Frontiers in tuberculosis最新文献

{"title":"An integrated psycho-social intervention to improve self-efficacy toward TB treatment uptake and infection prevention among patients and family caregivers: a multicentric implementation research study protocol.","authors":"Karikalan Nagaraj, Bella Devaleenal Daniel, Chandra Suresh, Dhanalakshmi Angamuthu, Shobana Palanisamy, Muniyandi Malaisamy","doi":"10.3389/ftubr.2026.1713844","DOIUrl":"10.3389/ftubr.2026.1713844","url":null,"abstract":"<p><strong>Background: </strong>The individuals with tuberculosis (TB) experience a variety of barriers, needs, and challenges when receiving the treatment. Evidence on holistic patient-centered psychosocial interventions that promote self-efficacy and the ability to complete treatment-related tasks and goals is scarce in India.</p><p><strong>Objectives: </strong>To adapt an intervention aimed at strengthening the self-efficacy of individuals on TB treatment and their family caregivers, and to evaluate its effectiveness compared with the standard of care on the primary outcome of improved TB treatment self-efficacy and secondary outcomes of improved medication adherence, reduced TB-related stigma, and improved infection control practices.</p><p><strong>Methods: </strong>A multicentric hybrid Type I mixed method implementation research design will be used to adapt and evaluate the implementation feasibility and effectiveness of delivering a self-efficacy-based intervention under National Tuberculosis Elimination Program (NTEP) settings in India. A two-arm non-randomized cluster intervention design will be employed to evaluate the impact of a self-efficacy intervention, which includes individual counseling and peer group sessions (<i>n</i> = 240) in comparison to the standard of care (<i>n</i> = 240) on primary and secondary outcomes. Qualitative in-depth interviews and focus group discussions, guided by the Consolidated Framework for Implementation Research (CFIR), will be conducted to explore contextual factors influencing implementation.</p><p><strong>Discussion: </strong>The proposed study could generate evidence for a holistic and evidence-informed psycho-social intervention for individuals with TB and their family caregivers. It aims to improve their self-efficacy in overcoming TB treatment challenges and address the key psycho-social barriers comprehensively. Qualitative insights from the study are expected to guide/facilitate the pragmatic scale-up of self-efficacy-based interventions under the National TB program of India.</p><p><strong>Clinical trial registration: </strong>The study has been registered in the Clinical Trial Registry of India CTRI/2024/05/066847.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"4 ","pages":"1713844"},"PeriodicalIF":0.0,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The \"yeast-drop\" treatment protocol in the <i>Drosophila</i> model for rapid and cost-effective TB drug testing.","authors":"Maria Vidal, Esther Fuentes, Nerea Escobar, Marta Arch, Pere-Joan Cardona","doi":"10.3389/ftubr.2026.1746664","DOIUrl":"10.3389/ftubr.2026.1746664","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary tuberculosis (TB), caused by <i>Mycobacterium tuberculosis</i>, is the leading infectious disease globally. The lengthy treatment regimen and the potential side effects increase the probability of relapse and of developing drug resistance. These factors highlight the need for new therapeutic strategies, including host-directed therapies and anti-virulence approaches. However, the drug discovery pipeline is often limited by the simplicity of <i>in vitro</i> models and the cost and scalability challenges of mammalian <i>in vivo</i> models. In this study, we developed a cost-effective administration method using the <i>Drosophila melanogaster</i>-<i>Mycobacterium marinum</i> infection model called \"yeast-drop\". This approach facilitates oral delivery and reduces the quantity of compound currently needed for treatment in the fly model.</p><p><strong>Methods: </strong>We compared the yeast-drop methodology with the standard method commonly used in <i>Drosophila</i> studies. Additionally, we assessed the efficacy of benchmarking antibiotics, host-directed therapies (HDTs), and anti-virulence compounds for TB treatment by measuring fly survival and bacterial burden.</p><p><strong>Results: </strong>Flies treated with the \"yeast-drop\" method showed a significant improvement in survival probability and a reduction in colony-forming units (CFUs) compared to non-treated flies. This was comparable to the results achieved with the standard feeding method. Among the compounds tested, linezolid proved to be the most effective antibiotic. HDTs such as aspirin, metformin, and simvastatin also enhanced survival rates and reduced CFUs following treatment, demonstrating conserved immune and metabolic mechanisms between flies and mammals. Similarly, BBH7 and ethoxzolamide, which act as anti-virulence agents, further reinforce the translational value of this type of treatment in the <i>Drosophila</i> model.</p><p><strong>Conclusion: </strong>Overall, the <i>Drosophila</i>-<i>M. marinum</i> model, combined with the yeast-drop methodology, offers a reliable, low-cost, and biologically relevant platform for early-stage screening of antimycobacterial, host-directed, and anti-virulence compounds, effectively bridging the gap between <i>in vitro</i> systems and mammalian models.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"4 ","pages":"1746664"},"PeriodicalIF":0.0,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of a short, all oral treatment regimen including bedaquiline, delamanid, linezolid, clofazimine, and pyrazinamide named \"Regimen C\" for pre-XDR tuberculosis in Niger.","authors":"Soumana Boubacar Soumana, Abdourahamane Yacouba, Cheikh Aboubacar Abdoul Lawi, Ibrahim Oumar, Bassirou Souleymane, Alphazazi Soumana, Tapha Ounoussa, Mahamadou Doutchi, Mamane Daou, Souleymane Brah, Eric Adehossi, Saidou Mamadou","doi":"10.3389/ftubr.2025.1718997","DOIUrl":"10.3389/ftubr.2025.1718997","url":null,"abstract":"<p><strong>Background: </strong>The emergence of extensively drug-resistant tuberculosis (XDR-TB) poses a serious challenge to global tuberculosis control, particularly in high-burden countries like Niger. In 2021, a new fully oral, shorter treatment regimen, named regimen C, was adopted nationally.</p><p><strong>Aim: </strong>This study aimed to assess its effectiveness under programmatic conditions.</p><p><strong>Methods: </strong>This was a retrospective, cross-sectional study conducted from April 2021 to December 2024. All patients with pre-XDR and XDR-TB treated in one of the four multidrug-resistant (MDR) TB units in Niger, who received the new standardized regimen and completed their treatment, were included in the study.</p><p><strong>Results: </strong>A total of 16 patients with pre-XDR-TB were included in the study. Clinical, microbiological, and radiological data were collected. The median age was 30.5 [interquartile range (IQR) 25-39 years], and 62.5% of patients were male. All patients had pulmonary pre-XDR TB. At the end of treatment, a therapeutic success rate of 75.0% was observed. Adverse events occurred in 88.0% of patients, including 2 cases (14.3%) of grade 4 adverse reactions. Undernourished patients tended to have an increased risk of unfavorable treatment outcomes, although this association was not statistically significant (<i>p</i> = 0.18).</p><p><strong>Conclusion: </strong>These findings suggest that the regimen evaluated in this study appears to be effective for the management of pre-XDR tuberculosis in Niger, with a promising treatment success rate.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"3 ","pages":"1718997"},"PeriodicalIF":0.0,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bidirectional pathogenesis between non-tuberculous mycobacteria and bronchiectasis: clinical insights, diagnostic challenges and future directions-Perspectives from South Asia.","authors":"Amresh Kumar Singh, Sneha Singh, Nandini Singh, Priyanka Gaur, Ashwini Kumar Mishra, Raj Kishore Singh, Sushil Kumar","doi":"10.3389/ftubr.2025.1735568","DOIUrl":"10.3389/ftubr.2025.1735568","url":null,"abstract":"<p><p>Non-tuberculous mycobacteria (NTM) are environmental opportunistic pathogens causing chronic pulmonary disease. NTM pulmonary disease (NTM-PD) and bronchiectasis exhibit a bidirectional pathogenic relationship that is particularly under recognized in South Asian regions with high tuberculosis (TB) burden. This review article covers most of the current evidence on the epidemiology, clinical spectrum, pathogenesis, therapeutic advances of NTM-associated bronchiectasis. A well-structured literature search was conducted across PubMed, Web of Science, Scopus, and Google Scholar for articles published within from 2008 to 2025. These studies were specifically focused on NTM -associated bronchiectasis for host pathogen interactions, diagnostic strategies, and treatment outcomes. The prevalence of NTM related bronchiectasis especially with species like <i>Mycobacterium avium</i> complex and <i>Mycobacterium abscessus</i> which were more frequent pathogens all over the world. Its diagnostic dilemma with TB remains widespread due to limited lab capacity and lack of exact species identification, which leads to late or wrong diagnosis. Integration of molecular diagnostic tools, inclusion of NTM within national TB programs, and establishment of regional reference laboratories are essential to improve early detection, targeted treatment, and disease surveillance for bronchiectasis.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"3 ","pages":"1735568"},"PeriodicalIF":0.0,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148814951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A synthesis of youth activation initiatives and their impact on tuberculosis knowledge, knowledge-seeking, and healthcare-seeking behavior in vulnerable populations.","authors":"Ana-Maria Ionescu, Joelle Mak, Qu Yan, Nishant Kumar, Raghuram Rao, Sanjay Mattoo, Deepak Balasubramanian, Rachana Acharya, Subhi Quraishi, Niraj Sharma, Kep Nurliyanti, Juliana Chin, Siva Anggita, Tiffany Pakasi, Sarah Rahma, Ingrid Eshun-Wilsonova","doi":"10.3389/ftubr.2025.1668711","DOIUrl":"10.3389/ftubr.2025.1668711","url":null,"abstract":"<p><strong>Background: </strong>Annually, up to 3 million people with tuberculosis (TB) fail to receive care due to delays in seeking TB care. Alongside active case finding, identifying cost-effective strategies that successfully mobilize vulnerable populations, such as young adults, to proactively present to care early is critical for ending the TB epidemic. Enabling populations to achieve optimized knowledge levels and proactively self-present to care may be more efficient than population-wide screening.</p><p><strong>Methods: </strong>Between August 2021 and December 2023, five youth activation initiatives (\"Be the Change\", MumbraTB-ACTS, and MTV Nishedh in India; TB Warriors in Indonesia; UVTB5+ in China) were implemented. Initiatives were assessed on reach and program engagement, TB knowledge improvement, knowledge-seeking behaviors, healthcare-seeking behaviors, TB volunteering, and TB self-screening, as precursors to presentation to care. Program outcomes measurements included number of individuals reached and knowledge change before and after implementation using knowledge, attitudes, and practices (KAP) surveys. Core healthcare-seeking behavior indicators were also tracked where feasible.</p><p><strong>Results: </strong>Across programs, various strategies were implemented to reach youth including social media, hybrid case-finding, mass media, gamification and peer education, and/or volunteer-driven health promotion. Variability in measurement and reporting of program outcomes confounded the synthesis of information across initiatives, but collectively the initiatives resulted in broad reach within each local context, resulting in more than 200 million youths reached and 100 million engaged. More than 800,000 individuals reported knowledge-seeking activities with >50,000 completed KAP surveys. Initiatives demonstrated evidence of empowering communities to proactively undertake screening and/or volunteer for TB initiatives. Three also measured positive improvements in knowledge of disease transmission, symptoms, and curability.</p><p><strong>Conclusion: </strong>These data highlight several locally successful strategies for increasing TB awareness and knowledge, and encouraging TB care seeking, as well as mobilizing youth to volunteer as community TB KAP advocates. Next steps to understanding the true impact of such activation TB initiatives should include the development of a global framework to provide guidance on best practices for impact assessment, particularly at the healthcare-seeking stage. This could support healthcare workers in their provision of equitable access to quality care and implementation of TB initiatives.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"3 ","pages":"1668711"},"PeriodicalIF":0.0,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148814560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunometabolic reprogramming of <i>Mycobacterium tuberculosis</i>-responsive memory CD4⁺ T cell subsets is linked to long-term protective immunity.","authors":"Vaishnavi Kaipilyawar, Samantha Leong, Arianne Lovey, Lorenzzo L Stringari, Reynaldo Dietze, Jerrold J Ellner, Rodrigo Ribeiro-Rodrigues, Padmini Salgame","doi":"10.3389/ftubr.2026.1783887","DOIUrl":"10.3389/ftubr.2026.1783887","url":null,"abstract":"<p><strong>Introduction: </strong>Memory CD4⁺ T cells are central to long-term immunity in tuberculosis (TB), yet their functional roles that define their protective capacity remain unclear. Understanding the immune mechanisms that prevent clinical progression from latent TB infection (LTBI) to active TB disease is critical for the development of next-generation vaccines and biomarkers.</p><p><strong>Methods: </strong>We characterized the transcriptomic, metabolic, and functional programs of Mycobacterium tuberculosis (Mtb) antigen-stimulated peripheral CD4⁺ T stem cell (T-SCM), central (T-CM), transitional (T-TM), and effector (T-EM) memory subsets from individuals with remote LTBI. We utilized a multi-platform validation strategy that integrated RNA-sequencing data with protein-level metabolic profiling using \"Met-Flow\" cytometry and functional growth restriction assays to link memory CD4⁺ T cell differentiation states to immunometabolism and antimycobacterial function. Finally, we evaluated the immunometabolic profiles of memory CD4⁺ T cell subsets in an independent, longitudinal cohort of Mtb-exposed progressors and non-progressors from Brazil (GSE112104).</p><p><strong>Results: </strong>We identified a differentiation gradient associated with distinct immunometabolic states. T-SCM and T-CM subsets exhibited elevated mitochondrial activity and oxidative metabolism (fatty acid oxidation), supporting their proliferative capacity. In contrast, T-TM and T-EM subsets underwent glycolytic reprogramming and engaged the pentose phosphate pathway, which fueled enhanced cytokine production and Mtb growth restriction. Importantly, we observed that non-progressors exhibit fatty acid oxidation-driven, stem/central memory-like signatures, while progressors and active TB cases display elevated exhaustion markers, glycolytic reprogramming and pro-inflammatory profiles aligned with disease progression.</p><p><strong>Conclusion: </strong>Collectively, findings from our proof-of-concept study suggest metabolic state as a key axis connecting Mtb antigen-induced memory T cell differentiation, restimulation-induced transcriptional programming, and durability of immune control. The findings provide the basis for future longitudinal studies to examine the dynamic metabolic and functional modulation in Mtb antigen-specific memory T cell subsets from contained infection to disease progression.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"4 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13299550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148348172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acceptability and feasibility of oral swabs for tuberculosis diagnosis in young children: a qualitative study from Uganda and Peru.","authors":"Francesca W Basile, Rodrigo Calderón-Flores, Franziska Held, Luisa Pollmeier, Emmanuel Nasinghe, Godfrey Bagenda, Lazaaro Mujumbusi, Rose Namaganda, Angel Kanyange, Prossy Mbekeeka, Abner Tagoola, Jerrold J Ellner, Susan E Dorman, Moses Joloba, Carlos Zamudio, Adeodata Kekitiinwa, Rinn Song, Nora Engel","doi":"10.3389/ftubr.2026.1726647","DOIUrl":"10.3389/ftubr.2026.1726647","url":null,"abstract":"<p><strong>Background: </strong>Tuberculosis (TB) remains a leading cause of morbidity and mortality in young children, particularly in settings with limited diagnostic capacity. Oral swabs represent a promising alternative specimen type due to their ease of collection, but evidence on their acceptability and feasibility remains limited.</p><p><strong>Methods: </strong>This qualitative sub-study was nested within the NOD-pedFEND diagnostic trial evaluating novel tests for pediatric TB. We conducted semi-structured interviews and focus group discussions with 81 participants across Uganda (n=57) and Peru (n=24), including caregivers (Uganda n=30; Peru n=7), healthcare workers (Uganda n=23; Peru n=12), and National TB Program stakeholders (Uganda n=4; Peru n=5). Participants were recruited purposively from among those involved in or linked to the parent NOD-pedFEND study. Data were analyzed using thematic analysis.</p><p><strong>Results: </strong>Oral swabs were widely perceived as acceptable due to their non-invasive nature, minimal discomfort, and ease of collection. Caregivers and healthcare workers valued the reduced burden on children compared to more invasive sampling methods. Across both countries, participants expressed concerns about perceived low diagnostic sensitivity in children, particularly when compared with reference standard specimens. Despite these reservations, oral swabs were welcomed as a complementary, rather than substitute, diagnostic modality. Stakeholders highlighted their potential role within future point-of-care diagnostic strategies in low-resource settings.</p><p><strong>Conclusions: </strong>Oral swabs are acceptable and feasible for pediatric TB diagnosis in diverse settings, though concerns about sensitivity persist. Their integration as an add-on test could expand diagnostic access, especially if incorporated into scalable, point-of-care approaches.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"4 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12927657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147286842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dose optimization of inhaled tigecycline in humans to overcome inherent adverse events and maximize bacterial clearance using a physiologically-based pharmacokinetic modeling approach.","authors":"Hyunseo Park, Amarinder Singh, Ashish Srivastava, Bhargavi Thalluri, Christelle J Mathieu, Paridhi Gupta, Camron M Pearce, Malik Zohaib Ali, Ilham M Alshiraihi, Sara E Maloney Norcross, Anthony J Hickey, Mercedes Gonzalez-Juarrero, Bernd Meibohm","doi":"10.3389/ftubr.2026.1762713","DOIUrl":"10.3389/ftubr.2026.1762713","url":null,"abstract":"<p><strong>Introduction: </strong>Intrapulmonary delivery of tigecycline has been highlighted as an optimal strategy for enhancing local drug concentrations at the site of infection in the treatment of <i>Mycobacterium abscessus</i> pulmonary infections. Therefore, determining an appropriate inhaled dose is imperative to optimize therapeutic use of tigecycline. In this study, we aimed at establishing a human dose rationale for inhaled tigecycline by leveraging various preclinical experimental datasets through physiologically-based pharmacokinetic (PBPK) modeling.</p><p><strong>Methods: </strong>The PBPK model developed to predict plasma and target-site exposure of inhaled tigecycline and to relate these exposures to adverse event thresholds was derived from plasma and tissue concentration-time courses of <i>in vivo</i> mouse studies. Following inter-species scaling, the predictive performance of the model was qualified by comparing model-based simulations with experimental data in rats and literature reports in humans, thereby demonstrating its applicability across species. The final human PBPK model was utilized to predict tigecycline exposure in plasma and major organs of interest, thereby establishing the clinical utility of tigecycline inhaled dosing.</p><p><strong>Results: </strong>Using model-based simulations, we predicted the longitudinal exposure profiles of tigecycline in the systemic circulation, the epithelial lining fluid (ELF) in the lungs as site of antibacterial activity, and other major organs following inhalation under clinically relevant conditions. Intrapulmonary aerosol dosing using the currently approved intravenous dose of tigecycline was predicted to result in significantly lower plasma exposure compared to the gastrointestinal adverse event threshold reported in the literature (AUC_0-24 6.87 mg·h/L). Additionally, simulated steady-state bone concentrations remained below a threshold which has been previously defined as a steady-state trough concentration leading to bone toxicity in rats. For efficacy, intrapulmonary aerosol administration produced markedly higher peak concentrations in ELF than intravenous dosing, and the simulated exposure in ELF exceeded effective exposure levels identified in murine infection models of <i>Mycobacterium abscessus</i>.</p><p><strong>Discussion: </strong>Our findings indicate that compared to conventional intravenous infusion, inhaled tigecycline offers an improved safety margin and enhances bacterial killing. Based on simulations for multiple dosing scenarios in humans, a dose of 135 mg given every third day by intrapulmonary delivery would result in ELF, bone and plasma exposures that effectively balance efficacy and safety.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"4 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13225866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148152961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research overview-2025: integrating scientific progress to accelerate global tuberculosis elimination.","authors":"Patrick K Moonan, Timothy H Holtz","doi":"10.3389/ftubr.2026.1805962","DOIUrl":"10.3389/ftubr.2026.1805962","url":null,"abstract":"<p><p>Major scientific advances across the tuberculosis research continuum emerged in 2025, offering new opportunities to accelerate progress toward global elimination. This review synthesizes developments in diagnosis, treatment, prevention, and post-disease care, highlighting innovations that broaden access, strengthen mechanistic insight, and expand the scope of actionable tools. Diagnostic progress included artificial intelligence-enabled chest imaging, noninvasive molecular testing using tongue and stool samples, simple stool-based procedures suitable for decentralized settings, biomarkers that support treatment monitoring, low-complexity nucleic acid tests for extrapulmonary disease, and new point-of-care methods for detecting infection. Culture-free sequencing approaches further improved rapid identification of drug resistance. Therapeutic advances featured shorter all-oral regimens for drug-susceptible and rifampin-resistant disease, along with emerging compounds that target essential microbial pathways. Additional progress in host-directed therapies, vaccines, and nanoparticle-based drug delivery broadened preventive and therapeutic options. Conceptual developments challenged the validity of symptom-based disease categories and supported biologically grounded terminology, while consensus definitions for post-tuberculosis lung disease clarified the substantial long-term respiratory burden among survivors. Despite this momentum, health-system limitations and inequitable access continue to constrain real-world impact. Collectively, the scientific advances of 2025 were substantial and outline a clearer mechanistic and programmatic path toward tuberculosis elimination, but their success will depend on effective implementation and integration into routine care.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"4 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13246150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148214000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic insights into mycobacterial responses to elevated riboflavin reveal a role for flavin-sequestering proteins in flavin homeostasis.","authors":"Nurudeen Oketade, Karen M Dobos","doi":"10.3389/ftubr.2025.1719707","DOIUrl":"10.3389/ftubr.2025.1719707","url":null,"abstract":"<p><p>Riboflavin biosynthesis is essential for most microorganisms, yet its production is tightly regulated due to the potential toxic effect of riboflavin and its derivatives. While regulatory mechanisms for this process have been described in other organisms, none has been identified in mycobacteria. Uncovering such a mechanism will be critical to fully exploit the riboflavin biosynthetic pathway as a pharmacological target. We previously observed that <i>Mycobacterium tuberculosis</i> (Mtb) and <i>Mycolicibacterium smegmatis</i> (Msm) can grow successfully under elevated riboflavin levels, prompting an investigation into how mycobacteria tolerates high intracellular riboflavin. Using a bioinformatic approach of proteomic data, we explored the global proteomic response of Mtb and Msm to elevated riboflavin. Our results revealed increased abundance of know flavin sequesters in response to high riboflavin levels, suggesting a role in flavin homeostasis. Using a transcription regulatory network analysis, we observed the employment of similar regulatory networks, most notably DosR, in both Mtb and Msm in response to elevated riboflavin. We also identified a potential link between the riboflavin induced response and isoniazid resistance mechanisms, warranting further investigation. Overall, this study provides evidence for the involvement of flavin sequesters in maintaining flavin homeostasis and highlights the potential regulatory role of DosR in this process.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"3 ","pages":"1719707"},"PeriodicalIF":0.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}