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    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
    Abstract2011)   HTML42)    PDF(pc) (907KB)(447)       Save

    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.

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    Efficacy and safety of recombinant Mycobacterium tuberculosis fusion proteins (EC) for the diagnosis of Mycobacterium tuberculosis infection: A system review
    Cheng Xiao, Chen Zhe, Jiao Xuefeng, Yang Nan, Diao Sha, Ni Xiaofeng, Liu Zheng, He Siyi, Zeng Linan, Wan Chaomin, Kang Deying, Wu Bin, Ying Binwu, Zhang Hui, Zhao Rongsheng, Zhang Lingli
    Chinese Journal of Antituberculosis    2022, 44 (9): 917-926.   DOI: 10.19982/j.issn.1000-6621.20220253
    Abstract1449)   HTML42)    PDF(pc) (1379KB)(381)       Save

    Objective: Compared with purified protein derivative of tuberculin (TB-PPD), to systematically evaluate the efficacy and safety of recombinant Mycobacterium tuberculosis fusion protein (EC) in the diagnosis of Mycobacterium tuberculosis (MTB) infection. Methods: Data were searched from the clinical guideline database, biomedical literature database, official websites of health administrative departments and industry associations, and official websites of adverse reaction monitoring. The retrieval time is from the time of building the database to February 2022. English search terms were recombinant Mycobacterium tuberculosis fusion protein and CFP10/ESAT6; Chinese search terms were recombinant Mycobacterium tuberculosis fusion protein, Yika, and CFP10/ESAT6. Guidelines, consensuses, group standards, systematic reviews, and original studies on the efficacy and safety of recombinant Mycobacterium tuberculosis fusion protein (EC) and TB-PPD in diagnosing MTB infection were collected. Two investigators independently screened literature, extracted data, and assessed the risk of bias of included studies. Meta-analysis or descriptive analysis were used according to the size of heterogeneity. Results: Two guidelines, three expert consensus papers, and two group standards were included, and all presented that both recombinant Mycobacterium tuberculosis fusion protein (EC) and TB-PPD could be used for the detection of MTB infection and tuberculosis. One systematic review was included, and the results showed that the recombinant Mycobacterium tuberculosis fusion protein (EC) skin test recruited a total of 887 participants, with the sensitivity of 86.06% (95%CI: 82.39%-89.07%). The four original studies included were randomized controlled trials. The effectiveness meta-analysis showed that, regardless of the population, the sensitivity (89.3% vs. 90.4%) and negative likelihood ratio (0.177 vs. 0.220) of recombinant Mycobacterium tuberculosis fusion protein (EC) and TB-PPD were not significantly different. The specificity (85.5% vs. 47.3%), diagnostic odds ratio (42.238 vs. 8.040), positive likelihood ratio (6.048 vs. 1.710), positive predictive value (66.0% vs. 35.1%) and negative predictive value (96.2% vs. 94.0%) of recombinant Mycobacterium tuberculosis fusion protein (EC) were significantly better than those of TB-PPD. The safety results showed that the adverse events of recombinant Mycobacterium tuberculosis fusion protein (EC) and TB-PPD were just local itching and pain, and no serious adverse events occurred. Conclusion: Recombinant Mycobacterium tuberculosis fusion protein (EC) can be used for the diagnosis of MTB infection and auxiliary diagnosis of tuberculosis, and has better efficacy when compared with TB-PPD.

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    Meta analysis of the differences between BCG-PPD and TB-PPD in tuberculosis screening
    Ding Xiaojuan, Wang Dan, Zhang Yaozhi, He Jianqing
    Chinese Journal of Antituberculosis    2022, 44 (10): 1096-1099.   DOI: 10.19982/j.issn.1000-6621.20220156
    Abstract1130)   HTML21)    PDF(pc) (1417KB)(250)       Save

    To investigate the differences between pure protein derivative of BCG (BCG-PPD) and pure protein derivative of tuberculin (TB-PPD) in tuberculosis screening. Relevant literatures published from the establishment of the databases to February 2022 were searched from PubMed, Embase, Medline, Cochrane Library, CNKI and Wanfang. Open Meta Analyst software was used for meta-analysis of the included literatures. Cochrane Risk of Bias Assessment tool with Rev Man 5.3 software was used to evaluate the quality of the literature. Finally, 7 articles were included, with a total of 36131 participants, including 18314 participants in BCG-PPD group and 17817 participants in TB-PPD group. Dichotomous random effect model was used to analyzed. The combined OR (95%CI) value was 2.072 (1.683-2.550), I2=78.73%, P<0.001, indicating high heterogeneity, and the source of heterogeneity should be further analyzed. The results of subgroup analysis showed that the OR (95%CI) value of students and newborns was 2.393 (2.132-2.686), I2=50.15%, P=0.091, and I2 value decreased significantly. The OR (95%CI) value of tuberculosis patients in the subgroup was 0.481 (0.236-0.978), I2=0, P=0.043, and the fixed-effect model was used. Differences in the positive detection rate of TB-PPD and BCG-PPD in different populations were found. The positive detection rate of BCG-PPD is higher than that of TB-PPD in students and neonates, and the positive detection rate of TB-PPD was higher than that of BCG-PPD in tuberculosis patients.

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    Analysis on the epidemic situation of pulmonary tuberculosis in schools in China from 2004 to 2021
    Chen Hui, Zhang Canyou, Zhang Hui, Cheng Jun, Li Tao
    Chinese Journal of Antituberculosis    2022, 44 (8): 768-776.   DOI: 10.19982/j.issn.1000-6621.20220200
    Abstract1115)   HTML94)    PDF(pc) (2813KB)(514)       Save

    Objective: To investigate the epidemic trend of pulmonary tuberculosis (PTB) of students and staff in China from 2004 to 2021. Methods: The reported data of PTB in students and staff (excluding Taiwan, Hongkong and Macao) from 2004 to 2021 were collected from Infectious diseases surveillance system and China statistical yearbook, and the trend of epidemic situation in schools was analyzed. Results: From 2004 to 2021, a total of 908171 student patients with PTB were reported, with the reported incidence of 19.26/100000, while 112336 staff patients with PTB were reported with the reported incidence of 34.12/100000. From 2008 to 2019, the reported incidence rates of PTB among students and staff both showed the downward trend (average annual percent change=―3.41% and ―8.22%, Z=―2.005 and ―6.626, P=0.045 and <0.001). Eighteen provinces showed significantly decreasing trends in incidence among students, and eleven provinces showed stable trends. However, two provinces (Tibet and Qinghai) showed significantly increasing trends. Conclusion: The PTB reported incidence in schools in China was decreasing, but incidences of Tibet and Qinghai were on the rise. PTB prevention and control in schools has achieved positive effects. It is still necessary to continue to strengthen the prevention and control of PTB in schools, and more attention should be paid to key areas and schools.

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    CT imaging of 56 cases of epididymal tuberculosis
    Li Xiang, Ma Zhongxu, Fu Xuwen, Qi Min, Xu Yanling, Shen Lingjun
    Chinese Journal of Antituberculosis    2022, 44 (10): 1100-1103.   DOI: 10.19982/j.issn.1000-6621.20220208
    Abstract1057)   HTML10)    PDF(pc) (1064KB)(156)       Save

    To understand the CT imaging features of epididymal tuberculosis, the author analyzed 56 patients with epididymal tuberculosis admitted to Kunming Third People’s Hospital from September 1, 2020 to October 31, 2021, who were diagnosed with pathology, bacteriology or effective with anti-tuberculosis treatment.The results revealed the median age of 56 patients with epididymal tuberculosis was found to be 42 years old, and 37 cases (66.1%) had symptoms of scrotal swelling and pain. Among them, 9 cases (16.1%) were combined with scrotal skin sinus tract formation. The number of cases with combined pulmonary tuberculosis, renal tuberculosis, syringomyelia and testicular involvement were 29 (51.8%), 26 (46.4%), 24 (42.9%) and 15 (26.8%).CT showed the epididymis was thickened in 56 cases (100.0%), multiple lesions in 34 cases (60.7%).The epididymis was involved unilaterally in 32 cases (57.1%), and the epididymis was calcified in 8 cases (14.3%). The number of cases with only nodular enhancement, only rim enhancement and both were 23 (41.1%), 19 (33.9%) and 14 (25.0%), respectively, on CT-enhanced scans of epididymal lesions in the portal vein phase. It is believed that patients with epididymal tuberculosis mostly have scrotal swelling and pain, and can be combined with pulmonary and renal tuberculosis. CT scans mostly show unilateral epididymal involvement with multiple lesions and nodular or rim enhancement on enhancement CT scans, which have certain CT imaging characteristics.

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    Progress in diagnosis and treatment of Mycobacterium avium-intracellular complex vertebral osteomyelitis
    Zhou Weidong, Zhang Zhengdong, Lin Mei, Li Tongxia
    Chinese Journal of Antituberculosis    2023, 45 (4): 420-425.   DOI: 10.19982/j.issn.1000-6621.20230020
    Abstract956)   HTML154)    PDF(pc) (779KB)(260)       Save

    In recent years, more and more reports have been reported about the spinal infection of Mycobacterium avium-intracellular complex (MAC) group, and more cases of clinical misdiagnosis and mistreatment have been reported. The treatment effect of this disease is poor. This paper reviews the epidemiology and susceptibility factors of MAC vertebral osteomyelitis, the clinical manifestations, imaging examination and laboratory examination, and analyzes the causes of misdiagnosis and unsatisfactory therapeutic effect, so as to help clinicians understand more about MAC spinal infection, and promote the standardized diagnosis and treatment of MAC vertebral osteomyelitis.

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    Expert consensus on diagnosis and treatment of latent tuberculosis infection in patients with rheumatic diseases
    National Clinical Research Centre for Infectious Disease/The Third People’s Hospital of Shenzhen, Peking University Shenzhen Hospital, Peking Union Medical College Hospital of Chinese Academy of Medical Sciences, Chinese Antituberculosis Association, Editorial Board of Chinese Journal of Antituberculosis, Shenzhen Key Laboratory of Inflammatory and Immune Diseases
    Chinese Journal of Antituberculosis    2022, 44 (9): 869-879.   DOI: 10.19982/j.issn.1000-6621.20220225
    Abstract912)   HTML61)    PDF(pc) (1599KB)(792)       Save

    Rheumatic diseases are autoimmune diseases that occur when an individual’s immune system mistakenly attacks healthy tissues, and are often treated with glucocorticoids, immunosuppressants, biological agents, and small-molecule targeted drugs, etc., which can lead to an increased risk of other autoimmune dysfunctions in patients and the activation of latent tuberculosis infection (LTBI). Therefore, LTBI screening in clinical is essential for patients with rheumatic diseases who meet the screening criteria. This requires greater collaboration and awareness between rheumatologists and tuberculosis physicians, to conduct scientific assessment for patients with rheumatic diseases who need LTBI screening, and to develop preventive treatment guidelines to prevent patients with rheumatic diseases from developing active tuberculosis after LTBI. Therefore, the National Clinical Research Centre for Infectious Disease/The Third People’s Hospital of Shenzhen, Peking University Shenzhen Hospital, Peking Union Medical College Hospital of Chinese Academy of Medical Sciences, Chinese Antituberculosis Association, Editorial Board of Chinese Journal of Antituberculosis and Shenzhen Key Laboratory of Inflammatory and Immune Diseases joint effort in the publication of an expert consensus on the diagnosis and treatment of LTBI in patients with rheumatic diseases. This consensus is based on the epidemiology, evidence-based medicine, and clinical research of rheumatic diseases complicated with LTBI, and has been discussed for many times and reached consensus. It can serve as a reference.

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    Interpretation of WHO consolidated guidelines on tuberculosis, Module 4: treatment-drug-resistant tuberculosis treatment, 2022 update
    Fu Liang, Ren Tantan, Zhang Peize, Lu Shuihua
    Chinese Journal of Antituberculosis    2023, 45 (4): 336-348.   DOI: 10.19982/j.issn.1000-6621.20220523
    Abstract909)   HTML80)    PDF(pc) (1104KB)(704)       Save

    World Health Organization (WHO) published the WHO consolidated guidelines on tuberculosis, Module 4: treatment-drug-resistant tuberculosis treatment, 2022 update on February 15, 2022. The author introduced the main points of the updated guidelines, including the recommendations on the treatment of drug-resistant tuberculosis (focusing on a new short-term plan), management, patient care, and treatment monitoring, and discussed the feasibility of the guidelines in clinical practice and future research directions in China.

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    Analysis of therapeutic effects and factors affecting treatment outcomes of Mycobacterium abscessus subspecies abscessus pulmonary disease for 6 months
    Bao Shengjuan, Shao Lingling, Wang Jing, Han Xiqin, Huang Hairong, Duan Hongfei
    Chinese Journal of Antituberculosis    2023, 45 (4): 349-354.   DOI: 10.19982/j.issn.1000-6621.20220522
    Abstract894)   HTML32)    PDF(pc) (774KB)(230)       Save

    Objective: To assess the efficacy of different antibiotics combined on Mycobacterium abscessus subspecies abscessus pulmonary disease (M.abscessus-PD) and analyze the influencing factors of treatment outcomes for 6 months. Methods: Sixty-six patients in Beijing Chest Hospital, Capital Medical University diagnosed with M.abscessus-PD were enro1led prospectively from January 1st, 2016 to October 1st, 2022. Clinical information of the patients were collected, including gender, age, body mass index, clinical manifestations, history of past illness and anti-tuberculosis treatment, imaging examinations, laboratory examinations and medications. The factors influencing treatment outcomes of M.abscessus-PD for 6 months among different therapicregimens was compared. Results: After 6 months of treatment, 32 (48.5%) achieved sputum culture conversion and 34 (51.5%) didn’t among the 66 patients. The result shows that the 6-month sputum culture conversion rate of azithromycin users (57.4%, 27/47) was higher than clarithromycin users (26.3%, 5/19), with statistically significant (χ2=5.250,P=0.022). In 24 cases (36.4%, 24/66) treated with imipenem, 17 (70.8%, 17/24) achieved 6 months sputum culture conversion, which was higher than that of non-imipenem (35.7%, 15/42), with statistically significant difference (χ2=7.542, P=0.006). The efficacy of multidrug therapy regimen showed that macrolide combined with amikacin, imipenem, linezolid and clofazimine achieved 68.4% (13/19) culture conversion rate after 6 months. Multivariate analysis shows that patients treated with macrolide combined with imipenem were more likely to achieve sputum culture conversion within 6 months (OR (95%CI)=0.229 (0.077-0.676)). Conclusion: In the initial stage of treatment, at least 4 weeks of injection use (amikacin and imipenem), and the combination of macrolides with amikacin, clofazimine, and linezolid in the continued treatment, may have good curative effect on M.abscessus-PD.

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    Research status of drug resistance of antituberculosis drugs bedaquiline and clofazimine
    Shang Yuanyuan, Nie Wenjuan, Huang Hairong, Chu Naihui
    Chinese Journal of Antituberculosis    2023, 45 (1): 116-122.   DOI: 10.19982/j.issn.1000-6621.20220292
    Abstract872)   HTML24)    PDF(pc) (815KB)(267)       Save

    The emergence of multidrug-/rifampicin-resistant tuberculosis (MDR/RR-TB) and extensively drug-resistant tuberculosis (XDR-TB) poses a huge threat to tuberculosis (TB) control worldwide. Due to the lack of effective drugs, the success rate for MDR-TB patients was only 59%, and less than 50% for XDR-TB patients. In recent years, the application of the new anti-TB drug bedaquiline (Bdq) and the old drug clofazimine (Cfz) in patients with MDR/RR-TB and XDR-TB can significantly improve the treatment outcomes of patients. Both drugs work by impairing energy metabolism of mycobacterium and are still used in combination by clinicians in clinical care despite cross-resistance. Therefore, in the process of clinical application, attention should be paid not only to the adverse drug reactions, but also to the drug resistance of Bdq and Cfz. The author aims to summarize the mechanisms associated with drug resistance of Bdq and Cfz, the emergence of drug resistance of Bdq and Cfz in clinical treatment, and to discuss how to delay the accumulation and spread of acquired drug resistance of Bdq and Cfz.

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    Evidence-based guidelines for active screening of pulmonary tuberculosis in Chinese communities
    Tuberculosis Control Branch of Chinese Antituberculosis Association, Elderly Tuberculosis Control Branch of Chinese Antituberculosis Association, Editorial Board of Chinese Journal of Antituberculosis
    Chinese Journal of Antituberculosis    2022, 44 (10): 987-997.   DOI: 10.19982/j.issn.1000-6621.20220321
    Abstract868)   HTML73)    PDF(pc) (1257KB)(642)       Save

    To achieve the goals of the End Tuberculosis Strategy, stronger measures are urgently needed to improve the detection and treatment of tuberculosis, and active screening is an important part of achieving the goals to ensure early diagnosis of tuberculosis. Tuberculosis Control Branch and Elderly Tuberculosis Control Branch of Chinese Antituberculosis Association, and Editorial Board of Chinese Journal of Antituberculosis organized experts to develop the Chinese guidelines for active screening of pulmonary tuberculosis in communities based on the evidence and recommendations of the latest World Health Organization guidelines in 2021. The guidelines also supplemented follow-up newly published literature and relevant literature and research evidence in China. The guidelines systematically summarized the characteristics of active screening techniques such as symptom screening, chest imaging and C-reactive protein, and proposed to conduct pulmonary tuberculosis active screening among close contacts of pulmonary tuberculosis patients, former tuberculosis patients, HIV/AIDS patients, the elderly, diabetic patients, and the general population in epidemic areas. It would provide a basis for the country and localities to improve and optimize the active tuberculosis screening strategy of key populations.

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    Expert consensus on the diagnosis and treatment of Brucella spondylitis
    The Joint Tuberculosis Professional Branch of Chinese Antituberculosis Association, The Western China Bone Tuberculosis Union, The North China Union of Bone Tuberculosis
    Chinese Journal of Antituberculosis    2022, 44 (6): 531-538.   DOI: 10.19982/j.issn.1000-6621.20220138
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    Brucellosis spondylitis has been increasing in recent years, because of the low early diagnosis rate, there is often the possibility of misdiagnosis and mistreatment, resulting in the difficulty of later treatment and disability of patients. In order to standardize the diagnosis and treatment process of patients with Brucella spondylitis, help more specialist to get the treatment details of such disease, and have evidence in the treatment, the Expert consensus on the diagnosis and treatment of Brucella spondylitis was jointly formulated by the Joint Tuberculosis Professional Branch of Chinese Antituberculosis Association, the Western China Bone Tuberculosis Union, the North China Union of Bone Tuberculosis. This consensus starts from the epidemiological characteristics of Brucella spondylitis, deeply expounds and discusses its common clinical manifestations, laboratory examination and diagnostic criteria, therapeutic drugs, surgical treatment methods, prognosis and so on.

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    Incidence and risk factors of catastrophic expenditure for multidrug-resistant tuberculosis in Guangdong Province
    Yu Meiling, Liang Hongdi, Zhou Fangjing, Chen Liang, Wu Ya, Gao Lijie, Wen Wenpei, Zhu Sui, Wu Huizhong
    Chinese Journal of Antituberculosis    2022, 44 (12): 1262-1272.   DOI: 10.19982/j.issn.1000-6621.20220235
    Abstract803)   HTML16)    PDF(pc) (1153KB)(208)       Save

    Objective: To investigate the incidence and risk factors of catastrophic expenditure among patients with multidrug-resistant tuberculosis (MDR-TB) in Guangdong Province. Methods: The MDR-TB patients diagnosed in 11 designated medical institutions in 9 prefecture-level cities in Guangdong Province from 2018 to 2019 were selected. Questionnaires for surveying basic characteristics, patients’ disease and medical visit history, financial burden, and health insurance policies of medical institutions, individuals and cities were collected. A two-level logistic regression model was used to explore the risk factors of catastrophic expenditure in MDR-TB patients. Results: A total of 398 patients were included in this study. The median direct medical expenses was 51100 (22600, 98200) yuan; the median direct non-medical expenses was 14600 (7100, 33300) yuan; the median indirect costs was 5100 (3100, 7300) yuan; the median total costs was 84300 (42900, 147600) yuan; and the median total out-of-pocket expenses was 58400 (29700, 111800) per case. A total of 259 MDR-TB patients suffered with catastrophic expenditure, with an incidence of 65.08%. The two-level logistic regression model showed that the risk of catastrophic expenditure for households with debt was 2.57 times of that for households without debt (95%CI: 1.43-4.62). The incidence of catastrophic expenditure increased gradually with the patients’ hospitalization length, and the incidence for patients hospitalized for 1 month and ≥2 months were 4.38 (95%CI:2.38-8.06) times and 31.37 (95%CI: 11.09-88.74) times of that for non-hospitalized patients. Conclusion: A high incidence of catastrophic expenditure for MDR-TB patients was found in Guangdong Province. Debt and length of hospitalization were the risk factors for incidence of catastrophic expenditure. Multiple measures should be taken to reduce the incidence of catastrophic expenditure in MDR-TB patients.

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    Expert consensus on clinical differential diagnosis and treatment of intrathoracic sarcoidosis and pulmonary tuberculosis under the background of tuberculosis epidemic
    Multidisciplinary Diagnosis and Treatment Committee of the Chinese Anti-tuberculosis Association, Editorial Board of Chinese Journal of Antituberculosis, Clinical Multidisciplinary Cooperation Working Group of the Radiology Branch of the Chinese Medical Association
    Chinese Journal of Antituberculosis    2022, 44 (12): 1227-1241.   DOI: 10.19982/j.issn.1000-6621.20220361
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    Common pathological features of both intrathoracic sarcoidosis and pulmonary tuberculosis are epithelioid granulomas, and the clinical manifestations of the two diseases are similar to some extent, which may lead to misdiagnosis and mistreatment. It is necessary to establish standardized identification and management procedures for the two diseases, especially in tuberculosis endemic areas. Therefore, the Multidisciplinary Diagnosis and Treatment Committee of the Chinese Antituberculosis Association, Editorial Board of Chinese Journal of Antituberculosis and Clinical Multidisciplinary Cooperation Working Group of the Radiology Branch of the Chinese Medical Association organized multidisciplinary experts to develop an Expert consensus on clinical differential diagnosis and treatment of intrathoracic sarcoidosis and pulmonary tuberculosis under the background of tuberculosis epidemic after combining clinical experiences and summarizing worldwide research results. The consensus provides the differentiation of the two diseases in terms of clinical manifestations, imaging characteristics, bronchoscopy, pathological and etiological examinations. It also proposes a specific framework of confirming the diagnosis of challenging cases through multidisciplinary cooperation with specific procedures and steps. Meanwhile, target population for the screening of potential tuberculosis infection amongst sarcoidosis patients are determined. Additionally, recommendations are given on the treatment and management of latent tuberculosis infection, so as to provide accurate treatment and improve the prognosis of patients.

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    Expert consensus on ultrasound diagnosis, classification and interventional therapy of tuberculous pleurisy (2022 Edition)
    Ultrasound Professional Committee of Tuberculosis Branch of Chinese Medical Association, Interventional Ultrasound Professional Committee of Interventional Physician Branch of Chinese Medical Doctor Association Danwei
    Chinese Journal of Antituberculosis    2022, 44 (9): 880-897.   DOI: 10.19982/j.issn.1000-6621.20220257
    Abstract783)   HTML62)    PDF(pc) (11822KB)(713)       Save

    Tuberculous pleurisy is pleural inflammation caused by delayed hypersensitivity response when Mycobacterium tuberculosis invades the pleural cavity. It is a kind of pulmonary tuberculosis, which is considered to be one of the main causes of exudative pleural effusion in clinic. Without timely and effective diagnosis or treatment, tuberculous pleurisy can lead to severe ventilatory dysfunction and pulmonary function damage. At present, chest ultrasound is the preferred imaging method for the diagnosis and evaluation of tuberculous pleurisy. One of the diagnostic criteria of tuberculous pleurisy is to obtain positive etiology or positive histopathology through ultrasound-guided pleural puncture biopsy. Classification and corresponding treatment of tuberculous pleurisy according to different ultrasound images can effectively improve the cure rate, reduce adverse complications and reduce the recurrence rate. Due to the differences in examination methods, diagnostic results and treatment between different hospitals and examiners, it is not conducive to the comprehensive management of patients with tuberculous pleurisy. Therefore, this consensus introduces ultrasound-guided pleural puncture biopsy, ultrasound classification of tuberculous pleurisy and clinical treatment of different types, aiming to provide precise, standardized and rational ultrasound diagnosis and treatment for tuberculous pleurisy patients at different stages.

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    Investigation and analysis of a school pulmonary tuberculosis aggregated epidemic in Chongqing
    Fan Jun, Su Qian, Chen Jian, Yu Ya, Wang Qingya, Zhang Ting, Cheng Jun, Feng Xinyu
    Chinese Journal of Antituberculosis    2022, 44 (8): 792-796.   DOI: 10.19982/j.issn.1000-6621.20220099
    Abstract779)   HTML39)    PDF(pc) (1420KB)(279)       Save

    Objective: To investigate and analyze a school aggregated pulmonary tuberculosis epidemic in Chongqing and to provide thoughts and suggestions for the prevention and control of tuberculosis in schools. Methods: Descriptive epidemiological methods were used to investigate and analyze a school pulmonary tuberculosis epidemic in Chongqing from December 2020 to May 2021. Pulmonary tuberculosis screening was conducted with symptom screening, tuberculin skin test (TST) and chest X-ray, and epidemiological investigation of close contacts was also carried out. Results: After confirming 1 case of pulmonary tuberculosis with positive etiology (the index case), 8 active pulmonary tuberculosis patients and 42 latent tuberculosis infection patients were detected after 4 close contacts screening and 1 follow-up screening. All the 8 pulmonary tuberculosis students were concentrated in the class of the indicator case, with the incidence rate of 12.7% (8/63) and the etiological positive rate of 2/8. There were 34 latent tuberculosis infection patients, the latent infection rate of pulmonary tuberculosis was 61.8% (34/55), and all of them had completed preventive treatment. The incidence risk and infection risk of students in the class of the indicator case (RR=27.6, 95%CI: 13.5-56.4) were higher than those in other classes. Among the 8 cases of pulmonary tuberculosis in school, 6 were male, and 2 were female. The age distribution of cases was most in the 15-year old group (6 cases). Due to the poor quality of the chest X-ray of the first contact screening, the student patients were not found in time, resulting in the subsequent diagnosis of 3 patients. Two latent infected students were transformed into pulmonary tuberculosis patients during preventive treatment due to non-standard medication. Conclusion: The clustering of the epidemic was obvious. The low quality of screening and the failure to complete preventive treatment were important reasons for the spread of the epidemic. Therefore, when dealing with the school pulmonary tuberculosis epidemic, the quality of screening should be improved, the window period should be fully considered according to the epidemiological survey, and the standardization and completion rate of preventive treatment should be ensured.

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    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
    Abstract773)   HTML26)    PDF(pc) (843KB)(176)       Save
    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.
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    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
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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.

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    Landscape and prospect of tuberculosis vaccine research and development in China
    Zhang Mengxian, Wang Ni, Huang Fei, Zhou Liping, Zhao Yanlin
    Chinese Journal of Antituberculosis    2023, 45 (2): 125-129.   DOI: 10.19982/j.issn.1000-6621.20220267
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    BCG is currently only available vaccine for tuberculosis (TB) at global level. It can mainly reduce the occurrence of tuberculous meningitis and disseminated tuberculosis in children, however, the protection effect on adolescents and adults is limited. In order to achieve “The End TB Strategy”, it is essential to research and develop novel tuberculosis vaccines that are effective for all ages. Encouraging research and development of new tuberculosis vaccines and participating in multi-regional clinical trials, which will help stimulate internal vitality, shorten the research and development cycle of TB vaccine, and accelerate the marketing and promotion speed. The author sorted out the current status of TB vaccine which are in clinic trial, the relevant supportive policies, the basic requirements of the multi-regional clinical trials and TB vaccine landscape.

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    Strive for excellence with an emphasis on fundamentals and innovations: interpretation of the WHO Global Tuberculosis Report 2022
    Shu Wei, Liu Yuhong
    Chinese Journal of Antituberculosis    2023, 45 (5): 454-457.   DOI: 10.19982/j.issn.1000-6621.20230102
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    Tuberculosis (TB) prevention and control work needs innovative research and development to accelerate the implementation of the World Health Organization (WHO) End TB Strategy. On 27th October 2022, WHO released the Global Tuberculosis Report 2022, updating the latest progress of global TB research and innovation. This paper reviews the key achievements in the areas of research and innovation for new diagnostics, drugs and regimens as well as vaccines introduced in the report, and discusses some of China’s indigenous progresses in related areas. This paper aims to make China’s TB professionals better informed about the latest research development in TB prevention and control around the globe, fostering indigenous TB innovation efforts with greater originality.

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    Structure and function of lipoarabinomannan and its application in tuberculosis diagnosis
    Tang Minghui, Li Hao
    Chinese Journal of Antituberculosis    2022, 44 (11): 1205-1212.   DOI: 10.19982/j.issn.1000-6621.20220276
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    Tuberculosis is a significant zoonosis caused by Mycobacterium tuberculosis complex. Mannose-capped-lipoarabinomannan (ManLAM), an essential glycolipid component of the cell wall, has immunomodulatory effects and is recognized by intrinsic cells and adaptive cells. ManLAM in body fluids is a biomarker with good specificity for the diagnosis of tuberculosis, and has the potential ability to differentiate the latent tuberculosis infection and active tuberculosis. It also plays a certain role in detecting tuberculosis patients whose sputum could not be obtained. This article mainly introduces the structure, biosynthesis, and the related antibodies of ManLAM and summarizes the research progress in the diagnosis of tuberculosis, in order to provide reference for the development of tuberculosis diagnostic technology.

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    Interpretation of the Operation specification of Mycobacterium tuberculosis recombinant protein skin test
    Guo Tonglei, Cao Xuefang, Gao Lei
    Chinese Journal of Antituberculosis    2023, 45 (2): 130-133.   DOI: 10.19982/j.issn.1000-6621.20220407
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    Operation specification of Mycobacterium tuberculosis recombinant protein skin test (T/CHATA 020—2022), one of the social organization standards issued by the Chinese Antituberculosis association, was put into force since February 24, 2022. The standard specifies the scope of application, contraindications, operating procedures, observation and treatment principles of common adverse reactions, and quality assurance of the Mycobacterium tuberculosis recombinant protein skin test. To help medical staff better understand and normatively apply the Mycobacterium tuberculosis recombinant protein skin test, this article explains the drafting process and major points of the content of this standard.

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    Prevalence of drug resistant tuberculosis in China: data from national drug resistant tuberculosis survey in 2018
    Wang Shengfen, Zhou Yang, Ou Xichao, Xia Hui, Zhao Bing, Song Yuanyuan, Zheng Yang, Du Xin, Zhao Yanlin
    Chinese Journal of Antituberculosis    2022, 44 (11): 1141-1147.   DOI: 10.19982/j.issn.1000-6621.20220268
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    Objective: The aim of this study is to analyze prevalence of drug resistant tuberculosis in China in 2018, and provide evidence for formulating policies about treatment and prevention of tuberculosis. Methods: The 70 clusters selected by the National Drug Resistant Tuberculosis Baseline Survey during 2007—2008 were used as survey sites, newly diagnosed smear positive pulmonary tuberculosis patients were recruited in this study in 2018. Standardized questionnaire was used to collect socio-demographic features, disease histories and medical treatment histories of these patients. Sputum samples were collected from presumptive pulmonary tuberculosis patients visiting the surveysites for smear and culture. Positive isolates were transferred to provincial or municipal Centers for Disease Control and Prevention or tuberculosis institutes for bacteria identification and drug susceptibility test. Survey procedures of SAS 9.4 software were used to calculate the weighted drug resistant prevalence considering the complex sampling design and sampling weight. Logistic regression model was used to assess changes in prevalence. Results: 3820 new smear positive pulmonary tuberculosis patients and 643 retreated smear positive patients were included in the survey. Prevalence of rifampicin resistant tuberculosis (RR-TB) was 5.08% (95%CI: 4.39%-5.77%) and 23.31% (95%CI: 20.14%-26.48%) in new cases and retreated patients, respectively. Multidrug resistant tuberculosis (MDR-TB) accounted for 3.52% (95%CI: 2.94%-4.11%) of new cases, and 18.01% (95%CI: 15.36%-20.67%) of retreated patients. Compared with the 2007—2008 baseline survey, the RR-TB prevalence in new cases (OR(95%CI): 0.71 (0.58-0.87);P<0.001) and retreated patients (OR(95%CI): 0.53 (0.41-0.68);P<0.001) decreased significantly. The MDR-TB prevalence of new cases (OR(95%CI): 0.53 (0.42-0.67);P<0.001) and retreated patients (OR(95%CI): 0.47 (0.36-0.61);P<0.001) also decreased significantly. It was estimated that the numbers of RR-TB patients were 12662 (95%CI: 10942-14382) and 8156 (95%CI: 7047-9265) among bacteriologically confirmed new cases and retreated patients nationwide in 2018. Conclusion: The prevalence of RR-TB and MDR-TB among new cases and retreated patients in 2018 decreased significantly while compared with that of the 2007—2008 baseline survey. However, due to the large number of population, China is still a country with high burden of drug resistant tuberculosis. It is suggested that comprehensive measures should be taken to reduce the emergence and spread of drug resistant tuberculosis, and then to reduce the overall burden of drug resistant tuberculosis in China.

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    Determination of the critical value of prophylactic medication in school population for the diagnosis of latent tuberculosis infection by tuberculin skin test
    Lu Peng, Wang Rong, Liu Jiasong, Liu Qiao, Ding Xiaoyan, Lu Wei, Zhu Limei
    Chinese Journal of Antituberculosis    2022, 44 (8): 797-801.   DOI: 10.19982/j.issn.1000-6621.20220197
    Abstract687)   HTML33)    PDF(pc) (1408KB)(245)       Save

    Objective: To explore the critical value of mean diameter of induration tuberculin by skin test (TST) for the diagnosis of late tuberculosis infection (LTBI) that needs preventive medication in the treatment of tuberculosis epidemic in school. Methods: From October 2020 to October 2021, 163 students and teachers from two schools with three or more student tuberculosis patients in Jiangsu Province were selected. All the subjects were tested by TST and QuantiFERON-TB gold in-tube (QFT). Using the QFT results as the reference standard, the receiver operating characteristic curve (ROC) was used to determine the critical value of mean diameter of induration tuberculin, to diagnosis LTBI students and teachers who needed to have preventive treatment. Results: Of the 163 individuals, 79 (48.5%) were positive and 84 (51.5%) were negative in QFT. Among 132 individuals with moderate positive in TST, 62 were QFT positive (47.0% (95%CI: 38.3%-55.6%)). Of the 163 individuals, using the QFT results as the reference standard, TST had the highest diagnostic value when the induration diameter of TST was 12.5 mm, with a sensitivity of 38.0% (95%CI: 27.3%-49.6%) and a specificity of 82.1% (95%CI: 72.3%-89.6%). The area under the curve (AUC) was 0.621 (95%CI: 0.542-0.696). Among 132 individuals with moderate positive TST, using the QFT results as the reference standard, TST had the highest diagnostic value when the induration diameter of TST was 12.5 mm, with a sensitivity of 25.8% (95%CI: 15.5%-38.5%) and a specificity of 87.1% (95%CI: 77.0%-93.9%), and the AUC was 0.572 (95%CI: 0.483-0.657). Conclusion: In the treatment of tuberculosis epidemic in school if there are three or more tuberculosis cases in a class or the moderate or strong positive rate of TST is much higher than the normal range in the region, attention should be paid to the population with moderate positive TST results.

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    The efficacy and safety of regimen containing bedaquiline in the treatment of elderly drug-resistant tuberculosis patients
    XUE Yu, ZHANG Jing, NIE Wen-juan
    Chinese Journal of Antituberculosis    2022, 44 (6): 582-586.   DOI: 10.19982/j.issn.1000-6621.20220019
    Abstract685)   HTML31)    PDF(pc) (843KB)(238)       Save

    Objective: To evaluate the early efficacy and safety of regimen containing bedaquiline in the treatment of elderly drug-resistant tuberculosis (TB) patients. Methods: From April 2020 to July 2021, 20 elderly patients over 65 years old with drug-resistant TB who used bedaquiline regimen in Beijing Chest Hospital were enrolled, including 2 (10.0%) with rifampicin-resistant (RR), 6 (30.0%) with multidrug-resistant (MDR), 11 (55.0%) with pre-extensively drug-resistant (pre-XDR) and 1 (5.0%) with extensively drug-resistant TB (XDR-TB), respectively. TB culture conversion rate and lesions absorption within 24 weeks were analyzed to assess the early treatment efficacy. The adverse events and QTc were recorded to assess the treatment safety. Results: Twelve (60.0%) cases achieved culture conversion within 24 weeks, 7 showed significant absorption in Chest CT scan, 5 showed partial absorption. Among 6 patients with lung cavities, 5 showed cavities reducing and 1 showed cavity closing, 4 (20.0%) cases died, and the reason of death was respiratory failure caused by severe infection, 1 (5.0%) patient stopped bedaquiline due to the happening of left anterior bundle branch block. QTc value >450 ms was found in 5 (25.0%) patients, with 1 (5.0%) >500 ms, 2 (10.0%) were 473 ms and 490 ms, respectively, and bedaquiline was stopped. The other 2 patients with QTc 479 ms and 452 ms persisted took bedaquiline until the end of 24 weeks. 2 patients (10.0%) with gastrointestinal reactions continuing regimen until the end of 24 weeks, including 1 (5.0%) with liver injury. Conclusion: The regimen containing bedaquiline can achieve high culture conversion rates in patients with drug-resistant TB, and the safety is also well in the elderly TB patients.

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    Diagnostic value of metagenomic next-generation sequencing in nontuberculous mycobacterial pulmonary disease
    Kong Jiao, Chen Yuanyuan, Cai Qingshan, Zhao Yafang, Yu Yihang
    Chinese Journal of Antituberculosis    2022, 44 (11): 1135-1140.   DOI: 10.19982/j.issn.1000-6621.20220298
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    Objective: To investigate the diagnostic value of metagenomic next-generation sequencing (mNGS) in nontuberculous mycobacterial pulmonary disease (NTM-PD). Methods: The data of 123 patients with suspected NTM-PD admitted to the Tuberculosis Diagnosis and Treatment Center of Hangzhou Chest Hospital, Zhejiang University School of Medicine from January 2020 to February 2022 were retrospectively selected. According to the diagnostic criteria, 123 suspected NTM-PD patients were finally diagnosed as NTM-PD patients (NTM-PD group; n=74) and non-NTM-PD patients (non-NTM-PD group; n=49). All the patients underwent mNGS, PCR-fluorescence probe and mycobacterial culture in alveolar lavage fluid, sputum and lung tissue simultaneously. The sensitivity and specificity of the three methods were compared. Results: Based on the final clinical diagnosis, the sensitivities of mNGS, liquid culture and PCR fluorescence probe for NTM-PD detection were 83.8% (62/74), 78.4% (58/74) and 67.6% (50/74), respectively, the specificities were 65.3% (32/49), 91.8% (45/49) and 87.8% (43/49), respectively, the consistencies in diagnosis were 76.4% (94/123), 83.7% (103/123) and 75.6% (93/123), respectively, with Kappa values of 0.524, 0.647 and 0.521, respectively. Using liquid culture results as the standard, of mNGS and PCR fluorescence probe for NTM-PD detection, the sensitivities were 87.1% (54/62) and 75.8% (47/62), and specificities were 59.0% (36/61) and 85.2% (52/61), respectively, the consistencies in diagnosis were 73.2% (90/123) and 80.5% (99/123), and the Kappa values were 0.462 and 0.587, respectively. The strains of 74 NTM-PD patients were identified by mNGS and gene chip method, and the concordance rate of two detecting methods was 63.8% (37/58) with gene chip method as the standard for strain identification. Conclusion: For the diagnosis of NTM-PD, of mNGS detection, the sensitivity is high, it can directly identify the strains; however, the specificity is low, the specificity should be focused on improving, to better serve the clinic.

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    Differential diagnosis between latent tuberculosis infection and active tuberculosis
    Xia Hui, Wang Ruibai, Zhao Yanlin
    Chinese Journal of Antituberculosis    2023, 45 (3): 253-259.   DOI: 10.19982/j.issn.1000-6621.20220391
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    China is a country with a high burden of tuberculosis and latent tuberculosis infection. The treatment and prognosis of latent tuberculosis infection and active tuberculosis are completely different. The current available diagnostic tools for tuberculosis infection cannot effectively predict the progress of infection and differentiate it from active tuberculosis, therefore, more accurate biomarkers need to be developed. The research progress, challenges and prospects of biomarkers for differential diagnosis between latent tuberculosis infection and active tuberculosis were reviewed in the present study.

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    Interpretation of WHO consolidated guidelines on tuberculosis: Module 3: diagnosis: tests for tuberculosis infection
    Xin Henan, Gao Lei
    Chinese Journal of Antituberculosis    2023, 45 (7): 639-643.   DOI: 10.19982/j.issn.1000-6621.20230128
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    On September 30, 2022, the World Health Organization (WHO) published the WHO consolidated guidelines on tuberculosis: Module 3: diagnosis: tests for tuberculosis infection. The medical evidence-based guideline systematically evaluated the performance of different tests and recommended using of Mycobacterium tuberculosis antigen-based skin tests for the diagnosis of tuberculosis infection for the first time. The author now introduces the development of the new guideline and interprets the three key recommendations hoping to provide evidence-based reference for tuberculosis infection test and control.

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    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.
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    Study on the significance of immune intervention and influencing factors of peripheral blood CD4+T lymphocytopenia in HIV-negative pulmonary tuberculosis patients
    LIU Sheng-sheng, YANG Juan, ZHA Zhao-yu, ZHANG Chao, XU Zi-wei, TANG Shen-jie, LIN Wen-hong
    Chinese Journal of Antituberculosis    2022, 44 (6): 587-594.   DOI: 10.19982/j.issn.1000-6621.20220087
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    Objective: To investigate the incidence, immune intervention value, and influencing factors of peripheral blood CD4+T lymphocytopenia in HIV-negative pulmonary tuberculosis (PTB) patients. Methods: The clinical data of 213 cases with HIV-negative PTB in Anhui Chest Hospital from December 2020 to July 2021 were analyzed, retrospectively. According to the CD4+T lymphocytes counts, 213 cases were divided into CD4+T lymphopenia group (count <410 cells/μl) and control group (count ≥410 cells/μl). The patients with CD4+T lymphopenia were divided into the immune intervention group and non-intervention group according to whether they received immune intervention. Demographic characteristics (gender, age, occupation, and education level), smoking, drinking, number of symptoms, treatment classifications, comorbid diseases, drug resistance, imaging, and laboratory test results were collected. Efficacy analysis between groups was compared using the Chi-square test. Multivariate logistic regression analysis was used after filtrating by univariate analysis to explore the influencing factors of peripheral blood CD4+T lymphocytopenia in HIV-negative PTB patients. Results: The incidence of CD4+T lymphopenia was 28.6% (61/213). The efficacy analysis showed that after 2-4 months of treatment, the negative rate of sputum smear in the immunological intervention group was 93.9%, higher than 75.0% in the non-intervention group (χ2=4.320, P<0.05). After 5-7 months of treatment, the absorption rate of lesions in the immunological intervention group was 51.5%, which was higher than 25.0% in the non-intervention group (χ2=4.462,P<0.05). Univariate analysis showed that in the CD4+T lymphopenia group, male, age ≥60 years, farming, illiterate culture, number of symptoms ≥4, complicated with extrapulmonary tuberculosis, involving 4-6 lung fields, pulmonary cavity, hemoglobin <110 g/L, platelet <125×109/L, albumin <35 g/L, CD8+T lymphocyte count <190/μl (77.0%, 44.3%, 36.1%, 26.2%, 36.1%, 34.4%, 77.0%, 55.7%, 45.9%, 18.0%, 68.9%, 29.5%) were significantly higher than that of control group (60.5%, 11.2%, 19.7%, 10.5%, 19.7%, 21.1%, 38.2%, 40.8%, 25.7%, 5.3%, 44.7%, 7.9%), the differences were statistically significant (χ2 values were 5.242, 29.060, 10.095, 13.650, 6.290, 4.165, 26.342, 3.929, 8.274, 8.738, 10.137, and 16.805, respectively, all P values <0.05). Multivariate logistic regression analysis showed that age ≥60 years old, lesion involvement of 4-6 lung fields, platelet <125×109/L, CD8+T lymphocytes count <190 cells/μl (OR=4.816,95%CI:1.650-14.052; OR=3.669,95%CI:1.548-8.696; OR=3.753,95%CI:1.069-13.173; OR=3.908,95%CI:1.394-10.954) were the risk factors of CD4+T lymphocytopenia. Conclusion: HIV-negative pulmonary tuberculosis patients were prone to a decrease in CD4+T lymphocytes, and immune intervention therapy had positive significance for improving the efficacy of this population. Old age, a wide range of lesions involved, thrombocytopenia, and CD8+T lymphocytopenia were the independent risk factors for CD4+T lymphocytopenia in HIV-negative PTB patients.

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    Research progress of sputum specimen collection in patients with pulmonary tuberculosis
    Xie Fanghui, Liang Li, Zhao Xia, Yao Rong, Lei Limei, Guo Hui, Meng Meng, Wan Bin
    Chinese Journal of Antituberculosis    2022, 44 (9): 978-982.   DOI: 10.19982/j.issn.1000-6621.20220188
    Abstract627)   HTML33)    PDF(pc) (820KB)(309)       Save

    The diagnosis of pulmonary tuberculosis is based on the results of etiology (including bacteriology and molecular biology), and the sensitivity of etiology is affected by the quality of sputum samples. The quality of sputum samples is related to the collection time and method. This paper reviews the collection time, collection methods and intervention measures of sputum samples from patients with pulmonary tuberculosis, so as to provide reference for improving the etiological detection rate.

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    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
    Abstract620)   HTML49)    PDF(pc) (3561KB)(225)       Save

    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.

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    Meta-analysis of the diagnostic value of metagenomic next-generation sequencing and GeneXpert MTB/RIF in tuberculosis
    Wang Yajuan, Cao Xinyi, Liu Shengming
    Chinese Journal of Antituberculosis    2022, 44 (12): 1327-1337.   DOI: 10.19982/j.issn.1000-6621.20220303
    Abstract589)   HTML20)    PDF(pc) (5901KB)(240)       Save

    Objective: To compare the diagnostic efficacy of metagenomic next-generation sequencing (mNGS) and GeneXpert MTB/RIF (Xpert) for tuberculosis using meta-analysis. Methods: Literatures about the diagnostic accuracy of mNGS and Xpert for tuberculosis were systematically searched in PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (CBM), Wanfang and VIP databases from the establishment to July 5, 2022. According to the inclusion and exclusion criteria, two reviewers independently conducted the screening and inclusion of literatures, data extraction, risk of bias evaluation, as well as analysis for the diagnostic performance of mNGS and Xpert. Results: Twelve literatures with a total of 1344 samples were ultimately included. As the meta-analysis showed, the pooled sensitivity, specificity, diagnostic odds ratio and AUC of mNGS in tuberculosis diagnosis were 63.4%, 99.8%, 58.6 and 0.931, respectively, which of Xpert were 50.3%, 99.9%, 23.8 and 0.860, respectively, while those of the parallel diagnosis of mNGS and Xpert were 68.7%, 99.8%, 91.2 and 0.978, respectively. Meanwhile, the sensitivities of mNGS on cerebrospinal fluid and other extra-pulmonary or multi-site specimens were 64.6% and 60.8%, respectively, and those of Xpert were 41.8% and 50.8%, respectively. Conclusion: Both mNGS and Xpert performed well in the diagnosis of tuberculosis. The sensitivities of mNGS single detection and detection combined with Xpert were higher than that of Xpert single detection, but there is no difference in the specificities. The combined detection with mNGS is expected to improve the detection rate of Xpert negative but clinically suspected tuberculosis infection, especially the pathogen of extrapulmonary tuberculosis.

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    Application value of two-step detection of Mycobacterium tuberculosis infection screening in schools
    Dong Xiaowei, Guo Huixin, Zhang Chenchen, Wang Jiawen, He Junlei, Li Guanhai, Li Jianwei, Wen Wenpei
    Chinese Journal of Antituberculosis    2022, 44 (8): 802-807.   DOI: 10.19982/j.issn.1000-6621.20220096
    Abstract585)   HTML31)    PDF(pc) (2413KB)(312)       Save

    Objective: To evaluate the application value of tuberculin skin test (TST) combined with interferon-gamma release assays (IGRA)(shorter form“two-step”) screening Mycobacterium tuberculosis (MTB) infection and active tuberculosis in students’ physical examination. Methods: A cross-sectional study was conducted in 74358 students in Guangdong during 2017—2021, 50701 (68.18%) were treated with chest X-ray and 74148 (99.72%) were tested with TST. And then, 9702 (13.08%) students positive in TST test received IGRA test (two-step approach). Finally, the students with abnormal chest X-ray and those who were positive in TST and IGRA tests (double positive) should be further examined to clarify the diagnosis of pulmonary tuberculosis. Results: Using the IGRA test results as the reference standard,taking the mean diameter of induration detected by TST of 5, 10 and 15 mm as the positive threshold, the consistency rates of MTB infection detected by TST and IGRA were 15.97% (1549/9702), 26.63% (2584/9702) and 81.11% (7869/9702), respectively, with the Kappa values of 0.014, 0.014 and 0.112, respectively. The rate of MTB infection detected by TST was significantly higher than that of the two-step method (11.67% (8652/74148) vs. 1.02% (759/74148), χ2=7068.423,P<0.001). The detection rate of pulmonary tuberculosis among students with moderate and strongly positive TST was significantly lower than that among students with double positive (0.29% (15/5219) vs. 1.84% (14/759), χ2=30.133,P<0.001). Conclusion: The consistency of detecting MTB infection by TST and IGRA is poor. The “two-step method” can significantly improve the detection rate of MTB infection and the screening efficiency of pulmonary tuberculosis in schools.

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    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.

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    Progress and reflections on development of laboratory diagnostic technology for tuberculosis
    Li Shanshan, Wang Yufeng, Shu Wei, Pang Yu
    Chinese Journal of Antituberculosis    2023, 45 (5): 446-453.   DOI: 10.19982/j.issn.1000-6621.20220535
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    Rapid and accurate laboratory diagnostic techniques are of great importance for the prevention and control of tuberculosis (TB). Since the discovery of Mycobacterium tuberculosis by Robert Koch in 1882, significant achievements have been made in the development of TB diagnosis from traditional etiological diagnostics to immunological and molecular diagnostics. Nevertheless, the current diagnostic technologies remain unable to meet current requirements, thereby hampering the achievement of the End TB Strategy by 2035. In view of these challenges, the authors discuss the core diagnostic needs of TB prevention and control, and explore the important development pipeline of future laboratory diagnosis.

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    Interpretation of WHO consolidated guidelines on tuberculosis: Module 1: prevention: tuberculosis preventive treatment
    Guo Tonglei, Xin Henan, Gao Lei
    Chinese Journal of Antituberculosis    2023, 45 (8): 723-727.   DOI: 10.19982/j.issn.1000-6621.20230199
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    World Health Organization (WHO) published the WHO consolidated guidelines on tuberculosis: Module 1: prevention: tuberculosis preventive treatment (2020 version guideline) on February 25, 2020, and guided the implementation of the 2020 version guideline through the implementation manual which contains the details of the implementation of guidance recommendations. The 2020 version guideline integrates the latest research since the WHO released Latent tuberculosis infection: updated and consolidated guidelines for programmatic management in 2018, and updates some recommendations. The author introduces the 2020 version guideline and interprets its key recommendations, hoping to provide a reference for the implementation of tuberculosis preventive treatment in China.

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    Immunologically active substances: novel treatment options for tuberculosis and nontuberculous mycobacteriosis
    Gong Wenping, Mi Jie, Wu Xueqiong
    Chinese Journal of Antituberculosis    2022, 44 (11): 1107-1121.   DOI: 10.19982/j.issn.1000-6621.20220239
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    Tuberculosis (TB) is not only an infectious disease, but also an immune disease. As a new potential treatment for diseases caused by the Mycobacterium tuberculosis (MTB) and nontuberculous mycobacteria (NTM), immunotherapy can inhibit or even eliminate MTB and NTM by influencing and regulating the immune system of the human body. In this article, we summarized the research progress of immunologically active substances such as cytokines, antibodies, small molecule active peptides, lysozyme, and immunoblockers in the treatment of MTB and NTM infections. This study will provide new ideas for TB and NTM treatment.

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    Effect of mindfulness level on mental health of middle-aged and elderly people with type 2 diabetes mellitus comorbidity latent tuberculosis infection in rural areas
    Dai Zhenwei, Zhang Haoran, Jing Shu, Xiao Weijun, Wang Hao, Huang Yiman, Chen Xu, Fu Jiaqi, Wu Yijin, Gao Lei, Su Xiaoyou
    Chinese Journal of Antituberculosis    2023, 45 (2): 188-194.   DOI: 10.19982/j.issn.1000-6621.20220341
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    Objective: To investigate the prevalence of latent tuberculosis infection (LTBI) in the middle-aged and elderly type 2 diabetes mellitus (T2DM) patients in rural areas of China, and to explore the influence of mindfulness on depression and the mediation effect of anxiety in T2DM comorbidity with LTBI patients. Methods: From November 2 to November 12, 2021, using a convenient sampling method, 469 middle-aged and elderly patients T2DM in rural areas of Zhongmu County, Henan Province were selected as the research participants for questionnaire survey and LTBI detection. The questionnaire includes general information, Five-item Mindful Awareness Attention Scale, Generalized Anxiety Disorder Questionnaire, and Patient Health Questionnaire. LTBI was detected by interferon-gamma release assay (IGRA). Structural equation modeling was used to test the mediation effect of anxiety between mindfulness and depression. Results: Of the 469 participants, 74 were IGRA positive, accounting for 15.78%. The score of Five-item Mindful Awareness Attention Scale in the 74 T2DM participants with LTBI was 5.00 (5.00, 10.00). The score of Patient Health Questionnaire and Generalized Anxiety Disorder Questionnaire in female were higher than male (0.00 (0.00, 2.00) vs. 0.00 (0.00, 0.00) and 0.50 (0.00, 3.00) vs. 0.00 (0.00, 0.75), respectively); the score of Patient Health Questionnaire in those with an annual income of less than RMB 20000 yuan was higher than those with an annual income of more than RMB 20000 yuan (0.00 (0.00, 2.25) vs. 0.00 (0.00, 0.00)); the score of Generalized Anxiety Disorder Questionnaire in those did not drink in the past 12 months was higher than those drank in the past 12 months (0.00 (0.00, 3.00) vs. 0.00 (0.00, 0.00)); the score of Patient Health Questionnaire in those without hypertension was higher than those with hypertension (1.00 (0.00, 4.00) vs. 0.00 (0.00, 0.75), all the differences were statistically significant (Z values were 1.789, 2.509, 2.572, 2.133, and 2.018, respectively, all P<0.10). The prevalence of anxiety and depression in T2DM patients with LTBI were 8.10% (6/74) and 5.40% (4/74), respectively, and 3 (4.10%, 3/74) had both depression and anxiety simultaneously. We used mindfulness as independent variable, depression as dependent variable, anxiety as mediator, and gender, annual income, whether drink in the past 12 months, and whether had hypertension as covariates, to build structural equation model. The model had good reliability, convergence validity and discrimination validity. In the model, the effects of mindfulness on anxiety (β=-0.394 (95%CI:-0.778-0.115), P=0.036), and anxiety on depression (β=0.878 (95%CI:0.446-0.979), P<0.001) were both statistically significant. The mediating effect of mindfulness on depression was statistically significant (β=-0.346 (95%CI:-0.628-0.103), P=0.011). Conclusion: The conditions of anxiety and depression in middle-aged and elderly T2DM patients comorbidity with LTBI of rural areas in China should be paid attention, preventive intervention and psychological mindfulness is suggested to be carried out.

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    Research progress on the drug resistance and mechanism of the anti-tuberculosis drug bedaquiline
    Yao Rong, Lu Yu
    Chinese Journal of Antituberculosis    2022, 44 (9): 973-977.   DOI: 10.19982/j.issn.1000-6621.20220122
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    With the increase of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains, drug resistance of Mycobacterium tuberculosis (MTB) has become an urgent problem worldwide. Bedaquiline (Bdq) is the first new drug specifically in the treatment of MDR-TB in recent 50 years, and its drug resistance been gradually concerned. The research progress of drug resistance characteristics and drug resistance gene mutations of Bdq were reviewed, in order to better guide clinical medication, improve the success rate of treatment, and reduce the occurrence of drug resistance.

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    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.
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    Clinical diagnostic value of combining four methods in detecting etiologically negative pulmonary tuberculosis
    Tian Lili, Chen Shuangshuang, Fan Ruifang, Zhang Jie, Wang Nenhan, Chen Hao, Dai Xiaowei, Ren Yixuan, Zhao Yanfeng, Li Chuanyou, Ding Beichuan, Li Bo, Yu Lan, Yi Junli, Wang Pei, Yang Xinyu, Song Weiping
    Chinese Journal of Antituberculosis    2023, 45 (2): 144-150.   DOI: 10.19982/j.issn.1000-6621.20220443
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    Objective: To analyze the diagnostic value of combining T-cell spot test for tuberculosis infection (T-SPOT.TB), antibody (TB-Ab) test, erythrocyte sedimentation rate (ESR) test, and hypersensitive C-reactive protein (hs-CRP) test in detecting etiologically negative pulmonary tuberculosis(PTB). Methods: Data of 216 PTB patients who were initially treated and had negative etiological test results (etiologically negative PTB group) were collected from the Tuberculosis Clinic of the Beijing Center for Disease Prevention and Control from July 2020 to July 2022. Meanwhile 147 primary PTB patients with positive etiological test results and 455 patients with other pulmonary diseases who were admitted during the same period were classified as the etiologically positive PTB group and other lung disease group respectively. All of them were tested with T-SPOT.TB, TB-Ab, ESR, and hs-CRP to analyze the diagnostic performance of single test and combined tests with those four methods, based on clinical diagnosis. Results: The detection positive rate of T-SPOT.TB in etiologically negative PTB group was 82.4% (178/216), no statistically significant difference was observed comparing with the detection positive rate in etiologically positive PTB group (87.8% (129/147); χ2=1.917,P=0.166), but the difference was statistically significant (χ2=160.746,P=0.000), while comparing with the detection positive rate in other pulmonary disease group (28.6%, 130/455). The sensitivity, specificity, positive and negative predictive value and accuracy of T-SPOT.TB were 82.9% (178/216), 71.4% (325/455), 57.8% (178/308), 89.5% (325/363), 75.0% (503/671), respectively. While for combination of all four methods, they were 91.7% (198/216), 53.4% (243/455), 48.3% (198/410), 93.1% (243/261), 65.7% (441/671), respectively. The area under ROC curve (AUC) of T-SPOT.TB, TB-Ab, ESR and hs-CRP test were 0.764, 0.600, 0.529 and 0.515, respectively, and the AUC of combining those four tests was 0.804. Conclusion: The sensitivity, negative predictive value and accuracy of the T-SPOT.TB test for detecting etiologically negative PTB were relatively good, and the sensitivity, negative predictive value and AUC of combining four test methods were relatively high, which indicates that combining tests could improve the diagnostic efficacy for detecting etiologically negative pulmonary tuberculosis.

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    Interpretation of Guideline on tuberculosis infection prevention and control in primary health care institute
    Cheng Jun, Lu Wei
    Chinese Journal of Antituberculosis    2022, 44 (8): 762-767.   DOI: 10.19982/j.issn.1000-6621.20220207
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    Guideline on tuberculosis infection prevention and control in primary health care institute (T/CHATA-018-2022), one of association standards launched by Chinese Antituberculosis Association, was put into force from Feb, 24th, 2022. In order to make the potential users to understand this standard well, the author described its background, main content and basis of measurements, and application.

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    Expert consensus on clinical monitoring and management of QTc interval prolongation caused by anti-tuberculous drugs
    Chinese Antituberculosis Association, Editorial Board of Chinese Journal of Antituberculosis, Beijing Chest Hospital, Capital Medical University
    Chinese Journal of Antituberculosis    2024, 46 (1): 8-17.   DOI: 10.19982/j.issn.1000-6621.20230271
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    Bedaquiline, delamanid, clofazimine and fluoroquinolones such as levofloxacin and moxifloxacin are essential to improve the global cure rate of multidrug resistant and extensively drug-resistant tuberculosis. However, these drugs may lead to the prolongation of QTc interval corrected by electrocardiograph, which may cause serious adverse effects. Clinicians need to timely find, properly deal with and prevent adverse effects. This article aims at the common problems in clinical monitoring and management of QTc interval prolongation caused by anti-tuberculous drugs. According to the published research data and the application experience of participating experts, it was formed through discussion among many experts. Professional advice was given on the discovery, treatment and prevention of QTc interval prolongation caused by anti-tuberculous drugs, aiming at timely and standardized prevention and treatment of adverse reactions in the process of anti-tuberculous treatment.

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    Development and challenges of Mycobacterium tuberculosis cfDNA in the diagnosis of tuberculosis
    Peng Lijun, Fang Tingting, Cai Long
    Chinese Journal of Antituberculosis    2022, 44 (10): 1091-1095.   DOI: 10.19982/j.issn.1000-6621.20220228
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    In order to achieve the goal of “End Tuberculosis by 2035”, it is urgent to develop new detection methods. Mycobacterium tuberculosis cfDNA (MTB-cfDNA) can indicate the presence of pathogens and is an attractive biomarker for tuberculosis (TB) diagnosis and treatment monitoring. Easily accessible MTB-cfDNA in urine and/or blood can be used to detect both pulmonary and extrapulmonary TB in any age group. The diagnostic performance of MTB-cfDNA in fluid samples such as pleural effusion, ascites and cerebrospinal fluid is higher than that of genomic DNA assays such as GeneXpert MTB/RIF. Research on cfDNA as a TB biomarker is still in its infancy, larger and clinical studies including more comprehensive patient types are needed to evaluate the utility of cfDNA in TB diagnosis. With further optimization of detection methods, cfDNA testing may improve TB diagnosis and become a “game changer”.

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    Application value of targeted next-generation sequencing for identification of non-tuberculous mycobacteria strains
    Chen Hua, Chen Pinru, Li Yanyang, Deng Zhengxian, Xu Liuqing, Liang Feng, Hu Jinxing
    Chinese Journal of Antituberculosis    2023, 45 (4): 362-366.   DOI: 10.19982/j.issn.1000-6621.20220530
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    Objective: To explore the application value of targeted next-generation sequencing (tNGS) in the identification of non-tuberculous mycobacteria (NTM) strains. Methods: From July 2021 to September 2022, 428 samples of hospitalized patients in the NTM Diagnosis and Treatment Center of Guangzhou Chest Hospital were collected for study, including 312 sputum samples and 116 bronchial lavage fluid samples. These samples were identified by tNGS mycobacterium identification (“tNGS” for short) and microbial culture (BACTEC MGIT 960)+DNA microarray chip method (“culture method” for short), and the detection results of the two methods were analyzed. Results: (1) tNGS and culture method respectively isolated 102 and 56 samples of Mycobacterium tuberculosis respectively, and 150 and 182 NTM samples. (2) Detection rate of mycobacterium by tNGS was 58.88% (252/428), but there was no significant difference between tNGS and culture method (55.61% (238/428), χ2=0.936,P=0.333). (3) Taking culture method as the reference standard, the sensitivity, specificity, false negative rate, false positive rate, positive predictive value, negative predictive value and Kappa value of tNGS to detect mycobacterium were 80.65% (200/248), 92.22% (166/180), 22.43% (48/214), 6.54% (14/214), 93.46% (200/214), 77.57% (166/214) and 0.710, respectively. Conclusion: tNGS result is consistent with culture method, has good timeliness, sensitivity and specificity, which is conducive to formulating clinical treatment plan in the early stage.

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    Interpretation of WHO consolidated guidelines on tuberculosis. Module 5: management of tuberculosis in children and adolescents
    Fan Lichao, Jiao Weiwei, Wu Haoyu, Shen Adong, Chen Yu
    Chinese Journal of Antituberculosis    2023, 45 (1): 6-12.   DOI: 10.19982/j.issn.1000-6621.20220403
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    On March 21, 2022, the World Health Organization (WHO) published the WHO consolidated guidelines on tuberculosis. Module 5: management of tuberculosis in children and adolescents (2022 version Guideline), and provide guidance for the implementation of the guidance recommendations through the published implementation manual. The 2022 version Guideline standardizes the management of tuberculosis in children and adolescents based on the latest evidence-based medical evidence, and focuses on updating the use of Xpert Ultra as the initial diagnosis tool and rifampicin resistance detection tool for children and adolescents with tuberculosis; integrated treatment decision-making paths is enabled; 4-month treatment program is enabled for non-severe children; treatment program containing bedaquiline is enabled for multidrug-/rifampicin-resistant tuberculosis (MDR/RR-TB) children under the age of 6; among MDR/RR-TB children under 3 years of age, the treatment plan with delamanid can be used; the option of intensive treatment with a course of 6 months can be used for tuberculous meningitis; and the decentralized tuberculosis care model sinking to the grass-roots level and the integrated tuberculosis care model with family as the core can be used. The author now introduces the 2022 version Guideline and interprets the updated key points, aiming to provide reference for staff in the field of tuberculosis diagnosis and treatment in children and adolescents based on evidence.

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    Diagnostic application of GeneXpert MTB/RIF in stool specimens for intestinal tuberculosis
    Liu Rongmei, Lyu Zizheng, Ma Liping, Li Qiang, Song Yanhua, Chen Hongmei, Kong Zhongshun, Gao Mengqiu
    Chinese Journal of Antituberculosis    2023, 45 (2): 139-143.   DOI: 10.19982/j.issn.1000-6621.20220381
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    Objective: To evaluate the diagnostic value of rifampicin resistance real-time fluorescence quantitative nucleic acid amplification assay (GeneXpert MTB/RIF) in testing stool specimens for detecting intestinal tuberculosis. Methods: From January 2019 to December 2021, the stool samples of 538 patients with clinically suspected intestinal tuberculosis were collected from Beijing Chest Hospital, Capital Medical University. Fluorescent smear microscopy, BACTEC MGIT 960 liquid rapid growth culture, GeneXpert MTB/RIF detection were performed. At the same time, the whole blood T-cell spot test, enteroscopy and intestinal mucosal tissue pathology were performed to analyze the diagnostic efficacy of fecal samples in diagnosing intestinal tuberculosis by GeneXpert MTB/RIF. Results: Out of 538 patients suspected of intestinal tuberculosis, 189 were diagnosed as intestinal tuberculosis according to clinical diagnostic criteria, 349 were diagnosed as non intestinal tuberculosis (including ulcerative colitis, intestinal infection, gastrointestinal ulcer, malignant tumor, Crohn’s disease, etc.). With the clinical diagnostic criteria as the gold standard, the sensitivity and specificity of GeneXpert MTB/RIF test on stool samples were 77.2% (95%CI: 70.5%-82.9%) and 51.0% (95%CI: 45.6%-56.3%), respectively; The sensitivity and specificity of stool fluorescent smear microscopy were 23.3% (95%CI: 17.6%-30.1%) and 92.8% (95%CI: 89.5%-95.2%); The sensitivity and specificity of fecal liquid rapid growth culture were 29.1% (95%CI: 22.9%-36.2%) and 83.7% (95%CI: 79.3%-87.3%). Conclusion: In the diagnosis of intestinal tuberculosis, stool GeneXpert MTB/RIF test showed relatively high sensitivity for detecting Mycobacterium tuberculosis in clinical diagnosed patients who lack bacteriological diagnosis evidence, which could improve the diagnosis level of intestinal tuberculosis.

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    Analysis on the trend of age change of pulmonary tuberculosis in Sichuan from 2011 to 2020
    Li Ting, Liu Shuang, Lu Jia, Wang Danxia, Xia Lan
    Chinese Journal of Antituberculosis    2022, 44 (8): 808-814.   DOI: 10.19982/j.issn.1000-6621.20220085
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    Objective: To analyze the epidemic characteristics and trends of pulmonary tuberculosis (PTB) in different age groups in Sichuan from 2011 to 2020. Methods: The reported incidence data and population data of PTB patients in Sichuan Province from 2011 to 2020 were collected through the Infectious Disease Reporting Information Management System and Basic Information System, the subsystem of China Disease Prevention and Control Information System, and the trend analysis was carried out using the JoinPoint regression model. Results: From 2011 to 2020, 567300 PTB cases were reported in Sichuan. The reported incidence rate decreased from 81.14/100000 (65250 cases) in 2011 to 55.19/100000 (46218 cases) in 2020 with the annual decreasing rate of 4.19%, the standardized incidence rate showed a downward trend (annual percent change, APC), the APC and average annual percent change (AAPC) both were -4.0% (95%CI: -4.7%--3.3%). The average onset age increased from 44.19 years in 2011 to 45.45 years in 2020 with increasement of 0.104 years every year (β=0.104, P=0.008). During the 10 years, the incidence rate of PTB was the highest in people aged 65 or above (96.94/100000, 99961 cases). The peak age of incidence rate moved from 65 years (113.08/100000, 9694 cases) in 2011 to 15-24 years (89.77/100000, 8688 cases) in 2020. The incidence rate of people aged 25 and above showed a downward trend. The incidence rates of 25-34, 35-44, 45-54, 55-64, and 65 years and above decreased from 87.83/100000 (8855 cases), 77.89/100000 (12596 cases), 97.37/100000 (9778 cases), 121.07/100000 (11308 cases) and 113.08/100000 (9694 cases), respectively in 2011 to 62.85/100000 (6663 cases), 40.57/100000 (4754 cases), 58.23/100000 (8376 cases), 62.67/100000 (6543 cases) and 73.43/100000 (9686 cases), respectively in 2020. The AAPCs were -4.5% (95%CI: -7.8%--1.1%), -7.7% (95%CI: -8.9%--6.6%), -4.9% (95%CI: -8.9%--0.8%), -6.8% (95%CI: -8.0%--5.6%) and -4.6% (95%CI: -5.8%--3.4%), respectively. The incidence rate of children aged 0-14 years increased from 6.96/100000 (923 cases) in 2015 to 10.98/100000 (1508 cases) in 2020 with the APC of 9.2% (95%CI: 4.1%-14.4%). Conclusion: Although the incidence of PTB in Sichuan Province has been decreasing, the incidence rate of children and adolescents under 25 years old has been increasing in recent years, comprehensive prevention and control measures should be taken. At the same time, we should also pay attention to the elderly people.

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    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
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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.

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

    Responsible Institution
    China Association for Science and Technology
    Sponsor
    Chinese Antituberculosis Association
    42 Dongsi Xidajie,Beijing 100710,China
    Editing
    Editorial Board of Chinese Journal of Antituberculosis
    5 Dongguang Hutong,Beijing 100035,China
    Tel(Fax): 0086-10-62257587
    http://www.zgflzz.cn
    Email: zgfIzz@163.com
    Editor-in-chief
    WANG Li-xia(王黎霞)
    Managing Director
    Ll Jing-wen(李敬文)
    Publishing
    Chinese Journal of Antituberculosis Publishing House
    5 Dongguang Hutong, Beijing 100035,China
    Tel(Fax):0086-10-62257257
    Email: zgflzz@163.com
    Printing
    Tomato Cloud Printing (Cangzhou) Co., Ltd.
    Overseas Distributor
    China International BookTrading Corporation
    P.O. Box 399,Beijing 100044,China
    Code No.M3721
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