Multigeneric resistance to monepantel on a UK sheep farm

The amino acetonitrile derivative, monepantel, represented the first new broad spectrum anthelmintic to be brought to market for use in sheep for over 25 years when it was introduced in 2009. This study characterised monepantel efficacy, using faecal egg count reduction and controlled efficacy tests, against gastrointestinal nematodes following a report of treatment failure in a UK lowland sheep flock. Twelve lambs were each artificially administered 15,000 infective larvae that had been propagated from lamb faeces collected from the farm of interest. The controlled efficacy test showed that a recommended dose rate of monepantel (2.5 mg/kg body weight) administered at day 28 post infection was ineffective at removing the infection in the treated lambs. The result demonstrated simultaneous resistance to monepantel in Teladorsagia circumcincta, Trichostrongylus vitrinus and Oesophagostomum venulosum with efficacies based on adult worm burden reductions, compared to untreated controls, of 78%, 27% and 22% respectively. Monepantel efficacy based on undifferentiated egg count in treated animals, seven day post administration, compared to untreated controls was 85%. The results raise questions about the origins of, and predisposing factors for, resistance development in the three different species, and reinforces the value of differentiating post treatment faecal egg counts to genus or species level

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) : third edition of the guideline for evaluating efficacy of anthelmintics in ruminants (bovine, ovine, caprine)

This guideline is aimed at those who are involved in the assessment of anthelmintic efficacy in ruminant livestock species (bovine, ovine and caprine). The intent is to provide a framework that can be adopted worldwide for the testing of anthelmintics in ruminants, such that studies carried out in different countries can be compared and thereby unnecessary duplication can be reduced. Recommendations are made for the selection, housing and feeding of study animals, the type of studies required, the method used to conduct those studies, the assessment of results and the standards for defining anthelmintic efficacy.https://www.elsevier.com/locate/vetparhj2024Veterinary Tropical DiseasesSDG-03:Good heatlh and well-bein

Proliferation, apoptosis and their regulatory protein expression in colorectal adenomas and serrated lesions

Background Adenomas and serrated lesions represent heterogeneous sets of early precursors in the colorectum with varying malignant potential. They are often distinguished by their histopathologic differences, but little is known about potential differences in regulation of epithelial proliferation and apoptosis. Methods We conducted a protein expression analysis using tissue microarrays of 625 colorectal adenomas and 142 serrated lesions to determine potential differences in regulation of epithelial proliferation and apoptosis. We quantitated proliferation with Ki-67; apoptosis with activated caspase-3 (CASP3); up- and down-regulators of proliferation with cyclin D1, p16INK2, and p21Cip1; and apoptosis regulators with BAX, BCL2, and survivin. Linear mixed effects models and circos diagrams were used to determine relationships among expression and lesion characteristics. Results Adenomas had a significantly higher CASP-3 labeling index (LI) than serrated lesions, resulting in a lower net growth ratio (Ki-67 LI/activated CASP-3 LI, p-value<0.0001). Cyclin D1 LI, p16 LI and p21 LI were lower in adenomas compared to serrated lesions, while expression of both BCL2 and BAX were higher (p <0.001). Among adenomas, cyclin D1 LI and p16 LI levels increased with greater villous component, and the highest BAX expression was detected in adenomas larger than 2 cm (both p<0.0001). Right-sided adenomas had higher CASP3 LI than left colorectal adenomas (p = 0.008). Significant differences in cyclin D1 LI, p21 LI and survivin LI were also observed across histopathologic subtypes of serrated lesions. Conclusions Our findings demonstrate different patterns of regulatory protein expression in adenomas than serrated lesions, especially involving apoptosis

To what extent is climate change adaptation a novel challenge for agricultural modellers?

Modelling is key to adapting agriculture to climate change (CC), facilitating evaluation of the impacts and efficacy of adaptation measures, and the design of optimal strategies. Although there are many challenges to modelling agricultural CC adaptation, it is unclear whether these are novel or, whether adaptation merely adds new motivations to old challenges. Here, qualitative analysis of modellers’ views revealed three categories of challenge: Content, Use, and Capacity. Triangulation of findings with reviews of agricultural modelling and Climate Change Risk Assessment was then used to highlight challenges specific to modelling adaptation. These were refined through literature review, focussing attention on how the progressive nature of CC affects the role and impact of modelling. Specific challenges identified were: Scope of adaptations modelled, Information on future adaptation, Collaboration to tackle novel challenges, Optimisation under progressive change with thresholds, and Responsibility given the sensitivity of future outcomes to initial choices under progressive change

Increasing importance of anthelmintic resistance in European livestock: creation and meta-analysis of an open database

Trabajo presentado al: COMBAR meeting (Combatting Anthelmintic Resistance in Ruminants). Atenas (Grecia). Febrero. 2022

Weak phenotypic reversion of ivermectin resistance in a field resistant isolate of Haemonchus contortus by verapamil

Recent advances in anthelmintic resistant phenotype reversion by Pgp modulating drugs in ruminant nematodes indicate that this can be a useful tool to helminth control. The aim of the present study was to evaluate the efficacy of ivermectin (IVM) in combination with verapamil (VRP), in oil or water-based vehicle, against an IVM-resistant field isolate of Haemonchus contortus through a larval migration assay and experimental infection trial. In the in vitro assay was observed a phenotypic reversion of H. contortus resistance to ivermectin at a high concentration of VRP, increasing IVM efficacy from 53.1% to 94.3. In the in vivo trial, IVM + VRP demonstrated 36.02% efficacy compared to the 7.75% of IVM alone. The vehicle formulation showed no influence in efficacy. These are the first results demonstrating the effect of VRP as a partial IVM-resistance phenotype reverser in a field isolate of IVM-resistant H. contortus experimentally inoculated in sheep