MR1-restricted T cell clonotypes are associated with "resistance" to Mycobacterium tuberculosis infection.

T cells are required for protective immunity against Mycobacterium tuberculosis. We recently described a cohort of Ugandan household contacts of tuberculosis cases who appear to "resist" M. tuberculosis infection (resisters; RSTRs) and showed that these individuals harbor IFN-γ-independent T cell responses to M. tuberculosis-specific peptide antigens. However, T cells also recognize nonprotein antigens via antigen-presenting systems that are independent of genetic background, known as donor-unrestricted T cells (DURTs). We used tetramer staining and flow cytometry to characterize the association between DURTs and "resistance" to M. tuberculosis infection. Peripheral blood frequencies of most DURT subsets were comparable between RSTRs and latently infected controls (LTBIs). However, we observed a 1.65-fold increase in frequency of MR1-restricted T (MR1T) cells among RSTRs in comparison with LTBIs. Single-cell RNA sequencing of 18,251 MR1T cells sorted from 8 donors revealed 5,150 clonotypes that expressed a common transcriptional program, the majority of which were private. Sequencing of the T cell receptor α/T cell receptor δ (TCRα/δ) repertoire revealed several DURT clonotypes were expanded among RSTRs, including 2 MR1T clonotypes that recognized mycobacteria-infected cells in a TCR-dependent manner. Overall, our data reveal unexpected donor-specific diversity in the TCR repertoire of human MR1T cells as well as associations between mycobacteria-reactive MR1T clonotypes and resistance to M. tuberculosis infection.

Incidence and risk factors of active tuberculosis among older individuals with latent tuberculosis infection: a cohort study in two high-epidemic sites in eastern China.

Background: The influencing factors of the process from latent tuberculosis infection (LTBI) to the onset of active tuberculosis (TB) remain unknown among different population groups, especially among older individuals in high-incidence areas. This study aimed to investigate the development of active TB among older adults with LTBI and identify groups in greatest need of improved prevention and control strategies for TB. Methods: In 2021, we implemented an investigation among older individuals (≥ 65 years old) in two towns in Zhejiang Province with the highest incidence of TB. All participants underwent assessment using standardized questionnaires, physical examinations, interferon-gamma release assays, and chest radiography. All the participants with suspected TB based on the clinical symptoms or abnormal chest radiography results, as well as those with LTBI, were referred for diagnostic investigation in accordance with the national guidelines. Those with an initial diagnosis of TB were then excluded, whereas those with LTBI were included in a follow-up at baseline. Incident patients with active TB were identified from the Chinese Tuberculosis Management Information System, and a multivariate Cox regression model was used to estimate the incidence and risk of TB among those with LTBI. Results: In total, 667 participants with LTBI were followed up for 1,315.3 person-years, revealing a disease density of 1,292.5 individuals/100,000 person-years (17/1,315.3). For those with LTBI, chest radiograph abnormalities had adjusted hazard ratios for active TB of 4.9 (1.6-15.3). Conclusions: The presence of abnormal chest radiography findings increased the risk of active TB among older individuals with LTBI in high-epidemic sites in eastern China.

High-parameter phenotypic characterization reveals a subset of human Th17 cells that preferentially produce IL-17 against M. tuberculosis antigen.

Background: Interleukin-17-producing CD4 T cells contribute to the control of Mycobacterium tuberculosis (Mtb) infection in humans; whether infection with human immunodeficiency virus (HIV) disproportionately affects distinct Th17-cell subsets that respond to Mtb is incompletely defined. Methods: We performed high-definition characterization of circulating Mtb-specific Th17 cells by spectral flow cytometry in people with latent TB and treated HIV (HIV-ART). We also measured kynurenine pathway activity by liquid chromatography-mass spectrometry (LC/MS) on plasma and tested the hypothesis that tryptophan catabolism influences Th17-cell frequencies in this context. Results: We identified two subsets of Th17 cells: subset 1 defined as CD4+Vα7.2-CD161+CD26+and subset 2 defined as CD4+Vα7.2-CCR6+CXCR3-cells of which subset 1 was significantly reduced in latent tuberculosis infection (LTBI) with HIV-ART, yet Mtb-responsive IL-17-producing CD4 T cells were preserved; we found that IL-17-producing CD4 T cells dominate the response to Mtb antigen but not cytomegalovirus (CMV) antigen or staphylococcal enterotoxin B (SEB), and tryptophan catabolism negatively correlates with both subset 1 and subset 2 Th17-cell frequencies. Conclusions: We found differential effects of ART-suppressed HIV on distinct subsets of Th17 cells, that IL-17-producing CD4 T cells dominate responses to Mtb but not CMV antigen or SEB, and that kynurenine pathway activity is associated with decreases of circulating Th17 cells that may contribute to tuberculosis immunity.

Evaluation of cytokine profiles related to Mycobacterium tuberculosis latent antigens using a whole-blood assay in the Philippines.

Introduction: There is no useful method to discriminate between latent tuberculosis infection (LTBI) and active pulmonary tuberculosis (PTB). This study aimed to investigate the potential of cytokine profiles to discriminate between LTBI and active PTB using whole-blood stimulation with Mycobacterium tuberculosis (MTB) antigens, including latency-associated antigens. Materials and methods: Patients with active PTB, household contacts of active PTB patients and community exposure subjects were recruited in Manila, the Philippines. Peripheral blood was collected from the participants and used for whole-blood stimulation (WBS) with either the early secretory antigenic target and the 10-kDa culture filtrate protein (ESAT-6/CFP-10), Rv3879c or latency-associated MTB antigens, including mycobacterial DNA-binding protein 1 (MDP-1), α-crystallin (Acr) and heparin-binding hemagglutinin (HBHA). Multiple cytokine concentrations were analyzed using the Bio-Plex™ multiplex cytokine assay. Results: A total of 78 participants consisting of 15 active PTB patients, 48 household contacts and 15 community exposure subjects were eligible. The MDP-1-specific IFN-γ level in the active PTB group was significantly lower than that in the household contact group (p < 0.001) and the community exposure group (p < 0.001). The Acr-specific TNF-α and IL-10 levels in the active PTB group were significantly higher than those in the household contact (TNF-α; p = 0.001, IL-10; p = 0.001) and community exposure (TNF-α; p < 0.001, IL-10; p = 0.01) groups. However, there was no significant difference in the ESAT-6/CFP-10-specific IFN-γ levels among the groups. Conclusion: The patterns of cytokine profiles induced by latency-associated MTB antigens using WBS have the potential to discriminate between LTBI and active PTB. In particular, combinations of IFN-γ and MDP-1, TNF-α and Acr, and IL-10 and Acr are promising. This study provides the first demonstration of the utility of MDP-1-specific cytokine responses in WBS.

Latent tuberculosis prevalence, diagnosis and treatment in Multiple Sclerosis as a strategy for reducing infection reactivation during immunosuppressant therapy.

BACKGROUND: Tuberculosis is an infectious disease with a risk of reactivation in Multiple Sclerosis patients on immunosuppressant therapy. Diagnosis and treatment of Latent Tuberculosis Infection (LTBI) prevents the infection. OBJECTIVE: To diagnose and treat LTBI in Multiple Sclerosis (MS). METHODS: Cross-sectional study of the prevalence and treatment of LTBI in MS, between February 2021 and June 2023. LTBI was defined as an absence of symptoms, positive PPD or IGRA and normal chest X-ray. RESULTS: Of the 58 patients with MS, 17 (29.3 %) were diagnosed with LTBI, 15 with PPD > 5 mm and 2 with positive IGRA, 10 (58.8 %) female and 7 (41.1 %) male, mean age of 41.3 (SD ±13.4) years. All patients with LTBI were treated with immunomodulators or immunosuppressants: Fingolimod 5 (29.4 %), Natalizumab 5 (29.4 %), Cladribine 2 (11.8 %), Glatiramer 2 (11.8 %), Ocrelizumab 2 (11.8 %), and Interferon beta 1 (5.9 %). Steroids therapy for relapses, were used in 5/17 (93.8 %) with LTBI and 30/37 (81.1 %) without LTBI. To treat LTBI, 11 (64.7 %) received Isoniazid and 6 (35.3 %) Isoniazid plus Rifapentine. Hepatotoxicity occurred in 3 (17.6 %) with INH. There were no interruptions of ILTB treatment during the study. CONCLUSION: The prevalence of LTBI was found to be high and treatment proved safe.

Analysis of the potential regulatory mechanisms of female and latent genital tuberculosis affecting ovarian reserve function using untargeted metabolomics.

Female and latent genital tuberculosis (FGTB and LGTB) in young women may lead to infertility by damaging ovarian reserve function, but the regulatory mechanisms remain unclear. In this study, we investigated the effects of FGTB and LGTB on ovarian reserve function and potential regulatory mechanisms by untargeted metabolomics of follicular fluid, aiming to provide insights for the clinical management and treatment approaches for afflicted women. We recruited 19 patients with FGTB, 16 patients with LGTB, and 16 healthy women as a control group. Clinical data analysis revealed that both the FGTB and LGTB groups had significantly lower ovarian reserve marker levels compared to the control group, including lower anti-Müllerian hormone levels (FGTB: 0.82 [0.6, 1.1] µg/L; LGTB: 1.57 [1.3, 1.8] µg/L vs. control: 3.29 [2.9, 3.5] µg/L), reduced antral follicular counts (FGTB: 6 [5.5, 9.5]; LGTB: 10.5 [7, 12.3] vs. control: 17 [14.5, 18]), and fewer retrieved oocytes (FGTB: 3 [2, 5]; LGTB: 8 [4, 8.3] vs. control: 14.5 [11.5, 15.3]). Conversely, these groups exhibited higher ovarian response marker levels, such as longer gonadotropin treatment days (FGTB: 12 [10.5, 12.5]; LGTB: 11 [10.8, 11.3] vs. control: 10 [8.8, 10]) and increased gonadotropin dosage requirements (FGTB: 3300 [3075, 3637.5] U; LGTB: 3037.5 [2700, 3225] U vs. control: 2531.25 [2337.5, 2943.8] U). All comparisons were statistically significant at P < 0.05. The results suggested that FGTB and LGTB have adverse effects on ovarian reserve and response. Untargeted metabolomic analysis identified 92 and 80 differential metabolites in the control vs. FGTB and control vs. LGTB groups, respectively. Pathway enrichment analysis revealed significant alterations in metabolic pathways in the FGTB and LGTB groups compared to the control group (P < 0.05), with specific changes noted in galactose metabolism, biotin metabolism, steroid hormone biosynthesis, and nicotinate and nicotinamide metabolism in the FGTB group, and caffeine metabolism, primary bile acid biosynthesis, steroid hormone biosynthesis, and glycerophospholipid metabolism in the LGTB group. The analysis of metabolic levels has revealed the potential mechanisms by which FGTB and LGTB affect ovarian reserve function, namely through alterations in metabolic pathways. The study emphasizes the importance of comprehending the metabolic alterations associated with FGTB and LGTB, which is of considerable relevance for the clinical management and therapeutic approaches in afflicted women.

A Mathematical Model for the Impact of 3HP and Social Programme Implementation on the Incidence and Mortality of Tuberculosis: Study in Brazil.

In this paper, we presented a mathematical model for tuberculosis with treatment for latent tuberculosis cases and incorporated social implementations based on the impact they will have on tuberculosis incidence, cure, and recovery. We incorporated two variables containing the accumulated deaths and active cases into the model in order to study the incidence and mortality rate per year with the data reported by the model. Our objective is to study the impact of social program implementations and therapies on latent tuberculosis in particular the use of once-weekly isoniazid-rifapentine for 12 weeks (3HP). The computational experimentation was performed with data from Brazil and for model calibration, we used the Markov Chain Monte Carlo method (MCMC) with a Bayesian approach. We studied the effect of increasing the coverage of social programs, the Bolsa Familia Programme (BFP) and the Family Health Strategy (FHS) and the implementation of the 3HP as a substitution therapy for two rates of diagnosis and treatment of latent at 1% and 5%. Based of the data obtained by the model in the period 2023-2035, the FHS reported better results than BFP in the case of social implementations and 3HP with a higher rate of diagnosis and treatment of latent in the reduction of incidence and mortality rate and in cases and deaths avoided. With the objective of linking the social and biomedical implementations, we constructed two different scenarios with the rate of diagnosis and treatment. We verified with results reported by the model that with the social implementations studied and the 3HP with the highest rate of diagnosis and treatment of latent, the best results were obtained in comparison with the other independent and joint implementations. A reduction of the incidence by 36.54% with respect to the model with the current strategies and coverage was achieved, and a greater number of cases and deaths from tuberculosis was avoided.

Interpreter usage and associations with latent tuberculosis infection treatment acceptance and completion in the USA among non-U.S.-born persons, 2012-2017.

BACKGROUND: Latent tuberculosis infection (LTBI) screening and treatment interventions that are tailored to optimize acceptance among the non-U.S.-born population are essential for U.S. tuberculosis elimination. We investigated the impact of medical interpreter use on LTBI treatment acceptance and completion among non-U.S.-born persons in a multisite study. METHODS: The Tuberculosis Epidemiologic Studies Consortium was a prospective cohort study that enrolled participants at high risk for LTBI at ten U.S. sites with 18 affiliated clinics from 2012 to 2017. Non-U.S.-born participants with at least one positive tuberculosis infection test result were included in analyses. Characteristics associated with LTBI treatment offer, acceptance, and completion were evaluated using multivariable logistic regression with random intercepts to account for clustering by enrollment site. Our primary outcomes were whether use of an interpreter was associated with LTBI treatment acceptance and completion. We also evaluated whether interpreter usage was associated treatment offer and whether interpreter type was associated with treatment offer, acceptance, or completion. RESULTS: Among 8,761 non-U.S.-born participants, those who used an interpreter during the initial interview had a significantly greater odds of accepting LTBI treatment than those who did not use an interpreter. There was no association between use of an interpreter and a clinician's decision to offer treatment or treatment completion once accepted. Characteristics associated with lower odds of treatment being offered included experiencing homelessness and identifying as Pacific Islander persons. Lower treatment acceptance was observed in Black and Latino persons and lower treatment completion by participants experiencing homelessness. Successful treatment completion was associated with use of shorter rifamycin-based regimens. Interpreter type was not associated with LTBI treatment offer, acceptance, or completion. CONCLUSIONS: We found greater LTBI treatment acceptance was associated with interpreter use among non-U.S.-born individuals.

Latent tuberculosis infection and infection-associated risk factors for miner workers with silicosis in eastern China.

OBJECTIVES: Silicosis people are at high risk of developing pulmonary tuberculosis. Whether silica exposure increases the likelihood of latent tuberculosis infection (LTBI) was not well understood, and potential factors involved in LTBI risk among silicosis people were not evaluated before. Thus, LTBI among silicosis people and potential risk factors for LTBI among silicosis people were evaluated in this study. METHODS: A cross-sectional study was undertaken for 130 miner workers with silicosis. The QFT-GIT was performed for LTBI detection. RESULTS: The LTBI was high to 31.6% (36/114) for silicosis participants, and 13.1% (13/99) had a history of tuberculosis. Drinking was associated with LTBI risk (OR = 6.92, 95%CI, 1.47-32.66, P = 0.015). Meanwhile, tunneling work was associated with an increased risk of LTBI compared with other mining occupations (OR = 3.91,95%CI,1.20-12.70, P = 0.024). CONCLUSIONS: The LTBI rate of silicosis participants was high and more than 10% had a history of tuberculosis. Drinking alcohol and tunneling were independent risk factors for LTBI in silicosis participants.

Gendered gaps to tuberculosis prevention and care in Kenya: a political economy analysis study.

BACKGROUND: Tuberculosis (TB) remains a public health concern in Kenya despite the massive global efforts towards ending TB. The impediments to TB prevention and care efforts include poor health systems, resource limitations and other sociopolitical contexts that inform policy and implementation. Notably, TB cases are much higher in men than women. Therefore, the political economy analysis (PEA) study provides in-depth contexts and understanding of the gender gaps to access and successful treatment for TB infection. DESIGN: PEA adopts a qualitative, in-depth approach through key informant interviews (KII) and documentary analysis. SETTING AND PARTICIPANTS: The KIIs were distributed among government entities, academia, non-state actors and community TB groups from Kenya. RESULTS: The themes identified were mapped onto the applied PEA analysis framework domains. The contextual and institutional issues included gender concerns related to the disconnect between TB policies and gender inclusion aspects, such as low prioritisation for TB programmes, limited use of evidence to inform decisions and poor health system structures. The broad barriers influencing the social contexts for TB programmes were social stigma and cultural norms such as traditional interventions that negatively impact health-seeking behaviours. The themes around the economic situation were poverty and unemployment, food insecurity and malnutrition. The political context centred around the systemic and governance gaps in the health system from the national and devolved health functions. CONCLUSION: Broad contextual factors identified from the PEA widen the disparity in targeted gender efforts toward men. Following the development of effective TB policies and strategies, it is essential to have well-planned gendered responsive interventions with a clear implementation plan and monitoring system to enhance access to TB prevention and care.

Construction of novel multi-epitope-based diagnostic biomarker HP16118P and its application in the differential diagnosis of Mycobacterium tuberculosis latent infection.

Tuberculosis (TB) is an infectious disease that significantly threatens human health. However, the differential diagnosis of latent tuberculosis infection (LTBI) and active tuberculosis (ATB) remains a challenge for clinicians in early detection and preventive intervention. In this study, we developed a novel biomarker named HP16118P, utilizing 16 helper T lymphocyte (HTL) epitopes, 11 cytotoxic T lymphocyte (CTL) epitopes, and 8 B cell epitopes identified from 15 antigens associated with LTBI-RD using the IEDB database. We analyzed the physicochemical properties, spatial structure, and immunological characteristics of HP16118P using various tools, which indicated that it is a hydrophilic and relatively stable alkaline protein. Furthermore, HP16118P exhibited good antigenicity and immunogenicity, while being non-toxic and non-allergenic, with the potential to induce immune responses. We observed that HP16118P can stimulate the production of high levels of IFN-γ+ T lymphocytes in individuals with ATB, LTBI, and health controls. IL-5 induced by HP16118P demonstrated potential in distinguishing LTBI individuals and ATB patients (p=0.0372, AUC=0.8214, 95% CI [0.5843 to 1.000]) with a sensitivity of 100% and specificity of 71.43%. Furthermore, we incorporated the GM-CSF, IL-23, IL-5, and MCP-3 induced by HP16118P into 15 machine learning algorithms to construct a model. It was found that the Quadratic discriminant analysis model exhibited the best diagnostic performance for discriminating between LTBI and ATB, with a sensitivity of 1.00, specificity of 0.86, and accuracy of 0.93. In summary, HP16118P has demonstrated strong antigenicity and immunogenicity, with the induction of GM-CSF, IL-23, IL-5, and MCP-3, suggesting their potential for the differential diagnosis of LTBI and ATB.

A systematic review and meta-analysis of circulating serum and plasma microRNAs in TB diagnosis.

BACKGROUND: Tuberculosis (TB) ranks as the second leading cause of death globally among all infectious diseases. This problem is likely due to the lack of biomarkers to differentiate the heterogeneous spectrum of infection. Therefore, the first step in solving this problem is to identify biomarkers to distinguish the different disease states of an individual and treat them accordingly. Circulating microRNA (miRNA) biomarkers are promising candidates for various diseases. In fact, we are yet to conceptualize how miRNA expression influences and predicts TB disease outcomes. Thus, this systematic review and meta-analysis aimed to assess the diagnostic efficacy of circulating miRNAs in Latent TB (LTB) and Active Pulmonary TB (PTB). METHODS: Literature published between 2012 and 2021 was retrieved from PubMed, Web of Science, Cochrane, Scopus, Embase, and Google Scholar. Articles were screened based on inclusion and exclusion criteria, and their quality was assessed using the QUADAS-2 tool. Funnel plots and forest plots were generated to assess the likelihood of study bias and heterogeneity, respectively. RESULTS: After the screening process, seven articles were selected for qualitative analysis. The study groups, which consisted of Healthy Control (HC) vs. TB and LTB vs. TB, exhibited an overall sensitivity of 81.9% (95% CI: 74.2, 87.7) and specificity of 68.3% (95% CI: 57.8, 77.2), respectively. However, our meta-analysis results highlighted two potentially valuable miRNA candidates, miR-197 and miR-144, for discriminating TB from HC. The miRNA signature model (miR197-3p, miR-let-7e-5p, and miR-223-3p) has also been shown to diagnose DR-TB with a sensitivity of 100%, but with a compromised specificity of only 75%. CONCLUSION: miRNA biomarkers show a promising future for TB diagnostics. Further multicentre studies without biases are required to identify clinically valid biomarkers for different states of the TB disease spectrum. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42022302729).

Detection of Mycobacterium tuberculosis DNA in CD34+ peripheral blood mononuclear cells of adults with tuberculosis infection and disease.

OBJECTIVES: To investigate whether Mycobacterium tuberculosis (Mtb) DNA is detected in peripheral blood mononuclear cells (PBMC) of subjects with tuberculosis (TB) or TB infection (TBI) living in a low-burden country. METHODS: We prospectively enrolled 57 patients with TB, 41 subjects with TBI, and 39 controls in Rome, Italy. PBMC were isolated, cluster of differentiation (CD)34+ and CD34- cells were immunomagnetic separated, DNA was extracted, and digital polymerase chain reaction for IS6110 and rpoB sequences was used to detect Mtb DNA in PBMC subsets and unfractionated PBMC. RESULTS: We detected Mtb DNA at a low copy number in CD34+ cells in 4o f 30 (13%) patients with TB, 2 of 24 (8%) subjects with TBI, and 1 of 24 (4%) controls. Mtb DNA was detected in unfractionated PBMC in 3 of 51 (6%) patients with TB, 2 of 38 (5%) subjects with TBI, and 2 of 36 (6%) controls. In CD34- cells, only 1 of 31 (3%) subjects with TBI tested positive for Mtb DNA. CONCLUSIONS: Mtb DNA was detected at low frequencies and levels in the PBMC of subjects with TBI and donors with TB living in a low-burden country. In particular, Mtb DNA was detected more frequently in CD34+ cells, supporting the hypothesis that these cells may represent a Mtb niche. This finding informs biological understanding of Mtb pathogenesis and may support the development of a microbial blood biomarker for Mtb infection.

Is the new tuberculous antigen-based skin test ready for use as an alternative to tuberculin skin test/interferon-gamma release assay for tuberculous diagnosis? A narrative review.

In recent years, novel specific Mycobacteria tuberculous (TB) antigen-based skin test (TBST) has become available for clinical use. The mechanism of TBST is similar to the interferon-gamma release assay (IGRA), making it a potential alternative for identifying latent tuberculous infection (LTBI), especially in subjects with history of bacille Calmette-Guérin vaccination. Three different commercial brands have been developed in Denmark, Russia, and China. Clinical studies in the respective countries have shown promising sensitivity, specificity, and safety profile. Some studies attempted to address the applicability of TBST in specific subject groups but the discrepancy in defining LTBI and problematic methodologies undermine the generalisation of the results to other communities across the world. Limited cost-effectiveness studies for TBST have been conducted without exploring the health economics for preventing development of LTBI into active TB. Unlike IGRA, no clinical studies have addressed the correlation of TBST results (magnitude of induration) with the likelihood of development of active TB. Moreover, the different TBSTs are not widely available for clinical use. While TBST is a promising test to overcome the shortcomings of tuberculin skin tests, more clinical data are needed to support its general application globally for the diagnosis of LTBI.

Mycobacterium bovis infection of the appendix: a case of appendiceal tuberculosis in rural England.

Appendiceal tuberculosis is a rare mimic of acute appendicitis, demonstrated by several case reports of patients from tuberculosis endemic countries. On literature review, there are few cases reported of appendiceal tuberculosis in urban England, and no reports from rural England. This case describes a patient with primary appendiceal tuberculosis from a remote district hospital in England who underwent a diagnostic laparoscopy for suspected acute appendicitis. Intraoperatively, an abnormal appearance with extensive intra-abdominal adhesions was seen in addition to appendicitis, making the diagnosis dubious. Histology of the appendix was positive for acid-fast bacilli and culture of the intra-abdominal fluid revealed a diagnosis of Mycobacterium bovis infection. The mode of infection was thought to be reactivation of latent bovine tuberculosis from drinking unpasteurised milk in adolescence. Taking a focused history, particularly in those with a farming background, and intraoperative sampling for histology and culture are vital in the diagnosis of appendiceal tuberculosis.

RATE OF INFECTION (TUBERCULOSIS) IN BRAZILIANS IBD PRIVATE PATIENTS: FOLLOW-UP 15 YEARS.

BACKGROUND: Latent tuberculosis (LTB) is a condition where the patient is infected with Mycobacterium tuberculosis but does not develop active TB. There's a possibility of tuberculosis (TB) activation following the introduction of anti-TNFs. OBJECTIVE: To assess the risk of biological therapy inducing LTB during inflammatory bowel diseases (IBD) treatment over 15 years in a high-risk area in Brazil. METHODS: A retrospective study of an IBD patients' database was carried out in a private reference clinic in Brazil. All patients underwent TST testing and chest X-ray prior to treatment, and once a year after starting it. Patients were classified according to the Montreal stratification and risk factors were considered for developing TB. RESULTS: Among the analyzed factors, age and gender were risk factors for LTB. DC (B2 and P) and UC (E2) patients showed a higher number of LTB cases with statistical significance, what was also observed for adalimumab and infliximab users, compared to other medications, and time of exposure to them favored it significantly. Other factors such as enclosed working environment have been reported as risk. CONCLUSION: The risk of biological therapy causing LTB is real, so patients with IBD should be continually monitored. This study reveals that the longer the exposure to anti-TNFs, the greater the risk. BACKGROUND: •Rate of infection (tuberculosis) in Brazilians IBD private patients: follow-up 15 years. BACKGROUND: •Patients treated with immunosuppressants and/or anti-TNFs have a higher risk of developing opportunistic infections, among them the most common is latent tuberculosis or even active tuberculosis. BACKGROUND: •Similar risks may be noted in patients with inflammatory bowel diseases (IBDs). BACKGROUND: •This study reveals that the longer the exposure to anti-TNFs, the greater the risk for de IBD patients. BACKGROUND: •The study demonstrated the importance of monitoring these patients permanently and continuously.