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Table of Content

    10 January 2023, Volume 45 Issue 1
    Special Topic
    Attach importance to childhood tuberculosis and care for children’s health
    Wang Qian, Wang Jia, Li Yuhong, Liu Eryong, Zhou Lin
    Chinese Journal of Antituberculosis. 2023, 45(1):  1-5.  doi:10.19982/j.issn.1000-6621.20220462
    Abstract ( 365 )   HTML ( 34 )   PDF (1147KB) ( 260 )   Save
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    Tuberculosis (TB) is a global public health problem that seriously endangers children’s health. Children aged 14 and under account for 11% of the global TB burden but 14% of TB deaths. Adult secondary TB mostly originates from childhood MTB infection. Improving the awareness of childhood TB and increasing the investment in the prevention, diagnosis and treatment of childhood TB are the key links to effectively control the incidence and mortality of childhood TB, which is of great significance for the control of TB in children and adults.

    Interpretation of Standard
    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
    Abstract ( 498 )   HTML ( 45 )   PDF (1099KB) ( 498 )   Save
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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.

    Interpretation of the standard of Detection and preventive treatment of latent tuberculosis infection in children
    Wang Zeming, Shen Adong
    Chinese Journal of Antituberculosis. 2023, 45(1):  13-17.  doi:10.19982/j.issn.1000-6621.20220426
    Abstract ( 416 )   HTML ( 45 )   PDF (1075KB) ( 323 )   Save
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    The standard of Detection and preventive treatment of latent tuberculosis infection in children (T/CHATA 015-2021) was published by the Chinese Antituberculosis Association on July 9, 2021. This standard was interpreted from the aspects of screening population, screening methods, diagnostic standards and anti-tuberculosis preventive treatment of latent tuberculosis infection, aiming to further improve the cognition of clinical pediatricians and staff related to tuberculosis diagnosis and treatment on latent tuberculosis infection in children, and standardize the management of latent tuberculosis infection in children.

    Interpretation of Social Organization Standard of Diagnosis of central nervous system tuberculosis in children
    Wang Zeming, Shen Adong
    Chinese Journal of Antituberculosis. 2023, 45(1):  18-24.  doi:10.19982/j.issn.1000-6621.20220425
    Abstract ( 321 )   HTML ( 15 )   PDF (2208KB) ( 253 )   Save
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    The Social Organization Standard for Diagnosis of central nervous system tuberculosis in children was published by the Chinese Antituberculosis Association in September 2022. In order to make this standard implied comprehensively, we give some additional interpretations of the recommendations for the diagnosis of central nervous system tuberculosis in children.

    Interpretation of Framework for collaborative action on tuberculosis and comorbidities
    Han Tingting, Liu Guizhen, Chen Qiuqi, Deng Guofang
    Chinese Journal of Antituberculosis. 2023, 45(1):  25-30.  doi:10.19982/j.issn.1000-6621.20220464
    Abstract ( 379 )   HTML ( 24 )   PDF (1083KB) ( 245 )   Save
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    Globally, tuberculosis (TB) remains one of the leading causes of death due to a single infectious agent. The main comorbidities and health-related risk factors of TB include human immunodeficiency virus (HIV), disorders due to the use of alcohol, undernutrition, tobacco smoking, diabetes mellitus, mental disorders, silicosis and viral hepatitis. Tacking both health-related risk factors and comorbidities among people with TB is essential for ending the TB epidemic. To achieve this, a well-rounded patient care approach is preferable to just targeting the disease alone. Substantial effort and global commitment are needed to achieve this collaboratively. Therefore, World Health Organization (WHO) has launched a framework for collaborative action on tuberculosis and comorbidities. The framework is organized into five sections, each of which lists key activities for scaling up joint efforts on TB and comorbidities. To know the contents of this document timely, we interpret the key points of the framework, key comorbidities and action principles to provide a reference for professionals.

    Original Article
    Exploration for improving the culture-positive rate of Mycobacterium tuberculosis in gastric fluid specimens from pediatric patients with pulmonary tuberculosis
    Li Guilian, Fang Min, Jiang Jingwei, Wang Ruihuan, Qian Chengyu, Yu Jinjie, Cao Bin, Xu Da, Zhao Xiuqin, Li Machao, Liu Haican, Sun Lin, Zhu Yu, Wan Kanglin
    Chinese Journal of Antituberculosis. 2023, 45(1):  31-37.  doi:10.19982/j.issn.1000-6621.20220319
    Abstract ( 349 )   HTML ( 16 )   PDF (973KB) ( 193 )   Save
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    Objective: To establish a method to improve the positive rate of culture for Mycobacterium tuberculosis (MTB) in gastric fluid specimens from pediatric patients with pulmonary tuberculosis, and to investigate the effect of culture medium pH on the correct interpretation of a tuberculosis antigen-colloidal gold assay and the effect of phosphate buffer solution (PBS) buffer on the pH of the NaOH-sample mix-solution. Methods: Seventy gastric juice samples received from suspected tuberculosis children were detected by self-established two-step culture method, traditional culture method and Xpert Ultra at the same time. The two-step culture method was to inoculate the gastric fluid specimens directly on the Lowenstein-Jensen (L-J) media first, and then, collect the suspected MTB colonies after about 20 to 30 days and treat them with sodium hydroxide-neutralization-centrifugation (traditional method) for MTB isolation. The difference of positive detection rate between traditional culture method and two-step method was compared. Take the Xpert Ultra test results of the sample as the bacterial load standard, the difference of positive detection rate of the two-step method in different bacterial load samples was analyzed. Meanwhile, a series of solutions with gradient pH were prepared to determine the optimal pH value for MTB antigen-colloidal gold diagnosis kit; the mixture of 3% or 4% NaOH and equal volume sample were neutralized with PBS buffer (pH=6.8) of a series of volumes, and the volume dilution ratio required when the pH value reaches 7-9 were determined. Results: The MTB positive rates were 26.5% (18/68) by the traditional method and 23.1% (15/65) by the two-step culture method, there was no statistically significant difference (χ2=0.125, P>0.05). The two-step method raised the positive detection rate from 26.5% (18/68) to 32.4% (22/68) based on the traditional method. The positive isolation rate of the two-step method in samples with bacterial load ≥low grade (44.0%, 11/25) was significantly higher than that in samples with load ≤very low grade (11.8%, 4/34) (χ2=7.896, P=0.005). The optimal pH range for the chosen tuberculosis antigen-colloidal gold diagnosis kit was 6-9. After being treated with 3% or 4% NaOH, adjustment of pH to 7-9 required at least 10- or 14-fold dilution with PBS buffer (pH=6.8) for gastric fluid simulative samples, and at least 12- or 16-fold dilution for sputum simulative samples. Conclusion: The positive detection rate of the two-step isolation culture method was not found better than the traditional method, however, it could be used as a supplement to the conventional method to improve the overall positive isolation rate of gastric fluid samples, and was especially recommended for the MTB detection in children with highly suspected but difficultly diagnosed pulmonary tuberculosis. In addition, this study investigated the optimal pH range for the use of MTB antigen-colloidal gold diagnosis kit and the optimal dilution ratio of neutralizing the NaOH-sample solution with PBS (pH=6.8), which could provide scientific basis for standardizing the isolation of MTB in China.

    The value of CT signs combined with peripheral blood eosinophils in differentiating pleuropulmonary paragonimiasis from pleural tuberculosis in children
    Li Xiang, Fu Xuwen, Xu Yanling, Gan Wei, Qi Min, Huang Ying
    Chinese Journal of Antituberculosis. 2023, 45(1):  38-44.  doi:10.19982/j.issn.1000-6621.20220229
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    Objective: To investigate the value of chest CT signs combined with peripheral blood eosinophil percentage in identifying pleuropulmonary paragonimiasis and pleural tuberculosis in children. Methods: Pediatric patients with pleuropulmonary paragonimiasis and pleural tuberculosis in children first diagnosed from January 2019 to December 2021 in The Third People’s Hospital in Kunming were retrospectively collected, including 58 pediatric patients with pleuropulmonary paragonimiasis (PG group) and 45 pediatric patients with pleural tuberculosis (TB group). The clinical symptoms, chest CT manifestations and laboratory test results were analyzed; an imaging model of CT signs and a combined model combining CT signs and eosinophils were established using binary logistic regression, the differential diagnostic efficacy of the two diagnostic models was calculated and compared. Results: The imaging model of CT signs showed that, encapsulated effusion (OR=5.11, 95%CI: 1.64-15.97) and pulmonary nodules (OR=12.33, 95%CI: 2.51-60.65) were more likely to be diagnosed as pleural tuberculosis, while pleural calcification (OR=0.17, 95%CI: 0.04-0.68) and tunnel sign (OR=0.01, 95%CI: 0.00-0.15) was less likely to be diagnosed as pleural tuberculosis. According to the ROC curve, when AUC=0.850 (95%CI: 0.777-0.922), the sensitivity was 79.3% (95%CI: 66.6%-88.8%), and the specificity was 75.6% (95%CI: 60.5%-87.1%). The combined model of CT signs and eosinophil percentage showed that, when pulmonary nodules (OR=11.56, 95%CI: 1.76-75.71) was found, pleural tuberculosis was more likely to be diagnosed, while tunnel signs (OR=0.02, 95%CI: 0.00-0.48) and elevated eosinophil percentage (OR=0.02, 95%CI: 0.01-0.08) were found, pleural tuberculosis was less likely to be diagnosed, and the ROC curve was plotted with AUC=0.934 (95%CI: 0.885-0.982), sensitivity of 89.7% (95%CI: 78.8%-96.1%), and specificity of 88.9% (95%CI: 75.9%-96.3%). The combined model had higher differential diagnostic efficacy than the imaging model, with a statistically significant difference in AUC (Z=-2.401, P=0.016). Conclusion: For the differentiation of pleuropulmonary paragonimiasis and pleural tuberculosis in children, the combined model have higher differential diagnostic efficacy than the imaging model; when there are pulmonary nodules and the percentage of eosinophils is not increased, the children are more likely to be diagnosed of tuberculous.

    Analysis of status and influencing factors associated with anti-tuberculosis drug-related liver injury in children
    Chen Fang, Zhang Xiaofo, Zhou Haiyi, Zhang Feng, Wang Manzhi
    Chinese Journal of Antituberculosis. 2023, 45(1):  45-51.  doi:10.19982/j.issn.1000-6621.20220290
    Abstract ( 307 )   HTML ( 17 )   PDF (846KB) ( 169 )   Save
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    Objective: To analyze the status and related influencing factors of anti-tuberculosis drug-induced liver injury (ATB-DILI) in children. Methods: A retrospective study was conducted to enroll 200 hospitalized or outpatient children who were diagnosed with tuberculosis and met the enrollment criteria from June 2018 to June 2022 in the Changsha Central Hospital Affiliated Hospital, Hengyang Medical School, University of South China. All children used hepatoprotective drugs throug the full course. Among them, 52 patients developed ATB-DILI, with an incidence rate of 26.0%. We analyzed the clinical manifestations, severity, pathological damage, onset time, and related influencing factors of ATB-DILI in those children. Results: Among the 52 children who developed liver injury, 20 cases (38.5%) had no obvious symptoms but only abnormal liver function test results, 32 cases (61.5%) were anorexic, 29 cases (55.8%) vomited, and 3 cases (5.8%) showed jaundice, all patients were recovering with liver-protecting drugs and symptomatic treatment; 51 cases had grade 1 (mild) ATB-DILI, 1 case got grade 2 (moderate), and there were no patients with grade 3-5 liver injury. Liver injury type were hepatocellular injury for all patients. ATB-DILI occurred in 29 cases (55.8%) within 2 weeks after anti-tuberculosis treatment started, 8 cases (15.4%) within 3-8 weeks, 5 cases (9.6%) within 9-12 weeks, 7 cases (13.5%) within 13-16 weeks, and 3 cases (5.7%) within 16-24 weeks. Multifactorial logistic regression analysis showed that body mass index <18.5 (OR (95%CI)=2.340 (1.104-4.959)), serum pre-albumin <200 mg/L (OR (95%CI)=2.337 (1.093-4.997)) and hemoglobin <120 g/L (OR (95%CI)=2.403 (1.176-4.908)) were independent risk factors for the development of ATB-DILI in children with tuberculosis. Conclusion: The incidence of ATB-DILI in tuberculosis children who used hepatoprotective drugs through the full course of anti-tuberculosis treatment is still not low, but its clinical manifestations, severity, and pathological damage are significantly reduced. Clinicians should pay attention to the risk of ATB-DILI in pediatric patients with tuberculosis whose body mass index, serum prealbumin, and hemoglobin are below normal values within 2 weeks after anti-tuberculosis treatment initiated.

    Efficacy and eligibility of high-dose moxifloxacin short-course regimen for rifampicin-resistant pulmonary tuberculosis
    Ren Fei, Ma Jinbao, Li Rong, Yang Han, Yang Hong, Wu Yanqin, Yang Xinjun, Dang Liyun
    Chinese Journal of Antituberculosis. 2023, 45(1):  52-59.  doi:10.19982/j.issn.1000-6621.20220297
    Abstract ( 354 )   HTML ( 15 )   PDF (797KB) ( 128 )   Save
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    Objective: To analyze the efficacy and safety of high-dose moxifloxacin short-course regimen in patients with rifampicin-resistant pulmonary tuberculosis (RR-PTB), as well as the factors restricting the clinical application. Methods: A retrospective cohort study was conducted in 272 RR-PTB patients admitted to Xi’an Chest Hospital and had treatment outcome from January 2020 to June 2021. The observation group included 27 patients who was treated with high-dose moxifloxacin short course regimen, while the other 127 patients treated with long course regimen were in the control group. The treatment outcomes and the occurrence of adverse events were compared between the two groups, and the causes 245 patients not using short-course regimen were also analyzed. Results: In the observation group, 15 patients were cured, and 6 patients completed the treatment. There was no significant difference between the treatment success rate in observation group and in control group (77.8% (21/27) vs.71.7% (91/127); χ2=0.421, P=0.516). The occurrence of adverse events in observation group and adverse events at grade 3 or above were significantly higher than those in the control group (88.9% (24/27) vs. 50.4% (64/127), χ2=13.473, P<0.001; and 40.7% (11/27) vs. 21.3% (27/127),χ2=4.546, P=0.033, respectively). The top 4 reasons for 245 patients high-dosenot using high-dose moxifloxacin short-course regimen were fluoroquinolone resistance (n=87, 35.5%), the second-line anti-tuberculosis drugs had been used for more than 1 month (n=52, 21.2%), combined tracheobronchial tuberculosis (n=40, 16.3%), and uncontrolled diabetes (n=20, 8.1%). Conclusion: High-dose moxifloxacin short-course regimens for RR-PTB patients could obtain a high success rate, while the incidence of adverse events was higher and the proportion of eligible patients was lower. We should pay more attention to the adverse events of short-course regimen and applicability studies should be carried out based on the actual conditions of Chinese patients.

    Study on high-concentration p-aminosalicylic acid resistant Mycobacterium tuberculosis induced in vitro and the mutation sites
    Yu Meiling, Zhang Chenchen, Wei Wenjing, Zhao Yuchuan, Zhuo Wenji, Zheng Lei
    Chinese Journal of Antituberculosis. 2023, 45(1):  60-66.  doi:10.19982/j.issn.1000-6621.20220457
    Abstract ( 336 )   HTML ( 7 )   PDF (967KB) ( 174 )   Save
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    Objective: To explore the potential mechanisms of action and resistance to para-aminosalicylic acid (PAS) by sequencing the whole genome (WGS) of lab-induced PAS-resistant Mycobacterium tuberculosis (MTB) and clinical isolates. Methods: The MTB standard strain was induced into standard PAS resistant strain and high-level drug resistant strain by in vitro drug concentration gradient induction method, and the induced strains of each generation were collected and preserved. The minimum inhibitory concentration (MIC) and cross resistance of the above induced strains were detected by liquid microplate method, and clinical isolates with similar drug resistance levels were screened. By sequencing the whole genome of PAS resistant laboratory mutants and clinical isolates, the mechanism of resistance of MTB to PAS was explored at the gene level. Results: A dynamic PAS-resistant model of MTB was established in vitro. The WGS results showed that PAS resistance may be directly related to three site mutations, plcC (Q462R), folC (S150R) and a thyA upstream site (3074495G→A). Except for genetic mutations, there were other regulatory mechanisms for the resistance to high levels PAS of MTB. Moreover, WGS results of PAS-susceptible and resistant clinical isolates revealed that some folC, thyA and thyX mutations were not caused by PAS. Conclusion: The PAS-resistant model of MTB constructed in this study provides an ideal biological model for the research and clinical practice of PAS-resistant tuberculosis. WGS analysis has clarified the resistance mechanism of MTB to PAS at the DNA level, and other regulatory mechanisms still need further investigation. The gene mutations associated with PAS resistance obtained in this study also need further experimental validation.

    Research on mechanisms of dendritic cell miR-17 regulating naive CD4+T lymphocytes unevenly differentiating to Treg/Th17
    Sheng Yunfeng, Qiu Meihua, Chen Yuanyuan, Sun Lifang, Zhen Libo
    Chinese Journal of Antituberculosis. 2023, 45(1):  67-72.  doi:10.19982/j.issn.1000-6621.20220280
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    Objective: To investigate the effect and molecular mechanism of miR-17 on affecting the differentiation of initial CD4+T cells into regulatory T cell (Treg) and T help cell 17 (Th17) by regulating peripheral blood dendritic cells (DC) of patients with pulmonary tuberculosis. Methods: Peripheral blood samples of 20 patients with pulmonary tuberculosis (tuberculosis group) and 20 outpatient visiting for health check-ups (healthy control group) from Hangzhou Chest Hospital Affiliated to Zhejiang University School of Medicine were collected between February 1 and April 30, 2022.Expressions of miR-17 in DC were detected with qPCR. The mature DC from tuberculosis group were co-cultured with the initial CD4+T lymphocytes from healthy control group, then the miR-negative control reagents (miR-negative control group), miR-17 mimic reagents (miR-17 mimic group) and miR-17 inhibitor were added to the cultures, respectively. The differentiation ratios of Treg cells and Th17 cells from the three groups were detected by flow cytometry, and the Eos gene transcription statuses in initial CD4+T cells were detected by qPCR and the expressions of Eos were detected by Western blot. Results: The expression of miR-17 in DC of pulmonary tuberculosis patients (12.546±1.572) was significantly higher than that of DC from healthy controls (2.409±1.097,t=28.356,P<0.05). The average proportion of Treg cells in the miR-17 mimic group (4.740%±0.901%) was significantly lower than that in the miR-negative control group (59.235%±4.652%,t=50.755,P<0.01). The average proportion of Th17 cells in the miR-17 mimic group (67.610%±3.495%) was significantly higher than that in the miR-negative control group (27.645%±2.075%,t=38.521, P<0.01). The average proportion of Treg cells in the miR-17 inhibitor group (83.080%±5.770%) was significantly higher than that in the miR-negative control group (59.235%±4.652%, t=14.988, P<0.01); the average proportion of Th17 cells in the miR-17 inhibitor group (11.405%±1.777%) was significantly lower than that in the miR-negative control group (27.645%±2.075%, t=27.044, P<0.01).The transcription level of Eos mRNA gene in the initial CD4+T lymphocytes in the miR-17 mimic group (0.181±0.123) was down-regulated to 38.4%, which was significantly lower than that in the miR-negative control group (0.471±0.217, t=10.449, P<0.05). The transcription level of Eos mRNA gene in the initial CD4+T lymphocytes in the miR-17 inhibitor group (0.889±0.295) was up-regulated to 1.887-fold, significantly higher than that in the miR-negative control group (0.471±0.217,t=16.635, P<0.05).The relative expression of Eos in the initial CD4+T lymphocytes of the miR-17 mimic group (3.626±1.319) was reduced to 77.7%, significantly lower than that in the miR-negative control group (4.664±1.456,t=8.528, P<0.05). The relative expression of Eos in the initial CD4+T lymphocytes in the miR-17 inhibitor group (6.148±1.701) increased to 1.318-fold, significantly higher than that in the miR-negative control group (4.664±1.456,t=8.035, P<0.05). Conclusion: DC miR-17 regulates the initial CD4+T lymphocytes unevenly differentiating to Treg/Th17, thus participates in the process of Mycobacterium tuberculosis infection.

    Analysis of genotype characteristics and drug resistance of Mycobacterium tuberculosis isolates in Fujian Province from 2017 to 2019
    Wei Shuzhen, Zhao Yong, Lin Jian, Lin Shufang, Dai Zhisong
    Chinese Journal of Antituberculosis. 2023, 45(1):  73-78.  doi:10.19982/j.issn.1000-6621.20220331
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    Objective: To investigate the genotype distribution and prevalence of Mycobacterium tuberculosis (MTB) isolates in Fujian Province, and to analyze the relationship between MTB genotypes and drug resistance. Methods: A total of 477 MTB clinical isolates from tuberculosis drug resistance surveillance sites in Fujian Province from 2017 to 2019 were selected as the research objects. The growth test method of p-nitrobenzoic acid (PNB)/thiophene-2-carboxylic acid hydrazide (TCH) was used for preliminary identification of bacteria. The drug sensitivity test of 9 kinds of anti-tuberculosis drugs (isoniazid (INH), rifampin (RFP), streptomycin (Sm), ethambutol (EMB), kanamycin (Km), ofloxacin (Ofx), capreomycin (Cm), propylamine (Pto), para aminosalicylic acid (PAS)) was carried out using the traditional solid proportion method. The strains were genotyped by the melting curve method of interval oligonucleotide typing (McSpoligotyping). Results: Among the 477 MTB strains, 245 strains (51.4%) were Beijing genotype, 44 strains (9.2%) were in T family (including 2 strains of T, 28 strains of T1, 7 strains of T2, 3 strains of T3 and T4, and 1 strain of T5), 35 strains (7.3%) were in H family (including 13 strains of H, 1 strain of H1, 21 strains of H3), 11 strains (2.3%) were in EAI family (including 10 strains of EAI2-Manila and 1 strain of EAI5), and 3 strains (0.2%) were in LAM3, Manu2 and X1 families, respectively, and the other 139 strains (29.1%) belonged to undefined or unknown families. Cluster analysis showed that the main epidemic types of each genotype family were SIT1 of Beijing family (44.9%, 214/477), SIT53 of T family (2.5%, 12/477), SIT742 of H family (1.9%, 9/477), and SIT19 of EAI family (1.5%, 7/477). The differences among the INH resistance rate of MTB strains of different family were statistically significant (χ2=10.311, P=0.036), the INH resistance rate of the EAI+LAM+Manu+X families was the highest (28.6%, 4/14). There was statistically significant difference among the RFP resistance rate MTB strains of different family (χ2=14.366, P=0.006), the RFP resistance rate of EAI+LAM+Manu+X families was the highest (21.4%, 3/14). There was statistically significant difference among Ofx resistance rate of MTB strains of different families (χ2=23.643, P=0.000), the Ofx resistance rate of H family strains was the highest (17.1%, 6/35). There was statistically significant difference among PAS resistance rate of MTB strains of different families (χ2=9.550, P=0.049), and the PAS resistance rate of strains of undefined family was the highest (4.3%, 6/139). Conclusion: The prevalent MTB genotype in Fujian Province is Beijing family, and the prevalence of the strains of T family, H family, EAI family and the undefined family should be pay attention and the monitoring should be strengthened. The resistance to INH, RFP, Ofx and PAS of MTB strains is related to different genotype families.

    The application value of SAT-TB in monitoring the curative effect of patients with tracheobronchial tuberculosis
    Xu Yinjuan, Zhao Guolian, Cui Xiaoli, Dang Liyun, Kang Lei, Zhou Yong
    Chinese Journal of Antituberculosis. 2023, 45(1):  79-84.  doi:10.19982/j.issn.1000-6621.20220337
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    Objective: To analyze the monitoring effect of real-time fluorescent RNA isothermal detection (SAT-TB) and real-time fluorescent quantitative PCR (qRT-PCR) in the early antituberculosis chemotherapy of patients with tracheobronchial tuberculosis. Methods: Data of 168 patients with initial treatment tracheobronchial tuberculosis who had been treated in Xi’an Chest Hospital were collected from January to December, 2021. We analyzed the results of mycobacterium MGIT 960 liquid culture, SAT-TB and qRT-PCR of 94 etiologically positive patients who had been treated with tracheoscopy and had alveolar lavage fluid sample collected every 2 weeks (2nd, 4th, 6th, 8th, 10th and 12th week) after admission (baseline), and the dynamic changes of SAT-TB, qRT-PCR and their detection efficiency using the MGIT 960 liquid culture test as reference. Then the relationship between the negative conversion time of MGIT 960 culture and the dt value of the first SAT-TB results of the 168 patients was analyzed. Results: For the 94 patients who undertook tracheoscopy every 2 weeks, the positive rates of MGIT 960 culture at baseline, 2nd, 4th, 6th, 8th, 10th and 12th week declined by 98.78% (81/82), from 87.23% (82/94) to 1.06% (1/94); and the results of qRT-PCR test decreased by 67.81% (59/87), from 92.55% (87/94) to 29.79% (28/94). In addition, the positive rates of SAT-TB decreased by 82.95% (73/88), from 93.62% (88/94) to 15.96% (15/95). The declines of positive rates of qRT-PCR and SAT-TB were less than MGIT 960 culture, the differences were statistically significant (χ2=28.472, 12.469; Ps<0.001). Taking MGIT 960 test as the reference standard, the consistency (Kappa values) of qRT-PCR and MGIT 960 test were 0.044-0.416, and the area under curve (AUC) were 0.553-0.715 at different test points, these were significantly lower than that of SAT-TB and MGIT 960 test at every test point (Kappa values were 0.107-0.620, AUC were 0.642-0.814). For all 168 patients, the average dt values of patients in the negative conversion time within 1-4 weeks group (7.264 (4.891, 10.990)) was longer than the 5-8 weeks group(5.113 (3.520, 6.390)) and the 9-weeks and above group (5.222 (4.068, 6.886)), respectively. The differences were statistically significant (Z=-4.318, P<0.001; Z=-2.017, P=0.044). Conclusion: SAT-TB did better than qRT-PCR in monitoring the early curative effect of etiologically positive tracheobronchial tuberculosis patients.

    Analysis on the trend and influencing factors of detection delay in patients with active tuberculosis in Guangdong Province from 2016 to 2020
    Zhou Fangjing, Feng Huiying, Fang Lanjun, Chen Yuhui, Wen Wenpei, Liao Qinghua, Wu Huizhong
    Chinese Journal of Antituberculosis. 2023, 45(1):  85-95.  doi:10.19982/j.issn.1000-6621.20220389
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    Objective: To analyze the trend of detection delay among patients with active pulmonary tuberculosis (APTB) in Guangdong Province during the 13rd five-year plan period and explore the influencing factors, so as to provide scientific basis for reducing the detection delay. Methods: Based on the Tuberculosis management information system, a retrospective cohort study was conducted to collected medical records of APTB patients registered in Guangdong Province from 2016 to 2020, demographic characteristics and latency trends of 277684 patients who were finally included in the analysis were described. Cox proportional hazard model was used to analyze influencing factors of detection delay. Results: The detection delay was found in 146345 APTB patients in Guangdong Province, with the average annual delay rate of 52.70% (146345/277684) from 2016 to 2020. And the median and quartile of detection delay were 30 (14, 63) days. From 2016 to 2020, the annual detection delay rates were 50.66% (30693/60591), 50.86% (30436/59841), 53.44% (30061/56253), 55.53% (29418/52980), and 53.60% (25737/48019), respectively, which increased with time ( χ t r e n d 2=380.599, P<0.001). The median of detection delayed days increased from 29 days in 2016 to 31 days in 2020. Cox proportional hazard model showed that male (HR=1.042, 95%CI: 1.033-1.051), other occupation (HR=1.077, 95%CI: 1.067-1.087), detention personnel (HR=1.108, 95%CI: 1.068-1.149), diagnosed in provincial or municipal medical institutions (HR=1.106, 95%CI: 1.094-1.118), diagnosed by CDC/TB Prevention and Control Institute and other professional institutions (HR=1.197, 95%CI: 1.184-1.210) and re-treatment (HR=1.146, 95%CI: 1.127-1.164) were the protective factors of detection delay of APTB. Migrants (HR=0.986, 95%CI: 0.978-0.995), patients found passively (HR=0.970, 95%CI: 0.962-0.978) and severe tuberculosis (HR=0.931, 95%CI: 0.919-0.942) were the risk factors of tuberculosis detection delay. Conclusion: The incidence of detection delay in APTB in Guangdong Province increased with time from 2016 to 2020. More attention should be paid to the migrants, patients found passively and severe tuberculosis patients.

    Patient delay and related factors among tuberculosis patient in Fujian Province, 2010—2019
    Chen Daiquan, Lin Shufang, Zhou Yinfa, Chen Kun, Dai Zhisong
    Chinese Journal of Antituberculosis. 2023, 45(1):  96-103.  doi:10.19982/j.issn.1000-6621.20220294
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    Objective: To analyze the trend and related factors of patients delay among tuberculosis patients in Fujian Province from 2010 to 2019, and to provide basis for the formulation and adjustment of tuberculosis control measures. Methods: The data of 174124 tuberculosis patients registered and treated in Fujian Province from 2010 to 2019 were collected to describe the distribution and trend of patient delay. The factors associated with patient delay were analyzed by multivariate logistic regression model. Results: The median number of days from symptom onset to seeking health care was 21 (6, 58) days in Fujian Province from 2010 to 2019, with an average patient delay rate of 59.12% (102940/174124). Multivariate logistic regression analysis showed that female (OR=1.058, 95%CI: 1.035-1.082), aged 25-64 (OR=1.272, 95%CI: 1.232-1.313) and ≥65 (OR=1.427, 95%CI: 1.372-1.483), manual labor (OR=1.195, 95%CI: 1.119-1.276) and retirement or unemployed (OR=1.112, 95%CI: 1.039-1.190), current residency address in other cities of Fujian Province (OR=1.681, 95%CI: 1.550-1.822), contact inspection (OR=1.704, 95%CI: 1.216-2.387) and passive case-finding (OR=3.715, 95%CI: 3.340-4.131), tuberculous pleurisy (OR=1.454, 95%CI: 1.354-1.562)and extrapulmonary tuberculosis (OR=1.935,95%CI: 1.645-2.276), designated hospital model (OR=1.103, 95%CI: 1.078-1.130) and the distance between the current residency address and hospital ≥30 km (OR=1.077, 95%CI: 1.048-1.107) were high risk factors for patient delay. Students or children (OR=0.864, 95%CI: 0.792-0.943) and negative etiological examination (OR=0.650, 95%CI: 0.637-0.663) were low risk factors for patient delay. Conclusion: The patient delay rate in Fujian Province is still at a high level. We should improve the quality and accessibility of medical services, strengthen health education for key populations, and actively carry out active screening to reduce the patient delay.

    Effect of “trinity” care service on the multidrug-/rifampicin-resistant tuberculosis patients in the intensive phase
    He Xiaomou, Luo Hui, Ma Jinbao, Ren Fei, Zhao Ali, Yuan Rong
    Chinese Journal of Antituberculosis. 2023, 45(1):  104-110.  doi:10.19982/j.issn.1000-6621.20220281
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    Objective: To analyze the effect of “trinity” care service on the multidrug-/rifampicin-resistant tuberculosis (MDR/RR-TB) patients in the intensive phase. Methods: A retrospective cohort study was conducted in the MDR/RR-TB patients diagnosed in Xi’an Chest Hospital. A total of 223 MDR/RR-TB patients diagnosed from March 2018 to February 2019 who were under the integrated prevention and control service management model combining hospitalization and community treatment were selected as the control group. A total of 253 MDR/RR-TB patients diagnosed from March 2019 to February 2020 who were implemented the “trinity” care service management model were selected as the intervention group. The treatment adherence and the rate of loss to follow-up between the two groups in the intensive phase were analyzed and compared. Results: The proportion of patients with good treatment adherence in the intervention group was 86.6% (219/253), higher than that in the control group (54.7% (122/223)), the difference was statistically significant (χ2=59.189, P<0.001). The proportion of patients with good injection treatment adherence in the intervention group was 89.8% (221/246), higher than that in the control group (60.6% (134/221)), the difference was statistically significant (χ2=54.460, P<0.001). The rate of loss to follow-up of the intervention group in the intensive phase was 6.3% (16/253), lower than that in the control group (30.9% (69/223)), the difference was statistically significant (χ2=48.970, P<0.001). Conclusion: The implementation of the “trinity” care service management model for MDR/RR-TB patients is helpful to improve the treatment adherence and reduce the rate of loss to follow-up, which is worthy of popularization and application.

    Analysis of tuberculosis screening results among freshmen of high schools and below in Beijing,2021
    Tao Liying, Xu Zheng, Zhao Xin, Li Yanyuan, Li Yamin, Xu Yan, Zhang Yanan, Gao Zhidong
    Chinese Journal of Antituberculosis. 2023, 45(1):  111-115.  doi:10.19982/j.issn.1000-6621.20220308
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    Objective: To analyze the tuberculosis (TB) screening results among freshmen of high schools and below in Beijing, and to provide a basis for more scientific and standardized TB screening among new students. Methods: A total of 467088 freshmen with complete screening information records in the “Beijing Freshmen Tuberculosis Screening System” in 2021 were selected as the research objects.The students were from 3804 high schools and below. Basic information, suspected symptoms of TB and history of close contact, TB skin test (TST) results and X-ray chest examination were collected and analyzed. Results: Among the 467088 subjects, 0.17‰ (80/467088) had suspicious symptoms of TB, and 0.40‰ (187/467088) had close contact history of TB. The TST was performed in 69519 subjects with the positive rate of 13.45% (935/69519).The positive rate of TST in boarding middle school was significant lower than that of high school (11.07% (960/8673) vs. 13.77% (8369/60758), χ2=52.927, P<0.001). The positive rate of moderate or above TST was 12.64% (23/182) in subjects with suspected TB symptoms or close contact history, which was significantly higher than that in those who without suspected TB symptoms or close contact history (4.77% (3305/69337), χ2=41.531, P<0.001). Of the 9514 students who finished X-ray chest examination, 7 were pulmonary TB patients. The abnormal rate of chest X-ray of subjects with suspicious symptoms, close contact history, moderately positive TST or above was 5.32% (183/3443), which was significantly higher than that of self-tested subjects (4.05% (246/6071, χ2=8.140, P=0.004). Conclusion: The results of this survey show that the proportion of students with suspected symptoms of pulmonary TB or close contact history increases with the increase of the school period. The 7 subjects of active pulmonary TB found in the screening were all high school students, which conformed to the characteristics of the peak incidence of pulmonary TB among students aged 16-22 years old was, and was basically consistent with the screening results over the years, suggesting that the screening of TB among freshmen should focus on students in high school.

    Review Article
    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
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    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.

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

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