TuberculosisPub Date : 2026-01-01Epub Date: 2025-12-18DOI: 10.1016/j.tube.2025.102723
Qiangsen Zhong , Xiaochun Wang , Yun Xu , Runlin Wang , Mingming Zhou , Xinkuang Liu
{"title":"Response to “Constructive appraisal of Zhong et al.’s study on Mycobacterium tuberculosis dormant antigens and PB2-DIMQ vaccine: Opportunities for translational strengthening”","authors":"Qiangsen Zhong , Xiaochun Wang , Yun Xu , Runlin Wang , Mingming Zhou , Xinkuang Liu","doi":"10.1016/j.tube.2025.102723","DOIUrl":"10.1016/j.tube.2025.102723","url":null,"abstract":"","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"156 ","pages":"Article 102723"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145828394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TuberculosisPub Date : 2026-01-01Epub Date: 2025-12-11DOI: 10.1016/j.tube.2025.102721
K.M. Venkatesh , Nicolas Lopez-Villalobos , Sandeep K. Gupta , Garry B. Udy , Richard Laven , Shih-Jiuan Chiu , Piyush Bugde , Yoichi Furuya , Venkata Sayoji Rao Dukkipati
{"title":"Responses to comments on “A comparative study between milk- and serum-based antibody detection assays for Johne's disease in New Zealand dairy cattle”","authors":"K.M. Venkatesh , Nicolas Lopez-Villalobos , Sandeep K. Gupta , Garry B. Udy , Richard Laven , Shih-Jiuan Chiu , Piyush Bugde , Yoichi Furuya , Venkata Sayoji Rao Dukkipati","doi":"10.1016/j.tube.2025.102721","DOIUrl":"10.1016/j.tube.2025.102721","url":null,"abstract":"","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"156 ","pages":"Article 102721"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145840561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comments on “A comparative study between milk- and serum-based antibody detection assays for Johne's disease in New Zealand dairy cattle”","authors":"Arun Kumar, Ankur Sharma, Saumya Das, Preeti Dnyandeo Sonje, Dhanya Dedeepya","doi":"10.1016/j.tube.2025.102719","DOIUrl":"10.1016/j.tube.2025.102719","url":null,"abstract":"","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"156 ","pages":"Article 102719"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145775947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TuberculosisPub Date : 2025-12-01Epub Date: 2025-10-14DOI: 10.1016/j.tube.2025.102698
Qiangsen Zhong , Xiaochun Wang , Yun Xu , Runlin Wang , Mingming Zhou , Xinkuang Liu
{"title":"Diagnostic value of five Mycobacterium tuberculosis dormant highly expressed antigens in latent infections and immunogenicity assessment of a novel subunit vaccine PB2-DIMQ","authors":"Qiangsen Zhong , Xiaochun Wang , Yun Xu , Runlin Wang , Mingming Zhou , Xinkuang Liu","doi":"10.1016/j.tube.2025.102698","DOIUrl":"10.1016/j.tube.2025.102698","url":null,"abstract":"<div><div>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 <em>Mycobacterium tuberculosis</em> (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<sup>+</sup>/CD8<sup>+</sup> IFN-γ<sup>+</sup> IL-2<sup>+</sup>), 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.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"155 ","pages":"Article 102698"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Diagnosing tuberculous meningitis from cell-free DNA by multi-targeted real-time PCR: An experience from 170 cases","authors":"Kusum Sharma , Megha Sharma , Ritu Shree , Neeraj Singla , Himanshu Joshi , Ashish Kumar Kakkar , Apinderpreet Singh , Aman Sharma , Navneet Sharma , Manish Modi","doi":"10.1016/j.tube.2025.102705","DOIUrl":"10.1016/j.tube.2025.102705","url":null,"abstract":"<div><h3>Setting</h3><div>and objective: To evaluate the diagnostic utility of Cell-free DNA (Cf-DNA)-based multi-targeted real-time PCR (Mrt-PCR) for diagnosing tuberculous meningitis, the most severe form of extrapulmonary tuberculosis.</div></div><div><h3>Design</h3><div>A total of 170 cerebrospinal fluid samples (CSF) of tuberculous meningitis [Definite TBM (n = 146), Probable TBM (n = 24)] and 100 non-TB controls were subjected to Cf-DNA Mrt-PCR test using IS6110, IS1081, and nrdZ gene targets. The performance was also evaluated against Truenat MTB Plus assay and GeneXpert MTB/RIF Ultra.</div></div><div><h3>Results</h3><div>The sensitivity, specificity, positive predictive value and negative predictive value of Cf-DNA M-rtPCR was 78.24 %, 100 %, 100 % and 72.99 %, respectively in overall diagnosis of TBM and 82.88 %, 100 %, 100 % and 80 %, respectively in diagnosing ‘definite’ TBM. Cf-DNA M-rtPCR detected 14 additional cases that were missed by Truenat MTB Plus assay and GeneXpert MTB/RIF Ultra. Among the different gene targets used, eight cases were detected only by IS1081, three only by IS6110 and one only by nrdZ gene. Six cases were reported rifampicin-resistant by both Truenat MTB Plus assay and GeneXpert MTB/RIF Ultra and were also confirmed by rpoB sequencing.</div></div><div><h3>Conclusion</h3><div>The detection of cell-free DNA, along with M-rtPCR could serve as a reliable tool for diagnosing tuberculous meningitis directly from CSF samples.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"155 ","pages":"Article 102705"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145460106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TuberculosisPub Date : 2025-12-01Epub Date: 2025-10-10DOI: 10.1016/j.tube.2025.102697
Eamonn Gormley , David E. MacHugh , Kieran G. Meade
{"title":"Epigenetic regulation of the immune response to Mycobacterium bovis infection in cattle: potential implications for diagnostic test sensitivity","authors":"Eamonn Gormley , David E. MacHugh , Kieran G. Meade","doi":"10.1016/j.tube.2025.102697","DOIUrl":"10.1016/j.tube.2025.102697","url":null,"abstract":"<div><div>As a zoonotic disease, with a global impact on animal health, welfare and trade, bovine tuberculosis (bTB), caused by infection with <em>Mycobacterium bovis</em>, 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 <em>M. bovis</em>-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 <em>M. bovis</em> 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 <em>Mycobacterium tuberculosis</em> 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 <em>M. bovis</em> 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 <em>M. tuberculosis</em> infection, this review explores the evidence for epigenetic control of the immune response to <em>M. bovis</em> and bTB disease by methylation and acetylation of host chromosomes. Understanding the extent and nature of epigenetic control may reveal how <em>M. bovis</em> coevolution with the bovine host shapes both immune outcomes and diagnostic test sensitivity.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"155 ","pages":"Article 102697"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145303558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TuberculosisPub Date : 2025-12-01Epub Date: 2025-10-24DOI: 10.1016/j.tube.2025.102701
Theophilus Afum, Prince Asare, Stephen Osei-Wusu, Dorothy Yeboah-Manu
{"title":"Restriction of the main lineages of Mycobacterium africanum to West Africa: Insights from host-pathogen interaction studies","authors":"Theophilus Afum, Prince Asare, Stephen Osei-Wusu, Dorothy Yeboah-Manu","doi":"10.1016/j.tube.2025.102701","DOIUrl":"10.1016/j.tube.2025.102701","url":null,"abstract":"<div><div>Tuberculosis (TB), a disease of old, continues to plague humans after its declaration as a global health emergency in 1993. Over the years, studies have focused on understanding the causative pathogen, <em>Mycobacterium tuberculosis</em> complex (MTBC), and its interaction with humans from TB infection to progression to active disease. It is now known that MTBC lineage diversity impacts several disease presentations and outcomes, including disease progression and severity, virulence and antimicrobial resistance, transmissibility, and host response. Some of these lineages are highly geographically restricted, and prominent amongst them are lineages 5 and 6 of <em>Mycobacterium africanum (Maf</em>), mainly found in West Africa, with cases outside of this region usually prevalent in individuals of West African descent. Several hypotheses have been propounded to investigate these restrictions, ranging from the locality of an animal reservoir in certain areas to the emigration of <em>Maf</em> into West Africa but not spreading globally because <em>Mycobacterium tuberculosis</em> sensu stricto (<em>Mtbss</em>) outcompeted it. Another hypothesis, which states that host genetic factors can influence host susceptibility to some MTBC lineages, as well as TB progression to the severe disease state, appears more widely accepted. However, the exact mechanisms mediating this susceptibility have not been fully explored. This review seeks to highlight the advances made towards understanding the geographical restrictions of <em>Maf</em> and the host-pathogen interactions leading to the coevolution of <em>Maf</em> and humans in West Africa.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"155 ","pages":"Article 102701"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145422961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Response to “Correspondence on ‘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”","authors":"Neha Jindal, Manisha Dass, Pratibha Sharma, Sagarika Haldar","doi":"10.1016/j.tube.2025.102699","DOIUrl":"10.1016/j.tube.2025.102699","url":null,"abstract":"","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"155 ","pages":"Article 102699"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145535028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TuberculosisPub Date : 2025-12-01Epub Date: 2025-09-19DOI: 10.1016/j.tube.2025.102693
Yufan Xu , Longlong Wang , Jijie Jiang , Guocheng Zhao , Zhe Wang
{"title":"Knockdown of argininosuccinate lyase influences the growth of Mycolicibacterium smegmatis in vitro and in vivo","authors":"Yufan Xu , Longlong Wang , Jijie Jiang , Guocheng Zhao , Zhe Wang","doi":"10.1016/j.tube.2025.102693","DOIUrl":"10.1016/j.tube.2025.102693","url":null,"abstract":"<div><div>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 <em>Mycolicibacterium smegmatis</em> (formerly <em>Mycobacterium smegmatis</em>). 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 <em>M. smegmatis</em> proliferation by disrupting amino acid homeostasis and interfering with aerobic respiration.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"155 ","pages":"Article 102693"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TuberculosisPub Date : 2025-12-01Epub Date: 2025-09-05DOI: 10.1016/j.tube.2025.102688
Promod K. Mehta, Jefry Sebastian
{"title":"Diagnosis of extrapulmonary tuberculosis by Truenat® MTB/MTB Plus assay","authors":"Promod K. Mehta, Jefry Sebastian","doi":"10.1016/j.tube.2025.102688","DOIUrl":"10.1016/j.tube.2025.102688","url":null,"abstract":"<div><div>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), <em>i.e</em>. in-house PCR/multiplex-PCR, commercial real-time PCR (<em>e.g.</em> Cobas TaqMan/LightCycler), line probe assay (<em>e.g.</em> 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 <em>nrdB</em>, while TruPlus targets IS<em>6110</em>+<em>nrdZ</em> for the identification of <em>Mtb</em> within 1 h. After a positive result, an ‘add-on’ chip, <em>i.e</em>. 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, <em>i.e</em>. 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.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"155 ","pages":"Article 102688"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145158213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}