Characterisation of IS1311 in Mycobacterium avium subspecies paratuberculosis genomes: Typing, continental clustering, microbial evolution and host adaptation.

Johne's disease (JD), caused by Mycobacterium avium subspecies paratuberculosis (MAP) is a global burden for livestock producers and has an association with Crohn's disease in humans. Within MAP there are two major lineages, S/Type I/TypeIII and C/Type II, that vary in phenotype including culturability, host preference and virulence. These lineages have been identified using the IS1311 element, which contains a conserved, single nucleotide polymorphism. IS1311 and the closely related IS1245 element belong to the IS256 family of insertion sequences, are dispersed throughout M. avium taxa but remain poorly characterised. To investigate the distribution and diversity of IS1311 in MAP, 805 MAP genomes were collated from public databases. IS1245 was absent, while IS1311 sequence, copy number and insertion loci were conserved between MAP S lineages and varied within the MAP C lineage. One locus was specific to the S strains, which contained nine IS1311 copies. In contrast, C strains contained either seven or eight IS1311 loci. Most insertion loci were associated with the boundaries of homologous regions that had undergone genome rearrangement between the MAP lineages, suggesting that this sequence may be a driver of recombination. Phylogenomic geographic clustering of MAP subtypes was demonstrated for the first time, at continental scale, and indicated that there may have been recent MAP transmission between Europe and North America, in contrast to Australia where importation of live ruminants is generally prohibited. This investigation confirmed the utility of IS1311 typing in epidemiological studies and resolved anomalies in past studies. The results shed light on potential mechanisms of niche/host adaptation, virulence of MAP and global transmission dynamics.

Assessing risks for bovine and zoonotic tuberculosis through spatial analysis and a questionnaire survey in Fiji - A pilot study.

Mycobacterium bovis causes tuberculosis in cattle and when transmitted to humans typically causes extra-pulmonary tuberculosis (EPTB). Bovine tuberculosis (bTB) has a global distribution and is controlled in most countries to protect animal and public health. Recent studies revealed that bTB is established on dairy farms in Fiji where EPTB cases have been reported in people. The aims of this pilot investigation were to look for putative zoonotic TB (EPTB) cases in people and to evaluate practices that might contribute to the persistence and transmission of M. bovis between cattle and to humans. Existing data sets were shared between the Fiji Ministry of Agriculture and Ministry of Health and a questionnaire-based survey was implemented using One Health principles. Statistically significant co-location and close proximity of EPTB cases and bovine TB affected farms were identified. The bTB infection status of farms was significantly associated with unfenced water sources where cattle grazed. Of 247 households, 65 % shared drinking water sources with cattle and 36 % consumed raw milk without boiling, while 62 % of participants reported backyard slaughter of cattle. Several participants reported current symptoms potentially suggestive of TB (chronic cough) but the impact of smoking and history of previous TB treatment could not be evaluated. Farmers had limited understanding of the practices required to prevent bTB at farm level. Further study is recommended and should include an assessment of lifetime EPTB diagnoses, classification of farms based on more recent bTB test data and molecular typing of mycobacterial isolates from humans, cattle and the environment. A targeted awareness and education approach is required to reduce the future risk of zoonotic TB and to help ensure uptake of recommendations and practices aimed at controlling and preventing bTB.

Zero Tolerance for Coercion? Historical, Cultural and Organisational Contexts for Effective Implementation of Coercion-Free Mental Health Services around the World.

Coercion of service users/patients when receiving care and treatment has been a serious dilemma for mental health services since at least the 18th century, and the debate about how best to minimise or even eradicate compulsion remains intense. Coercion is now, once again and rightly, at the top of the international policy agenda and the COST Action 'FOSTREN' is one example of a renewed commitment by service user advocates, practitioners and researchers to move forward in seriously addressing this problem. The focus of service improvement efforts has moved from pure innovation to practical implementation of effective interventions based on an understanding of the historical, cultural and political realities in which mental health services operate. These realities and their impact on the potential for change vary between countries across Europe and beyond. This article provides a novel overview by focusing on the historical, cultural and political contexts which relate to successful implementation primarily in Europe, North America and Australasia so that policy and practice in these and other regions can be adopted with an awareness of these potentially relevant factors. It also outlines some key aspects of current knowledge about the leading coercion-reduction interventions which might be considered when redesigning mental health services.

Association between major histocompatibility complex haplotypes and susceptibility of unvaccinated and vaccinated cattle to paratuberculosis.

Bovine Johne's disease (BJD) or paratuberculosis is caused by Mycobacterium avium spp. paratuberculosis (MAP) and is a worldwide problem among domestic and wild ruminants. While vaccines are available, natural differences in background immunity between breeds within species and between individuals within herds suggest that genetic differences may be able to be exploited in marker-assisted selection as an aid to disease control. The major histocompatibility complex (MHC) is an important component in immune recognition with considerable genetic variability. In this study, associations between the MHC and resistance to BJD were explored in dairy cattle across two herds in which some of the cattle had been vaccinated with Silirum® (n = 540 cows). A BJD susceptible animal was exposed to MAP and became infected, while a resistant animal was exposed but did not become infected. There are different ways to define both exposure and infection, with different levels of stringency, therefore many classifications of the same set of animals are possible and were included in the analysis. The polymorphic regions of major histocompatibility complex class I (MHC I) and class II (MHC II) genes were amplified from the genomic DNA by PCR and sequenced, targeting exons 2 and 3 of the classical and non-classical MHC I genes and exon 2 from the DRB3, DQA1, DQA2 + 3 and DQB MHC II genes. The frequencies of MHC I and MHC II haplotypes and alleles were determined in susceptible and resistant populations. In unvaccinated animals, seven MHC I haplotypes and seven MHC II haplotypes were associated with susceptibility while two MHC I and six MHC II haplotypes were associated with resistance (P < 0.05). In vaccinated animals, two MHC I and three MHC II haplotypes were associated with susceptibility, while one MHC I and two MHC II haplotypes were associated with resistance (P < 0.05). The alleles in significant haplotypes were also identified. Case definitions with higher stringency resulted in fewer animals being included in the analyses, but the power to detect an association was not reduced and there was an increase in strength and consistency of associations. Consistent use of stringent case definitions is likely to improve agreement in future association studies.

Immune Priming of Pacific Oysters (Crassostrea gigas) to Induce Resistance to Ostreid herpesvirus 1: Comparison of Infectious and Inactivated OsHV-1 with Poly I:C.

Pacific oyster mortality syndrome (POMS), which is caused by Ostreid herpesvirus 1 (OsHV-1), causes economic losses in Pacific oyster (Crassostrea gigas) aquaculture in many countries. Reducing the mortality in disease outbreaks requires changing the host, pathogen and environment interactions to favor the host. Survivors of natural exposure to OsHV-1 are able to survive subsequent outbreaks. This has been replicated under laboratory conditions, suggesting the existence of an immune response. The aim of the present study is to compare the effects of prior exposure to infectious OsHV-1, heat-inactivated OsHV-1 and the chemical anti-viral immune stimulant poly I:C on mortality following exposure to virulent OsHV-1. All treatments were administered by intramuscular injection. Oysters were maintained at 18 °C for 14 days; then, the temperature was increased to 22 °C and the oysters were challenged with virulent OsHV-1. Heat-inactivated OsHV-1, infectious OsHV-1 and poly I:C all induced significant protection against mortality, with the hazard of death being 0.41, 0.18 and 0.02, respectively, compared to the controls, which had no immune priming. The replication of OsHV-1 on first exposure was not required to induce a protective response. While the underlying mechanisms for protection remain to be elucidated, conditioning for resistance to POMS by prior exposure to inactivated or infectious OsHV-1 may have practical applications in oyster farming but requires further development to optimize the dose and delivery mechanism and evaluate the duration of protection.

The Resistance to Lethal Challenge with Ostreid herpesvirus-1 of Pacific Oysters (Crassostrea gigas) Previously Exposed to This Virus.

Pacific oyster (Crassostrea gigas) aquaculture has been economically impacted in many countries by Pacific oyster mortality syndrome (POMS), a disease initiated by Ostreid herpesvirus 1. The objectives of this study were to determine whether naturally exposed, adult C. gigas could act as reservoirs for OsHV-1 and explain the recurrent seasonal outbreaks of POMS and to test whether or not they were resistant to OsHV-1. In a laboratory infection experiment using thermal shock, OsHV-1 replication was not reactivated within the tissues of such oysters and the virus was not transmitted to naïve cohabitating spat. The adult oysters were resistant to intramuscular injection with a lethal dose of OsHV-1 and had 118 times lower risk of mortality than naïve oysters. Considered together with the results of other studies in C. gigas, natural exposure or laboratory exposure to OsHV-1 may result in immunity during subsequent exposure events, either in the natural environment or the laboratory. While adult C. gigas can carry OsHV-1 infection for lengthy periods, reactivation of viral replication leading to mortality and transmission of the virus to naïve oysters may require specific conditions that were not present in the current experiment. Further investigation is required to evaluate the mechanisms responsible for resistance to disease in oysters previously exposed to OsHV-1, whether immunity can be exploited commercially to prevent POMS outbreaks and to determine the source of the virus for recurrent seasonal outbreaks.

Applying the theory of planned behaviour to understand mental health professionals' intentions to work using a human rights-based approach in acute inpatient settings.

BACKGROUND: There has been a shift to implement human rights-based approaches in acute mental health care due to increasing concerns around quality of care. National Health Service (NHS) Trusts have a legal duty to uphold a person's human rights, therefore it is important to understand what any barriers might be. Using psychological theory may help to develop this understanding. AIM: To test whether the theory of planned behaviour can be an effective model in understanding mental health professionals' intentions to work using a human rights-based approach. METHOD: Participants were recruited from two NHS Trusts in the North West of England. A cross-sectional, survey design was used to examine mental health professionals' intentions to use human rights-based approaches. RESULTS: Multiple regression analyses were performed on the theory of planned behaviour constructs showing that attitude and subjective norm significantly predicted intention. Perceived behavioural control did not add any significant variance, nor any demographic variables. CONCLUSION: There could be factors outside of the individual clinician's control to fully work within a human rights-based framework on acute mental health wards. The theory of planned behaviour offers some understanding, however further development work into measuring human rights outcomes on acute mental health wards is needed.

Models, frameworks and theories in the implementation of programs targeted to reduce formal coercion in mental health settings: a systematic review.

Introduction: Implementation models, frameworks and theories (hereafter tools) provide researchers and clinicians with an approach to understand the processes and mechanisms for the successful implementation of healthcare innovations. Previous research in mental health settings has revealed, that the implementation of coercion reduction programs presents a number of challenges. However, there is a lack of systematized knowledge of whether the advantages of implementation science have been utilized in this field of research. This systematic review aims to gain a better understanding of which tools have been used by studies when implementing programs aiming to reduce formal coercion in mental health settings, and what implementation outcomes they have reported. Methods: A systematic search was conducted using PubMed, CINAHL, PsycINFO, Cochrane, Scopus, and Web of Science. A manual search was used to supplement database searches. Quality appraisal of included studies was undertaken using MMAT-Mixed Methods Appraisal Tool. A descriptive and narrative synthesis was formed based on extracted data. Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines were followed in this review. Results: We identified 5,295 references after duplicates were removed. Four additional references were found with a manual search. In total eight studies reported in nine papers were included in the review. Coercion reduction programs that were implemented included those that were holistic, and/or used professional judgement, staff training and sensory modulation interventions. Eight different implementation tools were identified from the included studies. None of them reported all eight implementation outcomes sought from the papers. The most frequently reported outcomes were acceptability (4/8 studies) and adaptation (3/8). With regards to implementation costs, no data were provided by any of the studies. The quality of the studies was assessed to be overall quite low. Discussion: Systematic implementation tools are seldom used when efforts are being made to embed interventions to reduce coercive measures in routine mental health care. More high-quality studies are needed in the research area that also involves perspectives of service users and carers. In addition, based on our review, it is unclear what the costs and resources are needed to implement complex interventions with the guidance of an implementation tool. Systematic review registration: [Prospero], identifier [CRD42021284959].

Femicide trends at the start of the 21st. century: Prevalence, risk factors and national public health actions.

Lethal violence requires a gender-based analysis which recognises that femicide is different from homicide in many ways. Structural factors such as national income and wealth equality together with government policies may influence the scale of the problem globally. This study is an original attempt to examine associations between femicide rates, these structural factors and national action plans using a longitudinal design. Data from two international surveys were combined to examine anti-femicide actions (n = 133 countries) and temporal femicide prevalence trends (n = 66 countries) in the context of national income and wealth inequality factors. The United Nations Survey of Crime Trends and Operations of Criminal Justice Systems was used to estimate femicide rates per country 2003-2014 and the World Health Organisation Global Status Report on Violence Prevention provided data on policy initiatives in place by 2014. Results indicate that femicide rates decreased by 32% worldwide but increased by 26% in low- and medium-income countries. The structural factors of low income and high inequality were significantly negatively associated with the 2014 femicide rate. Structural factors must be addressed alongside policy and legal initiatives if significant gains are to be made toward eradicating violence against women and girls.

Longitudinal investigation of the presence of different trajectories and associated health and socio-economic determinants, for participants who report suicidal ideation within a community-based public health survey.

OBJECTIVE: Given the paucity of evidence-based research investigating different suicidal ideation profiles and trajectories, this project sought to investigate health and socio-economic factors associated with the presence of suicidal ideation and changes in ideation over time. DESIGN: Longitudinal cohort design, using logistic regression analysis. SETTING: A public health survey was administered at two timepoints in a community setting across the North West of England. In the 2015/2016 survey, participants were recruited from high (n=20) and low (n=8) deprivation neighbourhoods. In the 2018 survey, only the 20 high-deprivation neighbourhoods were included. PARTICIPANTS: 4287 people were recruited in 2015/2016 and 3361 were recruited in 2018. The 2018 sample was subdivided into those who responded only in 2018 (n=2494: replication sample) and those who responded at both timepoints (n=867: longitudinal sample). PRIMARY OUTCOME MEASURES: Suicide ideation was the dependent variable which was assessed using item 9 of the Patient Health Questionnaire instrument. RESULTS: The prevalence of suicidal ideation was 11% (n=454/4319) at 2015/2016 and 16% (n=546/3361) at 2018.Replication study results highlighted: persistent debilitation from physical ill health and/or medication side effects; demographic factors (ie, middle-aged, single or never married); and personal coping strategies (ie, smoking) as risk factors for suicidal ideation. A static/improved financial position and high levels of empathy were protective factors.Longitudinal study results confirmed three suicidal ideation trajectories: 'onset', 'remission' and 'persistence'. Similar findings to the replication study were evidenced for the onset and persistence trajectories. Persistent suicidal ideation was synonymous with higher levels of practical support which may correspond to the higher levels of debilitation and functional disability reported within this group. Remission was characterised by fewer debilitating factors and higher levels of self-agency. CONCLUSION: A greater appreciation of the heterogeneity of suicidal trajectories should lead to the implementation of broad clinical assessments and targeted interventions.

Cold temperature stress and damaged skin induced high mortality in barramundi (Lates calcarifer) challenged with Vibrio harveyi.

Most diseases in aquaculture are caused by opportunistic pathogens. One of them, Vibrio harveyi, is a widespread Gram-negative bacterium that has become an important pathogen of aquatic species in marine environments. Here, we propose the use of the causal pie model as a framework to conceptualize the causation of vibriosis in juvenile barramundi (Lates calcarifer) and to establish an effective challenge model. In the model, a sufficient cause, or the causal pie, is a constellation of component causes that lead to an outcome (e.g. vibriosis). In the pilot study, a high cumulative mortality (63.3% ± 10.0%, mean ± SE) was observed when V. harveyi was administered by intraperitoneal injection using a high challenge dose [107 colony-forming units (CFU) fish-1 ], but low or no mortality was observed in fish subject to cold stress or fish with intact skin when challenged by immersion. We, therefore, tested the use of a skin lesion (induced with a 4-mm biopsy punch) combined with cold temperature stress to induce vibriosis following the causal pie model. After challenge, fish were immediately subject to cold stress (22°C) or placed at an optimal temperature of 30°C. All groups were challenged with 108 CFU mL-1 for 60 min. A considerably higher mortality level (72.7% ± 13.9%) was observed in fish challenged with both a skin lesion and cold stress compared with mortality in fish only having a skin lesion (14.6% ± 2.8%). V. harveyi was re-isolated from all moribund fish and was detected by species-specific real-time PCR in gills, head kidney and liver, regardless of challenge treatment confirming vibriosis as the cause of disease. Parenchymal tissues had histopathological changes consistent with vibriosis. Whole-genome sequence (WGS) is provided for the Vibrio harveyi isolate examined in this study. Overall, the causal pie model was a useful framework to conceptualize the design of the experimental challenge model, in which both cold stress and skin damage were identified as component causes of vibriosis with high mortality. This conceptual framework can be applied to other opportunistic pathogens in aquaculture or to the study of co-infections in fish.

Openness as Organizing Principle: Introduction to the Special Issue.

'Openness' has become an organizational leitmotif of our time, spreading across a growing set of organizational domains. However, discussions within these specialized domains (e.g. open data, open government or open innovation) treat openness in isolation and specific to the particularities of those domains. The intention of this Special Issue therefore is to foster cross-domain conversations to exchange insights and build cumulative knowledge on openness. To do so, this Introduction to the Special Issue argues that openness should be investigated as a general organizing principle, which we refer to as Open Organizing. Across domains, we define Open Organizing as a dynamic organizing principle along the primary dimension of transparency/opacity and the secondary dimensions of inclusion/exclusion and distributed/concentrated decision rights. As such, Open Organizing raises an overarching problem of design, which results from more specific epistemic, normative and political challenges.

Short-term risk assessment in the long term: A scoping review and meta-analysis of the Brøset Violence Checklist.

WHAT IS KNOWN ON THE SUBJECT?: The Brøset Violence Checklist (BVC) has been widely translated and implemented in diverse mental healthcare settings to improve prevention of violence. It is valued as a brief but effective tool in clinical practice. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: This review is the largest and most comprehensive international review of the BVC conducted in the 25+ years since the inception of the instrument in 1995. It integrates findings from existing studies and establishes that the tool has many impressive strengths considering the brief time investment required for completion. The review reveals that the tool has been used in more than 20 different countries around the world in a variety of mental health and other settings as both a risk assessment tool to guide clinical practice and as a formally structured intervention to minimize violence. There is much variation in how the tool is implemented and scored in different services. This variation questions its applicability as a resource and consistency and its use needs attention. This variation in use also limits the conclusions regarding best practices. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The review supports the use of the BVC as one part of the package for mental health services committed to preventive action aimed at reducing violence and coercion. The review identified that the patient perspective was often absent when completing the BVC, and so this should be considered as an option by services as part of a collaborative philosophy of care. ABSTRACT: INTRODUCTION: Existing literature on the Brøset Violence Checklist (BVC) is examined in the context of usability, implementation and validity to provide evidence-based recommendations on its application and identify opportunities for future development. AIM/QUESTION: To identify current knowledge on the BVC and guide clinicians and researchers toward the next steps in using this tool in clinical practice to prevent violence in healthcare settings. METHOD: A scoping review approach with a meta-analysis supplement was adopted to broadly identify and map available evidence on the BVC and provide specific estimates of predictive validity in different contexts. RESULTS: Sixty-two studies conducted in 23 countries addressed the implementation of the BVC across various settings. Many studies adapted the original BVC, and the clinical utility was noted as an important feature. A meta-analysis of the original BVC format estimated a pooled area under the curve at 0.83 (95% CI 0.78-0.87) in a subset of 15 studies. DISCUSSION: The BVC combines high predictive validity and good clinical utility across a wide range of settings and cultures. It should continue to be incorporated into routine practice in mental health services focused on preventing violence and coercion. IMPLICATIONS FOR PRACTICE: Development of collaborative approaches with service users involved in assessing their own risk of future violence.

IP10 is a predictor of successful vaccine protection against paratuberculosis infection in sheep.

The cell mediated immune response and ability of immune cells to migrate to the site of infection are both key aspects of protection against many pathogens. Mycobacterium avium subsp. paratuberculosis (MAP) is an intracellular pathogen and the causative agent of paratuberculosis, a chronic wasting disease of ruminants. Current commercial vaccines for paratuberculosis reduce the occurrence of clinical disease but not all animals are protected from infection. Therefore, there is a need to understand the immune responses triggered by these vaccines at the site of infection, in circulating immune cells and their relationships to vaccine-mediated protection. The magnitude and location of gene expression related to the cell mediated immune response and cellular migration were studied in the ileum of sheep. In addition, longitudinal IP10 (also known as IP10) secretion by circulating immune cells was examined in the same sheep. Animals were grouped based on vaccination status (vaccinated vs non-vaccinated) and MAP exposure (experimentally exposed vs unexposed). Vaccination of unexposed sheep increased the expression of IP10, CCL5 and COR1c. Sheep that were successfully protected by vaccination (uninfected following experimental exposure) had significantly reduced expression of IP10 in the ileum at 12 months post exposure compared to vaccine non-responders (those that became infected) and non-vaccinated infected sheep. Successfully protected sheep also had significantly increased secretion of IP10 in in vitro stimulated immune cells from whole blood compared to vaccine non responders at 4 months post exposure. Therefore, the IP10 recall response has the potential to be used as marker for infection status in vaccinated sheep and could be a biomarker for a DIVA test in sheep.

Diversity and molecular epidemiology of Ostreid herpesvirus 1 in farmed Crassostrea gigas in Australia: Geographic clusters and implications for "microvariants" in global mortality events.

Since 2010, mass mortality events known as Pacific oyster mortality syndrome (POMS) have occurred in Crassostrea gigas in Australia associated with Ostreid herpesvirus 1. The virus was thought to be an OsHV-1 µVar or "microvariant", i.e. one of the dominant variants associated with POMS in Europe, but there are few data to characterize the genotype in Australia. Consequently, the genetic identity and diversity of the virus was determined to understand the epidemiology of the disease in Australia. Samples were analysed from diseased C. gigas over five summer seasons between 2011 and 2016 in POMS-affected estuaries: Georges River in New South Wales (NSW), Hawkesbury River (NSW) and Pitt Water in Tasmania. Sequencing was attempted for six genomic regions. Numerous variants were identified among these regions (n = 100 isolates) while twelve variants were identified from concatenated nucleotide sequences (n = 61 isolates). Nucleotide diversity of the seven genotypes of C region among Australian isolates (Pi 0.99 × 10-3) was the lowest globally. All Australian isolates grouped in a cluster distinct from other OsHV-1 isolates worldwide. This is the first report that Australian outbreaks of POMS were associated with OsHV-1 distinct from OsHV-1 reference genotype, µVar and other microvariants from other countries. The findings illustrate that microvariants are not the only variants of OsHV-1 associated with mass mortality events in C. gigas. In addition, there was mutually exclusive spatial clustering of viral genomic and amino acid sequence variants between estuaries, and a possible association between genotype/amino acid sequence and the prevalence and severity of POMS, as this differed between these estuaries. The sequencing findings supported prior epidemiological evidence for environmental reservoirs of OsHV-1 for POMS outbreaks in Australia.

Acceptance and commitment therapy (ACT) for professional staff burnout: a systematic review and narrative synthesis of controlled trials.

BACKGROUND: Staff working in people-oriented professions are vulnerable to burnout which is negatively associated with professional well-being and service-user care. AIM: To investigate if interventions based on Acceptance and Commitment Therapy (ACT) are effective in reducing staff burnout. METHOD: Systematic database and reference list searches were conducted resulting in the inclusion of 14 quantitative papers. A narrative synthesis, including extraction of individual effect sizes, was performed. RESULTS: All studies were controlled trials. The settings for ACT delivery were varied across health, social care, and public services. The ACT interventions demonstrated statistically significant effects in favour of ACT on the outcome measure subscales across the majority of studies (n = 9). Thirteen studies demonstrated an effect in favour of ACT in at least one outcome measure subscale. Positive aspects of work engagement varied according to a professional role. CONCLUSIONS: The findings suggest that ACT-based interventions using a wide range of formats may have the potential to decrease burnout across a range of professional groups. However, samples were small in the studies reviewed and the interventions were not always defined. Further research would benefit from larger studies, incorporating process measures, with explicit protocols.

Correlates of vaccine protection against Mycobacterium avium sub-species paratuberculosis infection revealed in a transcriptomic study of responses in Gudair® vaccinated sheep.

A critical hindrance in the development of effective vaccine strategies to combat infectious disease is lack of knowledge about correlates of protection and of the host responses necessary for successful adaptive immunity. Often vaccine formulations are developed by stepwise experimentation, with incomplete investigation of the fundamental mechanisms of protection. Gudair® is a commercially available vaccine registered for use in sheep and goats for controlling spread of Mycobacterium avium sub-species paratuberculosis (MAP) infections and reduces mortality by up to 90%. Here, using an experimental infection model in sheep, we have utilized a transcriptomics approach to identify white blood cell gene expression changes in vaccinated, MAP-exposed Merino sheep with a protective response in comparison to those vaccinated animals that failed to develop immunity to MAP infection. This methodology facilitated an overview of gene-associated functional pathway adaptations using an in-silico analysis approach. We identified a group of genes that were activated in the vaccine-protected animals and confirmed stability of expression in samples obtained from naturally exposed commercially maintained sheep. We propose these genes as correlates of vaccine induced protection.

A survey to understand farmers' perceptions and risk factors for hoof diseases including footrot in sheep in New South Wales, Australia.

The aims of this study were to develop an understanding of farmers' perceptions and risk factors for footrot, including its less severe forms, and other hoof diseases in sheep in New South Wales (NSW). A questionnaire was developed and administered to sheep farmers in Local Land Services (LLS) regions across NSW. LLS staff selected sheep farmers who met the inclusion criteria which included farmers with a minimum of 100 sheep, a history of having had foot problems in their flock or having expressed an interest in improving sheep health and production. Farmers completed the questionnaire either by telephone or via the REDCap online survey platform. Descriptive analyses and multivariable logistic regression models were created. The survey was completed by 43 sheep farmers with a median farm size of 1,500 Ha and flock size of 2,300; footrot was present on 39% of farms while 75.6% had other hoof diseases. A flock of >3,000 sheep were more likely to have footrot than a smaller flock (OR = 11.99, 90% CI = 3.02-63.92, P-value = 0.005) and footrot was less likely to be present on farms when an Animal Health Statement was requested while purchasing sheep (OR = 0.10, 90% CI = 0.01-0.56, P-value = 0.04). Hoof conditions other than footrot were likely to be present in flocks when foot inspections were conducted at a time other than weekly inspections (OR = 0.13, 90% CI = 0.01-0.68, P-value = 0.04) and flocks kept on undulating ground were more likely to have diseases other than footrot compared to those kept on flat ground (OR = 3.72, 90% CI = 1.02-15.80, P-value = 0.09). Most farmers agreed that footrot including its less severe forms can cause production losses and negatively affect animal health and welfare. Limitations of the study were the sample size and dry environmental conditions prior to and during study period in many regions of NSW which limited the expression of footrot.

Bovine tuberculosis control in Fiji: Retrospective study findings for 2015 to 2020.

Control of bovine tuberculosis (bTB) is a priority for animal health, biosecurity, and human health authorities in Fiji as evident from the long-term funding of the Bovine Brucellosis and Tuberculosis Eradication and Control program (BTEC) and notable improvements to the program described in this paper. To evaluate the performance of the Fiji BTEC program from 2015 to 2020, all available bTB data for cattle were analyzed. Data sources included BTEC bTB testing records, abattoir records and laboratory records. We integrated all information to quantify the bTB tests applied, bTB positive farms and animals, meat inspection and laboratory findings. Test coverage was highest among dairy cattle in Central Division (~73%), where bTB was highly prevalent with 7.8% of dairy cattle and 61.7% of dairy farms found to be positive between 2015 and 2020. There was no visible downward trend in the apparent prevalence of bTB over the 6-year period. During 2019 and 2020, only 21.3% (51/239) of the tested dairy farms maintained their clear status, another 8.4% (20/239) reverted to infected status after 1 year or more of being bTB clear, and most farms remained infected during these 2 years. Factors observed to be contributing to this situation were persistent infections, related in part to the significant number of untested animals, uncontrolled animal movements, and larger farm size. Similar to other developing countries, bTB remains a serious concern and further strengthening of the program targeting the main contributors to bTB persistence, along with maintenance of a comprehensive reporting and traceability system, industry awareness and government support are needed. Control of bTB in Fiji is a long-term objective that must have multiple stakeholder engagement and regular review to measure success.

Sheep vaccinated against paratuberculosis have increased levels of B cells infiltrating the intestinal tissue.

Systemic immunisation delivered subcutaneously is currently used to control paratuberculosis, a chronic enteritis of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). These vaccines do not provide complete protection and a small cohort of animals still succumb to clinical disease. The aim of this study was to assess mycobacterial infection site-specific variations in immune cells in vaccinated sheep that did or did not develop the disease following controlled exposure to MAP. Immunohistochemical staining of terminal ileum demonstrated that vaccination increased infiltration of CD4 + T cells and B cells. Infiltration of large numbers of CD4 + T and B cells was also seen in sheep that successfully cleared infection. Vaccination promoted the polarisation of macrophages to an M1 activation state. The presence of certain cells at the site of infection, especially CD4 + T cells, is likely to contribute to vaccine success by increasing the speed and potency of the local immune response. Systemic immunisation against MAP can alter the composition of innate and adaptive immune cell populations at the predilection site for MAP infection in the ileum one year after vaccination. This informs understanding of the impact of vaccination at the site of infection and also the duration of vaccine-elicited changes. This information may assist vaccine development and allow targeting of protective immune responses in the gut of ruminants.