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PLoS Neglected Tropical Diseases May 2024Bovine tuberculosis (bTB) is a chronic zoonotic disease affecting cattle of all age groups including wild animals. It poses a significant threat to public health and...
Bovine tuberculosis (bTB) is a chronic zoonotic disease affecting cattle of all age groups including wild animals. It poses a significant threat to public health and high economic losses to dairy farmers. While the disease has been eradicated from most of the developed countries through extensive surveillance, testing and culling strategy, it is endemic in Africa, Asia, and the Middle East countries. Currently, there is limited research regarding the prevalence of bTB in cattle in Bhutan. This study aimed to determine the seroprevalence of bTB in cattle in six districts of eastern Bhutan. A two-stage probability proportional to size (PPS) sampling strategy was used to determine the number of animals from which serum samples needed to be collected in each district and sub-district. All farms and cattle for sampling were randomly selected from the data in the annual livestock census of 2020. The samples were tested using bTB ELISA test kit. The seroprevalence and their 95% confidence intervals were calculated. Logistic regression models were constructed to assess the influence of various individual animal and environmental risk factors (breed, age, sex, source of animal, body condition scores of animals, respiratory system status) associated with sero-positivity in animals. The study revealed an apparent seroprevalence of 2.57% (25/971 cattle; 95% CI:1.58-3.57), with an estimated true seroprevalence of 0.91% (95% CI: 0.0-2.81). However, none of the variables were found to be significantly associated with bTB seroprevalence in cattle. We recommend, further sampling and employment of confirmatory testing to fully ascertain the extent of bTB in the cattle herds in eastern Bhutan for prevention and control.
Topics: Animals; Cattle; Bhutan; Seroepidemiologic Studies; Tuberculosis, Bovine; Risk Factors; Female; Male; Mycobacterium bovis; Prevalence; Antibodies, Bacterial
PubMed: 38805568
DOI: 10.1371/journal.pntd.0012223 -
Frontiers in Immunology 2024Mycobacteria are known to exert a range of heterologous effects on the immune system. The mycobacteria-based Freund's Complete Adjuvant is a potent non-specific...
INTRODUCTION
Mycobacteria are known to exert a range of heterologous effects on the immune system. The mycobacteria-based Freund's Complete Adjuvant is a potent non-specific stimulator of the immune response used in immunization protocols promoting antibody production, and Mycobacterium bovis Bacille Calmette Guérin (BCG) vaccination has been linked with decreased morbidity and mortality beyond the specific protection it provides against tuberculosis (TB) in some populations and age groups. The role of heterologous antibodies in this phenomenon, if any, remains unclear and under-studied.
METHODS
We set out to evaluate antibody responses to a range of unrelated pathogens following infection with Mycobacterium tuberculosis (M.tb) and vaccination with BCG or a candidate TB vaccine, MTBVAC, in non-human primates.
RESULTS
We demonstrate a significant increase in the titer of antibodies against SARS-CoV-2, cytomegalovirus, Epstein-Barr virus, tetanus toxoid, and respiratory syncytial virus antigens following low-dose aerosol infection with M.tb. The magnitude of some of these responses correlated with TB disease severity. However, vaccination with BCG administered by the intradermal, intravenous or aerosol routes, or intradermal delivery of MTBVAC, did not increase antibody responses against unrelated pathogens.
DISCUSSION
Our findings suggest that it is unlikely that heterologous antibodies contribute to the non-specific effects of these vaccines. The apparent dysregulation of B cell responses associated with TB disease warrants further investigation, with potential implications for risk of B cell cancers and novel therapeutic strategies.
Topics: Animals; BCG Vaccine; Tuberculosis; Mycobacterium tuberculosis; Vaccination; Antibodies, Bacterial; Antibodies, Viral; Tuberculosis Vaccines; Female; Macaca mulatta; SARS-CoV-2; COVID-19; Immunity, Heterologous; Male
PubMed: 38799468
DOI: 10.3389/fimmu.2024.1387454 -
Scientific Reports May 2024We have previously reported the transcriptomic and lipidomic profile of the first-generation, hygromycin-resistant (Hyg) version of the BCGΔBCG1419c vaccine candidate,... (Comparative Study)
Comparative Study
Comparison of the transcriptome, lipidome, and c-di-GMP production between BCGΔBCG1419c and BCG, with Mincle- and Myd88-dependent induction of proinflammatory cytokines in murine macrophages.
We have previously reported the transcriptomic and lipidomic profile of the first-generation, hygromycin-resistant (Hyg) version of the BCGΔBCG1419c vaccine candidate, under biofilm conditions. We recently constructed and characterized the efficacy, safety, whole genome sequence, and proteomic profile of a second-generation version of BCGΔBCG1419c, a strain lacking the BCG1419c gene and devoid of antibiotic markers. Here, we compared the antibiotic-less BCGΔBCG1419c with BCG. We assessed their colonial and ultrastructural morphology, biofilm, c-di-GMP production in vitro, as well as their transcriptomic and lipidomic profiles, including their capacity to activate macrophages via Mincle and Myd88. Our results show that BCGΔBCG1419c colonial and ultrastructural morphology, c-di-GMP, and biofilm production differed from parental BCG, whereas we found no significant changes in its lipidomic profile either in biofilm or planktonic growth conditions. Transcriptomic profiling suggests changes in BCGΔBCG1419c cell wall and showed reduced transcription of some members of the DosR, MtrA, and ArgR regulons. Finally, induction of TNF-α, IL-6 or G-CSF by bone-marrow derived macrophages infected with either BCGΔBCG1419c or BCG required Mincle and Myd88. Our results confirm that some differences already found to occur in Hyg BCGΔBCG1419c compared with BCG are maintained in the antibiotic-less version of this vaccine candidate except changes in production of PDIM. Comparison with previous characterizations conducted by OMICs show that some differences observed in BCGΔBCG1419c compared with BCG are maintained whereas others are dependent on the growth condition employed to culture them.
Topics: Animals; Myeloid Differentiation Factor 88; Mice; Macrophages; Transcriptome; Lipidomics; BCG Vaccine; Cyclic GMP; Mycobacterium bovis; Biofilms; Cytokines; Membrane Proteins; Gene Expression Profiling; Lectins, C-Type
PubMed: 38789479
DOI: 10.1038/s41598-024-61815-8 -
Veterinary Sciences May 2024Bovine tuberculosis is a zoonotic disease of significant impact, particularly in countries where a pastoral economy is predominant. Despite its importance, few studies...
INTRODUCTION
Bovine tuberculosis is a zoonotic disease of significant impact, particularly in countries where a pastoral economy is predominant. Despite its importance, few studies have analysed the disease's behaviour in Colombia, and none have developed maps using geographic information systems (GIS) to characterise it; as such, we developed this study to describe the temporal-spatial distribution of bovine tuberculosis in Colombia over a period of 19 years.
METHODS
A retrospective cross-sectional descriptive study, based on reports by the Colombian Agricultural Institute (ICA), surveillance of tuberculosis on cattle farms in Colombia from 2001 to 2019 was carried out. The data were converted into databases using Microsoft Access 365, and multiple epidemiological maps were generated with the QGIS version 3.36 software coupled to shape files of all the country's departments.
RESULTS
During the study period, 5273 bovine tuberculosis cases were identified in multiple different departments of Colombia (with a mean of 278 cases/year). Regarding its temporal distribution, the number of cases varied from a maximum of 903 cases (17.12% of the total) in 2015 to a minimum of 0 between 2001 and 2004 and between 2017 and 2019 (between 2005 and 2016, the minimum was 46 cases, 0.87%).
CONCLUSIONS
GIS are essential for understanding the temporospatial behaviour of zoonotic diseases in Colombia, as is the case for bovine tuberculosis, with its potential implications for the Human and One Health approaches.
PubMed: 38787192
DOI: 10.3390/vetsci11050220 -
Veterinary Research May 2024Zoonotic diseases represent a significant societal challenge in terms of their health and economic impacts. One Health approaches to managing zoonotic diseases are... (Review)
Review
Zoonotic diseases represent a significant societal challenge in terms of their health and economic impacts. One Health approaches to managing zoonotic diseases are becoming more prevalent, but require novel thinking, tools and cross-disciplinary collaboration. Bovine tuberculosis (bTB) is one example of a costly One Health challenge with a complex epidemiology involving humans, domestic animals, wildlife and environmental factors, which require sophisticated collaborative approaches. We undertook a scoping review of multi-host bTB epidemiology to identify trends in species publication focus, methodologies, and One Health approaches. We aimed to identify knowledge gaps where novel research could provide insights to inform control policy, for bTB and other zoonoses. The review included 532 articles. We found different levels of research attention across episystems, with a significant proportion of the literature focusing on the badger-cattle-TB episystem, with far less attention given to tropical multi-host episystems. We found a limited number of studies focusing on management solutions and their efficacy, with very few studies looking at modelling exit strategies. Only a small number of studies looked at the effect of human disturbances on the spread of bTB involving wildlife hosts. Most of the studies we reviewed focused on the effect of badger vaccination and culling on bTB dynamics with few looking at how roads, human perturbations and habitat change may affect wildlife movement and disease spread. Finally, we observed a lack of studies considering the effect of weather variables on bTB spread, which is particularly relevant when studying zoonoses under climate change scenarios. Significant technological and methodological advances have been applied to bTB episystems, providing explicit insights into its spread and maintenance across populations. We identified a prominent bias towards certain species and locations. Generating more high-quality empirical data on wildlife host distribution and abundance, high-resolution individual behaviours and greater use of mathematical models and simulations are key areas for future research. Integrating data sources across disciplines, and a "virtuous cycle" of well-designed empirical data collection linked with mathematical and simulation modelling could provide additional gains for policy-makers and managers, enabling optimised bTB management with broader insights for other zoonoses.
Topics: Animals; Tuberculosis, Bovine; Cattle; Zoonoses; Humans; Animals, Wild; One Health; Mustelidae
PubMed: 38773649
DOI: 10.1186/s13567-024-01314-w -
Microbiology Spectrum May 2024causes animal tuberculosis in livestock and wildlife, with an impact on animal health and production, wildlife management, and public health. In this work, we sampled a...
UNLABELLED
causes animal tuberculosis in livestock and wildlife, with an impact on animal health and production, wildlife management, and public health. In this work, we sampled a multi-host tuberculosis community from the official hotspot risk area of Portugal over 16 years, generating the largest available data set in the country. Using phylogenetic and ecological modeling, we aimed to reconstruct the history of circulating lineages across the livestock-wildlife interface to inform intervention and the implementation of genomic surveillance within the official eradication plan. We find evidence for the co-circulation of European 1 (Eu1), Eu2, and Eu3 clonal complexes, with Eu3 providing sufficient temporal signal for further phylogenetic investigation. The Eu3 most recent common ancestor (bovine) was dated in the 1990s, subsequently transitioning to wildlife (red deer and wild boar). Isolate clustering based on sample metadata was used to inform phylogenetic inference, unravelng frequent transmission between two clusters that represent an ecological corridor of previously unrecognized importance in Portugal. The latter was associated with transmission at the livestock-wildlife interface toward locations with higher temperature and precipitation, lower agriculture and road density, and lower host densities. This is the first analysis of Eu3 complex in Iberia, shedding light on background ecological factors underlying long-term transmission and informing where efforts could be focused within the larger hotspot risk area of Portugal.
IMPORTANCE
Efforts to strengthen surveillance and control of animal tuberculosis (TB) are ongoing worlwide. Here, we developed an eco-phylodynamic framework based on discrete phylogenetic approaches informed by whole-genome sequence data representing a multi-host transmission system at the livestock-wildlife interface, within a rich ecological landscape in Portugal, to understand transmission processes and translate this knowledge into disease management benefits. We find evidence for the co-circulation of several clades, with frequent transmission of the Eu3 lineage among cattle and wildlife populations. Most transition events between different ecological settings took place toward host, climate and land use gradients, underscoring animal TB expansion and a potential corridor of unrecognized importance for maintenance. Results stress that animal TB is an established wildlife disease without ecological barriers, showing that control measures in place are insufficient to prevent long-distance transmission and spillover across multi-host communities, demanding new interventions targeting livestock-wildlife interactions.
PubMed: 38771094
DOI: 10.1128/spectrum.03829-23 -
Microbiology Spectrum May 2024Currently, tuberculosis immunoprophylaxis is based solely on Bacillus Calmette-Guérin (BCG) vaccination, and some of the new potential tuberculosis vaccines are based...
UNLABELLED
Currently, tuberculosis immunoprophylaxis is based solely on Bacillus Calmette-Guérin (BCG) vaccination, and some of the new potential tuberculosis vaccines are based on the BCG genome. Therefore, it is reasonable to analyze the genomes of individual BCG substrains. The aim of this study was the genetic characterization of the BCG-Moreau Polish (PL) strain used for the production of the BCG vaccine in Poland since 1955. Sequencing of different BCG lots showed that the strain was stable over a period of 59 years. As a result of comparison, BCG-Moreau PL with BCG-Moreau Rio de Janeiro (RDJ) 143 single nucleotide polymorphisms (SNPs) and 32 insertion/deletion mutations (INDELs) were identified. However, the verification of these mutations showed that the most significant were accumulated in the BCG-Moreau RDJ genome. The mutations unique to the Polish strain genome are 1 SNP and 2 INDEL. The strategy of combining short-read sequencing with long-read sequencing is currently the most optimal approach for sequencing bacterial genomes. With this approach, the only available genomic sequence of BCG-Moreau PL was obtained. This sequence will primarily be a reference point in the genetic control of the stability of the vaccine strain in the future. The results enrich knowledge about the microevolution and attenuation of the BCG vaccine substrains.
IMPORTANCE
The whole genome sequence obtained is the only genomic sequence of the strain that has been used for vaccine production in Poland since 1955. Sequencing of different BCG lots showed that the strain was stable over a period of 59 years. The comprehensive genomic analysis performed not only enriches knowledge about the microevolution and attenuation of the BCG vaccine substrains but also enables the utilization of identified markers as a reference point in the genetic control and identity tests of the stability of the vaccine strain in the future.
PubMed: 38757975
DOI: 10.1128/spectrum.04259-23 -
Veterinary Immunology and... Jun 2024The dynamics that develop between cells and molecules in the host against infection by Mycobacterium bovis, leads to the formation of granulomas mainly present in the...
The dynamics that develop between cells and molecules in the host against infection by Mycobacterium bovis, leads to the formation of granulomas mainly present in the lungs and regional lymph nodes in cattle. Cell death is one of the main features in granuloma organization, however, it has not been characterized in granulomatous lesions caused by M. bovis. In this study we aimed to identify the profiles of cell death in the granuloma stages and its relationship with the accumulation of bacteria. We identified necrosis, activated caspase-3, LC3B/p62 using immunohistochemistry and digital pathology analysis on 484 granulomatous lesions in mediastinal lymph nodes from 23 naturally infected cattle. Conclusions: greater amounts of mycobacterial antigens were identified in granulomas from calves compared with adult cattle. The highest percentage of necrosis and quantity of mycobacterial antigens were identified in granuloma stages (III/IV) from adults. The LC3B/p62 profile was heterogeneous in granulomas between adults and calves. Our data suggest that necrosis is associated with a higher amount of mycobacterial antigens in the late stages of granuloma and the development of autophagy appears to play an heterogeneous effector response against infection in adults and calves. These results represent one of the first approaches in the identification of cell death in the four stages of granulomas in bovine tuberculosis.
Topics: Animals; Cattle; Granuloma; Mycobacterium bovis; Necrosis; Tuberculosis, Bovine; Antigens, Bacterial; Lymph Nodes; Caspase 3; Immunohistochemistry
PubMed: 38723459
DOI: 10.1016/j.vetimm.2024.110757 -
Respiratory Research May 2024The association between tuberculous fibrosis and lung cancer development has been reported by some epidemiological and experimental studies; however, its underlying...
BACKGROUND
The association between tuberculous fibrosis and lung cancer development has been reported by some epidemiological and experimental studies; however, its underlying mechanisms remain unclear, and the role of macrophage (MФ) polarization in cancer progression is unknown. The aim of the present study was to investigate the role of M2 Arg-1 MФ in tuberculous pleurisy-assisted tumorigenicity in vitro and in vivo.
METHODS
The interactions between tuberculous pleural effusion (TPE)-induced M2 Arg-1 MФ and A549 lung cancer cells were evaluated. A murine model injected with cancer cells 2 weeks after Mycobacterium bovis bacillus Calmette-Guérin pleural infection was used to validate the involvement of tuberculous fibrosis to tumor invasion.
RESULTS
Increased CXCL9 and CXCL10 levels of TPE induced M2 Arg-1 MФ polarization of murine bone marrow-derived MФ. TPE-induced M2 Arg-1 MФ polarization facilitated lung cancer proliferation via autophagy signaling and E-cadherin signaling in vitro. An inhibitor of arginase-1 targeting M2 Arg-1 MФ both in vitro and in vivo significantly reduced tuberculous fibrosis-induced metastatic potential of lung cancer and decreased autophagy signaling and E-cadherin expression.
CONCLUSION
Tuberculous pleural fibrosis induces M2 Arg-1 polarization, and M2 Arg-1 MФ contribute to lung cancer metastasis via autophagy and E-cadherin signaling. Therefore, M2 Arg-1 tumor associated MФ may be a novel therapeutic target for tuberculous fibrosis-induced lung cancer progression.
Topics: Animals; Lung Neoplasms; Humans; Mice; Autophagy; Arginase; Disease Progression; Signal Transduction; Macrophages; Tuberculosis, Pleural; A549 Cells; Mice, Inbred C57BL; Pleural Effusion; Cell Polarity
PubMed: 38720340
DOI: 10.1186/s12931-024-02829-8 -
Investigative and Clinical Urology May 2024This study investigated the efficacy of intravesical gemcitabine as an alternative to bacillus Calmette-Guérin (BCG) therapy. (Comparative Study)
Comparative Study
Comparative analysis of recurrence rates between intravesical gemcitabine and bacillus Calmette-Guérin induction therapy following transurethral resection of bladder tumors in patients with intermediate- and high-risk bladder cancer: A retrospective multicenter study.
PURPOSE
This study investigated the efficacy of intravesical gemcitabine as an alternative to bacillus Calmette-Guérin (BCG) therapy.
MATERIALS AND METHODS
Data were retrospectively collected across seven institutions from February 1999 to May 2023. Inclusion criteria included patients with intermediate- or high-risk non-muscle invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumors (TURBT) and received at least four sessions of intravesical gemcitabine or BCG induction therapy. Patient characteristics, complete remission (CR), occurrence, and progression rates were compared.
RESULTS
In total, 149 patients were included in this study (gemcitabine, 63; BCG, 86). No differences were apparent between the two groups in baseline characteristics, except for the follow-up period (gemcitabine, 9.2±5.9 months vs. BCG, 43.9±41.4 months, p<0.001). There were no consistent significant differences observed between the two groups in the 3-month (gemcitabine, 98.4% vs. BCG, 95.3%; p=0.848), 6-month (94.9% vs. 90.0%, respectively; p=0.793) and 1-year CR rates (84.2% vs. 83.3%, respectively; p=0.950). Also, there was no significant statistical difference in progression-free survival between the two groups (p=0.953). The occurrence rates of adverse events were similar between the groups (22.2% vs. 22.1%; p=0.989); however, the rate of Clavien-Dindo grade 2 or higher was significantly higher in the BCG group (1.6% vs. 16.3%, respectively; p<0.001).
CONCLUSIONS
Intravesical gemcitabine demonstrated efficacy comparable to BCG therapy for the first year in patients with intermediate- and high-risk NMIBC. However, long-term follow-up studies are warranted.
Topics: Humans; Urinary Bladder Neoplasms; Gemcitabine; Deoxycytidine; Retrospective Studies; BCG Vaccine; Male; Female; Administration, Intravesical; Aged; Neoplasm Recurrence, Local; Antimetabolites, Antineoplastic; Middle Aged; Adjuvants, Immunologic; Cystectomy; Risk Assessment; Urethra
PubMed: 38714515
DOI: 10.4111/icu.20230313