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    10 July 2022, Volume 44 Issue 7
    Interpretation of Standards
    Interpretation of the Optimized broth microdilution plate methodology for drug susceptibility testing of Mycobacterium tuberculosis complex issued by World Health Organization
    XIA Hui, ZHENG Yang, SONG Yuan-yuan
    Chinese Journal of Antituberculosis. 2022, 44(7):  641-645.  doi:10.19982/j.issn.1000-6621.20220187
    Abstract ( 681 )   HTML ( 32 )   PDF (1100KB) ( 549 )   Save
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    The previous guidelines on the application and operational procedure of phenotypic drug susceptibility testing issued by World Health Organization (WHO) are all relevant to the modified L-J medium-based proportion drug susceptibility test (DST), liquid medium DST, and Middle 7H10/7H11 DST; however, the microdilution plate method has never been described in detail. Because of the advantages of the microplate method for DST, and based on the previous research results and application, the WHO first released the Optimized broth microdilution plate methodology for drug susceptibility testing of Mycobacterium tuberculosis complex in April 2022. Here we interprets the background of the document, advantages of microplate DST, drug layout design, issues to be considered in methodology, and implications for relevant work in China, so as to provide the reference for relevant scientific research, medical staffs and manufacturers in China.

    Original Articles
    A preliminary study on the synergy and mechanism of pyrifazimine and bedaquiline
    LIU Hai-ting, LI Dong-shuo, ZHANG Lei, WANG Ning, WANG Bin, DING Yang-ming, YAO Rong, LU Yu
    Chinese Journal of Antituberculosis. 2022, 44(7):  646-653.  doi:10.19982/j.issn.1000-6621.20220007
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    Objective: To evaluate the interaction between pyrifazimine (TBI-166) and bedaquiline (Bdq), moxifloxacin (Mfx), delamanid (Dlm), SQ109 and PBTZ169 on clinical isolates of Mycobacterium tuberculosis (MTB), and primarily explore the synergistic mechanism of TBI-166 and Bdq, so as to provide basis for TBI-166 combination therapy.Methods: MTB standard strain H37Rv (ATCC 27294), two drug-sensitive MTB clinical isolates (strain numbers: 30031 and 30091), and one clinical isolate of pre-extensively drug-resistant Mycobacterium tuberculosis (strain number: 13385) were selected. Checkerboard method was used to determine the interaction between TBI-166 and Bdq, Mfx, Dlm, SQ109, and PBTZ169 on MTB clinical isolates clinical isolates. Time sterilization curve method was used to evaluate the antibacterial activity of the synergistic of the two drug combinations. Bacterial reactive oxygen species (ROS) detection kit and adenosine triphosphate (ATP) detection kit were used to determine the ROS and ATP levels in H37Rv standard strain 24 hours after being treated with different concentrations of TBI-166 and Bdq.Results: After combining with Bdq, the minimum inhibitory concentration (MIC) of TBI-166 on MTB clinical isolates No. 30031, 30091 and 13385 were 0.08, 0.05 and 0.08 μg/ml, respectively, all of which decreased to 1/2 of the MIC values of TBI-166 alone. The fractional inhibitory concentration index (FICI) values of the two-drug combination of TBI-166 and Bdq on strains No. 30031, 30091 and 13385 were 1.00, 0.75 and 1.00, respectively. The time sterilization experiment showed that compared with TBI-166 alone, after being treated with TBI-166 and Bdq for 14 days, the viable bacteria of strains No. 30031, 30091 and 13385 decreased by 1.59log10 CFU/ml, 1.27log10 CFU/ml and 1.70log10 CFU/ml, respectively. Compared with the 0.3 μg/ml Bdq group, the ATP content of H37Rv standard strain 24 h after being treated with 0.4 μg/ml TBI-166 in combination with 0.3 μg/ml Bdq had a significant decrease (relative light unit value, 115160.67±19129.79 vs. 208599.20±24078.74; F=75.109, P=0.013), while the ROS content increased significantly (the fluorescence value, 21014.33±1189.19 vs. 13715.00±907.93; F=115.403, P<0.001).Conclusion: The combination of TBI-166 and Bdq had synergistic bactericidal activity, and the mechanism of synergistic bacteria might be related to the augmenting accumulation of ROS and the block of ATP synthesis.
    Clinical value of ESAT-6, immune and inflammatory indexes in the diagnosis of anti-tuberculosis drug-induced liver injury
    LU Ni-hong, SHEN Ling-jun, LIU Hong-lu, CHEN Yang-jun, YANG Yan, DU Ying-rong
    Chinese Journal of Antituberculosis. 2022, 44(7):  654-659.  doi:10.19982/j.issn.1000-6621.20220091
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    Objective: To analyze the diagnostic value of related immune and inflammatory indexes in anti-tuberculosis drug-induced liver injury.Methods: A total of 325 patients with pulmonary tuberculosis treated in the Third People’s Hospital of Kunming from January 2019 to January 2021 (including 115 patients with anti-tuberculosis drug-induced liver injury (group A) and 210 patients without liver injury (group B)) and 98 healthy outpatients in the same period (group C) were selected as subjects. Multivariate logistic regression model was used to analyze the factors related to anti-tuberculosis drug-induced liver injury in three groups: immune cells, inflammatory markers, early secretory target antigen-6 (ESAT-6), matrix metalloprotein-9 (MMP-9) and matrix metalloprotein-14 (MMP-14).Results: The age of patients in group A (51.2 (18.9, 77.2) years) was higher than that in group B (39.1 (19.7, 63.3) years) and group C (36.3 (20.1, 61.3) years), the difference was statistically significant (H=27.695,29.982; Ps=0.000). The CD4+ T lymphocyte count in group A patients (295.0 (155.0, 449.0) cells/μl) was lower than that in group B (571.0 (397.0, 642.0) cells/μl), and lower than that in group C (775.0 (710.0, 993.0) cells/μl), the difference were statistically significant (H=27.225, 40.117; Ps=0.000). The plasma procalcitonin (PCT)(4.3 (0.9, 11.5) ng/ml), D-dimer (4.5 (0.7, 8.4) μg/ml), ESAT-6 (59.3 (27.1, 66.5) pg/ml) and MMP-9 (29.1 (18.6, 39.6) ng/ml) in group A were higher than those of PCT (2.8 (0.5, 8.6) ng/ml), D-dimer (2.3 (0.5, 5.1) μg/ml), ESAT-6 (32.5 (25.8,59.2) pg/ml) and MMP-9 (17.2 (12.7,21.3) ng/ml) in group B, the differences were statistically significant (H=28.991, 29.879, 32.045, 31.122; Ps=0.000). The expression levels of MMP-14 in group A (54.7 (41.4, 66.7) ng/ml) and group B (60.2 (45.2, 65.1) ng/ml) were higher than those in group C (5.5 (2.8, 6.3) ng/ml). The differences were statistically significant (H=49.209,53.436; Ps=0.000). Multivariate logistic regression analysis showed that advanced age (>65 years old) and high expression of ESAT-6 (>30.5 pg/ml) were independent risk factors for the occurrence of anti-tuberculosis drug-induced liver injury (OR (95%CI)=11.289 (4.355-24.361), P=0.000; OR (95%CI)=9.479 (3.340-21.653), P=0.000).Conclusion: Early use of hepatoprotective drugs in pulmonary tuberculosis patients with advanced age and high expression of ESAT-6 may reduce the risk of anti-tuberculosis drug-induced liver injury.The vigilance should also be raised for pulmonary tuberculosis patients with low CD4+ T lymphocyte counts, high procalcitonin, D-dimer and MMP-9 expression.
    Meta analysis of efficacy and safety of the treatment containing bedaquiline for multidrug-resistant pulmonary tuberculosis
    YU Chun-hong, LIU Xing, SHEN Ling-jun, LI Hai-wen, LI Xie, WU Rong-shuang, LI Xian-rui, FAN Hao
    Chinese Journal of Antituberculosis. 2022, 44(7):  660-668.  doi:10.19982/j.issn.1000-6621.20220012
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    Objective: To systematically evaluate the efficacy and safety of the treatment containing bedaquiline for multidrug-resistant pulmonary tuberculosis (MDR-PTB). Methods: Randomized controlled trials (RCTs) of bedaquiline-containing regimens for the treatment of MDR-PTB were searched and collected from Chinese databases (China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP and China Biomedical Literature Database (CBM)) and English databases (The Cochrane Library, PubMed, Embase). The retrieval time was from the establishment of the database to December 2021. Two researchers independently screened the literature, extracted data, and evaluated the quality of the literature. RevMan 5.4 software was used to analyze the heterogeneity of the included data, and the publication bias. Results: A total of 802 patients were included in 10 articles. Meta-analysis results showed that compared with conventional anti-tuberculosis regimens, bedaquiline-containing regimens in the treatment of MDR-PTB could increase the negative conversion rate of sputum at the end of 12 weeks after treatment (OR=3.17, 95%CI: 1.85-5.43, P<0.01), improve the negative rate of sputum bacteria at the end of 24 weeks after treatment (OR=4.09, 95%CI: 2.74-6.12, P<0.01), the cavity closure rate (OR=3.11, 95%CI: 1.68-5.74, P<0.01), the absorption rate of lesions (OR=4.44, 95%CI: 2.40-8.22, P<0.01) and clinical cure rate (OR=4.15, 95%CI: 2.27-7.58, P<0.01), and reduce the level of mortality (OR=5.22, 95%CI: 1.16-16.96, P<0.01). However, there was no significant difference in sputum negative conversion rate at the end of 8 weeks after treatment (OR=1.79, 95%CI: 0.98-3.26, P=0.06) and incidence of adverse drug reactions (OR=2.72, 95%CI: 0.61-12.19, P=0.19) at the end of 8 weeks after treatment with bedaquiline-containing regimens for MDR-PTB. Conclusion: Compared with conventional anti-tuberculosis treatment, the chemotherapy regimens containing bedaquiline for MDR-PTB help to accelerate the negative conversion of sputum bacteria and improve the clinical efficacy, with no increase in adverse reactions; however, ECG should be closely monitored to be alert to the cardiotoxicity of bedaquiline.

    Assessing next-generation sequencing for Mycobacterium tuberculosis diagnosis in clinical sputum samples
    DAI Xiao-wei, WANG Nen-han, CHEN Shuang-shuang, YANG Xin-yu, TIAN Li-li, CHEN Hong, ZHANG Hong-tai, LI Chuan-you
    Chinese Journal of Antituberculosis. 2022, 44(7):  669-679.  doi:10.19982/j.issn.1000-6621.20220097
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    Objective: To evaluate detection efficacy of next-generation sequencing (NGS) to Mycobacterium tuberculosis from clinical sputum samples. Methods: Sputum samples of 49 suspected pulmonary tuberculosis patients diagnosed in Tuberculosis Outpatient Department of Beijing Center for Disease Prevention and Control (Beijing Center for Tuberculosis Research and Control) were collected from August to November, 2021. Suspected pulmonary tuberculosis were detected from sputum samples with acid-fast staining (smear),L-J culture and MGIT 960 liquid culture (culture), GeneXpert MTB/RIF (Xpert) and NGS methods. The positive detection rates of 4 kinds of methods were compared in the selected patients. We also evaluated the detection efficacy of different methods based on the results of clinical diagnosis. Results: There were 40 pulmonary tuberculosis patients (25 confirmed pathogen-positive pulmonary tuberculosis patients and 15 clinical diagnosed cases) and 9 non-pulmonary tuberculosis patients (6 cases of pneumonia, 1 case of nontuberculous mycobacteria infection, 1 case of COPD and 1 case of asthma). The positive detection rates are statistically difference (χ2=17.614,17.018,20.753;Ps=0.000) among smear 44.9% (22/49), culture 51.0% (25/49), Xpert 49.0% (24/49) and NGS 69.4% (34/49). For etiology-negative pulmonary tuberculosis patients, the positive detection rate by the NGS was 46.7% (7/15). Sensitivity were 55.0% (22/40), 60.0% (24/40), 60.0% (24/40), 80.0% (32/40), and specificity were 9/9, 8/9, 9/9, 7/9, and concordance rate were 63.3% (31/49), 65.3% (32/49), 67.3% (33/49), 79.6% (39/49), Kappa values were 0.310,0.297,0.355,0.459 based on smear, culture, Xpert and NGS respectively. Conclusion: NGS has the highest sensitivity and consistency based on the national clinical diagnosis standard of pulmonary tuberculosis, which can diagnose suspected pulmonary tuberculosis earlier and detect Mycobacterium tuberculosis from sputum samples rapidly and effectively.

    The clinical features of 653 cases of thoracic spinal tuberculosis
    RAO Hai-tao, DONG Wei-jie, QIN Shi-bing
    Chinese Journal of Antituberculosis. 2022, 44(7):  675-680.  doi:10.19982/j.issn.1000-6621.20220094
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    Objective: To depict the clinical features of thoracic spinal tuberculosis patients. Methods: A total of 653 thoracic spinal tuberculosis cases diagnosed between January 2011 and December 2018 in Beijing Chest Hospital were enrolled retrospectively.The demographic characteristics,clinical features, outcomes of pathological examination and laboratory testing, and the way of surgery of the cases were investigated. Results: The median age of the enrolled patients was 49.0 (30.0,62.0) years old,the median course before the surgery was 6.0 (3.0,12.0) months. 78.1% (510/653) of them had back pain as the chief complaint and 81.0% (417/515) were diagnosed according to the pathological examination outcomes. 65.7% (429/653) of the enrolled patients came from the outside Beijing, and more aged patients (over 65 years old) were observed in local patients than in patients from outside Beijing (34.8% (78/224) vs. 14.0% (60/429);χ2=38.330,P<0.001). 91.4% (597/653) of the cases had their middle and/or lower thoracic vertebra involvement, and 69.5% (454/653) of them had 2 vertebral bodies involved, and 28.2% (184/653) had 3 or more. 83.2% (543/653) underwent operations and 18.2% (99/543) of them had postoperative complications. 30.5% (199/653) of the cases were paraplegic patients, and the median sedimentation rate of red blood cells (ESR)(35.0 (16.0,66.3) mm/1 h),anemia happening rate (36.7%, 73/199),the median duration of the operation (210.0 (168.5,250.0)) and the blood lost during the operation (600.0 (400.0,1000.0) ml) of the paraplegic patients were significantly different with these of the non-paraplegic patients (27.0 (11.0,55.5) mm/1 h, 24.7% (112/454), 201.0 (150.0,240.0) min, 500.0 (400.0,800.0) ml)(Z=-2.867,P=0.004;χ2=9.835,P=0.002; Z=-2.494,P=0.013; Z=-3.182,P<0.001). Finally, all postoperative complications recovered after treatment, 581 patients (89.0%) got better and left hospital, 61 patients (9.0%) were transferred to other medical institutions for further rehabilitation or treatment of basic diseases, 8 patients were not recovered from paraplegia (1.2%), and 3 patients died (0.5%). Conclusion: Thoracic spinal tuberculosis patients are generally at old age with long preoperative course, and 2 or more vertebral bodies of the middle and/or lower thoracic vertebra involvement are common. Pathological examination is the main way to provide evidence for diagnosis, and operation is an important means of treatment. The operation of the paraplegic patients takes longer time and is generally more complicated.

    Study on the trend and prediction of reported incidence of national active pulmonary tuberculosis in China
    KANG Wan-li, LI Tian-jing, WANG Sai-sai, LI Chang-hua, ZHAO Qiu-yue, ZHENG Su-hua, LIU Yang
    Chinese Journal of Antituberculosis. 2022, 44(7):  681-684.  doi:10.19982/j.issn.1000-6621.20210672
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    Objective: To study the trend of reported incidence of national active pulmonary tuberculosis (PTB) in 2009—2018, and predict the reported incidence from 2019 to 2022 and the status of ending the TB epidemic in China. Methods: The active PTB reported incidence between 2009 and 2020 were collected. The Mann-Kendall test was used to analyze the trend of national active tuberculosis between 2009 to 2018 and grey model (GM (1,1)) was used to predict the reported incidence. Results: The reported incidence of active PTB in China decreased from 81.09/100000 in 2009 to 59.27/100000 in 2018 with a downward trend according to the Mann-Kendall trend test (Z=-3.940, P<0.001). In the past 10 years, it has decreased by 26.91% and the average annual decline rate is 3.42%. The grey model GM (1,1) has good fitting accuracy and could be used to predict, with an average relative error of 0.8255%, posteriori error ratio C=0.097, and small error probability P=1 between predicted value and actual value. Predicted by the GM (1,1) model, the reported incidence of active PTB in China from 2019 to 2022 were 56.7673/100000, 55.1394/100000, 53.5581/100000 and 52.0222/100000, respectively. If the concurrent TB control strategy remains unchanged, the reported incidence of active PTB will be 39.04/100000 in 2030 and 32.80/100000 in 2035 based on the average annual decline rate of 3.42%. Conclusion: From 2009 to 2018, the active PTB reported incidence in China showed a downward trend. It is difficult to achieve the WHO End TB Strategy if the current control strategy remains unchanged.

    Analysis of monitoring results of tuberculosis drug-resistance in Guangdong Province from 2016 to 2020
    CHEN Yan-mei, WEN Wen-pei, WU Hui-zhong, XU Liu-yue, PENG Ke-hao, YU Mei-ling
    Chinese Journal of Antituberculosis. 2022, 44(7):  685-689.  doi:10.19982/j.issn.1000-6621.20220028
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    Objective: To understand the situation and trend of drug resistance of tuberculosis patients in Guangdong Province from 2016 to 2020, so as to provide scientific basis for the prevention and control of drug-resistant tuberculosis. Methods: A total of 92851 patients with active pulmonary tuberculosis from 32 drug resistance surveillance sites in Guangdong Province from January 1, 2016 to December 31, 2020 were collected. The clinical information of the subjects was collected, the sputum samples were smeared, isolated and cultured, and the positive strains in culture were identified. A total of 30362 isolates of Mycobacterium tuberculosis (MTB) were obtained. The drug sensitivity test of 9 anti-tuberculosis drugs (isoniazid (INH), rifampicin (RFP), ethambutol (EMB), streptomycin (Sm), kanamycin (Km), ofloxacin (Ofx), capreomycin (Cm), propylthionicotinamide (Pto) and sodium aminosalicylate (PAS) was carried out on MTB isolates by proportional method, and the drug resistance of the strains was analyzed. Results: The total drug resistance rate of 30362 strains was 26.75% (8121/30362), the multidrug resistance rate was 3.34% (1014/30362), the single drug resistance rate was 15.88% (4820/30362), and the multidrug resistance rate was 7.53% (2286/30362). The resistance rate of the strain to any one of the nine anti-tuberculosis drugs from high to low was Sm (14.59%, 4430/30362)>INH (9.25%, 2810/30362)>RFP (6.22%, 1887/30362)>EMB (5.72%, 1737/30362)>Ofx (3.03%, 920/30362)>Pto (3.00%, 912/30362)>PAS (2.25%, 684/30362)>Cm (2.00%, 606/30362)>Km (1.63%, 494/30362), the difference was statistically significant (χ2=8889.800, P<0.01). Of the strains, 27783 were isolated from primary patients and 2579 strains were isolated from retreated patients. The drug resistance rate and multidrug resistance rate of retreated patients were significantly higher than those of primary patients (35.32% (911/2579) vs. 25.95% (7210/27783), χ 2=105.800, P<0.01; 10.35% (267/2579) vs. 2.69% (747/27783), χ 2=265.700, P<0.01). During the five years, the multidrug resistance rate of newly treated patients showed an upward trend (2.76% (152/5502) in 2016 and 3.19% (166/5203) in 2020), and the drug resistance rate of retreated patients showed a downward trend (38.85% (169/435) in 2016 and 35.02% (173/494) in 2020), the difference was statistically significant (χtrend2=6.584 and 6.334, P=0.010 and 0.012, respectively). The drug resistance rate and multidrug resistance rate of the strains from the Pearl River Delta region were significantly higher than those from the eastern and northwestern regions of Guangdong Province (27.35% (4540/16597) vs. 26.02% (3581/13765), χ 2=6.886, P=0.009; 3.59% (596/16597) vs. 3.04% (418/13765), χ 2=3.879, P=0.049). Conclusion: The epidemic situation of drug-resistant tuberculosis in Guangdong Province is still serious. Rifampicin resistance, drug resistance of newly treated patients and drug resistance of tuberculosis in floating population should be paid special attention.
    Analysis of recurrence rate of pulmonary tuberculosis patients in Foshan and the influencing factors from 2014 to 2018
    ZHONG Qian-hong, MA Xiao-hui, ZHONG Yong-hui, ZHAO Zhi-meng, ZHANG Xi-lin, XU Bang, LUO Jie-ying, ZHONG Li-ping, DAI Lei
    Chinese Journal of Antituberculosis. 2022, 44(7):  690-697.  doi:10.19982/j.issn.1000-6621.20220023
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    Objective: To investigate the recurrence rate of pulmonary tuberculosis patients in Foshan and its influencing factors,to provide scientific basis for preventing the recurrence of pulmonary tuberculosis. Methods: The medical record information of 15208 newly treated pulmonary tuberculosis patients who were reported and registered in Foshan City and whose treatment results were cured or the course of treatment was completed from January 2014 to December 2018 were collected from the “Tuberculosis Management Information System”, a subsystem of the “Chinese Disease Prevention and Control Information System”. Cox proportional hazards regression model was used to analyze the general data, clinical information, etiological results and treatment outcome of 161 patients with recurrent pulmonary tuberculosis. Results: A total of 15208 cases were included in this study. Of them, 161 cases (1.06%) relapse within 5 years. The cumulative recurrence rates were 0.40% (61/15208) after 1 year, 0.70% (106/15208) after 2 years, and 1.05% (159/15208) after 5 years. In the Cox proportional hazards regression model, local household registration (HR=1.56, 95%CI: 1.14-2.14, P=0.005), positive sputum smear at diagnosis (HR=2.92, 95%CI: 2.10-4.06, P<0.001), positive sputum smear after 2 months of treatment (HR=3.94, 95%CI: 2.41-6.47, P<0.001), abnormal blood urea nitrogen (HR=8.76, 95%CI: 5.00-15.36, P<0.001) were independent risk factors for the recurrence of pulmonary tuberculosis. Conclusion: The management of tuberculosis patients with local household registration, positive sputum smear at diagnosis, and abnormal blood urea nitrogen should be strengthened, and the quality of standardized treatment and management should be ensured. At the same time, targeted intervention measures should be carried out for this kind of high-risk population to reduce recurrence of pulmonary tuberculosis.

    Analysis of risk factors for recurrence within 2 years after successful treatment of newly treated active pulmonary tuberculosis in Tianjin
    GAO Li, PANG Xue-wen, ZHANG Guo-qin, LI Jing-xin, ZHANG Fan
    Chinese Journal of Antituberculosis. 2022, 44(7):  698-703.  doi:10.19982/j.issn.1000-6621.20220017
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    Objective: To investigate the influencing factors of recurrence within 2 years after successful treatment of newly treated active tuberculosis in Tianjin. Methods: Medical records of 8115 newly treated active tuberculosis patients registered in Tianjin City from January 1, 2016 to December 31, 2019 were retrieved from Tuberculosis Management Information System, a sub-system of Chinese Disease Control and Prevention Information System. Cox proportional risk model was used to analyze the general information, clinical information, etiological results and treatment outcomes of them. Results: Among the 8115 patients, 307 patients recurred within 2 years, the recurrence rate was 3.78%. The recurrence density was 0.85 per 100 person-years (307/36104),the proportion of recurrence within 6 months was 35.83% (110/307), 29.00% (89/307) within 6-12 months, and 35.17% (108/307) in 1-2 years. Among subjects enrolled from 2016 to 2019, the recurrence rates within 2 years were 4.20% (102/2427),4.03% (96/2383),3.53% (86/2433),2.64% (23/872) respectively, which decreased year by year ( χ trend 2=4.517, P=0.034).Cox proportional risk regression model showed that male (aHR=1.321,95%CI:1.021-1.710), 40-59 years old (aHR=2.220,95%CI:1.224-4.025), ≥60 years old (aHR=1.935,95%CI: 1.066-3.513), worker/migrant worker/herdsmen (aHR=2.303, 95%CI: 1.233-4.303), houseworker/unemployment (aHR=2.340,95%CI: 1.322-4.143), positive etiological result (aHR=1.785,95%CI:1.407-2.265), resistance to non-rifampicin drugs (aHR=1.968, 95%CI: 1.389-2.789), sputum smear positive after 2 months’ treatment (aHR=1.517,95%CI:1.033-2.228), complicated with diabetes mellitus (aHR=1.382, 95%CI: 1.028-1.857) were independent risk factors for recurrence. Conclusion: The risk of recurrence of newly treated active tuberculosis patients in Tianjin City was relatively high. We should focus on the standardized treatment and follow-up management of people over 40 years old, workers/farmers/herdsmen/unemployed patients, and patients with positive etiological results/non-rifampicin resistance/positive sputum smear results after 2 months’treatment/diabetes. Specialized intervention measures should be put on these high-risk groups in early stages.
    Analysis of the usage of electronic pillbox and WeChat App in pulmonary tuberculosis patients
    XUE Xiao, ZHANG Dong-yan, AI Ping, DENG Ling, CHEN Wei, HU Yuan-lian, JIA Xue-jiao, YANG Guo-liang, XIN Zhen-jiang, CHANG Li-jie
    Chinese Journal of Antituberculosis. 2022, 44(7):  704-710.  doi:10.19982/j.issn.1000-6621.20220102
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    Objective: To analyze the usage of electronic pillbox and WeChat App in pulmonary tuberculosis(PTB) patients and to provide experience for the promotion of such intelligent tools.Methods: We obtained data from the E-patient service system and the Surveillance Report Management Module of the Chinese Information System for Disease Control and Prevention, also data collected by health care workers providing community health services, analyzed the usage of electronic pillbox and WeChat App of 563 PTB patients supervised by 25 community health service centers, analyzed the adoption rate differences in different genders, age groups, occupations, household registrations, ethnic groups, educational levels and tuberculosis etiological test results, and the adherence rate to the electronic pillbox and WeChat App.Results: The adoption rate of electronic pillbox and WeChat App was 54.7% (308/563) together, 12.8% (72/563) and 41.9% (236/563) for each, the latter was higher than the former. Univariable analysis showed that the adoption rate of electronic pillbox in junior college or above was 11.1% (29/261), senior high school/technical secondary school was 20.5% (27/132),there was significant difference in the adoption rate of electronic pillbox among patients with different educational levels (χ2=9.352, P=0.009). Multivariable logistic regression analysis showed that the adoption rate of electronic pillbox in patients with senior high school/technical secondary school education was 2.407 times of that of patients with junior middle school and below education (OR=2.407,95%CI:1.215~4.767); The adoption rate of WeChat App was not affected by factors in analysis. The adherence rate for electronic pillbox was 22.2% (16/72) and 25.8% (61/236) for WeChat App, no significant difference detected (χ 2=0.387, P=0.534).Conclusion: Both intelligent tools can be popularized in PTB patients. Patients were more willing to choose WeChat App to assist treatment management. The adoption rate in patients with high school/technical secondary school education was higher. It is still necessary to further improve the adoption rate and quality utilization of electronic pillbox and WeChat App.
    Analysis of the application of tuberculosis telemedicine consultation and training platform based on internet technology
    PANG Yu, SUN Yu-xian, ZHANG Li-jie, XIE Shi-heng, LIU Yu-hong
    Chinese Journal of Antituberculosis. 2022, 44(7):  711-715.  doi:10.19982/j.issn.1000-6621.20220109
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    Objective: To analyze the application and development of tuberculosis telemedicine consultation and training platform based on internet technology.Methods: A retrospective study was conducted in various activities from the national tuberculosis telemedicine consultation and training platform (remote platform) from March 2012 to December 2021. The activities included training and academic lectures, training courses and academic conferences, case discussion and ward round, case consultation and consultation services, and working meetings. The activity related data were queried and analyzed through the remote platform, including the number of medical institutions covered, the number of various activities, the number of participants in various activities, etc.Results: From 2012 to 2021, the number of units covered by remote platform was increased from 10 to 286, with an average annual growth rate of 45.15%. A total of 1446 remote activities were carried out, and the total number of people participating in remote activities was 1641133. The highest number of activities and participants was in 2020, 459 and 854884, respectively. It had increased by 50 times and 1978 times respectively compared with numbers in 2012 (9 and 432). The activities with the largest cumulative number between 2012 and 2021 were training and academic lectures (617), followed by case consultation and consultation services (568). The activities with the largest number of cumulative participants were training and academic lectures (860093 persons), followed by training courses and academic conferences (699038 persons). The types of activities carried out by remote platform had changed from 2012 to 2021. From the composition ratio of the number of activities carried out, the composition ratio of training and academic lectures decreased the most, from 8/9 in 2012 to 37.98% (128/337) in 2021, while case consultation and consultation increased the most, from 0 in 2012 to 46.29% (156/337) in 2021. In terms of the composition ratio of the number of participants, the composition ratio of training and academic lectures decreased the most, from 89.58% (387/432) in 2012 to 53.92% (331396/614599) in 2021, while training courses and academic conferences increased the most, from 0 in 2012 to 39.68% (243895/614599) in 2021.Conclusion: The tuberculosis telemedicine consultation and training platform based on internet technology had played an important role in the training of tuberculosis diagnosis and control knowledge, the publicity and implementation of policy guidelines, the improvement of primary medical institutions’ capacity, academic exchanges and other aspects, and had great development potentials.
    Review Articles
    Research progress on pharmacokinetics and drug interaction of bedaquiline
    NIE Wen-juan, ZHOU Wen-qiang, CHU Nai-hui
    Chinese Journal of Antituberculosis. 2022, 44(7):  716-719.  doi:10.19982/j.issn.1000-6621.20220092
    Abstract ( 738 )   HTML ( 23 )   PDF (821KB) ( 412 )   Save
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    As the new anti-tuberculosis drug, bedaquiline is often used in combination with other second-line anti-tuberculosis drugs. In view of the increasing literature on the pharmacokinetics of bedaquiline and the limited understanding of some clinicians about its pharmacokinetics, especially drug interactions, this review summarized the relevant literature on the pharmacokinetics, effect of covariates on pharmacokinetics and exposure-response relationship drug interactions, etc. It is expected that this paper can provide help for guiding clinicians to use drugs and researchers to carry out research.

    Progress and clinical application of immunological detection technology for Mycobacterium tuberculosis infection
    JIA Hong-yan, DONG Jing, ZHANG Zong-de, PAN Li-ping
    Chinese Journal of Antituberculosis. 2022, 44(7):  720-726.  doi:10.19982/j.issn.1000-6621.20220103
    Abstract ( 1128 )   HTML ( 60 )   PDF (886KB) ( 840 )   Save
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    In the world and China, tuberculosis is still one of the infectious diseases requiring more attention to the prevention and control. Although the positive detection of Mycobacterium tuberculosis nucleic acid has been defined as one of the basis for the diagnosis of tuberculosis, there are still a large number of tuberculosis patients with negative etiology in clinic and need to rely on immunological detection technology for auxiliary diagnosis. The immunopathological response and anti-tuberculosis immune response caused by Mycobacterium tuberculosis infection are the basis for the development of immunological technologies. Various kinds of cells, cytokines, chemokines, and antibodies, etc., involved in different stages of the immune response, are all potential targets for immunological diagnosis. In recent years, a number of new immunological technologies have been developed based on these targets, including interferon-γ release assay, new tuberculin test, IP-10 test and IFN-γ/IL-2 dual release assay, offers new hopes for diagnosis of Mycobacterium tuberculosis infection and tuberculosis. In addition, some new protein biomarkers and poly-functional lymphocytes in the development process also show good potential diagnostic values. Herein, the current application status, advantages and disadvantages of immune diagnostic technologies that have been used in clinical practice are reviewed, and biomarkers and other potential targets that may be used in clinic in the future are discussed.

    Advances in research on treatments of multidrug-resistant tuberculosis with Chinese traditional medicine
    YANG Chi, WANG Zhen-wei, SHA Wei
    Chinese Journal of Antituberculosis. 2022, 44(7):  727-731.  doi:10.19982/j.issn.1000-6621.20220133
    Abstract ( 730 )   HTML ( 31 )   PDF (902KB) ( 1356 )   Save
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    Multidrug-resistant tuberculosis (MDR-TB) is caused by the primary infection of drug-resistant Mycobacterium tuberculosis (MTB) or improper tuberculosis treatment, which has become a major obstacle to end tuberculosis before 2035. Due to its poor cure rate, there is an urgent need to develop new anti-tuberculosis drugs or treatment strategy. Chinese traditional medicine could alleviate the patients’ symptoms, reduce the toxicity and enhance effect when combined with anti-tuberculosis therapy, as well as improve patients’ immunity. The authors review the progress of Chinese traditional medicine of anti-tuberculosis treatments, which may provide more thoughts and strategies for clinicians.

    Recent progress of Nano-drug delivery system for tuberculosis treatment
    TIAN Na, CHU Hong-qian, SUN Zhao-gang
    Chinese Journal of Antituberculosis. 2022, 44(7):  732-737.  doi:10.19982/j.issn.1000-6621.20220036
    Abstract ( 566 )   HTML ( 17 )   PDF (872KB) ( 609 )   Save
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    At present, the prevention and control of tuberculosis are still severe. However, the conventional anti-tuberculosis drug regimens have several limitations such as a long course of treatment, high incidence of adverse reactions, and poor patient compliance, which often lead to treatment failures. Therefore, there is an urgent need for new drugs or new dosage forms that can control tuberculosis. The nano-drug delivery system loaded with anti-tuberculosis drugs can actively or passively deliver drugs into infected macrophages or focal sites for sterilization, and it also have advantages of sustained-release administration, reducing dosing frequency and dose-dependent adverse reactions. etc. This article reviews the application and prospect of nano-drug delivery systems in the treatment of tuberculosis.

Monthly, Established in Novembar 1934
ISSN 1000-6621
CN 11-2761/R

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