BACKGROUND: Evidence on the combined effects of air pollutants and greenspace exposure on pulmonary tuberculosis (PTB) treatment is limited, particularly in developing countries with high levels of air pollution. OBJECTIVE: We aimed to examine the individual and combined effects of long-term exposure to air pollutants on PTB treatment outcomes while also investigating the potential modifying effect of greenspace. METHODS: This population-based study included 82,784 PTB cases notified in Zhejiang Province, China, from 2015 to 2019. The 24-month average concentrations of particulate matter with an aerodynamic diameter ≤2.5 µm (PM_2.5), ozone (O₃), nitrogen dioxide (NO₂), and sulfur dioxide (SO₂) before PTB diagnosis were estimated using a dataset derived from satellite-based machine learning models and monitoring stations. Greenspace exposure was assessed using the annual China Land Cover Dataset. We conducted analyses using time-varying Cox proportional hazards models and cumulative risk indices. RESULTS: In individual effect models, each 10 µg/m³ increase in PM_2.5, NO₂, O₃, and SO₂ concentrations was associated with hazard ratios for PTB treatment success of 0.95 (95% confidence interval (CI): 0.93-0.97), 0.92 (95% CI: 0.91-0.94), 0.98 (95% CI: 0.97-0.99), and 1.52 (95% CI: 1.49-1.56), respectively. In combined effect models, long-term exposure to the combination of air pollutants was negatively associated with PTB treatment success, with a joint hazard ratio (JHR) of 0.79 (95% CI: 0.63-0.96). Among the pollutants examined, O₃ contributed the most to the increased risks, followed by PM_2.5 and NO₂. Additionally, areas with moderate levels of greenspace showed a reduced risk (JHR = 0.81, 95% CI: 0.62-0.98) compared with the estimate from the third quantile model (JHR = 0.68, 95% CI: 0.52-0.83). CONCLUSIONS Combined air pollutants significantly impede successful PTB treatment outcomes, with O₃ and PM_2.5 accounting for nearly 75% of this detrimental effect. Moderate levels of greenspace can mitigate the adverse effects associated with combined air pollutants, leading to improved treatment success for patients with PTB.
Humans ; China/epidemiology* ; Air Pollutants/analysis* ; Tuberculosis, Pulmonary/drug therapy* ; Particulate Matter/adverse effects* ; Male ; Female ; Middle Aged ; Environmental Exposure/analysis* ; Ozone/adverse effects* ; Adult ; Sulfur Dioxide/adverse effects* ; Treatment Outcome ; Air Pollution/adverse effects* ; Aged ; Nitrogen Dioxide/adverse effects* ; Young Adult ; Adolescent

Objective: To evaluate the clinical value of the MeltPro MTB assays in the diagnosis of drug-resistant tuberculosis. Methods: A cross-sectional study design was used to retrospectively collect all 4 551 patients with confirmed tuberculosis between January 2018 and December 2019 at Beijing Chest Hospital, Capital Medical University. Phenotypic drug sensitivity test and GeneXpert MTB/RIF (hereafter referred to as "Xpert") assay were used as gold standards to analyze the accuracy of the probe melting curve method. The clinical value of this technique was also evaluated as a complementary method to conventional assays of drug resistance to increase the detective rate of drug-resistant tuberculosis. Results: By taking the phenotypic drug susceptibility test as the gold standard, the sensitivity of the MeltPro MTB assays to detect resistance to rifampicin, isoniazid, ethambutol and fluoroquinolone was 14/15, 95.7%(22/23), 2/4 and 8/9,respectively; and the specificity was 92.0%(115/125), 93.2%(109/117), 90.4%(123/136) and 93.9%(123/131),respectively; the overall concordance rate was 92.1%(95%CI:89.6%-94.1%),and the Kappa value of the consistency test was 0.63(95%CI:0.55-0.72).By taking the Xpert test results as the reference, the sensitivity of this technology to the detection of rifampicin resistance was 93.6%(44/47), the specificity was100%(310/310), the concordance rate was 99.2%(95%CI:97.6%-99.7%), and the Kappa value of the consistency test was 0.96(95%CI:0.93-0.99). The MeltPro MTB assays had been used in 4 551 confirmed patients; the proportion of patients who obtained effective drug resistance results increased from 83.3% to 87.8%(P<0.01); and detection rate of rifampicin, isoniazid, ethambutol, fluoroquinolone resistance, multidrug and pre-extensive drug resistance cases were increased by 3.2%, 14.7%, 22.2%, 13.7%, 11.2% and 12.5%, respectively. Conclusion: The MeltPro MTB assays show satisfactory accuracy in the diagnosis of drug-resistant tuberculosis. This molecular pathological test is an effective complementary method in improving test positivity of drug-resistant tuberculosis.
Humans ; Rifampin/therapeutic use* ; Antibiotics, Antitubercular/therapeutic use* ; Mycobacterium tuberculosis ; Ethambutol/pharmacology* ; Isoniazid/pharmacology* ; Paraffin Embedding ; Retrospective Studies ; Cross-Sectional Studies ; Drug Resistance, Bacterial ; Sensitivity and Specificity ; Tuberculosis, Multidrug-Resistant/drug therapy*

OBJECTIVE: This study aims to estimate the cost-effectiveness of the combined chemotherapy regimen containing Bedaquiline (BR) and the conventional treatment regimen (CR, not containing Bedaquiline) for the treatment of adults with multidrug-resistant tuberculosis (MDR-TB) in China. METHODS: A combination of a decision tree and a Markov model was developed to estimate the cost and effects of MDR patients in BR and CR within ten years. The model parameter data were synthesized from the literature, the national TB surveillance information system, and consultation with experts. The incremental cost-effectiveness ratio (ICER) of BR vs. CR was determined. RESULTS: BR ( vs. CR) had a higher sputum culture conversion rate and cure rate and prevented many premature deaths (decreased by 12.8%), thereby obtaining more quality-adjusted life years (QALYs) (increased by 2.31 years). The per capita cost in BR was as high as 138,000 yuan, roughly double that of CR. The ICER for BR was 33,700 yuan/QALY, which was lower than China's 1× per capita Gross Domestic Product (GDP) in 2020 (72,400 yuan). CONCLUSION BR is shown to be cost effective. When the unit price of Bedaquiline reaches or falls below 57.21 yuan per unit, BR is expected to be the dominant strategy in China over CR.
Adult ; Humans ; Antitubercular Agents/therapeutic use* ; Cost-Effectiveness Analysis ; Cost-Benefit Analysis ; Tuberculosis, Multidrug-Resistant/drug therapy* ; China/epidemiology*

Objective: To explore the influencing factors of the adverse outcome of pulmonary tuberculosis (PTB) among adolescents in Hangzhou City between 2005 and 2020. Methods: A retrospective cohort study was used to collect the information of adolescent PTB patients with the onset of PTB occurring from January 1, 2005 to December 31 in 12 designated tuberculosis hospitals in Hangzhou, mainly including demographic, epidemiological, clinical manifestations, bacteriological characteristics and other data, through the China Management Information System for Infectious Disease Surveillance and Reporting and the follow-up survey. All patients were followed up and the end time was December 31, 2021. Multivariate Cox regression model was used to analyze the factors affecting the adverse outcome of these patients. Results: The mean age of 4 921 adolescent PTB patients was (18.9±3.6) years old, and the number of male and female patients were 3 074 and 1 847 respectively. The adverse outcome accounted for 14.7% (725) of all patients. Multivariate Cox regression model showed that eight risk factors, including management model from patients themselves or family members (HR=5.87, 95%CI: 4.55-7.64), molecular biology examination positive for PTB (HR=4.62, 95%CI: 2.98-7.19), the number of sputum smears-positive≥1 (HR=3.72, 95%CI: 2.87-4.83), non-standardized therapy regimens of PTB (HR=3.69, 95%CI: 2.95-4.64), history of retreated PTB (HR=2.22, 95%CI: 1.46-3.36), migrant adolescents (HR=1.89, 95%CI: 1.54-2.34), the number of chest X-ray scan (HR=1.83, 95%CI: 1.65-2.04), and severe PTB (HR=1.38, 95%CI: 1.02-2.05), were associated with the adverse outcome of adolescent PTB patients. Age (HR=0.94, 95%CI: 0.92-0.96), as the only protective factor, was associated with the adverse outcome of these patients. Conclusion: The management mode, molecular biological examination, chemotherapy program, history of tuberculosis, sputum smear examination, severity of tuberculosis, household residence, chest X-ray examination and age are associated with the adverse outcomes of adolescent PTB patients in Hangzhou.
Humans ; Male ; Adolescent ; Female ; Young Adult ; Adult ; Retrospective Studies ; Tuberculosis, Pulmonary/drug therapy* ; Risk Factors ; Proportional Hazards Models ; Sputum ; Mycobacterium tuberculosis

Tuberculosis (TB) prophylactic therapy for latent infection, which can reduce the risk for the development of active TB, is an important measure in TB control. China recommends prophylactic therapy for latent tuberculosis infection (LTBI) in some key populations to reduce the risk for TB. Contacts of patients with multi-drug and rifampicin-resistant TB (MDR/RR-TB) are at high risk for the infection with drug-resistant pathogen, however, no unified prophylactic therapy regimen has been recommended for LTBI due to exposure to MDR/RR-TB patients. This paper summarizes the current MDR/RR-TB prophylactic therapy regimen and its protection effect based on the results of the retrieval of literature, guidelines, expert consensus and technical specifications to provide reference for the prevention and control of LTBI.
Humans ; Rifampin/therapeutic use* ; Tuberculosis, Multidrug-Resistant/prevention & control* ; Tuberculosis/drug therapy* ; Latent Tuberculosis/chemically induced* ; China ; Antitubercular Agents/therapeutic use*

Tuberculosis (TB) is an ancient infectious disease. Before the availability of effective drug therapy, it had high morbidity and mortality. In the past 100 years, the discovery of revolutionary anti-TB drugs such as streptomycin, isoniazid, pyrazinamide, ethambutol and rifampicin, along with drug combination treatment, has greatly improved TB control globally. As anti-TB drugs were widely used, multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis emerged due to acquired genetic mutations, and this now presents a major problem for effective treatment. Genes associated with drug resistance have been identified, including katG mutations in isoniazid resistance, rpoB mutations in rifampin resistance, pncA mutations in pyrazinamide resistance, and gyrA mutations in quinolone resistance. The major mechanisms of drug resistance include loss of enzyme activity in prodrug activation, drug target alteration, overexpression of drug target, and overexpression of the efflux pump. During the disease process, Mycobacterium tuberculosis may reside in different microenvironments where it is expose to acidic pH, low oxygen, reactive oxygen species and anti-TB drugs, which can facilitate the development of non-replicating persisters and promote bacterial survival. The mechanisms of persister formation may include toxin-antitoxin (TA) modules, DNA protection and repair, protein degradation such as trans-translation, efflux, and altered metabolism. In recent years, the use of new anti-TB drugs, repurposed drugs, and their drug combinations has greatly improved treatment outcomes in patients with both drug-susceptible TB and MDR/XDR-TB. The importance of developing more effective drugs targeting persisters of Mycobacterium tuberculosis is emphasized. In addition, host-directed therapeutics using both conventional drugs and herbal medicines for more effective TB treatment should also be explored. In this article, we review historical aspects of the research on anti-TB drugs and discuss the current understanding and treatments of drug resistant and persistent tuberculosis to inform future therapeutic development.
Humans ; Pyrazinamide/therapeutic use* ; Isoniazid/therapeutic use* ; Antitubercular Agents/therapeutic use* ; Tuberculosis, Multidrug-Resistant/microbiology* ; Mycobacterium tuberculosis/genetics* ; Tuberculosis/drug therapy* ; Rifampin/therapeutic use* ; Mutation ; Drug Resistance, Multiple, Bacterial/genetics*

One fourth of the global population has been infected with Mycobacterium tuberculosis, and about 5%-10% of the infected individuals with latent tuberculosis infection (LTBI) will convert to active tuberculosis (ATB). Correct diagnosis and treatment of LTBI are important in ending the tuberculosis epidemic. Current methods for diagnosing LTBI, such as tuberculin skin test (TST) and interferon-γ release assay (IGRA), have limitations. Some novel biomarkers, such as transcriptome derived host genes in peripheral blood cells, will help to distinguish LTBI from ATB. More emphasis should be placed on surveillance in high-risk groups, including patients with HIV infection, those using biological agents, organ transplant recipients and those in close contact with ATB patients. For those with LTBI, treatment should be based on the risk of progression to ATB and the potential benefit. Prophylactic LTBI regimens include isoniazid monotherapy for 6 or 9 months, rifampicin monotherapy for 4 months, weekly rifapentine plus isoniazid for 3 months (3HP regimen) and daily rifampicin plus isoniazid for 3 months (3HR regimen). The success of the one month rifapentine plus isoniazid daily regimen (1HP regimen) suggests the feasibility of an ultra-short treatment strategy although its efficacy needs further assessment. Prophylactic treatment of LTBI in close contact with MDR-TB patients is another challenge, and the regimens include new anti-tuberculosis drugs such as bedaquiline, delamanid, fluoroquinolone and their combinations, which should be carefully evaluated. This article summarizes the current status of diagnosis and treatment of LTBI and its future development direction.
Humans ; Rifampin/therapeutic use* ; Isoniazid/therapeutic use* ; Latent Tuberculosis/drug therapy* ; HIV Infections/epidemiology* ; Antitubercular Agents/therapeutic use*

Objective: To compare the characteristics of children's pulmonary tuberculosis (PTB) cases reported from 2019 to 2021 before and during the implementation of the Action Plan to Stop Tuberculosis. Methods: Based on the reported incidence data and population data of child pulmonary tuberculosis (PTB) notified to the Chinese Center for Disease Control and Prevention (CDC) Tuberculosis Information Management System (TBIMS) from 2019 to 2021, the population information and clinically relevant information in different years were compared. Results: From 2019 to 2021, the reported cases of PTB in children were 363, 664 and 655, respectively. The number of reported cases increased significantly. The median age of the cases in children increased from 10.4 years in 2019 to 11.7 years in 2021 (P=0.005) over a three-year period. The etiological positive rate increased significantly from 11.6% (42/363) in 2019 to 32.2% (211/655) in 2021 (P<0.001). The positive rate of molecular testing increased most significantly, which became the main means of etiological detection and accounted for 16.7% (7/42), 62.0% (57/92) and 75.4% (159/211) of the children with positive etiological results, respectively. The resistance rates of isoniazid and rifampicin were analyzed in children with PTB who underwent drug sensitivity tests. The results showed that the resistance rates of isoniazid and/or rifampicin were 2/9, 3.9% (2/51) and 6.7% (11/163), respectively, with an average of 6.7% (15/223) over three years. The median patients' delay was 27 (12, 49) days in 2019. It was reduced to 19 (10, 37) days in 2020 and 15 (7, 34) days in 2021, both significantly lower than 2019 (P=0.009 and 0.000 2, respectively). Conclusion: From 2019 to 2021, the reported numbers of children with PTB and children with positive etiological results increase significantly in Liangshan Prefecture, while the diagnosis delay of patients significantly reduces.
Humans ; Child ; Rifampin/therapeutic use* ; Isoniazid/therapeutic use* ; Tuberculosis, Pulmonary/drug therapy* ; Tuberculosis ; China/epidemiology*

Objective: To compare the characteristics of children's pulmonary tuberculosis (PTB) cases reported from 2019 to 2021 before and during the implementation of the Action Plan to Stop Tuberculosis. Methods: Based on the reported incidence data and population data of child pulmonary tuberculosis (PTB) notified to the Chinese Center for Disease Control and Prevention (CDC) Tuberculosis Information Management System (TBIMS) from 2019 to 2021, the population information and clinically relevant information in different years were compared. Results: From 2019 to 2021, the reported cases of PTB in children were 363, 664 and 655, respectively. The number of reported cases increased significantly. The median age of the cases in children increased from 10.4 years in 2019 to 11.7 years in 2021 (P=0.005) over a three-year period. The etiological positive rate increased significantly from 11.6% (42/363) in 2019 to 32.2% (211/655) in 2021 (P<0.001). The positive rate of molecular testing increased most significantly, which became the main means of etiological detection and accounted for 16.7% (7/42), 62.0% (57/92) and 75.4% (159/211) of the children with positive etiological results, respectively. The resistance rates of isoniazid and rifampicin were analyzed in children with PTB who underwent drug sensitivity tests. The results showed that the resistance rates of isoniazid and/or rifampicin were 2/9, 3.9% (2/51) and 6.7% (11/163), respectively, with an average of 6.7% (15/223) over three years. The median patients' delay was 27 (12, 49) days in 2019. It was reduced to 19 (10, 37) days in 2020 and 15 (7, 34) days in 2021, both significantly lower than 2019 (P=0.009 and 0.000 2, respectively). Conclusion: From 2019 to 2021, the reported numbers of children with PTB and children with positive etiological results increase significantly in Liangshan Prefecture, while the diagnosis delay of patients significantly reduces.
Humans ; Child ; Rifampin/therapeutic use* ; Isoniazid/therapeutic use* ; Tuberculosis, Pulmonary/drug therapy* ; Tuberculosis ; China/epidemiology*

BACKGROUND: Concerns exist regarding the potential development of tuberculosis in patients with rheumatoid arthritis (RA) treated with biological and targeted drugs. We assessed systematically whether biological therapy increased the risk of tuberculosis in patients with RA by meta-analysis of randomized controlled trials (RCTs). METHODS: A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, and China Biology Medicine disc for RCTs evaluating biological therapy in patients with RA from inception through August 2021. Traditional meta-analysis and network meta-analysis were performed to compare the risk of tuberculosis for each biologics class in patients with RA. Peto odds ratio (Peto OR) and its 95% confidence interval (CI) were calculated as the primary effect measure. RESULTS: In total, 39 studies with 20,354 patients were included in this meta-analysis, and 82 patients developed tuberculosis. The risk of tuberculosis was increased in patients treated with biologics compared with non-biologics (Peto OR: 3.86, 95% CI: 2.36-6.32, P < 0.001). Also, tumor necrosis factor-α (TNF-α) inhibitors had a higher probability of developing tuberculosis than placebo (Peto OR: 3.98, 95% CI: 2.30-6.88, P < 0.001). However, network meta-analysis demonstrated that there was no significant difference in the risk of tuberculosis for each biologics class in patients with RA. Noticeably, tuberculosis was significantly more common in patients treated with a high dose compared with patients receiving a low dose of tofacitinib (Peto OR: 7.39, 95% CI: 2.00-27.31, P = 0.003). CONCLUSION This meta-analysis demonstrates the evidence of an elevated risk of tuberculosis in patients with RA treated with TNF-α inhibitors, and a dose-dependent elevated risk of tuberculosis in patients treated with tofacitinib.
Antirheumatic Agents/adverse effects* ; Arthritis, Rheumatoid/drug therapy* ; Humans ; Network Meta-Analysis ; Pharmaceutical Preparations ; Randomized Controlled Trials as Topic ; Tuberculosis/drug therapy*