To scan or not to scan? The economics of transthoracic ultrasonography for 'whole-flock' ovine pulmonary adenocarcinoma screening in UK sheep flocks.

BACKGROUND: Transthoracic ultrasonography (TTUS) is currently the only widely used method to diagnose suspected preclinical or subclinical cases of ovine pulmonary adenocarcinoma/Jaagsiekte (OPA) in live sheep. However, the economic impact of using TTUS as a screening test has not been described previously. METHODS: Test characteristics for TTUS in a low-prevalence situation were obtained from a previous study of 1074 breeding ewes that underwent TTUS with an experienced operator. The economic impact was modelled using a 10,000-iteration partial budget simulation and probability sensitivity analysis to explore the relative influence of model variables. RESULTS: In flocks of this size, culling true-positive and false-positive cases resulted in an estimated median net loss of £4647 (interquartile range: £3537-£6006), determined primarily by replacement ewe value and the cost of TTUS per ewe. CONCLUSION: The results of this study emphasise that great caution should be exercised by practitioners when determining if TTUS is appropriate as a screening test for OPA in low-prevalence flocks or subpopulations within a flock, such as younger age groups, where the losses incurred through the inadvertent culling of healthy sheep may significantly exceed any benefit derived from culling preclinical/subclinical cases.

Molecular detection of Sarcocystis cruzi in three beef carcases with eosinophilic myositis lesions and in unaffected beef from animals in the same herd.

Eosinophilic myositis in bovine striated muscle thought to be caused by a hypersensitivity reaction to the degradation of Sarcocystis tissue cysts, is a rare reason for carcase condemnation in the United Kingdom. This paper describes the identification of Sarcocystis cruzi associated with lesions of generalised eosinophilic myositis in three English beef carcases, by gross and histopathological examination followed by PCR with subsequent sequencing. Samples from two unaffected animals were also examined. Although sarcocystosis caused by S.cruzi is not considered a public health risk, the clinically affected carcases were deemed unfit for human consumption due to the extensive lesions affecting meat quality. We believe this to be the first report from the UK describing the molecular-based identification of Sarcocystis cruzi in meat affected and unaffected with eosinophilic myositis.

To scan or not to scan? Efficacy of transthoracic ultrasonography for ovine pulmonary adenocarcinoma screening in a large commercial UK sheep flock.

BACKGROUND: Transthoracic ultrasonography (TTUS) is currently the only widely used method to diagnose preclinical or subclinical ovine pulmonary adenocarcinoma (OPA) in the live sheep. However, little is known about the test characteristics of TTUS. METHODS: One thousand and seventy-four breeding ewes in a flock with evidence of low OPA prevalence underwent TTUS by an experienced operator. Fifty-one sheep were diagnosed with OPA and underwent gross postmortem examination (PME). RESULTS: Lesions consistent with OPA were found in only 24% (12/51) of the culled ewes. Thirty-five percent (18/51) of culled ewes had gross lesions consistent with other pulmonary disease and 41% (21/51) had no detectable gross lesions on PME. Histopathology and immunohistochemistry confirmed OPA in only the 12 animals identified with OPA lesions from PME. CONCLUSION: Great caution should be exercised when deciding if TTUS is an appropriate screening test in groups of sheep where OPA prevalence may be anticipated to be low. TTUS is a subjective test and thus individual operator ability will influence the sensitivity and specificity of TTUS for OPA diagnosis while the underlying prevalence influences the eventual positive predictive value.

Investigation into an outbreak of Border disease virus in pigs in England.

Border disease (BD) was first reported in 1959 in lambs from the border region of England and Wales. The causative virus (BD virus; BDV) has since been identified in several other ruminant species and pigs. The virus is prevalent in sheep flocks of UK, Europe and USA and has potential to inflict substantial economic losses. Natural BDV infection of pigs was first reported in the UK in 1992 from pigs with haemorrhagic lesions and more recently from healthy pigs in Spain and Japan. Here, a persistent problem of poor growth and anaemia in a small proportion of growing pigs on a mixed pig and sheep holding was investigated and tissues were tested in a pan viral microarray. The microarray detected BDV RNA in several tissues which was further confirmed by sequencing, specific BDV PCR and immunohistochemistry. Phylogenetically, the virus clustered with other BDVs in the sub-genotype 1b. This investigation highlights likely interspecies transmission of pestiviruses and their impact on pestivirus detection and eradication programs.

Congenital heart defects in calves.

This focus article describes some of the cardiac anomalies detected in calves submitted to APHA Veterinary Investigation Centres and other postmortem examination providers.

Compound heterozygous PLA2G6 loss-of-function variants in Swaledale sheep with neuroaxonal dystrophy.

Sporadic occurrences of neurodegenerative disorders including neuroaxonal dystrophy (NAD) have been previously reported in sheep. However, so far no causative genetic variant has been found for ovine NAD. The aim of this study was to characterize the phenotype and the genetic aetiology of an early-onset neurodegenerative disorder observed in several lambs of purebred Swaledale sheep, a native English breed. Affected lambs showed progressive ataxia and stiff gait and subsequent histopathological analysis revealed the widespread presence of axonal spheroid indicating neuronal degeneration. Thus, the observed clinical phenotype could be explained by a novel form of NAD. After SNP genotyping and subsequent linkage mapping within a paternal half-sib pedigree with a total of five NAD-affected lambs, we identified two loss-of-function variants by whole-genome sequencing in the ovine PLA2G6 gene situated in a NAD-linked genome region on chromosome 3. All cases were carriers of a compound heterozygous splice site variant in intron 2 and a nonsense variant in exon 8. Herein we present evidence for the occurrence of a familial novel form of recessively inherited NAD in sheep due to allelic heterogeneity at PLA2G6. This study reports two pathogenic variants in PLA2G6 causing a novel form of NAD in Swaledale sheep which enables selection against this fatal disorder.

Deleterious AGXT Missense Variant Associated with Type 1 Primary Hyperoxaluria (PH1) in Zwartbles Sheep.

Severe oxalate nephropathy has been previously reported in sheep and is mostly associated with excessive oxalate in the diet. However, a rare native Dutch breed (Zwartbles) seems to be predisposed to an inherited juvenile form of primary hyperoxaluria and no causative genetic variant has been described so far. This study aims to characterize the phenotype and genetic etiology of the inherited metabolic disease observed in several purebred Zwartbles sheep. Affected animals present with a wide range of clinical signs including condition loss, inappetence, malaise, and, occasionally, respiratory signs, as well as an apparent sudden unexpected death. Histopathology revealed widespread oxalate crystal deposition in kidneys of the cases. Whole-genome sequencing of two affected sheep identified a missense variant in the ovine AGXT gene (c.584G>A; p.Cys195Tyr). Variants in AGXT are known to cause type I primary hyperoxaluria in dogs and humans. Herein, we present evidence that the observed clinicopathological phenotype can be described as a form of ovine type I primary hyperoxaluria. This disorder is explained by a breed-specific recessively inherited pathogenic AGXT variant. Genetic testing enables selection against this fatal disorder in Zwartbles sheep as well as more precise diagnosis in animals with similar clinical phenotype. Our results have been incorporated in the Online Mendelian Inheritance in Animals (OMIA) database (OMIA 001672-9940).

Anatomy and Pathology of the Texel Sheep Larynx.

Laryngeal chondritis, or "Texel throat", is a disease affecting the upper respiratory tract of sheep with breeds like the Texel appearing to be predisposed. Previous work suggests the conformation of these breeds of sheep may be predisposing these animals to laryngeal disease. This study evaluated the anatomy of the Texel sheep larynx and describes incidental pathology. Forty-three larynges from rams of the Texel and Bluefaced Leicester breeds of sheep were measured and photographed. A larynx from each breed was submitted for computed tomography (CT) and magnetic resonance imaging (MRI). Measurements, photography, CT, and MRI demonstrated a difference in the anatomy of the larynx between breeds and a higher proportion of Texel sheep had laryngeal lesions. This study supports the hypothesis that the anatomy of the Texel sheep could be pre-disposing the breed to laryngeal chondritis.

Identification of a New Antimicrobial Resistance Gene Provides Fresh Insights Into Pleuromutilin Resistance in Brachyspira hyodysenteriae, Aetiological Agent of Swine Dysentery.

Brachyspira hyodysenteriae is the aetiological agent of swine dysentery, a globally distributed disease that causes profound economic loss, impedes the free trade and movement of animals, and has significant impact on pig health. Infection is generally treated with antibiotics of which pleuromutilins, such as tiamulin, are widely used for this purpose, but reports of resistance worldwide threaten continued effective control. In Brachyspira hyodysenteriae pleuromutilin resistance has been associated with mutations in chromosomal genes encoding ribosome-associated functions, however the dynamics of resistance acquisition are poorly understood, compromising stewardship efforts to preserve pleuromutilin effectiveness. In this study we undertook whole genome sequencing (WGS) and phenotypic susceptibility testing of 34 UK field isolates and 3 control strains to investigate pleuromutilin resistance in Brachyspira hyodysenteriae. Genome-wide association studies identified a new pleuromutilin resistance gene, tva(A) (tiamulin valnemulin antibiotic resistance), encoding a predicted ABC-F transporter. In vitro culture of isolates in the presence of inhibitory or sub-inhibitory concentrations of tiamulin showed that tva(A) confers reduced pleuromutilin susceptibility that does not lead to clinical resistance but facilitates the development of higher-level resistance via mutations in genes encoding ribosome-associated functions. Genome sequencing of antibiotic-exposed isolates identified both new and previously described mutations in chromosomal genes associated with reduced pleuromutilin susceptibility, including the 23S rRNA gene and rplC, which encodes the L3 ribosomal protein. Interesting three antibiotic-exposed isolates harboured mutations in fusA, encoding Elongation Factor G, a gene not previously associated with pleuromutilin resistance. A longitudinal molecular epidemiological examination of two episodes of swine dysentery at the same farm indicated that tva(A) contributed to development of tiamulin resistance in vivo in a manner consistent with that seen experimentally in vitro. The in vitro studies further showed that tva(A) broadened the mutant selection window and raised the mutant prevention concentration above reported in vivo antibiotic concentrations obtained when administered at certain doses. We show how the identification and characterisation of tva(A), a new marker for pleuromutilin resistance, provides evidence to inform treatment regimes and reduce the development of resistance to this class of highly important antimicrobial agents.

Using oral fluids samples for indirect influenza A virus surveillance in farmed UK pigs.

Influenza A virus (IAV) is economically important in pig production and has broad public health implications. In Europe, active IAV surveillance includes demonstration of antigen in nasal swabs and/or demonstration of antibodies in serum (SER) samples; however, collecting appropriate numbers of individual pig samples can be costly and labour-intensive. The objective of this study was to compare the probability of detecting IAV antibody positive populations using SER versus oral fluid (OF) samples. Paired pen samples, one OF and 5-14 SER samples, were collected cross-sectional or longitudinally. A commercial nucleoprotein (NP)-based blocking ELISA was used to test 244 OF and 1004 SER samples from 123 pens each containing 20-540 pigs located in 27 UK herds. Overall, the IAV antibody detection rate was higher in SER samples compared to OFs under the study conditions. Pig age had a significant effect on the probability of detecting positive pens. For 3-9-week-old pigs the probability of detecting IAV antibody positive samples in a pen with 95% confidence intervals was 40% (23-60) for OF and 61% (0.37-0.80) for SER (P = 0.04), for 10-14-week-old pigs it was 19% (8-40) for OF and 93% (0.71-0.99) for SER (P < 0.01), and for 18-20-week-old pigs it was 67% (41-85) for OF and 81% (0.63-0.91) for SER (P = 0.05). Collecting more than one OF sample in pens with more than 25 less than 18-week-old pigs should be further investigated in the future to elucidate the suitability of OF for IAV surveillance in herds with large pen sizes.

Systemic necrotizing polyarteritis in three weaned lambs from one flock.

Systemic necrotizing polyarteritis was diagnosed in three 7-11-mo-old lambs from the same flock. Aneurysmal dilation and rupture of the gastroduodenal artery in 1 lamb resulted in fatal hemorrhage. All lambs had severe necrotizing vasculitis involving the small intestine, abomasum, mesentery, kidney, and heart with concurrent lymphocytic enteritis. Immunohistochemistry for T- and B-lymphocytes and macrophages found a T-cell- and macrophage-dominant transmural vascular infiltrate and T-cell-associated enteritis. PCR analysis for pestivirus failed to identify infection in 1 lamb, and more extensive viral microarray techniques applied to the second and third lamb failed to detect viral nucleic acid. The identification of 3 cases within 1 flock raises the possibility of a common etiology; however, no cause was established. A genetic etiology was not considered likely as not all of the lambs were related. The presence of concurrent T-lymphocyte-associated enteritis raises the possibility of an immune-mediated disease process linking the vasculitis and enteric lesions.