Comparison of gene targets and sampling regimes for SARS-CoV-2 quantification for wastewater epidemiology in UK prisons.

Prisons are high-risk settings for infectious disease transmission, due to their enclosed and semi-enclosed environments. The proximity between prisoners and staff, and the diversity of prisons reduces the effectiveness of non-pharmaceutical interventions, such as social distancing. Therefore, alternative health monitoring methods, such as wastewater-based epidemiology (WBE), are needed to track pathogens, including SARS-CoV-2. This pilot study assessed WBE to quantify SARS-CoV-2 prevalence in prison wastewater to determine its utility within a health protection system for residents. The study analysed 266 samples from six prisons in England over a 12-week period for nucleoprotein 1 (N1 gene) and envelope protein (E gene) using quantitative reverse transcriptase-polymerase chain reaction. Both gene assays successfully detected SARS-CoV-2 fragments in wastewater samples, with both genes significantly correlating with COVID-19 case numbers across the prisons (p < 0.01). However, in 25% of the SARS-positive samples, only one gene target was detected, suggesting that both genes be used to reduce false-negative results. No significant differences were observed between 14- and 2-h composite samples, although 2-h samples showed greater signal variance. Population normalisation did not improve correlations between the N1 and E genes and COVID-19 case data. Overall, WBE shows considerable promise for health protection in prison settings.

Unusual Presentation of Von Hippel-Lindau Syndrome With Gastric Variceal Bleeding.

Gastric varices are most commonly a complication of portal hypertension or splenic vein thrombosis (SVT). The presence of gastric varices due to portal hypertension is significantly less than the prevalence of esophageal varices. SVT is a known complication of pancreatitis due to inflammation or compression of the splenic vein coursing along the posterior surface of the pancreas. Occlusion of the splenic vein leads to left-sided portal hypertension. Left-sided portal hypertension results in the development of collateral vessels that bypass the splenic vein by connecting with the short gastric veins. The associated increased pressure within the gastric vessels results in gastric varices. Gastric varices due to SVT may occur in the absence of or be disproportionate to esophageal varices. We report an interesting case of gastrointestinal bleeding from gastric varices related to cirrhosis secondary to metabolic dysfunction-associated steatohepatitis and SVT secondary to chronic pancreatitis due to pancreatic neuroendocrine tumor (NET) in a patient diagnosed with von Hippel-Lindau (VHL) syndrome.

Antimicrobial resistance in rural rivers: Comparative study of the Coquet (Northumberland) and Eden (Cumbria) River catchments.

Many studies have characterised resistomes in river microbial communities. However, few have compared resistomes in parallel rural catchments that have few point-source inputs of antimicrobial genes (ARGs) and organisms (i.e., AMR) - catchments where one can contrast more nebulous drivers of AMR in rural rivers. Here, we used quantitative microbial profiling (QMP) to compare resistomes and microbiomes in two rural river catchments in Northern England, the Coquet and Eden in Northumberland and Cumbria, respectively, with different hydrological and geographical conditions. The Eden has higher flow rates, higher annual surface runoff, and longer periods of soil saturation, whereas the Coquet is drier and has lower flowrates. QMP analysis showed the Eden contained significantly more abundant microbes associated with soil sources, animal faeces, and wastewater than the Coquet, which had microbiomes like less polluted rivers (Wilcoxon test, p < 0.01). The Eden also had greater ARG abundances and resistome diversity (Kruskal Wallis, p < 0.05), and higher levels of potentially clinically relevant ARGs. The Eden catchment had greater and flashier runoff and more extensive agricultural land use in its middle reach, which explains higher levels of AMR in the river. Hydrological and geographic factors drive AMR in rural rivers, which must be considered in environmental monitoring programmes.

Characterising global antimicrobial resistance research explains why One Health solutions are slow in development: An application of AI-based gap analysis.

The global health crisis posed by increasing antimicrobial resistance (AMR) implicitly requires solutions based a One Health approach, yet multisectoral, multidisciplinary research on AMR is rare and huge knowledge gaps exist to guide integrated action. This is partly because a comprehensive survey of past research activity has never performed due to the massive scale and diversity of published information. Here we compiled 254,738 articles on AMR using Artificial Intelligence (AI; i.e., Natural Language Processing, NLP) methods to create a database and information retrieval system for knowledge extraction on research perfomed over the last 20 years. Global maps were created that describe regional, methodological, and sectoral AMR research activities that confirm limited intersectoral research has been performed, which is key to guiding science-informed policy solutions to AMR, especially in low-income countries (LICs). Further, we show greater harmonisation in research methods across sectors and regions is urgently needed. For example, differences in analytical methods used among sectors in AMR research, such as employing culture-based versus genomic methods, results in poor communication between sectors and partially explains why One Health-based solutions are not ensuing. Therefore, our analysis suggest that performing culture-based and genomic AMR analysis in tandem in all sectors is crucial for data integration and holistic One Health solutions. Finally, increased investment in capacity development in LICs should be prioritised as they are places where the AMR burden is often greatest. Our open-access database and AI methodology can be used to further develop, disseminate, and create new tools and practices for AMR knowledge and information sharing.

Fate and transport modelling for evaluating antibiotic resistance in aquatic environments: Current knowledge and research priorities.

Antibiotics have revolutionised medicine in the last century and enabled the prevention of bacterial infections that were previously deemed untreatable. However, in parallel, bacteria have increasingly developed resistance to antibiotics through various mechanisms. When resistant bacteria find their way into terrestrial and aquatic environments, animal and human exposures increase, e.g., via polluted soil, food, and water, and health risks multiply. Understanding the fate and transport of antibiotic resistant bacteria (ARB) and the transfer mechanisms of antibiotic resistance genes (ARGs) in aquatic environments is critical for evaluating and mitigating the risks of resistant-induced infections. The conceptual understanding of sources and pathways of antibiotics, ARB, and ARGs from society to the water environments is essential for setting the scene and developing an appropriate framework for modelling. Various factors and processes associated with hydrology, ecology, and climate change can significantly affect the fate and transport of ARB and ARGs in natural environments. This article reviews current knowledge, research gaps, and priorities for developing water quality models to assess the fate and transport of ARB and ARGs. The paper also provides inputs on future research needs, especially the need for new predictive models to guide risk assessment on AR transmission and spread in aquatic environments.