Optimized anti-tuberculosis duration for drug-susceptible pulmonary tuberculosis-diabetes mellitus comorbidities: study protocol for a multicenter randomized controlled trial.

BACKGROUND: The coexistence of tuberculosis (TB) and type 2 diabetes mellitus (DM) presents unique challenges in treatment optimization and management, given the mutual exacerbation of disease processes. OBJECTIVE: This multicenter, open-label, randomized controlled trial aims to evaluate the efficacy and safety of two different treatment durations (6-month versus 9-month regimens) regimen for patients with drug-susceptible pulmonary tuberculosis (DS-PTB) and concurrent type 2 diabetes (DM). METHODS: Patients with DS-PTB and type-2 DM from 22 hospitals in China are enrolled. They are randomized in a 1:1 ratio into either the 6-month regimen arm(2HRZE/4HR) or the 9-month regimen arm(2HRZE/7HR). At the end of the intensive phase (the 8th week), patients in both arms who with sputum positive smear will extent one more month of intensive treatment. The primary outcome is the proportion of unfavorable outcomes at 24 months after randomization. Secondary outcomes include treatment success rate at the end of treatment, proportion of recurrence at 24 months after randomization, time to recurrence after treatment completion, proportion of intensive phrase extension, occurrence of adverse events grade 3 or above during treatment. DISCUSSION: The study focuses on assessing the optimal treatment duration to maximize treatment success while minimizing recurrence and adverse events. The trial is expected to provide vital insights into the appropriate treatment duration for patients with TB-DM, aiming to reduce recurrence rates and improve overall treatment outcomes in this vulnerable population. TRAIL REGISTRATION: Chictr.org.cn, ChiCTR2100044663. Registered on March 25, 2021.

Study protocol for safety and efficacy of all-oral shortened regimens for multidrug-resistant tuberculosis: a multicenter randomized withdrawal trial and a single-arm trial [SEAL-MDR].

INTRODUCTION: The urgent need for new treatments for multidrug-resistant tuberculosis (MDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) is evident. However, the classic randomized controlled trial (RCT) approach faces ethical and practical constraints, making alternative research designs and treatment strategies necessary, such as single-arm trials and host-directed therapies (HDTs). METHODS: Our study adopts a randomized withdrawal trial design for MDR-TB to maximize resource allocation and better mimic real-world conditions. Patients' treatment regimens are initially based on drug resistance profiles and patient's preference, and later, treatment-responsive cases are randomized to different treatment durations. Alongside, a single-arm trial is being conducted to evaluate the potential of sulfasalazine (SASP) as an HDT for pre-XDR-TB, as well as another short-course regimen without HDT for pre-XDR-TB. Both approaches account for the limitations in second-line anti-TB drug resistance testing in various regions. DISCUSSION: Although our study designs may lack the internal validity commonly associated with RCTs, they offer advantages in external validity, feasibility, and ethical appropriateness. These designs align with real-world clinical settings and also open doors for exploring alternative treatments like SASP for tackling drug-resistant TB forms. Ultimately, our research aims to strike a balance between scientific rigor and practical utility, offering valuable insights into treating MDR-TB and pre-XDR-TB in a challenging global health landscape. In summary, our study employs innovative trial designs and treatment strategies to address the complexities of treating drug-resistant TB, fulfilling a critical gap between ideal clinical trials and the reality of constrained resources and ethical considerations. TRAIL REGISTRATION: Chictr.org.cn, ChiCTR2100045930. Registered on April 29, 2021.

A cross-sectional study: a breathomics based pulmonary tuberculosis detection method.

BACKGROUND: Diagnostics for pulmonary tuberculosis (PTB) are usually inaccurate, expensive, or complicated. The breathomics-based method may be an attractive option for fast and noninvasive PTB detection. METHOD: Exhaled breath samples were collected from 518 PTB patients and 887 controls and tested on the real-time high-pressure photon ionization time-of-flight mass spectrometer. Machine learning algorithms were employed for breathomics analysis and PTB detection mode, whose performance was evaluated in 430 blinded clinical patients. RESULTS: The breathomics-based PTB detection model achieved an accuracy of 92.6%, a sensitivity of 91.7%, a specificity of 93.0%, and an AUC of 0.975 in the blinded test set (n = 430). Age, sex, and anti-tuberculosis treatment does not significantly impact PTB detection performance. In distinguishing PTB from other pulmonary diseases (n = 182), the VOC modes also achieve good performance with an accuracy of 91.2%, a sensitivity of 91.7%, a specificity of 88.0%, and an AUC of 0.961. CONCLUSIONS: The simple and noninvasive breathomics-based PTB detection method was demonstrated with high sensitivity and specificity, potentially valuable for clinical PTB screening and diagnosis.

Sleep quality and influencing factors and correlation with T-lymphocyte subpopulation counts in patients with pulmonary tuberculosis: a cross-sectional study.

BACKGROUND: Patients diagnosed with pulmonary tuberculosis (TB) have poor sleep quality due to multiple factors. We aimed to assess the sleep status and related factors of TB patients in Shenzhen, China. METHODS: A questionnaire survey was conducted on 461 TB patients hospitalized at Shenzhen Third People's Hospital from March 2021 to January 2022, and sleep quality was assessed using the Pittsburgh sleep quality index (PSQI). RESULTS: A total of 459 valid questionnaires were collected, and 238 of the 459 TB patients had general or poor sleep quality (PSQI > 5). Patients' gender, marriage, nutritional screening score, family atmosphere, fear of discrimination, fear of interactions, and the impact of the disease on their work life had significant effects on sleep quality (P < 0.05); PSQI scores of TB patients were negatively correlated with lymphocyte counts (r = - 0.296, P < 0.01), T-lymphocyte counts (r = - 0.293, P < 0.01), helper T lymphocyte counts (r = - 0.283, P < 0.01), killer T lymphocyte counts (r = - 0.182, P < 0.05), and were positively correlated with depression scores (r = 0.424, P < 0.01). Multivariable logistic regression analysis showed that male (OR = 1.64,95% CI 1.11-2.42, P < 0.05), unmarried (OR = 1.57, 95% CI 1.02-2.42, P < 0.05), NRS score grade 3(OR = 5.35, 95% CI 2.08-15.73, P < 0.01), general family atmosphere (OR = 2.23, 95% CI 1.07-4.93, P < 0.05), and the disease affecting work (OR = 1.66, 95% CI 1.11-2.50, P < 0.05) were factors influencing poor sleep quality. CONCLUSION: Most TB patients had varying degrees of sleep disturbance, which may be affected by their gender, marriage, family atmosphere, nutritional status, the effect of the disease on work life, and, depression, as well as lower absolute T-lymphocyte subpopulation counts. Appropriate interventions should be implemented to improve their sleep quality, when treating or caring for such patients.

Decreased mortality seen in rifampicin/multidrug-resistant tuberculous meningitis treated with linezolid in Shenzhen, China.

BACKGROUND: The morbidity of rifampicin/multidrug-resistant tuberculous meningitis (RR/MDR-TBM) has shown an increasing trend globally. Its mortality rate is significantly higher than that of non-rifampicin/multidrug-resistant tuberculous meningitis (NRR/MDR-TBM). This article aimed to explore risk factors related to RR/MDR-TBM, and compare therapeutic effects of linezolid (LZD)- and non-linezolid-containing regimen for RR/MDR-TB patients in Shenzhen city. Furthermore, we aimed to find a better therapy for pathogen-negative TBM with RR/MDR-TBM related risk factors. METHODS: We conducted a retrospective study enrolling 137 hospitalized cases with confirmed TBM from June 2014 to March 2020. All patients were divided into RR/MDR-TBM group (12 cases) and NRR/MDR-TBM group (125 cases) based on GeneXpert MTB/RIF and (or) phenotypic drug susceptibility test results using cerebral spinal fluid (CSF). The risk factors related to RR/MDR-TBM were investigated through comparing clinical and examination features between the two groups. The mortality rate of RR/MDR-TBM patients treated with different regimens was analyzed to compare their respective therapeutic effects. A difference of P < 0.05 was considered statistically significant. RESULTS: Most patients (111/137, 81%) were from southern or southwestern China, and a large proportion (72/137, 52.55%) belonged to migrant workers. 12 cases were RR/MDR-TBM (12/137, 8.8%) while 125 cases were NRR/MDR-TBM (125/137, 91.2%). The proportion of patients having prior TB treatment history in the RR/MDR-TBM group was significantly higher than that of the NRR/MDR-TBM group (6/12 vs. 12/125, 50% vs. 10.5%, P < 0.01). No significant difference was observed on other clinical and examination features between the two groups. Mortality was significantly lower in RR/MDR-TBM patients on linezolid-containing treatment regimen than those who were not (0/7 versus 3/5, 0% versus 60%, P = 0.045). CONCLUSIONS: The main related risk factor of RR/MDR-TBM is the history of anti-tuberculosis treatment. Linezolid-containing regimen appears to lower mortality rate of RR/MDR-TBM significantly in our study. We think Linezolid should be evaluated prospectively in the treatment of RR/MDR-TBM.

Incidence and Predictors of Tracheobronchial Tuberculosis in Pulmonary Tuberculosis: A Multicentre, Large-Scale and Prospective Study in Southern China.

BACKGROUND: Patients with pulmonary tuberculosis (PTB) have a high risk of concomitant tracheobronchial tuberculosis (TBTB), which commonly causes severe complications such as tracheobronchial stenosis. The prevalence and predictors of TBTB in China remain unclear due to the lack of prospective and large-scale studies. OBJECTIVES: To investigate the incidence of TBTB in PTB patients in southern China, and elucidate the predictors of TBTB and related tracheobronchial stenosis. METHODS: We prospectively performed bronchoscopy in PTB patients to diagnose TBTB at four medical centres in southern China from September 2015 to August 2016. Clinical and epidemiological data were recorded and analysed to determine predictors of TBTB and related tracheobronchial stenosis. RESULTS: A total of 345 (23.9%) of the 1,442 PTB patients undergoing bronchoscopy were diagnosed with TBTB. Female sex (OR 2.53), age < 50 years (OR 1.88), living in urban (OR 2.19), diabetes (OR 1.84), coughing (OR 2.61), and symptoms ≥4 weeks (OR 1.66) were predictors of PTB concomitant with TBTB. About 59.7% TBTB patients developed tracheobronchial stenosis, of which 23.3% cases presented severe airway narrowing. Female sex (OR 2.27), age < 50 years (OR 2.11), shortness of breath (OR 1.97), and symptoms ≥4 weeks (OR 1.71) were predictors of TBTB-related tracheobronchial stenosis. CONCLUSIONS: About 23.9% of PTB patients undergoing bronchoscopy present with TBTB in Guangdong province, southern China. Young and middle-aged females with symptoms persisting for ≥4 weeks (the main predictors of TBTB and related tracheobronchial stenosis) should receive bronchoscopy immediately when diagnosed with PTB.

Successful Treatment of Intractable Tuberculous Peritonitis in a Woman with Chronic Kidney Allograft Dysfunction Using Contezolid Containing Regimen.

Tuberculosis(TB) is a serious infection that affects transplant recipients, particularly in high TB burden countries. Clinical presentation of these patients is atypical, and the care and management are frequently tricky as multi-drug interaction and intolerable adverse effects. Contezolid, a novel oxazolidinone antibacterial agent, had been demonstrated to be effective for TB in vitro and had been shown in some clinical cases with a more favorable safety profile than linezolid, the first-generation oxazolidinone, which had a commonly seen myelosuppression and neuropathy. Additionally, Contezolid has a unique metabolic mechanism that leads to less drug interaction. Here, we report a case of multi-system TB in a transplant recipient with chronic kidney allograft dysfunction. She was intolerant to most first and second-line anti-TB drugs and repeatedly developed ascites and nocturnal low-grade fever. She finally achieved good efficacy and safety results after enhanced anti-TB treatment with the addition of contezolid. Given the increased risk of TB in patients with organ transplantation and multi-drug interaction in patients with severe comorbidities, further clinical studies are needed to investigate the application and appropriate dosage of contezolid in patients with active TB.

A blood-based 3-gene signature score for therapeutic monitoring in patients with pulmonary tuberculosis.

OBJECTIVE: To assess the validity of Xpert Tuberculosis Fingerstick score for monitoring treatment response and analyze factors influencing its performance. METHODS: 122 adults with pulmonary tuberculosis were recruited and stratified into three cohorts: Diabetic-drug-susceptible-TB (DM-TB), Non-diabetic-drug-susceptible-TB (NDM-TB) and Non-diabetic Multidrug-resistant TB (MDR-TB). Fingerstick blood specimens were tested at treatment initiation (M0) and the end of the first (M1), second (M2), and sixth month (M6) to generate a TB-score. RESULTS: The TB-score in all participants yielded an AUC of 0.707 (95% CI: 0.579-0.834) at M2 when its performance was evaluated against sputum culture conversion. In all non-diabetes patients, the AUC reached 0.88 (95% CI: 0.756-1.000) with an optimal cut-off value of 1.95 at which sensitivity was 90.0% (95% CI: 59.6-98.2%) and specificity was 81.3% (95% CI: 70.0-88.9%). The mean TB score was higher in patients with low bacterial loads (n = 31) than those with high bacterial loads (n = 91) at M0, M1, M2, and M6, and was higher in non-cavitary patients (n = 71) than those with cavitary lesions (n = 51) at M0, M1, and M2. CONCLUSION: Xpert TB-score shows promising predictive value for culture conversion in non-diabetic TB patients. Sputum bacterial load and lung cavitation status have an influence on the value of TB score.

Variations in Quinolinic Acid Levels in Tuberculosis Patients with Diabetes Comorbidity: A Pilot Prospective Cohort Study.

Objective: We aimed to investigate dysregulated metabolic pathways and identify diagnostic and therapeutic targets in patients with tuberculosis-diabetes (TB-DM). Methods: In our prospective cohort study, plasma samples were collected from healthy individuals, diabetic (DM) patients, untreated TB-only (TB-0)/TB-DM patients (TB-DM-0), and cured TB (TB-6)/TB-DM patients (TB-DM-6) to measure the levels of amino acids, fatty acids, and other metabolites in plasma using high-throughput targeted quantification methods. Results: Significantly different biological processes and biomarkers were identified in DM, TB-DM-0, and TB-DM-6 patients. Moreover, quinolinic acid (QA) showed excellent predictive accuracy for distinguishing between DM patients and TB-DM-0 patients, with an AUC of 1 (95% CI 1-1). When differentiating between TB-DM-0 patients and TB-DM-6 patients, the AUC was 0.9297 (95% CI 0.8460-1). Compared to those in DM patients, the QA levels were significantly elevated in TB-DM-0 patients and decreased significantly after antituberculosis treatment. We simultaneously compared healthy controls and untreated tuberculosis patients and detected an increase in the level of QA in the plasma of tuberculosis patients, which decreased following treatment. Conclusion: These findings improve the current understanding of tuberculosis treatment in patients with diabetes. QA may serve as an ideal diagnostic biomarker for TB-DM patients and contribute to the development of more effective treatments.

Risk factors associated with pulmonary hypertension in patients with active tuberculosis and tuberculous destroyed lung: a retrospective study.

Pulmonary tuberculosis (TB) can result in irreversible damage and lead to tuberculous destructive lung (TDL), a severe chronic lung disease that is associated with a high mortality rate. Additionally, pulmonary hypertension (PH) is a hemodynamic disorder that can be caused by lung diseases. The objective of this study is to investigate the risk factors associated with PH in active TB patients diagnosed with TDL. We conducted a retrospective review of the medical records of 237 patients who were diagnosed with TDL, active pulmonary tuberculosis, and underwent echocardiography at the Third People' Hospital of Shenzhen from January 1, 2016, to June 30, 2023. Univariate and multivariate logistic regression analyses were performed to identify factors that correlated with the development of pulmonary hypertension. Univariate and multivariate logistic regression analyses revealed that several factors were associated with an increased risk of pulmonary hypertension (PH) in individuals with tuberculosis destroyed lung (TDL). These factors included age (OR = 1.055), dyspnea (OR = 10.728), D-dimer (OR = 1.27), PaCO2 (OR = 1.040), number of destroyed lung lobes (OR = 5.584), bronchiectasis (OR = 3.205), and chronic pleuritis (OR = 2.841). When age, D-dimer, PaCO2, and number of destroyed lung lobes were combined, the predictive value for PH in patients with TDL was found to be 80.6% (95% CI 0.739-0.873),with a sensitivity of 76.6% and specificity of 73.2%. Advanced age, elevated D-dimer levels, hypercapnia, and severe lung damage were strongly correlated with the onset of PH in individuals with active pulmonary tuberculosis (PTB) and TDL. Furthermore, a model incorporating age, D-dimer, PaCO2, and the number of destroyed lung lobes might be valuable in predicting the occurrence of PH in patients with active PTB and TDL.

Prevalence and Risk Factors of Diabetes in Patients with Active Pulmonary Tuberculosis: A Cross-Sectional Study in Two Financially Affluent China Cities.

Background: Tuberculosis (TB) and diabetes mellitus (DM) present a dual burden to public health. The screening of DM in TB patients may aid in the early detection and management of diabetes, ultimately improving treatment outcomes for those with the comorbidity of TB-DM. We aim to examine the prevalence and identify risk factors of diabetes in individuals with active pulmonary tuberculosis (PTB) in financially affluent China cities. Methods: A cross-sectional survey was conducted in adult patients with highly suspected TB in two cities of China, spanning from May 9, 2023, to June 30, 2023. We compare the clinical characteristics, nutrition status, fasting blood glucose (FBG) level, living style, and knowledge of TB and DM at admission between patients with and without DM. Univariate and multivariate logistic regression analyses were employed to identify risk factors associated with TB-DM comorbidities. Results: Of the 322 patients diagnosed with pulmonary tuberculosis (PTB), 54 individuals (16.8%) had comorbid diabetes mellitus (DM). This included 43 males (13.4%) and 11 females (3.4%). The average age was 55.44 ± 12.36 in DM patients and 46.09 ± 16.87 in non-DM patients. A multivariate logistic regression analysis revealed that male (adjusted odds ratio [aOR]=3.29, 95% confidence interval [CI]: 1.05-10.30), age older than 47 years (aOR = 1.04, 95% CI: 1.01-1.07), having a family history of diabetes (aOR = 5.09, 95% CI: 1.28-20.32), and an elevated random blood glucose level (aOR = 1.6, 95% CI: 1.38-1.86) were risk factors for DM in patients with PTB. Furthermore, it was found that diabetes awareness (aOR = 0.07, 95% CI: 0.03-0.21) and zero, light to moderate alcohol consumption were associated with a lower risk of diabetes. Conclusion: Diabetes is prevalent in patients with active PTB. Screening and raising awareness of DM are recommended, particularly in men after middle age with a family history of diabetes and elevated random blood glucose. Early diagnosis of diabetes and effective diabetes prevention may reduce the dual burden of TB-DM comorbidity.

Evaluation of Sulfasalazine as an Adjunctive Therapy in Treating Pulmonary Pre-XDR-TB: Efficacy, Safety, and Treatment Implication.

Background: The rising prevalence and limited efficacy of treatments for pre-extensively drug-resistant tuberculosis (pre-XDR-TB) underscore an immediate need for innovative therapeutic options. A combination of host-directed therapy (HDT) and anti-TB treatment presents a viable alternative for pre-XDR-TB management. Sulfasalazine (SASP), by targeting the amino acid transport system xc (xCT), potentially reduces the intracellular Mycobacterium tuberculosis load and mitigates lung pathology, positioning it as a promising TB HDT agent. This study aims to assess the efficacy of SASP as a supplementary therapy for pre-XDR-TB. Methods: A pilot study examined the safety and effectiveness of two 9-month short-course, all-oral regimens for pre-XDR-TB treatment: Bdq-regimen (consisting of Bdq, linezolid, cycloserine, clofazimine, and pyrazinamide) and SASP-regimen (comprising SASP, linezolid, cycloserine, clofazimine, and pyrazinamide). The primary endpoint was the incidence of unfavorable outcomes 12 months post-treatment. Results: Of the 44 participants enrolled, 43 were assessable 12 months post-treatment. Culture conversion rates stood at 73.2% by Month 2 and escalated to 95.1% by Month 6. Overall, 88.4% (38/43) of the participants exhibited favorable outcomes, 85.2% (19/23) for the Bdq-regimen and 93.8% (14/15) for the SASP-regimen. The SASP-regimen group recorded no deaths or treatment failures. Conclusion: Both 9-month short-course, all-oral regimens manifested commendable primary efficacy in treating pre-XDR-TB patients. The SASP-regimen emerged as effective, safe, well-tolerated, and cost-effective.

Call for special attention to the caregiver burden of patients with drug-resistant tuberculosis in low- and middle-income countries.

The tuberculosis (TB)-related caregiver burden (CB), and particularly the multidrug and extensively drug-resistant tuberculosis (M/XDR-TB)-related CB, is not rare in caregivers caring for TB patients, especially when a family member is the caregiver. However, the existing studies on this topic are insufficient. This study briefly summarized the risk factors for the imposition of a TB-related CB and reasons why caregivers for patients with M/XDR-TB are more susceptible to a CB. We propose that special measures should be implemented to alleviate the TB-related CB based on our clinical experience and insights from China. This may improve the situation of caregivers for TB patients and ultimately improve the quality of life of TB patients.

Pharmacokinetics of Antituberculosis Drugs in Plasma and Cerebrospinal Fluid in a Patient with Pre-Extensive Drug Resistant Tuberculosis Meningitis.

Drug-resistant tuberculous meningitis (TBM) is the most devastating and critical form of extrapulmonary tuberculosis. Here, we present a case of a 45-year-old male with pre-extensive drug-resistant tuberculosis meningitis (pre-XDR-TBM). He underwent emergency surgery for the long-tunneled external ventricular drainage (LTEVD). Molecular test and phenotypic drug sensitivity test (DST) of Mycobacterium tuberculosis in cerebrospinal fluid (CSF) showed that the isolate was resistant to both rifampin and fluoroquinolones. An anti-tuberculous regimen of isoniazid, pyrazinamide, cycloserine, moxifloxacin, clofazimine, and linezolid was tailored accordingly. We monitored the drug concentration in his plasma and CSF before (at 0-hour) and after anti-TB drugs administration (at 1-hour, 2-hour, 6-hour, and 12-hour) on 10th day after treatment initiation. We hope to provide reference values of drug exposures in plasma and CSF for patients with pre-XDR-TBM.

The association between type 2 diabetes and pulmonary cavitation revealed among IGRA-positive tuberculosis patients.

The co-occurrence of tuberculosis (TB) and diabetes mellitus (DM) presents a significant obstacle to TB eradication. Pulmonary cavitation can occur in severe cases of TB, particularly in patients with DM. From 1 May 2014 through 30 June 2019, we conducted a cross-sectional study of 1,658 smear- or culture-confirmed pulmonary TB (PTB) patients at the Second Department of Pulmonary Medicine and Tuberculosis, Shenzhen, China. A total of 861 participants who satisfied the criteria (chest CT scan for cavitation, interferon-gamma release assay (IGRA), diagnosis of diabetes mellitus), with the median age of 36.7 years, 63.6% of male, 79.7% IGRA positive, 13.8% with diabetes, and 40.8% with pulmonary cavitation, were included in the study. The association between diabetes and pulmonary cavitation was confirmed in these TB patients (adjusted OR, 2.54; 95% CI, 1.66-3.94; p < 0.001). No associations were observed between diabetes and IGRA, as well as between lung cavitary and IGRA. Based on the criteria of IGRA+/-, pulmonary cavitation+/-, and DM+/-, the further analysis with univariate and multivariate logistic regression were conducted in six subgroups. The significant association between diabetes and pulmonary cavitation was further confirmed in the IGRA+ subgroup (adjusted OR, 3.07; 95% CI, 1.86-5.16; p < 0.001) but not observed in IGRA- individuals. This observation suggests that different immunological mechanisms of pulmonary cavitary/DM may be employed in IGRA+ TB patients from IGRA- TB patients.

Factors associated with loss to follow-up before and after treatment initiation among patients with tuberculosis: A 5-year observation in China.

Background: Loss to follow-up (LTFU) is a significant barrier to the completion of anti-tuberculosis (TB) treatment and a major predictor of TB-associated deaths. Currently, research on LTFU-related factors in China is both scarce and inconsistent. Methods: We collected information from the TB observation database of the National Clinical Research Center for Infectious Diseases. The data of all patients who were documented as LTFU were assessed retrospectively and compared with those of patients who were not LTFU. Descriptive epidemiology and multivariable logistic regression analyses were conducted to identify the factors associated with LTFU. Results: A total of 24,265 TB patients were included in the analysis. Of them, 3,046 were categorized as LTFU, including 678 who were lost before treatment initiation and 2,368 who were lost afterwards. The previous history of TB was independently associated with LTFU before treatment initiation. Having medical insurance, chronic hepatitis or cirrhosis, and providing an alternative contact were independent predictive factors for LTFU after treatment initiation. Conclusion: Loss to follow-up is frequent in the management of patients with TB and can be predicted using patients' treatment history, clinical characteristics, and socioeconomic factors. Our research illustrates the importance of early assessment and intervention after diagnosis. Targeted measures can improve patient engagement and ultimately treatment adherence, leading to better health outcomes and disease control.

The interaction of macrophages and CD8 T cells in bronchoalveolar lavage fluid is associated with latent tuberculosis infection.

Mycobacterium tuberculosis (Mtb) infection, including active tuberculosis (TB) and latent Mtb infection (LTBI), leads to diverse outcomes owing to different host immune responses. However, the immune mechanisms that govern the progression from LTBI to TB remain poorly defined in humans. Here, we profiled the lung immune cell populations within the bronchoalveolar lavage fluid (BALF) from patients with LTBI or TB using single-cell RNA sequencing (scRNA-seq). We found that Mtb infection substantially changed the immune cell compartments in the BALF, especially for the three subsets of macrophages, monocyte macrophage (MM)-CCL23, MM-FCN1, and MM-SPP1, which were found to be associated with the disease status of TB infection. Notably, MM-CCL23 cells derived from monocytes after stimulation with Mtb were characterized by high levels of chemokine (CCL23 and CXCL5) production and might serve as a marker for Mtb infection. The MM-CCL23 population mainly recruited CD8-CCR6 T cells through CCL20/CCR6, which was a prominent feature associated with protection immunity in LTBI. This study improves our understanding of the lung immune landscape during Mtb infection, which may inform future vaccine design for protective immunity.

Selecting an appropriate all-oral short-course regimen for patients with multidrug-resistant or pre-extensive drug-resistant tuberculosis in China: A multicenter prospective cohort study.

OBJECTIVES: Long, ineffective, and toxic regimens hinder the treatment of patients with multidrug-resistant tuberculosis (MDR-TB) and pre-extensive drug-resistant tuberculosis (pre-XDR-TB). METHODS: We conducted a multicenter cohort study to prospectively evaluate the safety and efficacy of three 9-month, all-oral, 5-drug regimens. Regimen A (bedaquiline [Bdq]+linezolid [Lzd]+moxifloxacin [Mfx]+cycloserine [Cs]+pyrazinamide [Pza]) and Regimen B (Lzd+Mfx+Cs+clofazimine [Cfz]+Pza) were used to treat MDR-TB patients (Groups A and B, respectively, assigned according to the patient's treatment preference), while Regimen C (Bdq+Lzd+Cs+Cfz+Pza) was used to treat pre-XDR-TB patients (Group C). The primary endpoint was the occurrence of an unfavorable outcome within 12 months of treatment completion, regardless of regimen. RESULTS: A total of 104 patients (34 in Group A, 46 in Group B, and 24 in Group C), with a median age of 35.5 (29.0-54.0) years, were included in the analysis population. At 12 months after treatment completion, five patients were deemed non-assessable. Of the remaining 99 participants, seven (7.1%) had an unfavorable outcome (including two deaths from any cause, four with treatment failure, and one loss to follow-up) and 92 (92.9%) had a favorable outcome. Culture conversion was achieved in 82.5% (80/97) of participants at month 2 and in 97.9% (94/97) of participants at month 6. Adverse events (AEs) resulting in drug adjustment occurred in 69.2% (72/104) of participants, mainly due to Lzd and Pza use. A QT interval prolongation of ≥ 500 ms occurred in 5.8% (6/104) of participants. CONCLUSION: The primary outcome of the three tailored, 9-month, all-oral, 5-drug regimens was satisfactory in the vast majority of MDR-TB and pre-XDR-TB patients, with manageable and reversible AEs.

Detecting latent tuberculosis infection with a breath test using mass spectrometer: A pilot cross-sectional study.

Mycobacterium tuberculosis (M.tb) infects a quarter of the world's population and may progress to active tuberculosis (ATB). There is no gold standard for diagnosing latent tuberculosis infection (LTBI). Some immunodiagnostic tests are recommended to detect LTBI but can not distinguish ATB from LTBI. The breath test is useful for diagnosing ATB compared to healthy subjects but was never studied for LTBI. This proof-of-concept study (Chinese Clinical Trials Registry number: ChiCTR2200058346) was the first to explore a novel, rapid, and simple LTBI detection method via breath test on high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS). The case group of LTBI subjects (n = 185) and the control group (n = 250), which included ATB subgroup (n = 121) and healthy control (HC) subgroup (n = 129), were enrolled. The LTBI detection model indicated that a breath test via HPPI-TOFMS could distinguish LTBI from the control with a sensitivity of 80.0% (95% CI: 67.6%, 92.4%) and a specificity of 80.8% (95% CI: 71.8%, 89.9%). Nevertheless, further intensive studies with a larger sample size are required for clinical application.

Challenges in the screening and treatment of latent multidrug-resistant tuberculosis infection.

Individuals in close contact with multidrug-resistant tuberculosis (MDR-TB) patients are subject to an elevated risk of infection, and may develop latent MDR-TB infection. Numerous studies have described latent tuberculosis infection (LTBI) as a reservoir of new TB disease. The screening and treatment of latent MDR-TB infection are challenging. Hereby, we reviewed the epidemiology, current management and prevention approach of LTBI in MDR-TB close contacts, to provide additional information for future research direction and policy design formulation to reduce the LTBI reservoir.