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    10 January 2021, Volume 43 Issue 1
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    Tuberculosis research progress in 2020
    Chinese Antituberculosis Association
    Chinese Journal of Antituberculosis. 2021, 43(1):  6-11.  doi:10.3969/j.issn.1000-6621.2021.01.003
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    Tuberculosis (TB) is one of the most serious infectious diseases, and one of the top ten death causes of single infectious disease globally. In 2020, researchers have made many efforts, and many breakthroughs have been made in basic research, diagnosis, treatment and prevention on TB. These breakthroughs have brought a lot of inspiration and ideas to TB research, and also brought more hope for clinical work. For example, the research on the cough mechanism of MTB sulfolipid-1 has brought new ideas to control the infection of MTB. The good protective effect of M72/AS01E vaccine gave us hope for TB prevention after BCG. The results of the Nix-TB study bring new light to the retreated or refractory MDR/XDR-TB patients. New diagnostic methods such as mRNA markers are also making progress. In order to improve the diagnosis and treatment ability of national TB prevention and control personnel, and timely understand the breakthrough of global TB research in new technologies, new methods, new concepts and new drug research, Chinese Antituberculosis Association organized experts to interpret the important literatures published internationally from October 2019 to October 2020, so as to contribute to promoting the research work in the field of TB in China.

    Expert Consensus
    Expert consensus on treatment and management of tuberculosis-diabetes mellitus
    National Clinical Research Center for Infectious Disease/, The Third People’s Hospital of Shenzhen, National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital of Central South University, Chinese Antituberculosis Association, Editorial Board of Chinese Journal of Antituberculosis
    Chinese Journal of Antituberculosis. 2021, 43(1):  12-22.  doi:10.3969/j.issn.1000-6621.2021.01.004
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    Tuberculosis (TB) and diabetes mellitus (DM) are both frequently-occurring clinical diseases and global pandemics. The two can coexist and influence each other. DM increases the risk of active TB, and TB may provoke hyperglycemia. The double burden of TB and DM has become a major public health problem. Therefore, it is necessary to manage the two diseases jointly. This consensus focuses on the pandemics, two-way screening, pathogenesis, clinical features, diagnosis, treatment and management of comorbidity of TB-DM, providing guidance to health care workers.

    Original Articles
    Analysis of drug resistance characteristics of MDR/XDR-TB patients complicated with type 2 diabetes mellitus
    HU Wei-hua, JIN Long, CHU Nai-hui
    Chinese Journal of Antituberculosis. 2021, 43(1):  26-30.  doi:10.3969/j.issn.1000-6621.2021.01.006
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    Objective Understand and analyze the drug resistance characteristics of MDR/XDR-TB patients complicated with type 2 diabetes mellitus. Methods Collect 233 MDR/XDR-TB patients diagnosed by Mycobacterium tuberculosis culture and drug sensitivity test (referred to as “drug sensitivity test”) from the drug-resistant ward of Infectious Hospital of Heilongjiang Province from June 2018 to June 2020, among them, 84 cases were complicated with type 2 diabetes mellitus (referred to as “concurrent DM group”) and 149 cases were not complicated with DM (referred to as “non-concurrent DM group”). The initial retreatment, drug resistance and drug resistance spectrum of the two groups were analyzed, SPSS 18.0 software was used for statistical analysis, the count data was expressed as percentage, the constituent ratio or rate between groups was compared by Chi square test,P<0.05 as the statistically significant difference. Results There were 26 cases of initial treating pulmonary tuberculosis in the concurrent DM group, accounting for 30.95% (26/84), and 16 cases in the non-concurrent DM group, accounting for 10.74% (16/149), the difference between the two groups was statistically significant (χ 2=14.854, P<0.01). In terms of the number of drugs resistance, the concurrent DM group was compared with the non-concurrent DM group, the rates of resistance to isoniazid and rifampin were 10.71% (9/84), 7.39% (11/149), the rates of resistance to 3 drugs, respectively were 28.57% (24/84) and 24.16% (36/149), the rates of resistance to 4 drugs were 19.05% (16/84) and 24.83% (37/149), the rates of resistance to 5 drugs were 17.86% (15/84) and 19.46% (29/149), and the rates of resistance to 6 or more drugs were 23.81% (20/84) and 24.16% (36/149) respectively, there was no statistical significance difference between the two groups (χ 2 values were 0.759, 0.546, 1.023, 2.063 and 0.882, and the P values were 0.383, 0.460, 0.312, 0.151 and 0.348). In terms of drug resistance spectrum, the concurrent DM group was compared with the non-concurrent DM group, the resistance rates of isoniazid and rifampin were 10.71% (9/84) and 7.40% (11/149), the rates of fluoroquinolone resistance were 29.76% (25/84) and 29.53% (44/149), the rate of resistance to injection of second-line anti-tuberculosis drugs were 4.76% (4/84) and 6.71% (10/149), the rates of simultaneous resistance to isoniazid and rifampicin, fluoroquinolones, and second-line anti-tuberculosis drugs simultaneously were 8.33% (7/84) and 13.42% (20/149) respectively, there was no statistical significance difference between the two groups (χ 2 were 0.760, 0.009, 0.361 and 1.358, and the P values were 0.383, 0.926, 0.548 and 0.244). Conclusion The majority of MDR/XDR-TB patients complicated with type 2 diabetes mellitus were initial treating pulmonary tuberculosis. Whether complicated with diabetes mellitus had no effect on the number of resistant drugs and the drug resistance spectrum of MDR/XDR-TB patients. It is suggested that we should strengthen the protection of susceptible population such as diabetes, to avoid the occurrence of primary drug-resistant tuberculosis due to infection of drug-resistant Mycobacterium tuberculosis.

    Clinical characteristics of pulmonary tuberculosis in hospitalized patients with diabetes mellitus
    ZENG Jian-feng, YANG Min, TANG Fang, ZHU Hui-min, CHEN Tao, DENG Guo-fang, ZHANG Pei-ze
    Chinese Journal of Antituberculosis. 2021, 43(1):  31-35.  doi:10.3969/j.issn.1000-6621.2021.01.007
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    Objective To investigate the incidence rate of pulmonary tuberculosis (TB) in hospitalized patients with diabetes mellitus (including type 1 and type 2 diabetes) and analyze the correlation between the activity of TB and the incidence of tuberculosis. Methods We retrospectively reviewed the routine chest imaging and clinical data of 2648 patients with diabetes in our hospital from January 2018 to December 2019. We then calculated the incidence rate of pulmonary tuberculosis in diabetic patients. The basic characteristics, the level of glycosylated hemoglobin and the status of diabetes treatment were compared between active tuberculosis group and inactive tuberculosis group. Results Of the 2648 patients with diabetes, 2585 patients had no evidence of tuberculosis, accounting for 97.62% (2585/2648); 31 patients complicated with active tuberculosis, accounting for 1.17% (31/2648); 32 patients complicated with inactive tuberculosis, accounting for 1.21% (32/2648). Active tuberculosis and inactive tuberculosis were mainly male, accounting for 90.32% (28/31) and 84.38% (27/32)respectively. The average age of active tuberculosis patients was (51.16±13.06) years old, of inactive tuberculosis patients was (61.78±12.88) years old. The difference between the two groups was statistically significant (t=-3.236, P=0.002). The average glycosylated hemoglobin of patients with active tuberculosis was (9.18±2.85) %, of patients with inactive tuberculosis was (8.05±1.69) %. There was no significant difference between the two groups (t=1.884, P=0.070). Conclusion Diabetes inpatients have a high proportion of concurrent tuberculosis, most of them are male. We should pay attention to the screening and follow-up of pulmonary tuberculosis in diabetic inpatients; the correlation between blood glucose control level and tuberculosis activity of diabetic patients needs to be further confirmed.

    A comparative study of plasma metabolomics between diabetes and diabetes complicated with pulmonary tuberculosis
    WANG Mei-jie, LI Yu-ze, XIAO Yao, WU Ming-qi, HOU Shao-ying
    Chinese Journal of Antituberculosis. 2021, 43(1):  36-41.  doi:10.3969/j.issn.1000-6621.2021.01.008
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    Objective To explore the difference of plasma metabolomics between diabetes (DM) patients and diabetes complicated with tuberculosis (DM-PTB). Methods DM patients (DM group, n=10) and DM-PTB patients (DM-PTB group, n=10) diagnosed in Heilongjiang Provincial Infectious Disease Prevention and Treatment Hospital from January to June 2017 were collected. Venous blood were collected from these patients (10 ml per patient) with empty stomach in the early morning using Ethylenediaminetetraacetic acid (EDTA) anticoagulation tubes, and then the supernatant was collected by centrifugation. Metabolomics detection on the plasma samples of the two groups was performed by UPLC-Q-TOF MS technology, and then multivariate statistical analysis methods were used to compare their metabolic profiles and screen potential different metabolites. Results The plasma metabolism profiles of DM group and DM-PTB group were significantly different; 7 metabolites were preliminarily identified different between the two groups. Of them, the plasma 6-keto-prostaglandin F1a (multiple of difference 143.34, P=0.020), protoporphyrinogen Ⅸ (multiple of difference 33.18, P=0.040), linoleic acid (multiple of difference 8.18, P=0.000), 5-hydroxyeicosatetraenoic acid (multiple of difference 15.09, P=0.000), prostaglandin E2 (multiple of difference 8.88, P=0.000) and leukotriene B4 (multiple of difference 39.58, P=0.000) of the DM-PTB group were higher than those of the DM group, while hippuric acid content of the DM-PTB group (multiple of difference 2.69, P=0.010) was lower than that of the DM group. Conclusion Metabolism of arachidonic acid, linoleic acid, and amino acid happen changes after DM patients complicated with PTB, the above-mentioned plasma metabolites may be early screening indicators for DM-PTB.

    Nutritional risk screening and influencial factor analysis in hospitalized patients with comorbidity of tuberculosis and diabetes mellitus
    LUO Xiao-qing, DUAN Si-yu, LIN Ming-yu, DENG Xun, LIU Bi-fen, LI Lian, TANG Hui-wen, DING Li
    Chinese Journal of Antituberculosis. 2021, 43(1):  42-46.  doi:10.3969/j.issn.1000-6621.2021.01.009
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    Objective To analyze the nutritional risk and its influencial factors in patients with tuberculosis complicated with diabetes mellitus and provide evidence for early nutritional intervention. Methods Tuberculosis with diabetes mellitus inpatients admitted in the infectious disease prevention and control center of the fifth affiliated hospital of Sun Yat-sen University from April 1, 2018 to August 31, 2019 were enrolled. Clinical data was collected, including gender, age, complications, type of TB diagnosis, type of patients, mycobacterium tuberculosis detection, disease course, anti-tuberculosis treatment time, hospitalization days, score of nutritional risk screening 2002 (NRS 2002), hemoglobin (Hb), albumin (ALB), prealbumin (PAB), fasting blood sugar (FBS), glycosylated hemoglobin (GHB), neutrophil/lymphocyte ratio (NLR), prognosis of nutrition index (PNI) and weight. Multivariate logistic regression was used to analyze related factors of nutritional risk. Results According to the NRS-2002 score, 35 patients with scores ≥3 were included in the nutritional risk group, and 134 patients with scores <3 were included in the non-nutritional risk group, with an incidence of nutritional risk of 20.71% (35/169). Multivariate logistic regression analysis showed that disease course lasting over one month was a risk factor for the occurrence of nutritional risks (OR (95%CI)=6.003 (1.662,21.688)) while high blood albumin level was a protective factor (OR (95%CI)=0.876 (0.815,0.942)), the higher the albumin, the lower the incidence of nutritional risk. Conclusion The incidence of nutritional risk in patients with tuberculosis complicated with diabetes was 20.71%, associated with disease course and blood albumin. The incidence of nutritional risk for patients with disease course ≥1 month was significantly higher than those having <1 month disease courses, while blood albumin was negatively associated with the incidence of nutritional risk.

    The value of PCR-reverse dot blot hybridization in detecting the drug resistance of Mycobacterium tuberculosis in sputum specimens of retreatment smear-positive pulmonary tuberculosis patients
    LIU Zhi-bin, WU Min, WU Xiao-cui, HAN Min, XIAO He-ping, ZHANG Qing
    Chinese Journal of Antituberculosis. 2021, 43(1):  47-51.  doi:10.3969/j.issn.1000-6621.2021.01.010
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    Objective To investigate the value of PCR-reverse dot blot (RDB) hybridization in detecting the drug resistance of Mycobacterium tuberculosis(MTB) in sputum specimens of retreatment smear-positive pulmonary tuberculosis patients. Methods Sputum specimens from 400 retreatment smear-positive pulmonary tuberculosis patients diagnosed and treated in Shanghai Pulmonary Hospital from June 2015 to January 2019 were collected. The amount of each specimen was more than 2 ml. The same sputum specimen of each patient was tested for drug resistance detection using PCR-RDB, Gene Xpert MTB/RIF and Micropore-plate method (MicroDST). Three hundred and fifty-seven cases (strains) were finally included. The results of MicroDST were used as reference standard to evaluate the performance of PCR-RDB. Results Based on reference standard, the sensitivity, specificity, positive predictive value, negative predictive value, coincidence rate and Kappa value of PCR-RDB in detecting rifampicin resistance of MTB were 97.5% (115/118), 97.1% (232/239), 94.3% (115/122), 98.7% (232/235), 97.2% (347/357) and 0.937; the sensitivity, specificity, positive predictive value, negative predictive value, coincidence rate and Kappa value of PCR-RDB in detecting isoniazid resistance of MTB were 82.5% (113/137), 99.1% (218/220), 98.3% (113/115), 90.1% (218/242), 92.7% (331/357) and 0.841; the sensitivity, specificity, positive predictive value, negative predictive value, coincidence rate and Kappa value of PCR-RDB in detecting streptomycin resistance of MTB were 86.5% (115/133), 99.1% (222/224), 98.3% (115/117), 92.5% (222/240), 94.4% (337/357) and 0.877; the sensitivity, specificity, positive predictive value, negative predictive value, coincidence rate and Kappa value of PCR-RDB in detecting ethambutol resistance of MTB were 60.7% (37/61), 98.6% (292/296), 90.2% (37/41), 92.4% (292/316), 92.2% (329/357)and 0.682. Conclusion PCR-reverse dot blot hybridization shows a good capability in detecting the drug resistance of MTB in sputum specimen of retreatment smear-positive pulmonary tuberculosis patients.

    Analysis of the results of etiology and drug resistance in different surgical specimens of tuberculous empyema by two techniques
    LI Qian, WANG Lin-bao, LUO Pei-jia, WEI Lin, LIU Yu-gang, REN Lei-peng, DING Chao
    Chinese Journal of Antituberculosis. 2021, 43(1):  52-57.  doi:10.3969/j.issn.1000-6621.2021.01.011
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    Objective BACTEC MGIT 960 (MGIT 960) and fluorescence PCR melting curve method (PCR melting curve method) were used to detect the etiology and drug resistance of different surgical specimens of tuberculous empyema, and comparative study was conducted. Methods From January 2019 to June 2020, 150 patients with tuberculous empyema were enrolled (MTB MGIT 960 was positive and MPB64 monoclonal antibody was MTB strain of thoracic puncture before surgery, or histopathological examination showed typical tuberculous granulomatous inflammation with caseous necrosis). MGIT 960 liquid culture, phenotypic drug sensitivity test (drug sensitivity test) and PCR melting curve method were used to detect nucleic acid and drug resistance genes of different surgical specimens (150 lesions and 150 pus). Positive rate of etiological diagnosis between two kinds of techniques in different surgical specimens, and drug resistance results of 40 pathogenic positive cases (copies) detected by two kinds of techniques at the same time were comparatively analyzed. Results In 300 surgical specimens (pus and tissue), the overall positive rate of MTB detection by PCR fusion curve method (44.0%, 132/300) was significantly higher than that of MGIT 960 (18.0%, 54/300) (χ2=47.405, P=0.000). The positive rate of PCR melting curve nucleic acid detection in tissue samples (50.0% (75/150)) was significantly higher than that in pus samples (38.0%, (57/150)) (χ 2=4.383, P=0.048); while the positive rate of MGIT 960 in tissue samples (12.7% (19/150)) was significantly lower than that in pus samples (23.3% (35/150)) (χ 2=5.781, P=0.024). Further analysis of the positive rate of MGIT 960, fluorescent PCR and two combined techniques in etiological diagnosis of 150 patients was made (if one of the methods is positive, the patient woulde be judged pathogenic positive). The results showed that the positive rate of the former (30.7% (46/150)) was significantly lower than those of the latter two (66.7% (100/150) and 70.7% (106/150), respectively) (χ 2=38.908, 48.009; both P=0.000), no significant difference was found between the latter two (χ 2=0.558, P=0.455). The results of drug resistance of 40 pathogenic positive cases (copies) detected by two methods at the same time showed that the detection rates of isoniazid, rifampicin, ethambutol, streptomycin and levofloxacin by MGIT 960 and PCR melting curve method were 20.0% (8/40) and 17.5% (7/40), 17.5% (7/40) and 15.0% (6/40), 17.5% (7/40) and 17.5% (7/40), 17.5% (7/40) and 22.5% (9/40), 5.0% (2/40) and 7.5% (3/40), respectively, and the differences were not significant (χ 2=0.082, 0.092, 0.000, 0.313, 0.213, all P>0.05). Conclusion In tuberculous empyema patients, the overall positive rate of MTB detected by PCR melting curve method was significantly higher than that of MGIT 960 culture, and the positive rate of tissue samples was higher than that of pus samples; the detection rate of drug resistance was similar to that of MGIT 960 phenotype drug sensitivity test, which could quickly detect the etiology and drug resistance.

    Dynamic changes of lung function and hormone-assisted therapy in patients with tuberculous pleurisy
    RUAN Hong-yun, LI Qi, CHEN Xiao-you, DUAN Hong-fei, GUO Chao, CAO Min, LIANG Qing-tao, WANG Zhi-ru, YANG Yang, SUN Gui-xin, LI Hua, DENG Ling, SHAO Ling-ling, XING Wei-xiang, ZHANG Yun, YANG Xin-ting
    Chinese Journal of Antituberculosis. 2021, 43(1):  58-65.  doi:10.3969/j.issn.1000-6621.2021.01.012
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    Objective To investigate the dynamic changes of pulmonary function in patients with tuberculous pleurisy after chemotherapy with glucocorticoid. Methods All of 172 patients with tuberculous pleurisy admitted to Beijing Chest Hospital affiliated to Capital Medical University from May 2015 to May 2018 were retrospectively analyzed. The pulmonary ventilation, volume, diffusion function and respiratory muscle mechanics indexes of patients were tested for 4 times: before treatment, at the end of the 1st, 6th and 12th months of treatment. On the basis of anti-tuberculosis drug treatment regimen, patients were divided into two groups: 60 patients in the plus group (prednisone acetate +2H-R-Z-E/10H-R-E) and 112 patients in the non-plus group (2H-R-Z-E/10H-R-E).Pulmonary ventilation function of patients were tested with percentage of forced vital capacity values over the expected value (expected value of pulmonary function factory default value formula), percentage of forced expiratory volume in 1 second readings over the expected value, percentage of forced expiratory volume in 1 second readings versus a forced vital capacity values, percentage of forcibly exhale 75% total lung moment expiratory flow values over the expected value (FEF75% pred), percentage of the maximum values of the expected minute ventilation (MVV% pred);The measurement index of lung volume function were percentage of residual volume detected value over the estimated value, percentage of total lung detected value over the estimated value, and percentage of residual volume/total lung ratio over the estimated value.The measurement index of dispersion function were percentage of the detected lung dispersion amount over the predicted value and percentage of the detected lung dispersion rate in the corrected alveolar volume over the predicted value.The measurement indexes of respiratory muscle mechanics were percentage of airway resistance detected, percentage of peak expiratory flow detected and the measured value of peak inspiratory flow. Results (1)Before chemotherapy, patients with tuberculous pleurisy were mainly affected by restricted ventilation dysfunction (FVC (62.1±13.4) %, FEV1 (64.4±15.5) %, FEV1/FVC (87.0±11.1) %, MVV (65.7±21.1) %, FEF75 (61.6 (41.6,83.0) %, RV (111.3 (89.8,131.4) %, TLC (77.0±16.9) %, RV/TLC (146.9±35.9) %,DLCO (62.6±18.3) %, DLCO/VA (92.3±16.6) %, PEF (64.1±18.13) %, PIF (3.2 (2.3,4.1) %, Rtot 96.0 (69.3,118.9) %).(2) During the course of treatment, 80.2% (138/172), 75.0% (129/172), and 0.0% (0/0) of patients were tested as having FVC <80% at the end of 1st, 6th, and 12th months. At the end of the 6th month of treatment, up to 44.2% (76/172) of patients had DLCO <80%. (3) FEF75 for glucocorticoid plus group and non plus group patients before treatment, at 1, 6, 12 months of treatment were (68.7 (49.8,84.1)% and 60.7 (39.4, 80.7) %;87.1 (70.5, 94.4) % and 73.1 (51.9, 87.0) %; 80.1 (66.5, 111.9) % and 66.8 (59.9, 87.2) %;90.4 (55.3, 102.9) % and 78.4 (54.6,87.3) % respectively, improvements after treatment were not significant (Z values were -1.091, -0.111, -1.609, -1.171, all P values were >0.05). MVV% pred were (65.8±19.4) % and (65.5±18.6) %; (86.9±18.6) % and (79.5±18.7) %; (90.3±16.0) % and (86.3±16.0) %;(96.8±11.1) % and (87.3±19.8) %) respectively, the improvement were not significant too(t values were 1.043, 0.444, 0.708, 1.113, all P values were >0.05). Conclusion Patients with tuberculous pleurisy showed restrictive ventilation dysfunction and diffusion function decline before treatment and at the end of the first month of treatment. At the end of 6 months’ treatment, only ventilation function returned to normal. Dispersion function returned to normal at the end of 12 months’ treatment. Early adjuvant treatment of glucocorticoid had no significant effect on pulmonary function in patients with tuberculous pleurisy.

    A case of multisystemic disseminated infection caused by Mycobacterium abscess diagnostic and treatment process analysis
    ZHANG Kai-yi, LYU Zheng-xuan, LIU Yong-li, ZHANG Le, ZHU Jiang-chun, YU Ming-li
    Chinese Journal of Antituberculosis. 2021, 43(1):  66-71.  doi:10.3969/j.issn.1000-6621.2021.01.013
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    Objective To investigate the pathogenic characteristics of Mycobacterium abscess, helping clinicians to improve the awareness of the disease and the level of diagnosis and treatment. Methods The clinical data, diagnosis and treatment, as well as follow-up and prognosis of a multisystemic disseminated infection in a patient caused by Mycobacterium abscess admitted to the Third People’s Hospital of Kunming on June 9, 2018 were reviewed. Results The patient visited the People’s Hospital of Lancang County in July 2017 with the chief complaint of fever and cough for more than one month. Then, the patient was transferred to the People’s Hospital of Pu’er County because of two-week ineffective anti-pulmonary infection treatment for, and was treated with “tuberculosis” diagnostic anti-tuberculosis drugs until December, 2017. The symptoms of cough and fever were relieved. However, on December 20th, 2017, the patient was admitted to the Pu’er City People’s Hospital because that fever and cough suddenly worsened with chest tighness, and continued to be treated with anti-tuberculosis and anti-infective treatment based on the diagnosis of pulmonary tuberculosis complicated with pulmonary infection. One month later, the patient was transferred to an affiliated hospital of Kunming Medical University due to poor effect, however, the condition did not improve after treatment. On February 14, 2018, the patient returned to the original residence, and received intermittent anti-infection and symptomatic treatment in the outpatient clinic of the local hospital. On May 8, the patient was admitted to a tumor hospital in Yunnan Province due to the aggravation of the condition and the swollen right cervical lymph node. No malignant cells were detected in the pathological examination of the lymph node specimen, therefore, the possibility of “drug-resistant tuberculosis” was considered. On June 9, the patient was transferred to our hospital. After blood culture, lymph node pus culture, and 22 molecular diagnostic tests for mycobacterium in alveolar lavage fluid, Mycobacterium abscess was identified. After 40-day combination therapy of linezolid, moxifloxacin, clofazimine, amikacin and clarithromycin, the condition was improved. The patient discharged from our hospital, and the follow-up showed a good prognosis. Conclusion If repeatedly positive in acid-fast bacilli test was found in patients with suspected tuberculosis, and the effect of diagnostic anti-tuberculosis treatment was poor, in addition to considering the possibility of drug-resistant tuberculosis, new molecular biology tests should be activety performed to exclude NTM disease, to improve the diagnostic rate and cure rate.

    Analysis of drug resistance of tuberculosis patients and its influencing factors in Hangzhou from 2014 to 2018
    FAN Da-peng, YUE Yong-ning, ZHANG Yan, CHEN Yuan-yuan, BAO Zhi-jian, ZHU Min, CAI Long
    Chinese Journal of Antituberculosis. 2021, 43(1):  72-79.  doi:10.3969/j.issn.1000-6621.2021.01.014
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    Objective To analyze the characteristics and influencing factors of tuberculosis patients’ resistance to first-line anti-tuberculosis drugs in Hangzhou from 2014 to 2018, and to provide scientific basis for the prevention and treatment of drug-resistant tuberculosis in Hangzhou. Methods A total of 12851 active tuberculosis patients were collected from the permanent residents of Hangzhou who visited the Tuberculosis Diagnosis and Treatment Center of Integrated Chinese and Western Medicine Hospital of Zhejiang Province from 2014 to 2018. All of 3807 patients with positive Mycobacterium tuberculosis culture and comprehensive information of drug sensitivity test (“ drug susceptibility test ”) for first-line anti-tuberculosis drugs were enrolled. Through the National Tuberculosis Information Management System and the Tuberculosis Laboratory Information System to collect the sex, age, household registration, occupation, classification of treatment (initial and retreated), pulmonary cavity, case sources and current residence of the patients, Mycobacterium tuberculosis culture and drug susceptibility test results. Drug resistance characteristics and influencing factors of drug-resistant pulmonary tuberculosis patients in Hangzhou were studied by univariate and multi-factor logistic regression analysis. Results Of the 3807 strains, 907 strains (23.82%) were resistant to four first-line anti-tuberculosis drugs. The drug resistance sequence was isoniazid (18.57%, 707 cases), streptomycin (18.41%, 701cases), rifampicin (12.03%,458 cases) and ethambutol (6.41%,244 cases). The multidrug-resistance and polyresistance rates were 11.11% (423/3807) and 4.44% (169/3807). Of the tuberculosis patients in different years from 2014 to 2018, the drug resistance rates were 22.87% (185/809), 25.55% (198/775), 25.60% (181/707), 23.04% (188/816) and 22.14% (155/700), respectively, with no significant difference ($χ^{2}_{trend}$=4.275, P=0.370). The multidrug-resistance rates (11.12% (90/809), 13.16% (102/775), 11.88% (84/707), 11.40% (93/816) and 7.71% (54/700)) had statistically significant difference ( $χ^{2}_{trend}$=11.276, P=0.024). Multivariate logistic regression analysis showed that, compared to men and initial patients, women and retreated pulmonary tuberculosis patients were risk factors for drug resistance (OR (95%CI)=1.308(1.111-1.540), OR (95%CI)=4.281(3.498-5.238)). Compared to Xiasha District, patients living in the other six districts were more likely to develop drug resistance, Xiaoshan District and Fuyang District were at higher risk (OR (95%CI)=4.400(2.559-7.565), OR (95%CI)=3.803(2.037-7.098)).Compared with male, less than 40 years old and newly treated patients, female, over 40 years old and retreated patients were risk factors for multi-drug resistance (OR (95%CI)=1.724 (1.364-2.178); 40-year-old group: OR (95%CI)=3.418 (1.599-7.305), 60-year-old group: OR (95%CI)=3.885 (1.832-8.239); retreatment: OR (95%CI)=7.645 (5.984-9.766)). Conclusion The key to reducing the development and transmission of drug-resistant and multidrug-resistant tuberculosis in Hangzhou is to strengthen the management and treatment of patients aged over 40 years old, retreated, female, living in Xiaoshan and Fuyang District.

    Influencing factors of pulmonary tuberculosis diagnosis delay in Guangzhou, 2008—2018
    LIU Jian-xiong, DU Yu-hua, SHEN Hong-cheng, ZHANG Guang-chuan, WU Gui-feng, LAI Keng, LEI Yu, LI Tie-gang
    Chinese Journal of Antituberculosis. 2021, 43(1):  80-86.  doi:10.3969/j.issn.1000-6621.2021.01.015
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    Objective To analyze the trend and influencing factors of pulmonary tuberculosis diagnosis delay in Guangzhou from 2008 to 2018, and to provide scientific evidence for the development of prevention and control policy and measures. Methods Information of 125180 pulmonary tuberculosis cases in Guangzhou from 2008 to 2018 was collected from Tuberculosis Information Management System of China Information System for Disease Control and Prevention, including gender, age, ethnicity, occupation, cases source, cases classification and complication. Influencing factors of pulmonary tuberculosis diagnosis delay were analyzed by univariate and multivariate logistic regression. Results The median of pulmonary tuberculosis patient from seeking medical service to diagnosis was 5 (2, 15) days in Guangzhou from 2008 to 2018, and the rate of the diagnosis delay was 27.43% (34343/125180). Univariate analysis showed that diagnosis delay rates of aged 65-102 (29.70% (4610/15524)), ethnic HAN (27.50% (33829/123013)), occupation as teacher or doctor (33.22% (1320/3974)), health examination (37.86% (1017/2686)) were significantly higher than those aged 25-<45 (26.69% (13585/50894); χ 2=65.253, P<0.001), ethnic minorities (23.72% (514/2167); χ 2=15.291, P<0.001), worker/civilian worker (21.10% (4752/22520); χ 2=879.541, P<0.001), referrals (25.36% (14416/56835); χ 2=570.472, P<0.001), respectively. Multivariate logistic regression analysis showed those with the following characteristics were more likely to be diagnosis delayed: aged 25-<45, 45-<65, 65-102 (aged <25 as reference, OR (95%CI) values were 1.072 (1.033-1.110), 1.136 (1.090-1.184), 1.168 (1.105-1.235), respectively), ethnic HAN (minorities as reference, OR (95%CI)=1.155(1.044-1.278)), children/student, business services, teachers or doctors, farmers, resigned or retired, housekeeping or unemployment, others (worker/civilian worker as reference, OR (95%CI) values were 1.730 (1.617-1.851), 1.784 (1.683-1.890), 1.828 (1.698-1.968), 1.167 (1.111-1.227), 1.632 (1.535-1.736), 1.436 (1.378-1.497), 1.525 (1.462-1.590), respectively), health examination, contact screening, clinical consultation, recommendation, tracing (referrals as reference, OR (95%CI) values were 1.704 (1.572-1.848), 1.531 (1.227-1.910), 1.031 (1.003-1.060), 1.346 (1.192-1.520), 1.535(1.467-1.606), respectively). Conclusion Diagnosis delay of pulmonary tuberculosis cases appears to be increased year by year in Guangzhou from 2008 to 2018. It is necessary to pay more attention to the factors affecting the above diagnosis delay.

    Review Articles
    Progress in the treatment and management of tuberculosis complicated with diabetes
    YANG Min, FU Liang, DENG Guo-fang
    Chinese Journal of Antituberculosis. 2021, 43(1):  87-90.  doi:10.3969/j.issn.1000-6621.2021.01.016
    Abstract ( 421 )   HTML ( 17 )   PDF (856KB) ( 272 )   Save
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    It is estimated that the number of patients with diabetes mellitus (DM) may increase to 700 million by 2045 in the world, and about 16% of tuberculosis patients may have DM, so the double burden caused by tuberculosis complicated with diabetes mellitus (TB-DM) will become a major global public health problem. Diabetes (including type 1 and type 2) can increase the risk of getting active tuberculosis. Compared with the patients who only have tuberculosis, the patients with TB-DM have worse treatment outcomes. Therefore, the increasing incidence of diabetes will not only increase the risk of having tuberculosis, but also pose a serious challenge to the treatment and management of tuberculosis. In this article, the authors reviewed the following issues related to TB-DM: the two-way screening, interactions of the two diseases, treatment and management, and drug interactions, etc.

    Progress in diagnosis and treatment of latent tuberculosis infection
    LI Guo, PANG Xian-qiong, XU Hua, JING Ming-yan, FAN Pang-shuang, CHEN Shao-ping
    Chinese Journal of Antituberculosis. 2021, 43(1):  91-95.  doi:10.3969/j.issn.1000-6621.2021.01.017
    Abstract ( 876 )   HTML ( 54 )   PDF (879KB) ( 2476 )   Save
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    Latent tuberculosis infection (LTBI) is a status of persistent immune response to stimulation by Mycobacterium tuberculosis antigens. Because of the risk of developing active tuberculosis, LTBI has been paid more and more attentions worldwide. The screening and preventive treatment of LTBI is an important component in the comprehensive prevention and control program of tuberculosis. However, there is no direct diagnosis method and unified treatment regimen for LTBI. In addition to the two conventional methods using for LTBI screening, tuberculin skin test and interferon gamma release assays, a newly developed method of recombinant Mycobacterium tuberculosis fusion protein (EC) (The generic name in Chinese of this product determined by the Chinese Pharmacopoeia Committee is used. “EC” is the recombinant fusion protein of “early secretory antigenic target-6 (ESAT-6) and culture filtrate protein 10 (CFP-10)”) can also be used in China. Currently, the preventive treatment with single-drug isoniazid is the most widely used regimen, but the regimen with rifamycin has more obvious advantages due to the shorter treatment duration and higher treatment compliance. So far, there are relatively few studies in the field of LTBI in China, and the coverage rate of preventive treatment for LTBI is low. Researchers related to LTBI should be conducted actively to explore the preventive treatment regimen in line with national conditions.

    Research progress of clinical endpoints in clinical trials of novel antituberculosis agents
    DUAN Hong-fei, CHU Nai-hui
    Chinese Journal of Antituberculosis. 2021, 43(1):  96-99.  doi:10.3969/j.issn.1000-6621.2021.01.018
    Abstract ( 414 )   HTML ( 16 )   PDF (859KB) ( 218 )   Save
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    Bactericidal activity and sterilizing activity should be evaluated in clinical trials of novel antituberculosis agents. Early bactericidal activity and sputum culture conversion used to be main indicators for evaluating clinical responses in phase Ⅱ trials, while cure without relapse were frequently used as endpoint in phase Ⅲ trials. Recent studies showed that sputum culture conversion time, quantification of CT and PET-CT lesions and GeneXpert MTB/RIF threshold cycle could be used as surrogate endpoints of clinical trials.

    Short Articles
    Evaluation of the implementation effect of “mobile tuberculosis clinic” service in the prevention and control of tuberculosis in Changshan County, Zhejiang Province
    LIU Wen-feng, ZHOU Lin, XU Tian-liang, YI Huai-ming, WANG Yong, WANG Qian-xin
    Chinese Journal of Antituberculosis. 2021, 43(1):  100-102.  doi:10.3969/j.issn.1000-6621.2021.01.019
    Abstract ( 402 )   HTML ( 12 )   PDF (835KB) ( 167 )   Save
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    In this study, a descriptive study was used to compare the data of patient detection and treatment management in Changshan County in the four years before(2013-2016) (referred to as “before implementation”) and the three years after (2017-2019) (referred to as “after implementation”) the implementation of “mobile tuberculosis clinic” service. Chi-square test was used for count data comparison before and after implementation, with P<0.05 for the difference was statistically significant. The results showed that 146 patients and 263 times were served after the implementation. The registration rate of tuberculosis patients was decreased from 118.31/100000 (1144/966944) to 99.25/100000 (746/751611), and the difference was statistically significant (χ 2=13.54, P=0.000). The cure rate of pathogenic positive patients increased from 87.47% (363/415) to 94.12% (336/357), with statistically significant difference (χ 2=9.91, P=0.002). The completion rate of treatment for patients with negative etiology increased from 88.89% (648/729) to 93.83% (365/389), with a statistically significant difference (χ 2=7.28, P=0.007). The treatment success rate of tuberculosis patients who interrupted treatment increased from 52.14% (122/234) to 93.15% (136/146), with statistically significant difference (χ 2=69.38, P=0.000). Conclusion After the implementation of “mobile tuberculosis clinic” service, the quality of tuberculosis patient management in Changshan County has been improved, which provides the basis and reference for further improving the management mode of tuberculosis prevention and treatment.

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

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    China Association for Science and Technology
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