Antimicrobial resistance and antimicrobial use animal monitoring policies in Europe: Where are we?

The World Health Organization has recognized antimicrobial resistance as one of the top three threats to human health. Any use of antibiotics in animals will ultimately affect humans and vice versa. Appropriate monitoring of antimicrobial use and resistance has been repeatedly emphasized along with the need for global policies. Under the auspices of the European Union research project, EFFORT, we mapped antimicrobial use and resistance monitoring programs in ten European countries. We then compared international and European guidelines and policies. In resistance monitoring, we did not find important differences between countries. Current resistance monitoring systems are focused on food animal species (using fecal samples). They ignore companion animals. The scenario is different for monitoring antibiotics use. Recently, countries have tried to harmonize methodologies, but reporting of antimicrobial use remains voluntary. We therefore identified a need for stronger policies

Impact of guidelines and recommendations on the level and patterns of antimicrobial use in livestock and companion animals: Systematic Review

Background: There are currently several voluntary guidelines and recommendations that aim topromote the responsible use of antimicrobials (AMU) and to reduce misuse of these medicines in bothfood-producing animals and companion animals. They have been developed by a number oforganisations and implemented in several European countries with the aim of reducing the impact ofAMU on antimicrobial resistance (AMR). However, the extent of implementation of these guidelinesand their effectiveness in changing behaviours associated with AMU are unknown in most cases. Thisreview assesses the extent of implementation of guidelines, and the impact of these on levels andpatterns of AMU in food-producing animals and companion animals in order to inform thedevelopment and implementation of better voluntary approaches for reducing AMU in the animalhealth sector.Methods: Databases including Science Direct and MEDLINE were searched for studies assessing theextent of implementation and impact of guidelines on levels and patterns of AMU in food-producinganimals and companion animals. Additional searches using reference tracking, snowballing and greyliterature were also performed. Quality of evidence and risk of bias assessment were conducted. Anarrative synthesis approach was followed to assess and present the evidence gathered across eligiblestudies.Results: A total of 784 studies were screened. Fourteen studies were deemed eligible for inclusion.All, apart from three, were conducted in Europe. Several voluntary guidelines on prudent AMU werereferred to in these studies, mostly developed by international or regional bodies. There is limitedevidence on the extent of implementation and the effectiveness of these guidelines in food-producinganimals and companion animals. In food-producing animals, the quality of studies was deemed low asmost were cross-sectional and based on convenience sampling. There were differences in uptake ofprudent AMU guidelines including use of antimicrobial susceptibility testing (ASTs) and criticallyimportant antimicrobials (CIAs) among countries. Voluntary initiatives from levy bodies supportingfarmers involving reduction and ban of use of CIAs (e.g. third generation cephalosporins), combinedwith changes in animal husbandry and farming practices, and improvement of vaccination strategieswere deemed amongst the most effective in the swine (UK and Denmark) and poultry (UK) sectors,and to a lesser extent in the dairy cattle production sector (Denmark). There may be lessons to belearnt from these countries for more effective AMU reduction strategies. Nevertheless, there are stillscarce data on the potential impact of voluntary interventions on animal health and welfare, andproductivity. One of the few countries to have assessed the impact of the promotion of prudent usecampaigns, on animal health and welfare, and productivity was Denmark which has recently reportedthat their impact waslow in the short term according to surveillance data, though further assessmentsare required to assess impact in the long-term. There was even less evidence available for companionanimals, and the quality of studies was lower; as consequence, these studies were not deemedsuitable for the assessment of impact of prudent use recommendations and guidelines.Conclusions: Prudent use guidelines are available in most European countries, at different levels:international (Europe-wide); national (countrywide or for members of associations); and local (e.g. athospital level). In some countries like the UK, the livestock and poultry industries have taken theinitiative to reduce the use of AMs by adopting national and international recommendations for thereduction of use the use of critically important antimicrobials. However, there is currently limitedquantitative evidence of the impact of the recommendations voluntary interventions in AMU in bothfood-producing and companion animals, and, particularly, their impact on animal health and welfare,and productivity. This is due to the lack of systematic assessment of surveillance data and oflongitudinal studies to investigate the effectiveness of guidelines in changing antibiotic use in animalpopulations the promotion of prudent AMU. Targeted adoption of prudent use practices by farmersand veterinarians were reported to be an effective approach to reduce AMU, including CIAs in poultry,swine and dairy cattle

Effectiveness of alternative measures to reduce antimicrobial usage in pig production in four European countries

Background The reduction of antimicrobial usage (AMU) is in the focus in modern pig production. The objective of this study was to assess the effectiveness of alternatives to reduce AMU at herd level. In a prospective study, 68 farrow-to-finish pig herds located in Belgium, France, Germany and Sweden were recruited on a voluntary basis to implement tailor-made intervention plans to reduce their AMU. Alternative measures included improvement of biosecurity (n = 29 herds), vaccination (n = 30), changes of feeding schemes or drinking water quality (n = 45), improved pig health and welfare care (n = 21) as well as changes in stable climate and zootechnical measures (n = 14). Herds were followed for 1 year after implementation of measures. Annual antimicrobial expenditures or treatment records, as well as disease incidence scores were collected and compared to those of the year before intervention. AMU was measured as the treatment incidence and calculated by age category, antimicrobial class and administration route. Results Compliance with the intervention plans was high (median 93%). AMU was significantly reduced following the implementation of alternative measures: in the median herd of the four countries, pigs were treated before intervention 25% of their expected lifespan (200 days from birth to slaughter) and after intervention 16%. AMU of suckling and weaned pigs were significantly reduced by 37 and 54%, respectively. The usage of polymyxins and tetracyclines was significantly reduced by 69 and 49%, respectively. AMU via feed and water, as well as parenteral AMU were significantly reduced by 46 and 36%, respectively. Herds with a higher AMU level before intervention achieved a bigger reduction. The majority of disease incidence were similar before and after intervention, with a few exceptions of disorders related to the gastro-intestinal tract in suckling pigs (decreased) and in breeding pigs (increased). Conclusion Following tailor-made implementation of alternative measures, a substantial reduction of AMU in pig production was achievable without jeopardizing animal health. The AMU reduction in the youngest age categories (suckling and weaned pigs) and the reduction of group treatments via feed and water was in line with the recent European Guidelines on the prudent use of antimicrobials in veterinary medicine

Evaluation of bovine viral diarrhoea virus control strategies in dairy herds in Hokkaido, Japan, using stochastic modelling

Bovine viral diarrhoea virus (BVDV) infection in cattle can result in growth retardation, reduced milk production, reproductive disorders and death. Persistently infected animals are the primary source of infection. In Hokkaido, Japan, all cattle entering shared pastures in summer are vaccinated before movement for disease control. Additionally, these cattle may be tested for BVDV and culled if positive. However, the effectiveness of this control strategy aiming to reduce the number of BVDV-infected animals has not been assessed. The aim of this study was to evaluate the effectiveness of various test-and-cull and/or vaccination strategies on BVDV control in dairy farms in two districts of Hokkaido, Nemuro and Hiyama. A stochastic model was developed to compare the different control strategies over a 10-year period. The model was individual-based and simulated disease dynamics both within and between herds. Parameters included in the model were obtained from the literature, the Hokkaido government and the Japanese Ministry of Agriculture, Forestry and Fisheries. Nine different scenarios were compared as follows: no control, test-and-cull strategies based on antigen testing of either calves or only cattle entering common pastures, vaccination of all adult cattle or only cattle entering shared pastures and combinations thereof. The results indicate that current strategies for BVDV control in Hokkaido slightly reduced the number of BVDV-infected animals; however, alternative strategies such as testing all calves and culling any positives or vaccinating all susceptible adult animals dramatically reduced those. To our knowledge, this is the first report regarding the comparison of the effectiveness between the current strategies in Hokkaido and the alternative strategies for BVDV control measures

Potential of Polygonum cuspidatum Root as an Antidiabetic Food: Dual High-Resolution α‑Glucosidase and PTP1B Inhibition Profiling Combined with HPLC-HRMS and NMR for Identification of Antidiabetic Constituents

The worldwide increasing incidence of type 2 diabetes has fueled an intensified search for food and herbal remedies with preventive and/or therapeutic properties. Polygonum cuspidatum Siebold & Zucc. (Polygonaceae) is used as a functional food in Japan and South Korea, and it is also a well-known traditional antidiabetic herb used in China. In this study, dual high-resolution α-glucosidase and protein-tyrosine phosphatase 1B (PTP1B) inhibition profiling was used for the identification of individual antidiabetic constituents directly from the crude ethyl acetate extract and fractions of P. cuspidatum. Subsequent preparative-scale HPLC was used to isolate a series of α-glucosidase inhibitors, which after HPLC-HRMS and NMR analysis were identified as procyanidin B2 3,3″-<i>O</i>-digallate (<b>3</b>) and (−)-epicatechin gallate (<b>5</b>) with IC₅₀ values of 0.42 ± 0.02 and 0.48 ± 0.0004 μM, respectively, as well as a series of stilbene analogues with IC₅₀ value in the range from 6.05 ± 0.05 to 116.10 ± 2.04 μM. In addition, (<i>trans</i>)-emodin-physcion bianthrone (<b>15b</b>) and (<i>cis</i>)-emodin-physcion bianthrone (<b>15c</b>) were identified as potent PTP1B inhibitors with IC₅₀ values of 2.77 ± 1.23 and 7.29 ± 2.32 μM, respectively. These findings show that P. cuspidatum is a potential functional food for management of type 2 diabetes

Active and inactive orientations of the transmembrane and cytosolic domains of the erythropoietin receptor dimer

Binding of erythropoietin to the erythropoietin receptor (EpoR) extracellular domain orients the transmembrane (TM) and cytosolic regions of the receptor dimer into an unknown activated conformation. By replacing the EpoR extracellular domain with a dimeric coiled coil, we engineered TM EpoR fusion proteins where the helical TM domains were constrained into seven possible relative orientations. We identify one dimeric TM conformation that imparts full activity to the cytosolic domain of the receptor and signals via JAK2, STAT proteins, and MAP kinase, one partially active orientation that preferentially activates MAP kinase, and one conformation corresponding to the inactive receptor. The active and inactive conformations were independently identified by computational searches for low-energy TM dimeric structures. We propose a specific EpoR-activated interface and suggest its use for structural and signaling studies

High-Resolution Screening Combined with HPLC-HRMS-SPE-NMR for Identification of Fungal Plasma Membrane H⁺‑ATPase Inhibitors from Plants

Crude extracts of 33 plant species were assessed for fungal plasma membrane (PM) H⁺-ATPase inhibition. This led to identification of 18 extracts showing more than 95% inhibition at a concentration of 7.5 mg/mL and/or a concentration-dependent activity profile. These extracts were selected for semi-high-resolution fungal PM H⁺-ATPase inhibition screening, and, on the basis of these results, Haplocoelum foliolosum (Hiern) Bullock and Sauvagesia erecta L. were selected for investigation by high-resolution fungal PM H⁺-ATPase inhibition screening. Structural analysis performed by high-performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance spectroscopy (HPLC-HRMS-SPE-NMR) led to identification of chebulagic acid (<b>1</b>) and tellimagrandin II (<b>2</b>) from H. foliolosum. Preparative-scale isolation of the two metabolites allowed determination of IC₅₀ values for PM H⁺-ATPase, and growth inhibition of Saccharomyces cerevisiae and Candida albicans. Chebulagic acid and tellimagrandin II are both potent inhibitors of the PM H⁺-ATPase with inhibitory effect on the growth of S. cerevisiae