146 research outputs found

    Non-invasive monitoring of environmental Mycobacterium bovis shedding in wild European badger (Meles meles) populations

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    The herd-level incidence of Mycobacterium bovis has been increasing in the United Kingdom (UK) and Republic or Ireland (RoI) for the past thirty years, resulting in substantial economic and animal welfare issues. Failure to control this pathogen in cattle is in part due to European badgers (Meles meles), a wildlife reservoir that are responsible for a proportion of transmission of M. bovis to cattle. Monitoring infection in badger populations is currently limited due to the need to trap badgers, which requires highly trained field staff and is expensive. In addition, although contact with infected badger faeces is a potential transmission route to cattle, very little is known about the extent and variability of the environmental pool of M. bovis shed by badgers. In this project we evaluated the suitability of using environmental badger faeces and a quantitative PCR (qPCR) assay to diagnose and monitor M. bovis in badger populations and described the extent of this environmental pool of potential infection. The first study identified that intensive environmental faecal sampling and analysis with qPCR is at least, if not more, sensitive at diagnosing M. bovis in badger populations than the currently used immunoassays. This study also identified that even within a high prevalence population, the levels of shedding of M. bovis in faeces are highly variable between groups and between seasons, suggesting that there may be heterogeneity in transmission risk throughout the year. Using this non-invasive qPCR method to monitor the first field trial of oral BCG vaccination identified a trend of decreasing levels of M. bovis in faeces with increasing vaccination levels however, these results failed to reach statistical significance, highlighting the importance of adequate sample sizes when implementing this method. Finally, characterisation of the gut and faecal microbiota from animals shedding M. bovis in faeces confirmed that the source of faecal M. bovis is most likely sputum that has been expelled from the lungs, and not from colonisation of the gut. The work presented here suggests that this non-invasive monitoring method can be applied to examine the variable pool of M. bovis over periods of time and large areas, providing an epidemiological tool which has the potential to be implemented to monitor infection in badger populations and disease intervention strategies

    Survival of the ovine footrot pathogen Dichelobacter nodosus in different soils

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    Dichelobacter nodosus (D. nodosus) is the causative agent of footrot in sheep; one of the most important health and welfare issues of sheep worldwide. For control programmes to be effective, it is essential that the transmission cycle of D. nodosus is understood and bacterial reservoirs in the environment are better defined. This study evaluated the survival of D. nodosus in different soils using soil microcosms. Cultivation independent and dependent methods were used to detect D. nodosus over 40 days from seeding in soil. A D. nodosus specific probe was used for quantification by qPCR and viability was assessed by cell permeability to an intercalating dye, PMA, and by culture. Survival varied dramatically depending on soil type, matric potential (MP) and temperature. Our findings indicate that D. nodosus survival was higher at 5 °C compared with 25 °C in all soils and significantly longer at both temperatures in clay soil (>44% clay) compared with other soil types. Survival under all conditions was longer than 30 days for both culture independent and dependent methods, this is substantially longer than previous studies and, if this is an infectious dose, longer than the current recommendation of resting a field for 14 days to prevent onward infection

    The UK ME/CFS Biobank for biomedical research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis.

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    The UK ME/CFS Biobank was launched in August 2011 following extensive consultation with professionals and patient representatives. The bioresource aims to enhance research on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), related to pathophysiology, biomarkers and therapeutic approaches. The cohort includes 18-60 year olds, encompassing 284 clinically-confirmed ME/CFS cases, 60 neurologist-diagnosed multiple sclerosis (MS) cases, and 135 healthy individuals. The Biobank contains blood samples, aliquoted into serum, plasma, peripheral blood mononuclear cells (PBMC), red blood cells/granulocyte pellet, whole blood, and RNA (totalling 29,863 aliquots). Extensive dataset (700 clinical and socio-demographic variables/participant) enables comprehensive phenotyping. Potential reuse is conditional to ethical approval

    Performance of a non-invasive test for detecting mycobacterium bovis shedding in European badger (meles meles) populations

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    The incidence of Mycobacterium bovis, the causative agent of bovine tuberculosis, in cattle herds in the United Kingdom is increasing, resulting in substantial economic losses. The European badger (Meles meles) is implicated as a wildlife reservoir and is the subject of control measures aimed at reducing incidence in cattle populations. Understanding the epidemiology of M. bovis in badger populations is essential to direct control interventions and understand disease spread; however, accurate diagnosis in live animals is challenging and currently uses invasive methods. Here we present a non-invasive diagnostic procedure and sampling regime using field sampling of latrines and detection of M. bovis with qPCR, the results of which strongly correlate with the results of immunoassay testing in the field at the social group level. This method allows M. bovis infection in badger populations to be monitored without trapping and provides additional information on the quantity of bacterial DNA shed. Our approach may therefore provide valuable insights into the epidemiology of bovine tuberculosis in badger populations and inform disease control interventions

    The variability and seasonality of the environmental reservoir of Mycobacterium bovis shed by wild European badgers

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    The incidence of Mycobacterium bovis, the causative agent of bovine tuberculosis, has been increasing in UK cattle herds resulting in substantial economic losses. The European badger (Meles meles) is implicated as a wildlife reservoir of infection. One likely route of transmission to cattle is through exposure to infected badger urine and faeces. The relative importance of the environment in transmission remains unknown, in part due to the lack of information on the distribution and magnitude of environmental reservoirs. Here we identify potential infection hotspots in the badger population and quantify the heterogeneity in bacterial load; with infected badgers shedding between 1 × 103 − 4 × 105 M. bovis cells g−1 of faeces, creating a substantial and seasonally variable environmental reservoir. Our findings highlight the potential importance of monitoring environmental reservoirs of M. bovis which may constitute a component of disease spread that is currently overlooked and yet may be responsible for a proportion of transmission amongst badgers and onwards to cattle

    Do Interventions Designed to Support Shared Decision-Making Reduce Health Inequalities? : A Systematic Review and Meta-Analysis

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    Copyright: © 2014 Durand et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Increasing patient engagement in healthcare has become a health policy priority. However, there has been concern that promoting supported shared decision-making could increase health inequalities. Objective: To evaluate the impact of SDM interventions on disadvantaged groups and health inequalities. Design: Systematic review and meta-analysis of randomised controlled trials and observational studies.Peer reviewe

    The Type III Effectors NleE and NleB from Enteropathogenic E. coli and OspZ from Shigella Block Nuclear Translocation of NF-κB p65

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    Many bacterial pathogens utilize a type III secretion system to deliver multiple effector proteins into host cells. Here we found that the type III effectors, NleE from enteropathogenic E. coli (EPEC) and OspZ from Shigella, blocked translocation of the p65 subunit of the transcription factor, NF-κB, to the host cell nucleus. NF-κB inhibition by NleE was associated with decreased IL-8 expression in EPEC-infected intestinal epithelial cells. Ectopically expressed NleE also blocked nuclear translocation of p65 and c-Rel, but not p50 or STAT1/2. NleE homologues from other attaching and effacing pathogens as well OspZ from Shigella flexneri 6 and Shigella boydii, also inhibited NF-κB activation and p65 nuclear import; however, a truncated form of OspZ from S. flexneri 2a that carries a 36 amino acid deletion at the C-terminus had no inhibitory activity. We determined that the C-termini of NleE and full length OspZ were functionally interchangeable and identified a six amino acid motif, IDSY(M/I)K, that was important for both NleE- and OspZ-mediated inhibition of NF-κB activity. We also established that NleB, encoded directly upstream from NleE, suppressed NF-κB activation. Whereas NleE inhibited both TNFα and IL-1β stimulated p65 nuclear translocation and IκB degradation, NleB inhibited the TNFα pathway only. Neither NleE nor NleB inhibited AP-1 activation, suggesting that the modulatory activity of the effectors was specific for NF-κB signaling. Overall our data show that EPEC and Shigella have evolved similar T3SS-dependent means to manipulate host inflammatory pathways by interfering with the activation of selected host transcriptional regulators

    Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

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    Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy
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