Companion animal tuberculosis: clinical presentations, outbreak investigations, improved diagnostics and the early macrophage response

Tuberculosis caused by the Mycobacterium (M.) tuberculosis-complex (MTBC) of organisms remains one of the most prevalent and deadly infectious diseases of man and other animals. The mycobacteria responsible are a highly conserved group of pleomorphic acid-fast bacilli which cause chronic granulomatous infections. Tuberculous infections in humans and cattle often remain latent for prolonged periods of time before progressing to disease that has severe, negative consequences for the health and welfare of the infected host. Some of the organisms within the MTBC are highly specialised and limited to just a single or small number of host species whereas others, such as M. bovis, can infect a broad range of mammals including humans. Companion animals are susceptible to MTBC infections and understanding of the significance and frequency of these infections has grown in recent years. Cats and dogs share unrivalled proximity to their owners and therefore pose a small but real risk for the zoonotic transmission of tuberculous infections. Despite the high frequency of mycobacterial infections observed in companion animals, diagnostic tests to identify the commonly encountered mycobacterial species are lacking. The first aim of this work was therefore to improve on the currently available diagnostic test methodologies for companion animals. A diagnostic PCR assay was developed and applied to 380 histologically confirmed feline and eight canine mycobacteriosis samples. This novel assay specifically targeted the mycobacterial species most frequently identified by mycobacterial culture (M. bovis and M. microti) and was optimised for use with formalin-fixed tissue; a prerequisite for the safe handling of tuberculous tissue from companion animals by UK laboratories. The assay was suitable for both feline and canine tissue with a significantly quicker turnaround time, higher rate of test positive results and a significant increase in the proportion of M. microti diagnoses compared to culture results. Since evaluation of cytokines has shown diagnostic potential in other species, this project explored the potential of cytokine profiling in cats for the rapid and sensitive detection of mycobacteriosis. By evaluating serum/plasma from 116 naturally infected cats, this study demonstrated a consistent elevation in the cytokines associated with macrophage activation and antigenic stimulation compared to control cats. Sub-group analysis showed that elevations in PDGF-BB were specifically associated with M. microti infections whereas elevated TNF-α sensitively identified cats infected with M. bovis. Investigation of an unprecedented outbreak of M. bovis associated with the ingestion of a putatively contaminated raw food product led to the use of the interferon-γ release assay (IGRA) as a screening test for clinically healthy cats, a purpose for which it had not previously been evaluated. Nearly a third of clinically normal IGRA test-positive cats were subsequently found to have structural disease detected by diagnostic imaging. Though this raises questions regarding the specificity of the IGRA in clinically normal cats, it was an invaluable diagnostic tool to evaluate individual cats involved in the outbreak. The work on feline TB was complemented by similar investigations of canine TB. When an outbreak of M. bovis tuberculosis occurred in a kennel of 164 working Foxhounds, a testing strategy to successfully bring the outbreak under control and investigate the cause was developed. Collaborative work undertaken to screen at risk humans exposed to the hounds identified a latently infected person, highlighting the zoonotic risk posed by M. bovis infections in companion animals. Eight novel and existing diagnostic testing methodologies were evaluated for use in dogs of which a cell-based IGRA, and three serological tests comprising a novel comparative peptide ELISA, the Chembio DPP VetTB assay and the Idexx M. bovis Ab ELISA showed diagnostic potential for canine TB. Additional analysis employing a Bayesian latent class modelling approach revealed that the IGRA developed herein was as sensitive and specific as comparable tests in other species. The serological assays were shown to have markedly lower sensitivity than the IGRA but had higher specificities. All four tests had positive and negative predictive value estimates which indicate that these tests can be informative to clinicians who suspect cases of canine TB. A review of 1012 cases of canine TB highlighted an apparently lower incidence of infections in dogs compared to cats, but an increased severity of clinical signs when disease occurred. To investigate this discrepancy a protocol to derive macrophages from canine and feline bone marrow was developed. These cells acquired cell surface molecules indicative of a macrophage phenotype during ten days of culture with recombinant CSF-1. The response of primary macrophages and the DH82 canine histiocytic cell line was assessed following stimulation with LPS, infection with M. bovis Bacille Calmette Guerin, M. bovis AF2122/97 (the reference strain) or a clinical isolate of M. bovis. These investigations consistently revealed that DH82 cells do not accurately represent primary canine macrophage biology which was associated with altered morphology, lack of nitrite production and significantly reduced secretion of the pro-inflammatory cytokines IL-6 and TNF-α. Overall, the work presented in this thesis demonstrates novel advancement of the diagnostic methodologies for identifying cases of companion animal mycobacteriosis and in particular cases of TB. It further begins to explore the immunological basis for the clinical differences seen between species that may further contribute to novel testing and treatment strategies in the future

Mapping research across the undergraduate curriculum in UCC

UCC identifies itself as a research-led University and has stated the ambition to strengthen the integration of research, teaching and learning by maximising opportunities for students to participate in research programmes throughout their undergraduate studies. The number of undergraduate programmes with student-involved research from first year onwards is an important measure of this ambition. A curriculum analytics project was enacted by CIRTL staff and Academic Systems Administration to gather evidence of research-oriented and research-based teaching in undergraduate programmes offered to students via the CAO system in 2015/2016. The review showed that 55% of undergraduate programmes make explicit mention of research and inquiry in their programme learning outcomes. Analysis of module learning outcomes further showed that 45% of the reviewed programmes provide students with exposure to research-based or research-oriented teaching across the duration of their programme. The project provides an important baseline of existing research in the undergraduate curriculum, it uncovers exemplar activities across a range of subject areas and disciplines, and extends the vocabulary around research and inquiry to include discipline-specific approaches and understandings. Future work will include gathering feedback from staff and qualitative research with students to correct any inaccuracies in the data with a view to refining the search query and running a regular, more automated analysis

Natural succession and clearcutting as drivers of environmental heterogeneity and beta diversity in North American boreal forests

<div><p>Clear-cutting alters natural ecosystem processes by reducing landscape heterogeneity. It is the dominant harvesting technique across the boreal zone, yet understanding of how environmental heterogeneity and beta diversity are structured in forest ecosystems and post-clear cut is lacking. We use ground-dwelling arthropods as models to determine how natural succession (progression from deciduous to mixed to coniferous cover types) and clear-cutting change boreal forests, exploring the role of environmental heterogeneity in shaping beta diversity across multiple spatial scales (<i>between-cover types</i> and <i>between-stands of the same cover type</i> (1600 to 8500 m), <i>between-plots</i> (100 to 400 m) and <i>within-plots</i> (20 to 40 m)). We characterise environmental heterogeneity as variability in combined structural, vegetational and soil parameters, and beta diversity, as variability in assemblage composition. Clear-cutting homogenised forest environments across all spatial scales, reducing total environmental heterogeneity by 35%. Arthropod beta diversity reflected these changes at larger scales suggesting that environmental heterogeneity is useful in explaining beta diversity both <i>between-cover types</i> and <i>between-stands</i> of the same cover type. However, at smaller scales, <i>within-</i> and <i>between-plots</i> spider beta diversity reflected the lower environmental heterogeneity in regenerating stands, whereas staphylinid and carabids assemblages were not homogenised 12 years post-harvest. Differences in environmental heterogeneity and staphylinid beta diversity between cover types were also important at small scales. In regenerating stands, we detected a subtle yet notable effect of pre-felling cover type on environmental heterogeneity and arthropods, where pre-felling cover type accounted for a significant amount of variance in beta diversity, indicating that biological legacies (e.g. soil pH reflecting pre-harvest conditions) may have a role in driving beta diversity even 12 years post-harvest. This study highlights the importance of understanding site history when predicting impacts of change in forest ecosystems. Further, to understand drivers of beta diversity we must identify biological legacies shaping community structure.</p></div

Hen Harrier Circus cyaneus population trends in relation to wind farms

Capsule: The data presented here demonstrate a considerable spatial overlap between wind farms and the breeding distribution of Hen Harriers in Ireland, but evidence for a negative impact of wind farms on their population is weak. Aims: To assess the extent of the overlap between wind farms and breeding Hen Harriers and to investigate their potential impact on Hen Harrier population trends. Methods: Data on Hen Harrier breeding distribution in 10 km × 10 km survey squares from national surveys were used in conjunction with information on the location of wind farms to examine whether, and to what extent, changes in Hen Harrier distribution and abundance between 2000 and 2010 were related to wind energy development. Results: Of the 69 survey squares holding Hen Harriers during the 2010 breeding season, 28% also overlapped with one or more wind farms. Data from 36 of the squares with breeding Hen Harriers during the 2000 survey revealed a marginally non-significant negative relationship between wind farm presence and change in the number of breeding pairs between 2000 and 2010. Conclusions: A considerable overlap exists between Hen Harrier breeding distribution and the location of wind farms in Ireland, particularly in areas between 200 and 400 m above sea level. The presence of wind farms is negatively related to Hen Harrier population trends in squares surveyed in 2000 and 2010, but this relationship is not statistically significant, and may not be causal. This is the first study to assess the influence of wind energy development on Hen Harriers at such a large geographic and population scale

Contemporary forest loss in Ireland; quantifying rare deforestation events in a fragmented forest landscape

Accurate quantification of forest loss is required to meet international reporting requirements, even in countries where deforestation rates are low. In Ireland, recent evidence has suggested the rate of gross annual deforestation is increasing. However, no spatially explicit data on the extent and character of contemporary deforestation exists. Here, we quantify deforestation in a region where forest loss is rare. Deforestation estimates derived from wall-to-wall photointerpretation, official records (e.g. felling licences), the CORINE land-use/land cover changes dataset and a combined approach (hereafter termed “the Deforestation Map”) are compared in two regions in Ireland for the period 2000 to 2012. Deforestation area based on the Deforestation Map (1497 ha) was greater than estimates derived from using photo-interpretation (730 ha), official records (908 ha) and CORINE (139 ha) alone. Independent accuracy assessment highlighted high errors of omission for photo-interpretation (68.9%), official records (66.7%) and CORINE (91.84%) estimates compared to the Deforestation Map (20%). No general increase in the deforestation rate during the study period was recorded, despite regional variations. Post deforestation land-use transitions were principally to wetland, grassland and settlement although the magnitude and proportion of change varied regionally. Gross annual deforestation was higher in older broadleaf forests than in conifer plantation forests, a surprising finding considering the small area and conservation status of many broadleaf forests in Ireland. For countries with small forest area and/or low rates of deforestation, the use of methodologies employed herein can provide a valuable record of forest loss and be used to validate sample-based or remotely sensed deforestation estimates

The iconography of Asphyxiophilia: From fantasmatic fetish to forensic fact

This is a post print version of the article. The official published version can be accessed from the link below

The impact of frailty on healthcare utilisation in Ireland: evidence from the Irish longitudinal study on ageing

Introduction: To examine the impact of frailty on medical and social care utilisation among the Irish community-dwelling older population to inform strategies of integrated care for older people with complex needs. Methods: Participants aged >= 65 years from the Irish Longitudinal Study on Ageing (TILDA) representative of the Irish community-dwelling older population were analysed (n = 3507). The frailty index was used to examine patterns of utilisation across medical and social care services. Multivariate logistic and negative binomial regression models were employed to examine the impact of frailty on service utilisation outcomes after controlling for other factors. Results: The prevalence of frailty and pre-frailty was 24% (95% CI: 23, 26%) and 45% (95% CI: 43, 47%) respectively. Frailty was a significant predictor of utilisation of most social care and medical care services after controlling for the main correlates of frailty and observed individual effects. Conclusions: Frailty predicts utilisation of many different types of healthcare services rendering it a useful risk stratification tool for targeting strategies of integrated care. The pattern of care is predominantly medical as few of the frail older population use social care prompting questions about sub-groups of the frail older population with unmet care needs