Immunohistochemical characterization of clear cell variant of hepatocellular carcinoma in a sheep.

The cadaver and viscera of a mature female sheep (Ovis aries) underwent routine abattoir meat inspection. The liver was expanded by an infiltrative neoplastic mass comprising multifocal to coalescing, well-demarcated, pink to white-yellow nodules, up to 25 mm in diameter. An unencapsulated, moderately densely cellular, infiltrative neoplasm was present within the hepatic parenchyma. The neoplastic cells were arranged in solid sheets and acini supported by a moderately fine collagenous vascularized stroma. The neoplastic cells were moderately sized and polygonal, with clearly delineated cell borders and a moderate amount of cytoplasm that was clear or exhibited either globular eosinophilic deposits or fine fibrillar eosinophilic strands. The neoplastic cell nuclei were round and centrally located. The chromatin was lightly stippled and there was frequently a single, prominent, basophilic nucleolus. There were eight mitoses in 10 high-power fields (2.37 mm2). Most of the neoplastic cells had intense cytoplasmic immunolabelling for arginase 1, with frequent concurrent nuclear positivity, and mild to moderately intense punctate cytoplasmic labelling for hepatocyte specific antigen (Hep Par-1). The neoplastic cells did not label with anti-cytokeratin 19 antibody. Based on the histological appearance and the immunolabelling pattern, the neoplasm was diagnosed as the clear cell variant of a hepatocellular carcinoma.

Post COVID-19: a solution scan of options for preventing future zoonotic epidemics.

The crisis generated by the emergence and pandemic spread of COVID-19 has thrown into the global spotlight the dangers associated with novel diseases, as well as the key role of animals, especially wild animals, as potential sources of pathogens to humans. There is a widespread demand for a new relationship with wild and domestic animals, including suggested bans on hunting, wildlife trade, wet markets or consumption of wild animals. However, such policies risk ignoring essential elements of the problem as well as alienating and increasing hardship for local communities across the world, and might be unachievable at scale. There is thus a need for a more complex package of policy and practical responses. We undertook a solution scan to identify and collate 161 possible options for reducing the risks of further epidemic disease transmission from animals to humans, including potential further SARS-CoV-2 transmission (original or variants). We include all categories of animals in our responses (i.e. wildlife, captive, unmanaged/feral and domestic livestock and pets) and focus on pathogens (especially viruses) that, once transmitted from animals to humans, could acquire epidemic potential through high rates of human-to-human transmission. This excludes measures to prevent well-known zoonotic diseases, such as rabies, that cannot readily transmit between humans. We focused solutions on societal measures, excluding the development of vaccines and other preventive therapeutic medicine and veterinary medicine options that are discussed elsewhere. We derived our solutions through reading the scientific literature, NGO position papers, and industry guidelines, collating our own experiences, and consulting experts in different fields. Herein, we review the major zoonotic transmission pathways and present an extensive list of options. The potential solutions are organised according to the key stages of the trade chain and encompass solutions that can be applied at the local, regional and international scales. This is a set of options targeted at practitioners and policy makers to encourage careful examination of possible courses of action, validating their impact and documenting outcomes.

A One Health Study of the Genetic Relatedness of Klebsiella pneumoniae and Their Mobile Elements in the East of England.

BACKGROUND: Klebsiella pneumoniae is a human, animal, and environmental commensal and a leading cause of nosocomial infections, which are often caused by multiresistant strains. We evaluate putative sources of K. pneumoniae that are carried by and infect hospital patients. METHODS: We conducted a 6-month survey on 2 hematology wards at Addenbrooke's Hospital, Cambridge, United Kingdom, in 2015 to isolate K. pneumoniae from stool, blood, and the environment. We conducted cross-sectional surveys of K. pneumoniae from 29 livestock farms, 97 meat products, the hospital sewer, and 20 municipal wastewater treatment plants in the East of England between 2014 and 2015. Isolates were sequenced and their genomes compared. RESULTS: Klebsiella pneumoniae was isolated from stool of 17/149 (11%) patients and 18/922 swabs of their environment, together with 1 bloodstream infection during the study and 4 others over a 24-month period. Each patient carried 1 or more lineages that was unique to them, but 2 broad environmental contamination events and patient-environment transmission were identified. Klebsiella pneumoniae was isolated from cattle, poultry, hospital sewage, and 12/20 wastewater treatment plants. There was low genetic relatedness between isolates from patients/their hospital environment vs isolates from elsewhere. Identical genes encoding cephalosporin resistance were carried by isolates from humans/environment and elsewhere but were carried on different plasmids. CONCLUSION: We identified no patient-to-patient transmission and no evidence for livestock as a source of K. pneumoniae infecting humans. However, our findings reaffirm the importance of the hospital environment as a source of K. pneumoniae associated with serious human infection.

One Health Genomic Surveillance of Escherichia coli Demonstrates Distinct Lineages and Mobile Genetic Elements in Isolates from Humans versus Livestock.

Livestock have been proposed as a reservoir for drug-resistant Escherichia coli that infect humans. We isolated and sequenced 431 E. coli isolates (including 155 extended-spectrum ß-lactamase [ESBL]-producing isolates) from cross-sectional surveys of livestock farms and retail meat in the East of England. These were compared with the genomes of 1,517 E. coli bacteria associated with bloodstream infection in the United Kingdom. Phylogenetic core genome comparisons demonstrated that livestock and patient isolates were genetically distinct, suggesting that E. coli causing serious human infection had not directly originated from livestock. In contrast, we observed highly related isolates from the same animal species on different farms. Screening all 1,948 isolates for accessory genes encoding antibiotic resistance revealed 41 different genes present in variable proportions in human and livestock isolates. Overall, we identified a low prevalence of shared antimicrobial resistance genes between livestock and humans based on analysis of mobile genetic elements and long-read sequencing. We conclude that within the confines of our sampling framework, there was limited evidence that antimicrobial-resistant pathogens associated with serious human infection had originated from livestock in our region.IMPORTANCE The increasing prevalence of E. coli bloodstream infections is a serious public health problem. We used genomic epidemiology in a One Health study conducted in the East of England to examine putative sources of E. coli associated with serious human disease. E. coli from 1,517 patients with bloodstream infections were compared with 431 isolates from livestock farms and meat. Livestock-associated and bloodstream isolates were genetically distinct populations based on core genome and accessory genome analyses. Identical antimicrobial resistance genes were found in livestock and human isolates, but there was limited overlap in the mobile elements carrying these genes. Within the limitations of sampling, our findings do not support the idea that E. coli causing invasive disease or their resistance genes are commonly acquired from livestock in our region.

Genomic Surveillance of Enterococcus faecium Reveals Limited Sharing of Strains and Resistance Genes between Livestock and Humans in the United Kingdom.

Vancomycin-resistant Enterococcus faecium (VREfm) is a major cause of nosocomial infection and is categorized as high priority by the World Health Organization global priority list of antibiotic-resistant bacteria. In the past, livestock have been proposed as a putative reservoir for drug-resistant E. faecium strains that infect humans, and isolates of the same lineage have been found in both reservoirs. We undertook cross-sectional surveys to isolate E. faecium (including VREfm) from livestock farms, retail meat, and wastewater treatment plants in the United Kingdom. More than 600 isolates from these sources were sequenced, and their relatedness and antibiotic resistance genes were compared with genomes of almost 800 E. faecium isolates from patients with bloodstream infection in the United Kingdom and Ireland. E. faecium was isolated from 28/29 farms; none of these isolates were VREfm, suggesting a decrease in VREfm prevalence since the last UK livestock survey in 2003. However, VREfm was isolated from 1% to 2% of retail meat products and was ubiquitous in wastewater treatment plants. Phylogenetic comparison demonstrated that the majority of human and livestock-related isolates were genetically distinct, although pig isolates from three farms were more genetically related to human isolates from 2001 to 2004 (minimum of 50 single-nucleotide polymorphisms [SNPs]). Analysis of accessory (variable) genes added further evidence for distinct niche adaptation. An analysis of acquired antibiotic resistance genes and their variants revealed limited sharing between humans and livestock. Our findings indicate that the majority of E. faecium strains infecting patients are largely distinct from those from livestock in this setting, with limited sharing of strains and resistance genes.IMPORTANCE The rise in rates of human infection caused by vancomycin-resistant Enterococcus faecium (VREfm) strains between 1988 to the 2000s in Europe was suggested to be associated with acquisition from livestock. As a result, the European Union banned the use of the glycopeptide drug avoparcin as a growth promoter in livestock feed. While some studies reported a decrease in VREfm in livestock, others reported no reduction. Here, we report the first livestock VREfm prevalence survey in the UK since 2003 and the first large-scale study using whole-genome sequencing to investigate the relationship between E. faecium strains in livestock and humans. We found a low prevalence of VREfm in retail meat and limited evidence for recent sharing of strains between livestock and humans with bloodstream infection. There was evidence for limited sharing of genes encoding antibiotic resistance between these reservoirs, a finding which requires further research.

Pursuing a career in veterinary public health.

Milorad Radakovic is a teaching fellow in veterinary public health (VPH) at the University of Cambridge. Here, he explains why he believes the challenges in this field of veterinary medicine make for an exciting career path. In a second article to be published in Vet Record Careers next week, he will share some of his own experiences of working in this field.