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1,862 results for “tuberculosis”
Data from: Context-dependent costs and benefits of tuberculosis resistance traits in a wild mammalian host
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Data from: IFN-γ-independent control of M. tuberculosis requires CD4 T cell-derived GM-CSF and activation of HIF-1α
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Data from: Bovine tuberculosis disturbs functional trait composition in African buffalo
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Antigen-specific CD4+ T cells promote monocyte recruitment and differentiation into glycolytic lung macrophages to control Mycobacterium tuberculosis
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Targeted metabolomics data for dimethyl-ribityl lumazine (DMRL) and riboflavin in Mycobacterium tuberculosis and Mycolicibacterium smegmatis mutants of the riboflavin biosynthetic pathway
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Prevalence and individual level enablers and barriers for COVID-19 vaccine uptake among adult tuberculosis patients attending selected clinics in Nairobi County, Kenya
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Mass spectrometry data from: Deficiency in Galectin-3, -8, and -9 impairs immunity to chronic Mycobacterium tuberculosis infection but not acute infection with multiple intracellular pathogens
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Dynamic post-translational modification profiling of M. tuberculosis-infected primary macrophages
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Rapid diagnosis of HIV-associated tuberculosis in the emergency centre
<p>Dataset used to developed a multi-parameter clinical decision tree to facilitate rapid diagnosis of tuberculosis using point-of-care diagnostic tests in HIV-positive patients presenting to an emergency centre</p>
Large Scale Computational Analysis of Coding and Non-coding Element Expression in Mycobacterium tuberculosis Unannotated CDS
<p>Large Scale Computational Analysis of Coding and Non-coding Element Expression in Mycobacterium tuberculosis Unannotated CDS data for the Applied Medical Science MSci Research Project. </p>
Data from: Natural resistance to worms exacerbates bovine tuberculosis severity independently of worm coinfection
<p class="CxSpFirst">Pathogen interactions arising during coinfection can exacerbate disease severity, for example, when the immune response mounted against one pathogen negatively affects defense of another. It is also possible that host immune responses to a pathogen, shaped by historical evolutionary interactions between host and pathogen, may modify host immune defenses in ways that have repercussions for other pathogens. In this case, negative interactions between two pathogens could emerge even in the absence of concurrent infection. Parasitic worms and tuberculosis (TB) are involved in one of the most geographically extensive of pathogen interactions, and during coinfection, worms can exacerbate TB disease outcomes. Here, we show that in a wild mammal, natural resistance to worms affects bovine tuberculosis (BTB) severity independently of active worm infection. We found that worm-resistant individuals were more likely to die of BTB than were non-resistant individuals, and their disease progressed more quickly. Anthelmintic treatment moderated, but did not eliminate, the resistance effect, and the effects of resistance and treatment were opposite and additive with untreated, resistant individuals experiencing the highest mortality. Furthermore, resistance and anthelmintic treatment had non-overlapping effects on BTB pathology. The effects of resistance manifested in the lungs (the primary site of BTB infection), while the effects of treatment manifested almost entirely in the lymph nodes (the site of disseminated disease), suggesting that resistance and active worm infection affect BTB progression via distinct mechanisms. Our findings reveal that interactions between pathogens can occur as a consequence of processes arising on very different timescales.</p>
Data for paper "Characterization of new, efficient Mycobacterium tuberculosis topoisomerase-I inhibitors..."
<p>FILES containd dataset for paper:</p> <p><strong>Characterization of new, efficient <em>Mycobacterium tuberculosis</em> topoisomerase-I inhibitors and their interaction with human ABC multidrug transporters</strong></p> <p> </p> <p>Csilla Temesszentandrási-Ambrus<sup>1,2</sup>, Balázs Sarkadi<sup>1</sup>, Gergely Szakács<sup>1</sup>, Szilárd Tóth<sup>1</sup>, László Őrfi<sup>3,4</sup>, Csaba Szántai-Kis<sup>3</sup>, Péter Bánhegyi<sup>3</sup>, István Szabadkai<sup>3</sup>, Ferenc Baska<sup>3</sup>, Ruben C. Hartkoorn<sup>5</sup>, Rinkee Verma<sup>6</sup>, Valakunja Nagaraja<sup>6</sup>, Mary A Lingerfelt <sup>7</sup>, Sean Ekins<sup>7</sup> and Ágnes Telbisz<sup>1,*</sup></p> <p> </p> <p>This work is dedicated to late Prof. György Kéri, founder and CEO of Vichem Ltd.</p> <p> </p> <p><sup>1</sup> Institute of Enzymology, RCNS-HAS, Budapest, Hungary</p> <p><sup>2</sup> Molecular Medicine Doctoral School, Semmelweis University, Budapest, Hungary</p> <p><sup>3</sup> Vichem Chemie Research Ltd., Budapest, Hungary.</p> <p><sup>4 </sup>Department of Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary</p> <p><sup>5</sup> Chemical Biology of Antibiotics, Center for Infection and Immunity, Inserm, CNRS, Institut Pasteur de Lille, Université de Lille, Lille, France</p> <p><sup>6</sup> Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India</p> <p><sup>7</sup> Collaborations Pharmaceuticals, Inc., 840 Main Campus Drive, Lab 3510, Raleigh, USA</p> <p> </p> <p> </p> <p>*Corresponding author:</p> <p>e-mail: telbisz.agnes@ttk.mta.hu<br> </p>
Evaluating the contributions of purifying selection and progeny-skew in dictating within-host Mycobacterium tuberculosis evolution
<p class="BodyA"><span><span><span><span><span><span><span><span><span><span>The within-host evolutionary dynamics of TB remain unclear, and underlying biological characteristics render standard population genetic approaches based upon the Wright-Fisher model largely inappropriate. In addition, the compact genome combined with an absence of recombination is expected to result in strong purifying selection effects. Thus, it is imperative to establish a biologically-relevant evolutionary framework incorporating these factors in order to enable an accurate study of this important human pathogen. Further, such a model is critical for inferring fundamental evolutionary parameters related to patient treatment, including mutation rates and the severity of infection bottlenecks. We here implement such a model and infer the underlying evolutionary parameters governing within-patient evolutionary dynamics. Results demonstrate that the progeny skew associated with the clonal nature of TB severely reduces genetic diversity and that the neglect of this parameter in previous studies has led to significant mis-inference of mutation rates. As such, our results suggest an underlying <i>de novo</i> mutation rate that is considerably faster than previously inferred, and a progeny distribution differing significantly from Wright-Fisher assumptions. This inference represents a more appropriate evolutionary null model, against which the periodic effects of positive selection, associated with drug-resistance for example, may be better assessed.</span></span></span></span></span></span></span></span></span></span></p>
Data from: Assessment of lung function in successfully treated Tuberculosis reveals high burden of ventilatory defects and COPD
<p>Background: Burden, phenotype and risk-factors of lung function defects in successfully treated tuberculosis cases are unclear. Methods: We performed spirometry with bronchodilators in new drug-sensitive adult (>18 years) pulmonary tuberculosis cases during the 12 months following successful treatment in India. Airflow obstruction was defined as pre-bronchodilator FEV1/FVC<5th percentile of Global Lung Initiative mixed-ethnicity reference (lower limit of normal [LLN]). Chronic obstructive pulmonary disease (COPD) was defined as post-bronchodilator FEV1/FVC</p> <p>Methods: We performed spirometry with bronchodilators in new drug-sensitive adult (≥18 years) pulmonary tuberculosis cases during the 12 months following successful treatment in India. Airflow obstruction was defined as pre-bronchodilator FEV1/FVC<5<sup>th</sup> percentile of Global Lung Initiative mixed-ethnicity reference (lower limit of normal [LLN]). Chronic obstructive pulmonary disease (COPD) was defined as post-bronchodilator FEV1/FVC<LLN among participants with obstruction. Restrictive spirometry pattern was defined as FVC<LLN among participants without obstruction. Multivariable logistic and linear regression was used to identify risk-factors for obstruction, restriction and low lung function despite successful treatment.</p> <p>Results: Of the 172 participants included in the analysis, 82 (48%) were female, 22 (13%) had diabetes and 34 (20%) ever-smoked with a median (IQR) exposure of 3.5 (0.2–9.9) pack-years. Median (IQR) age and body-mass index (BMI) at enrollment was 32 (23–39) years and 18.1 (16.0–20.5) kg/m<sup>2</sup> respectively. Airflow obstruction was detected in 42 (24%) participants; of whom 9 (21%) responded to short-acting bronchodilators and 25 (56%) had COPD; and was associated with duration of illness prior to treatment (aOR = 1.32 per 30-days, 95%CI 1.04–1.68, p = 0.02). A restrictive spirometry pattern was detected in 89 (52%) participants and was associated with female sex (aOR = 3.73, 95%CI 1.51–9.17, p = 0.004) and diabetes (aOR = 4.06, 95%CI 1.14–14.42, p = 0.03). Higher HbA1c at treatment initiation was associated with greater odds of a restrictive spirometry pattern (aOR = 1.29 per unit higher HbA1c, 95%CI 1.04 to 1.60, p = 0.02).</p> <p>We found a high burden of lung function defects and COPD in tuberculosis cases who successfully completed treatment. Screening for chronic lung diseases following treatment and linkage to respiratory health clinics should be included in the routine management plan of all tuberculosis cases in India, regardless of conventional COPD risk-factors such as older age and smoking.</p>
Data from: A chromosome 5q31.1 locus associates with tuberculin skin test reactivity in HIV-positive individuals from tuberculosis hyper-endemic regions in east Africa
One in three people has been infected with Mycobacterium tuberculosis (MTB), and the risk for MTB infection in HIV-infected individuals is even higher. We hypothesized that HIV-positive individuals living in tuberculosis-endemic regions who do not get infected by Mycobacterium tuberculosis are genetically resistant. Using an "experiment of nature" design that proved successful in our previous work, we performed a genome-wide association study of tuberculin skin test positivity using 469 HIV-positive patients from prospective study cohorts of tuberculosis from Tanzania and Uganda to identify genetic loci associated with MTB infection in the context of HIV-infection. Among these individuals, 244 tested were tuberculin skin test (TST) positive either at enrollment or during the >8 year follow up, while 225 were not. We identified a genome-wide significant association between the dominant model of rs877356 and binary TST status in the combined cohort (OR=0.2671, p=1.22x10-8). Association was replicated with similar significance when examining TST induration as a continuous trait. The variant lies in the 5q31.1 region, 57kb downstream from IL9. Two-locus analyses of association of variants near rs877356 showed a haplotype comprised of rs877356 and an IL9 missense variant rs2069885 had the most significant association (p=1.59x10-12). We also replicated previously linked loci on chromosomes 2, 5, and 11. IL9 is a cytokine produced by mast cells and T¬H2 cells during inflammatory responses, providing a possible link between airway inflammation and protection from MTB infection. Our results indicate that studying uninfected participants with extensive exposure increases the power to detect associations in complex infectious disease.
Data from: Patient characteristics associated with tuberculosis treatment default: a cohort study in a high-incidence area of Lima, Peru
Background: Although tuberculosis (TB) is usually curable with antibiotics, poor adherence to medication can lead to increased transmission, drug resistance, and death. Prior research has shown several factors to be associated with poor adherence, but this problem remains a substantial barrier to global TB control. We studied patients in a high-incidence district of Lima, Peru to identify factors associated with premature termination of treatment (treatment default). Methods: We conducted a prospective cohort study of adult smear-positive TB patients enrolled between January 2010 and December 2011 with no history of TB disease. Descriptive statistics and multivariable logistic regression analyses were performed to determine risk factors associated with treatment default. Results: Of the 1233 patients studied, 127 (10%) defaulted from treatment. Patients who defaulted were more likely to have used illegal drugs (OR = 4.78, 95% CI: 3.05-7.49), have multidrug-resistant TB (OR = 3.04, 95% CI: 1.58-5.85), not have been tested for HIV (OR = 2.30, 95% CI: 1.50-3.54), drink alcohol at least weekly (OR = 2.22, 95% CI: 1.40-3.52), be underweight (OR = 2.08, 95% CI: 1.21-3.56), or not have completed secondary education (OR = 1.55, 95% CI: 1.03-2.33). Conclusions: Our study identified several factors associated with defaulting from treatment, suggesting a complex set of causes that might lead to default. Addressing these factors individually would be difficult, but they might help to identify certain high-risk patients for supplemental intervention prior to treatment interruption. Treatment adherence remains a barrier to successful TB care and reducing the frequency of default is important for both the patients' health and the health of the community.
Data from: Disease, predation and demography: assessing the impacts of bovine tuberculosis on African buffalo by monitoring at individual and population levels
1. Understanding the effects of disease is critical to determining appropriate management responses, but estimating those effects in wildlife species is challenging. We used bovine tuberculosis (BTB) in the African buffalo Syncerus caffer population of Kruger National Park, South Africa, as a case study to highlight the issues associated with estimating chronic disease effects in a long-lived host. 2. We used known and radiocollared buffalo, aerial census data, and a natural gradient in pathogen prevalence to investigate if: (i) at the individual level, BTB infection reduces reproduction; (ii) BTB infection increases vulnerability to predation; and (iii) at the population level, increased BTB prevalence causes reduced population growth. 3. There was only a marginal reduction in calving success associated with BTB infection, as indexed by the probability of sighting a known adult female with or without a calf ( P = 0·065). 4. Since 1991, BTB prevalence increased from 27 to 45% in the southern region and from 4 to 28% in the central region of Kruger National Park. The prevalence in the northern regions was only 1·5% in 1998. Buffalo population growth rates, however, were neither statistically different among regions nor declining over time. 5. Lions Panthera leo did not appear to preferentially kill test-positive buffalo. The best (Akaike's Information Criterion corrected for small sample size) AIC c model with BTB as a covariate [exp( β ) = 0·49; 95% CI = (0·24–1·02)] suggested that the mortality hazard for positive individuals was no greater than for test-negative individuals. 6. Synthesis and applications . Test accuracy, time-varying disease status, and movement among populations are some of the issues that make the detection of chronic disease impacts challenging. For these reasons, the demographic impacts of bovine tuberculosis in the Kruger National Park remain undetectable despite 6 years of study on known individuals and 40 years of population counts. However, the rainfall and forage conditions during this study were relatively good and the impacts of many chronic diseases may be a non-linear function of environmental conditions such that
Data from: Interspecific visitation of cattle and badgers to fomites: a transmission risk for bovine tuberculosis?
In Great Britain and Ireland, badgers (Meles meles) are a wildlife reservoir of Mycobacterium bovis and implicated in bovine tuberculosis transmission to domestic cattle. The route of disease transmission is unknown with direct, so‐called "nose‐to‐nose," contact between hosts being extremely rare. Camera traps were deployed for 64,464 hr on 34 farms to quantify cattle and badger visitation rates in space and time at six farm locations. Badger presence never coincided with cattle presence at the same time, with badger and cattle detection at the same location but at different times being negatively correlated. Badgers were never recorded within farmyards during the present study. Badgers utilized cattle water troughs in fields, but detections were infrequent (equivalent to one badger observed drinking every 87 days). Cattle presence at badger‐associated locations, for example, setts and latrines, were three times more frequent than badger presence at cattle‐associated locations, for example, water troughs. Preventing cattle access to badger setts and latrines and restricting badger access to cattle water troughs may potentially reduce interspecific bTB transmission through reduced indirect contact.
Data from: Badgers prefer cattle pasture but avoid cattle: implications for bovine tuberculosis control
Effective management of infectious disease relies upon understanding mechanisms of pathogen transmission. In particular, while models of disease dynamics usually assume transmission through direct contact, transmission through environmental contamination can cause different dynamics. We used Global Positioning System (GPS) collars and proximity-sensing contact-collars to explore opportunities for transmission of Mycobacterium bovis [causal agent of bovine tuberculosis] between cattle and badgers (Meles meles). Cattle pasture was badgers' most preferred habitat. Nevertheless, although collared cattle spent 2914 collar-nights in the home ranges of contact-collared badgers, and 5380 collar-nights in the home ranges of GPS-collared badgers, we detected no direct contacts between the two species. Simultaneous GPS-tracking revealed that badgers preferred land > 50 m from cattle. Very infrequent direct contact indicates that badger-to-cattle and cattle-to-badger M. bovis transmission may typically occur through contamination of the two species' shared environment. This information should help to inform tuberculosis control by guiding both modelling and farm management.
Data from: Diagnostic pathways and direct medical costs incurred by new adult pulmonary tuberculosis patients prior to anti-tuberculosis treatment – Tamil Nadu, India
Background: Tuberculosis (TB) patients face substantial delays prior to treatment initiation, and out of pocket (OOP) expenditures often surpass the economic productivity of the household. We evaluated the pre-diagnostic cost and health seeking behaviour of new adult pulmonary TB patients registered at Primary Health Centres (PHCs) in Vellore district, Tamil Nadu, India. Methods: This descriptive study, part of a randomised controlled trial conducted in three rural Tuberculosis Units from Dec 2012 to Dec 2015, collected data on number of health facilities, dates of visits prior to the initiation of anti-tuberculosis treatment, and direct OOP medical costs associated with TB diagnosis. Logistic regression analysis examined the factors associated with delays in treatment initiation and OOP expenditures. Results: Of 880 TB patients interviewed, 34.7% presented to public health facilities and 65% patients sought private health facilities as their first point of care. The average monthly individual income was $77.79 (SD 57.14). About 69% incurred some pre-treatment costs at an average of $39.74. Overall, patients experienced a median of 6 days (3-11 IQR) of time to treatment initiation and 21 days (10-30 IQR) of health systems delay. Age ≤ 40 years (aOR: 1.73; CI: 1.22 - 2.44), diabetes (aOR: 1.63; CI: 1.08 - 2.44) and first visit to a private health facility (aOR: 17.2; CI: 11.1 - 26.4) were associated with higher direct OOP medical costs, while age ≤ 40 years (aOR: 0.64; CI: 0.48 - 0.85) and first visit to private health facility (aOR: 1.79, CI: 1.34 - 2.39) were associated with health systems delay. Conclusion: The majority of rural TB patients registering at PHCs visited private health facilities first and incurred substantial direct OOP medical costs and delays prior to diagnosis and anti-tuberculosis treatment initiation. This study highlights the need for PHCs to be made as the preferred choice for first point of contact, to combat TB more efficiently.
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Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
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DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.