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opencc-zeroJun 2022View details →

Habitat availability alters the relative risk of a bovine tuberculosis breakdown in the aftermath of a commercial forest clearfell disturbance

1. Human modification of landscapes and associated disturbances may facilitate the emergence and spread of zoonotic diseases. Policy-makers need better understanding of the link between anthropogenic disturbances and wildlife disease hosts at the interface of human society and the natural environment, e.g. agriculture, forestry and aquaculture. Empirical research is strongly needed for the control of novel zoonoses which might emerge, as well as the management of existing zoonoses with significant economic repercussions such as bovine tuberculosis (bTB). 2. We aimed to examine the link between ecological disturbance and relative bTB risk using Ireland as a case study. We analysed clearfell forestry operations and assessed bTB breakdowns within cattle farms across different spatio-temporal scales over multiple years, examining how ecological conditions may modulate this relationship using conditional logistic regression models. 3. We found a significant effect of the interaction between the extent of clearfell forestry removed and the extent of natural grassland and mixed forestry present on relative bTB risk. This interaction was dynamic, leading to an increase or decrease of the relative bTB risk depending on where (between 2 and 6 km from the farm) and when (between 0 and 36 months prior to the bTB outbreak) the clearfell operations occurred. 4. Our study provides empirical evidence of the link between mechanised forestry operations and fluctuating relative bTB risk in cattle farms, although the mechanism behind it is yet to be elucidated. Given our data, we hypothesise that wildlife hosts may abandon the area subjected to clearfell when disturbance is highest (during active operations and shortly afterward) but are subsequently attracted back to the site as they regenerate, potentially affecting the contact rates with livestock and thus, relative bTB risk. 5. Our analysis demonstrates that landscape modification is correlated with a change in relative bTB risk that is dynamic in time and space, allowing managers to understand the risk in landscape modification and inform policy accordingly. Landscape-level studies are necessary to unveil subtle ecological processes, shifting research and management efforts away from cattle herd-centric and toward macroecological surveillance of wildlife hosts and longitudinal assessment of bTB risk.

opencc-zeroDec 2017View details →

Data from: Type 1 interferon-inducible gene expression in QuantiFERON Gold TB-positive uveitis: a tool to stratify a high versus low risk of active tuberculosis?

QuantiFERON-Gold TB (QFT)-positive patients with undetermined cause of uveitis are problematic in terms of whether to diagnose and treat them for tuberculosis (TB). Here, we investigated whether peripheral blood expression of type 1 interferon (IFN)-inducible genes may be of use to stratify QFT-positive patients with uveitis into groups of high versus low risk of having active TB-associated uveitis. We recruited all new uveitis patients in Cipto Mangunkusumo Hospital, Jakarta, Indonesia for one year. We included 12 patients with uveitis and clinically diagnosed active pulmonary TB, 58 QFT-positive patients with uveitis of unknown cause, 10 newly diagnosed sputum-positive active pulmonary TB patients without uveitis and 23 QFT-negative healthy controls. Expression of 35 type 1 IFN-inducible genes was measured in peripheral blood cells from active pulmonary TB patients without uveitis and healthy controls. Differentially expressed genes were identified and used for further clustering analyses of the uveitis groups. A type-1 IFN gene signature score was calculated and the optimal cut-off value for this score to differentiate active pulmonary TB from healthy controls was determined and applied to QFT-positive patients with uveitis of unknown cause. Ten type 1 IFN-inducible genes were differentially expressed between active pulmonary TB and healthy controls. Expression of these 10 genes in QFT-positive patients with uveitis of unknown cause revealed three groups: 1); patients resembling active pulmonary TB, 2); patients resembling healthy controls, and 3); patients displaying an in-between gene expression pattern. A type 1 IFN gene signature score ≥5.61 displayed high sensitivity (100%) and specificity (91%) for identification of active TB. Application of this score to QFT-positive patients with uveitis of unknown cause yielded two groups with expected different likelihood (high vs. low) of having active-TB uveitis, and therefore may be useful in clinical management decisions.

opencc-zeroOct 2022View details →

Applications of machine learning tools for ultra-sensitive detection of lipoarabinomannan with plasmonic grating biosensors in clinical samples of tuberculosis

Background Tuberculosis is one of the top ten causes of death globally and the leading cause of death from a single infectious agent. Eradicating the Tuberculosis epidemic by 2030 is one of the top United Nations Sustainable Development Goals. Early diagnosis is essential to achieving this goal because it improves individual prognosis and reduces transmission rates of asymptomatic infected. We aim to support this goal by developing rapid and sensitive diagnostics using machine learning algorithms to minimize the need for expert intervention. Methods and Findings A single-molecule fluorescence immunosorbent assay was used to detect the Tuberculosis biomarker lipoarabinomannan from a set of twenty clinical patient samples and a control set of spiked human urine. Tuberculosis status was separately confirmed by GeneXpert MTB/RIF and cell culture. Two machine learning algorithms, an automatic and a semiautomatic model, were developed and trained by the calibrated lipoarabinomannan titration assay data and then tested against the ground truth patient data. The semiautomatic model differed from the automatic model by an expert review step in the former, which calibrated the lower threshold to determine single molecules from background noise. The semiautomatic model was found to provide 88.89% clinical sensitivity, while the automatic model resulted in 77.78% clinical sensitivity. Conclusions The semiautomatic model outperformed the automatic model in clinical sensitivity as a result of the expert intervention applied during calibration and both models vastly outperformed manual expert counting in terms of time-to-detection and completion of analysis. Meanwhile, the clinical sensitivity of the automatic model could be improved significantly with a larger training dataset. In short, semiautomatic, and automatic Gaussian Mixture Models have a place in supporting rapid detection of Tuberculosis in resource-limited settings without sacrificing clinical sensitivity.

opencc-zeroMay 2024View details →

Data from: Tuberculosis research in road construction sites

Introduction: Workers with occupational exposure to respirable silica dust like casual labourers at road construction sites (RCSs) are known to be at a high risk of developing pulmonary tuberculosis (TB). There is limited literature about the burden of PTB among this sub-population with high occupational exposures to silica dust at road construction sites. We aimed to determine the prevalence of PTB among casual labourers working at road construction sites in Central Uganda. Methods: We enrolled 297 participants by consecutive sampling into a cross-sectional study in September 2022 at four road construction sites in four districts in Central Uganda. A structured questionnaire was administered and the PTB cases were identified using a Gene Xpert and/or Computer Aided Detection for TB (CAD4TB). Data were analyzed in STATA version 17.0. Descriptive statistics adjusted for clustering were used to summarize the data and the relationship between PTB and independent variables were assessed using a mixed effects modified Poisson regression model to estimate the adjusted prevalence ratios. Results: Most participants were males (95.6% (284/297)), median age was 29 years [Interquartile range (IQR); 25, 33]. The prevalence of PTB among casual labourers was 2.4% (95% CI: 1.9, 2.8). Being vaccinated with BCG (3.45, 95% CI (1.02, 11.61)), alcohol use (2.70, 95% CI (1.52, 4.80)) and staying in overcrowded house (8.13, 95% CI (4.37, 15.12)) were positively associated with having PTB.s Conclusion: There is a high prevalence of PTB among casual labourers working at road construction sites in Central Uganda. Individuals who had never been vaccinated with BCG, alcohol users and those staying in overcrowded houses were at an increased risk of having PTB. We recommend routine screening of casual labourers at road construction sites to optimize active TB case finding.

opencc-by-4.0Jun 2024View details →

Supplementary materials for publication Hlanze H. et al. Universal lineage-independent markers of multidrug re-sistance in M. tuberculosis. IJMS 2024.

Drug resistance mutations stat.xlsx - this is an Excel file with data on the statistical evaluation of associations between mutations in protein-coding genes of M. tuberculosis and multidrug resistance; Drug mutation associations for Cytoscape.cys - this is a Cytoscape 3.10.2 dataset with predicted epistatic interactions among global markers of drug resistance in the overall M. tuberculosis population.

opencc-by-4.0Jul 2024View details →

A non-invasive BCG skin challenge model for assessing tuberculosis vaccine efficacy

Flow cytometry FCS files for Figure 3 days 7 and 14.

opencc-by-4.0Sep 2024View details →

Mycobacterium tuberculosis FtsB and PerM interact via a C-terminal helix: MD trajectories and microscopy data

Data accompanying the manuscript "Mycobacterium tuberculosis FtsB and PerM interact via a C-terminal helix in FtsB to modulate cell division" currently published at bioRxiv at https://doi.org/10.1101/2024.03.11.584518 Molecular dynamics trajectories (only protein atoms to limit size) are provided to reproduce analysis in the paper. Raw microscope image data is provided to reproduce analysis and figures in the paper. Other files and scripts required to reproduce the paper are available at https://github.com/smmlab/mtb-perm-ftsb

opencc-by-4.0Jan 2025View details →

Integrative genomics sheds light on the immunogenetics of tuberculosis in cattle

Mycobacterium bovis causes bovine tuberculosis (bTB), an infectious disease of cattle that represents a zoonotic threat to humans. Research has shown that the peripheral blood (PB) transcriptome is perturbed during bTB disease but the genomic architecture underpinning this transcriptional response remains poorly understood. Here, we analyse PB transcriptomics data from 63 control and 60 confirmed M. bovis infected animals and detect 2,592 differently expressed genes perturbing multiple immune response pathways. Leveraging imputed genome-wide SNP data, we characterise thousands of cis-expression quantitative trait loci (eQTLs) and show that the PB transcriptome is substantially impacted by intrapopulation genomic variation during M. bovis infection. Integrating our cis-eQTL data with bTB susceptibility GWAS summary statistics, we perform a transcriptome-wide association study and identify 132 functionally relevant genes (including RGS10, GBP4, TREML2, and RELT) and provide important new omics data for understanding the host response to mycobacterial infections that cause tuberculosis in mammals.

opencc-by-4.0Sep 2024View details →

Data and Scripts for "Timing matters in Macrophage / CD4+ T cell interactions: An agent-based model comparing Mycobacterium tuberculosis host-pathogen interactions between latently infected and naïve individuals"

This contains the data and graphing scripts necessary to recreate all figures in the paper "Timing matters in Macrophage / CD4+ T cell interactions: An agent-based model comparing Mycobacterium tuberculosis host-pathogen interactions between latently infected and naïve individuals". Supplemental Material for the paper is also provided here. Please refer to the README.md for instructions on how to use. The model can be found at: https://github.itap.purdue.edu/ElsjePienaarGroup/LTBINaiveinvitroModel/ along with the uncalibrated parameter files and scripts to run on HPCs.

opencc-zeroMar 2020View details →

Data from: Risk factors associated to a high Mycobacterium tuberculosis complex seroprevalence in wild boar (Sus scrofa) from a low bovine tuberculosis prevalence area

Animal tuberculosis is a worldwide zoonotic disease caused principally by Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex (MTC). In southern Iberian peninsula, wild reservoirs such as the wild boar, among other factors, have prevented the eradication of bovine tuberculosis. However, most of the studies have been focused on south-central Spain, where the prevalence of tuberculosis is high among wild ungulates and cattle herds. In northern regions, where wild boar density and bovine tuberculosis prevalence are lower, fewer studies have been carried out and the role of this species is still under debate. The aim of this study was to describe the temporal and spatial distribution of antibodies against MTC in wild boar from the Basque Country, northern Spain. Sera from 1902 animals were collected between 2010 and 2016. The seroprevalence was determined with an in house enzyme-linked immunosorbent assay and the search of risk factors was assessed by Generalized Linear Models. Overall, 17% of wild boars (326/1902; 95%CI, [15.5%–18.9%]) showed antibodies against MTC. Risk factors associated with seropositivity were the year and location of sampling, the number of MTC positive cattle, the distance to positive farms and the percentage of shrub cover. Age was associated with increased antibody titres among seropositive individuals. The seroprevalence detected was higher than those previously reported in neighbouring regions. Hence, further studies are needed to better understand the role of wild boar in the epidemiology of tuberculosis in low tuberculosis prevalence areas and consequently, its relevance when developing control strategies.

opencc-zeroAug 2021View details →

Improving Tuberculosis case finding in Nigeria

Paper I Background: Case detection for Tuberculosis remains low in high burden communities. Community Health Workers (CHWs) are the first point of contact for many Nigerians in the rural areas and have been found useful in active case finding. This study assessed the effect of cash incentives and training on tuberculosis case detection by CHWs in six Local Government Areas in Nigeria. Materials and Methods: A randomised control trial was conducted in three PHC clusters. The intervention Arm (A) received cash incentives for every presumptive case referred. The Training Arm B had no cash incentives and the control had neither training nor cash incentives. Case notification rates from the TB program were used to assess the effect of cash incentives on TB case finding. Data was analyzed using Graph Pad Prism. Descriptive data was presented in tables and bivariate data was analyzed using chi square. Mean increases in case notification rates was calculated Statistical significance was set as P=0.05. Results: Findings showed an increase of 14.4% (ꭓ2=2.976,P value=0.2258) in case notification rates for the Arm A that received cash incentives alongside training, there was also an increase of 7.4% (ꭓ2= 1.999,P value=0.1575) in Arm B that received Training only. For secondary outcomes, there was an increase in the total knowledge score (25.4%), knowledge of general symptoms (24.4%), knowledge of prevention (22.6%) and knowledge of diagnosis and treatment (30.0%) across all study arms post-intervention (p<0.0001). Secondary outcomes also indicated a 144.8%(ꭓ2= 4.147, P value=0.1258) increase in community outreaches conducted in the Arm that were given cash incentives. Conclusion: The study demonstrated an increase in TB control activities of case notification and outreaches among community health workers that received cash incentives and training. These findings support the use of incentives for CHWs in high burden TB settings to improve TB case detection rates. Paper II Background: Intensified efforts to improve tuberculosis (TB) diagnosis, treatment, and prevention are needed to meet global EndTB targets. Community health workers' (CHWs) knowledge with respect to case finding is vital in tuberculosis elimination. This study aimed to determine the effect of tuberculosis training on the knowledge of community health workers in Nigeria. Methods: As part of a larger multicomponent intervention study, a randomised control trial was conducted with CHWs in 18 Primary Health Care(PHC [TF1] [CA2]) clusters in Nigeria. The clusters were allocated to three arms: training and cash incentive (A), training only (B), and control (C) arms. Arms (A) and (B) received training on tuberculosis symptoms, prevention, diagnosis and treatment while the control arm (C) did not receive training. Participants' knowledge on tuberculosis was assessed using questionnaires administered pre- and post-intervention. Data was analyzed using GraphPad Prism. Descriptive data was presented in tables and bivariate data was analyzed using chi square. Statistical significance was set as P<0.05. Results: There was a significant increase in the total knowledge score (25.4%), knowledge of general symptoms (24.4%), prevention (22.6%) and diagnosis and treatment (30.0%) across all study arms post-intervention (p<0.0001). Compared with the control, training arm (A) had a higher proportion of good total knowledge score (94.4%) and arm (B) had lower proportion of good total knowledge score (83.1%) when compared to the control group (93.1%). These were, however, not statistically significant. Conclusions: An improvement in the CHWs' knowledge of symptoms, prevention, diagnosis and treatment of tuberculosis was observed after a training intervention was done. Integration of routine tuberculosis training is recommended to improve tuberculosis case finding in high burden communities.

opencc-zeroSep 2021View details →

Lipidomic profiling of Mycobacterium tuberculosis treated with JCP276, BMB034, or THL

The increasing incidence of antibiotic-resistant Mycobacterium tuberculosis infections is a growing global health threat necessitating the development of new antibiotics. Serine hydrolases (SHs) are a promising class of targets because of their importance for the synthesis of the mycobacterial cell envelope. We screened a library of small molecules containing serine-reactive electrophiles and identified a series of narrow spectrum inhibitors of M. tuberculous growth. Using these lead molecules we performed competitive activity-based protein profiling and identified SH targets, including enzymes with uncharacterized functions. Lipidomic analyses of compound-treated cultures revealed an accumulation of free lipids and a substantial decrease in lipooligosaccharides, linking SH inhibition to defects in cell envelope biogenesis. Mutant analysis revealed a path to resistance via the synthesis of mycocerates, but not through mutations to target enzymes. We conclude that simultaneous inhibition of multiple SH enzymes is likely to be an effective therapeutic strategy.

opencc-zeroNov 2022View details →

Multi-ancestry meta-analysis of host genetic susceptibility to tuberculosis identifies shared genetic architecture

The heritability of susceptibility to tuberculosis disease (TB) has been well recognized. Over one-hundred genes have been studied as candidates for TB susceptibility, and several variants were identified by genome-wide association studies (GWAS), but few replicates. We established the International Tuberculosis Host Genetics Consortium (ITHGC) to perform a multi-ancestry meta-analysis of GWAS including 14,153 cases and 19,536 controls of African, Asian, and European ancestry. Our analyses demonstrate a substantial degree of heritability (pooled polygenic h2=26.3% 95% CI 23.7–29.0%) for susceptibility to TB that is shared across ancestries, highlighting an important host genetic influence on disease. We identified one global host genetic correlate for TB at genome-wide significance (p < 5x10-8) in the human leukocyte antigen (HLA)-II region (rs28383206, p-value = 5.2x10-9). These data demonstrate the complex shared genetic architecture of susceptibility to TB and the importance of large-scale GWAS analysis across multiple ancestries experiencing different levels of infection pressures.

opencc-by-4.0Mar 2023View details →

Aspectos clínico-epidemiológicos de pacientes con tuberculosis, Guantánamo 2013-2018

Base de datos de Aspectos clínico-epidemiológicos de pacientes con tuberculosis, Guantánamo 2013-2018. Las variables que aparecen son: edad, sexo, grupos de riesgo (fumadores, alcohólicos, desnutridos, retrasados mentales, reclusos, sida y gestantes), municipio al que pertenece y forma clínica (pulmonar, extrapulmonar). Los datos inherentes a cada una de las variables se obtuvieron de la base de datos del Centro Provincial de Higiene, Epidemiología y Microbiología Guantánamo, Cuba.

restrictedIPD-UNDECIDEDFeb 2026View details →

Immune Response to Mycobacterium Tuberculosis Infection

ClinicalTrials.gov study NCT00257907. IPD Sharing: Not stated. Countries: 2. Publications: 3.

restrictedIPD-UNDECIDEDFeb 2026View details →

Efficacy of Tenofovir-Emtricitabine and Efavirenz in HIV Infected Patients With Tuberculosis (ANRS129)

ClinicalTrials.gov study NCT00115609. IPD Sharing: Not stated. Countries: 1. Publications: 0.

closedIPD-NOFeb 2026View details →

The INSTITUT Study Tuberculosis Nutritional Support

ClinicalTrials.gov study NCT06084715. IPD Sharing: NO. Countries: 2. Publications: 1.

restrictedIPD-UNDECIDEDFeb 2026View details →

Evaluation of PATHFAST-LAM as a Tuberculosis Treatment Monitoring Tool in Kenya

ClinicalTrials.gov study NCT07157904. IPD Sharing: Not stated. Countries: 1. Publications: 1.

closedIPD-NOFeb 2026View details →

Effect of Integrating Traditional Tuberculosis Care With Modern Health Care on Case Detection

ClinicalTrials.gov study NCT05236452. IPD Sharing: NO. Countries: 1. Publications: 3.