The parasitic nematode Teladorsagia circumcincta is one of the most important pathogens of sheep and goats in temperate climates worldwide and can rapidly evolve resistance to drugs used to control it. To understand the genetics of drug resistance, we have generated a highly contiguous genome assembly for the UK T. circumcincta isolate, MTci2. Assembly using PacBio long-reads and Hi-C long-molecule scaffolding together with manual curation resulted in a 573 Mb assembly (N50 = 84 Mb, total scaffolds = 1,286) with five autosomal and one sex-linked chromosomal-scale scaffolds consistent with its karyotype. The genome resource was further improved via annotation of 22,948 genes, with manual curation of over 3,200 of these, resulting in a robust and near complete resource (96.3% complete protein BUSCOs) to support basic and applied research on this important veterinary pathogen. Genome-wide analyses of drug resistance, combining evidence from three distinct experiments, identified selection around known candidate genes for benzimidazole, levamisole and ivermectin resistance, as well as novel regions associated with ivermectin and moxidectin resistance. These insights into contemporary and historic genetic selection further emphasise the importance of contiguous genome assemblies in interpreting genome-wide genetic variation associated with drug resistance and identifying key loci to prioritise in developing diagnostic markers of anthelmintic resistance to support parasite control.

The outbreak of a previously unknown and new disease in the United Kingdom, known as ‘Schmallenberg disease’, a disease associated with abortions, stillbirths and fetal deformities in naïve ewes, was reported for the first time in South West England during the 2012/13 early lambing season. Epidemiological studies confirmed that the Schmallenberg virus (SBV) had a severe negative impact upon animal welfare and the productivity of affected flocks. By contrast, there was a specific lack of research on the impact of SBV on sheep farmer well-being. This study aimed to improve our understanding of sheep farmers’ experiences of Schmallenberg disease, and the impact of the first outbreak on sheep farmer well-being during the 2012/13 early lambing season in South West England. Face-to-face, semi-structured interviews with six farmers with small flocks of pedigree and purebred sheep in South West England were conducted in 2013. The data were analysed via thematic analysis. The main themes regarding the impact of disease on farmer well-being included: (i) emotional highs and lows are part of a normal lambing season; (ii) negative emotions and memories associated with the Schmallenberg disease outbreak; and (iii) resilience and coping with the unexpected disease outbreak. These novel data present preliminary findings from a small number of sheep farmers, and indicate that for some farmers, an unexpected outbreak of a new and emerging disease for the first time during lambing, and dealing with high levels of dystocia, deformities and deaths in their animals, had a negative impact on their emotional well-being during the peak period of the sheep production cycle.

Background The first cases of Schmallenberg virus (SBV) infection in the UK were confirmed in congenitally malformed lambs born in South East England in January 2012. Epidemiological studies confirmed that SBV infection could have severe negative impacts on animal welfare and productivity in affected flocks of sheep (Ovis aries), but there was a lack of specific research on the impacts of infection on recorded reproductive performance, animal welfare, financial performance, and farmers’ emotional well-being in some of the first affected early lambing flocks in South West England in 2012 / 2013. Objectives This mixed methods veterinary practice-based descriptive study aimed to describe the clinical signs observed by sheep farmers in the region experiencing outbreaks of disease due to SBV for the first time; to evaluate physical records (quantitative data) on reproductive performance in early lambing flocks prior to and during the affected 2012 / 2013 production year; and to gauge farmers’ perceptions (qualitative interview data and quantitative severity scores) of the impacts of SBV infection on animal welfare, financial performance, and their emotional well-being, and risks of future outbreaks of disease and preventive strategies including SBV vaccination. Evidentiary value This mixed-methods descriptive study reported farmers’ detailed experiences, and recorded and perceived impacts, of SBV infection in six pedigree and purebred flocks in South West England, lambing early between November 2012 and January 2013. Previous surveys were larger than the current study and assessed the impacts of SBV at farm rather than flock level and on a more diverse range of British sheep farms lambing over extended periods; impacts were compared between three categories of farms based on laboratory confirmation or farmers’ suspicions of infection i.e. ‘SBV confirmed’, ‘SBV suspected’ and ‘SBV not suspected’. This study was able to capture and compare the reproductive performance of these flocks in the SBV affected production year in 2012 / 2013 with up to three previous unaffected years; it found variable negative effects of SBV not only on ewe and lambs losses, stillbirths and abortions, levels of dystocia and need for variable levels of assistance to deliver lambs, but also on overall flock reproductive performance, barren rate, lambing percentage and lamb rearing percentage. The qualitative elements of the study enabled new insights into the variable effects of SBV infection in flocks on ewes and lambs and on farmers’ perceptions of the impacts on animal welfare, flock financial performance and their own emotional well-being. The findings suggest previous surveys may not have fully captured the impacts of SBV infection in high value pedigree and purebred early lambing flocks infected for the first time during the second wave of virus circulation and peak midge vector activity in the southwest region in summer and autumn 2012. The findings highlight the need for further research to explore factors influencing uptake of SBV vaccination by farmers to protect flocks against future waves of infection, and to develop more rational vaccination programmes based on ‘early warning’ surveillance systems. Methods Face-to-face semi-structured interviews were conducted in 2013. Qualitative interview data were thematically analysed to gain an understanding of the perspectives, perceptions and lived experiences of sheep farmers. Quantitative data in the form of (i) farmers’ self-appraised severity scores of the perceived impacts on flock welfare, financial performance and their emotional well-being; and (ii) flock records of pregnancy scanning results, lambing dates, and mortality records for ewes and lambs, were collected for the SBV affected 2012/2013 production year and for up to 3 previous years for comparison. Results Farmers perceived generally high but widely variable negative impacts of SBV infection on animal welfare (median score: 3.5/5, range: 2–5), financial performance (median score: 3.5/5, range: 2–5) and their own well-being (median score: 4/5, range: 2–5); variation between farmers in the severity of impacts appeared not to be directly related to recorded lamb losses (of all lambs born, an overall average of 21% (range: 13.7–42.6%) were stillborn or died within 7 days; 15% (range: 4.1–42.6%) were stillborn or died due to SBV), or to reductions in lamb rearing percentage (10–38% fewer lambs reared in the affected year compared to previous reproductive performance or an industry benchmark). The qualitative elements of the study enabled new insights into the variable effects of SBV infection in flocks on ewes and lambs and on farmers’ perceptions of the impacts on animal welfare, flock financial performance and their own emotional well-being. The semi-structure interviews captured narrative descriptions of the distressing clinical signs seen in ewes and lambs, the variable levels of dystocia, and the lived experiences of farmers caring for affected sheep including the increased workload during the lambing period, greater feelings of tiredness and anxiety than in ‘normal’ lambing periods, depression, and also more positive emotions of resilience and ability to cope with an unexpected and novel disease outbreak. Three of the six farmers subsequently vaccinated with SBV vaccine to protect their early lambing flocks before the next early breeding season. Of the three farmers who decided not to vaccinate: one delayed the start of the subsequent breeding season; the second felt uncertain about using the rapidly developed and authorised vaccine so close to the start of the breeding season but was reassured by veterinary advice that the risk of a further disease outbreak in the subsequent breeding season was low as flock SBV seroprevalence was high (~90% of ewe were...

The parasitic nematode Teladorsagia circumcincta is one of the most important pathogens of sheep and goat farming in temperate climates worldwide and can rapidly evolve resistance to drugs used to control it. To understand the genetics of drug resistance, we have generated a highly contiguous genome assembly for the UK T. circumcincta isolate, MTci2. Assembly using PacBio long-reads and Hi-C long-molecule scaffolding together with manual curation resulted in a 573 Mb assembly (N50 = 84 Mb, n = 1,286) with five autosomal and one sex-linked chromosomal-scale scaffolds consistent with its karyotype. The genome resource was further improved via annotation of 22,948 genes, with manual curation of over 3,200 of these, resulting in a robust and near complete resource (96.3% complete protein BUSCOs) to support basic and applied research on this important veterinary pathogen. Genome-wide analyses of drug resistance, combining evidence from three distinct experiments, identified selection around known candidate genes for benzimidazole, levamisole and ivermectin resistance, as well as novel regions associated with ivermectin and moxidectin resistance. These insights into contemporary and historic genetic selection further emphasise the importance of contiguous genome assemblies in interpreting genome-wide genetic variation associated with drug resistance and identified key loci to prioritise in developing diagnostic markers of anthelmintic resistance to support parasite control. AUTHOR SUMMARY Understanding the genetics of anthelmintic resistance is a critical part of the sustainable control of parasitic worms. Here, we have generated a chromosome-scale genome assembly for the gastrointestinal nematode, Teladorsagia circumcincta, one of the most important pathogens of sheep in temperate climates worldwide. This genome and its annotation offers a substantial improvement over existing genetic resources, and will enable new insight into the biology for this parasite and new opportunities to characterise therapeutic targets such as drug and vaccine candidates. We used this resource to map genetic variation associated with resistance to multiple anthelmintic drug classes used as the primary means of parasite control, confirming known candidate genes and variants (i.e., beta-tubulin isotypes 1 and 2 associated with benzimidazole resistance, and acr-8 associated with levamisole resistance, and pgp-9 copy number variation, of which overexpression is associated broadly with anthelmintic resistance) and revealing new regions of the genome associated with drug treatment responses (i.e. 34-38 Mb on chromosome 5 associated with ivermectin resistance). Our results highlight the importance of a contiguous genome assembly and the use of complementary experimental approaches to reveal the impact of drug-mediated selection, both historically and directly in response to treatment, on genome-wide genetic variation.

Background: Laparoscopic intrauterine artificial insemination (Lap‐AI) is used in sheep genetic improvement programmes. However, the lambing rate (LR) (i.e., the proportion of inseminated ewes that lamb) following Lap‐AI is variable. Previously, one small UK study investigated factors associated with LR, but it did not adjust for dependencies or confounding in the data. Methods: Data were collected from 11,493 Lap‐AIs carried out commercially in Southwest England and Wales between 1995 and 2005. Multilevel multivariable analyses were then used to identify factors associated with LR. Results: The mean unadjusted average LR was 71%. However, ewes inseminated with fresh semen on days when the maximum ambient temperature (MAT°C) was lower than 25°C had a higher LR (adjusted LR ∼78%; OR 1.51, 95% CI 1.30‐1.77) than ewes inseminated with frozen semen (adjusted LR ~70%). LRs were lower on days when MAT°C was ≥25°C (adjusted LRs: fresh ~64%; frozen ~65%). LR decreased as the time between sponge removal and insemination increased (OR: 0.08, 95% CI: 0.01‒0.87) and varied between months and years. Limitations: Due to the design of the study, individual ewe‐ and ram‐level factors could not be investigated. Furthermore, some breeds were less well represented, which hindered breed‐level analysis. Conclusion: Keeping ewes and rams cool on the day of insemination and inseminating ewes earlier after sponge removal may improve LR.