Table of Content

10 May 2025, Volume 47 Issue 5

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Guideline·Standard·Consensus

Expert consensus on the standardization of broth microdilution method for drug susceptibility testing of Mycobacterium tuberculosis in China

Tuberculosis Basic Professional Branch, Chinese Antituberculosis Association

Chinese Journal of Antituberculosis. 2025, 47(5):  535-545.  doi:10.19982/j.issn.1000-6621.20250070

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Drug resistant tuberculosis has long been a serious challenge in the field of global public health. At present, it is difficult to provide accurate and effective treatment plans for patients based solely on binary phenotypic drug sensitivity and genotypic drug sensitivity tests. The microbroth dilution drug sensitivity test based on the microplate not only covers a variety of drugs and multiple concentrations at one time, but also provides quantitative drug resistance information for the clinic, so it is receiving more and more attention. In order to use the microbroth dilution drug sensitivity test in a reasonable, scientific, and standardized manner, the Tuberculosis Basic Professional Branch of Chinese Antituberculosis Association had organized experts in relevant fields to formulate this consensus on technical characteristics, application value, standardized operation, result interpretation, and precautions in actual operation of this drug sensitivity method, and proposed 12 recommendations, aiming to provide unified guiding principles for clinical and laboratory staff who are related to tuberculosis.

Expert consensus on the diagnosis and treatment of urological tuberculosis

Senior Department of Tuberculosis, the 8th Medical Center of Chinese PLA General Hospital, Editorial Board of Chinese Journal of Antituberculosis, Basic and Clinical Speciality Committees of Tuberculosis Control Branch of China International Exchange and Promotive Association for Medical and Health Care

Chinese Journal of Antituberculosis. 2025, 47(5):  546-558.  doi:10.19982/j.issn.1000-6621.20250058

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Urological tuberculosis has an insidious onset and lacks specificity in clinical manifestations, which often leads to delayed diagnosis, resulting in decline in renal function or even end-stage renal failure. Treatment of urological tuberculosis includes systemic anti-tuberculosis drug therapy combined with local therapy, surgical intervention, and integrated traditional Chinese and Western medicine, etc. The selection of appropriate treatment methods is essential to maximize the preservation of renal function and improve the prognosis of the patients. At present, there is a lack of relevant and reasonable guiding documents for the diagnosis and treatment program of urological tuberculosis in China. To standardize the diagnosis and treatment of urological tuberculosis and improve the level of clinicians so that the patients can be cured early and damage to renal function can be reduced, Senior Department of Tuberculosis, the Eighth Medical Center of the Chinese People’s Liberation Army General Hospital, the Editorial Board of Chinese Journal of Antituberculosis, and Basic and Clinical Specialty Committees of Tuberculosis Control Branch of China International Exchange and Promotive Association for Medical and Health Care jointly organized experts to formulate the “Expert consensus on the diagnosis and treatment of urological tuberculosis”, based on the experience and methods of diagnosis and treatment of urological tuberculosis in China, as well as the relevant research achievements in diagnosis and treatment abroad. This consensus integrates China’s diagnostic and therapeutic experience and methods with international research achievements in the diagnosis and treatment of urological tuberculosis. This consensus outlines the epidemiological characteristics, pathophysiological process, main clinical manifestations, and common examination methods of urological tuberculosis, puts forward the diagnostic criteria and differential diagnosis, and gives specific treatment suggestions on the program and indications for systemic anti-tuberculosis drug therapy, local treatment, and surgical intervention of this disease. It aims to provide clinicians with a scientific and practical reference for accurate diagnosis and rational treatment of the patients with urological tuberculosis.

Special Topic

Study on the status, problems and countermeasures of tuberculosis control service system in China

Liu Qiao, Li Zhongqi, Zhu Limei, Lu Wei

Chinese Journal of Antituberculosis. 2025, 47(5):  559-568.  doi:10.19982/j.issn.1000-6621.20240544

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Tuberculosis control service system is the main body of implementing tuberculosis control program. Since the 21st century, China has been trying to establish a “Trinity” tuberculosis prevention and control mode in which designated tuberculosis hospitals are mainly responsible for tuberculosis diagnosis and treatment, Centers for Disease Control and Prevention for planning, managing and evaluating the prevention and control work, and primary medical and health institutions for following-up and managing tuberculosis patients during their treatment process. Currently, the construction of the “Trinity” tuberculosis prevention and control service system in China has achieved good results. However, there are still some problems remained, such as insufficient government leadership, insufficient system capacity building, lack of funding, and poor interdepartmental coordination. This study aims to analyse current operation situation of the tuberculosis prevention and control service system in China, identify problems and put forward suggestions, so as to further optimize the tuberculosis prevention and control service system and improve the quality of tuberculosis prevention and control work in China.

Original Articles

Construction of a biosafety management indicator system for tuberculosis clinical testing laboratories

Liu Fangchao, Zhang Di, Mi Fengling, Li Zihui, Huang Hairong, Pan Liping, Shi Guangli, Jiang Guanglu, Pan Junhua

Chinese Journal of Antituberculosis. 2025, 47(5):  569-576.  doi:10.19982/j.issn.1000-6621.20240521

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Objective: To construct a biosafety management indicator system for clinical testing laboratories dealing with tuberculosis. Methods: Based on the research team’s previous experience in laboratory biosafety management and inspection supervision, a literature review was conducted to collect domestic laboratory biosafety standards, including “WS 233—2017 General Guidelines for Biosafety in Pathogen Microorganism Laboratories”,“CNAS—CL05—2009 Laboratory Biosafety Accreditation Criteria”, and “GB 19489—2008 General Requirements for Laboratory Biosafety”. After internal discussions within the research team, a preliminary pool of candidate biosafety management indicators was developed, and a framework for the system was constructed. Two rounds of external expert consultations were conducted based on this framework, with experts determining inclusion/exclusion of each indicator and evaluating their importance rate. Analytic Hierarchy Process (AHP) was used to calculate weight coefficients of each indicator, ultimately forming a three-level evaluation indicator system for biosafety management in tuberculosis clinical testing laboratories. Results: A total of 15 and 14 expert consultation forms were collected in the first and second round, with response rates of 100.0% and 93.3%, respectively. The first round mainly focused on revising the structure of the indicator system, while the second round involved rating importance of indicators. The authority coefficient of experts in the second round was 0.76, indicating high reliability. The coordination coefficients of indicators at all levels in both rounds were greater than 0.1, and the Kendall’s W consistency test showed that, except for the first-level indicators, all P-values were less than 0.05, indicating good consistency among expert opinions. A practical and operational three-level biosafety management indicator system for tuberculosis clinical testing laboratories was finalized, comprising 5 first-level indicators, 13 second-level indicators, and 44 third-level indicators. Conclusion: A biosafety management indicator system for tuberculosis clinical testing laboratories has been constructed based on scientific theory. It can be used to evaluate the biosafety management level of tuberculosis clinical testing laboratories and guide laboratories to improve management efficiency through regular self-inspections. It also provides a scientific basis for healthcare institution managers to develop management systems and policies.

Evaluation of the diagnostic performance of the MiniDock MTB Test for rapid tuberculosis detection

Wu Zhuhua, Wang Yong, Lai Xiaoyu, Ji Liwei, Chen Ruiming, LYU Chunfang, Xu Liuyue, Guo Huixin, Chen Yuhui, Liang Hongdi, Liu Shengyuan, Zhong Xinguang, Chen Xunxun

Chinese Journal of Antituberculosis. 2025, 47(5):  577-581.  doi:10.19982/j.issn.1000-6621.20250022

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Objective: To assess the diagnostic performance of the MiniDock MTB Test (hereafter referred to as “MiniDock”) for the rapid detection of tuberculosis (TB). Methods: A prospective study was conducted at three clinical sites in Guangdong Province—Dongguan Sixth People’s Hospital, Shantou Institute of Tuberculosis Prevention and Control, and Shenzhen Nanshan Center for Chronic Disease Control. Between May and August 2024, consecutive patients with suspected pulmonary TB who met the inclusion criteria were enrolled. Relevant clinical data were collected. Sputum specimens were subjected to Ziehl-Neelsen smear microscopy, solid culture on L?wenstein-Jensen medium, GeneXpert MTB/RIF (Xpert), and MiniDock testing, all performed by trained laboratory personnel. Results: A total of 213 patients with suspected pulmonary TB were enrolled. The positivity rates for smear microscopy, solid culture on L?wenstein-Jensen medium, Xpert, and MiniDock were 22.07% (47/213), 36.62% (78/213), 32.86% (70/213), and 36.62% (78/213), respectively. When clinical diagnosis was used as the reference standard, MiniDock achieved a sensitivity of 47.24% (77/163) and specificity of 98.00% (49/50), while Xpert showed a sensitivity of 42.94% (70/163) and specificity of 100.00% (50/50). Using culture as the reference, MiniDock yielded a sensitivity of 84.62% (66/78) and specificity of 91.11% (123/135), whereas Xpert demonstrated a sensitivity of 78.21% (61/78) and specificity of 93.33% (126/135). Agreement analysis between the two methods indicated a high level of concordance, with a Kappa coefficient of 0.88. Conclusion: The MiniDock MTB Test demonstrated robust diagnostic performance, with high sensitivity and specificity for TB detection, and showed strong concordance with the results of the Xpert assay.

The value of nanopore-targeted sequencing technology in the diagnosis of granulomatous diseases in formalin-fixed paraffin-embedded tissues

Sun Xiaoke, Wei Jinxing, Zhang Chunyan, Liang Ruixia, Shi Huimin, Ruan Xianglin, Duan Hongfei

Chinese Journal of Antituberculosis. 2025, 47(5):  582-588.  doi:10.19982/j.issn.1000-6621.20240466

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Objective: To evaluate the detection ability of nanopore-targeted sequencing (NTS) on granulomatous diseases in formalin-fixed paraffin-embedded (FFPE) tissues. Methods: According to inclusion criteria, clinical data of 82 patients admitted to Henan Provincial Chest Hospital from January to June 2023 who underwent lobectomy, lymph node dissection, and bone and joint surgical treatment due to therapeutic needs, and whose post-operative tissues were tested with traditional pathological tests which suggested granulomatous inflammation were collected (including the results of traditional pathological tests, etc.). NTS was applied on FFPE specimen from post-operative lesion tissue to compare its diagnostic value with traditional pathological methods on detecting granulomatous diseases, taking final clinical diagnosis as reference. Results: Of the 82 patients, histopathological test reported 73 cases (89.0%) of suspected tuberculosis, 4 cases (4.9%) of tuberculosis combined with aspergillosis, 3 cases (3.7%) of cryptococcosis, and 2 cases (2.4%) of granulomatous inflammation. The NTS detected 31 cases (37.8%) of Mycobacterium tuberculosis (MTB), 14 cases (17.1%) of Fungi, 9 cases (11.0%) of non-tuberculous mycobacterial (NTM), 5 cases (6.1%) of Nocardia, 2 cases (2.4%) of Brucella, 2 cases (2.4%) of MTB combined with Aspergillus niger, 16 cases (19.5%) of undetectable pathogens, and 1 case (1.2%) each of MTB combined with Pneumocystis carinii, Aspergillus polysporus, and M.avium. The final clinical diagnosis were 43 cases (52.4%) of tuberculosis, 13 cases (15.9%) of fungal disease, 9 cases (11.0%) of NTM disease, 5 cases (6.1%) of each nocardiosis and tuberculosis in combination with fungal disease, 2 cases (2.4%) of brucellosis, 1 case (1.2%) of tuberculosis in combination with NTM disease, and 4 patients (4.9%) with an unspecified diagnosis. With reference to the final clinical diagnosis, the sensitivities of pathological diagnosis and NTS for the detection of granulomatous inflammation were 60.3% (47/78) and 83.3% (65/78), with a Kappa value of 0.129 and 0.328, respectively; and the sensitivity of combing these two methods was 97.4% (76/78), with a Kappa value of 0.788; the specificities of three methods were all 4/4. Conclusion: NTS could detect granulomatous inflammation to strain level, with combination with traditional histopathological test, it can significantly improve the efficacy of diagnosing etiology of infectious diseases, thus could be recommended as a complementary method to traditional histopathological test.

Diagnostic value of Nanopore targeted sequencing for detecting nontuberculous mycobacteria in respiratory specimens

Ying Guangzhi, Cai Qingshan, Ma Xiaoqing, Chen Lingyan, Chen Yuanyuan

Chinese Journal of Antituberculosis. 2025, 47(5):  589-596.  doi:10.19982/j.issn.1000-6621.20250007

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Objective: To investigate the diagnostic value of Nanopore targeted sequencing for detecting non-tuberculous mycobacteria (NTM) in respiratory samples. Methods: Data from 455 patients who underwent Nanopore targeted sequencing of respiratory samples from December 2021 to September 2022 at the Tuberculosis Treatment Center of Hangzhou Red Cross Hospital in Zhejiang Province was retrospectively collected. According to diagnostic criteria, these 455 patients were finally diagnosed as NTM-PD patients (NTM-PD group; 65 patients) and non-NTM-PD patients (non-NTM-PD group; 390 patients), their alveolar lavage fluid or sputum were subjected to simultaneous Nanopore targeted sequencing, BACTEC MGIT 960 liquid cultures (liquid culture) and/or PCR fluorescent probes to compare their efficacy in diagnosing NTM-PD. Results: Using clinical diagnostic results as standard, the sensitivities of Nanopore targeted sequencing, liquid culture, and PCR fluorescent probe for detecting NTM in respiratory samples were 92.3% (60/65), 83.1% (54/65), and 57.1% (36/63), respectively; the specificities were 96.2% (375/390), 98.7% (385/390), and 99.5% (380/382), respectively; and the positive predictive values were 80.0% (60/75), 91.5% (54/59), and 94.7% (36/38); negative predictive values were 98.7% (375/380), 97.2% (385/396), and 93.4% (380/407); Kappa values were 0.831, 0.851 and 0.679, respectively. Using liquid culture as standard, the sensitivities of Nanopore targeted sequencing, and PCR fluorescent probe were 86.4% (51/59), and 73.5% (36/49), respectively; the specificities were 98.0% (388/396) and 94.4% (374/396), respectively; the positive predictive values were 86.4% (51/59) and 62.1% (36/58), respectively; and the negative predictive values were 98.0% (388/396) and 96.6% (374/387), respectively; Kappa values were 0.844 and 0.629, respectively. Among the 65 cases clinically diagnosed as NTM-PD, 50 samples got positive results for both Nanopore targeted sequencing and liquid culture+gene chip, and their strain identification consistency was 96.0% (48/50). Conclusion: Nanopore targeted sequencing demonstrated high sensitivity and specificity in diagnosing NTM-PD and showed strong concordance with conventional identification methods. In terms of strain identification, this method also exhibited high agreement with results obtained from liquid culture combined with gene chips. Consequently, Nanopore targeted sequencing is well-suited for rapid detection of clinical respiratory samples from patients suspected of having NTM-PD, and it can simultaneously provide strain identification results for informing subsequent development of anti-NTM therapeutic regimen.

High-throughput screening and identification of compounds with anti-Mycobacterium kansasii activity

Hu Qianfang, Zhong Rujie, Shang Yuanyuan, Zhang Xuxia, Li Shanshan, Wang Wei

Chinese Journal of Antituberculosis. 2025, 47(5):  597-604.  doi:10.19982/j.issn.1000-6621.20240518

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Objective: To establish a high-throughput screening (HTS) platform for compounds actively against Mycobacterium kansasii and identify novel candidates. Methods: A 96-well plate-based HTS system was developed to screen a G protein-coupled receptor (GPCR) compound library for candidates with anti-M.kansasii activity. Selected candidates were evaluated for antibacterial activity against clinical strains, time-kill kinetics, biofilm inhibition, and cytotoxicity. Data were statistically analyzed using t-tests and analysis of variance (ANOVA) at P<0.05. Results: Seventeen candidate compounds with anti-M.kansasii activity were identified. Promethazine hydrochloride and vorapaxar exhibited best performance against the M.kansasii standard strain (ATCC 12478), with minimum inhibitory concentrations (MIC) of 1.6 μg/ml and 1.23 μg/ml, respectively, and both of them showed a MIC of 2 μg/ml against rifampin-resistant clinical isolates. Time-kill curve experiments and Biofilm inhibition assays demonstrated their anti-ATCC 12478 activity and anti-biofilm effect were both concentration-dependent. Promethazine hydrochloride exhibited an inhibitory effect only at 8 μg/ml (A₄₅₀=3.027 vs. 1.984, t=4.183, P=0.014), whereas vorapaxar showed significant inhibitory effects at both 4 μg/ml (A₄₅₀=3.027 vs. 1.959, t=4.342, P=0.012) and 8 μg/ml (A₄₅₀=3.027 vs. 2.024, t=4.493, P=0.019), with all differences being statistically significant. There was no statistically significant difference in cell viability compared to the control group after cell being cultured with Promethazine hydrochloride for 24 hours. Vorapaxar caused a slight reduction in cell viability only at a concentration of 20 μmol/L compared with control group (survival rate=84.97% vs. 99.97%, t=3.098, P=0.021). Conclusion: A high-throughput screening platform for compounds with anti-M.kansasii activity was successfully established, and both promethazine hydrochloride and vorapaxar exhibited significant anti-M.kansasii activity as well as concentration-dependent antibiofilm activity, providing potential candidate compounds for the development of new anti-M.kansasii drugs.

The performance of Mycobacterium tuberculosis-specific antigens-induced cytokines in the diagnosis of tuberculosis among HIV-infected individuals

Yao Mingxu, Wang Zeqi, Song Ruixue, Jia Hongyan, Sun Qi, Zhang Lanyue, Du Boping, Zhang Zongde, Wang Wen, Wu Liang, Pan Liping

Chinese Journal of Antituberculosis. 2025, 47(5):  605-612.  doi:10.19982/j.issn.1000-6621.20250039

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Objective: To evaluate the clinical value of Mycobacterium tuberculosis (MTB)-specific antigens-induced cytokines in the diagnosis of tuberculosis in HIV-infected individuals. Methods: A total of 132 HIV-infected individuals who visited Beijing Ditan Hospital and Beijing You’an Hospital from December 2021 to June 2024 were prospectively included as study subjects. Twelve milliliters of peripheral blood were collected from each patient, and the interferon-γ release assays were performed on peripheral blood. The whole blood with or without MTB-specific antigens stimulation was collected and the total RNA was extracted automatically, and then the expression levels of cytokines (interleukin-2 (IL-2), IL-5, IL-18, IL-24, monocyte chemoattractant protein-1 (MCP-1), MCP-2, MCP-3, chemokine CXC ligand 9 (CXCL9), chemokine CXC ligand 10 (CXCL10), CC motif chemokine ligand 19 (CCL19), macrophage colony-stimulating factor (CSF-1), and interferon-γ (IFNG)) were tested by SYBG-qPCR. The differences in the expression level of cytokines were analyzed between the TB group and the non-TB group, and the performance of cytokines in differentiating TB was investigated by receiver operating curve (ROC) analysis. Lasso analysis was also performed to evaluate the combined performance of the cytokines in identifying TB patients among HIV-infected individuals. Results: According to the clinical diagnosis information of the subjects, 35 cases with unknown diagnosis were excluded, and 97 cases were finally included in the analysis, including 44 cases of TB patients and 53 cases of non-TB patients. The ΔΔCt values (median (quartile)) of MTB-antigen specific IL-18 and IFNG in the TB group were 0.5601 (-0.0207, 1.2880) and 1.0130 (0.0284, 3.9950), respectively, which were significantly higher than those in the non-TB group (0.0364 (-0.6420, 0.7438) and 0.3727 (-0.5992, 1.2460), respectively), with statistically significant differences (Z values were -2.284 and -1.989, P values were 0.018 and 0.028). The ΔΔCt values (median (quartile)) of MCP-1, MCP-2, CXCL9, and CXCL10 in the TB group were -1.1660 (-1.8920, -0.5699), -1.4640 (-3.5530, 0.5763), -1.7680 (-6.3950, -0.2807), -1.8260 (-4.6000, -0.0814), respectively, which were significantly lower than those in the non-TB group (-0.5803 (-1.0040, 0.1794), -0.2367 (-1.3010, 0.7079), 0.2730 (-1.2750, 1.8360), -0.2505 (-0.6528, 0.9105)), with statistically significant differences (Z values were 3.162, 2.529, 3.745, 3.743, respectively; P values were 0.003, 0.014, 0.001, and <0.001). ROC analysis showed that the area under the curve for IL-18, MCP-1, MCP-2, CXCL9, CXCL10, and IFNG ranged from 0.632 to 0.724. Based on Lasso analysis, the area under the curve for the combined detection of IL18, MCP-2, and CXCL10 was 0.797, which was higher than any single indicator. Conclusion: The combination of IL18, MCP-2, and CXCL10 can assist in identifying TB cases among HIV-infected individuals.

Development and application of an HPLC-MS/MS method for simultaneous determination of bedaquiline, pretomanid, and linezolid in plasma

Cheng Wen, Zhu Hui, Fu Lei, Zhang Weiyan, Zhang Liqun, Lu Yu

Chinese Journal of Antituberculosis. 2025, 47(5):  613-622.  doi:10.19982/j.issn.1000-6621.20250004

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Objective: To establish a high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method for simultaneous determination of the plasma concentrations of bedaquiline (Bdq), pretomanid (Pa), and linezolid (Lzd), providing a method for monitoring clinical therapeutic drugs. Methods: Plasma samples were precipitated using acetonitrile, meanwhile, propranolol (PR) was added as an internal standard, followed by centrifugation to obtain the supernatant. Using a gradient elution method for HPLC-MS/MS analysis of Bdq, Pa, and Lzd concentrations in the supernatant with mobile phases A (0.1% formic acid and 5 mM ammonium formate in water) and B (acetonitrile). Chromatographic separation conditions were determined based on peak shape and resolution with a column temperature of 35 ℃, flow rate of 0.4 ml/min, and analysis time of 4 min. Mass spectrometry detection was performed using an electrospray ionization source (ESI) in positive ion mode with multiple reaction monitoring (MRM). The established HPLC-MS/MS method was validated through specificity, standard curve establishment and limit of quantification determination, precision and accuracy, recovery and matrix effect, and stability studies. Finally, the method was applied and validated using experimental mice. Results: MRM mode scanning of plasma samples showed that the declustering voltages for Bdq, Pa, Lzd, and PR were 80, 91, 80, and 100 V, respectively, and the collision energies were 80, 32, 28, and 30 V, respectively, with parent ion/product ion pairs of 555.2/58.2, 360.2/175.2, 338.1/296.3, and 260.2/116.2, respectively. Methodological validation results showed that the retention times for Bdq, Pa, and Lzd were 1.93, 1.79, and 1.53 min, respectively, with good peak shapes and no interfering peaks signals at the elution positions; the linear correlation coefficients R² were 0.993, 0.999, and 0.999, respectively, with good linear relationships in the concentration ranges of 0.05-12.5, 0.1-25, and 0.2-50 μg/ml, respectively; the intra-day and inter-day accuracies for the three drugs were above 90% and the precision fluctuations were less than 15%; the extraction recoveries of three drugs and the internal standard PR at different concentrations ranged from 78.45% to 108.78%. The method has the following characteristics: little affected by plasma processing methods. Matrix effects above 90%, meeting the ±15% requirement and stability errors under different storage conditions were within ±15%; the method successfully detected plasma concentrations of Bdq, Pa, and Lzd in 36 mouse plasma samples, with ranges of 0.03-1.82, 0.11-14.21, and 0.02-16.54 μg/ml, respectively. Conclusion: The established HPLC-MS/MS method can stably and rapidly detect the drug concentrations of Bdq, Pa, and Lzd in plasma samples simultaneously. Methodological validation showed that the method is stable, accurate, and sensitive. This method can serve as a reference for clinical application.

A preliminary study on the role of miRNA-451a in the pathogenesis of disseminated tuberculosis

Zhao Lingjuan, Liu Haoran, Nie Wenjuan, Wang Wei

Chinese Journal of Antituberculosis. 2025, 47(5):  623-628.  doi:10.19982/j.issn.1000-6621.20240524

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Objective: Preliminary exploration of miRNA-451a’s involvement in the pathogenesis of hematogenous disseminated pulmonary tuberculosis. Methods: (1) A prospective research method was adopted, from December 2018 to December 2019, 56 patients with secondary pulmonary tuberculosis and 24 patients with hematogenous disseminated pulmonary tuberculosis (HDPTB) treated at Beijing Chest Hospital were consecutively included as the case group, 17 healthy controls were selected from those who passed the physical examination in our hospital. Venous blood samples were collected along with sociodemographic and clinical data from all subjects. The expression levels of miRNA-451a and its target gene, macrophage migration inhibitory factor (MIF), in peripheral blood, were analyzed by real-time PCR (qRT-PCR). (2) Human acute monocytic leukemia cells (THP-1) were cultured and differentiated, and the miRNA-451a overexpression cell model was constructed by cell transfection technology, the cells were infected with H37Rv, qRT-PCR verified the gene expression level, and the protein expression level of was verified by Western blotting. The clearance ability of macrophages against H37Rv was determined by colony forming unit (CFU) assay. Results: (1) The relative expression levels of miRNA-451a in the secondary pulmonary tuberculosis patients, HDPTB patients, and healthy controls were 24.177 (5.150, 46.066), 81.742 (29.003, 117.388), and 77.762 (54.422, 134.633) respectively, with statistically significant differences (H=19.040, P<0.001); the relative expression levels of MIF were 0.306 (0.168, 0.795), 0.189 (0.073, 0.443), and 0.025 (0.012, 0.085) respectively, with statistically significant differences (H=35.967, P<0.001). (2) The relative expression level of MIF in the miRNA-451a overexpressed THP-1 cell model (0.442±0.019) was lower than that in the negative control group (1.477±0.190), with statistically significant differences (t=-9.384, P<0.001); 24 hours after H37Rv infection, the total intracellular bacterial survival rate in the miRNA-451a overexpression cell group (42.55%, 40/94) was higher than that in the negative control group (7.24%, 21/290) with statistically significant differences (χ²=66.247, P<0.001). Conclusion: miRNA-451a is involved in the pathogenesis of HDPTB by regulating the expression of MIF and then affecting the survival of bacteria in macrophages.

Study on the association between single nucleotide polymorphisms in TMEM173,IFNGR1,IFNGR2, and IRF8 genes and susceptibility to tuberculosis

Huang Huimin, Wang Lei, Cheng Liping, Sun Qin, Wang Wenjuan, Yang Hua

Chinese Journal of Antituberculosis. 2025, 47(5):  629-638.  doi:10.19982/j.issn.1000-6621.20240592

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Objective: To investigate the association between genetic polymorphisms in the stimulator of interferon genes (TMEM173), interferon gamma receptor 1 (IFNGR1), interferon gamma receptor 2 (IFNGR2), and interferon regulatory factor 8 (IRF8) and tuberculosis susceptibility. Methods: A case-control study was conducted, including 286 pulmonary tuberculosis cases (Observation group) admitted to Shanghai Pulmonary Hospital from January 2020 to December 2022 and 484 healthy individuals (Control group). Peripheral venous blood was collected from both groups for genomic DNA extraction, genetic analysis and single nucleotide polymorphism (SNP) screening. Genotyping was performed using the SNPscan^TM multiplex SNP genotyping assay. Logistic regression and Chi-square tests were used to compare differences in allele, genotype, and haplotype frequencies between the observation and control groups. Associations between SNPs and tuberculosis susceptibility were analyzed under dominant, recessive, and over-dominant genetic models. Multivariate logistic regression was performed to analyze the association between the interaction among SNPs and tuberculosis susceptibility. Results: All SNP allele frequency distributions conformed to Hardy-Weinberg equilibrium. Carriers of the rs8064189 T allele (OR=1.290, 95%CI: 1.047-1.590, P=0.017), TT genotype (OR=1.689, 95%CI: 1.098-2.597, P=0.017), GT-TT genotype (OR_dominant=1.231, 95%CI: 0.999-1.517, P=0.047) and rs805252 (OR=1.628, 95%CI: 1.033-2.565, P=0.035;OR_recessive=1.306, 95%CI: 1.037-1.645, P=0.037), as well as the CTGAA haploid type (OR=1.271, 95%CI: 1.078-1.513, P=0.011) of IRF8 gene significantly increased the tuberculosis risk. Rs9808753 AG genotype (OR=1.450, 95%CI: 1.038-2.025, P=0.029) and AA-GG genotype (OR_{hyper-dominance}=0.807, 95%CI: 0.671-0.970, P=0.025) of IFNGR2 gene also significantly increased the risk of tuberculosis. The IFNGR1 TTGG haplotype (OR=1.160, 95%CI: 1.014-1.350, P=0.047) was linked to increased tuberculosis susceptibility. Multivariate logistic regression revealed that the CT genotype in TMEM173 gene rs7380824 increased the tuberculosis risk by 1.431-fold. (OR=1.431, 95%CI: 1.034-1.979, P=0.031). No significant associations were observed between tuberculosis susceptibility and other SNPs. Conclusion: TMEM173, IFNGR1, IFNGR2, and IRF8 genes may serve as susceptibility genes for tuberculosis in the Chinese population.

Spatio-temporal analysis and risk assessment of multidrug-resistant tuberculosis in Guangdong Province, 2014—2019

Hu Yijun, Xu Yiting, Jian Ronghua, Wu Huizhong, Su Jing, Xiao Jianpeng, Jiang Chenqi, Liu Tao, Wang Jiawen, Chen Liang

Chinese Journal of Antituberculosis. 2025, 47(5):  639-646.  doi:10.19982/j.issn.1000-6621.20240560

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Objective: To analyze the spatial and temporal distribution characteristics of multidrug resistant tuberculosis (MDR-TB) in Guangdong Province from 2014 to 2019, identify high-risk areas for MDR-TB and explore its influencing factors, so as to provide scientific basis and technical support for health department and governmental agencies. Methods: Basic data of MDR-TB patients registered in Guangdong Province from 2014 to 2019 was collected using the “Tuberculosis Information Management System”, a subsystem of the “China Information System for Disease Control and Prevention”. Related social and meteorological factors were collected and local weighted regression and spatial autocorrelation analysis were used to explore the spatial and temporal distribution of the incidence of MDR-TB; a two-stage zero-inflated Poisson model (ZIP) was established to analyze influencing factors associated with the incidence of MDR-TB. Results: During the period of 2014—2019, a total of 3358 MDR-TB patients were registered in Guangdong Province, with an average annual registered incidence rate of 0.47/100000 (3358/720530000); temporally the registered MDR-TB cases in Guangdong Province showed a statistically significant trend of increasing ( {\chi }_{\mathrm{t}\mathrm{r}\mathrm{e}\mathrm{n}\mathrm{d}}^2=158.980, P<0.001), with a registered incidence rate of 0.20/100000 in 2014 (233/114890000) increased to 0.53/100000 (667/124890000) in 2019, and the onset of the disease was mostly concentrated in the fall and winter seasons. Spatially, higher mean SIR were identified in Shenzhen, Dongguan, and Guangzhou (2.36, 2.36, and 1.74, respectively). The ZIP model showed that the risk of MDR-TB incidence was positively associated with relative humidity (RR=1.168, 95%CI: 1.031-1.323), sex ratio (RR=1.312, 95%CI: 1.192-1.473), and proportion of floating population (RR=1.176, 95%CI: 1.094-1.263), and was negatively associated with nighttime light index (RR=0.752, 95%CI: 0.668-0.848) and medical beds per 1000 population (RR=0.672, 95%CI: 0.589-0.776). Conclusion: MDR-TB morbidity has temporal and spatial distribution differences and is significantly associated with socio-economic and meteorological factors. Public health interventions, TB control strategies and resource allocation should be implemented in high-risk areas and high-risk populations accordingly in the future.

Short-term effect analysis of intervention measures to strengthen patient registration management in tuberculosis designated medical institutions at provincial and municipal levels in Sichuan Province

Li Ting, Xia Lan, Liu Shuang, Wang Danxia, Lu Jia, Yu Yifan, Cheng Qianqian

Chinese Journal of Antituberculosis. 2025, 47(5):  647-652.  doi:10.19982/j.issn.1000-6621.20240496

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Objective: To analyze the implementation of the intervention measures to strengthen the registration and management of patients in tuberculosis designated medical institutions at the provincial and municipal levels that Sichuan Province has explored since 2022, as well as the changes in the level of detection and treatment management of tuberculosis patients before and after the implementation in Sichuan Province, so as to provide reference for further optimization of prevention and control strategies. Methods: Data on the registration and reporting of ordinary pulmonary tuberculosis cases in Sichuan Province between July 1, 2022, and December 31, 2023, were extracted from the Chinese Information System for Disease Control and Prevention. Descriptive analyses were conducted to assess patient registration coverage and treatment outcomes at both provincial and municipal designated medical institutions. A comparative analysis was performed between pre-intervention (2019) and post-intervention (2023) periods to evaluate changes in registration-to-reporting ratios, bacteriological positivity rates, and treatment success rates, thereby assessing the short-term impact of the intervention. Results: Between July 2022 and December 2023, a total of 5688 ordinary pulmonary tuberculosis cases were registered at the three provincial-level designated medical institutions, representing 50.27% of the 11315 reported cases during the same period. By 2023, 18 of the 21 municipal-level designated institutions (85.71%) had begun registering cases diagnosed outside their administrative jurisdictions, collectively reporting 6222 cases—accounting for 29.40% of the 21161 total reported cases that year. The registration-to-reporting ratio was significantly higher in city-owned hospitals (33.78%, 5892/17442) than in province-owned hospitals (8.87%, 330/3719), and similarly higher in institutions located in ethnic minority regions (37.63%, 1429/3797) compared to non-ethnic regions (27.60%, 4793/17364), with all differences being statistically significant (χ²=916.128 and 151.057; all Ps<0.001). The treatment success rate among patients registered at provincial-level designated institutions was 85.84% (1721/2005). Following the implementation of the intervention in 2023, the provincial registration-to-reporting ratio increased from 88.05% (44324/50337) in 2019 to 96.38% (43794/45393), while the bacteriological positivity rate rose markedly from 40.27% (17107/42482) to 71.05% (29854/42021). Both improvements were statistically significant (χ²=2247.317 and 8104.576, respectively; all Ps<0.001). By contrast, the overall treatment success rate remained stable, increasing slightly from 94.33% (42390/45516) before implementation to 95.49% (35495/38027) after, with no statistically significant difference (χ²=1.440, P=0.230). Conclusion: The implementation of tuberculosis registration measures at provincial and municipal designated medical institutions has substantially mitigated the risk of undetected and unmanaged cases, contributing positively to patient identification and treatment oversight in Sichuan Province. Nonetheless, suboptimal registration coverage persists, underscoring the need for enhanced and more standardized follow-up management systems.

Causality between coronavirus disease 2019 and tuberculosis in Europeans: a two-sample Mendelian randomization study

Wang Lei, Chen Chidao, Su Lianzheng, Li Lingwei, Wang Xinmiao, Wang Peng, Huang Zhonghao

Chinese Journal of Antituberculosis. 2025, 47(5):  653-659.  doi:10.19982/j.issn.1000-6621.20240474

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Objective: To investigate the causality between coronavirus disease 2019 (COVID-19) and tuberculosis (TB) using Mendelian randomization analysis. Methods: Summary data on COVID-19 was extracted from the Integrative Epidemiology Unit (IEU) Open Genome-Wide Association Studies (GWAS) pool (https://gwas.mrcieu.ac.uk/). GWAS data on TB was also retrieved from the UK Biobank database (https://www.ukbiobank.ac.uk/). The relationship between COVID-19 and TB was examined using five methods, the major method being inverse variance weighting (IVW), while additional methods included weighted median, MR-Egger regression, simple mode and weighted mode (626151 cases of COVID-19, including 3886 cases and 622265 controls; 462933 cases of TB, including 2277 cases and 460656 controls). Cochran’s Q statistic, MR-Egger regression analysis, and the “leave-one-out-method” analysis were used to evaluate heterogeneity and sensitivity, and finally inverse Mendelian randomization was done. Results: Fourteen independent single nucleotide polymorphisms (SNPs) associated with COVID-19 were selected as instrumental variables from GWAS (SNP IDs: rs1064213, rs10875713, rs113488799, rs11634857, rs13050728, rs1566837, rs2269899, rs2277732, rs2597569, rs2781267, rs28815269, rs4782434, rs622568, and rs787642). IVW showed no significant correlation between COVID-19 and TB (IVW odds ratio=1.001, 95% confidence interval=0.995-1.002, P=0.527). MR-Egger regression showed that horizontal pleiotropy was unlikely to influence the results (intercept=0.0002435, P=0.101), neither IVW nor MR-Egger regression revealed heterogeneity (Q=13.205, P=0.432; Q=10.040, P=0.612). The “leave-one-out-method” analysis revealed that Mendelian randomization overall estimates were reliable, with no significant bias, and the funnel plot did not exhibit asymmetry. Reverse MR analysis also confirmed the absence of a causality between COVID-19 and TB risk (P (IVW)=0.805). Conclusion: Bidirectional MR analysis based on genetic data of European population revealed no significant bidirectional relationship between COVID-19 and TB in this population.

Review Articles

Research progress of nanomaterials in the treatment of tuberculosis

Yang Tingyu, Sarina , Wang Furong, Chen Chen, Zheng Lanbing

Chinese Journal of Antituberculosis. 2025, 47(5):  660-665.  doi:10.19982/j.issn.1000-6621.20240548

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At present, tuberculosis (TB) treatment still faces serious challenges. Traditional drug therapy has brought various issues, such as long treatment time, poor patient compliance, and low bioavailability. Especially, the emergence of drug-resistance seriously affects the effectiveness of treatment. However, the emergence of nanomaterials can overcome current problems in the treatment of TB, change treatment approaches, and thus improve treatment effect. Based on this, this article reviews the latest research progress of nanomaterials in the treatment of TB, classifies and discusses the functions of nanomaterials in the treatment process, briefly describes the nanomaterials used for direct treatment, focuses on nanomaterials used for drug delivery, and discusses the latest phototherapy nanomaterials. Finally, a summary and outlook are provided on the challenges faced by nanomaterials and their future development.

Research progress on CRISPR/Cas molecular diagnosis of drug-resistant Mycobacterium tuberculosis

Wang Yuanning, Du Zongmin

Chinese Journal of Antituberculosis. 2025, 47(5):  666-672.  doi:10.19982/j.issn.1000-6621.20240523

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Tuberculosis (TB) remains a significant global public health challenge. China is a high-burden country of TB and also a country with high burden of multidrug-resistant and rifampin-resistant TB. The development of rapid and sensitive methods for detecting the drug resistance of Mycobacterium tuberculosis is of great significance for the control and treatment of TB. Clustered regularly interspaced short palindromic repeats (CRISPR) as a component bacterial adaptive immunity can efficiently and specifically recognize and cleave exogenous nucleic acid targets. Meanwhile, some CRISPR-associated proteins (Cas) have trans-cleavage activity, paving the way for novel applications in CRISPR/Cas-based diagnostics for TB drug resistance. Therefore, this review summarizes the latest advancements in CRISPR/Cas technologies for detection Mycobacterium tuberculosis and its drug resistance, and discusses the future trends in this field.