Evaluation of diagnostic tests for Trypanosoma evansi and their application in epidemiological studies in Indonesia

The diagnosis of Trypanosoma evansi infections is problematic because low, fluctuating parasitaemias are typical of sub-acute and chronic infections. Antigen-detection ELlSAs (Ag-ELISAs) that have been developed to detect trypanosomal antigens in serum are reported to be better indicators of current T. evansi infections than either parasitological or antibody-detection tests. Two T. evansi Ag-ELISAs based on different monoclonal antibodies (2G6 Ag-ELISA and Tr7 Ag-ELISA) were evaluated using buffaloes in Southeast Asia, where T. evansi is endemic and livestock are important for draught power, meat and investment. The two Ag-ELISAs were standardised in the UK, following international guidelines on data expression and quality assurance. Diagnostic sensitivities were estimated using buffaloes either experimentally infected (n=35) or naturally infected (n=l 39) with T. evansi and compared with estimates obtained for the microhaematocrit test (MHCT), mouse inoculation (MI), three antibody-detection tests (IgM ELISA, IgG ELISA and card agglutination test {CATT}). Diagnostic specificities were estimated with nonexposed British cattle (n=249) and Australian buffaloes (n=263), and positive and negative predictive values were calculated. Field studies were conducted in Central Java to estimate prevalence and true incidence rates of T. evansi infections in buffaloes. No previous studies have compared two T. evansi Ag-ELISAs, estimated the prevalence of T. evansi infections in multiple villages within a district or true incidence rates.The repeatability and robustness of the two Ag-ELISAs were shown to be high. Profiles of antigenaemia varied between individual buffaloes and between the two Ag-ELISAs. Antigen and antibody responses were first detected 7 to 42 days after infection, but in some buffaloes responses fluctuated below cut-off values during infection, whilst in other buffaloes antigen and antibody responses persisted after trypanocidal drug treatment. With the naturally-infected buffaloes, the diagnostic sensitivity estimate of the Tr7 Ag-ELISA (81%) was significantly higher than that of the 2G6 Ag-ELISA (71%), and the IgG ELISA sensitivity (89%) was significantly higher than either the IgM ELISA or CATT sensitivities (78%). The diagnostic specificity estimates obtained with the British cattle were 83% for the 2G6 Ag-ELISA and 78% for the Tr7 Ag-ELISA, and with the Australian buffaloes were 75% for the 2G6 Ag-ELISA, 78% for the Tr7 Ag-ELISA, 100% for the CATT, 89% for the IgM ELISA and 92% for the IgG ELISA. Only slight agreement was found between the two Ag-ELISAs (kappa = 0.20), but moderate agreement between the IgG ELISA and CATT (kappa = 0.58). Positive and negative predictive values ranged from 24% to 99% for prevalence values from 10% to 90%, and true prevalence was underestimated at higher test prevalence values and overestimated at lower test prevalence valuesIn Central Java, 2387 buffaloes were blood sampled in 59 villages, and estimates of test prevalence were 4% with the MHCT, 9% with MI, 58% with the 2G6 Ag-ELISA and 70% with the Tr7 Ag-ELISA, but prevalence values differed between districts and between villages. True incidence rates per animal-year at risk were 0.44 with the Tr7 Ag-ELISA and 0.22 with the 2G6 Ag-ELISA. Of 239 market buffaloes sampled, 10% were parasitaemic, 39% antigenaemic, 56% positive by IgG ELISA and 47% positive by CATT, representing an important source of T. evansi.The T. evansi Ag-ELISAs and antibody-detection tests used in this study have many advantages as screening tests over commonly used parasitological tests, in terms of their diagnostic sensitivity and ability to rapidly test large numbers of samples. The two T. evansi Ag-ELISAs could be applied in high prevalence areas, whilst antibody-detection tests (in particular, the IgG ELISA or CATT) would be more appropriate to test buffaloes in low prevalence areas or to confirm the negative-status of buffaloes prior to movement within Indonesia or export. Future work should aim to improve the specificities of the Ag-ELISAs, which were low in this study in contrast to previous reports. The CATT had a high positive predictive value even with low prevalence and could be adapted more readily to test individual buffaloes in the field. The selection of diagnostic tests for T. evansi depends not only on test validity parameters, but also on the prevalence of T. evansi in the test population, the principal testing objectives and practical consideration

What psychiatrists should know about environmental sustainability and what they should be doing about it

The 2013 report from the Intergovernmental Panel on Climate Change has caused renewed concern among both clinicians and health policy makers. Climate change is continuing at an increasing rate. This guest editorial describes how climate change might affect global mental health and proposes three things that psychiatrists from every country could implement to respond appropriately to this urgent and severe global threat. These responses are mitigation and adaptation strategies for mental health services, and the integration of sustainability into training.</jats:p

Investigating the evolution and ecology of obscure bacterial symbioses found in invertebrates, ciliates and algae.

Bacterial symbioses form a fundamental part of the biology of most eukaryotic lifeforms, influencing their evolution, ecology, and behaviour. Their importance has been increasingly recognised in the last few decades, aided by advances in genomic and bioinformatic methods and analyses. As with most emerging fields, most of our knowledge comes from selected ‘model’ case studies, leaving the breadth of possible symbioses poorly explored. In this thesis I utilise a combination of bioinformatics, genomics, fieldwork, and microscopy to explore obscure symbioses across invertebrates, algae, and ciliates. First, I broaden the scope of available genomic and metabolic data available for rarer symbionts in invertebrates, a group that are often studied for their heritable symbionts. I argue that the group previously called Torix Rickettsia is distinct and diverse and should be regarded as a genus with at least three species, which I name ‘Candidatus Tisiphia’. I also report the first genome for the genus ‘Candidatus Megaira’, a widely recorded but poorly understood symbiont of microeukaryotes. I then explored the distribution of various symbiotic bacteria found in ciliates and algae, two host groups that are known to have strong links to symbiotic bacteria and the origins of symbioses but are rarely examined. I show the genus ‘Ca. Megaira’ appears as a deeply diverse, multi-species group of symbionts that is deserving of family status. I find ‘Ca. Megaira’ in both algae and ciliate species and infer that they have the potential to form protective symbioses. Likewise, I find diverse Parachlamydiales in algae and ciliates and propose three new species groups to aid taxonomic clarification of these bacteria. I provide potential microeukaryotic hosts for a group that are often divorced from host species when described and propose the possibility of nutritional and protective symbioses. Lastly, I develop a potential host-symbiont study system for future functional studies. Here, I demonstrate the existence of a likely heritable Ca. Tisiphia symbiont in the mosquito Anopheles plumbeus. It represents a potentially important system for onward application in manipulation of anopheline vector populations, which are currently restricted to a single symbiont. Finally, I synthesize these findings and argue future research should focus on the phenotypes of real-world symbioses discovered within this research

Computational layout design optimization of frame structures

Engineers often expend considerable effort identifying the most efficient cross-section sizes for the individual structural members forming a structure, but may neglect to check whether members are optimally positioned, or are even needed at all. This can lead to far more material being used to form a building structure than is needed. To address this, layout optimization can potentially be used early in the design process to identify efficient arrangements of structural members. This paper introduces an interactive design approach that combines parametric modelling and layout optimization, using an adaptive ‘member adding’ technique to allow large scale problems to be solved on a standard desktop PC. Incorporation of the approach in Rhino-Grasshopper allows integration of geometric modelling and structural layout optimization within a single interactive modeling environment. This paper briefly outlines the underlying theory and implementation details, and then describes application of the approach to benchmark problems and a case study problem, a three-centred space frame arch roof. In this case it is shown that a 30% reduction in material usage can potentially be achieved through the use of a layout optimization-based approach, but that measures to improve the practicality of the solutions for use in practice are required. This is being addressed as part of a new collaborative research project involving the Universities of Bath, Sheffield and Edinburgh

Prevention is better than cure, but...: Preventive medication as a risk to ordinariness?

Preventive health remains at the forefront of public health concerns; recent initiatives, such as the NHS health check, may lead to recommendations for medication in response to the identification of 'at risk' individuals. Little is known about lay views of preventive medication. This paper uses the case of aspirin as a prophylactic against heart disease to explore views among people invited to screening for a trial investigating the efficacy of such an approach. Qualitative interviews (N=46) and focus groups (N=5, participants 31) revealed dilemmas about preventive medication in the form of clashes between norms: first, in general terms, assumptions about the benefit of prevention were complicated by dislike of medication; second, the individual duty to engage in prevention was complicated by the need not to be over involved with one's own health; third, the potential appeal of this alternative approach to health promotion was complicated by unease about the implications of encouraging irresponsible behaviour among others. Though respondents made different decisions about using the drug, they reported very similar ways of trying to resolve these conflicts, drawing upon concepts of necessity and legitimisation and the special ordinariness of the particular dru

Bacterial genomics reveal the complex epidemiology of an emerging pathogen in Arctic and boreal ungulates

Northern ecosystems are currently experiencing unprecedented ecological change, largely driven by a rapidly changing climate. Pathogen range expansion, and emergence and altered patterns of infectious disease, are increasingly reported in wildlife at high latitudes. Understanding the causes and consequences of shifting pathogen diversity and host-pathogen interactions in these ecosystems is important for wildlife conservation, and for indigenous populations that depend on wildlife. Among the key questions are whether disease events are associated with endemic or recently introduced pathogens, and whether emerging strains are spreading throughout the region. In this study, we used a phylogenomic approach to address these questions of pathogen endemicity and spread for Erysipelothrix rhusiopathiae, an opportunistic multi-host bacterial pathogen associated with recent mortalities in arctic and boreal ungulate populations in North America. We isolated E. rhusiopathiae from carcasses associated with large-scale die-offs of muskoxen in the Canadian Arctic Archipelago, and from contemporaneous mortality events and/or population declines among muskoxen in northwestern Alaska and caribou and moose in western Canada. Bacterial genomic diversity differed markedly among these locations; minimal divergence was present among isolates from muskoxen in the Canadian Arctic, while in caribou and moose populations, strains from highly divergent clades were isolated from the same location, or even from within a single carcass. These results indicate that mortalities among northern ungulates are not associated with a single emerging strain of E. rhusiopathiae, and that alternate hypotheses need to be explored. Our study illustrates the value and limitations of bacterial genomic data for discriminating between ecological hypotheses of disease emergence, and highlights the importance of studying emerging pathogens within the broader context of environmental and host factors