Evaluation of Latent Tuberculosis Infection Using the ESAT6-CFP10 Skin Test Among International Freshmen With Diverse Skin Tones at a University - Nanjing City, Jiangsu Province, China, September 2023.

Introduction: Newer skin tests, including the ESAT6-CFP10 (EC) skin test, were recommended for diagnosing Mycobacterium tuberculosis (M. tb) infection. However, no data exist assessing the diagnostic performance of the EC skin test among foreign students with different skin tones. Methods: A cohort study at Nanjing Medical University screened incoming foreign freshmen. The EC skin test was used to assess for M. tb infection, and results were read at 24, 48, 72, and 96-hours post-administration. Results: Among 96 participants, M. tb infection rates at 24, 48, 72, and 96-hours post-injection were 3.13%, 7.29%, 13.54%, and 9.38%, respectively. While infection rates were lower among individuals with darker skin tones, the difference was not statistically significant (P=0.186), and variations were consistent across different measurement times. Trajectory analysis revealed 5.3% in the continuous-increasing group, 86.5% in the low-stable group, and 5.2% in the elevated-decreasing group. Notably, participants in the elevated-decreasing group had lighter skin tones, with trajectory patterns consistent across different skin colors. Discussion: The EC skin test is safe, and redness diameter is a more reliable indicator than induration. Results should be collected within 48 to 72 hours, with verification at 72 hours crucial if initial results are negative. Importantly, skin color does not affect EC skin test outcomes.

Evaluation of the Tuberculosis Infection Care Cascade Among Pregnant Individuals in a Low-Tuberculosis-Burden Setting.

In the United States, tuberculosis (TB) screening is recommended for pregnant individuals with TB risk factors. We conducted a retrospective study of perinatal TB infection testing and treatment in a tertiary health system. Of 165 pregnant individuals with positive TB infection tests, only 9% completed treatment within 4.6 years of follow-up.

Higher blood manganese level associated with increased risk of adult latent tuberculosis infection in the US population.

Background: The associations between blood heavy metal levels and latent tuberculosis infection (LTBI) have not been fully elucidated. The aim of this study was to investigate the potential association between blood heavy metal levels and LTBI in adults using National Health and Nutrition Examination Survey data from 2011 to 2012. Methods: We enrolled 1710 participants in this study, and compared the baseline characteristics of participants involved. Multivariate logistic regression analysis, restricted cubic splines (RCS) analysis, along with subgroup analysis and interaction tests were utilized to explore the association between blood manganese (Mn) level and LTBI risk. Results: Participants with LTBI had higher blood Mn level compared to non-LTBI individuals (p < 0.05), while the levels of lead, cadmium, total mercury, selenium, copper, and zinc did not differ significantly between the two groups (p > 0.05). In the fully adjusted model, a slight increase in LTBI risk was observed with each 1-unit increase in blood Mn level (OR = 1.00, 95% CI: 1.00-1.01, p = 0.02). Participants in the highest quartile of blood Mn level had a threefold increase in LTBI risk compared to those in the lowest quartile (OR = 4.01, 95% CI: 1.22-11.33, p = 0.02). RCS analysis did not show a non-linear relationship between blood Mn level and LTBI (non-linear p-value = 0.0826). Subgroup analyses and interaction tests indicated that age, alcohol consumption, and income-to-poverty ratio significantly influenced LTBI risk (interaction p-values<0.05). Conclusion: Individuals with LTBI had higher blood Mn level compared to non-LTBI individuals, and higher blood Mn level associated with increased LTBI risk.

Combined analysis of host IFN-γ, IL-2 and IP-10 as potential LTBI biomarkers in ESAT-6/CFP-10 stimulated blood.

Background: Accurate diagnosis of latent tuberculosis infected (LTBI) individuals is important in identifying individuals at risk of developing active tuberculosis. Current diagnosis of LTBI routinely relies on the detection and measurement of immune responses using the Tuberculin Skin Test (TST) and interferon gamma release assays (IGRAs). However, IGRA, which detects Mycobacterium tuberculosis specific IFN-γ, is associated with frequent indeterminate results, particularly in immunosuppressed patients. There is a need to identify more sensitive LTBI point of care diagnostic biomarkers. The aim of this study was to assess the validity of early secreted antigen target 6 kDa (ESAT-6) and culture filtrate protein 10 (CFP-10) stimulated plasma to identify additional cytokines and chemokines as potential biomarkers of LTBI. Method: The levels of 27 cytokines and chemokines were measured by Bio-Plex Pro cytokine, chemokine and growth factor assay in ESAT-6 and CFP-10 co-stimulated plasma from 20 LTBI participants with positive IGRA (Quantiferon TB Gold plus) and 20 healthy controls with negative IGRA. Traditional ELISA was used to validate the abundance of the best performing markers in 70 LTBI and 72 healthy participants. All participants were HIV negative. Results: We found that Interleukin 1 receptor antagonist (IL1ra) (p = 0.0056), Interleukin 2 (IL-2) (p < 0.0001), Interleukin 13 (IL-13) (p < 0.0001), Interferon gamma-induced protein 10 (IP-10) (p < 0.0001), and Macrophage inflammatory protein-1 beta (MIP1b) (p = 0.0010) were significantly higher in stimulated plasma of LTBI compared to healthy individuals. Stimulated plasma IL-2 (cutoff 100 pg/mL), IP-10 (cutoff 300 pg/mL) and IL-13 (5 pg/mL) showed potential in diagnosing LTBI with PPV = 100%, 0.89.4%, and 80.9% and NPV = 86.9%, 0.85.7%, and 84.2%, respectively. Conclusion: Our data shows that co-stimulating whole blood with ESAT-6 and CFP-10 may help distinguish LTBI from healthy individuals. We also identified IL-2 and IP-10 as potential biomarkers that could be added to the currently used IFN-γ release assays in detection of LTBI.

Evaluating the cost-effectiveness of Cy-Tb for LTBI in India: a comprehensive economic modelling analysis.

BACKGROUND: Latent tuberculosis infection (LTBI) remains a significant challenge, as there is no gold standard diagnostic test. Current methods used for identifying LTBI are the interferon-γ release assay (IGRA), which is based on a blood test, and the tuberculin skin test (TST), which has low sensitivity. Both these tests are inadequate, primarily because they have limitations with the low bacterial burden characteristic of LTBI. This highlights the need for the development and adoption of more specific and accurate diagnostic tests to effectively identify LTBI. Herein we estimate the cost-effectiveness of the Cy-Tb test as compared with the TST for LTBI diagnosis. METHODS: An economic modelling study was conducted from a health system perspective using decision tree analysis, which is most widely used for cost-effectiveness analysis using transition probabilities. Our goal was to estimate the incremental cost and number of TB cases prevented from LTBI using the Cy-Tb diagnostic test along with TB preventive therapy (TPT). Secondary data such as demographic characteristics, treatment outcome, diagnostic test results and cost data for the TST and Cy-Tb tests were collected from the published literature. The incremental cost-effectiveness ratio was calculated for the Cy-Tb test as compared with the TST. The uncertainty in the model was evaluated using one-way sensitivity analysis and probability sensitivity analysis. RESULTS: The study findings indicate that for diagnosing an additional LTBI case with the Cy-Tb test and to prevent a TB case by providing TPT prophylaxis, an additional cost of 18 658 Indian rupees (US${\$}$223.5) is required. The probabilistic sensitivity analysis indicated that using the Cy-Tb test for diagnosing LTBI was cost-effective as compared with TST testing. If the cost of the Cy-Tb test is reduced, it becomes a cost-saving strategy. CONCLUSIONS: The Cy-Tb test for diagnosing LTBI is cost-effective at the current price, and price negotiations could further change it into a cost-saving strategy. This finding emphasizes the need for healthcare providers and policymakers to consider implementing the Cy-Tb test to maximize economic benefits. Bulk procurements can also be considered to further reduce costs and increase savings.

Specific Cytokines Analysis Incorporating Latency-Associated Antigens Differentiates Mycobacterium tuberculosis Infection Status: An Exploratory Study.

Introduction: Current immunologic methods cannot distinguish Mycobacterium tuberculosis (Mtb) infection statuses, especially to discriminate active tuberculosis (ATB) from latent tuberculosis infection (LTBI). This study explored the potential of latency-associated antigens (Rv1733cSLP and Rv2028c) and multifactorial cytokine detection to distinguish tuberculosis infection states. Methods: ATB patients (20), LTBI healthcare workers (25), fever patients (11), and healthy controls (10) were enrolled. Cytokine levels (IFN-γ, TNF-α, IL-2, IL-6, IP-10, IL-1Ra, CXCL-1, and MCP-1) were measured using Luminex with/without MTB-specific virulence factor and latency-associated antigens stimulation. Results: Without antigen stimulation, IL-6, IP-10, MCP-1, and IL-1Ra were higher in the ATB group than in the LTBI group (p<0.05), but no significant differences between the ATB group and the fever group. Stimulated with the four antigens, respectively, the cytokines, including IP-10Esat-6, IP-10CFP-10, IFN-γRv1733cSLP, IFN-γRv2028c, IL-6Esat-6, IL-6Rv1733cSLP, IL-6Rv2028c, IL-2Rv1733cSLP, IL-2 Rv2028c, IL-1RaEsat-6, IL-1RaCFP-10, IL-1RaRv2028c, CXCL-1Esat-6, CXCL-1CFP-10, CXCL-1Rv1733cSLP, CXCL-1Rv2028c, MCP-1Esat-6 and MCP-1CFP-10, demonstrated accurate discrimination between ATB and LTBI (p<0.05). Additive concentrations demonstrated significant secretion differences of IFN-γ, IP-10 and IL-2, primarily by virulence factors in ATB and latency-associated antigens in LTBI. Latency-associated antigens synergized with virulence factors, enhancing TH1-type cytokine diagnostic efficacy for discriminating ATB from LTBI, the AUC for TNF-α increased from 0.696 to 0.820 (p=0.038), IFN-γ increased from 0.806 to 0.962 (p=0.025), and IL-2 increased from 0.565 to 0.868 (p=0.007). Model selected by forward likelihood method indicated combined detection of IFN-γCFP-10, IFN-γRv1733cSLP, IP-10Rv1733cSLP, and CXCL-1Rv1733cSLP achieved ATB diagnosis (AUC=0.996) and ATB-LTBI differentiation (AUC=0.992). Combined detection of IFN-γCFP-10 and IFN-γRv1733cSLP achieved tuberculosis infection diagnosis (AUC=0.943). Conclusion: Latency-associated antigens enhance multiple cytokine discriminatory ability, particularly TH1-type cytokines, for differentiating Mtb infection statuses.

Knowledge and Attitudes About Screening and Preventive Treatment of Latent Tuberculosis Infection Among Patients with Rheumatic Diseases in Beijing, China.

Objective: Tuberculosis preventive treatment (TPT) is an important strategy for tuberculosis (TB) control. Rheumatic diseases (RD) patients are at high risk for active TB development. More researches are needed in terms of patient compliance in clinical practice. This study aims to explore the potential difficulties and obstacles in latent tuberculosis infection (LTBI) screening and TPT in RD patients. Methods: Convenience sampling was used to recruit RD outpatients who had indications for LTBI screening and TPT. All participants were given questionnaires on knowledge and attitudes regarding screening and preventive treatment of LTBI. Results: Of the 200 RD patients, most people were aware that they were at increased risk of ATB due to their rheumatic disease and knew that TB was curable. The main association with willingness to have screening for LTBI was tertiary education (P = 0.013). The main association with willingness to take treatment for LTBI was a sense of personal risk and belief that the treatment would reduce risk of ATB (P < 0.001). More than half of the people surveyed could not accept taking 6 or more pills per day, while more than half of the patients could tolerate a treatment course of 9 months or longer. Most (65.4%) preferred their own rheumatologists to initiate treatment. Conclusion: Educating RD patients about their individual risks of TB and the side effects of treatment, and educating/empowering rheumatologists to discuss these aspects with their patients and to offer LTBI screening and treatment, may help improve patients' compliance with LTBI screening and TPT.

Acute Leukemia and Latent Tuberculosis Infection in Italy: Quantiferon-Tb Test Screening in a Low Tuberculosis Incidence Country.

Background: Identification of latent tuberculosis infection (LTBI) is a critical step of tuberculosis surveillance, especially in low-incidence countries. However, it is limited to situations with a higher probability of developing active disease, e.g., patients with hematological malignancies. According to guidelines, in TB non-endemic countries, no clear screening program is established at diagnosis for patients with acute leukemia (AL). The primary endpoint of this study was to establish the prevalence of LTBI in patients with a diagnosis of AL using QuantiFERON (QFT)-TB. Secondarily, radiological and clinical features driving the increased risk of LTBI were evaluated. Methods: QFT-TB screening was performed before induction or consolidation in all patients with AL (myeloid and lymphoid) treated at our Institution between October 2019 and August 2023. Results: We accrued 62 patients, of whom 7 (11,3%) tested positive, without any symptoms or signs of active TB, and 2 (3,2%) resulted as indeterminate. All positive patients started prophylaxis with isoniazid 300 mg daily, while patients whose test was indeterminate did not receive any prophylaxis. Active TB was excluded by imaging, as well as microscopic, cultural, and molecular examination on bronchoalveolar lavage if signs of any infection were detected. During the 46 months of observation, no patients developed TB reactivation. Conclusions: Despite the low sample size, 1/10 of our patients had prior TB exposure, hinting that LTBI could be more common than expected in Italy. This finding suggests implementing TB screening in the pre-treatment setting, particularly at a time when more active treatments are becoming available also for patients ineligible for intensive chemotherapy.

Accelerated Bacille Calmette-Guérin reactions: More than meets the eye.

An accelerated local injection site reaction following Bacille Calmette-Guérin (BCG) vaccination has been associated with underlying active tuberculosis (TB) in high TB-prevalence settings. The clinical significance of this accelerated BCG reaction in individuals without TB symptoms, particularly in low TB-prevalence countries, is unclear. Using safety surveillance data and baseline interferon-gamma release assays (IGRA) within an international randomised trial of BCG vaccination in healthcare workers (the BRACE trial), we aimed to determine the incidence, and investigate for clinical implications, of an accelerated BCG reaction in asymptomatic adults in low and high TB-prevalence settings. An accelerated BCG reaction occurred in 755/1984 (38 %) of BCG-vaccinees. Although more frequently painful, tender, erythematous and/or swollen within the first fourteen days of vaccination, compared with non-accelerated reactions, the majority of injection site reactions were mild and did not meet criteria for an adverse event. Prior mycobacterial exposure, through prior BCG vaccination (OR 2.46, 95%CI 1.93-3.13, p < 0.001) or latent TB infection (OR 4.17, 95%CI 1.16-14.93, p = 0.03), and female sex (OR 1.27, 95%CI 1.03-1.57, p = 0.02), were key determinants for the occurrence of an accelerated BCG reaction. The development of an accelerated local reaction to BCG vaccination in an individual without prior history of BCG vaccination, should prompt consideration of further investigations for potential underlying TB infection.

Evaluation of concordance of new QuantiFERON-TB Gold Plus platforms for Mycobacterium tuberculosis infection diagnosis in a prospective cohort of household contacts.

Interferon-gamma (IFN-γ) release assays play a pivotal role in tuberculosis infection (TBI) diagnosis, with QuantiFERON-TB Gold Plus-an enzyme-linked immunosorbent assay (ELISA)-among the most widely utilized. Newer QuantiFERON-TB platforms with shorter turnaround times were recently released. We aimed to evaluate these platforms' agreement in the diagnosis of TBI. Blood samples from a prospective cohort of tuberculosis household contacts were collected at baseline and after 12 weeks of follow-up, and tested with LIAISON, an automated chemiluminescence immunoassay (CLIA) system, QIAreach, a lateral flow (QFT-LF) semi-automated immunoassay, and the ELISA QuantiFERON-TB Gold Plus platform. Test concordances were analyzed. ELISA vs CLIA overall agreement was 83.3% for all tested samples (120/144) [Cohen's kappa coefficient (κ): 0.66 (95% CI: 0.54-0.77)]. Samples positive with CLIA provided consistently higher IFN-γ levels than with ELISA (P < 0.001). Twenty-four (16.7%) discordant pairs were obtained, all CLIA-positive/ELISA-negative: 15 (62.5%) had CLIA IFN-γ levels within borderline values (0.35-0.99 IU/mL) and 9 (37.5%) >0.99 IU/mL. QFT-LF showed only 76.4% (68/89) overall agreement with ELISA [κ: 0.53 (95% CI: 0.37-0.68)] with 21 (23.6%) discordant results obtained, all QFT-LF-positive/ELISA-negative. Overall concordance between ELISA and CLIA platforms was substantial, and only moderate between ELISA and QFT-LF. The CLIA platform yielded higher IFN-γ levels than ELISA, leading to an almost 17% higher positivity rate. The techniques do not seem interchangeable, and validation against other gold standards, such as microbiologically-confirmed tuberculosis disease, is required to determine whether these cases represent true new infections or whether CLIA necessitates a higher cutoff. IMPORTANCE: Tuberculosis is an airborne infectious disease caused by Mycobacterium tuberculosis that affects over 10 million people annually, with over 2 billion people carrying an asymptomatic tuberculosis infection (TBI) worldwide. Currently, TBI diagnosis includes tuberculin skin test and the blood-based interferon-gamma (IFN-γ) release assays, with Qiagen QuantiFERON-TB Gold Plus (QFT) being among those most widely utilized. We evaluated Qiagen's newer QFT platforms commercially available in a prospective cohort of tuberculosis contacts. A substantial agreement was obtained between the current QFT-enzyme-linked immunosorbent assay (ELISA) and the new QFT-chemiluminescence immunoassay (CLIA) platform, although QFT-CLIA provided higher concentrations of IFN-γ, leading to a 16.6% higher positivity rate. We highlight that both platforms may not be directly interchangeable and that further validation is required.

Identification of MORN3 and LLGL2 as novel diagnostic biomarkers for latent tuberculosis infection using machine learning strategies and experimental verification.

BACKGROUND: Current diagnostic methods cannot effectively distinguish between latent tuberculosis infection (LTBI) and active tuberculosis (ATB). This study aims to explore novel non-invasive diagnostic biomarkers for LTBI and to elucidate possible molecular mechanisms of LTBI pathogenesis. METHODS: Three GEO datasets (GSE19439, GSE19444, and GSE62525) were utilized to analyze the differentially expressed genes (DEGs). Functional enrichment studies were then performed on these DEGs. To ascertain potential diagnostic biomarkers, we utilized two different machine learning techniques: LASSO and RF. ROC curves were constructed in both the training and validation datasets to assess the diagnostic efficacy. The expression of identified biomarkers was verified by RT-qPCR in our own Chinese cohort. Using CIBERSORT, we estimated the abundances of 22 immune cell types in LTBI group, and subsequently analyzed the relationship between biomarker expression and immune cell infiltration. RESULTS: 166 DEGs were identified between ATB and LTBI groups, which are primarily associated with immune responses, inflammatory signaling pathways, and infection factors. Following that, 22 candidate diagnostic biomarkers for LTBI were selected in the machine learning process. Three up-regulated genes, MORN3, LLGL2, and IFT140, whose expression levels were not previously reported in TB, were validated using the training and validation cohort datasets. In our own Chinese cohort, we also found that MORN3 and LLGL2 showed good diagnostic effect using RT-qPCR method. Finally, we revealed the specific infiltration features of immune cells in LTBI and observed a notable correlation between potential marker expression and immune cells. CONCLUSIONS: MORN3 and LLGL2 emerged as candidate diagnostic biomarkers for LTBI, following the elucidation of the key immune cell types involved. Our findings will contribute to providing a potential target for early noninvasive diagnosis of LTBI patients.

Adherence to preventive treatment for latent tuberculosis infection in close contacts of pulmonary tuberculosis patients: A cluster-randomized controlled trial in China.

OBJECTIVES: This study examined adherence rates to tuberculosis preventive treatment (TPT) among close contacts of individuals with pulmonary tuberculosis (PTB) and identified factors associated with TPT adherence in China. METHODS: A multicenter, cluster-randomized, open-label control trial was carried out across three sites involving 34 counties in China. Close contacts of bacteriologically confirmed rifampin and isoniazid-susceptible PTB cases were identified and screened for latent tuberculosis infection (LTBI). Eligible participants were randomly assigned to either the 3H2P2 group, which consisted of a 3-month, twice-weekly regimen of rifapentine and isoniazid, or the 6H group, which entailed a 6-month daily regimen of isoniazid. To assess the factors influencing adherence, a two-level logistic regression model was utilized. RESULTS: Out of the 2434 close contacts who initiated TPT, 2121 (87.1%) completed the regimen. Of the 313 individuals who did not complete TPT, 60.1% refused to continue, and 27.8% discontinued due to adverse effects. The two-level logistic regression model revealed several factors associated with enhanced TPT adherence: enrollment in the 3H2P2 group (odds ratio [OR] = 2.09), management by a TB dispensary responsible for TPT (OR = 2.55), supervision by healthcare workers (OR = 6.40), and clinician incentives (OR = 2.49). Conversely, the occurrence of any adverse effects (OR = 0.08) was identified as a risk factor for nonadherence. CONCLUSION: Administering TPT to individuals with LTBI is feasible among close contacts. Adherence to TPT can be enhanced through shorter, safer treatment regimens and supportive interventions, such as directly supervised therapy for TPT recipients and incentives for healthcare providers managing TPT.

Incidence of Tuberculosis Among Immigrants in Korea Who Participated in a Latent Tuberculosis Infection Screening Program.

BACKGROUND: With a rapid decrease in tuberculosis (TB) incidence, the significance of latent tuberculosis infection (LTBI) has been underscored in South Korea. Although South Korea does not have a high proportion of immigrants compared to other countries, there is a growing argument that it should actively embrace immigrants as a solution to address issues of low birth rates and population aging. This study aimed to assess TB incidence among immigrants who participated a pilot LTBI screening program in South Korea. METHODS: Records of immigrants participated in a pilot LTBI screening program in South Korea between 2018 and 2019 were linked with Korean National TB Surveillance System to determine TB development. Participants underwent interferon-gamma release assay (IGRA) and chest X-rays. Standardized incidence ratios (SIRs) stratified by age, country of origin's TB burden was calculated with a reference group of general South Korean population. RESULTS: Of a total of 9,517 participants, 14 TB cases were identified. Participants with positive IGRA results who did not initiate LTBI treatment showed TB incidence of 312.5 per 100,000 person-years, whereas those with negative results showed TB incidence of 34.4 per 100,000 person-years, resulting in an incidence rate ratio of 9.08 (95% confidence interval [CI], 2.50-32.99). SIR of TB among total participants including those with negative IGRA results was 2.60 (95% CI, 1.54-4.38; P < 0.001), whereas SIR among those with positive IGRA results was 5.86 (95% CI, 3.15-10.89; P < 0.001). In the calculation of SIR among participants with positive IGRA results, those aged under 35 from high TB-burden countries or intermediate TB-burden countries showed a high SIR (18.08; 95% CI, 2.55-128.37; P = 0.004), and 11.30 (95% CI, 2.82-45.16; P < 0.001), respectively). Contrary to previous reports that suggest the majority of elderly population with a positive IGRA result were due to remote infection and had a lower TB risk compared to younger ages, SIR among those aged 65 or over from intermediate TB-burden countries was 6.15 (95% CI, 0.87-43.69; P = 0.069), which was comparable to that in younger participants aged between 35 and 49 (SIR, 4.87; 95% CI, 1.22-19.49; P = 0.025) or those aged between 50 and 64 (SIR, 4.62; 95% CI, 1.73-12.31; P = 0.002). CONCLUSION: Young immigrants with positive IGRA results from countries with high or intermediate TB burden showed a relatively high TB risk compared to a general South Korea population. In addition, unexpected high TB risk was observed among elderly immigrants with positive IGRA results. In establishing future policies for LTBI in immigrants in South Korea, screenings should primarily focus on younger age group (who aged under 35). Additionally, further research is needed on the high TB risk observed in elderly immigrants.

Exosomal Small RNA Sequencing Profiles in Plasma from Subjects with Latent Mycobacterium tuberculosis Infection.

Despite huge efforts, tuberculosis (TB) is still a major public health threat worldwide, with approximately 23% of the human population harboring a latent TB infection (LTBI). LTBI can reactivate and progress to active and transmissible TB disease, contributing to its spread within the population. The challenges in diagnosing and treating LTBI patients have been major factors contributing to this phenomenon. Exosomes offer a novel avenue for investigating the process of TB infection. In this study, we conducted small RNA sequencing to investigate the small RNA profiles of plasma exosomes derived from individuals with LTBI and healthy controls. Our findings revealed distinct miRNA profiles in the exosomes between the two groups. We identified 12 differentially expressed miRNAs through this analysis, which were further validated via qRT-PCR using the same exosomes. Notably, six miRNAs (hsa-miR-7850-5p, hsa-miR-1306-5p, hsa-miR-363-5p, hsa-miR-374a-5p, hsa-miR-4654, has-miR-6529-5p, and hsa-miR-140-5p) exhibited specifically elevated expression in individuals with LTBI. Gene ontology and KEGG pathway analyses revealed that the targets of these miRNAs were enriched in functions associated with ferroptosis and fatty acid metabolism, underscoring the critical role of these miRNAs in regulating the intracellular survival of Mycobacterium tuberculosis (Mtb). Furthermore, our results indicated that the overexpression of miR-7850-5p downregulated the expression of the SLC11A1 protein in both Mtb-infected and Mtb-uninfected THP1 cells. Additionally, we observed that miR-7850-5p promoted the intracellular survival of Mtb by suppressing the expression of the SLC11A1 protein. Overall, our findings provide valuable insights into the role of miRNAs and repetitive region-derived small RNAs in exosomes during the infectious process of Mtb and contribute to the identification of potential molecular targets for the detection and diagnosis of latent tuberculosis.

One-month daily and three-month weekly rifapentine plus isoniazid are comparable in completion rate and safety for latent tuberculosis infection in non-HIV Population: a randomized controlled trial.

OBJECTIVES: The weekly rifapentine plus isoniazid for 3 months (3HP) improves completion rate of latent tuberculosis infection treatment, but flu-like symptoms are common. The novel 1HP regimen, involving daily rifapentine plus isoniazid for 28 days, has demonstrated low toxicity in HIV-infected populations. We aimed to investigate whether 1HP has a lower incidence rate of systemic drug reaction (SDR) compared with 3HP during treatment in non-HIV populations. METHODS: This randomized, multicentre trial compared the completion rate and risks of SDRs of 1HP and 3HP in aged ≥13 years non-HIV subjects with latent tuberculosis infection between September 2019 and September 2023 (ClinicalTrials.gov: NCT04094012). We also investigated associations between SDRs and plasma levels of drugs and their metabolites. RESULTS: A total of 251 and 239 individuals were randomly assigned to 1HP and 3HP groups, respectively, with completion rates of 82.9% (208/251) and 84.5% (202/239), respectively. Among them, 12.7% (32/251) and 10.9% (26/239) of 1HP and 3HP groups experienced SDRs, respectively (p 0.522), predominantly urticaria in 1HP group (59.4% [19/32]) and flu-like syndrome in 3HP group (80.8% [21/26]). Among participants experiencing SDRs, 43.8% (14/32) and 34.6% (9/26) in 1HP and 3HP groups, respectively, completed treatment (p 0.470). Cutaneous reactions were more common in 1HP than 3HP group (32.7% [82/251] vs. 13.0% [31/239], p < 0.001). In 1HP group, urticaria was associated with a higher plasma desacetyl-rifapentine level (ug/mL) at both 2 (median [interquartile range]: 36.06 [17.46-50.79] vs. 22.94 [14.67-31.65], p 0.018) and 6 hours (26.13 [15.80-53.06] vs. 29.83 [18.13-34.01], p 0.047) after dosing. DISCUSSION: In non-HIV population, the incidence rate of SDR under 1HP is not lower than 3HP. Notably, urticaria, rather than flu-like syndrome, was the predominant SDR associated 1HP. The findings of this study underscore the feasibility of 1HP regimen in non-HIV populations with a high-completion rate exceeding 80%.

Gene Regulatory Mechanism of Mycobacterium Tuberculosis during Dormancy.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) complex, is a zoonotic disease that remains one of the leading causes of death worldwide. Latent tuberculosis infection reactivation is a challenging obstacle to eradicating TB globally. Understanding the gene regulatory network of Mtb during dormancy is important. This review discusses up-to-date information about TB gene regulatory networks during dormancy, focusing on the regulation of lipid and energy metabolism, dormancy survival regulator (DosR), White B-like (Wbl) family, Toxin-Antitoxin (TA) systems, sigma factors, and MprAB. We outline the progress in vaccine and drug development associated with Mtb dormancy.

Mixed methods study on latent tuberculosis among agate stone workers and advocacy for testing silica dust exposed individuals in India.

The 2021 tuberculosis (TB) preventive treatment guidelines in India included silicosis as a screening group, yet latent TB infection (LTBI) testing for silica-dust-exposed individuals is underemphasized. Focusing on an estimated 52 million silica-dust-exposed workers, particularly agate-stone workers in Khambhat, Gujarat, our study aims to estimate LTBI prevalence, identify predictors, and gather insights from TB and silicosis experts. Employing a sequential explanatory mixed-methods approach, a cross-sectional study involved 463 agate-stone workers aged ≥ 20 years in Khambhat, using IGRA kits for LTBI testing. In-depth interviews with experts complemented quantitative findings. Among agate-stone workers, 58% tested positive for LTBI, with predictors including longer exposure, type of work, and BCG vaccination. Our findings reveal a nearly double burden of LTBI compared to the general population, particularly in occupations with higher silica dust exposure. Experts advocate for including silica-dust-exposed individuals in high-risk groups for LTBI testing, exploring cost-effective alternatives like improved skin sensitivity tests, and shorter TB preventive treatment regimens to enhance compliance. Future research should explore upfront TB preventive treatment for silica-dust-exposed individuals with high LTBI prevalence and optimal exposure duration. This study underscores the urgent need for policy changes and innovative approaches to TB prevention among silica-dust-exposed populations, impacting global occupational health strategies.

Factors Associated With the Discontinuation of Two Short-Course Tuberculosis Preventive Therapies in Programmatic Settings in the United States.

Background: The objective of this study was to investigate timing and risk factors for discontinuation of short-course tuberculosis preventive therapy (TPT) comparing directly observed 3-month isoniazid/rifapentine (3HP) vs self-administered 4-month rifampin (4R). Methods: This was a subanalysis of a 6-month health department cohort (2016-2017) of 993 latent tuberculosis infection (LTBI) patients initiating 3HP (20%) or 4R (80%). Time at risk of TPT discontinuation was compared across regimens. Risk factors were assessed using mixed-effects Cox models. Results: Short-course TPT discontinuation was higher with 4R (31% vs 14%; P < .0001), though discontinuation timing was similar. Latino ethnicity (hazard ratio [HR], 1.80; 95% CI, 1.20-2.90) and adverse events (HR, 4.30; 95% CI, 2.60-7.30) increased 3HP discontinuation risk. Social-behavioral factors such as substance misuse (HR, 12.00; 95% CI, 2.20-69.00) and congregate living (HR, 21.00; 95% CI, 1.20-360.00) increased 4R discontinuation risk. Conclusions: TPT discontinuation differed by regimen, with distinct risk factors. Addressing social determinants of health within TPT programs is critical to enhance completion rates and reduce TB disease risk in marginalized populations.

Screening of household contacts for TB infection in Cote d'Ivoire.

SETTING: Côte d'Ivoire is a country with a high incidence of TB. The control of TB infection is focused on high-risk patients but has limited implementation. OBJECTIVE: Cost-benefit analysis of TB infection (TBI) screening of household contacts in Côte d'Ivoire to evaluate economic implications of the implementation of interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST). DESIGN: We compared the effectiveness of QuantiFERON-TB Gold Plus (QuantiFERON) with the TST using an economic model previously evaluated in medium TB incidence settings. Principal outcomes relating to TBI screening, as well as the lifetime costs and benefits of the patient cohort, were captured using a decision tree, followed by a Markov model. RESULTS: QuantiFERON proved to be both more effective and less costly than TST. Compared to QuantiFERON, TST use leads to an approximate 33% increase in the lifetime risk of developing active TB. CONCLUSIONS: For household contacts of active TB cases in Côte d'Ivoire, QuantiFERON is cost-effective when compared with TST. R shiny interactive interface enables model customisation for different scenarios, settings, risk groups and TBI screening methods. Further research should be conducted in similar settings to generalise the results.

CONTEXTE: La Côte d'Ivoire est un pays où l'incidence de la TB est élevée. La lutte contre l'infection à TB est axée sur les patients à haut risque, mais sa mise en œuvre est limitée. OBJECTIF: Analyse coût-bénéfice du dépistage de l'infection à TB (TBI) chez les contacts familiaux en Côte d'Ivoire afin d'évaluer les implications économiques de la mise en œuvre des tests de libération de l'interféron-gamma (IGRA) et du test cutané à la tuberculine (TST). DESIGN: Nous avons comparé l'efficacité de QuantiFERON-TB Gold Plus (QuantiFERON) avec celle du TST en utilisant un modèle économique précédemment évalué dans des contextes d'incidence moyenne de la TB. Les principaux résultats relatifs au dépistage de la TBI, ainsi que les coûts et bénéfices à vie de la cohorte de patients, ont été saisis à l'aide d'un arbre de décision, suivi d'un modèle de Markov. RÉSULTATS: QuantiFERON s'est avéré à la fois plus efficace et moins coûteux que le TST. Par rapport à QuantiFERON, l'utilisation du TST entraîne une augmentation d'environ 33% du risque de développer une TB active au cours de la vie. CONCLUSIONS: Pour les contacts familiaux des cas de TB active en Côte d'Ivoire, QuantiFERON est rentable par rapport au TST. L'interface interactive R shiny permet de personnaliser le modèle pour différents scénarios, contextes, groupes à risque et méthodes de dépistage de la TBI. D'autres recherches devraient être menées dans des contextes similaires pour généraliser les résultats.

Post-COVID-19 Pulmonary Inflammatory Pseudotumors Treated With Steroid Taper.

The aftermath of COVID-19 continues to unveil an array of pulmonary complications, extending beyond the acute phase of the viral infection. Among these emerging sequelae, we present the case of a 58-year-old individual who developed pulmonary inflammatory pseudotumors (PIPs) following recovery from COVID-19. PIPs are exceedingly rare benign lesions that can pose a diagnostic challenge due to their clinical and radiological resemblance to malignant neoplasms. Histologically, PIPs are characterized by a proliferation of myofibroblastic spindle cells accompanied by inflammatory infiltrates, including lymphocytes, plasma cells, and histiocytes. As our understanding of post-COVID-19 complications evolves, this case serves as the first exploration into the complex interplay between COVID-19 infections and the subsequent development of inflammatory pseudotumors. In this report, an investigation is performed into the clinical presentation, diagnostic challenges, and successful management of post-COVID-19 PIPs with a focus on the pivotal role of corticosteroid therapy in mitigating the inflammatory response associated with this unique post-viral entity and resolution of the masses.