Search Results (332)

Background/Objectives: Several subunit vaccines for tuberculosis (TB), such as MVA85A and H4:IC31, have not demonstrated ideal protective efficacy in clinical trials, which may be attributed to their limited antigenic profile and lack of effective latency-associated antigens. In this study, we combined bioinformatics with experimental validation to screen for latency-associated antigens that have immune-protective effects. Methods: Highly expressed antigens were identified from models related to latent infections, such as hypoxia and nutritional starvation. Their physicochemical properties and immunogenicity were predicted using online tools such as Expasy-ProParam, IEBD, and VaxiJen. The immunogenicity of these antigens was then evaluated in multiple mycobacterium infection models. Finally, a systematic evaluation of the immune response and protective effects induced by the candidate antigens was performed in a mouse model using intracellular cytokine detection, mycobacterium growth inhibition assays (MGIAs), antibody-dependent cellular phagocytosis (ADCP), and a latent tuberculosis infection (LTBI) mouse model. Results: The antigen Rv2656c is highly expressed in the nutritional starvation model and demonstrates strong immunogenicity in both infected humans and cattle. Moreover, Rv2656c exerted a significant inhibitory effect against Mycobacterium tuberculosis (M. tuberculosis) and Mycobacterium avium (M. avium) infections in MGIA. The humoral immune response elicited by Rv2656c enhanced the phagocytosis and killing of Mycobacteria by macrophages in vitro. Furthermore, in a mouse model of LTBI established using the attenuated M. tuberculosis H37Ra strain, treatment with Rv2656c significantly decreased the bacterial load in the lungs of the mice. Conclusions: Latency-associated Rv2656c may serve as an immune-protective antigen, offering potential for the development of novel multi-stage antigen subunit vaccine against TB. Full article

Background/Objectives: Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains a major global health problem. Drug resistance and the limitations of sputum-based diagnostic methods highlight the need for additional host-response biomarkers. Protein tyrosine phosphatase receptor type O (PTPRO) has been implicated in inflammatory signaling and macrophage immune regulation, but its relationship with TB-related host transcriptional responses remains unclear. This study aimed to identify and preliminarily evaluate a PTPRO-related blood transcriptional signature with potential relevance to TB discrimination and treatment-response assessment. Methods: Genes correlated with PTPRO expression were first screened using TCGA-LUSC as a large human transcriptomic discovery resource. The resulting candidate genes were then filtered in TB-related whole-blood datasets by intersecting genes upregulated in TB compared with healthy controls, pneumonia, and lung cancer. This strategy yielded a five-gene PTPRO-related signature, termed PO5. The signature was evaluated in independent GEO cohorts and further explored by RT-qPCR in H37Ra-infected THP-1-derived macrophages and in a small clinical blood cohort. A PO5-derived TB risk score was calculated for each sample, and receiver operating characteristic analysis was used to assess discriminatory performance. Changes in TB risk scores during anti-TB treatment were also examined. Results: PTPRO expression was increased in TB whole-blood transcriptomic data and in H37Ra-infected macrophages. In public datasets, PO5 showed potential for distinguishing TB from healthy controls, latent TB, pneumonia, and lung cancer. PO5-derived TB risk scores also decreased after anti-TB treatment. In the exploratory clinical cohort, several PO5 genes showed expression changes in the same general direction as those observed in the public datasets, although the small sample size limited the strength of this evidence. Conclusions: PO5 represents a preliminary PTPRO-related blood transcriptional signature with potential relevance to TB discrimination and treatment-response assessment. These findings remain exploratory and require validation in larger prospective multicenter cohorts, together with further mechanistic studies. Full article

Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide, with children representing a particularly vulnerable population in whom diagnosis is often challenging. Pediatric TB is typically paucibacillary and presents with non-specific clinical manifestations, limiting the sensitivity of microbiological confirmation and increasing reliance on immunological tests. The Tuberculin Skin Test (TST) and Interferon-Gamma Release Assays (IGRAs) are the most widely used tools for detecting Mycobacterium tuberculosis infection, yet both have important limitations, especially in young children and in Bacillus Calmette–Guérin (BCG)-vaccinated populations. TST lacks specificity due to cross-reactivity with BCG and environmental mycobacteria, while IGRAs, although more specific, require laboratory infrastructure and may have reduced sensitivity in early childhood. The Tuberculosis Skin Test (TBST), based on M. tuberculosis-specific antigens such as ESAT-6 and CFP-10, has emerged as a promising alternative that combines the operational simplicity of TST with the antigenic specificity of IGRA. This paper reviews the immunological principles, diagnostic performance, and practical considerations of TBST in pediatric populations, with direct comparison to TST and IGRA. Evidence from recent studies suggests that TBST may offer improved specificity over TST, with broadly comparable diagnostic accuracy to IGRA in some settings, although findings are not fully consistent across studies. Particular attention is given to its performance in BCG-vaccinated children and, based on emerging evidence, in those under five years of age. The potential role of TBST in clinical algorithms and public health strategies is discussed, along with current evidence gaps and future research priorities. Full article

Background/Objectives: Tuberculosis remains one of the preventable causes of mortality among liver transplant recipients. The prevalence of tuberculosis in solid organ transplant recipients is higher than in the general population. The aim of this study was to evaluate the incidence of latent tuberculosis infection (LTBI) and active tuberculosis after liver transplantation. Methods: This is a retrospective, single-center, case–control study. Adult liver transplant candidates who were evaluated between 1 January 2016 and 31 December 2022 were retrospectively assessed. Patients with pre-transplant tuberculin skin test (TST) and/or interferon-gamma release assay (IGRA) results who underwent transplantation were included in this study. Results: A total of 111 liver transplant recipients with available IGRA and/or TST results were included; 70 were men (63.1%) and 41 were women (36.9%), with a mean age of 53.5 ± 11.3 years. Demographic, clinical, and laboratory characteristics were evaluated. The most common indication for liver transplantation was viral hepatitis (33.3%), followed by cryptogenic cirrhosis (19.8%) and hepatocellular carcinoma (10.8%). All patients had a Bacillus Calmette–Guérin (BCG) vaccination scar. Ten patients received grafts from deceased donors, while 101 underwent living-donor liver transplantation. No patient received LTBI treatment before transplantation, whereas LTBI treatment was initiated in four patients after transplantation. None of the patients had a diagnosis of active tuberculosis prior to transplantation. Thoracic computed tomography revealed findings compatible with tuberculosis sequelae in 11 patients (9.9%). During a median follow-up period of 49 [27–64] months after transplantation, no cases of active tuberculosis were observed among patients with positive TST and/or IGRA results. Patients were divided into two groups according to their TST and IGRA results. Group 1 consisted of patients with IGRA positivity and/or a TST ≥ 5 mm, while Group 2 included patients with a TST < 5 mm and negative IGRA results. The only statistically significant difference between the groups was the administration of LTBI treatment (p = 0.027); four patients in Group 1 received LTBI therapy. None of these patients were able to continue prophylaxis due to treatment-related adverse effects. Conclusions: Prophylaxis with hepatotoxic agents poses a substantial risk in liver transplant candidates. Since the hepatotoxicity may cause early cessation of LTBI treatment, the risk–benefit ratio of post-transplant LTBI therapy should be carefully assessed. In situations where LTBI treatment is deferred, close clinical monitoring is strongly recommended. Full article

This study develops an integrated mathematical model to investigate the interaction between tuberculosis (TB) transmission and childhood stunting, which is aligned with the United Nations Sustainable Development Goals (SDG 3). The population is structured into two age groups (0–5 years and ≥5 years), with stunting explicitly incorporated into the pediatric population to capture its potential influence on TB dynamics. The model is formulated as a system of ordinary differential equations and analyzed using equilibrium and stability analysis, with the basic reproduction number, $R_0$. The disease-free equilibrium is locally asymptotically stable when $R_0<1$, while an endemic equilibrium exists when $R_0>1$. Sensitivity analysis indicates that the transmission rate ($\beta$), progression rate from latent to active infection ($\sigma$), and recovery rate ($\gamma$) are the most influential parameters affecting $R_0$. These parameters are therefore selected as control variables in an optimal control framework to design effective intervention strategies. Numerical simulations show that the combined control strategy significantly reduces TB transmission, resulting in a reduction of more than $80\%$ in active TB cases within a relatively short intervention period. The results suggest that integrated interventions targeting transmission, disease progression, and recovery are substantially more effective than single-measure strategies. This study provides a quantitative framework to support integrated public health policies addressing TB and childhood stunting simultaneously. Full article

Background: Tuberculosis (TB) remains a major global health challenge, with Mycobacterium tuberculosis (M. tuberculosis) causing significant morbidity and mortality mainly in high-burden countries. Following exposure to M. tuberculosis, individuals may become infected, developing TB infection (TBI) through inhalation of the bacillus: this affects approximately one-fourth of the global population and serves as a critical reservoir for potential disease reactivation and transmission. The risk of being infected with M. tuberculosis is shaped by bacterial load of people with TB, contact patterns, environmental factors, and host susceptibility, particularly in high-risk congregate settings. Elucidating these determinants is instrumental for optimising TB prevention and control strategies. Methods: A preliminary PubMed search was conducted on 25 August 2024, using the keywords “latent tuberculosis infection,” “risk factors,” and “systematic review.” Targeted reviews were then performed in November 2024 to examine factors influencing progression from exposure to M. tuberculosis to TBI. Systematic reviews published between January 2000 and November 2024 were included. Results: The scoping review analysed eight systematic reviews, grouping findings into three key themes: (1) proximity and behavioural risk factors; (2) environmental risk factors; and (3) host immune vulnerabilities. Close contact with people with TB in crowded settings, such as dormitories, healthcare facilities, and prisons, was strongly associated with an elevated risk of TBI. Healthcare workers travelling from low- to high-incidence regions faced the highest risk due to frequent exposure to M. tuberculosis, while military personnel and general travellers had lower risks. Environmental exposures, including second-hand smoke and inadequate ventilation, further heightened susceptibility among children and adults. Host immune risk factors, such as advanced age, low body mass index, lack of BCG vaccination, and metabolic disorders such as diabetes, markedly increase susceptibility to TBI. The interplay between proximity, behavioural and environmental risk factors, and host immune vulnerabilities highlights the multifactorial nature of TBI risk. Conclusion: Effective TBI control demands a multifaceted approach, combining robust infection prevention and control measures, comorbidity management, and mitigation of behavioural risk factors like smoking. Tailored strategies are crucial for high-risk settings such as healthcare facilities and prisons. Multisectoral collaboration is essential to address key risk factors and protect vulnerable populations from progressing to TBI. Full article

Background: Patients with latent tuberculosis infection are mainly asymptomatic, but they still carry a notable risk of developing active TB, particularly when the host becomes immunosuppressed. Hence, appropriate diagnosis and management for LTBI are essential. Tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) are among the most commonly utilized methods for detecting LTBI. Until now, no agreement has been established regarding the most effective diagnostic test, either TST or IGRA, so our study aims to evaluate the diagnostic utility of TST versus IGRA in detecting LTBI. Methods: An extensive literature search was executed in several databases from inception till June 2024. We included all the available studies that compared TST versus IGRA concurrently applied to the same study participants, utilizing one of the following proxy reference standards: previous contact with a tuberculosis patient, tuberculosis history, chest x-ray suggestive of tuberculosis, or a combination of them. The sensitivity (SN) and specificity (SP) were imputed with their 95% confidence interval (CI). A bivariate random-effects model within the OpenMeta-Analyst software was utilized for data analysis. Results: We included 39 studies, and our primary analysis regarding LTBI revealed that TST has an SN of 0.320 (95% CI [0.254–0.393]) and an SP of 0.808 (95% CI [0.752–0.854]). Nevertheless, the IGRA exhibited a higher SN estimated at 0.362 (95% CI [0.295–0.434]) and a lower SP estimated at 0.758 (95% CI [0.700–0.808]). Regarding the adult population, TST consistently showed a lower SN and a higher SP relative to IGRA. However, within the pediatric population, TST showed higher SN and lower SP when compared to IGRA. Furthermore, TST also showed a lower SN and a higher SP within hemodialysis and organ transplant patients than IGRA. Conclusions: Our diagnostic test meta-analysis revealed that TST was associated with a lower SN and a higher SP than IGRA. Clinicians should interpret these findings with caution, considering the substantial heterogeneity observed across the included studies, the reliance on proxy reference standards, the potential influence of BCG vaccination status, and the considerable overlap in confidence intervals between TST and IGRA estimates across most analyses. Full article

Background and Objectives: Isoniazid monotherapy has been the most widely used treatment for latent tuberculosis infection (LTBI). Although effective, it has been associated with poor adherence and a higher incidence of adverse events. The shorter duration of rifamycin-based regimens has become increasingly preferable. The one month of daily rifapentine plus isoniazid (1HP) has demonstrated low toxicity and higher completion rates in HIV-infected populations. This study aims to compare the completion rate and adverse events between the 1HP and daily isoniazid for 6 months (6H) regimens in the non-HIV adult population. Materials and Methods: Retrospective, observational, longitudinal study, followed at the National Reference Center for Tuberculosis (Lisbon, Portugal), from January 2024 to January 2025. Treatment-related symptoms and liver function were assessed throughout the treatment. Relevant hepatic toxicity was defined as aspartate transaminase (AST) and/or alanine transaminase (ALT) > 1.5 times the upper limit of normal (ULN). Results: A total of 90 and 74 patients were assigned to the 1HP and 6H groups, respectively. No significant differences were observed in the frequency of reported adverse symptoms between the 1HP and 6H groups (28.9% vs. 23.0%, p = 0.4). The 1HP regimen was associated with a significantly lower risk of relevant hepatic toxicity (4.6% vs. 32.9%, p < 0.001) and a higher rate of treatment completion (97.8% vs. 67.6%, p < 0.001). Adverse drug reactions were the leading cause of treatment discontinuation in both groups, with hepatic toxicity and gastrointestinal intolerance being the most frequent events. A therapeutic switch to rifampicin was required in 16.2% of patients receiving the 6H regimen, whereas no switch was needed in the 1HP group. Conclusions: The 1HP regimen was associated with a higher rate of treatment completion and lower hepatic toxicity with no significant differences in the reported adverse symptoms. Full article

The lack of reliable diagnostic tools and relapse monitoring for latent tuberculosis infection (LTBI) constitutes a major obstacle to global tuberculosis (TB) control. This highlights an urgent need for robust animal models and predictive biomarkers. To address this, we report the successful establishment of a rapid murine model of recapitulating the active, latent, and relapse phases of TB within a compressed ten-week timeframe—hence termed the rapid multi-stage TB murine model. In this model, mice were first intravenously infected with Mycobacterium tuberculosis, followed by a four-week isoniazid (INH) regimen starting at two weeks post-infection. By week six, pulmonary bacterial loads in most mice dropped below the detection limit, signifying the establishment of latency. Reactivation was subsequently triggered by a four-week administration of anti-TNF-α (Tumor Necrosis Factor-α) monoclonal antibody. Leveraging this reproducible and time-efficient model, we performed transcriptomic profiling of peripheral blood and identified a distinct sixteen-gene signature (including Ets2, Fam111a, Fosl2, Gadd45b, Nfkbid, Rgs1, Bhlhe40, Il1r2, Clec2d, Kmo, Lynx1, Papd4, Trim34a, Wrb, Nlrp12, Spns1) that dynamically tracks disease progression. Collectively, these findings not only provide a valuable and efficient preclinical tool but also deliver transformable candidate biomarkers with immediate potential to guide the development of novel diagnostic strategies for LTBI surveillance and management. Full article

Antitubercular drug-induced liver injury (ATDILI) poses a significant obstacle to successful tuberculosis treatment, including for tuberculous lymphadenitis. Its global incidence varies considerably, typically ranging from 2% to 30%, influenced by factors like patient demographics, co-morbidities, and geographical context. Despite some findings suggesting potentially lower rates in tuberculous lymphadenitis, the inherent hepatotoxic nature of standard anti-TB drugs means the risk remains clinically relevant. Key risk factors for ATDILI encompass older age, female gender, pre-existing liver conditions, HIV co-infection, malnutrition, alcoholism, and genetic polymorphisms, particularly in N-acetyltransferase 2 which affects isoniazid metabolism. The mechanisms of injury are drug-specific: isoniazid primarily causes hepatocellular damage via oxidative stress from toxic metabolites, while rifampicin induces cholestasis and endoplasmic reticulum stress, and pyrazinamide is linked to mitochondrial dysfunction. Management involves prompt withdrawal of antitubercular therapy when liver enzyme thresholds are exceeded, followed by careful reintroduction. Challenges are amplified in resource-limited settings due to higher prevalence of risk factors and limited access to consistent monitoring and sophisticated diagnostics. Promising advancements include safer regimens like the 3-month once-weekly isoniazid-rifapentine (3HP) for latent TB, which significantly reduces hepatotoxicity. The development of shorter active TB regimens and novel anti-TB drugs with improved safety profiles further aims to enhance treatment adherence and reduce ATDILI incidence, ultimately improving patient outcomes globally. Full article

Background: Latent tuberculosis infection (LTBI) is the principal reservoir for active tuberculosis, with >85% of cases attributable to reactivation. Bacillus Calmette-Guérin fails to block this transition, leaving a critical gap in prevention. Methods: An immunoinformatics/reverse-vaccinology pipeline was applied to seven dormancy-related antigens retrieved from Mycobrowser. T-cell epitopes were predicted with NetMHCI/IIpan-4.1 and B-cell epitopes with ABCpred; antigenicity, allergenicity, and toxicity were evaluated with VaxiJen, AllerTOP, and ToxinPred. Secondary/tertiary structures were modeled with PSIPRED and AlphaFold-3; docking to Toll-like receptors (TLR) 2/4 and 100 ns molecular dynamics simulations assessed complex stability. Immune responses were simulated with C-ImmSim, and the mRNA sequence was human-codon-optimized using ExpOptimizer. Results: The resulting construct, RP14914P, encodes 14 cytotoxic T lymphocyte, 9 helper T lymphocyte, and 14 B-cell epitopes within an 866-aa, 90.4 kDa polypeptide. Antigenicity score = 0.7797, immunogenicity score = 8.58629. and no toxicity or allergenicity was predicted. Physicochemical analysis: instability index = 28.65, and solubility = 0.513. Estimated population coverage is 82.35% and 99.67% for Human Leukocyte Antigen (HLA)-I and HLA-II globally. Docking energies: −1477.8 kcal/mol (TLR2) and −1480.1 kcal/mol (TLR4). Molecular dynamics trajectories confirm stable binding. Immune simulation predicts potent activation of Natural Killer cells, macrophages, and dendritic cells, Th1 polarization, high interferon-γ/interleukin-2 secretion, and durable memory. Conclusions: In silico analyses predict that RP14914P exhibits favorable immunogenicity, safety, and broad population coverage, suggesting its potential as a promising mRNA vaccine candidate to prevent LTBI reactivation. However, these computational predictions require thorough experimental validation to confirm the vaccine’s immunogenicity and protective efficacy. Full article

Approximately 25% of the global population is estimated to have latent tuberculosis infection (LTBI), with a 5–10% lifetime risk of progression to active disease. Although interferon-gamma release assays (IGRAs) are widely used for LTBI diagnosis, their high cost and operational complexity limit large-scale implementation in resource-limited settings. This study evaluated the diagnostic performance of a low-complexity, rapid, fluorescence-based point-of-care assay, ichroma IGRA-TB, for LTBI detection. A total of 300 participants enrolled at TB Screening and Treatment Centers and the Dhaka Hospital of icddr,b were categorized as healthy controls (n = 130), household contacts of TB patients (n = 70), GeneXpert MTB/RIF Ultra-positive active TB patients (n = 80), or individuals with a previous history of TB (n = 20). ichroma IGRA-TB was compared with QuantiFERON-TB Gold Plus (QFT-Plus) across all groups. Overall agreement between ichroma IGRA-TB and QFT-Plus was 91.9%, with a Cohen’s kappa of 0.83, indicating almost perfect concordance. Using culture as a surrogate reference standard, QFT-Plus demonstrated higher sensitivity (74.6%) than ichroma IGRA-TB (69.0%). Overall, ichroma IGRA-TB demonstrates high agreement with QFT-Plus and acceptable sensitivity, supporting its potential as a near-point-of-care tool for LTBI screening in resource-constrained settings. Full article

Tuberculosis (TB) remains a major public health challenge in China despite substantial long-term progress. Using data from the Global Burden of Disease Study 2023, this study reassessed trends and determinants of TB burden in China from 1990 to 2023. Age-standardized incidence, mortality, and disability-adjusted life year (DALY) rates were analyzed using estimated annual percentage change, age–period–cohort modeling, and demographic decomposition, with comparative risk assessment to quantify behavioral and metabolic contributions. Between 1990 and 2023, age-standardized incidence, mortality, and DALY rates declined by approximately 73.24%, 94.00%, and 92.40%, respectively. Negative net and local drift values indicated sustained reductions across age groups; however, the decline slowed after 2021, with a modest rebound in incidence. Since 2015, reductions in incidence have been more moderate than the pace required to achieve the 2035 End TB Strategy targets. Decomposition analysis demonstrated that improvements in age-specific rates were the primary drivers of long-term reductions, whereas demographic shifts—particularly population aging—partially offset these gains. The burden increasingly shifted toward older adults, and males consistently experienced higher rates than females. Tobacco and alcohol use contributed substantially to sex differentials, while undernutrition and metabolic disorders remained relevant risk factors. These findings indicate that China’s TB epidemic has entered a phase shaped by demographic aging and evolving risk structures, requiring sustained and adaptive control efforts. Full article

Background/Objectives: Mycobacterial infections and autoimmune diseases affect many worldwide, and growing evidence suggests that there is a bidirectional relationship. This review examines mechanisms by which various autoimmune diseases predispose patients to mycobacterial infections, and vice versa. Methods: We conducted a PubMed/MEDLINE search using the keywords “mycobacterium” and the names of the autoimmune conditions to identify relevant papers. Results: Rheumatoid arthritis therapies, especially TNF-α inhibitors, raise tuberculosis (TB) and non-tuberculous mycobacteria (NTM) risk. Type 1 diabetes features impaired cell-mediated immunity and macrophage dysfunction, with evidence for Mycobacterium avium subspecies paratuberculosis (MAP) mimicry involving HSP65–GAD65. In systemic lupus erythematosus, immune dysregulation plus corticosteroids and cytotoxins elevates TB and NTM risk, amplified in endemic settings. In multiple sclerosis, heightened TLR2/4/9 signaling agents that inhibit pyrimidine synthesis may increase IL-10 and reduce antimycobacterial immunity. Crohn’s disease shows genetic susceptibility (e.g., NOD2 variants) and MAP detection, supporting impaired clearance of intracellular mycobacteria. Conclusions: Overall, evidence supports a bidirectional relationship: mycobacterial antigens can initiate or amplify autoimmunity via molecular mimicry and chronic stimulation, while autoimmune biology and iatrogenic immunosuppression increase susceptibility to infection. Implications include latent TB screening before immunosuppression, attention to local epidemiology, and vigilance for NTM. Research priorities include prospective cohorts, mechanistic studies of mimicry and NOD2–TLR pathways, safety registries, and trials of screening and prophylaxis. Full article

Background/Objectives: An important diagnostic problem is to differentiate between active tuberculosis (TB) and latent TB infection (LTBI). Furthermore, the current biomarkers also offer minimal insight into disease pathogenesis to direct treatment. This triggered us to design a two-mode biomarker signature based on the multicohort analysis using a transcriptomic and stringent machine learning pipeline. Methods: When analyzing active TB, latent TB, and healthy control samples, a rigorous filter (ANOVA, p < 0.001) was used, followed by the selection of features with the help of Boruta-XGBoost and LASSO regression. This determined a small four-gene signature (TAP2, SORT1, WARS, and ANKRD22), which was selectively and highly upregulated in the active TB clinical state (p < 0.001). An ensemble staking classifier based on this signature (Random Forest and XGBoost) had a very high diagnostic performance (ROC-AUC = 0.991 (95% CI: 0.983–0.997)) in the stratification of infection phases, which was strongly confirmed in another cohort (GSE19444). Results: Importantly, the analysis of the functional pathways showed that all the genes are mapped to core dysregulated host pathways in active TB: antigen presentation (TAP2), lipid trafficking (SORT1), interferon response (WARS), and inflammasome signaling (ANKRD22). In such a way, the signature has a dual advantage: (1) high specificity, non-sputum transcriptional diagnostic of active TB, and (2) a mechanistic map of key host pathways, which describes targets of intervention. Conclusions: Thus, the signature provides a two-fold response: a biomarker panel aligned with WHO performance targets for TB triage and a mechanistic plan of therapy, which provides an easy way to implement transcriptomic discovery into clinical action against TB. Full article