Identification of datasets on climate change in relation to livestock productivity (production and fitness traits) and livestock infectious disease

Datasets from Germany and the United Kingdom containing information on geographic  (European Union 27 countries), climatic, meteorological, host and infectious agents’  parameters (figure 2) have been completed and are now available for preliminary analysis  relating to data quality and consistency. Data set information will continue to be added over  the next 12 months

Genotypic characterisation of monepantel resistance in historical and newly derived field strains of Teladorsagia circumcincta

Recent reports of monepantel (MPTL) resistance in UK field isolates of Teladorsagia circumcincta has highlighted the need for a better understanding of the mechanism of MPTL-resistance in order to preserve its anthelmintic efficacy in this economically important species. Nine discrete populations of T. circumcincta were genotypically characterised; three MPTL-susceptible isolates, three experimentally selected MPTL-resistant strains and three field derived populations. Full-length Tci-mptl-1 gene sequences were generated and comparisons between the MPTL-susceptible isolates, MPTL-resistant strains and one field isolate, showed that different putative MPTL-resistance conferring mutations were present in different resistant isolates. Truncated forms of the Tci-mptl-1 gene were also observed. The genetic variability of individual larvae, within and between populations, was examined using microsatellite analyses at 10 ‘neutral’ loci (presumed to be unaffected by MPTL). Results confirmed that there was little background genetic variation between the populations, global FST <0.038. Polymorphisms present in exons 7 and 8 of Tci-mptl-1 enabled genotyping of individual larvae. A reduction in the number of genotypes was observed in all MPTL-resistant strains compared to the MPTL-susceptible strains that they were derived from, suggesting there was purifying selection at Tci-mptl-1 as a result of MPTL-treatment. The potential link between benzimidazole (BZ)-resistance and MPTL-resistance was examined by screening individual larvae for the presence of three SNPs associated with BZ-resistance in the β-tubulin isotype-1 gene. The majority of larvae were BZ-susceptible homozygotes at positions 167 and 198. Increased heterozygosity at position 200 was observed in the MPTL-resistant strains compared to their respective MPTL-susceptible population. There was no decrease in the occurrence of BZ-resistant genotypes in larvae from each population. These differences, in light of the purifying selection at this locus in all MPTL-resistant isolates, suggests that Tci-mptl-1 confers MPTL-resistance in T. circumcincta, as in Haemonchus contortus, but that different mutations in Tci-mptl-1 can confer resistance in different populations

COMBAR COST EU. A mobile application proposal

Diagnosis and treatment options/strategies for helminth parasitic diseases are not standardized globally, or even across Europe, due to factors such as epidemiology, resources availability, socio-economics, and the lack of adequate information. Good communication of options can help to overcome some of these problems. In this sense, it is proposed to develop a mobile application (Abozeid et al., 2021) that allows the tailoring, and sharing, of knowledge (Abu-El-Noor et al., 2021; Kunkel et al., 2021) related to the various diagnoses and treatments in a format appropriate for all stakeholders (e.g. farmers, veterinarians, universities, researchers, laboratories, industries). The proposal aims to present the theoretical functionalities for the creation of a mobile application (Muashekele et al., 2021), the application should have a sequence of options that must be grounded in theoretical requirements. First of all, there is a necessity to have inputs standardized by the application (e.g. country/region, applicable legislation, animal typology, disease characteristics, symptoms) that should be entered into the application. The aim is to provide a range of tailored options to the end-user. Second, given the user's choices, the application can offer information and guidelines (including veterinarians available, laboratories, diagnosis, treatments, stores, among others). It is highlighted that the main gain may be the collection of information, whenever the user allows it. Finally, considering that most farmers use the language of their country, it is crucial to have the application in different European languages.info:eu-repo/semantics/publishedVersio

Understanding the perception of biosecurity measures surrounding sheep scab disease and round worm control on the island of Lewis and Harris.

The phrase ‘biosecurity’ was not commonly recognised, but when talking, some participants described good biosecurity practices. “Best-fit” biosecurity practices are adopted on the island Awareness of the issues, available diagnostics and control options for sheep scab and roundworm vary considerably Few participants were familiar with the Sustainable Control of Parasites in Sheep recommendations (https://www.scops.org.uk/) Leisure users were identified as a risk to livestock Disease risks posed by wild geese and red deer are believed to be a threat to livestock (and human) health

Microbiome analysis as a platform R&D tool for parasitic nematode disease management

The relationship between bacterial communities and their host is being extensively investigated for the potential to improve the host’s health. Little is known about the interplay between the microbiota of parasites and the health of the infected host. Using nematode co-infection of lambs as a proof-of-concept model, the aim of this study was to characterise the microbiomes of nematodes and that of their host, enabling identification of candidate nematode-specific microbiota member(s) that could be exploited as drug development tools or for targeted therapy. Deep sequencing techniques were used to elucidate the microbiomes of different life stages of two parasitic nematodes of ruminants, Haemonchus contortus and Teladorsagia circumcincta, as well as that of the co-infected ovine hosts, pre- and post infection. Bioinformatic analyses demonstrated significant differences between the composition of the nematode and ovine microbiomes. The two nematode species also differed significantly. The data indicated a shift in the constitution of the larval nematode microbiome after exposure to the ovine microbiome, and in the ovine intestinal microbial community over time as a result of helminth co-infection. Several bacterial species were identified in nematodes that were absent from their surrounding abomasal environment, the most significant of which included Escherichia coli/Shigella. The ability to purposefully infect nematode species with engineered E. coli was demonstrated in vitro, validating the concept of using this bacterium as a nematode-specific drug development tool and/or drug delivery vehicle. To our knowledge, this is the first description of the concept of exploiting a parasite’s microbiome for drug development and treatment purposes

Interactions between Teladorsagia circumcincta infections and microbial composition of sheep with or without successful monepantel treatment:A preliminary study

Nematodes are one of the main impactors on the health, welfare and productivity of farmed animals. Teladorsagia circumcincta are endemic throughout many sheep-producing countries, particularly in the northern hemisphere, and contribute to the pathology and economic losses seen on many farms. Control of these nematode infections is essential and heavily reliant on chemotherapy (anthelmintics), but this has been compromised by the development of anthelmintic resistance. In mammals, the composition of the intestinal microbiota has been shown to have a significant effect on overall health. The interactions between host, microbiota and pathogens are complex and influenced by numerous factors. In this study, comparisons between intestinal and faecal microbiota of sheep infected with sensitive or resistant strains of T. circumcincta, with or without monepantel administration were assessed. The findings from both faecal samples and terminal ileum mucosal scrapings showed clear differences between successfully treated animals and those sheep that were left untreated and/or those carrying resistant nematodes. Specifically, the potentially beneficial genus Bifidobacterium was identified as elevated in successfully treated animals. The detection of these and other biomarkers will provide the basis for new therapeutic reagents particularly relevant to the problems of emerging multidrug anthelmintic resistance

The confounding effects of high genetic diversity on the determination and interpretation of differential gene expression analysis in the parasitic nematode Haemonchus contortus

Differential expression analysis between parasitic nematode strains is commonly used to implicate candidate genes in anthelmintic resistance or other biological functions. We have tested the hypothesis that the high genetic diversity of an organism such as Haemonchus contortus could complicate such analyses. First, we investigated the extent to which sequence polymorphism affects the reliability of differential expression analysis between the genetically divergent H. contortus strains MHco3(ISE), MHco4(WRS) and MHco10(CAVR). Using triplicates of 20 adult female worms from each population isolated under parallel experimental conditions, we found that high rates of sequence polymorphism in RNAseq reads were associated with lower efficiency read mapping to gene models under default TopHat2 parameters, leading to biased estimates of inter-strain differential expression. We then showed it is possible to largely compensate for this bias by optimising the read mapping single nucleotide polymorphism (SNP) allowance and filtering out genes with particularly high single nucleotide polymorphism rates. Once the sequence polymorphism biases were removed, we then assessed the genuine transcriptional diversity between the strains, finding ≥824 differentially expressed genes across all three pairwise strain comparisons. This high level of inter-strain transcriptional diversity not only suggests substantive inter-strain phenotypic variation but also highlights the difficulty in reliably associating differential expression of specific genes with phenotypic differences. To provide a practical example, we analysed two gene families of potential relevance to ivermectin drug resistance; the ABC transporters and the ligand-gated ion channels (LGICs). Over half of genes identified as differentially expressed using default TopHat2 parameters were shown to be an artifact of sequence polymorphism differences. This work illustrates the need to account for sequence polymorphism in differential expression analysis. It also demonstrates that a large number of genuine transcriptional differences can occur between H. contortus strains and these must be considered before associating the differential expression of specific genes with phenotypic differences between strains

Implications of between-isolate variation for climate change impact modelling of Haemonchus contortus populations

The impact of climate change on parasites and parasitic diseases is a growing concern and numerous empirical and mechanistic models have been developed to predict climate-driven spatial and temporal changes in the distribution of parasites and disease risk. Variation in parasite phenotype and life-history traits between isolates could undermine the application of such models at broad spatial scales. Seasonal variation in the transmission of the haematophagous gastrointestinal nematode Haemonchus contortus, one of the most pathogenic helminth species infecting sheep and goats worldwide, is primarily determined by the impact of environmental conditions on the free-living stages. To evaluate variability in the development success and mortality of the free-living stages of H. contortus and the impact of this variability on future climate impact modelling, three isolates of diverse origin were cultured at a range of temperatures between 15°C and 37°C to determine their development success compared with simulations using the GLOWORM-FL H. contortus model. No significant difference was observed in the developmental success of the three isolates of H. contortus tested, nor between isolates and model simulations. However, development success of all isolates at 37°C was lower than predicted by the model, suggesting the potential for overestimation of transmission risk at higher temperatures, such as those predicted under some scenarios of climate change. Recommendations are made for future climate impact modelling of gastrointestinal nematodes

Modelling climate change adaptation in European agriculture: Definitions and Current Modelling

Confidential content, in preparation for a peer-reviewed publication

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome