BACKGROUND: Indonesia is among countries with a high incidence of multi drug-resistant tuberculosis (MDR-TB) globally. In this study, we aim to determine the prevalence of silico-tuberculosis among TB patients and to investigate the association of radiographic silicosis and the role of drug supervisor as well as other socio-clinical factors, in the development of MDR-TB in Indonesia. METHODS: A hospital-based study in West Java among 148 MDR-TB patients (case) and 164 drug-sensitive/DS-TB patients (control) was conducted. Chest x-rays were evaluated by two radiologists and one NIOSH B reader according to the ILO Classification. Face-to-face interviews were conducted using structured questionnaires to collect patients' information, including the task of drug supervisor. RESULTS: Findings indicate that supportive drug supervisor reduces the risk of developing MDR-TB, but silicosis showed no significant association. Nevertheless, in this study we found that 17 cases (5.4%) had silico-tuberculosis mostly exhibited as ILO profusion 3; predominated by q shape, 52.9% with large opacities and dominated by size A. Other factors significantly associated with the risk of developing MDR-TB were marital status, low income, longer traveling time to hospital, unsuccessful previous treatment and suffering drug side effects. CONCLUSION This study reveals that one of preventive healthcare strategy to protect TB patients from developing MDR-TB is supportive drug supervisor. While, the development of MDR-TB was not significantly influenced by silicosis; however, there is a notable prevalence of silicosis as determined by chest radiography, highlighting the critical need for dust control, occupational hygiene, and health screening for high-risk populations.
Indonesia/epidemiology* ; Humans ; Silicosis/diagnostic imaging* ; Male ; Tuberculosis, Multidrug-Resistant/etiology* ; Middle Aged ; Adult ; Female ; Prevalence ; Risk Factors ; Aged ; Antitubercular Agents/therapeutic use*

OBJECTIVE: We aimed to understand the willingness and barriers to the acceptance of tuberculosis (TB) preventive treatment (TPT) among people with latent TB infection (LTBI) in China. METHODS: A multicenter cross-sectional study was conducted from May 18, 2023 to December 31, 2023 across 10 counties in China. According to a national technical guide, we included healthcare workers, students, teachers, and others occupations aged 15-65 years as our research participants. RESULTS: Overall, 17.0% (183/1,077) of participants accepted TPT. There were statistically significant differences in the acceptance rate of TPT among different sexes, ages, educational levels, and occupations ( P < 0.05). The main barriers to TPT acceptance were misconceptions that it had uncertain effects on prevention (57.8%, 517/894), and concerns about side effects (32.7%, 292/894). CONCLUSION An enhanced and comprehensive understanding of LTBI and TPT among people with LTBI is vital to further expand TPT in China. Moreover, targeted policies need to be developed to address barriers faced by different groups of people.
Humans ; China/epidemiology* ; Adult ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; Young Adult ; Adolescent ; Aged ; Latent Tuberculosis/prevention & control* ; Patient Acceptance of Health Care ; Tuberculosis/prevention & control* ; Antitubercular Agents/therapeutic use* ; Health Knowledge, Attitudes, Practice

Tuberculosis (TB) remains a significant global health challenge, ranking second only to COVID-19 as the leading cause of death from a single infectious agent, with 1.3 million TB-related deaths reported in 2022. Treatment efficacy has been compromised by the emergence of drug-resistant strains, including rifampin-resistant TB (RR-TB), multidrug-resistant TB (MDR-TB), and extensively drug-resistant TB (XDR-TB). Although first-line drugs like isoniazid, rifampicin, pyrazinamide, and ethambutol form the cornerstone of TB therapy, the rise of resistant strains necessitates the use of second-line drugs, which often come with increased toxicity and limited accessibility. Recent advances have focused on repurposing existing compounds and developing new drugs with novel mechanisms of action. Promising agents such as second-generation bedaquiline analogs (TBAJ-587, TBAJ-876), sudapyridine (WX-081), delamanid, pretomanid, and TBI-166 (pyrifazimine) have shown efficacy against resistant Mtb strains. Innovative treatment regimens like the BPaLM protocol-combining bedaquiline, pretomanid, linezolid, and moxifloxacin-offer shorter, all-oral therapies with higher cure rates. Personalized treatment durations and dose optimizations are becoming feasible through risk stratification algorithms and pharmacokinetic/pharmacodynamic studies. Immunotherapy is emerging as a complementary strategy to enhance the host's immune response against Mtb. Agents such as vitamin D, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), statins, metformin, and biological agents like interleukins and granulocyte-macrophage colony-stimulating factor are under exploration. Additionally, cell therapies involving mesenchymal stem cells and immune effector cells present new therapeutic avenues. Despite these advancements, significant challenges remain in achieving the World Health Organization's "End TB Strategy" goals, particularly as the COVID-19 pandemic has diverted resources and attention. Ongoing research and global collaboration are crucial to develop novel therapeutic strategies, optimize treatment regimens, and ultimately reduce the global burden of TB.
Humans ; Antitubercular Agents/therapeutic use* ; COVID-19/epidemiology* ; Tuberculosis/epidemiology*

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 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*

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*

Humans ; Mycobacterium tuberculosis/genetics* ; Microspheres ; Antitubercular Agents/pharmacology* ; Mutation ; Microbial Sensitivity Tests ; Fluoroquinolones ; Drug Resistance, Bacterial/genetics* ; Tuberculosis, Multidrug-Resistant/microbiology*

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*

Humans ; Isoniazid/pharmacology* ; Mycobacterium tuberculosis/genetics* ; Rifampin/pharmacology* ; Antitubercular Agents/pharmacology* ; Mutation ; Microbial Sensitivity Tests ; Tuberculosis, Multidrug-Resistant/microbiology* ; Drug Resistance, Multiple, Bacterial/genetics* ; Bacterial Proteins/genetics*