搜索结果：tuberculosis

Background: Pulmonary tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (M. tuberculosis). Drug-resistant TB remains a major public health challenge and calls for new approaches to drug development. Targeted delivery of antibacterial agents using nanoscale carriers represents one such approach. A decisive factor for efficient targeting is the judicious selection of the carrier platform. Methods: In the present study, diamond nanoparticles were evaluated as a prospective vehicle for conveying anti-TB drugs to lung cells. Conventional and analytical transmission electron microscopy were used to analyze the localization of the nanodiamonds (NDs) in the lungs of M. tuberculosis-infected mice 30 days after nanoparticle administration and 44 days post-infection. Results: The study shows that the NDs co-localize with M. tuberculosis in foamy macrophages of the lung, residing in the same cellular compartments-phagosomes/phagolysosomes and lipid droplets. These in vivo results demonstrate a high degree of macrophage-specific accumulation of NDs relative to M. tuberculosis. Conclusions: Consequently, NDs can be considered a promising carrier for targeted delivery of anti-TB therapeutics to the lungs during TB-induced inflammation.

During infection, host immune cells deploy a variety of strategies to neutralize invading pathogens, including the manipulation of metal availability, a process traditionally understood as nutritional immunity. While depriving microbes of essential metals, such as iron and manganese, inhibits their growth, host cells also engage in metal intoxication, actively overloading phagosomes with toxic levels of transition metals, such as copper and zinc. To survive these dual pressures, Mycobacterium tuberculosis, the etiological agent of tuberculosis, has evolved specialized metal resistance mechanisms. This review explores how M. tuberculosis counters host-imposed metal stress through an arsenal of P-type ATPases, particularly the diverse P1B subfamily of transition metal exporters. We detail the structural features, metal specificities, and regulatory mechanisms of M. tuberculosis' 12 P-type ATPases, focusing on three key systems, CtpC, CtpG, and CtpV, and their cognate scaffold proteins PacL1, PacL2, and PacL3. These PacL-Ctp pairs form dynamic membrane assemblies termed effluxosomes, which mediate resistance to transition metals such as zinc and cadmium. The review also highlights several distinctive features of M. tuberculosis P1B-ATPases relative to canonical transporters such as CopA and ZntA, suggesting unique adaptations to the intracellular environment. Finally, we discuss the challenges of functionally and structurally characterizing these systems and propose future directions to elucidate effluxosome assembly and function. Together, these insights reveal how M. tuberculosis leverages metal export as a critical survival strategy and suggest novel therapeutic opportunities targeting metal detoxification pathways.

In searching for novel molecules to act as antibacterial agents, particularly against Mycobacterium tuberculosis bacteria, three series of C5- and C6-substituted 1,2,3-triazine compounds were investigated: 1,2,3-triazine-4-carboxylate 1-oxide (series 1), 1,2,3-triazine-4-carboxylate (series 2), and 3,6-dihydro-1,2,3-triazine-4-carboxylate 1-oxide derivatives (series 3). Their structural elucidation was confirmed by 1H-NMR, 13C-NMR, and HRMS. We determined their antibacterial activity (MIC value) using the MABA against the M. tuberculosis H37Rv strain, as well as their physicochemical and pharmacokinetic properties. Finally, to determine their potential mode of action, an inhibition assay against M. tuberculosis DNA gyrase was performed. Compounds 4-ethoxycarbonyl-5-(3-methoxyphenyl)-1,2,3-triazine (2l) and 4-ethoxycarbonyl-5 -(n-propyl)-1,2,3-triazine (3s) exhibited high activity against M. tuberculosis with MIC values < 5.90 &#xb5;g/mL and selectivity index of 18.56 and 8.36, respectively. Additionally, compound 2m also exhibited anti-mycobacterial activity with MIC values < 10.0 &#xb5;g/mL. However, none of the selected compounds inhibited the activity of M. tuberculosis DNA gyrase, suggesting that another drug target may be involved as a mode of action. These results encourage exploring the use of 1,2,3-triazine as a scaffold for the development of new anti-mycobacterium agents.

The reproductive toxicity of first-line antituberculosis drugs remains poorly understood, particularly when used in combination. Rifampicin, isoniazid, pyrazinamide, and ethambutol are essential in tuberculosis therapy, but their potential influence on female fertility is uncertain. This pilot study evaluated their effects, given alone or in dual, triple, and quadruple combinations, on oxidative stress, endocrine markers, and reproductive outcomes in healthy female rats. Ninety-six albino Wistar-type female rats were divided into sixteen groups of six animals each and treated with single, dual, triple, or quadruple regimens of first-line antituberculosis drugs for 28 days. After treatment, two sexually mature males were introduced per group, and therapy continued for seven additional days. Serum malondialdehyde (MDA), total glutathione (tGSH), prolactin, and anti-Mullerian hormone (AMH) levels were measured, and fertility outcomes were evaluated. In single-drug groups, MDA increased and tGSH decreased, but detectable infertility was not recorded. Prolactin remained stable except in the pyrazinamide group, where it declined. Dual-drug regimens increased oxidative imbalance; fertility failure occurred only in pyrazinamide-lacking groups and was accompanied by higher prolactin and lower AMH. Triple and quadruple combinations produced prominent oxidative imbalance. In triple-drug regimens, infertility was lower in pyrazinamide-containing groups than in the pyrazinamide-free group, but this pattern was not maintained in the quadruple regimen. Fertility impairment was not consistently aligned with the degree of oxidative stress and may involve prolactin and AMH alterations. These findings suggest that reproductive impairment under these experimental conditions may involve endocrine alterations and cannot be explained solely by serum oxidative imbalance. Pyrazinamide-associated fertility preservation appeared context-dependent and requires further confirmation in larger mechanistic studies with broader reproductive and endocrine assessment.

Drug-resistant (DR) mycobacterial infections present escalating threats in Iran, where facility-specific transmission dynamics and demographic disparities remain poorly characterized. This study evaluated the epidemiology of DR Mycobacterium tuberculosis and pulmonary nontuberculous mycobacterial disease over a 9-year period (2016-2024). This retrospective study analyzed 21,700 molecular and culture-confirmed mycobacterial samples. Species identification used line probe assays and Xpert Mycobacterium tuberculosis/rifampin. Drug susceptibility testing followed World Health Organization standards. Statistical analyses identified associations between resistance patterns, hospital sections, gender, and specimen types. MDR-TB prevalence surged from 0.35% (2017) to 3.27% (2022), peaking during pandemic disruptions. M. simiae dominated nontuberculous mycobacteria (NTM) resistance (55.63% of resistant isolates), with significant increases in 2024 (7.91%). Airborne infection isolation rooms (AIIRs) paradoxically harbored 18.22% of Multidrug-resistant tuberculosis (MDR-TB)isolates (p < 0.0001), while pulmonary medicine units contained zoonotic M. bovis reservoirs (0.27% MDR prevalence). Male patients carried higher burdens of MDR-TB (26.01% vs. 12.45%, p = 0.005) and M. kansasii (2.05% vs. 0.53%, p = 0.012). Diagnostic challenges included 38.14% smear-negative M. abscessus and gastrointestinal NTMs (M. genavense 66.66%). Sample type analysis revealed M. fortuitum in 25.0% of abscesses (p < 0.05) and M. chelonae in 5.55% of synovial fluid (SF) specimens. Iran faces converging epidemics of MDR-TB and climate-adapted NTMs concentrated in hospital hotspots, with significant gender disparities. Precision interventions targeting AIIR protocols, water safety regulations, and gender-specific screening are urgently needed.

Tuberculosis (TB), a respiratory infectious disease caused by Mycobacterium tuberculosis (M.tb), poses a serious threat to human health due to its complex pathogenesis and limited treatment options. Diagnosing TB is challenging due to the poor sensitivity and specificity of current methods, while drug-resistance mechanisms further diminish the effectiveness of treatment. In this study, we developed a fluorescent nanoprobe named BM2-AgNCs by functionalizing silver nanoclusters with the DNA aptamer BM2. BM2-AgNCs facilitate efficient detection of lipoarabinomannan (LAM) and exhibit effective anti-M.tb activity, reducing bacterial viability by 80% both intracellularly and extracellularly. BM2 enhances the biocompatibility and targeting capabilities of AgNCs, which retain their fluorescence properties and antibacterial activity. AgNCs can serve as efficient quenchers of the FAM-labeled BM2, with fluorescence recovering in the presence of targets. Leveraging this property, we constructed a biosensor for the highly sensitive detection of LAM and for fluorescent tracking of M.tb. Regarding treatment, we demonstrated that BM2-AgNCs significantly inhibited M.tb activity while inducing M1 polarization in macrophages, resulting in a synergistic therapeutic effect. Furthermore, BM2-AgNCs can counteract immune evasion of M.tb by promoting phagolysosomal maturation. This work presents an integrated approach for TB diagnosis and treatment based on the fluorescent nanoprobe, utilizing the diverse fluorescent properties of the nanoprobe to visualize the underlying mechanisms.

Pulmonary tuberculosis (TB), caused by mycobacterium tuberculosis (M.tb) infection, remains a major global health threat. Macrophages serve as the primary host cells for M.tb, and the bacterium's ability to manipulate macrophage function is critical for its survival and pathogenesis. However, the specific molecular mechanisms regulating M.tb-induced macrophage injury require further elucidation. This study aimed to screen key regulatory genes and investigate the underlying mechanisms involving m6A modification in M.tb-induced THP-1 macrophages. Differentially expressed genes (DEGs) between M.tb-induced THP-1 macrophages and normal THP-1 macrophages were identified through bioinformatics analysis of the GSE203261 dataset. Expression levels of the target gene were validated in clinical blood samples and M.tb-induced THP-1 cells via quantitative real-time PCR (qRT-PCR) and Western blotting. Loss-of-function experiments were performed using small interfering RNA (siRNA), while overexpression plasmids were utilized for gain-of-function studies. The association between N6-methyladenosine (m6A) modification and the target gene was investigated using methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), and dual-luciferase reporter assays. Cell viability, apoptosis, inflammatory cytokine levels, and oxidative stress markers were assessed to evaluate cellular injury, and flow cytometry was employed to analyze M1 macrophage polarization. Colony-forming unit (CFU) assay was performed to assess the survival of M.tb. NF-&#x3ba;B pathway-related markers were detected by Western blotting. Sialic acid binding Ig like lectin 1 (SIGLEC1) was identified as a significantly upregulated gene in M.tb-induced THP-1 macrophages, and its high expression was confirmed in the blood of pulmonary TB patients and M.tb-induced THP-1 macrophages. Knockdown of SIGLEC1 attenuated M.tb-induced injury by enhancing cell viability, suppressing apoptosis, reducing the levels of inflammatory cytokines (IL-6, TNF-&#x3b1;), reactive oxygen species (ROS), and malondialdehyde (MDA), and increasing superoxide dismutase (SOD) levels. Additionally, SIGLEC1 silencing inhibited M1 polarization. Mechanistically, the methyltransferase-like 3 (METTL3) was found to bind to SIGLEC1 mRNA and enhance its stability in an m6A-dependent manner, a process dependent on the reader protein insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2). Rescue experiments demonstrated that while METTL3 knockdown alleviated M.tb-induced macrophage injury and inactivated the NF-&#x3ba;B pathway, these protective effects were reversed by SIGLEC1 overexpression. This study elucidated a novel METTL3/IGF2BP2/SIGLEC1 regulatory axis that mediated M.tb-induced macrophage injury and M1 polarization via the NF-&#x3ba;B signaling pathway. These findings highlight the potential of SIGLEC1 as a promising biomarker and provide a rationale for its further investigation as a therapeutic target for pulmonary TB.

Smear microscopy remains widely used for tuberculosis (TB) diagnosis due to its rapid turnaround and low cost, despite its relatively low sensitivity. With the advent of molecular tests, there is growing debate on whether the smear test remains relevant in clinical settings. An artificial intelligence (AI)-aided automated smear slide reader system (Zopomed, Zhengzhou, China) was evaluated at Beijing Chest Hospital. Sputum samples from suspected TB patients were used to prepare both Ziehl-Neelsen (ZN) and auramine O-stained slides. These were scanned by the automated reader under predefined field-of-view settings. Manual light-emitting diode fluorescence microscopy (for auramine O slides), MGIT960 culture, and Xpert MTB/RIF assay served as reference standards. Among 352 clinically confirmed TB patients, the detection rates were 18.75% by manual microscopy, 20.74% by automated ZN (1,000 fields), 32.67% by automated auramine O (300 fields), 30.68% by MGIT960 culture, and 42.05% by Xpert. Expanding the field of view significantly enhanced detection rates for both staining methods, with auramine O staining consistently outperforming ZN. The automated auramine O method (300 fields) identified 78.70% of culture-positive and 66.89% of Xpert-positive TB cases. All methods maintained specificities exceeding 99% when tested on 158 patients with non-mycobacterial pulmonary diseases. AI-aided auramine O smear testing represents a sensitive, rapid, and cost-effective approach to TB diagnosis. With the one-time investment in the automated system, this technique achieves sensitivity comparable to MGIT960 culture, offering a practical diagnostic solution for high-throughput clinical laboratories and resource-limited settings. This study demonstrated that an AI-aided automated smear microscopy system, when used with auramine O-stained slides scanning 300 fields, achieves a sensitivity comparable to MGIT960 culture, while offering the advantages of rapid, same-day results and significant cost-effectiveness; this one-time investment in equipment, which is compatible with routine staining protocols, provides a highly practical and scalable solution to enhance tuberculosis diagnosis in both high-throughput laboratories and resource-limited settings.

The dual epidemic of tuberculosis (TB) and type 2 diabetes mellitus (T2DM) presents a critical global health challenge, as diabetic immunosuppression increases TB susceptibility while TB infection exacerbates glucose intolerance. Because nuclear receptors (NRs) regulate both metabolic pathways and infectious disease responses, they represent promising therapeutic targets. This study aimed to evaluate the therapeutic potential of targeting overlapping NRs to manage TB-T2DM comorbidity. A comorbid mouse model was established by inducing T2DM via a high-fat diet and streptozotocin, followed by an aerosol challenge with Mycobacterium tuberculosis (M. tb). Mice were categorized into three groups: uninfected controls, M. tb-infected non-diabetic, and M. tb-infected diabetic mice. NR expression profiling was performed on alveolar macrophages, specifically screening endocrine, adopted orphan, and orphan NRs. Based on this profile, comorbid mice were treated with a combination therapy (CT) consisting of specific ligands for the most promising NR targets Vdr, Lxr and Rev-erb&#x3b1;. Expression screening identified Vdr, Rev-erb&#x3b1;, and Lxr as key dysregulated receptors with dual roles in TB and T2DM pathogenesis. Administration of the triple-ligand CT to comorbid mice significantly alleviated both metabolic and infectious symptoms compared to untreated comorbid controls. Specifically, CT-treated mice demonstrated reduced T2DM severity (stabilized body weight, decreased blood glucose, and lowered glycated hemoglobin) alongside reduced TB disease burden, evidenced by lower bacterial colony-forming unit (CFU) counts and fewer pulmonary granulomatous lesions. These findings demonstrate that simultaneous modulation of Vdr, Rev-erb&#x3b1;, and Lxr effectively mitigates the severe manifestations of TB-T2DM comorbidity. Integrating metabolic and antimicrobial treatments via host-directed nuclear receptor therapies offers a potent, novel strategy to combat this complex dual epidemic, particularly in high-prevalence regions.

Background: Pulmonary tuberculosis (TB) is a significant trigger of acute exacerbations of chronic obstructive pulmonary disease (AECOPD), so its timely and accurate diagnosis is essential. Also, the risk factors for TB occurrence in this population remain unclear. This study aimed to evaluate the performance of metagenomic next-generation sequencing (mNGS) for TB diagnosis in AECOPD patients, as well as to identify the associated risk factors. Methods: A retrospective observational cohort of 659 AECOPD patients with suspected pulmonary infection was enrolled. The microbial cell-free nucleic acids in bronchoalveolar lavage fluid samples were extracted and subjected to mNGS detection. The clinical data for each patient were collected from the hospital information system. The statistical analyses were performed with SPSS version 25.0. Results: A total of 170 cases, included for final analyses, were categorized into TB (n = 41), bacterial infection (n = 73), and non-infective control (n = 56) groups. Among these groups, the TB group had the highest intensive care unit (ICU) admission rate (46.34%) and longest median hospital stay (19.50 days) (p < 0.01). For TB diagnosis, mNGS demonstrated a greater sensitivity (86.00%), a lower specificity (93.30%), and a higher area under the curve (AUC, 0.877) than TB-DNA detection (70.21%, 100%, 0.848, respectively) and Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) assay (63.83%, 100.00%, 0.870, respectively). Notably, mNGS identified the bacterial or viral co-infections in 18.00% of TB cases. Furthermore, the stringently mapped read number determined by mNGS showed a positive correlation with ICU admission rate (r = 0.76) and in-hospital mortality (r = 0.77). The lower body mass index (BMI) and reduced natural killer (NK) cell count were identified as the independent risk factors in the TB group (both p < 0.05). Conclusions: For the diagnosis of pulmonary TB in AECOPD patients, mNGS demonstrated comparable performance to TB-DNA detection and Xpert MTB/RIF assay, and also mNGS identified co-infections. In addition, a lower BMI and reduced NK cell count were identified as the independent risk factors for TB occurrence in this cohort.

In public health, meaningful community engagement has consistently been linked to improved access to timely diagnosis, strengthened treatment adherence, reduced stigma, and better overall health outcomes, particularly among marginalized and underserved populations. Effective engagement fosters trust, enhances service utilization, and promotes sustained care-seeking behaviour. However, genuine empowerment extends beyond simple participation in health programs; it encompasses the ability of communities to influence local governance processes and address broader social determinants such as nutrition, sanitation, education, and livelihood security, while functioning as a dynamic and transformative process that shifts communities from passive beneficiaries to active agents of health action. Community empowerment operates through interconnected logistical and psychological pathways. Logistical support improves access to diagnosis, treatment continuation, and linkage with health systems, while psychosocial reinforcement through peer support and survivor engagement strengthens motivation, reduces internalized stigma, and sustains long-term adherence. At the same time, empowerment is shaped by local socio-economic realities, including poverty and livelihood insecurity, and may face risks such as volunteer burnout, stigma toward community workers, inequitable reliance on unpaid labor, and limited financial sustainability-underscoring the need for ethical safeguards and social protection. Tuberculosis (TB) remains a major global public health challenge despite the availability of effective chemotherapy. According to the World Health Organization, TB continues to affect millions annually and remains a leading cause of infectious disease mortality worldwide. Within the End TB Strategy, community engagement and civil-society participation-including contributions from national and nongovernmental organizations-are recognized as critical to sustainable TB control. TB elimination therefore requires not only biomedical interventions but also ethically supported, economically feasible, and institutionally sustained community empowerment capable of transforming participation into shared ownership of tuberculosis control.

Tuberculosis has been one of the biggest issues of public health in India with constant diagnostic delays, stigma, and poor treatment-seeking behaviour serve as barriers to Disease elimination process. Although the diagnostic and surveillance technologies have been improved at a rapid pace. The society is still Stemming from lagging in community engagement and thus the awareness cannot be converted to action. This research explores the opportunities of tele-education as a scaled process to enhance the community involvement in the issue of the control of tuberculosis in opposite high-case environments in an urban slum cluster and a tribal village network. An intervention based on the use of four videos, audio modules, quizzes, and ASHA-promoted reinforcement was implemented on 112 households over a period of four weeks via tele-education. The results showed that both sites had great improvements in TB literacy in addition to behaviour change that was observed through the self-initiated referrals, increased uptake of screening, and the facilitation of information with peers. Despite the fact that the urban slum had a higher level of digital participation, the tribal community acquired knowledge the same way by a hybrid offline-based model. The findings highlight the relevance of contextual differentiation, trusted intermediaries and blended learning methods in realizing the maximum impact of tele-education. Tele-education as a potential solution to speed up eliminating TB nationally can be viewed offenders by considering communities as active participants not as passive recipients, through a reformulation of communities as active partners, which facilitates population health initiatives beyond biomedical innovation.

Tuberculosis (TB) remains a significant public health threat in urbanizing regions of China, where shifting population dynamics and migration may amplify TB transmission. We conducted a nine-year prospective epidemiological study of culture-positive TB patients diagnosed in Shenzhen, between 1 January 2014 and 31 December 2022, and employed whole-genome sequencing analysis to describe local transmission of Mycobacterium tuberculosis (Mtb). Mtb transmission hotspots were identified using a non-parametric distance-based mapping approach. We applied a spatially structured logistic regression and hierarchical Bayesian pairwise regression analysis to identify demographic, pathogen, and spatial factors associated with local transmission. A Bayesian phylogenetic analysis was used to infer probable transmission events. Among 4,560 individuals with culture-positive TB, 93.4% (4,261) were internal migrants in China. 21.8% (996/4,560) of individuals had Mtb isolates that belonged to genomic clusters, with multiple transmission foci detected in the central business district and suburban industrial areas. Transmission was more likely to occur among patients of similar age, close geographic proximity, and migrants with a shared provincial origin. Mtb isolates from communities with higher proportions of migrants had an increased risk of clustering. In this rapidly growing urban setting, a significant proportion of cases were documented to arise as a result of local transmission, which appears to be driven by specific social and geographical factors, particularly within migrant populations. Control strategies should therefore move beyond static models toward dynamic interventions that specifically target social networks, high-risk communities, and urban hotspots in dynamic urban environments.

This study compared Virtual Reality (VR) simulation training with matched standard instruction for tuberculosis (TB) diagnosis in a controlled simulation lab. The aim was to assess whether immersive simulation improves standardized TB diagnostic competency and whether VR is tolerable for trainees. Trainees completed a starting assessment, received assigned training, and completed the same standardized post-training assessment within 7 days, with a retention assessment around 8 weeks. Post-training competency accuracy was higher with VR simulation training, with an estimated mean difference of 0.08 [0.03, 0.13], p&#xa0;=&#xa0;0.003, and planned additional checks showed the same direction. These findings are limited to performance on standardized simulations and recorded VR tolerability, not patient outcomes or routine diagnosis in practice. The results may inform medical educators, TB program implementers, and simulation and skills lab leads when considering whether to add VR modules to TB diagnosis training.

Tuberculosis (TB) remains a major public health problem in India, which reported about a quarter of the world's TB cases in 2023. Awareness programs are vital for early diagnosis and treatment, yet reaching rural populations in states like Bihar is challenging because of low digital literacy, poor internet coverage and a reliance on shared devices. This intervention study compared facilitator-supported e-learning modules with a more informal mobile-based education approach to assess which method better improves community TB knowledge. Adults from rural and semi-urban Bihar were assigned at the cluster level to either group sessions at community centres or to self-directed mobile messaging. Both interventions provided identical content tailored to local language and literacy levels and were evaluated using pre- and post-intervention knowledge tests, retention assessments, engagement logs, completion rates, satisfaction surveys and reported willingness to share information. Results showed that the structured e-learning group achieved higher gains in knowledge (37.6% vs 34.1%), stronger retention after four weeks (82.3% vs 77.5%) and higher engagement and completion rates. Participant satisfaction and willingness to discuss TB topics with peers were also higher in the e-learning arm. The study suggests that community-based digital learning delivered through facilitated group sessions can overcome barriers posed by low literacy and variable connectivity and may be preferable to unstructured mobile messaging for TB awareness. Expanding such models alongside digital literacy initiatives could contribute to better TB control.

The complex lipid composition of Mycobacterium tuberculosis (MTB) plays a pivotal role in pathogenesis, immune evasion, and antimicrobial resistance. The continued surge in drug-resistant strains underscores the need for a deeper understanding of the molecular architecture underlying MTB pathogenesis and drug resistance. In this study, a comparative lipidomics approach was applied to explore the resistance-associated lipid alterations in drug-sensitive (DS), drug-resistant (DR), multidrug-resistant (MDR), and pre-extensively drug-resistant (PXDR) MTB clinical isolates. Lipids derived from whole bacilli (TL) and cell wall (CWL) extracts were separately analyzed using untargeted and targeted lipidomics approaches. Untargeted analysis revealed the abundance of fatty acyls, glycerolipids, glycerophospholipids, prenol lipids, polyketides, and saccharolipids, with distinct phenotypes and compartment-specific distributions. Notably, CWL extracts showed clearer resistance-associated separations relative to TL extracts. Targeted profiling further demonstrated enrichment of glycerolipids and PC and LPC lipids among drug-resistant isolates. Biomarker analysis identified discriminative lipid species in both extracts, albeit with greater discriminatory power in CWL. Overall, these findings elucidate coordinated and compartment-associated lipid alterations at the species level in different MTB clinical isolates. This will help to provide a valuable source for screening diagnostic biosignatures and intersecting biosynthetic pathways of mycobacterial lipids in the evolution of drug resistance in MTB for therapeutic interventions.

This study compares a digital case-based learning module with standard training for improving guideline-concordant clinical decisions in tuberculosis (TB) care. Evidence on whether digital training improves TB decision accuracy is limited when both groups complete the same scored case assessment. In a two-arm parallel trial, clinicians or trainees were assigned to either the digital module or standard lecture or continuing medical education training, then completed a standardized vignette test within 7 days. Guideline-concordant decision accuracy was higher with the digital module, with an intention-to-treat risk difference of 0.06 [0.02, 0.1]. Because the scoring rules and assessment content were the same in both arms, this comparison indicates the added value of digital cases for standardized decisions on the vignette test, within the reported interval. These findings reflect vignette performance rather than patient outcomes and may inform TB program implementers and medical educators planning scalable decision-making training.

This study compared digital storytelling with standard community education to reduce tuberculosis (TB) stigma. Prior work on digital storytelling in TB control often focuses on uptake, so effects measured during follow-up are less clear. A prospective mixed-methods evaluation compared community clusters. Surveys were completed before exposure and again at 3 months (90 days), alongside interviews and 30-day engagement records. The between-group difference in mean change in stigma score was -1.4 [-2.3, -0.4] with p&#xa0;=&#xa0;0.006, which is consistent with larger average stigma reductions with digital storytelling. The between-group difference in mean change in knowledge score was 0.9 [0.1, 1.7] with p&#xa0;=&#xa0;0.028. Combining the survey results with engagement data and interview themes linked score changes to engagement and acceptability. Because communities were not assigned at random and spillover was possible, these findings should be interpreted as comparative evidence from the evaluated setting and may inform TB program implementers and community health worker supervisors planning stigma-safe education activities.

Tuberculosis (TB) has been a major health issue of concern globally, where timely diagnosis has been a major factor in spreading the disease and causing death, especially in underprivileged environments. The aim of the presented study was to construct and analyze an Information and Communication Technology (ICT)-enabled model of engaging communities in the effort of increasing the rates of early TB detection by means of increased community engagement and simplified diagnostic routes. It was a prospective, quasi-experimental study that was carried out in twelve community health centers in three districts over a period of eighteen months where ICT-enabled intervention sites (n&#xa0;=&#xa0;6) were compared with the conventional screening sites (n&#xa0;=&#xa0;6). ICT framework also incorporated a mobile health application to the community health worker, automated short message service (SMS) to monitor the symptoms, cloud-based case management, and geographic information system (GIS) to monitor the hotspots. One thousand eight hundred four hundred and seventy seven presumptive TB cases were registered where 923 were ICT-enabled and 924 were control sites. Findings indicated that ICT-enabled sites recorded much higher rates of case detection (78.4% vs. 52.1, p&#xa0;<&#xa0;0.001), median time to diagnosis was lower (12.3&#xa0;&#xb1;&#xa0;4.2 days vs. 28.7&#xa0;&#xb1;&#xa0;8.9 days, p&#xa0;<&#xa0;0.001), and higher rates of treatment initiation within 48&#xa0;h were recorded (89.2% vs. 61.4, p&#xa0;<&#xa0;0.001). The efficiency of community health workers increased by 43.6 and there was 2.8 fold greater number of household contacts screened by the worker per monthly. ICT-enabled model had better performance with regard to the facilitance of early TB detection using enhanced community engagement, which is a cost-effective and scalable solution to TB control programs fortification.