Projecting the effect of crop yield increases, dietary change and different price scenarios on land use under two different state security regimes

Peer reviewedPublisher PD

Biomarkers for ragwort poisoning in horses: identification of protein targets

BACKGROUND: Ingestion of the poisonous weed ragwort (Senecio jacobea) by horses leads to irreversible liver damage. The principal toxins of ragwort are the pyrrolizidine alkaloids that are rapidly metabolised to highly reactive and cytotoxic pyrroles, which can escape into the circulation and bind to proteins. In this study a non-invasive in vitro model system has been developed to investigate whether pyrrole toxins induce specific modifications of equine blood proteins that are detectable by proteomic methods. RESULTS: One dimensional gel electrophoresis revealed a significant alteration in the equine plasma protein profile following pyrrole exposure and the formation of a high molecular weight protein aggregate. Using mass spectrometry and confirmation by western blotting the major components of this aggregate were identified as fibrinogen, serum albumin and transferrin. CONCLUSION: These findings demonstrate that pyrrolic metabolites can modify equine plasma proteins. The high molecular weight aggregate may result from extensive inter- and intra-molecular cross-linking of fibrinogen with the pyrrole. This model has the potential to form the basis of a novel proteomic strategy aimed at identifying surrogate protein biomarkers of ragwort exposure in horses and other livestock

Investigating interactions between UK horse owners and prescribers of anthelmintics

Helminths are common pathogens of equids and anthelmintic resistance is a major issue in cyathostomin species and Parascaris equorum. At the heart of mitigating the impact of increasing anthelmintic resistance levels, is the responsible dissemination and use of these medicines following best practice principles. There is a paucity of information on interactions between horse owners and anthelmintic prescribers and how this shapes control. Here, a study was undertaken to determine opinions and experiences of horse owners as they relate to anthelmintics purchase and implementation of best practice control. An online survey was distributed via email and social media to explore owners’ experiences of purchasing anthelmintics from United Kingdom prescribers, these being veterinarians, suitably qualified persons (SQPs) and pharmacists. Owner responses (n = 494) were analysed statistically to compare answers of respondents grouped according to: (i) from whom they bought anthelmintics (Veterinarians n = 60; SQPs n = 256; Pharmacists n = 42; More than one channel n = 136), and (ii) by which route (Face-to-face n = 234; Telephone n = 31; Online n = 226) they purchased. Owners who purchased from veterinarians predominantly did so face-to-face (81.3%), whilst those that bought from SQPs purchased via face-to-face (48.8%) and online (46.0%) interactions. Those who purchased from pharmacists predominantly bought anthelmintics online (76.2%). Participants who bought from veterinarians were more likely to view certain factors (i.e. time to talk to the supplier, supplier knowledge) as more important than those who purchased from other prescribers. Those who purchased from veterinarians were more likely to be recommended faecal egg count (FEC) test analysis; however, there was high uptake of FEC testing across all groups. There was a low uptake of anthelmintic efficacy testing; regardless of the prescriber type from whom anthelmintics were purchased. Those who purchased from veterinarians were more likely to agree that anthelmintics should be sold as veterinary prescription-only medicines. Those who purchased online (regardless of which type of prescriber they bought from) were less likely to consider prescriber advice or knowledge when deciding which product to buy and indicated that sellers were less likely to raise use of anthelmintics for targeting parasites. Across all groups, many owners stated that they were aware of or used non-chemical control measures such as dung removal and diagnostic FEC testing to target treatments. In summary, there were some differences in the type of advice provided at the point of purchase and this was dependent upon whom anthelmintics were purchased from and by which route they were bought

Development of the larval migration inhibition test for comparative analysis of ivermectin sensitivity in cyathostomin populations

Cyathostomins are the most prevalent parasitic pathogens of equids worldwide. These nematodes have been controlled using broad-spectrum anthelmintics; however, cyathostomin resistance to each anthelmintic class has been reported and populations insensitive to more than one class are relatively commonplace. The faecal egg count reduction test (FECRT) is considered the most suitable method for screening anthelmintic sensitivity in horses, but is subject to variation and is relatively time-consuming to perform. Here, we describe a larval migration inhibition test (LMIT) to assess ivermectin (IVM) sensitivity in cyathostomin populations. This test measures the paralysing effect of IVM on the ability of third stage larvae (L3) to migrate through a pore mesh. When L3 from a single faecal sample were examined on multiple occasions, variation in migration was observed: this was associated with the length of time that the L3 had been stored before testing but the association was not significant. Half maximal effective concentration (EC50) values were then obtained for cyathostomin L3 from six populations of horses or donkeys that showed varying sensitivity to IVM in previous FECRTs. Larvae from populations indicated as IVM resistant by FECRT displayed significantly higher EC50 values in the LMIT than L3 from populations classified as IVM sensitive or L3 from populations that had not been previously exposed to IVM or had limited prior exposure. The analysis also showed that EC50 values obtained using L3 from animals in which IVM faecal egg count reduction (FECR) levels had been recorded as 95%. For one of the populations, time that had elapsed since IVM administration had an effect on the EC50 value obtained, with a longer time since treatment associated with lower EC50 values. These results indicate that the LMIT has value in discriminating IVM sensitivity amongst cyathostomin populations, but several factors were identified that need to be taken into account when executing the test and interpreting the derived data

Heritable, heterogeneous, and costly resistance of sheep against nematodes and potential feedbacks to epidemiological dynamics

Infected hosts may preserve fitness by resisting parasites (reducing parasite burden) and/or tolerating them (preventing or repairing infection-induced damage). Theory predicts that these individual-level defense strategies generate divergent population-level feedbacks that would maintain genetic heterogeneity for resistance but purge heterogeneity for tolerance. Because resistance reduces parasite abundance, selection for costly resistance traits will weaken as resistance becomes common. Such negative frequency-dependent selection contrasts with predictions for tolerance, which maintains parasite abundance and so is expected to generate positive frequencydependent selection, unless, for example, tolerance trades off with resistance. Thus far, there have been few tests of this theory in natural systems. Here, we begin testing the predictions in a mammalian field system, using data on individual gastrointestinal nematode burdens, nematode-specific antibody titers (as a resistance metric), the slope of body weight on parasite burden (as a tolerance metric), and fitness from an unmanaged population of Soay sheep. We find that nematode resistance is costly to fitness and underpinned by genetic heterogeneity, and that resistance is independent of tolerance. Drawing upon empirical metrics such as developed here, future work will elucidate how resistance and tolerance feedbacks interact to generate population-scale patterns in the Soay sheep and other field systems