Tuberculosis (Edinburgh, Scotland)[JOURNAL]
Sun
200 papers
Diagnostic value of five Mycobacterium tuberculosis dormant highly expressed antigens in latent infections and immunogenicity assessment of a novel subunit vaccine PB2-DIMQ.
Zhong Q, Wang X, Xu Y … +3 more , Wang R, Zhou M, Liu X
Tuberculosis (Edinb) · 2025 Dec · PMID 41108940 · Publisher ↗
Tuberculosis (TB) is the leading cause of death in global infectious diseases, and precise diagnosis and preventive intervention of latent tuberculosis infection (LTBI) are important to end the TB epidemic. In this study...
Tuberculosis (TB) is the leading cause of death in global infectious diseases, and precise diagnosis and preventive intervention of latent tuberculosis infection (LTBI) are important to end the TB epidemic. In this study, we explored the diagnostic value of five Mycobacterium tuberculosis (MTB) dormant highly expressed antigens (Rv0470c, Rv2026c, Rv2466c, Rv3334, and Rv3406) in LTBI and evaluated the immunologic efficacy of a novel subunit vaccine, PB2-DIMQ (antigen PB2:Rv0470c-Rv1846c; adjuvant DIMQ: liposome dimethyl dioctadecylammonium bromide [DDA] + imiquimod [IMQ]). It was found that all five antigens were generally capable of eliciting immune responses among patients with LTBI and those with active tuberculosis (ATB). Although differences in the intensity of responses were present for some antigens between the two groups, their discriminatory power in differentiating LTBI from ATB was limited (AUC = 0.6622-0.7473). Nevertheless, these antigens still hold promising potential for application in the diagnosis of MTB infection (AUC = 0.7415-0.9556). On the other hand, under the prime-boost strategy, the PB2-DIMQ vaccine induced a significantly stronger Th1-type immune response than BCG in a mouse model, promoting the expansion of multifunctional T cells (CD4/CD8 IFN-γ IL-2), and enhanced in vitro bacterial inhibition. This study provides new targets and strategies (fusion antigen PB2 + adjuvant DIMQ) for the development of novel TB diagnostic tools and next-generation TB vaccines with important clinical translational prospects.
Letter to Editor: manuscript entitled "Utility of pleural fluid-derived extracellular vesicles as a source of Mycobacterium tuberculosis antigens MPT51 and MPT64 for pleural TB diagnosis: a proof-of-concept study" by Jindal et al. published in Tuberculosis150 (2025) 102578.
Mehta PK
Tuberculosis (Edinb) · 2025 Dec · PMID 41107155 · Publisher ↗
Abstract loading — click title to view on PubMed.
Epigenetic regulation of the immune response to Mycobacterium bovis infection in cattle: potential implications for diagnostic test sensitivity.
Gormley E, MacHugh DE, Meade KG
Tuberculosis (Edinb) · 2025 Dec · PMID 41092792 · Publisher ↗
As a zoonotic disease, with a global impact on animal health, welfare and trade, bovine tuberculosis (bTB), caused by infection with Mycobacterium bovis, has been subject to strict control measures in many countries to r...
As a zoonotic disease, with a global impact on animal health, welfare and trade, bovine tuberculosis (bTB), caused by infection with Mycobacterium bovis, has been subject to strict control measures in many countries to reduce the impact of the disease on cattle and their handlers. However, eradication efforts have been constrained in some countries for several reasons, including limitations in diagnostic test sensitivity. As a result, a proportion of M. bovis-infected cattle are being misdiagnosed, which then become reservoirs of infection contributing to further spread of disease. A significant amount of research effort has focused on understanding the immune responses to M. bovis infection in cattle and on investigating how these can be leveraged to improve diagnostic performance. More recently, and predominantly in human and murine models of Mycobacterium tuberculosis infection, there has been a growing recognition that chemical modifications to DNA and proteins (referred collectively to as epigenetic mechanisms), which spatially govern gene activity across host chromosomes, can directly regulate the immune responses. However, knowledge of epigenetic changes in response to M. bovis infection in cattle is still in its infancy. Epigenetic "marks" (e.g., DNA methylation and histone modifications) are dynamic, and alterations induced by the infecting pathogen lead to a complex biochemical interplay that can ultimately determine the infection outcome. Drawing on the extensive wealth of epigenetic findings from studies on M. tuberculosis infection, this review explores the evidence for epigenetic control of the immune response to M. bovis and bTB disease by methylation and acetylation of host chromosomes. Understanding the extent and nature of epigenetic control may reveal how M. bovis coevolution with the bovine host shapes both immune outcomes and diagnostic test sensitivity.
Comparative analysis of lymphocyte subsets in tuberculosis, NTM infections, and other respiratory diseases.
Wang L, Cheng LP, Shen XN … +7 more , Yu Y, Cao J, Liu ZB, Qu Q, Wu XC, Sha W, Sun Q
Tuberculosis (Edinb) · 2025 Dec · PMID 41086538 · Publisher ↗
OBJECTIVE: This study aimed to analyze the differences in lymphocyte subsets and immune function between tuberculosis (TB) and nontuberculous mycobacterial pulmonary disease (NTM-PD), thereby deepening the understanding...
OBJECTIVE: This study aimed to analyze the differences in lymphocyte subsets and immune function between tuberculosis (TB) and nontuberculous mycobacterial pulmonary disease (NTM-PD), thereby deepening the understanding of the pathogenesis of these diseases and providing important insights for clinical diagnosis, treatment, and prognosis evaluation. METHODS: Patients with pulmonary imaging abnormalities admitted to the Tuberculosis Department of Shanghai Pulmonary Hospital from January 2023 to December 2023 were included. Based on diagnostic assessments, they were categorized into active tuberculosis (ATB), NTM-PD, and other pulmonary diseases (including inflammatory and neoplastic lung diseases). Flow cytometry was used to detect lymphocyte subset counts. RESULTS: (1) There were no significant differences in lymphocyte subset counts between the ATB and NTM groups; however, both groups showed marked differences when compared with the group of patients with other respiratory diseases. Specifically, the percentages and absolute counts of CD3 T cells, CD4 T cells, CD8 T cells, and CD19 B cells were significantly lower in the ATB and NTM groups, whereas the levels of CD1656 natural killer (NK) cells were higher compared to those with other respiratory diseases.(2) Patients in the non-severe ATB (nSATB) group exhibited higher levels of CD3 T cells and CD19 B cells compared to those in the severe ATB (SATB) group.(3) Among patients with ATB, those with concomitant diabetes had lower CD8 T cell counts and percentages, as well as a higher CD4/CD8 ratio, compared to those without diabetes.(4) In patients with NTM-PD, those with severe disease had lower percentages of CD1656 NK cells than those with non-severe NTM-PD.(5) No significant differences in lymphocyte subset parameters were observed between drug-resistant and drug-sensitive ATB patients, or between patients with rapidly growing and slowly growing NTM species. CONCLUSION: This study revealed the lymphocyte subset characteristics of patients with TB and NTM infections and identified potential associations between disease severity, diabetes comorbidities, and immune cell subsets with disease status. These findings provide a basis for further research on the immune mechanisms of infectious pulmonary diseases and contribute to the development of precision medicine strategies.
Analysis of tuberculosis infection dynamics using Caputo fractional-order models with diagnosis and treatment interventions.
Abiodun OE, Olayiwola MO
Tuberculosis (Edinb) · 2025 Dec · PMID 41067169 · Publisher ↗
This paper develops and analyzes a Caputo fractional-order mathematical model for tuberculosis (TB) transmission that incorporates testing, therapy, isolation, and treatment interventions. The model divides the populatio...
This paper develops and analyzes a Caputo fractional-order mathematical model for tuberculosis (TB) transmission that incorporates testing, therapy, isolation, and treatment interventions. The model divides the population into five compartments-susceptible, exposed, infectious, isolated, and recovered-and its qualitative properties, including positivity, boundedness, existence, and uniqueness of solutions, are established. The basic reproduction number R is derived, and sensitivity analysis identifies transmission, progression, testing, and treatment rates as critical drivers of TB dynamics. Using the Laplace-Adomian decomposition method (LADM), numerical simulations are performed to assess the impact of fractional-order derivatives on disease spread and control. The results show that increasing the order of the fractional derivative enhances the accuracy of the model and reveals memory effects in TB dynamics. Moreover, early diagnosis, therapy, and isolation significantly reduce infection levels and improve recovery outcomes. These findings highlight the advantages of fractional-order models over classical approaches and provide valuable insights for designing effective TB control strategies.
Evaluating selection at intermediate scales within genes provides robust identification of genes under positive selection in M. tuberculosis clinical isolates.
Ioerger TR, Shatby A
Tuberculosis (Edinb) · 2025 Dec · PMID 41033137 · Full text
Multiple studies have reported genes in the M. tuberculosis (Mtb) genome that are under diversifying selection, based on genetic variants among Mtb clinical isolates. These might reflect adaptions to selection pressures...
Multiple studies have reported genes in the M. tuberculosis (Mtb) genome that are under diversifying selection, based on genetic variants among Mtb clinical isolates. These might reflect adaptions to selection pressures associated with modern clinical treatment of TB. Many, but not all, of these genes under selection are related to drug resistance. Most of these studies have evaluated selection at the gene-level. However, positive selection can be evaluated on different scales, including individual sites (codons) and local regions within an ORF. In this paper, we use GenomegaMap, a Bayesian method for calculating selection, to evaluate selection of genes in the Mtb genome at all three levels. We present evidence that the intermediate analysis (windows of codons) yields the most credible list of candidate genes under selection (excluding PPE and PE_PGRS genes, which are predicted less reliably due to frequent sequencing errors). A further advantage of this approach is that it identifies specific regions within proteins that are under selective pressure, which is useful for structural and functional interpretation. In an analysis of two separate collections of Mtb clinical isolates (from Moldova; and a globally-representative set), we observed 53 and 173 significant genes under selection, with 36 % overlap. The lists of genes under selection include many drug-resistance genes, as well as other genes that have previously been reported to be under selection (resR, phoR). The specific regions under selection identified within drug-resistance genes are shown to correspond to protein structural features known to be involved in resistance, supporting accuracy of the method. Positive selection in several ESX-1-related genes was also observed, suggesting adaptation to immune pressure.
Diagnosis of extrapulmonary tuberculosis by Truenat® MTB/MTB Plus assay.
Mehta PK, Sebastian J
Tuberculosis (Edinb) · 2025 Dec · PMID 41014808 · Publisher ↗
Diagnosis of extrapulmonary tuberculosis (EPTB) is challenging. During the last two decades, several nucleic acid amplification tests have been deliberated to diagnose TB (including EPTB) and drug resistance (DR), i.e. i...
Diagnosis of extrapulmonary tuberculosis (EPTB) is challenging. During the last two decades, several nucleic acid amplification tests have been deliberated to diagnose TB (including EPTB) and drug resistance (DR), i.e. in-house PCR/multiplex-PCR, commercial real-time PCR (e.g. Cobas TaqMan/LightCycler), line probe assay (e.g. GenoType MTBDRplus), GeneXpert®/GeneXpert® Ultra and Truenat®MTB/MTB Plus (TruPlus). However, we still need a simple and reliable diagnostic test especially for remote areas. Markedly, both GeneXpert/Xpert Ultra require a constant power supply and their high cost is a major hindrance in resource-limited settings. To overcome this, Molbio Diagnostics, India, introduced a Truenat/TruPlus assay (the WHO endorsed), which is chip-based micro real-time PCR system that targets nrdB, while TruPlus targets IS6110+nrdZ for the identification of Mtb within 1 h. After a positive result, an 'add-on' chip, i.e. Truenat® MTB-RIF Dx (TruRif) is utilized to detect rifampicin-resistance (RIF-R) that takes another 1 h. Although there is adequate literature on the diagnosis of pulmonary TB by Truenat/TruPlus, limited information is available on EPTB diagnosis. In this review, we assessed the performance of Truenat/TruPlus in different EPTB types, i.e. TB lymphadenitis, TB pleuritis, TB meningitis, osteoarticular TB, etc. that exhibits moderate to good sensitivity/specificity. Meanwhile, few false negative/positive RIF-R results are obtained by TruRif. Since Truenat/TruPlus is portable, battery-operated and relatively cost-effective as compared to GeneXpert/Xpert Ultra, it can be utilized for preliminary screening of EPTB specimens in peripheral settings, which may be further confirmed by other tests.
Exploring CHIT1 and YKL-40 in tuberculous pleural effusion: Insights and implications.
Przysucha N, Paplińska-Goryca M, Górska K … +4 more , Misiukiewicz-Stępień P, Mlącki M, Cyran A, Krenke R
Tuberculosis (Edinb) · 2025 Dec · PMID 40992204 · Publisher ↗
BACKGROUND: Chitinases and chitinase-like proteins are implicated in the pathophysiology of lung diseases. This study aimed to evaluate the significance of chitotriosidase (CHIT1) and YKL-40 in tuberculous pleural effusi...
BACKGROUND: Chitinases and chitinase-like proteins are implicated in the pathophysiology of lung diseases. This study aimed to evaluate the significance of chitotriosidase (CHIT1) and YKL-40 in tuberculous pleural effusion (TPE), identify their cellular sources, and assess their diagnostic potential as TPE biomarkers. METHODS: This observational, retrospective study included 66 patients with pleural effusion of different origins: malignant (MPE), tuberculous (TPE), parapneumonic (PPE), and transudative (TE). Pleural fluid levels of YKL-40 and CHIT1 were measured. Expressions of YKL-40 and CHIT1 in tuberculous pleural granulomas were also assessed using immunohistochemical staining. RESULTS: We found the highest median CHIT1 and YKL-40 levels for TPE: 70.51 (interquartile range [IQR] 49.65-136.98) ng/mL and 569.84 (IQR 530.32-706.01) ng/mL, respectively. YKL-40 was significantly higher in TPE than in PPE (387.98 [IQR 262.94-539.09] ng/mL, p < 0.01)] and TE (254.95 [IQR 188.93-334.1 ng/ml] ng/mL, p < 0.001). There was a strong positive correlation between the YKL-40 level in TPE and the percentage of macrophages (r = 0.73, p = 0.003) and the adenosine deaminase activity (r = 0.82, p < 0.001). We revealed strong YKL-40 expression in tuberculoid pleural granulomas. CONCLUSION: YKL-40, but not CHIT-1, may contribute to the pleural inflammatory response associated with tuberculosis.
Knockdown of argininosuccinate lyase influences the growth of Mycolicibacterium smegmatis in vitro and in vivo.
Xu Y, Wang L, Jiang J … +2 more , Zhao G, Wang Z
Tuberculosis (Edinb) · 2025 Dec · PMID 40992203 · Publisher ↗
The rising prevalence of drug-resistant tuberculosis (DR-TB), coupled with stagnation in the development of novel therapeutics, underscores the urgent need for new drug targets and innovative anti-tuberculosis agents. In...
The rising prevalence of drug-resistant tuberculosis (DR-TB), coupled with stagnation in the development of novel therapeutics, underscores the urgent need for new drug targets and innovative anti-tuberculosis agents. In this study, we demonstrate that CRISPR interference-mediated knockdown of argH, a nitrogen metabolism-associated gene encoding argininosuccinate lyase, significantly impairs the growth of Mycolicibacterium smegmatis (formerly Mycobacterium smegmatis). This growth defect was alleviated in a concentration-dependent manner by arginine supplementation. In a goldfish infection model, argH knockdown led to a marked reduction in bacterial burden within both liver and kidney tissues. Notably, bacitracin and 5-fluorouracil exhibited synergistic effects when combined with argH knockdown. Metabolomic profiling revealed significant perturbations in multiple amino acids, as well as in succinyl-CoA and lactate levels, suggesting that suppression of argH impairs M. smegmatis proliferation by disrupting amino acid homeostasis and interfering with aerobic respiration.
Whole-genome sequencing-based surveillance system for Mycobacterium tuberculosis in Portugal.
Pinto M, Macedo R
Tuberculosis (Edinb) · 2025 Dec · PMID 40967101 · Publisher ↗
To improve TB surveillance and diagnosis, the Portuguese National Reference Laboratory (NRL) began implementing whole-genome sequencing (WGS) for all RR/MDR-TB cases in 2019. Since 2020, this approach has been expanded t...
To improve TB surveillance and diagnosis, the Portuguese National Reference Laboratory (NRL) began implementing whole-genome sequencing (WGS) for all RR/MDR-TB cases in 2019. Since 2020, this approach has been expanded to indiscriminately include all received isolates. We describe the current WGS-based surveillance system in Portugal, framed in prospective and retrospective data (n = 1171), upgraded for antimicrobial resistance (AMR) prediction and epidemiological analysis. This system relies on three main steps: QC/QA and contamination assessment, with a novel data filtering step; genotyping and AMR prediction; and dynamic SNP-based approach, maximizing variable sites under analysis. While lineage 4 was the most prevalent (84.3 %) followed by lineage 2 (9.1 %), less common EU/EEA sub-lineages (e.g., lineages 3 and 6) showcased cross-border transmissions. Molecular clusters (n = 157) displayed distinct AMR profiles and diverse possible epidemiological contexts. Among the pipeline upgrades, we highlight: i) the novel filtering step that allowed the improvement of 123 out of 128 contaminated samples; ii) tolerating missing data per site more than doubled core variable site resolution; iii) automatic maximization of shared variable sites for in-depth cluster analysis, key for consolidating genetic links in epidemiological investigation. This study highlights the importance of sustained prospective genomic surveillance towards strengthening TB management and diagnosis in Portugal.
M. bovis FadR mutant exhibits an altered colony morphotype and increased virulence.
Singh V, Ansari MM, Dutta D … +3 more , Rajmani RS, Singh A, Singh BN
Tuberculosis (Edinb) · 2025 Dec · PMID 40939556 · Publisher ↗
FadR, a GntR family transcriptional regulator, is known to maintain fatty acid homeostasis in prokaryotes. In this study, a fadR deletion mutant was generated in Mycobacterium bovis, which exhibited distinct morphologica...
FadR, a GntR family transcriptional regulator, is known to maintain fatty acid homeostasis in prokaryotes. In this study, a fadR deletion mutant was generated in Mycobacterium bovis, which exhibited distinct morphological changes, along with enhanced permeability and increased antibiotic susceptibility. Interrupted cell-wall homeostasis often leads to such collateral phenotype. To gain insight into the lipid profile, we conducted lipidomics analysis, which revealed that the levels of DAT and PAT were higher in the mutant, while keto-mycolate methyl esters were lower. Further, key proteins responsible for altered phenotypes and lipid profiles were identified using a comparative proteomics approach between M. bovis and the ΔfadR mutant. In addition to lipid metabolism, several intermediary metabolic and stress response proteins predicted to have roles in the growth, survival, and pathogenicity of mycobacteria were also altered in the mutant. Notably, deletion of fadR led to hypervirulence in the animal model. Taken together, this study establishes a crucial role of FadR in the survival of mycobacteria by regulating lipid metabolism, providing insights into its potential as a target for therapeutic strategies against slow-growing mycobacteria.
A comparative study between milk- and serum-based antibody detection assays for Johne's disease in New Zealand dairy cattle.
Venkatesh KM, Lopez-Villalobos N, Gupta SK … +6 more , Udy GB, Laven R, Chiu SJ, Bugde P, Furuya Y, Dukkipati VSR
Tuberculosis (Edinb) · 2025 Dec · PMID 40908228 · Publisher ↗
Dairy cattle are affected by Johne's disease. It is caused by Mycobacterium avium subspecies paratuberculosis (MAP). Suboptimal diagnostic tests add more to the productivity loss resulting from this disease. Agreement be...
Dairy cattle are affected by Johne's disease. It is caused by Mycobacterium avium subspecies paratuberculosis (MAP). Suboptimal diagnostic tests add more to the productivity loss resulting from this disease. Agreement between and within different commercial kits is crucial in the decision-making process of disease surveillance programmes. This study compared two ELISAs, that is, Johne's disease commercial antibody detection kits (A and B), using milk and serum samples from New Zealand dairy cattle. These results were also compared with a subset of faecal PCR results. Five scenarios were considered for the comparison of ELISA tests. The point estimates of kappa coefficients (k) between the serum (0.84-0.94) assays were higher than the milk assays (0.59-0.82). The point estimates of kappa coefficients between serum and milk ELISA outcomes were higher for kit B (k = 0.79-0.86) than for kit A (k = 0.55-0.79). The point estimates of kappa coefficients between the ELISA and faecal PCR outcomes varied between 0.43 and 0.74. ELISA tests had point estimates of sensitivity ranging from 0.67 to 0.88 and specificity from 0.62 to 0.93, relative to the faecal PCR test. Results suggest that serum provides a better choice of sample type when both commercial kits A and B are used for Johne's disease surveillance of dairy cattle in New Zealand. Milk assays can be cost-effective to diagnose MAP-positive animals; kit B can be best suited for New Zealand conditions, provided the repeatability of the results is validated.
ESAT-6 of Mycobacterium tuberculosis downregulates cofilin1, leads to filamentous actin enrichment and reduces the phagosome acidification in infected macrophages, which are partially reversed by a single methionine mutation.
Mahesh PP, Retnakumar RJ, Sivakumar KC … +1 more , Mundayoor S
Tuberculosis (Edinb) · 2025 Dec · PMID 40902220 · Publisher ↗
Mycobacterium tuberculosis (M. tuberculosis) persists within macrophages by evading phagosome maturation. In this study, we considered the role of actin dynamics in this process. Macrophages infected with virulent M. tub...
Mycobacterium tuberculosis (M. tuberculosis) persists within macrophages by evading phagosome maturation. In this study, we considered the role of actin dynamics in this process. Macrophages infected with virulent M. tuberculosis showed high F-actin/G-actin ratio, accompanied by reduced expression of the actin-depolymerizing protein cofilin1 and increased levels of its inactive phosphorylated form. Overexpression of a constitutively active cofilin1 variant reduced F-actin accumulation and enhanced phagosome acidification. Similar effects were observed with sorafenib, a PI3K-dependent activator of cofilin1, which decreased F-actin levels and promoted phagosome acidification in infected macrophages. Ectopic expression of the mycobacterial virulence factor ESAT-6 in macrophages led to cofilin1 downregulation. ESAT-6 also increased F-actin, altered cell morphology and impaired phagosome acidification in infections with avirulent M. tuberculosis strain. As cofilin1 is positively regulated by reactive oxygen species (ROS), we examined the role of methionine in ESAT-6-mediated ROS suppression. Mutation of methionine 93 in ESAT-6 increased intracellular ROS, enhanced phagosome acidification, and decreased F-actin levels. These findings reveal that M. tuberculosis impairs phagosome acidification by modulating host actin dynamics at least partially through ESAT-6-mediated suppression of cofilin1 and ROS. Enhancing cofilin1 activity may represent a potential therapeutic strategy to restore phagosome function and improve bacterial clearance, more specifically during the initial establishment of infection.
Response to "Correspondence on 'Analysis of the cross-study replicability of tuberculosis gene signatures using 49 curated human transcriptomic datasets'".
Wang X, Harper K, Sinha P … +2 more , Johnson WE, Patil P
Tuberculosis (Edinb) · 2025 Sep · PMID 40816961 · Publisher ↗
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Biomarkers for diagnosing pulmonary tuberculosis in adolescents: Peripheral blood monocyte myotubularin-related protein 4 and oncostatin M genes.
Sha Y, Zhou H, Yan B … +4 more , Da X, Shao M, Li Y, Ding S
Tuberculosis (Edinb) · 2025 Sep · PMID 40795778 · Publisher ↗
BACKGROUND/OBJECTIVES: Although research has increasingly been focused on pulmonary tuberculosis (PTB) in adolescents, its diagnosis remains complex and challenging. Thus, the use of host transcription markers in the dia...
BACKGROUND/OBJECTIVES: Although research has increasingly been focused on pulmonary tuberculosis (PTB) in adolescents, its diagnosis remains complex and challenging. Thus, the use of host transcription markers in the diagnosis of adolescent PTB was evaluated in this study. METHODS: The study cohort comprised 40 adolescents (aged 14-18 years) with PTB who had received their first PTB diagnosis at Anhui Provincial Chest Hospital, China, between January and December 2023 (case group) and 32 healthy adolescents who had undergone physical examinations at The First Affiliated Hospital of the University of Science and Technology of China during the same period (control group). Peripheral blood samples were collected from both groups, and isolated monocytes were subjected to transcriptome sequencing and bioinformatic analysis. The relevant genes were confirmed through quantitative polymerase chain reaction. The diagnostic value of these genes in adolescent PTB patients was analysed using receiver operating characteristic curves. Furthermore, an in vitro model was constructed by infecting THP-1 cells with the Mycobacterium tuberculosis strain H37Ra to assess whether the in vitro expression levels of the identified genes were consistent with those of the genes in the peripheral blood monocytes of adolescents with PTB. The specific mechanisms were explored using methods such as lentiviral infection, flow cytometry, immunofluorescence, Western blotting, and qRT‒PCR. RESULTS: The results revealed that the expression level of the myotubularin-related protein 4 gene (MTMR4) was lower in the case group than in the control group (P < 0.0001; area under the curve: 0.946; 95 % confidence interval: 0.893-0.999; cut-off value: 0.844; sensitivity: 0.875; specificity: 0.969). The expression level of the oncostatin M gene (OSM) was greater in the case group than in the control group (P = 0.014; area under the curve: 0.962; 95 % confidence interval: 0.914-1.000; cut-off value: 0.919; sensitivity: 0.950; specificity: 0.969). However, no significant between-group difference was detected in the expression level of the complement component 1q subcomponent A gene. The results from the in vitro experiment indicated that the expression levels of MTMR4 and OSM were consistent between the H37Ra-infected cells and the case group samples. Bioinformatics analysis revealed that cytokine-cytokine receptor interactions, JAK/STAT signalling and PI3K/cell survival-related pathways play key roles in the pathogenesis of adolescent PTB. Additionally, we found that H37Ra infection affected tuberculosis progression via the OSM/PI3K/GPX4 pathway. CONCLUSIONS: Peripheral blood monocyte OSM and MTMR4 may serve as biomarkers of adolescent PTB. We speculate that targeting the OSM signalling pathway by knocking down OSM expression or inhibiting its ligand/receptor might be a strategy to reduce pulmonary tuberculosis-related tissue damage.
Correspondence on "Analysis of the cross-study replicability of tuberculosis gene signatures using 49 curated human transcriptomic datasets".
Daungsupawong H, Wiwanitkit V
Tuberculosis (Edinb) · 2025 Sep · PMID 40774838 · Publisher ↗
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Incidence of infectious diseases in children with Mycobacterium tuberculosis in Japan, 2007-2022.
Hamaguchi Y, Yamaguchi T, Yoshiyama T
Tuberculosis (Edinb) · 2025 Sep · PMID 40752240 · Publisher ↗
The objective of this study was to understand the descriptive epidemiology of childhood tuberculosis (TB) in Japan under the 2013 Bacillus Calmette-Guérin (BCG) immunization program modification. The median percentage of...
The objective of this study was to understand the descriptive epidemiology of childhood tuberculosis (TB) in Japan under the 2013 Bacillus Calmette-Guérin (BCG) immunization program modification. The median percentage of annual vaccination coverage for infants aged <13 months was 97.0 % during follow-up (2007-2022). The age at which most infants received their vaccinations was 3 months before 2013 and 5 months after 2013. During follow-up, the number of childhood TB notifications and annual incidence declined by approximately 60 % and 40 %, respectively. A multivariate-adjusted model analysis was performed by birth year to determine the association between childhood TB and the 2013 BCG immunization program modification. However, childhood TB was associated with age and BCG vaccination history but not with the 2013 BCG immunization program modification. This study represents a valuable resource for future research, elucidating the efficacy of BCG as well as the impact of BCG policies.
Population pharmacokinetics of levofloxacin in drug-susceptible and drug-resistant tuberculosis patients: Optimal dose suggestion based on renal function.
Cho YS, Jayanti RP, Lee HK … +13 more , Kim HJ, Jang TW, Kim YS, Ko Y, Min J, Lee H, Soedarsono S, Seong HJ, Choi YK, Kim HS, Kim DH, Shin JG, cPMTb
Tuberculosis (Edinb) · 2025 Sep · PMID 40738019 · Publisher ↗
BACKGROUND: Levofloxacin (LFX) has gained attention as an effective drug to reduce treatment duration in tuberculosis (TB). We aimed to evaluate factors related to interindividual variability (IIV) and describe the pharm...
BACKGROUND: Levofloxacin (LFX) has gained attention as an effective drug to reduce treatment duration in tuberculosis (TB). We aimed to evaluate factors related to interindividual variability (IIV) and describe the pharmacokinetics (PK) of LFX in both DS- and DR-TB, as well as explore the optimal dose for TB treatment. METHODS: We included demographics, clinical information, and LFX concentrations from multinational hospitals. All data were utilized for model establishment. The population PK model was built using nonlinear mixed-effects method. Dose simulation was carried out thereafter using Monte Carlo simulation. RESULTS: A one-compartment model with allometric scaling described LFX PK adequately. PK parameters were similar between DS- and DR-TB. eGFR significantly affected CL/F, which decreased by 22 % and 48 % in mild and moderate-severe renal impairment, respectively (normal CL/F: 6.6 L/h). Considering LFX's AUC/MIC target of 146 and epidemiological cut-off value of MIC 0.5 μg/mL, doses of 1000 mg, 1250 mg, and 1500 mg may achieve 90 % probability of target attainment in patients with normal renal function weighing <40 kg, 40-70 kg, and >70 kg, respectively. CONCLUSION: Renal impairment reduced LFX clearance. Doses equal to or greater than 1000 mg may improve AUC/MIC target attainment but require cautious use considering safety and clinical efficacy.
Identification of non-tuberculous mycobacteria in slaughtered cattle from Chennai, India.
Ramanujam H, Nesakumar M, Thiruvengadam K … +4 more , Kannan R, Palanisamy S, Shanmugam S, Palaniyandi K
Tuberculosis (Edinb) · 2025 Sep · PMID 40730079 · Publisher ↗
Non-tuberculous mycobacteria (NTM) are emerging pathogens in human and veterinary medicine, with a globally increasing incidence. In India, sporadic studies have identified an upward trend in NTM infections, but accurate...
Non-tuberculous mycobacteria (NTM) are emerging pathogens in human and veterinary medicine, with a globally increasing incidence. In India, sporadic studies have identified an upward trend in NTM infections, but accurate prevalence estimates are lacking due to the absence of nationwide surveillance. Non-tuberculous mycobacteria have been reported in clinically healthy cattle and wildlife globally, complicating tuberculosis (TB) diagnostics and surveillance. This study aimed to characterize NTM species isolated from tissue samples of slaughtered cattle in Chennai using culture and targeted hsp65 gene sequencing. A total of 118 presumed NTM samples from 115 animals were processed, and 49 isolates were confirmed as NTMs by PCR. Sequencing identified 18 different species, with Mycobacterium intracellulare (9/49) being the most frequent, followed by Mycobacterium sp. strain 79_MI18_10584 (6/49) and Mycobacterium elephantis (6/49). Several identified species, including M. intracellulare, M. fortuitum (5/49), M. kansasii (4/49), and M. avium, have caused infections in humans as well. NTMs in cattle lymph nodes without visible lesions suggest their asymptomatic persistence, albeit there being a possibility of transient colonization. Non-tuberculous mycobacteria complicate bovine tuberculosis (bTB) diagnostics by inducing cross-reactive immune responses and forming granulomatous lesions resembling those caused by Mycobacterium tuberculosis complex (MTBC). This study highlights the presence and diversity of NTMs in Indian cattle and emphasizes the need for better surveillance, improved molecular characterization, and better understanding of their epidemiological and immunological roles in both veterinary and public health contexts.
MicroRNAs in exhaled breath Condensate: Novel non-invasive biomarkers for tuberculosis diagnosis.
Jaya T, Bijay P, Divyanjali R … +17 more , Naveen B, Adwika PP, Sunil B, Yadav S, Kumar S, Kumari S, Verma U, Yadav G, Dhaliwal RS, Mittal S, Tiwari P, Hadda V, Madan K, Agrawal A, Guleria R, Srivastava T, Mohan A
Tuberculosis (Edinb) · 2025 Sep · PMID 40684536 · Publisher ↗
BACKGROUND: Tuberculosis remains a significant global health issue. Sputum smear microscopy has low sensitivity, making it difficult to diagnose. Analysis of miRNA from EBC (exhaled breath condensate) offers a potential...
BACKGROUND: Tuberculosis remains a significant global health issue. Sputum smear microscopy has low sensitivity, making it difficult to diagnose. Analysis of miRNA from EBC (exhaled breath condensate) offers a potential non-invasive diagnostic method that could improve sensitivity and specificity for TB detection, including extrapulmonary TB (EPTB). METHOD: EBC was collected from 65 treatment naïve TB patients and 65 healthy controls. miRNA profiling was done on an exploratory set (n = 40) using the qRT-PCR-based miRNome profiler kit, and shortlisted miRNAs were validated in a separate set (n = 25) using qRT-PCR. ROC curves were used to evaluate diagnostic performance. RESULT: In this study, we identified eight differentially expressed miRNAs in TB vs healthy subjects (seven upregulated, one downregulated). Comparing PTB with EPTB, five miRNAs were upregulated and 68 miRNAs were downregulated in PTB. Between PTB and healthy controls, six miRNAs were upregulated and 16 miRNAs were downregulated in PTB, while in EPTB, 132 miRNAs were upregulated compared with controls. Validation confirmed upregulation of miR-454, miR-139, and miR-143 in tuberculosis. CONCLUSION: The findings of our study indicate that the expression of miR-143, miR-454, and miR-139 in exhaled breath condensate has strong potential as a non-invasive biomarker for TB diagnosis.
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