSTRACT

The increasing spread of highly pathogenic avian influenza (HPAI) A/H5 viruses poses a pandemic threat. Circulating clade 2.3.4.4b viruses have demonstrated rapid transcontinental dissemination, extensive reassortment, epizootic spread and potential sustained mammal-to-mammal transmission, signifying a heightened risk of becoming a human pathogen of high consequence. A broadly protective, future-proof vaccine against multiple clades of H5 influenza is urgently needed for pandemic preparedness. Here, we combine two novel vaccine technologies to generate a Digitally Immune Optimised and Selected H5 antigen (DIOSvax-H5inter) displayed multivalently on the mi3 nanocage using the SpyTag003/SpyCatcher003 conjugation system. Mice immunised with DIOSvax-H5inter Homotypic Nanocages at low doses demonstrate potent, cross-clade neutralising antibody and T cell responses against diverse H5 strains. DIOSvax-H5inter Homotypic Nanocages provide a scalable vaccine candidate with the potential for pan-H5 protection against drifted or newly emergent H5 strains. This World Health Organization preferred characteristic is essential for prospective strategic stockpiling in the pre-pandemic phase.Trial registration: ClinicalTrials.gov identifier: NCT06145178..

PMID:40476519 | DOI:10.1080/22221751.2025.2511132

Sci Rep. 2025 Jun 5;15(1):19728. doi: 10.1038/s41598-025-05223-6.

ABSTRACT

Tuberculin skin tests (TST), the primary diagnostic tool for bovine tuberculosis (bTB), cross-react with BCG vaccine. Recently developed defined antigen skin tests (DSTs) aim to differentiate infected amongst vaccinated animals. We evaluated the field performance of different interpretations of the TST and DSTs relative to IGRA and IDEXX M. bovis antibody tests. This panel of tests was assessed in 446 unvaccinated cattle across 22 Ethiopian dairy herds using Bayesian latent class models. We extended the standard Walter-Hui model to include age-related effects to explore evidence of the presence of diagnostic anergy. The latent class models estimate sensitivity and specificity of the DSTs to be between 84-88% and 79-85% respectively. The DSTs perform intermediately between the comparative intradermal test (CIT, sensitivity 77%, specificity 100%) and single intradermal test (SIT, sensitivity 99%, specificity 76%). We observed significant age-related declines in test sensitivity, most notably for CIT (declining from 75 to 52% over 9 years) and DST10 (83% to 68%), while other tests showed more stable sensitivity across age groups. This variable pattern across tests suggests mechanisms beyond simple age-related anergy. Together, these findings demonstrate that DSTs' superior sensitivity to CIT and comparable or better specificity than SIT, combined with their ability to distinguish vaccinated animals, creates a viable pathway for implementing BCG vaccination programs. Given the absence of any gold standard definition of infection with bTB, latent class analyses are essential to assess the relative performance of different diagnostic tests. While our results provide encouraging news for the sensitivity of the new DST tests, the high prevalence of bTB within our study population makes our design underpowered to assess the specificity of the DSTs. Future research, including assessment of the specificity of DSTs in disease-free populations and optimization of test formulation and validation through large-scale field trials is essential to fully establish the case for use in vaccination and surveillance programs.

PMID:40473835 | DOI:10.1038/s41598-025-05223-6

Vet Surg. 2025 Jun 2. doi: 10.1111/vsu.14270. Online ahead of print.

ABSTRACT

OBJECTIVE: To describe the complication rate and outcomes of dogs undergoing multilevel airway surgery for brachycephalic airway syndrome (BOAS) with and without the addition of uni- or bilateral cuneiformectomy.

STUDY DESIGN: Retrospective study.

ANIMALS: A total of 180 dogs undergoing BOAS surgery: 94 dogs undergoing modified multilevel surgery (non-PC); 86 additionally undergoing cuneiformectomy (PC).

METHODS: Case records from the University of Cambridge and Animal Health Trust databases between 2014 and 2021 were analyzed including data on laryngeal collapse grade, respiratory functional grading scores, BOAS index, hospitalization length and complications.

RESULTS: Neither the incidence risk of overall (non-PC = 19.4%, PC = 16.3%, p = .758), nor major (non-PC = 7.4%, PC = 11.6%, p = .482) complications differed between non-PC and PC dogs. Median hospitalization duration (non-PC = 1 day, PC = 1 day) did not differ between the two groups (p = .743). Both BOAS grade (median reduction = 1, p < .0001) and BOAS index (median reduction = 28.5%, p < .0001) reduced in dogs that underwent cuneiformectomy. Lower BCS was associated with increased postoperative complications (odds ratio = 0.452, p = .004) when preoperative BOAS grade and gender were controlled.

CONCLUSION: Cuneiformectomy was not associated with a higher incidence risk of complications than multilevel BOAS surgery alone. Significant improvements in respiratory parameters were observed following cuneiformectomy in addition to multilevel airway surgery.

CLINICAL SIGNIFICANCE: Cuneiformectomy represents a safe and effective adjunctive technique to manage higher grade laryngeal collapse in dogs with BOAS.

PMID:40457630 | DOI:10.1111/vsu.14270

J Appl Microbiol. 2025 May 29:lxaf131. doi: 10.1093/jambio/lxaf131. Online ahead of print.

ABSTRACT

AIMS: This study aims to evaluate the therapeutic efficacy of bacteriophage therapy alone or in combination with antibiotics in the treatment of acute infection caused by multidrug-resistant (MDR) Klebsiella pneumoniae.

METHODS AND RESULTS: In this study, we isolated and characterized a lytic bacteriophage vB_Kpn_FOPMU1, which exhibits potent antibacterial activity against K. pneumoniae. Whole-genome sequencing identified vB_Kpn_FOPMU1 as a member of the Przondovirus genus and revealed the presence of key lysis-associated genes, including those encoding endolysin, holin, and Rz-like spanin proteins. In vitro work demonstrated that incubation of bacteriophage and cefotaxime with K. pneumoniae significantly decreased the MIC of cefotaxime from 128µg mL-1 to 1 µg mL-1, indicating strong synergistic activity. Using a murine model of acute K. pneumoniae lung infection, we further demonstrated that the combination therapy significantly enhanced bacterial clearance compared to phage monotherapy. This synergistic approach restored sensitivity of K. pneumoniae to cefotaxime, prevented the emergence of phage-resistant bacterial mutants, and achieved superior bacterial eradication from both the lung and blood. Moreover, administration of the phage-antibiotic combination resulted in complete protection of infected mice, with a 100% survival rate, compared to a 60% survival rate observed in animals that received phage monotherapy. Therapeutic application of the bacteriophage-cefotaxime combination resulted in significantly improved lung pathology, characterized by reduced inflammatory cell infiltration and diminished tissue damage, compared to bacteriophage monotherapy.

CONCLUSION: Our findings underscore the potential of bacteriophage-antibiotic synergy as a promising therapeutic strategy to combat MDR K. pneumoniae infections and mitigate the risk of phage resistance development.

PMID:40440204 | DOI:10.1093/jambio/lxaf131

Vet Oncol. 2025;2(1):13. doi: 10.1186/s44356-025-00026-3. Epub 2025 May 26.

ABSTRACT

Canine malignant insulinoma is a rare, highly metastatic and life-threatening neuroendocrine tumour of pancreatic beta cells. To map the single-cell transcriptomic landscape of canine insulinoma for the first time, transcriptomic profiles of 5,532 cells were captured from two spontaneous insulinomas (Patient 1 and 2) and one associated metastasis (Patient 2) in two Boxer dogs. Distinct cancer, endocrine, and immune cell populations were identified. Notably, all three tumour samples contained two transcriptionally distinct insulin-expressing tumour cell populations (INS+ and INS+FOS low ), characterised here for the first time. These two cancer cell populations significantly differed by ~ 8,000 differentially expressed genes (DEGs), particularly tumour suppressor genes (e.g. TP53, EGR1) and cancer-related pathways (e.g., MAPK, p53). In contrast, COX7A2L was one of a few genes ubiquitously expressed and significantly upregulated (> 20-fold) in both insulin-expressing tumour populations compared to other captured populations. Both populations were also characterised by expression of chromogranin/secretogranin neuroendocrine tumour marker genes (e.g. CHGA, SCGN). There were far fewer gene expression differences observed between insulin-expressing tumour cells from the two patients (~ 600 DEGs) than between the two cancer cell populations within each patient. These DEGs included CLTRN, TMSB4X, CSRP2, LGALS2, and C15orf48. Unexpectedly for a tumour of endocrine origin, the metastasis in Patient 2 exhibited > 20-70 fold upregulation of exocrine pancreatic genes including CLPS, PRSS2, PRSS and CTRC. Immune cell analyses identified distinct infiltrating immune populations, including memory T cells and macrophages and revealed likely tumour-immune interactions, including the CD40-CD40L interaction. This study provides the first single-cell RNA sequencing (scRNA-seq) analysis of naturally occurring insulinoma in any species, revealing tumour cell heterogeneity, novel immune microenvironment features, and potential therapeutic targets. Despite its small scale, the findings highlight the utility of scRNA-seq in veterinary oncology and its translational potential for pancreatic neuroendocrine tumours across species.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s44356-025-00026-3.

PMID:40438247 | PMC:PMC12106163 | DOI:10.1186/s44356-025-00026-3

PLoS Negl Trop Dis. 2025 May 28;19(5):e0013072. doi: 10.1371/journal.pntd.0013072. eCollection 2025 May.

ABSTRACT

Parasitic diseases represent a substantial public health challenge worldwide. Traditional educational strategies have often fallen short in driving sustained behavioral shifts that are nonetheless essential for reducing the burden of these diseases. Edutainment, a blend of education and entertainment, is the synthesis of pedagogical content with recreational frameworks, leveraging narrative and visual appeal to elevate the learning experience through enriched experiences, aligning with the principles of "warm cognition". Human cognitive processes, including attention, learning and memory, are influenced by emotions. As a result, emotional experiences are remembered vividly and accurately, with great resilience over time. Several edutainment approaches have been successfully utilized to inspire positive behavioral changes against soil-transmitted helminths (STHs), schistosomiasis, echinococcosis, and other diseases. This scoping review delves into several documented approaches with sustainable positive post-intervention outcomes. Approaches such as animated cartoons, gamification, songs, videos, and music, mobile health applications, hands-on experience, posters, comics and educational booklets, puppet shows, toy animals, cardboard and plastic-coated drawings, drawing activities and competitions, group discussions, illustrated booklets and questionnaires have yielded statistically significant improvements in participant's knowledge related to parasitic diseases (up to 60% increase in knowledge scores), alongside notable reductions in risks of parasite transmission and infection prevalence. These improvements highlight the potential of edutainment to enhance community awareness, promote long-term behavioral changes, and ultimately contribute to reducing spread of disease. Moreover, artificial intelligence (AI) can be integrated into edutainment approaches to meet the growing demand for personalized and effective learning methods. We argue that such AI-driven edutainment can underpin sustainable progress in the control of parasitic diseases.

PMID:40435280 | DOI:10.1371/journal.pntd.0013072