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438 result(s) for "Allen, Adrian"
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Does Mycobacterium tuberculosis var. bovis Survival in the Environment Confound Bovine Tuberculosis Control and Eradication? A Literature Review
Bovine tuberculosis (bTB) is one of the globe’s most common, multihost zoonoses and results in substantial socioeconomic costs for governments, farming industries, and tax payers. Despite decades of surveillance and research, surprisingly, little is known about the exact mechanisms of transmission. In particular, as a facultative intracellular pathogen, to what extent does survival of the causative agent, Mycobacterium tuberculosis var. bovis (M. bovis), in the environment constitute an epidemiological risk for livestock and wildlife? Due largely to the classical pathology of cattle cases, the received wisdom was that bTB was spread by direct inhalation and exchange of bioaerosols containing droplets laden with bacteria. Other members of the Mycobacterium tuberculosis complex (MTBC) exhibit differing host ranges, an apparent capacity to persist in environmental fomites, and they favour a range of different transmission routes. It is possible, therefore, that infection from environmental sources of M. bovis could be a disease transmission risk. Recent evidence from GPS-collared cattle and badgers in Britain and Ireland suggests that direct transmission by infectious droplets or aerosols may not be the main mechanism for interspecies transmission, raising the possibility of indirect transmission involving a contaminated, shared environment. The possibility that classical pulmonary TB can be simulated and recapitulated in laboratory animal models by ingestion of contaminated feed is a further intriguing indication of potential environmental risk. Livestock and wildlife are known to shed M. bovis onto pasture, soil, feedstuffs, water, and other fomites; field and laboratory studies have indicated that persistence is possible, but variable, under differing environmental conditions. Given the potential infection risk, it is timely to review the available evidence, experimental approaches, and methodologies that could be deployed to address this potential blind spot and control point. Although we focus on evidence from Western Europe, the concepts are widely applicable to other multihost bTB episystems.
Internet-delivered cognitive behaviour therapy for post-traumatic stress disorder: a randomised controlled trial and outcomes in routine care
Background:Despite its potential scalability, little is known about the outcomes of internet-based cognitive behaviour therapy (iCBT) for post-traumatic stress disorder (PTSD) when it is provided with minimal guidance from a clinician.Aim:To evaluate the outcomes of minimally guided iCBT for PTSD in a randomised control trial (RCT, Study 1) and in an open trial in routine community care (Study 2).Method:A RCT compared the iCBT course (n=21) to a waitlist control (WLC, n=19) among participants diagnosed with PTSD. The iCBT group was followed up 3 months post-treatment. In Study 2, treatment outcomes were evaluated among 117 adults in routine community care. PTSD symptom severity was the primary outcome in both studies, with psychological distress and co-morbid anxiety and depressive symptoms providing secondary outcomes.Results:iCBT participants in both studies experienced significant reductions in PTSD symptom severity from pre- to post-treatment treatment (within-group Hedges’ g=.72–1.02), with RCT findings showing maintenance of gains at 3-month follow-up. The WLC group in the RCT also significantly improved, but Study 1 was under-powered and the medium between-group effect favouring iCBT did not reach significance (g=0.64; 95% CI, –0.10–1.38).Conclusions:This research provides preliminary support for the utility of iCBT for PTSD when provided with minimal clinician guidance. Future studies are needed to clarify the effect of differing levels of clinician support on PTSD iCBT outcomes, as well as exploring how best to integrate iCBT into large-scale, routine clinical care of PTSD.
Combining genomics and epidemiology to analyse bi-directional transmission of Mycobacterium bovis in a multi-host system
Quantifying pathogen transmission in multi-host systems is difficult, as exemplified in bovine tuberculosis (bTB) systems, but is crucial for control. The agent of bTB, , persists in cattle populations worldwide, often where potential wildlife reservoirs exist. However, the relative contribution of different host species to bTB persistence is generally unknown. In Britain, the role of badgers in infection persistence in cattle is highly contentious, despite decades of research and control efforts. We applied Bayesian phylogenetic and machine-learning approaches to bacterial genome data to quantify the roles of badgers and cattle in infection dynamics in the presence of data biases. Our results suggest that transmission occurs more frequently from badgers to cattle than (10.4x in the most likely model) and that within-species transmission occurs at higher rates than between-species transmission for both. If representative, our results suggest that control operations should target both cattle and badgers.
Reduced Amygdala and Ventral Striatal Activity to Happy Faces in PTSD Is Associated with Emotional Numbing
There has been a growing recognition of the importance of reward processing in PTSD, yet little is known of the underlying neural networks. This study tested the predictions that (1) individuals with PTSD would display reduced responses to happy facial expressions in ventral striatal reward networks, and (2) that this reduction would be associated with emotional numbing symptoms. 23 treatment-seeking patients with Posttraumatic Stress Disorder were recruited from the treatment clinic at the Centre for Traumatic Stress Studies, Westmead Hospital, and 20 trauma-exposed controls were recruited from a community sample. We examined functional magnetic resonance imaging responses during the presentation of happy and neutral facial expressions in a passive viewing task. PTSD participants rated happy facial expression as less intense than trauma-exposed controls. Relative to controls, PTSD participants revealed lower activation to happy (-neutral) faces in ventral striatum and and a trend for reduced activation in left amygdala. A significant negative correlation was found between emotional numbing symptoms in PTSD and right ventral striatal regions after controlling for depression, anxiety and PTSD severity. This study provides initial evidence that individuals with PTSD have lower reactivity to happy facial expressions, and that lower activation in ventral striatal-limbic reward networks may be associated with symptoms of emotional numbing.
Genomic Prediction for Tuberculosis Resistance in Dairy Cattle
The increasing prevalence of bovine tuberculosis (bTB) in the UK and the limitations of the currently available diagnostic and control methods require the development of complementary approaches to assist in the sustainable control of the disease. One potential approach is the identification of animals that are genetically more resistant to bTB, to enable breeding of animals with enhanced resistance. This paper focuses on prediction of resistance to bTB. We explore estimation of direct genomic estimated breeding values (DGVs) for bTB resistance in UK dairy cattle, using dense SNP chip data, and test these genomic predictions for situations when disease phenotypes are not available on selection candidates. We estimated DGVs using genomic best linear unbiased prediction methodology, and assessed their predictive accuracies with a cross validation procedure and receiver operator characteristic (ROC) curves. Furthermore, these results were compared with theoretical expectations for prediction accuracy and area-under-the-ROC-curve (AUC). The dataset comprised 1151 Holstein-Friesian cows (bTB cases or controls). All individuals (592 cases and 559 controls) were genotyped for 727,252 loci (Illumina Bead Chip). The estimated observed heritability of bTB resistance was 0.23±0.06 (0.34 on the liability scale) and five-fold cross validation, replicated six times, provided a prediction accuracy of 0.33 (95% C.I.: 0.26, 0.40). ROC curves, and the resulting AUC, gave a probability of 0.58, averaged across six replicates, of correctly classifying cows as diseased or as healthy based on SNP chip genotype alone using these data. These results provide a first step in the investigation of the potential feasibility of genomic selection for bTB resistance using SNP data. Specifically, they demonstrate that genomic selection is possible, even in populations with no pedigree data and on animals lacking bTB phenotypes. However, a larger training population will be required to improve prediction accuracies.
Field-Isolated Genotypes of Mycobacterium bovis Vary in Virulence and Influence Case Pathology but Do Not Affect Outbreak Size
Strains of many infectious agents differ in fundamental epidemiological parameters including transmissibility, virulence and pathology. We investigated whether genotypes of Mycobacterium bovis (the causative agent of bovine tuberculosis, bTB) differ significantly in transmissibility and virulence, combining data from a nine-year survey of the genetic structure of the M. bovis population in Northern Ireland with detailed records of the cattle population during the same period. We used the size of herd breakdowns as a proxy measure of transmissibility and the proportion of skin test positive animals (reactors) that were visibly lesioned as a measure of virulence. Average breakdown size increased with herd size and varied depending on the manner of detection (routine herd testing or tracing of infectious contacts) but we found no significant variation among M. bovis genotypes in breakdown size once these factors had been accounted for. However breakdowns due to some genotypes had a greater proportion of lesioned reactors than others, indicating that there may be variation in virulence among genotypes. These findings indicate that the current bTB control programme may be detecting infected herds sufficiently quickly so that differences in virulence are not manifested in terms of outbreak sizes. We also investigated whether pathology of infected cattle varied according to M. bovis genotype, analysing the distribution of lesions recorded at post mortem inspection. We concentrated on the proportion of cases lesioned in the lower respiratory tract, which can indicate the relative importance of the respiratory and alimentary routes of infection. The distribution of lesions varied among genotypes and with cattle age and there were also subtle differences among breeds. Age and breed differences may be related to differences in susceptibility and husbandry, but reasons for variation in lesion distribution among genotypes require further investigation.
Integrating whole-genome sequencing and epidemiology to characterise Mycobacterium bovis transmission in Ireland: a proof of concept
Background In the Republic of Ireland, the herd-level incidence of bovine tuberculosis (bTB), caused by Mycobacterium bovis , reached 6.40% by June 29th 2025, highlighting bTB’s risk to animal health, biosecurity and the economy. The complexity of bTB epidemiology, driven by multiple host species, undetected transmission and incomplete diagnostic sensitivity, makes surveillance and control challenging. Pathogen whole-genome sequencing (WGS) can clarify transmission dynamics but is constrained by the slow, variable mutation rate of M. bovis . This pilot case study integrates WGS with epidemiological data to elucidate transmission event pathways and could be a starting point for future automation. A decision-tree framework was developed to classify likely transmission event pathways by integrating M. bovis WGS sourced from the BTBGenie research project and epidemiological data. As proof-of-concept, one farm with multiple isolates was randomly selected from a national WGS database. Twenty-eight near-identical isolates (pairwise ≤ 3 SNP divergence), from other herds, were identified across databases of the Republic of Ireland and Northern Ireland, with full metadata was available for 16 isolates. These were analysed using TracebTB, a research tool linking national animal health, movement, wildlife and land management databases. Results Transmission event pathways for this case herd were classified as “local area transmission” (43.75%), “within-herd transmission” (12.5%), and “cattle movement-associated transmission” (also 43.75%), divided into between-herd (25%) and within-herd (18.8%) transmission. No evidence of residual within-herd transmission was found in this herd. Homebred animals served as spatial anchors, delineating the cluster’s ‘home range’ or kernel. A spatially distant homebred case, alongside the overall home range size, suggested an undetected movement-associated transmission event, likely via undetected carriers. Conclusions Integrating WGS with detailed epidemiology enables identification of probable bTB transmission event pathways, revealing undetected infections and highlighting biosecurity concerns associated with undetected carriers. The decision-tree framework provides a scalable approach for retrospective outbreak investigation, targeted surveillance, and efficient resource allocation, particularly in high-risk systems such as Controlled Finishing Units. These findings highlight the importance of transboundary collaboration in persistent bTB hotspots. Automating this approach could support validation of disease epidemiological models, guide targeted interventions, and optimising resource allocation, supporting Ireland’s goal of bTB eradication.
Herd-level bovine tuberculosis risk factors: assessing the role of low-level badger population disturbance
Bovine TB (bTB) is endemic in Irish cattle and has eluded eradication despite considerable expenditure, amid debate over the relative roles of badgers and cattle in disease transmission. Using a comprehensive dataset from Northern Ireland (>10,000 km 2 ; 29,513 cattle herds), we investigated interactions between host populations in one of the first large-scale risk factor analyses for new herd breakdowns to combine data on both species. Cattle risk factors (movements, international imports, bTB history, neighbours with bTB) were more strongly associated with herd risk than area-level measures of badger social group density, habitat suitability or persecution (sett disturbance). Highest risks were in areas of high badger social group density and high rates of persecution, potentially representing both responsive persecution of badgers in high cattle risk areas and effects of persecution on cattle bTB risk through badger social group disruption. Average badger persecution was associated with reduced cattle bTB risk (compared with high persecution areas), so persecution may contribute towards sustaining bTB hotspots; findings with important implications for existing and planned disease control programmes.
Molecular Epidemiology of Brucella abortus in Northern Ireland—1991 to 2012
Brucellosis is the most common bacterial zoonoses worldwide. Bovine brucellosis caused by Brucella abortus has far reaching animal health and economic impacts at both the local and national levels. Alongside traditional veterinary epidemiology, the use of molecular typing has recently been applied to inform on bacterial population structure and identify epidemiologically-linked cases of infection. Multi-locus variable number tandem repeat VNTR analysis (MLVA) was used to investigate the molecular epidemiology of a well-characterised Brucella abortus epidemic in Northern Ireland involving 387 herds between 1991 and 2012. MLVA identified 98 unique B. abortus genotypes from disclosing isolates in the 387 herds involved in the epidemic. Clustering algorithms revealed the relatedness of many of these genotypes. Combined with epidemiological information on chronology of infection and geographic location, these genotype data helped to identify 7 clonal complexes which underpinned the outbreak over the defined period. Hyper-variability of some VNTR loci both within herds and individual animals led to detection of multiple genotypes associated with single outbreaks. However with dense sampling, these genotypes could still be associated with specific clonal complexes thereby permitting inference of epidemiological links. MLVA- based epidemiological monitoring data were congruent with an independent classical veterinary epidemiology study carried out in the same territory. MLVA is a useful tool in ongoing disease surveillance of B. abortus outbreaks, especially when combined with accurate epidemiological information on disease tracings, geographical clustering of cases and chronology of infection.