Whole-transcriptome sequencing of phagocytes reveals a ceRNA network contributing to natural resistance to tuberculosis infection.

Tuberculosis (TB) is a major fatal infectious disease globally, exhibiting high morbidity rates and impacting public health and other socio-economic factors. However, some individuals are resistant to TB infection and are referred to as "Resisters". Resisters remain uninfected even after exposure to high load of Mycobacterium tuberculosis (Mtb). To delineate this further, this study aimed to investigate the factors and mechanisms influencing the Mtb resistance phenotype. We assayed the phagocytic capacity of peripheral blood mononuclear cells (PBMCs) collected from Resisters, patients with latent TB infection (LTBI), and patients with active TB (ATB), following infection with fluorescent Mycobacterium bovis Bacillus Calmette-Guérin (BCG). Phagocytosis was stronger in PBMCs from ATB patients, and comparable in LTBI patients and Resisters. Subsequently, phagocytes were isolated and subjected to whole transcriptome sequencing and small RNA sequencing to analyze transcriptional expression profiles and identify potential targets associated with the resistance phenotype. The results revealed that a total of 277 mRNAs, 589 long non-coding RNAs, 523 circular RNAs, and 35 microRNAs were differentially expressed in Resisters and LTBI patients. Further, the endogenous competitive RNA (ceRNA) network was constructed from differentially expressed genes after screening. Bioinformatics, statistical analysis, and quantitative real-time polymerase chain reaction were used for the identification and validation of potential crucial targets in the ceRNA network. As a result, we obtained a ceRNA network that contributes to the resistance phenotype. TCONS_00034796-F3, ENST00000629441-DDX43, hsa-ATAD3A_0003-CYP17A1, and XR_932996.2-CERS1 may be crucial association pairs for resistance to TB infection. Overall, this study demonstrated that the phagocytic capacity of PBMCs was not a determinant of the resistance phenotype and that some non-coding RNAs could be involved in the natural resistance to TB infection through a ceRNA mechanism.

Completion of isoniazid preventive therapy for latent tuberculosis infection among children and adolescents compared to adults living with HIV in Kinshasa, Democratic Republic of the Congo.

BACKGROUND: Little is known about isoniazid preventive therapy (IPT) completion rates among children or adolescents compared to adults living with HIV in Kinshasa, Democratic Republic of the Congo (DRC). METHODS: We conducted a retrospective cohort analysis including children, adolescents, and adults living with HIV who were treated at FHI360 and partners-implemented HIV care programs at six health zones in Kinshasa, DRC, from 2004 to 2020. The primary outcome was the proportion of children, adolescents versus adults who did complete 6 months of daily self-administered IPT. Log-binomial regression assessed independent predictors of IPT non-completion and Kaplan-Meier technique for survival analysis. RESULTS: Of 11,691 eligible patients on ART who initiated IPT, 429 were children (<11 years), 804 adolescents (11-19 years), and 10,458 adults (≥20 years). The median age was 7 (IQR: 3-9) years for children, 15 (IQR: 13-17) years for adolescents, and 43 (35-51) years for adults. Among those who were initiated on IPT, 5625 out of 11,691 people living with HIV (PLHIV) had IPT completion outcome results, and an overall 3457/5625 (61.5%) completion rate was documented. Compared to adults, children and adolescents were less likely to complete IPT [104/199 (52.3%) and 268/525 (51.0%), respectively, vs. 3085/4901 (62.9%)]. After adjustment, the only independent predictors for IPT non-completion were health zone of residence and type of ART regimen. Kaplan-Meier analysis showed comparable poor survival among patients who completed IPT versus those who did not (p-value for log-rank test, 0.15). CONCLUSIONS: The overall sub-optimal IPT completion rate in adults as well as children/adolescents in this setting is of great concern. Prospective studies are needed to elucidate the specific barriers to IPT completion among children, adolescents, and adults in DRC as well as the scale-up of evidence-informed interventions to improve IPT completion, such as adoption of shorter TB preventive regimens.

Tuberculosis Infection among Non-US-Born Persons and Persons ≥60 Years of Age, United States, 2019-2020.

We examined tuberculosis (TB) infection results for the United States from the 2019-2020 National Health and Nutrition Examination Survey. Over this period, 10% of non-US-born persons and 7% of those >60 years of age tested positive for TB infection. These results provide up-to-date information on TB infection among study subpopulations.

Prevalence of LTBI in patients with autoimmune diseases and accuracy of IGRA in predicting TB relapse.

OBJECTIVES: The current study evaluated latent tuberculosis infection (LTBI) positivity in a cohort of Indian subjects and the accuracy of IFN-gamma release assay (IGRA) in predicting tuberculosis (TB) reactivation. METHODS: This cross-sectional, retrospective chart-based study considered patients diagnosed with autoimmune rheumatic diseases (AIRDs), especially those who received treatment with biologics or targeted synthetic (ts)DMARDs. The patients had undergone LTBI screening and IGRA test. The study excluded patients with inadequate information and those who had undergone test exclusively for diagnostic purpose. Statistical analyses were carried out for descriptive, demographic and clinical variables. Accuracy and error rate in predicting the absence of TB reactivation were calculated for IGRA test. RESULTS: The study selected 943 patients who had undergone IGRA pre-screening prior to the initiation of biologics or tsDMARDs with a mean age of 42.93 ± 14.01 years and male-to-female ratio of 1:2.08. RA was the most common primary diagnosis (43.16%). The proportion of subjects who received single, double and triple or more DMARDs or immune suppressants were 54.35%, 33.33% and 7.69%, respectively. Among the selected subjects, 125 patients were LTBI positive and 816 were negative. All patients, except one who tested positive at baseline, received antitubercular prophylaxis. Accuracy of IGRA in predicting the absence of TB reactivation was 99.6%, with an error rate of 0.46. CONCLUSION: LTBI screening is beneficial in AIRDs patients prior to the prescription of biologics or tsDMARDs. IGRA is ideal for identifying patients with increased likelihood of developing TB upon receiving biologics or tsDMARDs with reasonable accuracy.

Excluding Participants With Mycobacteria Infections From Clinical Trials: A Critical Consideration in Evaluating the Efficacy of BCG Against COVID-19.

In the context of the coronavirus disease 2019 (COVID-19) pandemic, Bacillus Calmette-Guérin (BCG), a tuberculosis (TB) vaccine, has been investigated for its potential to prevent COVID-19 with conflicting outcomes. Currently, over 50 clinical trials have been conducted to assess the effectiveness of BCG in preventing COVID-19, but the results have shown considerable variations. After scrutinizing the data, it was discovered that some trials had enrolled individuals with active TB, latent TB infection, or a history of TB. This finding raises concerns about the reliability and validity of the trial outcomes. In this study, we explore the potential consequences of including these participants in clinical trials, including impaired host immunity, immune exhaustion, and the potential masking of the BCG vaccine's protective efficacy against COVID-19 by persistent mycobacterial infections. We also put forth several suggestions for future clinical trials. Our study underscores the criticality of excluding individuals with active or latent TB from clinical trials evaluating the efficacy of BCG in preventing COVID-19.

HIV-Differentiated Metabolite N-Acetyl-L-Alanine Dysregulates Human Natural Killer Cell Responses to Mycobacterium tuberculosis Infection.

Mycobacterium tuberculosis (Mtb) has latently infected over two billion people worldwide (LTBI) and caused ~1.6 million deaths in 2021. Human immunodeficiency virus (HIV) co-infection with Mtb will affect the Mtb progression and increase the risk of developing active tuberculosis by 10-20 times compared with HIV- LTBI+ patients. It is crucial to understand how HIV can dysregulate immune responses in LTBI+ individuals. Plasma samples collected from healthy and HIV-infected individuals were investigated using liquid chromatography-mass spectrometry (LC-MS), and the metabolic data were analyzed using the online platform Metabo-Analyst. ELISA, surface and intracellular staining, flow cytometry, and quantitative reverse-transcription PCR (qRT-PCR) were performed using standard procedures to determine the surface markers, cytokines, and other signaling molecule expressions. Seahorse extra-cellular flux assays were used to measure mitochondrial oxidative phosphorylation and glycolysis. Six metabolites were significantly less abundant, and two were significantly higher in abundance in HIV+ individuals compared with healthy donors. One of the HIV-upregulated metabolites, N-acetyl-L-alanine (ALA), inhibits pro-inflammatory cytokine IFN-γ production by the NK cells of LTBI+ individuals. ALA inhibits the glycolysis of LTBI+ individuals' NK cells in response to Mtb. Our findings demonstrate that HIV infection enhances plasma ALA levels to inhibit NK-cell-mediated immune responses to Mtb infection, offering a new understanding of the HIV-Mtb interaction and providing insights into the implication of nutrition intervention and therapy for HIV-Mtb co-infected patients.

Tuberculosis incidence in country of origin is a key determinant of the risk of active tuberculosis in people living with HIV: Data from a 30-year observational cohort study.

INTRODUCTION: People living with HIV (PLWH) are at high risk of active tuberculosis (TB) but this risk in the era of antiretroviral treatment (ART) remains unclear. It is critical to identify the groups who should be prioritised for latent TB (LTBI) screening. In this study we identified the risk factors associated with developing incident TB disease, by analysing a 30-year observational cohort. METHODS: We evaluated PLWH in Leicester, UK, between 1983 and 2017 to ascertain those who developed active TB and the timing of this in relation to HIV diagnosis; whether before, concurrently with, or more than 3 months after the diagnosis of HIV (incident TB). Predictors of incident TB were ascertained using Cox proportional hazards models. RESULTS: In all, 325 out of 2158 (15.1%) PLWH under care had had active TB; 64/325 (19.7%) prior to HIV diagnosis, 161/325 (49.5%) concurrently with/within 3 months of HIV diagnosis and 100/325 (30.8%) had incident TB. Incident TB risk was 4.57/1000 person-years. Increased TB incidence in the country of birth was associated with an increased risk of developing incident TB [50-149/100 000 population, adjusted hazard ratio (AHR) = 3.10, 95% CI: 0.94-10.20; 150-249/100 000 population, AHR = 7.14, 95% CI: 3.46-14.74; 250-349/100 000 population, AHR = 5.90, 95% CI: 2.32-14.99; ≥ 350/100 000 population, AHR = 3.96, 95% CI: 1.39-11.26]. CONCLUSIONS: Tuberculosis risk remains high among PLWH and is related to TB incidence in the country of birth. Further work is required to determine whether specific groups of PLWH should be targeted for programmatic LTBI screening, and whether it will result in high uptake and completion of chemoprophylaxis and is cost-effective for widespread implementation.

Effect of SARS-CoV-2 seropositivity on antigen - specific cytokine and chemokine responses in latent tuberculosis.

SARS-CoV-2 and latent Mycobacterium tuberculosis infection are both highly co-prevalent in many parts of the globe. Whether exposure to SARS-CoV-2 influences the antigen specific immune responses in latent tuberculosis has not been investigated. We examined the baseline, mycobacterial antigen and mitogen induced cytokine and chemokine responses in latent tuberculosis (LTBI) individuals with or without SARS-CoV-2 seropositivity, LTBI negative individuals with SARS-CoV-2 seropositivity and healthy control (both LTBI and SARS-CoV-2 negative) individuals. Our results demonstrated that LTBI individuals with SARS-CoV-2 seropositivity (LTBI+/IgG +) were associated with increased levels of unstimulated and TB-antigen stimulated IFNγ, IL-2, TNFα, IL-17, IL-1ß, IL-6, IL-12, IL-4, CXCL1, CXCL9 and CXCL10 when compared to those without seropositivity (LTBI+/IgG-). In contrast, LTBI+/IgG+ individuals were associated with decreased levels of IL-5 and IL-10. No significant difference in the levels of cytokines/chemokines was observed upon mitogen stimulation between the groups. SARS-CoV-2 seropositivity was associated with enhanced unstimulated and TB-antigen stimulated but not mitogen stimulated production of cytokines and chemokines in LTBI+ compared to LTBI negative individuals. Finally, most of these significant differences were not observed when LTBI negative individuals with SARS-CoV-2 seropositivity and controls were examined. Our data clearly demonstrate that both baseline and TB - antigen induced cytokine responses are augmented in the presence of SARS-CoV-2 seropositivity, suggesting an augmenting effect of prior SARS-CoV-2 infection on the immune responses of LTBI individuals.

QuantiFERON-TB Gold plus testing for the detection of LTBI among health care workers in major TB hospitals of the Northern Kyrgyz Republic.

BACKGROUND: Health care workers (HCW) are at increased risk of TB infection due to their close contact with infected patients with active TB. The objectives of the study were (1) to assess the prevalence of LTBI among HCW in the Northern Kyrgyz Republic, and (2) to determine the association of LTBI with job positions or departments. METHODS: HCWs from four TB hospitals in the Northern Kyrgyz Republic were tested with the interferon-gamma release assay (IGRA) Quantiferon-TB Gold plus (QFT) for the detection of an immune response to TB as marker of TB infection. Age was controlled for as a confounder. Univariate and multivariable analysis were performed using logistic regression to assess the association of the risk factors (job position, and department) with having a QTF positive result. Firth's penalized-likelihood estimates were used to account for the small-sample size. Pairwise comparisons using the Bonferroni correction (conservative) and comparisons without adjusting for multiple comparisons (unadjusted) were used to identify the categories where differences occurred. RESULTS: QFT yielded valid results for 404 HCW, with 189 (46.7%) having a positive test. In the National Tuberculosis Center there was an increased odds to have a positive QFT test for the position of physician (OR = 8.7, 95%, CI = 1.2-60.5, p = 0.03) and laboratory staff (OR = 19.8, 95% CI = 2.9-135.4, p < 0.01) when administration staff was used as the baseline. When comparing departments for all hospitals combined, laboratories (OR 7.65; 95%CI 2.3-24.9; p < 0.001), smear negative TB (OR 5.90; 95%CI 1.6-21.8; p = 0.008), surgery (OR 3.79; 95%CI 1.3-11.4; p = 0.018), and outpatient clinics (OR 3.80; 95%CI 1.1-13.0; p = 0.03) had higher odds of a positive QFT result than the admin department. Fifteen of the 49 HCW with follow-up tests converted from negative to positive at follow-up testing. CONCLUSIONS: This is the first report on prevalence and risk factors of LTBI for HCW in the Kyrgyz republic, and results indicate there may be an increased risk for LTBI among physicians and laboratory personnel. Further research should investigate gaps of infection control measures particularly for physicians and laboratory staff and lead to further improvement of policies.

Evidence for the Use of Triage, Respiratory Isolation, and Effective Treatment to Reduce the Transmission of Mycobacterium Tuberculosis in Healthcare Settings: A Systematic Review.

Evidence is limited for infection prevention and control (IPC) measures reducing Mycobacterium tuberculosis (MTB) transmission in health facilities. This systematic review, 1 of 7 commissioned by the World Health Organization to inform the 2019 update of global tuberculosis (TB) IPC guidelines, asked: do triage and/or isolation and/or effective treatment of TB disease reduce MTB transmission in healthcare settings? Of 25 included articles, 19 reported latent TB infection (LTBI) incidence in healthcare workers (HCWs; absolute risk reductions 1%-21%); 5 reported TB disease incidence in HCWs (no/slight [high TB burden] or moderate [low burden] reduction) and 2 in human immunodeficiency virus-positive in-patients (6%-29% reduction). In total, 23/25 studies implemented multiple IPC measures; effects of individual measures could not be disaggregated. Packages of IPC measures appeared to reduce MTB transmission, but evidence for effectiveness of triage, isolation, or effective treatment, alone or in combination, was indirect and low quality. Harmonizing study designs and reporting frameworks will permit formal data syntheses and facilitate policy making.

Optimal Testing Choice and Diagnostic Strategies for Latent Tuberculosis Infection Among US-Born People Living with Human Immunodeficiency Virus (HIV).

BACKGROUND: Increased risk of progression from latent tuberculosis infection (LTBI) to tuberculosis (TB) disease among people living with human immunodeficiency virus (HIV; PLWH) prioritizes them for LTBI testing and treatment. Studies comparing the performance of interferon gamma release assays (IGRAs) and the tuberculin skin test (TST) among PLWH are lacking. METHODS: We used Bayesian latent class analysis to estimate the prevalence of LTBI and diagnostic characteristics of the TST, QuantiFERON Gold In-Tube (QFT), and T.SPOT-TB (TSPOT) among a prospective, multicenter cohort of US-born PLWH ≥5 years old with valid results for all 3 LTBI tests using standard US cutoffs (≥5 mm TST, ≥0.35 IU/mL QFT, ≥8 spots TSPOT). We also explored the performance of varying LTBI test cutoffs. RESULTS: Among 1510 PLWH (median CD4+ count 532 cells/mm3), estimated LTBI prevalence was 4.7%. TSPOT was significantly more specific (99.7%) and had a significantly higher positive predictive value (90.0%, PPV) than QFT (96.5% specificity, 50.7% PPV) and TST (96.8% specificity, 45.4% PPV). QFT was significantly more sensitive (72.2%) than TST (54.2%) and TSPOT (51.9%); negative predictive value of all tests was high (TST 97.7%, QFT 98.6%, TSPOT 97.6%). Even at the highest cutoffs evaluated (15 mm TST, ≥1.00 IU/mL QFT, ≥8 spots TSPOT), TST and QFT specificity was significantly lower than TSPOT. CONCLUSIONS: LTBI prevalence among this cohort of US-born PLWH was low compared to non-US born persons. TSPOT's higher PPV may make it preferable for testing US-born PLWH at low risk for TB exposure and with high CD4+ counts.

Longitudinal Mycobacterium tuberculosis-Specific Interferon Gamma Responses in Ethiopian HIV-Negative Women during Pregnancy and Postpartum.

Pregnancy may influence cellular immune responses to Mycobacterium tuberculosis. We investigated M. tuberculosis-specific interferon-γ responses in women followed longitudinally during pregnancy and postpartum. Interferon-γ levels (stimulated by M. tuberculosis antigens [TB1 and TB2] and mitogen included in the QuantiFERON-TB Gold Plus assay) were measured in blood from pregnant HIV-negative women identified from a prospective cohort at Ethiopian antenatal care clinics. Longitudinal comparisons included women without active tuberculosis (TB) with M. tuberculosis-triggered interferon-γ responses of ≥ 0.20 IU/ml, sampled on two and/or three occasions (1st/2nd trimester, 3rd trimester, and 9 months postpartum). Among 2,093 women in the source cohort, 363 met inclusion criteria for longitudinal comparisons of M. tuberculosis-stimulated interferon-γ responses. Median M. tuberculosis-triggered interferon-γ concentrations were higher at 3rd than those at the 1st/2nd trimester (in 38 women with samples available from these time points; TB1: 2.8 versus 1.6 IU/ml, P = 0.005; TB2: 3.3 versus 2.8 IU/ml, P = 0.03) and postpartum (in 49 women with samples available from these time points; TB1: 3.1 versus 2.2 IU/ml, P = 0.01; TB2: 3.1 versus 2.3 IU/ml, P = 0.03). In contrast, mitogen-stimulated interferon-γ levels were lower at 3rd than those at 1st/2nd trimester (in 32 women with samples available from these time points: 21.0 versus 34.9 IU/ml, P = 0.02). Results were similar in 22 women sampled on all 3 occasions. In HIV-negative women, M. tuberculosis-stimulated interferon-γ responses were higher during the 3rd trimester than those at earlier stages of pregnancy and postpartum, despite decreased mitogen-triggered responses. These findings suggest increased M. tuberculosis-specific cellular responses due to dynamic changes of latent TB infection during pregnancy.

Latent Tuberculosis Therapy Outcomes in Dialysis Patients: A Retrospective Cohort.

RATIONALE & OBJECTIVES: Maintenance dialysis patients are at an increased risk for active tuberculosis (TB). In 2012, British Columbia, Canada, began systematically screening maintenance dialysis patients for latent TB infection (LTBI) and treating people with evidence of LTBI when appropriate. We examined LTBI treatment outcomes and compared treatment outcomes before and after rollout of the systematic screening program. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: The study comprised 365 people in British Columbia, Canada, initiating at least 90 days of dialysis from January 1, 2001, to May 31, 2017, and starting LTBI therapy: 290 (79.5%) people in the recent cohort and 75 (20.5%) in the historical cohort. People starting LTBI therapy from January 1, 2012, onward were classified as the recent cohort, whereas people starting LTBI therapy before January 1, 2012, were classified as the historical cohort. EXPOSURE: Systematic LTBI screening and therapy. OUTCOMES: Proportion of people who experience grade 3 to 5 adverse events (AEs) or any grade rash and end-of-treatment outcomes. ANALYTICAL APPROACH: Outcomes were reported using descriptive statistics. 2-sample test of proportions using χ2 distribution was used to test for statistical significance between the recent and historical cohorts. RESULTS: 298 (81.6%) people successfully completed LTBI therapy. The proportion of people experiencing a grade 3 to 4 AE or any grade rash was 21.1%. Most AEs were related to gastrointestinal events, general malaise, or pruritus that resulted in regimen changes. 2 (0.5%) people were hospitalized for AEs related to LTBI therapy. No significant difference was found between the recent and historical cohorts in all outcomes of interest. No grade 5 AEs (deaths) were attributed to LTBI therapy. LIMITATIONS: Retrospective data and generalizability outside low-TB-burden settings. CONCLUSIONS: Our findings suggest that a high proportion of people receiving maintenance dialysis can complete LTBI therapy. The rate of grade 3 to 4 AEs was high and associated with frequent medication changes during therapy. LTBI therapy in maintenance dialysis may be safe but requires close monitoring.

Role of resuscitation promoting factors in reactivation of latent tuberculosis during high glucose conditions employing human granuloma in vitro model.

BACKGROUND: Diabetes aggravates the risk of tuberculosis (TB) through impairment of immunity which may lead to the activation of latent tuberculosis (LTBI). LTBI serves as a homeostatic state where host does not develop any symptoms of the disease as host immune system assist in the containment of infection leading to granuloma formation. However, the compromised immunity imbalances this equilibrium which further leads to reactivation of LTBI. The aim of this study was to assess if hyperglycemia like conditions contribute towards activation of latent tuberculosis. MATERIAL/METHODS: In vitro granuloma model was developed using peripheral blood monocytic cells (PBMCs) under normal and high glucose conditions and the characteristics of dormancy i.e. tolerance towards rifampicin, loss of acid fastness were monitored. Further, activation was assessed by expression analysis of various resuscitation promoting factors rpfA-E. RESULTS: Granuloma formation was not observed in the presence of high glucose. The gene expression of hspX was downregulated whereas the expression of rpfA-E genes was upregulated under high glucose conditions after 48 h of glucose treatment. The expression of rpfD gene remained upregulated till 72 h of glucose treatment. CONCLUSION: High glucose concentrations impede the granuloma formation and may lead to activation of latent tubercle bacilli through resuscitation promoting factors. Thus, rpfs represent an important targets for new interventions that can abate the burden from co-pathogenesis of tuberculosis and diabetes.

Surveillance of Employees of Swiss Federal Asylum Centres for Latent Tuberculosis Infection.

BACKGROUND: Asylum seekers in Switzerland have to register in federal asylum centres (FACs) before formal permission to enter the country. Some of them may have active tuberculosis (TB), exposing fellow refugees and employees. OBJECTIVES: The aim of this study was to assess the risk of TB infection among employees of Swiss FACs. METHODS: Between 2010 and 2018, a free interferon-gamma release assay (IGRA) was offered to all employees of 8 FACs, at employment and at yearly intervals. We defined latent TB infection as IGRA conversion from negative to positive. IGRA-positive employees were referred to a medical centre for further clinical follow-up. RESULTS: 1,427 tests were performed among 737 employees (54.6% male). 403 (55%) persons were tested only once; 330 (44.5%) were tested several times; for 4 (0.5%) persons, the number of IGRA tests is unknown. Twenty employees (2.7%) had a positive IGRA at baseline, 2 (0.6%) converted from negative to positive during follow-up, resulting in an incidence of 22/10,000 person-years. We observed no case of active TB among employees. CONCLUSIONS: The prevalence of latent TB among employees to Swiss FACs and the risk of acquiring TB infection through work-related exposure are low. Yearly IGRA controls in the absence of documented TB exposure seem unnecessary.

Prevalence of latent tuberculosis infection and feasibility of TB preventive therapy among Thai prisoners: a cross-sectional study.

BACKGROUND: Prisons are considered as major reservoirs for tuberculosis. Preventive therapy for latent TB infection (LTBI) is an adjunctive strategy to control TB. However, LTBI data in Thai prisoners is limited. This study assessed the prevalence of LTBI and feasibility of isoniazid preventive therapy (IPT). METHODS: A cross-sectional study was conducted among prisoners in Klong Prem Central Prison, Bangkok. Participants were screened for active TB by questionnaire and chest X-ray. LTBI was evaluated by Tuberculin skin test (TST) and QuantiFERON-TB Gold Plus (QFTP) among subgroup. Participants with positive TST or QFTP were considered to have LTBI. Participants with LTBI were offered IPT. RESULTS: From August 2018-November 2019, 1002 participants were analyzed. All participants were male with a median age of 38 (IQR 32-50) years. LTBI identified by either TST/QFTP was present in 466 (46.5%) participants. TST was positive in 359 (36%) participants. In the subgroup of 294 participants who had both TST and QFTP results, 181/294 (61.6%) tested positive by QFTP. Agreement between TST and QFTP was 55.1% (Kappa = 0.17). The risk factors associated with LTBI were previous incarceration (aOR 1.53, 95%CI, 1.16-2.01, p = 0.002), history of prior active TB (aOR 3.02, 95%CI, 1.74-5.24, p < 0.001) and duration of incarceration ≥10 years (aOR 1.86, 95%CI, 1.24-2.79, p = 0.003). Majority of LTBI participants (82%) agreed to take IPT. Three hundred and 56 (93%) participants completed treatment whereas 27 (7%) participants discontinued IPT due to the side effects of INH. CONCLUSION: This is the first study to evaluate the prevalence of LTBI and feasibility of IPT among Thai prisoners. LTBI prevalence in male prisoners in Thailand is high. LTBI screening and treatment should be implemented together with other preventive components.

An observational study on prevalence of latent tuberculosis infection and outcome of 3HP treatment in patients under hemodialysis in Taiwan.

BACKGROUND: Identification and treatment for latent tuberculosis infection (LTBI) are of great epidemiological importance of controlling tuberculosis (TB) worldwide. Identification in high-risk population on dialysis and treatment with 12-week weekly rifapentine plus isoniazid (3HP) help improve prevention outcomes effectively. METHODS: We conducted a single-center, nonrandomized follow-up study on end-stage renal disease patients on hemodialysis. The interferon-gamma release assay (IGRA) was used for the diagnosis of LTBI. Participants were treated with 3HP, and treatment responses were recorded and analyzed. RESULTS: A total of 123 of the 641 patients showed positive IGRA results. The male sex, age >60 years, low serum albumin level (<4.0 g/dL), and hypercalcemia (serum calcium level > 10.2 mg/dL) were associated with IGRA positivity. Seventy-five patients were treated with 3HP, with a completion rate of 66.67%. The male sex, albumin level >4.0 g/dL, and absence of adverse drug reaction were associated with increased completion rates. Adverse drug reactions included dizziness, fatigue, nausea and vomiting, fever, and hypertension. CONCLUSION: Risk factors for LTBI in dialysis patients were identified to prioritize LTBI screening and initiate early treatment. The completion rate in dialysis patients were approximately 2 of 3 patients with mild adverse drug reaction, leading to discontinuation of the treatment.

Targeting Non-Replicating Mycobacterium tuberculosis and Latent Infection: Alternatives and Perspectives (Mini-Review).

Latent tuberculosis infection (LTBI) represents a major challenge to curing TB disease. Current guidelines for LTBI management include only three older drugs and their combinations-isoniazid and rifamycins (rifampicin and rifapentine). These available control strategies have little impact on latent TB elimination, and new specific therapeutics are urgently needed. In the present mini-review, we highlight some of the alternatives that may potentially be included in LTBI treatment recommendations and a list of early-stage prospective small molecules that act on drug targets specific for Mycobacterium tuberculosis latency.

Tuberculosis among First Nations, Inuit and Métis children and youth in Canada: Beyond medical management.

First Nations, Inuit and Métis people in Canada continue to be disproportionately affected by tuberculosis (TB), a disparity rooted primarily in factors such as poverty, crowded and inadequate housing, food insecurity, and inequitable health care access. Historical TB control practices in Canada have contributed to stigma and discrimination toward those with the disease, as well as fear and mistrust of the health system. These individual and system-level factors result in delays in TB diagnoses, ongoing transmission, poorer outcomes, and lower treatment completion rates. Children are especially vulnerable, as they are more likely to develop disease once infected with TB bacteria and to experience life-threatening conditions such as TB meningitis. Paediatric health professionals can help to increase TB awareness and literacy, reduce stigma and discrimination, and ultimately, improve the quality and uptake of services for treatment and prevention in families and communities at risk. They can also advocate for sustainable, community-driven TB elimination strategies that incorporate First Nations, Inuit and Métis principles of wellness, healing and self-determination.

Enhanced Human Immunodeficiency Virus-1 Replication in CD4+ T Cells Derived From Individuals With Latent Mycobacterium tuberculosis Infection.

BACKGROUND: Mycobacterium tuberculosis (Mtb) and human immunodeficiency virus (HIV) coinfection increases mortality, accelerates progression to acquired immune deficiency syndrome, and exacerbates tuberculosis disease. However, the impact of pre-existing Mtb infection on subsequent HIV infection has not been fully explored. We hypothesized that Mtb infection creates an immunological environment that influences the course of HIV infection, and we investigated whether pre-existing Mtb infection impacts the susceptibility of CD4+ T cells to HIV-1 infection. METHODS: Plasma and blood CD4+ T cells isolated from HIV-negative individuals across the Mtb infection spectrum and non-Mtb-infected control individuals were analyzed for inflammation markers and T-cell phenotypes. CD4+ T cells were infected with HIV-1 in vitro and were monitored for viral replication. RESULTS: We observed differences in proinflammatory cytokines and the relative proportion of memory T-cell subsets depending on Mtb infection status. CD4+ T cells derived from individuals with latent Mtb infection supported more efficient HIV-1 transcription, release, and replication. Enhanced HIV-1 replication correlated with higher percentages of CD4+ TEM and TTD cells. CONCLUSIONS: Pre-existing Mtb infection creates an immunological environment that reflects Mtb infection status and influences the susceptibility of CD4+ T cells to HIV-1 replication. These findings provide cellular and molecular insights into how pre-existing Mtb infection influences HIV-1 pathogenesis.