First detected case of rabbit Haemorrhagic disease virus 2 (RHDV2) in the Irish hare (Lepus timidus hibernicus).

BACKGROUND: Rabbit haemorrhagic disease virus (RHDV) is a Lagovirus, a subgroup of the family Caliciviridae. RHDV2 is a variant first described in France in 2010, and has since spread globally. It has been reported in several Lagomorph species (rabbits, hares, and their relatives) as well as other mammals including voles and shrews. The disease has raised international concerns for its potential impact on population abundance trajectories, particularly as 25% of Lagomorphs are currently Red-Listed by the International Union for the Conservation of Nature (IUCN). The Irish hare (Lepus timidus hibernicus) is a subspecies of the mountain hare, L. timidus, and is endemic to Ireland, making it an Evolutionarily Significant Unit of intrinsic value. CASE PRESENTATION: The first case of RHDV2 was detected in a wild Irish hare in July 2019. The individual exhibited atypical neurological behaviour (running in circles) prior to death. On necropsy, pink tinged foam was seen in the trachea and congestion was noted in the lungs, but there was no evidence of haemorrhages in any other organ. Both the liver and spleen were tested by reverse transcription real time qPCR confirming high levels of RHDV2 RNA. Histopathology confirmed multifocal necrotising hepatitis. CONCLUSION: The Irish hare is susceptible to RHDV2 infection. Further investigation is warranted to explore the clinical, epidemiological, and population biology implications.

Fasciola hepatica products can alter the response of bovine immune cells to Mycobacterium avium subsp. paratuberculosis.

BACKGROUND: Fasciola hepatica causes economically important disease in livestock worldwide. The relevance of this parasitic infection extends beyond its direct consequences due to its immunoregulatory properties. OBJECTIVES: Given the importance of the T helper 1 (Th1) immune response in controlling infections with Mycobacterium avium subspecies paratuberculosis (MAP) in cattle, we aimed to establish the immunological consequences that co-infection with F. hepatica might have on the course of Johne's disease (JD). METHODS: This study compared the in vitro response of bovine immune cells to infection with MAP or exposure to MAP antigens following F. hepatica infection or stimulation with F. hepatica products. RESULTS: We found a decreased proliferation of peripheral blood mononuclear cells (PBMCs) after infection with F. hepatica. This reduction was inversely correlated with fluke burden. Pre-stimulation with F. hepatica molecules produced a significant reduction of ileocaecal lymph node leucocyte proliferation in response to MAP antigens. Additionally,F. hepatica products reduced expression of the CD14 receptor by macrophages and increased levels of apoptosis and bacterial (MAP) uptake. CONCLUSIONS: Overall, F. hepatica infection had little impact on the in vitro response of immune cells to MAP, whereas in vitro co-stimulation with F. hepatica molecules had a measurable effect. Whether this is likely to affect JD progression during in vivo chronic conditions remains unclear.

Potential application of emerging diagnostic techniques to the diagnosis of bovine Johne's disease (paratuberculosis).

Mycobacterium avium subspecies paratuberculosis (MAP) causes Johne's disease (paratuberculosis), a chronic wasting disease in cattle with important welfare, economic and potential public health implications. Current tests are unable to recognise all stages of the disease, which makes it difficult to diagnose and control. This review explores emerging diagnostic techniques that could complement and enhance the diagnosis of MAP infection, including bacteriophage analysis, new MAP-specific antigens, host protein expression in response to infection, transcriptomic studies, analysis of microRNAs and investigation of the gastrointestinal microbiome. It emphasises the inherent challenges of diagnosing bovine Johne's disease and investigates novel areas which may have the potential both to advance our understanding of the immunopathology of MAP infection and to augment current diagnostic tests.

The Identification of Circulating MiRNA in Bovine Serum and Their Potential as Novel Biomarkers of Early Mycobacterium avium subsp paratuberculosis Infection.

Mycobacterium avium subspecies paratuberculosis (MAP) is the aetiological agent of Johne's disease (JD), a chronic enteritis in ruminants that causes substantial economic loses to agriculture worldwide. Current diagnostic assays are hampered by low sensitivity and specificity that seriously complicate disease control; a new generation of diagnostic and prognostic assays are therefore urgently needed. Circulating microRNAs (miRNAs) have been shown to have significant potential as novel biomarkers for a range of human diseases, but their potential application in the veterinary sphere has been less well characterised. The aim of this study was therefore to apply RNA-sequencing approaches to serum from an experimental JD infection model as a route to identify novel diagnostic and prognostic miRNA biomarkers. Sera from experimental MAP-challenged calves (n = 6) and age-matched controls (n = 6) were used. We identified a subset of known miRNAs from bovine serum across all samples, with approximately 90 being at potentially functional abundance levels. The majority of known bovine miRNAs displayed multiple isomiRs that differed from the canonical sequences. Thirty novel miRNAs were identified after filtering and were found within sera from all animals tested. No significant differential miRNA expression was detected when comparing sera from MAP-challenged animals to their age-matched controls at six-month's post-infection. However, comparing sera from pre-infection bleeds to six-month's post-infection across all 12 animals did identify increased miR-205 (2-fold) and decreased miR-432 (2-fold) within both challenged and control groups, which suggests changes in circulating miRNA profiles due to ageing or development (P<0.00001). In conclusion our study has identified a range of novel miRNA in bovine serum, and shown the utility of small RNA sequencing approaches to explore the potential of miRNA as novel biomarkers for infectious disease in cattle.

Prescribed real-ear and achieved real-life differences in children's hearing aids adjusted according to the NAL-NL1 and the DSL v.4.1 prescriptions.

This paper examined how hearing aids adjusted for comparing NAL-NL1 with DSLv.4.1 prescription formulas matched prescriptive targets. The real-ear-to-coupler differences (RECD) of 48 children (24 in Australia and 24 in Canada) were measured and used to derive coupler gain targets. Verification of gain and output were carried out in an HA2-2cc coupler. Electroacoustic measurements revealed a minimal difference between NAL-NL1 and DSLv.4.1 frequency-response slopes due to practical limitations of the devices, even though the prescribed differences were large (up to 13 dB/octave). The difference in overall gain was generally achieved in the hearing aids, with DSLv.4.1 prescribing higher overall gain than NAL-NL1. The mean RECD at 4 kHz was 5 dB higher for children in Australia than in Canada. As the same RECDs were used in deriving targets for both prescriptions, this is unlikely to affect the results of the comparison. The impact of a gain difference between prescriptions on children's performance and preferences in real life is reported in separate papers.

Children's speech perception and loudness ratings when fitted with hearing aids using the DSL v.4.1 and the NAL-NL1 prescriptions.

This paper reports speech and loudness measures on a group of children in a double-blind cross-over trial comparing the NAL-NL1 and DSL[i/o] prescriptions. Twenty-four children with hearing impairment were fitted with digital WDRC hearing aids at each site (Australia, Canada). Speech recognition was measured for nonsense syllables and for the 50% correct threshold for sentence recognition in noise. Loudness ratings for sentences were made on a 7-point scale. Measures were made at fitting and repeated following 8-week trials. Fitting orders were randomized and counterbalanced. Significant differences in consonant recognition occurred for individual children. On average, scores at the 80 dB SPL presentation level were better with the NAL-NL1 fitting. Loudness ratings differed at baseline but did not differ following home trials. Speech recognition scores revealed a small but significant interaction of prescription with level in quiet but not in noise. Individual children had significant performance differences. Loudness ratings showed significant acclimatization effects for children at both sites.

Evaluation of the NAL-NL1 and the DSL v.4.1 prescriptions for children: Paired-comparison intelligibility judgments and functional performance ratings.

This paper reports intelligibility judgments and real-life functional performance of 48 children in a double-blind, cross-over trial comparing the NAL-NL1 and the DSL v.4.1 prescriptions. Intelligibility judgments were obtained by using a paired-comparisons procedure with audiovisual stimuli. Functional performance of children during two eight-week periods, each with hearing aids adjusted to one prescription, was assessed by parents and teachers (PEACH and TEACH) and by children's self reports (SELF). Consistently across reports, performance was significantly better in quiet than in noise. On average, better performance in noise (a higher Noise subscale score) was associated with NAL-NL1 than with DSL v.4.1, both for the PEACH and the SELF. This difference was significant for the SELF in Australia. Intelligibility judgments revealed preferences that were equally split between prescriptions in both countries, on average. In the Australian sample, intelligibility judgments agreed with the questionnaire ratings and with parents' ratings. An increase in preference for NAL was significantly associated with lesser hearing loss. The effect was not significant in the Canadian sample.

Evaluation of the NAL-NL1 and DSL v4.1 prescriptions for children: Preference in real world use.

This paper reports real world preferences of children in a double-blind, cross-over trial comparing NAL-NL1 and DSL v.4.1 prescriptions. Twenty-four children wore digital WDRC hearing aids at each site (Australia, Canada). Multi-memory hearing aids provided the NAL and DSL programs in each of two memories. Diaries were completed during two counterbalanced trials, providing overall preference, situational preference, and preference comments. Ratings were reliable, and situational preferences factored into quiet/low level situations versus noisy/reverberant/high level situations. Children at both sites used DSL v4.1 for hearing low level speech, or when they wanted to hear loudly and clearly. Children used NAL-NL1 when they wished to hear sounds at a lower level, or to reduce background noise. Children expressed strong preferences for having the choice of both programs. Canadian children were more likely to prefer DSL than were the Australian children. Factors such as listening environment and prior listening experience are discussed in interpreting these findings.