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        <title>Frontiers in Tuberculosis | New and Recent Articles</title>
        <link>https://www.frontiersin.org/journals/tuberculosis</link>
        <description>RSS Feed for Frontiers in Tuberculosis | New and Recent Articles</description>
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        <pubDate>2026-04-04T09:52:40.919+00:00</pubDate>
        <ttl>60</ttl>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2026.1819209</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2026.1819209</link>
        <title><![CDATA[Editorial: Non-tuberculous mycobacteria and bronchiectasis]]></title>
        <pubdate>2026-04-01T00:00:00Z</pubdate>
        <category>Editorial</category>
        <author>Octavio M. Rivero-Lezcano</author><author>Ramiro López-Medrano</author><author>Jaime Esteban</author>
        <description></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2026.1762713</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2026.1762713</link>
        <title><![CDATA[Dose optimization of inhaled tigecycline in humans to overcome inherent adverse events and maximize bacterial clearance using a physiologically-based pharmacokinetic modeling approach]]></title>
        <pubdate>2026-03-26T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Hyunseo Park</author><author>Amarinder Singh</author><author>Ashish Srivastava</author><author>Bhargavi Thalluri</author><author>Christelle J. Mathieu</author><author>Paridhi Gupta</author><author>Camron M. Pearce</author><author>Malik Zohaib Ali</author><author>Ilham M. Alshiraihi</author><author>Sara E. Maloney Norcross</author><author>Anthony J. Hickey</author><author>Mercedes Gonzalez-Juarrero</author><author>Bernd Meibohm</author>
        <description><![CDATA[IntroductionIntrapulmonary delivery of tigecycline has been highlighted as an optimal strategy for enhancing local drug concentrations at the site of infection in the treatment of Mycobacterium abscessus 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.MethodsThe 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 in vivo 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.ResultsUsing 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 (AUC0−24 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 Mycobacterium abscessus.DiscussionOur 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.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2026.1760581</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2026.1760581</link>
        <title><![CDATA[Advanced diagnostic methods for nontuberculous mycobacterial infections]]></title>
        <pubdate>2026-03-25T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Sneha Singh</author><author>Amresh Kumar Singh</author><author>Sushil Kumar</author><author>Nandini Singh</author><author>Ashwini Kumar Mishra</author><author>Aroop Mohanty</author>
        <description><![CDATA[Nontuberculous mycobacteria (NTM) represent an increasingly significant cause of pulmonary and extrapulmonary infections, but are sometimes misinterpreted as tuberculosis (TB) owing to overlapping clinical and microbiological characteristics. Conventional diagnostic approaches, such as Ziehl-Neelsen staining and culture in a Mycobacterial Growth Indicator Tube (MGIT) system, are constrained by extended incubation times, are insufficient for accurate species differentiation, and are limited by prolonged incubation periods. Recent molecular and genomic advances have transformed NTM diagnostics by enabling rapid, specific, and high-resolution identification. Line probe assays (e.g., GenoType Mycobacterium CM/AS assay) and multiplex PCR have enhanced the ability to distinguish between NTM species such as Mycobacterium absessus, M. fortuitum, and M. avium complex and M. tuberculosis complex, which is essential for proper treatment and epidemiological mapping. Among newer proteomic platforms, matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry has emerged as a transformative, cost-effective technology capable of identifying Mycobacterium species directly from culture isolates through protein fingerprinting. It provides rapid, reproducible, and highly discriminatory identification between closely related species. Next-generation sequencing (NGS) and whole genome sequencing approaches now offer unprecedented insight into species identification, strain typing, and drug-resistance prediction, complementing traditional culture-based susceptibility testing. Newer techniques such as metagenomics NGS (mNGS), targeted NGS (tNGS) multilocus sequence typing, and mycobacterial interspersed repetitive unit-variable number tandem repeats (MIRU-VNTR) genotyping facilitate subspecies-level resolution and real-time outbreak surveillance. Moreover, molecular beacons, insertion sequence analysis, and repetitive sequence-based polymerase chain reaction (Rep-PCR) enhance detection sensitivity even in paucibacillary samples. The integration of genomic data with automated diagnostic system promises earlier intervention, accurate species delineation, and improved patient outcome.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2025.1678039</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2025.1678039</link>
        <title><![CDATA[Evaluation of host-immune biomarker signatures as multiplex qPCR diagnostic assays: a pilot study toward meeting WHO target product profiles for TB diagnosis in India]]></title>
        <pubdate>2026-02-16T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Harriet N. Garlant</author><author>Kalaiarasan Ellappan</author><author>Noyal Mariya Joseph</author><author>Carrie Turner</author><author>Vishnukanth Govindaraj</author><author>Saka Vinod Kumar</author><author>Sanjeev Kumar</author><author>Seshadri Vasan</author><author>Karen E. Kempsell</author>
        <description><![CDATA[BackgroundTuberculosis (TB) remains the leading cause of death from a single infectious agent. Current diagnostic tools are limited, especially in low-resource settings. The World Health Organization's (WHO) Target Product Profiles (TPPs) call for rapid, non-sputum-based diagnostics with high sensitivity and specificity. This study evaluates our previously published TB-associated host-immune biomarkers alongside small-size signatures from other studies, in our previously published non-human primate (NHP) TB infection study dataset (GSE76703) and two previously published human datasets (GSE144127, GSE42834), which include other disease group comparators, including sarcoidosis. These were also evaluated in a small-scale, exploratory qPCR pilot study to assess the feasibility of implementing these previously validated signatures in a South Indian TB patient cohort, comparing their diagnostic performance against WHO TPP criteria.MethodsTwenty-six genes from published signatures (INDUK, Roe1/Roe3, Sweeney3, RISK6) were analyzed in these NHP and human datasets, using network and machine learning approaches, prior to exploratory evaluation using single and multiplex qPCR assays. These were tested using peripheral blood sample RNAs from pulmonary TB (PTB) (n = 15) and extrapulmonary TB (EPTB) (n = 15) patients and high-incidence controls (n = 15). The diagnostic performance of biomarkers, prior signatures, and novel promising combinations were assessed against WHO TPPs for triage and confirmatory tests.ResultsSeveral biomarker signatures successfully distinguished active TB ((ATB) PTB and EPTB combined) from controls. The minimal INDUK signature (GBP1 + IFIT3) met the optimal TPP criteria for both triage and confirmatory testing for PTB (100% sensitivity and specificity, area under the receiver operating characteristic curve (AUROC:1)) and achieved the 80% sensitivity, 100% specificity threshold for EPTB (AUROC: 0.92 CI: 0.8261–1.00). Combined signatures incorporating genes from INDUK, Roe1, and Sweeney3 further improved diagnostic accuracy for ATB overall (AUROC: 0.98 95% CI: 0.9472–1.00).ConclusionThis preliminary pilot study demonstrates successful evaluation of biomarker signatures as diagnostic qPCR assays for TB diagnosis and, to our knowledge, is the first study to demonstrate the potential for combined host-immune biomarker signatures from different studies that meet WHO TPP benchmarks. These findings support the potential for the development of low-cost, field-adaptable diagnostic tools. Further validation is now under way on a larger cohort of TB patients and controls.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2026.1713844</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2026.1713844</link>
        <title><![CDATA[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]]></title>
        <pubdate>2026-02-13T00:00:00Z</pubdate>
        <category>Study Protocol</category>
        <author>Karikalan Nagaraj</author><author>Bella Devaleenal Daniel</author><author>Chandra Suresh</author><author>Dhanalakshmi Angamuthu</author><author>Shobana Palanisamy</author><author>Muniyandi Malaisamy</author>
        <description><![CDATA[BackgroundThe 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.ObjectivesTo 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.MethodsA 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 (n = 240) in comparison to the standard of care (n = 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.DiscussionThe 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.Clinical trial registrationThe study has been registered in the Clinical Trial Registry of India CTRI/2024/05/066847.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2026.1726647</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2026.1726647</link>
        <title><![CDATA[Acceptability and feasibility of oral swabs for tuberculosis diagnosis in young children: a qualitative study from Uganda and Peru]]></title>
        <pubdate>2026-02-12T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Francesca W. Basile</author><author>Rodrigo Calderón-Flores</author><author>Franziska Held</author><author>Luisa Pollmeier</author><author>Emmanuel Nasinghe</author><author>Godfrey Bagenda</author><author>Lazaaro Mujumbusi</author><author>Rose Namaganda</author><author>Angel Kanyange</author><author>Prossy Mbekeeka</author><author>Abner Tagoola</author><author>Jerrold J. Ellner</author><author>Susan E. Dorman</author><author>Moses Joloba</author><author>Carlos Zamudio</author><author>Adeodata Kekitiinwa</author><author>Rinn Song</author><author>Nora Engel</author>
        <description><![CDATA[BackgroundTuberculosis (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 regarding their acceptability and feasibility remains limited.MethodsThis 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.ResultsOral 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.ConclusionsOral 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.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2026.1746664</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2026.1746664</link>
        <title><![CDATA[The “yeast-drop” treatment protocol in the Drosophila model for rapid and cost-effective TB drug testing]]></title>
        <pubdate>2026-01-27T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Maria Vidal</author><author>Esther Fuentes</author><author>Nerea Escobar</author><author>Marta Arch</author><author>Pere-Joan Cardona</author>
        <description><![CDATA[BackgroundPulmonary tuberculosis (TB), caused by Mycobacterium tuberculosis, 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 in vitro models and the cost and scalability challenges of mammalian in vivo models. In this study, we developed a cost-effective administration method using the Drosophila melanogaster–Mycobacterium marinum infection model called “yeast-drop”. This approach facilitates oral delivery and reduces the quantity of compound currently needed for treatment in the fly model.MethodsWe compared the yeast-drop methodology with the standard method commonly used in Drosophila 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.ResultsFlies 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 Drosophila model.ConclusionOverall, the Drosophila–M. marinum 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 in vitro systems and mammalian models.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2025.1718997</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2025.1718997</link>
        <title><![CDATA[Evaluation of a short, all oral treatment regimen including bedaquiline, delamanid, linezolid, clofazimine, and pyrazinamide named “Regimen C” for pre-XDR tuberculosis in Niger]]></title>
        <pubdate>2026-01-13T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Soumana Boubacar Soumana</author><author>Abdourahamane Yacouba</author><author>Cheikh Aboubacar Abdoul Lawi</author><author>Ibrahim Oumar</author><author>Bassirou Souleymane</author><author>Alphazazi Soumana</author><author>Tapha Ounoussa</author><author>Mahamadou Doutchi</author><author>Mamane Daou</author><author>Souleymane Brah</author><author>Eric Adehossi</author><author>Saidou Mamadou</author>
        <description><![CDATA[BackgroundThe 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.AimThis study aimed to assess its effectiveness under programmatic conditions.MethodsThis 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.ResultsA 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 (p = 0.18).ConclusionThese 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.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2025.1735568</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2025.1735568</link>
        <title><![CDATA[Bidirectional pathogenesis between non-tuberculous mycobacteria and bronchiectasis: clinical insights, diagnostic challenges and future directions—Perspectives from South Asia]]></title>
        <pubdate>2026-01-12T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Amresh Kumar Singh</author><author>Sneha Singh</author><author>Nandini Singh</author><author>Priyanka Gaur</author><author>Ashwini Kumar Mishra</author><author>Raj Kishore Singh</author><author>Sushil Kumar</author>
        <description><![CDATA[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 Mycobacterium avium complex and Mycobacterium abscessus 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.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2025.1668711</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2025.1668711</link>
        <title><![CDATA[A synthesis of youth activation initiatives and their impact on tuberculosis knowledge, knowledge-seeking, and healthcare-seeking behavior in vulnerable populations]]></title>
        <pubdate>2026-01-09T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Ana-Maria Ionescu</author><author>Joelle Mak</author><author>Qu Yan</author><author>Nishant Kumar</author><author>Raghuram Rao</author><author>Sanjay Mattoo</author><author>Deepak Balasubramanian</author><author>Rachana Acharya</author><author>Subhi Quraishi</author><author>Niraj Sharma</author><author>Kep Nurliyanti</author><author>Juliana Chin</author><author>Siva Anggita</author><author>Tiffany Pakasi</author><author>Sarah Rahma</author><author>Ingrid Eshun-Wilsonova</author>
        <description><![CDATA[BackgroundAnnually, 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.MethodsBetween 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.ResultsAcross 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.ConclusionThese 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.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2025.1719707</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2025.1719707</link>
        <title><![CDATA[Proteomic insights into mycobacterial responses to elevated riboflavin reveal a role for flavin-sequestering proteins in flavin homeostasis]]></title>
        <pubdate>2025-12-17T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Nurudeen Oketade</author><author>Karen M. Dobos</author>
        <description><![CDATA[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 Mycobacterium tuberculosis (Mtb) and Mycolicibacterium smegmatis (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.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2025.1735950</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2025.1735950</link>
        <title><![CDATA[Mycobacteria as evolutionary drivers of host innate immunity: insights from comparing experimental host models]]></title>
        <pubdate>2025-12-12T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Mariona Cortacans</author><author>Pere-Joan Cardona</author>
        <description><![CDATA[The genus Mycobacterium exerts a strong selective force, shaping the evolution and structure of innate immune systems across various hosts and revealing overarching, conserved principles of host defense. Despite their phylogenetic distance, amoebae, nematodes, insects, wax moth larvae, and zebrafish share fundamental innate immune strategies while also exhibiting key differences in tissue organization, immune complexity, and the presence or absence of adaptive immunity. This comparative review synthesizes insights from these systems to highlight both the conserved mechanisms that mycobacteria repeatedly exploit and the lineage-specific features that shape host susceptibility. Amoebae demonstrate ancient, cell-autonomous defenses, including nutritional immunity through metal trafficking (Nramp1/zinc intoxication) and membrane repair pathways (ESCRT/autophagy) against the ESX-1 system. Moving to metazoans, the importance of conserved signaling, such as the p38 MAPK (PMK-1) pathway in C. elegans, becomes evident, which M. marinum actively suppresses via VHP-1. In other invertebrates, such as Drosophila, integrated immunometabolism is present, in which disruption of the Akt–FOXO axis causes a conserved wasting syndrome, and Galleria mimics chronic TB pathology by forming granuloma-like structures with lipid-accumulating hemocytes and demonstrating innate immune priming. Larval zebrafish, which depend solely on innate immunity, show pathogen-driven granuloma formation and spread, with ESX-1 mediating pro-necrotic cell death and the Asc-dependent inflammasome contributing to restriction. Overall, these cross-species comparisons demonstrate how mycobacteria exploit foundational host mechanisms while revealing the evolutionary breadth and limits of innate immune strategies across the animal kingdom.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2025.1721361</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2025.1721361</link>
        <title><![CDATA[Implementing TB-Stigma reduction interventions in High Burden Countries: a perspective on a conceptual framework]]></title>
        <pubdate>2025-11-28T00:00:00Z</pubdate>
        <category>Perspective</category>
        <author>Bushra Bibi</author><author>Mark Goodall</author><author>Injety Ranjit</author><author>Stephanie Jones</author><author>Colette Miller</author>
        <description><![CDATA[Tuberculosis (TB) is a preventable, curable disease but still impacts people in high-burden countries, who face challenges, including stigma, in accessing and engaging with healthcare services. The Nuttall's review examined the quality of existing TB-stigma intervention studies and developed a conceptual framework of pathways to stigma reduction. We critically appraised the methods used and expanded upon these findings in the context of the WHO End TB Strategy. The included studies showed significant heterogeneity in design, aims, populations, type of TB-stigma targeted and took place across diverse countries. Only three of 11 studies were rated as high quality. This systematic review synthesized existing interventions and outcomes into a conceptual framework outlining pathways to reduce TB-stigma. The conceptual framework highlights the need for educational, emotional, and psychosocial support for TB patients, Health Care Workers, and Communities, and provides a useful guide of pathways needed in TB-stigma reduction interventions. However, to be effective, stigma reduction interventions must be part of a well-organized, and committed multi-sectoral collaboratives, which extend beyond national and global TB programs, including mental health services, social support systems, and public health programs.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2025.1710215</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2025.1710215</link>
        <title><![CDATA[Low treatment completion rates reveal gaps in the LTBI care cascade among university students]]></title>
        <pubdate>2025-11-06T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Anu K. Murthy</author><author>Richard A. Goodman</author><author>Miranda A. Moore</author>
        <description><![CDATA[BackgroundUniversity students, particularly those from tuberculosis (TB)-endemic countries and students in health professions, are at increased risk for latent tuberculosis infection (LTBI). In the United States (U.S.), TB screening is required for applicants for permanent residency and refugee status but not for individuals entering on student visas, and institutional policies vary. At our university, which requires pre-matriculation TB screening for all incoming students, low LTBI treatment completion rates prompted a review of care delivery.MethodsWe conducted a retrospective chart review of students diagnosed with LTBI at a medium-sized private university from 2018 to 2023. Records identified by ICD-10 codes were reviewed for demographics, school enrollment, testing method, regimen, and treatment outcome.ResultsOf 687 students with TB-related visits, 82 (12%) were diagnosed with LTBI. Median age was 27 years (interquartile range 23–31); 55% were female and 65% were non-U.S.-born, most often from China and India. Students represented nine schools, with Medicine (17%) and Nursing (14%) comprising about one-third of cases. Forty-eight students (59%) initiated treatment, while 34 (41%) did not, primarily due to declining therapy or incomplete follow-up. Among those treated, 22 (46%) completed therapy, corresponding to 27% overall. Completion was highest for nine months of isoniazid (88%) and lowest for 4 months of rifampin (17%). Several documentation and follow-up gaps were identified.ConclusionLosses across the LTBI care cascade were common in this university setting and reflect patterns reported in other U.S. and international studies. Strengthening education, follow-up, access to shorter regimens, and documentation may improve completion rates and support TB elimination goals.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2025.1659333</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2025.1659333</link>
        <title><![CDATA[Predicting treatment adherence in patients with drug-resistant tuberculosis: insights from socioeconomic, demographic, and clinical factors of patients in the rural Eastern Cape]]></title>
        <pubdate>2025-10-01T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Lindiwe Modest Faye</author><author>Mojisola Clara Hosu</author><author>Ntandazo Dlatu</author><author>Joshua Iruedo</author><author>Teke Apalata</author>
        <description><![CDATA[BackgroundDrug-resistant tuberculosis (DR-TB) poses a serious challenge to global health. Patients must follow complex medication regimens over long periods, and any failure to comply with these treatment plans can result in treatment failure, higher mortality rates, and an increased risk of developing additional drug resistance.SettingThe study was conducted in the rural Eastern Cape.AimThis study aims to identify the key factors influencing treatment adherence among patients with DR-TB. Furthermore, it rigorously evaluates the predictive accuracy of machine learning models in assessing treatment adherence, with a strong focus on socioeconomic, demographic, and clinical factors.MethodsA retrospective analysis was conducted on patients with DR-TB. Data were collected from medical records. Four different models were developed and tested to evaluate their effectiveness in predicting treatment adherence: Random Forest, Logistic regression, Support Vector Machine (SVM), and Gradient Boosting.ResultsThe Random Forest model achieved an accuracy of 53.3% in predicting treatment adherence. An analysis of feature importance indicated that age, income, education, social history, patient category, and comorbidities were the most significant factors influencing adherence. Patients with higher incomes, higher levels of education, and fewer comorbidities were more likely to follow their treatment plans.ConclusionAdhering to treatment for DR-TB involves a range of socioeconomic and clinical factors. Income, education level, and pre-existing health conditions significantly influence how well patients follow their prescribed treatment regimens. Understanding these influences is crucial for enhancing treatment outcomes and facilitating patients' journey toward improved health.ContributionThese findings suggest that machine-learning models, especially Random Forest algorithms, can effectively support clinical decision-making by identifying patients at risk of non-adherence to their treatment.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2025.1667354</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2025.1667354</link>
        <title><![CDATA[Country-level heterogeneity in MDR-TB drug susceptibility supports country-specific policy development]]></title>
        <pubdate>2025-09-25T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Naomi M. Fuller</author><author>Nicholas G. Davies</author><author>Timothy D. McHugh</author><author>Gwenan M. Knight</author>
        <description><![CDATA[ObjectivesThe global challenge of tuberculosis (TB) is exacerbated by multidrug-resistant TB (MDR/RR-TB), confounded by country-level differences in TB prevention and care. The impact of local differences in drug-resistance selection pressure and transmission may be observed by analyzing distributions of minimum inhibitory concentrations (MICs). Using the Bedaquiline Drug-Resistance Emergence Assessment in MDR-TB (DREAM) dataset, we analyzed MIC distributions derived from a standard protocol across 11 countries and 12 antibiotics to explore country-level variation in drug susceptibility.MethodsWe analyzed 71,135 MICs from 5,928 MDR/RR-TB isolates sampled from bedaquiline-naive patients. We compared MIC distributions across countries and WHO resistance classes, then used Spearman rank correlations to compare the drug-susceptibility within individual isolates by country. To explore the effect of bedaquiline use on resistance, we used linear regression to compare bedaquiline MICs with WHO data on bedaquiline usage.ResultsMIC distributions between countries were heterogeneous, especially for fluoroquinolones and isoniazid. The correlation analysis revealed a relationship between bedaquiline and clofazimine MICs in six countries. Analysis of isolates by resistance class demonstrated that XDR-TB isolates had higher MICs than MDR-TB isolates for antibiotics not part of the XDR definition. We found limited evidence to suggest that past bedaquiline usage at the national level led to raised bedaquiline MICs in patients not exposed to the drug.ConclusionsOur research shows clear variations in drug susceptibility within M. tuberculosis across different countries and resistance classes, providing evidence of distinct drug-susceptibility dynamics per country. This expands the evidence for MDR-TB country differences and supports further country-specific policy development.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2025.1540194</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2025.1540194</link>
        <title><![CDATA[Targeted transcriptomic analyses of tuberculosis treatment response and outcomes in The Gambia]]></title>
        <pubdate>2025-09-02T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Ismaila L. Manneh</author><author>Fatoumatta Darboe</author><author>Haddijatou Jobe</author><author>Binta Sarr Kuyateh</author><author>Ousainou Cham</author><author>Olumuyiwa Owolabi</author><author>Brezesky Kotanmi</author><author>Andrea Rachow</author><author>Salome Charalambous</author><author>Kathrin Held</author><author>Hazel M. Dockrell</author><author>Jayne S. Sutherland</author>
        <description><![CDATA[BackgroundDespite availability of effective treatment regimens for drug-susceptible Tuberculosis (TB), some patients still experience poor treatment outcomes. Currently tools for monitoring treatment outcomes are dependent on detection of mycobacteria in sputum, which are slow, expensive and poor at predicting relapse and failure. This study aims to identify new blood-derived markers for predicting treatment response and outcomes.MethodsWhole blood was collected in PAXgene tubes from patients with microbiologically confirmed TB at diagnosis, week 2, and at months 2, 4, and 6. Treatment response and outcomes were determined by culture and gene expression was compared between slow and fast responders; and between patients with good (cured) and poor treatment outcomes (failure and recurrent TB) using targeted RNA gene expression. Gene signatures were developed using random forest classification models.ResultsSignificant changes in gene expression were detected over the course of the TB treatment. Notably, major gene expression differences were observed at diagnosis between subsequently cured patients and patients who experienced poor treatment outcomes while minimal changes were detected between slow and fast responders among cured patients at diagnosis. A 7-gene end of treatment signature distinguished patients with good outcomes from those with poor treatment outcomes with area under the curve (AUC) of 0.91 (95% CI 0.85–0.99), 0.98 (95% CI 0.96–0.99), and 1.0 (95% CI 0.99–1.00), at baseline, month 2 and 6, respectively. Additionally, a 6-gene month 2 signature discriminates slow from fast responders with AUCs of 0.49 (95% CI 0.33–0.64), 0.58 (95% CI 0.07–1.00), and 0.93 (95% CI 0.78–1.00) at diagnosis, week 2 and month 2, respectively.ConclusionThe study identified genes signatures associated with TB treatment response and outcomes suggesting potential utility for treatment monitoring.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2025.1608780</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2025.1608780</link>
        <title><![CDATA[The value of LAM and LprG in extracellular vesicles in the diagnostic and therapeutic field of renal tuberculosis]]></title>
        <pubdate>2025-08-12T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Xuefeng Peng</author><author>Yue Li</author><author>Suiyang Jin</author><author>Qiang Wang</author>
        <description><![CDATA[Extracellular vesicles have been a hot research topic in recent years, and the diagnostic and therapeutic value of LprG and LAM, two key markers present in extracellular vesicles secreted by Mycobacterium tuberculosis or Mycobacterium tuberculosis-infected immune cells, in tuberculosis, has been widely emphasized in recent years. Genitourinary tuberculosis is a common form of extrapulmonary tuberculosis, and renal tuberculosis accounts for more than 20% of patients with Genitourinary tuberculosis. In this paper, we summarize the findings and research ideas of LprG and LAM in the diagnosis and treatment of renal tuberculosis in recent years and conclude that LprG and LAM have their unique diagnostic value in the intrapulmonary and extrapulmonary fields and can be used as a new potential idea for vaccine or immunotherapy in the future for research.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2025.1587839</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2025.1587839</link>
        <title><![CDATA[Assessment of knowledge, attitudes, and practices regarding TB prevention and treatment among college students in Wuhan, central China]]></title>
        <pubdate>2025-08-01T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Gang Wu</author><author>Chao Quan</author><author>Aiping Yu</author><author>Li Li</author><author>Jun Chen</author><author>Yun Yang</author><author>Guiyang Wang</author><author>Zhouqin Lu</author><author>Xiaojun Wang</author><author>Qionghong Duan</author><author>Haoze Zhang</author><author>Jing Hu</author><author>Zhengbin Zhang</author>
        <description><![CDATA[BackgroundTuberculosis (TB) is recognized as a serious public health concern in many developing countries. As the new main force and inheritors of national health construction, college students bear important social responsibilities and missions of practicing TB prevention and control, volunteer mobilization, and health concept dissemination. Improving college students' health literacy is crucial to preventing and treating infectious diseases. This study aims to assess college students' knowledge, attitudes, and practices (KAP) about TB prevention and treatment in Wuhan, China.MethodsA descriptive cross-sectional study survey among college students was conducted from May to June 2022 at 22 colleges using the judgment sampling method in Wuhan. KAP regarding TB was recorded and assessed using an online questionnaire platform. The status quo of KAP regarding TB prevention and treatment was statistically described, and the formation of students' TB prevention and treatment behavior was analyzed using single-factor and multifactor logistic regression.ResultsA total of 15,290 college students completed the questionnaire, and 15,272 valid questionnaires were collected. The total awareness rate of knowledge, attitudes, and practices of TB prevention and treatment was 79.69%. Among them, the awareness rate of key knowledge was 79.28%, and the passing rate was 92.46%. The holding rate of correct attitudes was 89.69%, and the passing rate was 90.56%. The formation rate of correct behaviors was 72.11%, and the passing rate was 96.62%. A single-factor analysis showed that gender, grade, parents' education level, contact history of TB patients, and passing rate of key knowledge were statistically different in the formation of prevention and treatment behaviors. Multivariate logistic regression analysis showed that for females (odds ratio [OR] = 1.86, 95% CI [1.50, 2.30], p < 0.01), students with father's educational background of primary school (OR = 2.94, 95%CI [1.62, 5.33], p < 0.01), junior school and equivalent (OR = 2.94, 95%CI [1.62, 5.33], p < 0.01), high school and equivalent (OR = 3.05, 95%CI [1.70, 5.46], p < 0.01), and diploma or undergraduate (OR = 3.24, 95% CI [1.73, 6.09], p < 0.01); no history of TB (OR = 3.32, 95% CI [1.49, 7.41], p < 0.01); a passing key knowledge score (OR = 9.91, 95% CI [8.11, 12.11], p < 0.01); and a passing attitude score (OR = 7.35, 95% CI [6.01, 8.99], p < 0.01) were likely to form TB prevention and treatment behaviors.ConclusionSchool health promotion should not only focus on improving students' personal knowledge and skills of TB prevention and treatment but also emphasize the level of family participation, strengthen the comprehensive mobilization action of schools, formulate policies to support health action, create a supportive social environment, and radiate the health education effect of students to the whole society.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/ftubr.2025.1608364</guid>
        <link>https://www.frontiersin.org/articles/10.3389/ftubr.2025.1608364</link>
        <title><![CDATA[Risk factors associated with multidrug-resistant pulmonary tuberculosis in patients over 15 years old: a retrospective case-control study]]></title>
        <pubdate>2025-07-18T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Odete Bambi Receado</author><author>Paulo Ney Solary</author><author>Emanuel Catumbela</author><author>Carlos Alberto Pinto de Sousa</author>
        <description><![CDATA[IntroductionMultidrug-Resistant Pulmonary Tuberculosis (MDR-TB) represents a serious public health problem, hindering disease control and increasing morbidity and mortality. This study aimed to identify risk factors associated with MDR-TB in patients over 15 years old at the Sanatorium Hospital of Luanda during the period 2015–2016.MethodsA retrospective case-control study (1:1) was conducted with 500 participants, including 250 cases (MDR-TB) and 250 controls (drug-sensitive TB). Data were obtained from clinical records and analyzed using logistic regression in Epi-Info 7.2.1.0 software, considering a significance level of p < 0.05.ResultsMDR-TB was more prevalent in men (61.6%), in the age group 20–29 years (36.8%), and among employed individuals (73.2%). The associated risk factors were irregular medication adherence [odds ratio (OR) = 12.3; p < 0.001], previous TB treatment (OR = 9.0; p < 0.001), contact with an MDR-TB patient (OR = 4.1; p < 0.001), and lower educational level (OR = 2.1; p = 0.03).ConclusionIrregular adherence to treatment and a history of previous TB were the main factors associated with MDR-TB, reinforcing the need for effective strategies to ensure treatment follow-up.]]></description>
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