Table of Content

10 September 2024, Volume 46 Issue 9

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Special Topie

Short-course treatment for tuberculosis: past achievements and future directions

Li Yang, Sun Feng, Zhang Wenhong

Chinese Journal of Antituberculosis. 2024, 46(9):  991-997.  doi:10.19982/j.issn.1000-6621.20240219

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The global decline in tuberculosis (TB) incidence has been disappointingly slow, significantly lagging behind the milestones set by the World Health Organization’s End TB Strategy. Consequently, the development and implementation of effective short-course treatment regimens have become imperative. This review aims to examine the progress of short-course TB treatments over the past few decades and evaluate the efficacy of current therapeutic approaches, providing essential references and support for optimizing future treatment strategies. Through a systematic review of the literature and the latest clinical trial data, we analyzed the efficacy, safety, and application scenarios of various short-course treatment regimens. Furthermore, we summarized the main strategies for current short-course treatments. Despite existing challenges, significant progress in tuberculosis short-course treatment is anticipated in the coming years, driven by the development of novel drugs, dose optimization, and more precise patient evaluation.

Comparative study and suggestions on the return to school policy of students with tuberculosis

Huang Xian, Meng Weiyu, Luo Tao, Zhang Weihua, Li Xinyan, Lai Yanfen, Guo Hongge, Tang Vengkai, Lai Xiaoyu, Li Kefeng, Huang Mingxing

Chinese Journal of Antituberculosis. 2024, 46(9):  998-1005.  doi:10.19982/j.issn.1000-6621.20240149

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Students represent a critical demographic in the prevention and control of tuberculosis, with return-to-school policies after the contraction of active tuberculosis playing an essential role in safeguarding the health and developmental trajectories of adolescents. Notably, policy variations exist internationally, and China experiences relatively prolonged absences from school, potentially affecting students’ academic performance, social interactions, and psychological well-being. Recent advancements in diagnosing and treating tuberculosis in children and adolescents now facilitate more practical adjustments to these policies for cases responsive to treatment. This paper reviews global return-to-school policies, presents a case study from Zhuhai City highlighting decreased infectivity following regulated treatment, and proposes new policy recommendations. These aim to permit earlier school re-entry for affected children and adolescents, thereby laying a groundwork for policy optimization in China.

Interpretation of Standards

Interpretation of the third edition of WHO consolidated guidelines on tuberculosis: module 3: diagnosis: rapid diagnostics for tuberculosis detection

Wang Xiaomin, Chen Jinyun, Zeng Yuqin, Ma Quan, Kong Xingxing, Meng Jianzhou, Lu Shuihua

Chinese Journal of Antituberculosis. 2024, 46(9):  1006-1022.  doi:10.19982/j.issn.1000-6621.20240221

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On 20 March 2024, the World Health Organization (WHO) published the WHO consolidated guidelines on tuberculosis: Module 3: diagnosis: rapid diagnostics for tuberculosis detection. The third edition of the guidelines focuses on three areas: initial diagnostic tests for diagnosis of tuberculosis with drug-resistance detection, initial diagnostic tests for diagnosis of tuberculosis without drug-resistant detection, and follow-on diagnostic tests for detection of additional drug-resistance after tuberculosis confirmation. In addition, this current guidelines include for the first time a chapter on targeted next generation sequencing (tNGS) tests for the diagnosis of drug-resistant tuberculosis in people with diagnosed tuberculosis with or without rifampicin-resistant tuberculosis. The author now introduces the compilation and key points of the third edition of the guidelines in order to promote the implementation and dissemination of these guidelines.

Original Articles

Treatment outcomes and influencing factors in elderly patients with multidrug/rifampicin-resistant pulmonary tuberculosis: a national multicenter, retrospective cohort study

Ye Zhiteng, Ren Fei, Wang Hua, Yang Ming, Chen Yu, Chen Xiaohong, Wang Yun, Fan Lin

Chinese Journal of Antituberculosis. 2024, 46(9):  1023-1029.  doi:10.19982/j.issn.1000-6621.20240215

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Objective: To analyze treatment outcomes and influencing factors of multidrug/rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB) in elderly patients. Methods: A national multicenter retrospective cohort study was conducted to include 475 elderly (≥60 years) MDR/RR-PTB patients who were admitted to six provincial tuberculosis hospitals from January 1, 2018 to December 31, 2020. Clinical characteristics of those patients were recorded and full course treatment was followed up. Multivariable logistic regression model was used to analyze factors affecting treatment outcomes. Results: Successful treatment rate of 475 elderly MDR/RR-PTB patients was 65.89% (313/475), cure rate and treatment completion rate were 50.74% (241/475) and 15.16% (72/475) respectively. Treatment failure rate was 13.05% (62/475), loss of follow-up rate was 17.05% (81/475) and mortality rate was 4.00% (19/475). Multivariable logistic regression analysis showed that 70-79 years old (OR=1.560, 95%CI: 1.001-2.431), ≥80 years old (OR=3.306, 95%CI: 1.370-7.974), lung cavities (OR=1.832, 95%CI: 1.195-2.808) were risk factors affecting MDR/RR-PTB treatment success in elderly patients. Inclusion of Bedaquiline in treatment regimen (OR=0.193, 95%CI: 0.044-0.841) was a protective factor for successful treatment. Conclusion: The treatment of elderly MDR/RR-PTB patients is complicated and difficult for which the successful treatment rate is low. Special attention should be paid to elderly patients aged ≥70 years and those with pulmonary cavities.

Single-cell sequencing reveals differences in natural killer cells between young and elderly patients with severe pulmonary tuberculosis

Tang Mi, Li Yao, Hu Yanmei, Wen Xinmin, Tang Zhigang, Huang Sheng, Zhang Yong, Luo Danlin, Yi Hengzhong

Chinese Journal of Antituberculosis. 2024, 46(9):  1030-1036.  doi:10.19982/j.issn.1000-6621.20240197

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Objective: To investigate the differences in immune cell subsets between young and elderly patients with severe pulmonary tuberculosis, with particular emphasis on the functions and pathways of natural killer (NK) cell subsets. Methods: Single-cell sequencing data and other clinically relevant indicators were obtained by contacting the corresponding authors of publicly available research literature. Data were collected from four patients with severe pulmonary tuberculosis, comprising two young patients (age ≤40 years) and two elderly patients (age ≥65 years). The single-cell RNA sequencing data underwent quality control and statistical analysis. After excluding unqualified cells, the data were subjected to nonlinear dimensionality reduction and clustering. Recognized cellular markers were used to annotate immune cells and determine the percentage of each cell type in each sample and group. This enabled the comparison of cell subtype trends across different groups. Differential gene expression between cell types was analyzed, and the roles of these genes in biological processes and pathways were investigated using enrichment analysis in the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results: A total of 15359 cells from young patients and 9571 cells from elderly patients with severe pulmonary tuberculosis were analyzed, leading to the identification of 11 distinct cell subpopulations. The most prevalent cell types included monocytes (61%), CD4⁺ T cells (17%), CD8⁺ T cells (8%), megakaryocytes (5%), B cells (4%), and NK cells (3%). The analysis revealed that the percentage of NK cells was higher in young patients (median (IQR): 4.339% (3.955%, 4.722%)) compared to elderly patients (median (IQR): 0.822% (0.813%, 0.831%)), although this difference was not statistically significant (Z=-0.431, P=0.667). Statistical analysis using the ratio of observed to expected cell numbers indicated an increasing trend of NK cells in the young group. Further clustering analysis identified three distinct NK cell subgroups. The median percentage of NK cells with high CD16 expression was 44.409% (IQR: 41.672%, 47.147%) in young patients, slightly higher than the 35.172% (IQR: 32.169%, 38.174%) observed in elderly patients; however, this difference was not statistically significant (Z=-0.431, P=0.667). A comparison between NK cells with high CD16 expression and those with moderate expression revealed 435 significantly altered genes, comprising 388 upregulated genes and 47 downregulated genes. KEGG pathway analysis indicated that these differentially expressed genes were predominantly involved in signaling pathways related to cell perception, cytokine signaling, B cell receptor activity, and antigen processing and presentation. Conclusion: This study examined the differences in peripheral blood immune cells between young and elderly patients with severe pulmonary tuberculosis, highlighting an increased percentage of NK cells and CD16⁺ NK cells in young patients. These findings may offer a new theoretical basis and identify potential therapeutic targets for the stratified clinical management of tuberculosis patients.

Diagnostic accuracy of GeneXpert MTB/RIF in detecting pulmonary tuberculosis with extremely low loads of MTB in bronchoalveolar lavage fluid in general hospitals

Mei Chunlin, Yang Chengqing, Du Ronghui, Cao Tanze, Feng Wei, Chen Shufang, Liu Xiuping, Ou Jiali

Chinese Journal of Antituberculosis. 2024, 46(9):  1037-1041.  doi:10.19982/j.issn.1000-6621.20240062

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Objective: To evaluate the accuracy of diagnosing pulmonary tuberculosis (PTB) with extremely low loads of Mycobacterium tuberculosis (MTB) (Ct value >28) in bronchoalveolar lavage fluid by GeneXpert MTB/RIF (BALF-Xpert) in Wuhan general hospitals. Methods: A prospective study was conducted on PTB patients admitted to the Department of Respiratory and Critical Care Medicine of Wuhan Pulmonary Hospital from January 1, 2019 to December 30, 2022, who were referred from 12 general hospitals with extremely low loads of MTB detected by BALF-Xpert. The results of retesting BALF-Xpert, acid-fast bacilli smear microscopy, mycobacterial culture, TB-RNA, and TB-DNA were analyzed. All patients were clinically diagnosed by 3 or more associate professors and followed up for at least 1 year to evaluate the accuracy of BALF-Xpert in detecting MTB with extremely low loads in general hospitals. Results: A total of 67 patients were included. After retesting with BALF-Xpert, 38.81% (26/67) were detected as MTB positive, including 20 cases (76.92%) with extremely low loads, 5 cases (19.23%) with low loads, 1 case (3.85%) with medium loads, and 0 case with high loads of MTB. The positive rate of BALF-Xpert was higher than that of smear microscopy (4.48% (3/67)) and TB-RNA (17.91% (12/67)), with statistically significant difference (χ²=23.280, P=0.001; χ²=7.200, P=0.007). There was no significant difference between BALF-Xpert and culture (29.85% (20/67)) and TB-DNA (25.37% (17/67))(χ²=1.192, P=0.275; χ²=2.774, P=0.096). The total positive rate of combining 5 diagnostic methods was 40.30% (27/67). Forty-three patients were finally diagnosed with tuberculosis and 24 patients were diagnosed as non-tuberculosis disease, with a misdiagnosis rate of 35.82%. Conclusion: BALF-Xpert has a high false positive rate for detection of PTB cases with extremely low loads MTB. A comprehensive diagnosis should be made based on the patient’s clinical manifestations, imaging findings, and immunological results for MTB infection and re-examination is recommended, if necessary.

A machine learning model based on CT images combined with radiomics and semantic features for diagnosis of nontuberculous mycobacterium lung disease and pulmonary tuberculosis

Zhong Lingshan, Wang Li, Zhang Shuo, Li Nan, Yang Qingyuan, Ding Wenlong, Chen Xingzhi, Huang Chencui, Xing Zhiheng

Chinese Journal of Antituberculosis. 2024, 46(9):  1042-1049.  doi:10.19982/j.issn.1000-6621.20240095

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Objective: To explore a machine learning model based on chest CT images for differential diagnosis of nontuberculous mycobacterium lung disease (NTM-LD) and pulmonary tuberculosis (PTB). Methods: Chest CT images of 120 patients (NTM-LD) and 120 patients (PTB) were retrospectively collected in Tianjin Haihe Hospital from January 2017 to December 2020. 168 cases (70%) were randomly selected as the training set, and 72 cases (30%) were selected as the testing set. Chest CT images of 25 patients (NTM-LD) and 25 patients (PTB) from Xi’an Chest Hospital were collected as an external validation set. A total of 12 radiologist semantic features and 2107 radiomic features were extracted from chest CT images, and 40 radiomic features were retained through feature dimensionality reduction. Three distinct machine learning classification models were constructed utilizing the Support Vector Machines (SVM) algorithm. These models encompass a semantic model, a radiomics model, and a hybrid radiomics-semantic model. The diagnostic performance of the three models were evaluated by the receiver operating characteristic (ROC) curve and the area under the curve (AUC). The statistical significance of differences between the three models were compared by DeLong test. Results: In the testing set, the AUC of radiomics-semantic model, radiomics model and semantic model were 0.9853, 0.9282, and 0.7901, respectively. There were statistically significant differences between semantic model and radiomics-semantic model, as well as between semantic model and radiomics model (Z=2.759, P=0.006; Z=2.230,P=0.026). However, there was no statistically significant difference between radiomics-semantic model and radiomics model (Z=0.761, P=0.502).In the external validation set, the AUC of radiomics-semantic model, radiomics model and semantic model were 0.9216, 0.9024 and 0.7624, respectively. There was a statistically significant difference between radiomics-semantic model and semantic model (Z=2.126,P=0.034). However, there was no statistically significant difference between radiomics-semantic model and radiomics model (Z=0.368,P=0.713). Conclusion: Compared with semantic model, the machine learning model combining radiomics and semantic features showed an excellent diagnostic efficiency and great clinical application value in distinguishing NTM-LD and PTB. Although its performance improvement was not significant compared to radiomics model.

Analysis of bacteriological positivity and rifampicin resistance in patients with severe pulmonary tuberculosis

Geng Zimei, Wang Chaohong, Long Sibo, Zheng Maike, Shi Yiheng, Sun Yong, Zhao Yan, Wang Guirong

Chinese Journal of Antituberculosis. 2024, 46(9):  1050-1055.  doi:10.19982/j.issn.1000-6621.20240165

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Objective: To assess the bacteriological positivity rate and rifampicin resistance in sputum samples from patients with severe pulmonary tuberculosis. Methods: A retrospective analysis was conducted on 369 cases of pulmonary tuberculosis admitted to Beijing Chest Hospital, Capital Medical University, between January and December 2023, including 145 severe and 224 non-severe cases. The positive detection rates of Mycobacterium tuberculosis (MTB) in sputum samples were evaluated using acid-fast staining smear microscopy (smear), BACTEC MIGT 960 culture (culture), and Xpert MTB/RIF (Xpert). Rifampicin resistance was also assessed. Results: In severe pulmonary tuberculosis, the positive rates for smear, culture, and Xpert tests, as well as the overall bacteriological positivity rate, were 47.41% (55/116), 68.75% (77/112), 85.82% (115/134), and 80.69% (117/145), respectively. In non-severe cases, these rates were 29.44% (63/214), 53.17% (109/205), 68.35% (149/218), and 71.43% (160/224), respectively. The differences between severe and non-severe cases were statistically significant(χ²=10.580,P=0.001;χ²=7.250,P=0.007;χ²=12.512,P<0.001;χ²=4.034,P=0.045).There was no significant difference in rifampicin resistance rates between patients with severe pulmonary tuberculosis and those with non-severe cases (11.30% (13/115) vs. 8.05% (12/149);χ²=0.800, P=0.371). However, rifampicin resistance rates were higher in previously treated cases compared to new cases among Xpert-positive patients (24.24% (8/33) vs. 6.10% (5/82); χ²=7.727,P=0.005). Conclusion: Patients with severe pulmonary tuberculosis exhibited a higher bacteriological positivity rate; however, there was no significant difference in rifampicin resistance rates between severe and non-severe cases. Rifampicin resistance rates were notably higher in previously treated cases compared to newly diagnosed cases.

Analysis of in vitro antibacterial effects of 17 antibiotics against rapidly growing mycobacteria in the Beijing area

Chen Shuangshuang, Tian Lili, Wang Nenhan, Yang Xinyu, Zhao Yanfeng, Li Chuanyou, Dai Xiaowei

Chinese Journal of Antituberculosis. 2024, 46(9):  1056-1062.  doi:10.19982/j.issn.1000-6621.20240167

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Objective: To analyze the antibacterial effects of 17 antibiotics on clinical isolates of rapidly growing mycobacteria (RGM) in Beijing, and to provide a reliable theoretical basis for the clinical treatment of nontuberculosis mycobacteriosis caused by RGM. Methods: A total of 130 nontuberculous mycobacteria (NTM) strains isolated from the Tuberculosis Laboratory of the Beijing Center for Disease Control and Prevention between January 2016 and December 2020 were collected for strain identification. After reviving the RGM clinical isolates and corresponding standard strains, sensitivity tests were conducted on 17 antibiotics (amikacin, ciprofloxacin, compound sulfamethoxazole, clarithromycin, linezolid, moxifloxacin, doxycycline, minocycline, cefoxitin, tigecycline, tobramycin, imipenem, meropenem, amoxicillin/clavulanic acid, bedaquiline, delamanid, and clofazimine) using the micro broth dilution method. The minimum inhibitory concentration (MIC) and the MIC values required to inhibit 50% (MIC₅₀) or 90% (MIC₉₀) of the tested bacteria were recorded. Results: After strain identification and successful recovery, 37 strains of RGM were identified, including 19 Mycobacterium (M.) abscesses, 17 M.fortuitum, and 1 M.chelonae. Among the 14 antibiotics with established resistance breakpoints, all RGM clinical isolates were found to be sensitive to tigecycline. Clinical isolates of M.chelonae and M.abscessus were sensitive to clarithromycin, and M.abscesses were also sensitive to linezolid. All M.fortuitum clinical isolates were sensitive to amikacin, ciprofloxacin, compound sulfamethoxazole, and moxifloxacin. Additionally, the sensitivity rate of M.abscessus to amikacin was 73.7% (14/19), while the sensitivity rates of M.fortuitum to linezolid and meropenem were 82.4% (14/17) and 88.2% (15/17), respectively. All M.abscessus isolates were resistant to doxycycline, amoxicillin/clavulanic acid, while all M.fortuitum isolates were resistant to tobramycin. Additionally, the MIC₉₀ of bedaquiline and clofazimine for RGM clinical isolates were both lower than the minimum detection limit of the drug sensitivity plate, whereas the MIC₉₀ of delamanid was higher than the maximum detection limit of the drug sensitivity plate. Conclusion: Tigecycline, amikacin, linezolid, betaquiline, and clofazimine all exhibit good in vitro antibacterial activity against RGM, while doxycycline, amoxicillin/clavulanic acid, and delamanid show almost no in vitro antibacterial activity. There is a significant difference in the drug resistance spectrum between NTM species. Therefore, it is recommended to conduct species identification and drug sensitivity testing before treatment to select appropriate antibiotics.

Immunomodulatory effect of orelabrutinib in host macrophages infected with mycobacterium

Wang Yilin, Wu Xiao, Pang Yu, Li Shanshan

Chinese Journal of Antituberculosis. 2024, 46(9):  1063-1068.  doi:10.19982/j.issn.1000-6621.20240240

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Objective: To investigate the immunomodulatory effect of a novel Bruton tyrosine kinase (BTK) inhibitor orelabrutinib, in host macrophages infected with Mycobacterium tuberculosis (MTB). Methods: Human acute monocytic leukemia (THP-1) cells were cultured and differentiated. The differentiated THP-1 cells were infected with Mycobacterium smegmatis (M.smeg) and then treated with different concentrations of orelabrutinib to compare the ability of macrophages to engulf and clear M.smeg. BTK protein expression was knocked down by using siRNA interference technology, and the knockdown effect was verified by Western blotting. The colony-forming unit (CFU) assay was used to measure the clearance ability of macrophages against M.smeg by treated with orelabrutinib. Results: Orelabrutinib significantly inhibited the tyrosine phosphorylation of BTK without changing the level of BTK protein expression. Additionally, the CFU count of M.smeg in macrophages treated with orelabrutinib decreased from 130.0 (120.3-137.5)×10³/ml to 59.0 (55.8-65.3)×10³/ml, with statistical significance (U=0.000, P=0.014). After knocking down BTK protein expression, the bacterial load of M.smeg in macrophages decreased from 52.0 (44.0-61.5)×10³/ml to 25.0 (22.0-28.0)×10³/ml, with statistical significance (U=9.000, P=0.002). Conclusion: BTK plays a crucial role in macrophage functional regulation. As a novel BTK inhibitor, orelabrutinib not only suppresses BTK tyrosine phosphorylation but also significantly enhances the clearance ability of macrophage against M.smeg, providing a new perspective for its potential anti-tuberculosis applications.

Characteristic analysis of non-tuberculous mycobacterial pulmonary disease patients in Wuhan area from 2021 to 2023

Wang Fei, Hua Duo, Guo Jianjian, Liu Chang, Han Lu, Ren Yi

Chinese Journal of Antituberculosis. 2024, 46(9):  1069-1076.  doi:10.19982/j.issn.1000-6621.20240179

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Objective: This study aims to offer critical insights into the prevention and treatment of non-tuberculous mycobacterial pulmonary disease (NTM-PD) by analyzing the isolation rates and drug resistance patterns of respiratory non-tuberculous mycobacteria (NTM) in the Wuhan area, as well as the clinical characteristics of patients diagnosed with NTM-PD. Methods: This retrospective study encompassed 8619 hospitalized patients with suspected mycobacterial pulmonary infections at Wuhan Pulmonary Hospital from March 2021 to October 2023. All participants were aged 15 years or older, and their respiratory samples (including sputum, induced sputum, and bronchiolar lavage fluid) tested positive for mycobacterial etiology (via mycobacterium culture) and were identified as NTM. Comprehensive data on medical history, clinical features, radiological findings, clinical diagnosis, and treatment were collected for all subjects. The isolation rates, demographic characteristics, and drug resistance profiles of NTM strains were analyzed. Patients diagnosed with NTM-PD were categorized into three groups based on the infecting species: M.intracellular (M.intracellular group), M.abscessus (M.abscessus group), and M.kansasii (M.kansasii group). The baseline characteristics, clinical symptoms, radiological features, underlying diseases, and concomitant pulmonary conditions of each group were compared. Results: Among the 8619 subjects, 629 clinical isolates were identified as NTM strains, resulting in an NTM isolation rate of 7.30%. A total of 653 NTM strains were isolated, comprising 398 (60.95%) strains of M.intracellular, 138 (21.13%) strains of M.abscessus, 41 (6.28%) strains of M.avium, and 41 (6.28%) strains of M.kansasii. Among the 510 patients diagnosed with NTM-PD, 297 (58.24%) were female. The primary clinical symptoms included cough (71.96%, 367/510), expectoration (51.76%, 264/510), and hemoptysis (26.67%, 136/510). Key radiological features were patchy infiltrates (61.57%, 314/510), nodules (65.49%, 334/510), bronchiectasis (79.02%, 403/510), and cavities (40.98%, 209/510). The most common underlying conditions were anemia (24.12%, 123/510) and hypoproteinemia (24.90%, 127/510). Pulmonary diseases were predominantly associated with emphysema bullosa (18.63%, 95/510) and chronic obstructive pulmonary disease (17.84%, 91/510). The study categorized NTM-PD patients into three groups: 332 cases in the M.intracellular group, 115 cases in the M.abscessus group, and 35 cases in the M.kansasii group. The proportion of females was 55.12% (183/332) in the M.intracellular group, 75.65% (87/115) in the M.abscessus group, and 17.14% (6/35) in the M.kansasii group, with a statistically significant difference (χ²=39.534, P<0.001). The mean ages were (63.60±10.67) years for the M.intracellular group, (60.60±10.26) years for the M.abscessus group, and (53.30±13.20) years for the M.kansasii group, also showing a statistically significant difference (F=15.724, P<0.001). Significant differences were observed in the proportions of smokers (23.19% (77/332), 12.17% (14/115), 42.86% (15/35); χ²=15.623, P<0.001) and alcohol users (10.54% (35/332), 4.35% (5/115), 22.86% (8/35); χ²=10.079, P=0.006) across the groups. Additionally, the incidence of bronchiectasis (78.31% (260/332), 90.43% (104/115), 54.29% (19/35); χ²=22.345, P<0.001) and cavity formation (42.77% (142/332), 29.57% (34/115), 68.57% (24/35); χ²=17.534, P<0.001) varied significantly among the M.intracellular, M.abscessus, and M.kansasii groups. There were statistically significant differences in the incidence of chronic obstructive pulmonary disease (COPD)(18.67% (62/332), 15.65% (18/115), 37.14% (13/35); χ²=8.222, P=0.016) and pulmonary aspergillosis (6.93% (23/332), 1.74% (2/115), 11.43% (4/35); χ²=7.016, P=0.030) among the M.intracellular, M.abscessus, and M.kansasii groups. The resistance rates of M.avium and M.intracellular to clarithromycin, amikacin, and linezolid were 0, 0, and 23.53% (4/17) for M.avium, and 3.14% (5/159), 6.92% (11/159), and 13.21% (21/159) for M.intracellular, respectively. The resistance rate of M.kansasii to clarithromycin, amikacin, linezolid, moxifloxacin, rifampin, and rifabutin was 0, while the resistance rate to ciprofloxacin was 43.75% (7/16). The resistance rates of M.abscessus to clarithromycin, amikacin, linezolid, and cefoxitin were 7.02% (4/57), 1.75% (1/57), 43.86% (25/57), and 8.77% (5/57), respectively. Conclusion: The predominant NTM strains isolated from the respiratory tracts of hospitalized patients with suspected mycobacterial pulmonary infection in the Wuhan area were M.intracellular, M.abscessus, and M.kansasii. Except for M.kansasii, other NTM strains exhibited higher resistance to common antituberculosis drugs. There were notable differences in sex distribution, radiological features, and associated pulmonary diseases among patients with M.intracellular pulmonary disease, M.abscessus pulmonary disease, and M.kansasii pulmonary disease.

Distribution of Mycobacterium tuberculosis genotypes in Kashgar region and their association with clinical characteristics of pulmonary tuberculosis patients

Palidanguli Abudureheman, Wang Senlu, Gulina Badeerhan, Wang Le, Zulikatiayi Abudula, Wang Xinqi, Maiwulajiang Yimamu, Wang Xijiang

Chinese Journal of Antituberculosis. 2024, 46(9):  1077-1082.  doi:10.19982/j.issn.1000-6621.20240206

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Objective: To investigate the distribution of Mycobacterium tuberculosis (MTB) genotypes in the Kashgar region and to analyze the correlation between these genotypes and the clinical characteristics of pulmonary tuberculosis patients. Methods: MTB strains were collected from tuberculosis-designated hospitals in Kashgar in 2020. The study included 810 tuberculosis patients with complete case information and their corresponding 810 MTB clinical isolates. Case information for the pulmonary tuberculosis patients was retrieved from the “Tuberculosis Management Information System” encompassing the patient’s name, gender, age, occupation, clinical symptoms, imaging findings, treatment history, treatment plan, and treatment outcome. MTB strains were genotyped and their lineages identified using the Illumina HiSeq second-generation sequencing platform. Results: Among the 810 MTB strains, 292 strains (36.0%) belonged to Lineage2, 321 strains (39.6%) belonged to Lineage3, and 197 strains (24.4%) belonged to Lineage4. The distribution of MTB lineages varied across different counties and cities, including Kashgar, Shufu County, and Shule County. Among the 572 effectively measured sublineages, Lineage 2.2.1 accounted for 44.6% (255/572) and Lineage2.2.2 accounted for 6.8% (39/572); the Lineage3.1.3 sublineage accounted for 14.9% (85/572). Lineage4 showed a wide differentiation into sublineages, namely Lineage4.1 to Lineage4.9, with the Lineage4.5 sublineage comprising 29.9% (171/572). There was no significant difference between the strain lineage and the clinical symptoms of the patients. However, compared with other lineages, individuals infected with Lineage3 strains had a lower proportion of sputum smear positivity (27.7%, 89/321) and a higher proportion of clear cure (37.1%, 119/321). These differences were statistically significant (χ² values were 6.192 and 24.558, respectively, with P values <0.05). Conclusion: The distribution of MTB lineages and sublineages in the Kashgar region demonstrates genetic polymorphism. Lineage3 infections are associated with a low sputum smear positivity rate and a high clinical cure rate.

Analysis of influencing factors of treatment outcomes in patients with pulmonary tuberculosis complicated with diabetes mellitus in Xinjiang Uygur Autonomous Region

Huang Tao, Jian Huiyong, Wang Xinqi, Liu Nianqiang, Yipar Aihaiti, Wang Mingzhe, Jiayinati Jingesi, Wang Senlu

Chinese Journal of Antituberculosis. 2024, 46(9):  1083-1088.  doi:10.19982/j.issn.1000-6621.20240124

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Objective: To analyze the characteristics and factors affecting treatment outcomes of pulmonary tuberculosis-diabetes mellitus (PTB-DM) in Xinjiang Uygur Autonomous Region (hereinafter referred to as Xinjiang), to provide scientific basis for tuberculosis prevention and control. Methods: Epidemiological data of reported tuberculosis cases in Xinjiang from January 1, 2021 to December 31, 2022 were obtained through the “Tuberculosis Management Information System”, a subsystem of the “Chinese Disease Prevention and Control Information System”, and a descriptive analysis was conducted. Characteristics of PTB-DM patients and PTB patients without DB registered at the same time were compared. The factors affecting treatment outcomes of PTB-DM patients were analyzed. Results: Among 36729 patients registered in Xinjiang in 2021—2022, 34286 were patients with PTB alone and 2443 were PTB-DM patients. Multivariable logistic regression analysis showed that age ≥65 years (OR=3.826, 95%CI: 1.942-7.536), retreatment (OR=1.809, 95%CI: 1.264-2.588), smear positive (OR=1.620, 95%CI: 1.183-2.218), and sputum smear not turning negative at the end of 2 months’ treatment (OR=1.591, 95%CI: 1.057-2.394) were risk factors for adverse treatment outcomes. Conclusion: For patients with PTB-DM in Xinjiang, risk factors of adverse treatment outcomes included age ≥65 years, retreatment, smear positive, and sputum smear not turning negative at the end of 2 months’ treatment. Thus, we should strengthen follow-up management of PTB-DM patients, improve their treatment compliance, ensure treatment effectiveness, and reduce the occurrence of adverse outcomes.

Investigation and analysis of laboratory diagnostic capabilities in tuberculosis-designated hospitals in China

Wang Biao, Liu Yuhong, Sun Yuxian, Zhang Lijie, Li Zhili, Shu Wei

Chinese Journal of Antituberculosis. 2024, 46(9):  1089-1097.  doi:10.19982/j.issn.1000-6621.20240295

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Objective: To evaluate the diagnostic capabilities and quality control measures in tuberculosis-designated hospitals across China. Methods: This study utilized data from the 2023 ‘Research on the Prevention and Control System and Operation Mechanism of National Tuberculosis Medical Institutions’ conducted by the Clinical Center for Tuberculosis Prevention and Control of China CDC. These data were compared with survey data from 2015 to analyze the status and trends of tuberculosis laboratory testing technologies. Both surveys encompassed 46 units, including general hospitals, infectious disease hospitals, tuberculosis prevention and control institutions, public health centers, and specialized tuberculosis hospitals. Results: Among the 46 designated medical institutions for tuberculosis, 19 (41.3%) were provincial institutions and 27 (58.7%) were municipal institutions. In 2022, the average number of outpatient visits per institution was 16424, including 185 visits for multidrug/rifampicin-resistant tuberculosis. On average, 1460 tuberculosis patients were admitted per institution, including 131 patients with multidrug/rifampicin-resistant tuberculosis. In terms of laboratory testing, these institutions primarily utilized three routine techniques in 2022: smear microscopy, culture, and drug susceptibility testing. From the perspective of different types of institutions, the implementation rates of PCR detection (70.8%, 17/24), gene chip detection (37.5%, 9/24), and molecular strain identification (58.3%, 14/24) in third-grade class-A medical institutions were significantly higher than those in other grade medical institutions (27.3% (6/22), 4.5% (1/22), and 22.7% (5/22), respectively; χ²=8.712, 5.518, and 6.002, P=0.003, 0.019, and 0.014). Additionally, the overall workload of traditional tuberculosis laboratory detection techniques (sputum smear, sputum culture, and traditional drug susceptibility testing; 19825 (11253, 38363), 13266 (4164, 24213), and 1264 (534, 2523) cases) was significantly higher than that in other medical institutions (8072 (2132, 17239), 2292 (1076, 10075), and 323 (101, 1572) cases, respectively; Z=-2.452, -2.702, and -2.225, P=0.014, 0.007 and 0.026). From a regional distribution perspective, the high-resolution melting curve detection rate in the eastern region (35.3%, 6/17) was slightly lower than that in the central region (76.5%, 13/17), with the difference being statistically significant (χ²=6.494, P=0.039). Historically, in 2022, simple and rapid diagnostic techniques such as GeneXpert MTB/RIF detection (93.5%, 43/46) and gene chip detection (21.7%, 10/46) were more widely used compared to 2014 (41.3% (19/46) and 8.7% (4/46), respectively). Furthermore, the diagnostic workload of GeneXpert MTB/RIF increased from 38 (11, 150) cases diagnosed in 2014 to 2485 (856, 8349) cases in 2022 (Z=-3.724, P<0.001), and antibody detection increased from 500 (200, 1010) cases in 2014 to 3401 (1066, 7275) cases in 2022 (Z=-4.235, P<0.001), indicating an upward trend. In terms of laboratory quality control, the oversight of cultivation techniques remained a critical focus area. In 2022, only 76.1% (35/46) of medical institutions participated in inter-laboratory quality control, with the majority being monitored by third-party institutions (74.3%, 26/35). Conclusion: Since 2014, the laboratory detection capabilities of tuberculosis-designated medical institutions in China have improved to varying degrees, particularly in molecular biology detection. Moving forward, while continuing to enhance tuberculosis laboratory detection capabilities, ensuring the quality of laboratory work will be a critical area of focus.

Review Articles

Research progress of artificial intelligence in pulmonary tuberculosis imaging diagnosis and drug resistance prediction

Li Wenhan, Yang Jing, Li Chunhua

Chinese Journal of Antituberculosis. 2024, 46(9):  1098-1103.  doi:10.19982/j.issn.1000-6621.20240123

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Tuberculosis (TB) is the leading cause of death from a single infectious disease worldwide. Early diagnosis of pulmonary tuberculosis (PTB) and identification of drug resistant tuberculosis are of great significance, but non-invasive and precise diagnosis and treatment are still limited. With the development of medical mega data, artificial intelligence (AI) has been gradually applied to PTB research. AI mining high flux characteristics from image, to provide the possibility of non-invasive and reproducible evaluation of lesions. In this paper, the research progress of AI technology in PTB image diagnosis and differential diagnosis, disease monitoring and drug resistance prediction in recent years is reviewed, with a view to promoting the clinical translation of AI diagnosis and drug resistance prediction technology for PTB, and providing support for the realization of precision medicine.

Research progress on the application of 3D printed artificial bone in spinal tuberculosis bone defect grafting

Yang Jun, Deng Qiang, Zhang Yanjun, Guo Tiefeng, Li Junjie, Du Jianqiang, Tian Hongjing, Liu Xinfeng

Chinese Journal of Antituberculosis. 2024, 46(9):  1104-1108.  doi:10.19982/j.issn.1000-6621.20230361

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Spinal tuberculosis bone defect is a common tuberculous infectious lesion in clinical practice. It has the characteristics of being difficult to perform operation on, and having long treatment cycle and many complications. Bone graft materials that could quickly and efficiently promote the repair of bone defects are new materials sought by all clinicians. In recent years, 3D printing technology has been more and more widely used in the medical field, and has shown a good development prospect in the field of bone tissue engineering scaffold preparation. The author reviews researches on the repair of spinal tuberculosis bone defects with 3D printing drug-loaded artificial bone scaffolds, and expounds the optimization strategy and future development direction of 3D printing drug-loaded artificial bone.

Short Articles

Clinical and imaging characterization of fungal spondylitis misdiagnosed as spinal tuberculosis

Li Xiang, Pu Ying, Fu Xuwen, Qi Min, Wei Jialu, Cun Xinhua

Chinese Journal of Antituberculosis. 2024, 46(9):  1109-1114.  doi:10.19982/j.issn.1000-6621.20240064

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Six fungal spondylitis cases initially misdiagnosed as spinal tuberculosis in Kunming Third People’s Hospital from January 2021 to January 2024 were collected, and their clinical data and imaging data were analyzed. It was found that out of the six patients, four cases were male, with a median age of 58 years. Two cases had a history of surgery at the infection site, and one case had combined chronic liver failure. Four cases had positive pus/blood fungal culture or positive pathologic fungal test result; five cases presented pain in the infected spinal segment, and only 1 case presented fever; 2 cases presented elevated peripheral blood leukocyte counts and neutrophil counts, 6 cases had elevated C-reactive protein and erythrocyte sedimentation rate, and 3 cases had positive G test result. Five cases had lumbar spine lesions and 1 case had cervical spine lesions; five cases had single-segment involvement and 1 case had short-segment involvement. Only 3 cases showed bone destruction with X-rays; 6 cases showed lesions in anterior and middle columns of the spine with CT examination, among them, 4 cases had bone destruction centered at the intervertebral discs, and 2 cases centered at the vertebral bodies. In 5 cases, there was no osteosclerotic band around the bone destruction, and MRI showed bone destruction as isotropic T₁WI high T₂WI/T₂WI fat-suppressed signal, while the bone around the bone destruction showed low T₁WI low T₂WI signal/T₂WI fat-suppressed high signal, and in the other one case, there was osteosclerosis around the bone destruction, and MRI showed bone destruction as isotropic T₁WI high T₂WI/T₂WI fat-suppressed signal, while the bone surrounding the bone destruction showed low T₁WI high T₂WI/T₂WI fat-suppressed signal. Six cases all had no compression fracture, posterior convexity deformity, or lumbar masseter abscess on imaging.