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    10 August 2021, Volume 43 Issue 8
    Expert Note
    Validation, demonstration, and promotion of the “Three Technical Innovations Plus Health System Strengthening” comprehensive tuberculosis prevention and control model: the China National Health Commission-Bill and Melinda Gates Foundation Tuberculosis Project
    ZHANG Hui, CHENG Jun, QU Yan, HUANG Fei, WANG Ni, HUAN Shi-tong
    Chinese Journal of Antituberculosis. 2021, 43(8):  757-760.  doi:10.3969/j.issn.1000-6621.2021.08.001
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    So far, tuberculosis has still been a major infectious disease that seriously endangers human health. Particularly, the global pandemic of the Corona Virus Disease 2019 has brought new challenges to global tuberculosis prevention and control. This article reviews the 10-year history of the China National Health Commission-Bill and Melinda Gates Foundation Tuberculosis Project based on the validation, demonstration and promotion of the “Three Technical Innovations Plus Health System Strengthening” comprehensive tuberculosis prevention and control model, to provide a reference for strengthening the prevention and control of tuberculosis in China and the world.

    Inspiration of the WHO Updated on the use of nucleic acid amplification tests to detect TB and drug-resistant TB: rapid communication
    XIA Hui, ZHAO Yan-lin
    Chinese Journal of Antituberculosis. 2021, 43(8):  761-765.  doi:10.3969/j.issn.1000-6621.2021.08.002
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    Rapid and accurate diagnosis of tuberculosis and drug-resistant tuberculosis is essential to tuberculosis prevention and control. The World Health Organization issued the Update on the use of nucleic acid amplification tests to detect TB and drug-resistant TB: rapid communication in February 18th 2021. This inspiration provided an interpretation of detailed introduction of the technologies and their technical performance, and elaborated the experience, potential effects on the current national tuberculosis control program and implementation considerations of these technologies.

    Original Articles
    Evaluation of medical expenses and financing models of pulmonary tuberculosis patients in three districts of Yinchuan City in 2016 and 2019
    LIU Guang-tian, DING Xiao-yan, LEI Juan, LIU Tao, PAN Li, TIAN Xiao-mei, CHEN Lin-lin, WANG Xiao-lin
    Chinese Journal of Antituberculosis. 2021, 43(8):  766-771.  doi:10.3969/j.issn.1000-6621.2021.08.003
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    Objective To evaluate the effectiveness of the new financing mode (government funding after medical insurance, financial support from different sources) by comparing the medical expenses of pulmonary tuberculosis patients among the three districts (Xingqing, Jinfeng, and Xixia) in Yinchuan City in 2016 and 2019. Methods Derive a total of 823 cases of pulmonary tuberculosis patients registered in the three districts from the “Tuberculosis Management Information System”, screen all patients’ inpatient and outpatient expenses during the entire treatment period form the “Hospital Information System” of the Fourth People’s Hospital in Ningxia Hui Autonomous Region, 805 cases were retrieved, and to compare the changes of hospital expenses generated by patients in 2016 and 2019. Results A total of 805 cases of tuberculosis patients were enrolled in this study, including 459 patients in 2019 and 346 patients in 2016, the number of males was 437, while the number of females was 368, and a male-to-female ratio of 1.2∶1. The total cost of patients’ self-pay proportion in 2019 was 25.9% (13.1%, 37.1%), compared with 30.9% (6.8%, 39.6%) in 2016 (Z=-2.935, P=0.003). The proportion of outpatient expenses paid by patients was 28.6% (24.4%, 33.4%) in 2019, lower than 34.6% (30.1%, 40.0%) in 2016 (Z=-8.076, P<0.001). There was no statistical significance in the proportion of outpatient expenses paid by patients. In 2016, the cost of drugs accounted for the highest proportion of the total treatment cost of tuberculosis patients which was 42.8% (1890000 yuan/4416000 yuan), and this was reduced to 31.0% (2181000 yuan/7027000 yuan) in 2019. In 2016 and 2019, the outpatient examination cost accounted for 67.8% (259000 yuan/382000 yuan) and 67.2% (602000 yuan/896000 yuan) respectively, both accounted for the highest proportion of the outpatient cost in the same year. Among hospitalization expenses, the highest proportion in 2016 was drug expenses accounting for 44.8% (1806000 yuan/4034000 yuan) and this was reduced to 32.0% (1963000 yuan/6129000 yuan) in 2019. Conclusion After the implementation of the fund-raising mode for tuberculosis patients in Yinchuan, the financial burden of tuberculosis patients was reduced to a certain extent. We should continue to ensure the sustainability of the special subsidy funds, expand the scope of medical insurance, optimize the contents of the coverage, and implement the “one-stop” model.

    Analysis on the effect of diagnosis and treatment management of rifampicin-resistant pulmonary tuberculosis and financing mode in Ningxia
    TIAN Xiao-mei, LEI Juan, LIU Jing, LIU Guang-tian, PAN Li, LIU Tao, SHI Feng, WANG Xiao-lin
    Chinese Journal of Antituberculosis. 2021, 43(8):  772-777.  doi:10.3969/j.issn.1000-6621.2021.08.004
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    Objective To analyze the effect of diagnosis and treatment management of rifampicin-resistant pulmonary tuberculosis (RR-PTB) and financing mode in Ningxia Hui Autonomous Region (Ningxia) during the third phase of China National Health and Family Planning Commission-Bill and Melinda Gates Foundation Tuberculosis Prevention Cooperation Project (Ningxia Zhonggai tuberculosis project). Methods From the Tuberculosis Management Information System of China Center for Disease Control and Prevention, information of 406 RR-PTB patients with positive pathogens (smear-positive, positive-only, positive-only in molecular biology) diagnosed in tuberculosis-designated hospitals of all levels in Ningxia between January 1, 2016 and December 31, 2020 was collected. In addition, the cost information of 120 outpatients and inpatients with RR-PTB successfully treated from January 1, 2016 to December 31, 2018 was collected from the Hospital Information System of Ningxia Fourth People’s Hospital. The changes of rifampicin-resistance screening, detection, treatment and successful treatment in PTB patients with positive etiology during 2016-2020 were analyzed (in 2019 and 2020, all the RR-PTB patients were not included in the analysis because that they had not yet finished treatment). Ratioes of outpatient critical illness medical insurance (medical insurance) expenses, government expenses and personal expenses were also analyzed. Results From 2016 to 2020, the detection rate of rifampicin resistance in etiologically positive PTB patients increased from 45.48% (392/862) to 96.96% (1116/1151), and the positive rate decreased from 17.09% (67/392) to 5.65% (63/1116). The differences were statistically significant (X2trend values were 942.974 and 61.904, both P values were 0.000). The treatment rate of RR-PTB patients increased from 76.12% (51/67) to 88.89% (56/63), the difference was statistically significant (X2trend=11.749, P=0.001). From 2016 to 2018, the success rate of treatment increased from 52.94% (27/51) to 61.84% (47/76), but the difference was not statistically significant (X2trend=0.952, P=0.329). The cost analysis of patients successfully treated showed that, from 2016 to 2018,the costs of the full course of treatment for every paient were 104326 (99670, 107100) yuan, 102589 (96718, 106016) yuan, and 102774 (96429, 104643) yuan, respectively. Among them, proportions of medical insurance expenses (16.43% (13.83%,19.63%),36.56% (28.40%,45.48%), and 50.61% (34.80%,63.57%), respectively) and government expenses (0.00%, 0.00%, and 10.74% (9.17%,22.52%), respectively) increased year by year, while the proportion of personal expenses (53.57% (50.40%,62.23%),30.11% (29.68%,48.92%) and 15.74% (15.27%,24.29%), respectively) decreased year by year; all the differences were statistically significant (Z values were 34.741,47.247 and 50.296, respectively; all P values were 0.000). Conclusion The comprehensive model of tuberculosis prevention and treatment of “policy development, medical insurance first, government support, graded burden” implemented in the third phase of Ningxia Zhonggai tuberculosis project was significantly beneficial to the screening, treatment and reducing the economic burden of RR-PTB patients.

    Analysis of the effect of the new medical insurance payment model in reducing economic burden of pulmonary tuberculosis patients
    ZHANG Tie-juan, PAN Yan, MA Jian-jun, HOU Wei, ZHANG Bin
    Chinese Journal of Antituberculosis. 2021, 43(8):  778-782.  doi:10.3969/j.issn.1000-6621.2021.08.005
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    Objective To evaluate the effect of disease based full-course payment in Dehui City, a pilot area for the payment reform of National Health Commission of China-Bill and Melinda Gates Foundation TB Collaboration Project Phase Ⅲ in Jilin Province, and provide reference for tuberculosis (TB) prevention and control strategies during the 14th Five-Year Plan. Methods In 2018, under the guidance of national experts, a localized clinical pathway was formulated. The payment standard was determined according to this clinical pathway and actual costs (3600 yuan for outpatient and 9000 yuan for full course treatment). Outpatient expenses were packaged and paid per person for the full treatment course, while hospitalization expenses were paid in accordance with disease based payment. Reimbursement threshold for outpatients and inpatients was cancelled and medical expenses were reimbursed at a proportion of 70%. Data was collected and analyzed for costs of diagnosis and treatment of outpatient and inpatient pulmonary tuberculosis (PTB) patients in Dehui City before and after pilot project implementation during 2017 and 2018. Results The proportion of hospitalization for PTB patients decreased from 16.9% (87/515) in 2017 to 14.5% (100/689) in 2018. In 2018, outpatient expenses decreased by 18.1% (167706.8/928481.2) year-on-year, and hospitalization expenses decreased by 6.6% (29318.4/445946.6) year-on-year. The average expense of outpatient per visit and the average expense of inpatient per visit were 340.2 yuan and 4044.9 yuan in 2018, which had decreased by 29.5% (142.6/482.8) and 21.1% (1080.9/5125.8) compared with 2017, respectively. The median expense per PTB patient (not including pleurisy TB) who completed the full treatment course in 2018 was 3651.3 (1952.5, 6122.9) yuan, which decreased by 20.5% (941.3/4592.6) compared with 2017. In 2018, the outpatient and inpatient out-of-pocket proportions were both 30.0% (228232.3/760774.4; 124988.5/416628.2), which were lower than those in 2017 (outpatient 38.5% (357674.5/928481.2) and inpatient 33.2% (147865.9/445946.6)). The difference was statistically significant (χ2=1016.000, P<0.001; χ2=186.000, P<0.001). Conclusion The disease based payment model for full treatment course in Dehui City adopted intervention measures including standardized mechanism, patient service packages, which limited the unreasonable growth of medical expenses and reduced the patients’ economic burden.

    Evaluation of using GeneXpert MTB/RIF technology in rapid detection of pulmonary tuberculosis and rifampicin resistance in Ningxia
    LIU Jing, XIAO Hui-xia, TIAN Xiao-mei, WANG Fu-rui, TIAN Xu-sheng, WANG Xiao-ping, CHEN Min, LEI Juan, WANG Xiao-lin
    Chinese Journal of Antituberculosis. 2021, 43(8):  783-789.  doi:10.3969/j.issn.1000-6621.2021.08.006
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    Objective To evaluate the application effect of GeneXpert MTB/RIF (GeneXpert for short) technology in rapid detection of pulmonary tuberculosis (PTB) and drug-resistant PTB patients in Ningxia Hui Autonomous Region (Ningxia). Methods Medical records of active PTB patients in Ningxia in 2016 and 2018—2020 were derived from the Tuberculosis Management Information System, a subsystem of China Disease Control and Prevention Information System. Numbers and results of active PTB patients detected by GeneXpert in each city in each year were obtained. The changes of rapid diagnosis of PTB patients and discovery of rifampicin resistance in them before and after the application of GeneXpert detection technology were analyzed and evaluated. Results The percentage of using GeneXpert for detection (application rate) in 2016, 2018—2020 were 22.55% (537/2381), 69.65% (1641/2356), 87.36% (2004/2294) and 89.78% (1634/1820), respectively. The annual difference was statistically significant (χ2=2929.500, P=0.000). From 2018 to 2020, the average application rate was 81.59% (5279/6470), which was about four times of that in 2016 (22.55%, 537/2381). In 2016, the application rate of five cities in the region were as follows: 25.77% (158/613) in Yinchuan City, 23.53% (32/136) in Shizuishan City, 22.80% (140/614) in Wuzhong City, 18.62% (105/564) in Guyuan City, 22.47% (102/454) in Zhongwei City, while the average rates from 2018 to 2020 were: 89.29% (1776/1989) in Yinchuan, 84.47% (555/657) in Shizuishan, 79.44% (1163/1464) in Wuzhong, 70.01% (810/1157) in Guyuan, 81.05% (975/1203) in Zhongwei. There was statistical significance among cities (χ2=190.245, P=0.000). From 2018 to 2020, through GeneXpert detection, the etiological positive rate reached 57.51% (3721/6470), which was 1.6 times of that in 2016 (36.20%, 862/2381). The difference was statistically significant (χ2=359.543, P=0.000). Among patients with smear negative results, 583 cases were GeneXpert positive, accounting for 15.67% (583/3721) of all etiological positive cases. In 2016 and 2018 to 2020, 291 rifampicin resistance tuberculosis (RR-TB) patients were detected by GeneXpert, accounting for 97.32% (291/299) of all RR-TB patients, and 21.40% (64/299) of those RR-TB patients were found in smear negative patients. Conclusion GeneXpert detection technology has covered the whole Ninxia region. Application of GeneXpert has greatly improved the detection rate of patients, especially for smear negative and RR-TB patients.

    Analysis of the efficiency of tuberculosis diagnosis progress based on GeneXpert MTB/RIF application in Zhejiang Province
    LIU Zheng-wei, PENG Ying, ZHANG Ming-wu, ZHANG Yu, CHEN Song-hua, CHEN Bin, WANG Xiao-meng
    Chinese Journal of Antituberculosis. 2021, 43(8):  790-795.  doi:10.3969/j.issn.1000-6621.2021.08.007
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    Objective To evaluate the effectiveness of the diagnostic process of tuberculosis based on the GeneXpert MTB/RIF (Xpert) in increasing the proportion of positive etiology and shorten the time of drug-resistant screening. Methods From the Tuberculosis Information Management System, the subsystem of China Disease Prevention and Control Information System, the registered treatment, laboratory results and drug-resistant screening, etc. of 151526 active pulmonary tuberculosis patients registered from 90 designated tuberculosis medical institutions in Zhejiang Province between 2015 and 2020. The positive etiology results of pulmonary tuberculosis at different times in Zhejiang Province were analyzed to evaluate the effectiveness of drug-resistant tuberculosis. Results From 2015 to 2017, the positive etiology rates of active pulmonary tuberculosis in Zhejiang were 39.05% (10695/27385), 37.75% (9877/26166) and 40.68% (10580/26009), respectively, the differences were statistically significant (χ2=47.206, P<0.01). From 2018 to 2020, the pathogenic positive rate of active tuberculosis in Zhejiang Province was 56.11% (14197/25302), 62.27% (15161/24348) and 64.39% (14369/22316), showing an increasing trend year by year. The differences were statistically significant (χ2trend=374.701, P<0.01). From 2017 to 2020, the contribution rate of Xpert in etiology-positive cases increased from 0.63% (67/10580) to 24.02% (3452/14369), and the detection rate and positive contribution rate in smear-negative pulmonary tuberculosis increased from 2.00% (321/16048) and 40.81% (131/321) to 54.62% (7338/13434) and 60.63% (4449/7338), respectively. When smear, culture and Xpert were combined used to detect tuberculosis, the etiological detection rate in 2020 reached 99.62% (22178/22262); and the positive rate of detection was 64.37% (14275/22178), significantly higher than those of smear (39.30%, 8697/22131) and culture only (50.66%, 7629/15059) (χ2=2788.140, 695.491, both P<0.01). Compared with the traditional proportional method of phenotypic susceptibility test, the drug-resistant tuberculosis screening process based on Xpert could shorten the diagnosis time (median (quartiles)) of drug-resistant from 62.5 (34.0, 94.3) d in 2015 to 1.0 (0.0, 7.0) d in 2020. Conclusion The tuberculosis diagnosis process based on the Xpert molecular detection technology could not only significantly improve the etiological positive rate of tuberculosis, but also obviously shorten the diagnosis time of drug-resistant patients.

    Analysis of epidemiologic characteristics of pulmonary tuberculosis patients in floating population in Guangzhou City from 2014 to 2020
    LAI Keng, JIANG Kun-hong, XIE Wei, YANG Jie-ying, LEI Yu, DU Yu-hua
    Chinese Journal of Antituberculosis. 2021, 43(8):  796-802.  doi:10.3969/j.issn.1000-6621.2021.08.008
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    Objective To analyze the characteristics of pulmonary tuberculosis (PTB) in floating population in Guangzhou City, and provide evidence for PTB control strategies of floating population. Methods The data of PTB patients of floating population in Guangzhou City from 2014 to 2020 was collected in the “Tuberculosis Information Management System”, which included age, gender, occupation, patient discovery method, treatment classification, etiological results and so on. The distribution characteristics of this population were analyzed, and the seasonal effect of time series was analyzed by using seasonal index. Results From 2014 to 2020, a total of 68329 cases of PTB patients were registered in Guangzhou, among which 30692 cases were from floating population, accounting for 44.92% of total cases, from 30.81% (3530/11457) in 2014 to 50.73% (4185/8249) in 2020 (χ2trend=441.57, P<0.01). The median age was 33 (23,46) years and the main age group was 25-34 years old (32.69%, 10034/30692). The main occupation was housework and unemployment (45.85%, 14073/30692). The main source of patients was due to symptoms (44.22%, 13572/30692), and the patients were generally delayed (47.12%, 14462/30692). With the change of the year, the proportion of provincial mobility of household registration type increased (χ2=208.57, P<0.01), increasing from 25.89% (914/3530) in 2014 to 36.39% (1523/4185) in 2020; the source of clinical consultation decreased first then increased (χ2=971.89, P<0.01), from 45.69% (1613/3530) in 2014 to 30.74% (1285/4180) in 2017, and then up to 57.51% (2407/4185) in 2020. The prevalence of PTB in floating population was from March to September per year, with peak incidence in April and July. The proportion of PTB patients of floating population mainly concentrated in Baiyun and Tianhe Districts, increasing from 13.85% (489/3530) and 11.47% (405/3530) in 2014 to 24.64% (1031/4185) and 16.94% (709/4185) in 2020, respectively. Conclusion The epidemic situation of PTB among the floating population in Guangzhou is still severe, and shows seasonal variation. The patients are mainly male, young adults, housekeeping, housework and unemployment and have high delay rates and regional distribution, corresponding prevention and control strategies should be formulated according to the epidemic characteristics.

    Analysis of the control and prevention of MTB/HIV coinfection in Hefei from 2014 to 2019
    CAO Hong, DENG Xiao-lan, QIAN Bing, ZHANG Jie-ying, CHEN Wei
    Chinese Journal of Antituberculosis. 2021, 43(8):  803-807.  doi:10.3969/j.issn.1000-6621.2021.08.009
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    Objective To analyze the control and prevention effects of Mycobacterium tuberculosis and human immunodeficiency virus (MTB/HIV) coinfection in Hefei, and to provide scientific basis for the control and prevention of MTB/HIV coinfection in Hefei. Methods From 2014 to 2019, the AIDS Prevention and Control Department of each district (county) Center for Disease Control and Prevention (CDC) in Hefei referred HIV/AIDS patients to local tuberculosis designated hospitals for chest X-ray examination (chest X-ray). All of 2084 newly diagnosed HIV/AIDS patients and 8326 previous HIV/AIDS patients were screened for tuberculosis. Tuberculosis patients were tested for HIV antibody in designated TB hospitals, and those confirmed positive HIV antibody patients were referred to the AIDS Prevention Department of CDC for treatment. A total of 18146 TB patients registered from 2014 to 2019 were tested for HIV antibody. Results From 2014 to 2019, 2137 new HIV/AIDS patients were detected, among whom 2084 were screened for tuberculosis, and the screening rate was 97.52%. Twenty-four tuberculosis patients were detected, and the detection rate was 1.15% (24/2084). Among 8326 previous HIV/AIDS patients, 37 tuberculosis patients were detected. The HIV antibody test rates from 2014 to 2019 were 60.72% (2806/4621), 60.86% (2676/4397), 63.84% (2770/4339), 75.16% (3128/4162), 84.41% (3638/4310) and 82.42% (3128/3795). The HIV antibody test rate showed an upward trend in 6 years, and the difference was statistically significant (χ2trend=1068.000, P=0.000). Twelve patients with positive HIV antibody were detected in 18146 tuberculosis patients, and the detection rate was 0.07%. Conclusion The detection rate of tuberculosis among newly-detected HIV/AIDS patients in Hefei is relatively high. To improve the tuberculosis screening rate of newly detected HIV/AIDS patients, and realize the sharing of tuberculosis and AIDS data and information, in order to achieve early detection and treatment of MTB/HIV coinfected patients, reduce the mortality of coinfected patients, and effectively control the MTB/HIV epidemic in Hefei.

    T lymphocyte exhaustion on the expression of immune effect in patients with multidrug-resistant pulmonary tuberculosis
    WANG Li, XIONG Kun-long, ZHU Chang-tai, FAN Lin
    Chinese Journal of Antituberculosis. 2021, 43(8):  808-812.  doi:10.3969/j.issn.1000-6621.2021.08.010
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    Objective To explore the characteristics of T lymphocyte exhaustion in immune responses from peripheral blood of patients with multidrug-resistant pulmonary tuberculosis (MDR-PTB) by flow cytometry. Methods Fifty-eight patients with pulmonary tuberculosis hospitalized in Shanghai Pulmonary Hospital affilicated to Tongji University were prospectively included from January 2020 to August in 2020, including 20 patients with MDR-PTB, 38 patients with drug susceptible pulmonary tuberculosis (DS-PTB), and 20 healthy donors as control (HD).The elbow vein anticoagulant blood (10ml) of each patient was collected, peripheral blood mononuclear (PBMC) cells were isolated, MTB-specific programmed death-ligand-1 (PD-1), T lymphocyte immunoglobulin and mucin-domain-containing molecules-3 (Tim-3) and lymphocyte activation gene-3 (Lag-3) on CD4+ and CD8+ T lymphocytes and intracellular cytokines of interleukin-2 (IL-2), interferon gamma (IFN-γ) and tumor necrosis factor-α (TNF-α) were detected by flow cytometry. Results The expression of CD4-PD-1, CD8-PD-1, CD4-Tim-3 and CD8-Tim-3 in MDR-PTB (median (quartile))(respectively were 24.50% (21.58%, 26.00%), 19.95% (16.10%, 21.65%), 3.75% (3.20%, 4.68%) and 12.65% (10.65%, 14.10%)), which were significantly higher than those of HD (respectively were 13.10% (11.80%, 17.80%), 12.55% (9.61%, 18.18%), 0.67% (0.46%, 2.41%) and 3.78% (2.35%, 6.55%)) and DS-PTB (respectively were 14.50% (11.90%, 20.00%), 13.20% (8.61%, 18.23%), 1.12% (0.71%, 3.36%) and 3.59% (2.10%, 7.52%)), the differences were statistically significant (Z=-4.009, -4.159, -3.027, -3.284, -3.565, -3.967, -5.568, -3.261, all P values <0.05). CD4-IL-2 and CD8-IL-2 levels of MDR-TB (1.30% (0.73%, 2.71%), 2.27% (1.03%, 3.11%)) were higher than those of HD (0.67% (0.44%, 1.10%),0.59% (0.39%, 0.91%)), the differences were statistically significant (Z=-2.670, -3.917,all P values <0.05). CD4-IFN-γ of DS-PTB (0.92% (0.59%, 2.02%)) was significantly higher than that of HD group (0.65% (0.38%, 0.82%)), CD8-IFN-γ of MDR-PTB and DS-PTB (1.16% (0.53%, 2.03%) and 1.80% (0.97%, 3.04%)) were significantly higher than that of HD group (0.69% (0.35%, 0.91%)), the differences were statistically significant (Z=-2.337, -1.988,-4.455, all P values <0.05). TNF-α level of DS-PTB (0.83% (0.67%, 1.22%)) was higher than that of HD (0.44% (0.28%, 0.71%)) and MDR-PTB (0.41% (0.28%, 0.82%)), the differences were statistically significant (Z=-3.903, -2.919,all P values <0.05). Conclusion T lymphocyte exhaustion exists in patients with MDR-PTB, T lymphocyte immune effect was inhibited by cells exhaustion.

    Establishment and evaluation of rapid detection of pyrazinamide resistance of Mycobacterium tuberculosis by probe enzyme digestion using Surveyor
    HU Yan-jie, GONG Shi-wei, REN Yi
    Chinese Journal of Antituberculosis. 2021, 43(8):  813-816.  doi:10.3969/j.issn.1000-6621.2021.08.011
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    Objective To establish a probe enzyme digestion method using Surveyor for rapid detection of pyrazinamide (PZA) resistance detection of Mycobacterium tuberculosis (MTB) and evaluate the clinical value. Methods A total of 91 multidrug-resistant (MDR) MTB strains from Wuhan Pulmonary Hospital were collected. All strains were amplified using the above primers∶the downstream primer with the ratio of 2∶5, and the standard strain H37Rv of MTB was amplified using the upstream primer: the downstream primer with the ratio of 5∶2. Then, the PCR products were mixed in a ratio of 1∶1, and the electrophoresis was carried out after being digested by the endonuclease Surveyor enzyme. The gene mutation of pncA gene and its promoter sequence were determined based that the hybridization bands could be cleaved by the endonuclease Surveyor. The application value of endonuclease Surveyor digestion method was evaluated compared to BACTEC MGIT 960 method used to detect PZA resistance and pncA gene and its promoter gene sequencing method. Results For the detection of PZA resistance of MTB, compared to the BACTEC MGIT 960 method, the sensitivity, specificity and accuracy of the probe enzyme digestion method were 100.0% (29/29), 87.1% (54/62) and 91.2% (83/91), respectively. Compared to the sequencing results of pncA gene and its promoter region, the sensitivity, specificity and accuracy of the probe enzyme digestion method were 100.0% (37/37),100.0% (54/54) and 100.0% (91/91), respectively. Conclusion The probe enzyme digestion method demonstrated very high concordance with pncA gene and its promoter region, it might provide a new way for the detection of PZA resistance of MTB in areas without sequencing conditions.

    Application value of thermostatic microfluidic system in detection and identification of Mycobacterium tuberculosis complex and nontuberculous mycobacteria
    WANG Quan, MA Rui-ying, YANG Ting, ZHANG Ya-li, XU Miao, SA Yu-ling, CHEN Qing-bo
    Chinese Journal of Antituberculosis. 2021, 43(8):  817-820.  doi:10.3969/j.issn.1000-6621.2021.08.012
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    Objective To evaluate the application value of thermostatic microfluidic system in detection and identification of Mycobacterium tuberculosis complex (MTBC) and nontuberculous mycobacteria (NTM). Methods A total of 624 sputum specimens positive in acid-fast staining were collected from the Eighth Affiliated Hospital of Xinjiang Medical University from September 2018 to December 2019. Roche solid culture, p-nitrobenzoic acid (PNB) and thiophene-2-carboxylic acid hydrazine (TCH) growth test, and constant temperature microfluidic system were used for mycobacterial detection and strain identification; bacterial species identification results of Roche solid culture and PNB/TCH growth test were used as reference to evaluate the efficiency of the thermostatic microfluidic system in detecting mycobacteria and identifying bacterial species. Results Among 624 sputum samples, 612 (98.1%) were positive using Roche solid culture, and 607 (97.3%) were positive by thermostatic microfluidic system. The difference was not statistically significant (χ2=0.021, P=0.950). Using the results of Roche solid culture method as the standard, the sensitivity and specificity of the thermostatic microfluidic system for detecting mycobacteria in sputum samples with positive acid-fast staining were 99.2% (607/612) and 100.0% (12/12), respectively, the Kappa value was 0.82. Using the results of the PNB/TCH growth test as the standard, the sensitivity and specificity of the thermostatic microfluidic system for detecting MTBC in sputum samples were 99.6% (513/515) and 100.0% (97/97), respectively, and the Kappa value was 0.99; the sensitivity and specificity of the thermostatic microfluidic system for detecting NTM in sputum samples were 96.9% (94/97) and 100.0% (515/515), respectively, and the Kappa value was 0.98. Conclusion The thermostatic microfluidic system has good performance in identifying MTBC and NTM in sputum specimens when based on acid-fast staining.

    Diagnostic value of GeneXpert MTB/RIF in detecting patients with coal workers’ pneumoconiosis complicated with pulmonary tuberculosis
    YANG Xiao-li, HE Bing, WANG Jiao-lei, ZHANG Yun-yun, ZHANG Chun-xia, LI Yue, LI Jian-jun, SHI Wen-tao
    Chinese Journal of Antituberculosis. 2021, 43(8):  821-825.  doi:10.3969/j.issn.1000-6621.2021.08.013
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    Objective To investigate the clinical diagnostic value of GeneXpert MTB/RIF (Xpert for short) in detecting patients with coal workers’ pneumoconiosis complicated with pulmonary tuberculosis. Methods Morning sputum specimens of 64 patients diagnosed with coal workers’ pneumoconiosis complicated with pulmonary tuberculosis in Beijing Beijing Coal Cooperation General Hospital from January 2019 to December 2020 were collected continuously. Sputum smear, BACTEC MGIT 960 liquid culture (referred to as “MGIT 960 culture”) and Xpert test were performed at the same time. Using MGIT 960 culture as the standard, sensitivity and specificity of Xpert in detecting MTB from sputum samples were evaluated. Culture positive strains were tested for rifampicin resistance, compared with Xpert test results. Results Using the liquid culture results of MGIT 960 as the golden standard, the sensitivity of smear test and Xpert test in detection MTB were 27.8% (5/18) and 88.9% (16/18), respectively. The sensitivity of Xpert test was higher than that of smear test, difference was statistically significant (χ2=13.829, P=0.000).The consistency between Xpert test and MGIT 960 liquid culture was moderate (Kappa=0.537). The areas under the receiver operating characteristic curve (ROC) of Xpert test and sputum smear test were 0.836 and 0.628, respectively, which suggested that Xpert test was of good diagnostic value. Using drug sensitivity test (DST) results with MGIT 960 as the reference standard, the sensitivity, specificity and consistency of Xpert were (4/4), 78.6% (11/14) and 83.3% (15/18) for detecting rifampicin resistance. The difference between the two detection methods was statistically significant (χ2=4.889, P=0.027). The consistency of the two methods was moderate (Kappa=0.620). Conclusion Xpert has high clinical application value in the early diagnosis of coal workers’ pneumoconiosis complicated with pulmonary tuberculosis and the determination of rifampicin resistance.

    Evaluation of the effectiveness of bronchoscopy in the treatment of lymph node fistula tracheobronchial tuberculosis in children
    LIU Fang, RAO Xiao-chun, MA Yu-yan, MENG Chen-fang, PAN Yue-na, JIAO An-xia, SHEN A-dong
    Chinese Journal of Antituberculosis. 2021, 43(8):  826-831.  doi:10.3969/j.issn.1000-6621.2021.08.014
    Abstract ( 395 )   HTML ( 17 )   PDF (2231KB) ( 260 )   Save
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    Objective To evaluate the safety and effectiveness of bronchoscopy in the treatment of lymph node fistula tracheobronchial tuberculosis (TBTB) in children. Methods The basic information, bronchoscopic characteristics of lesions, efficacy, frequency and complications of bronchoscopic treatment of 130 children with lymph node fistula TBTB admitted in Beijing Children’s Hospital affiliated Capital Medical University between January 2012 and December 2019 were retrospectively analyzed. All the children were treated with bronchoscope clamp combined with lavage and local spray. The safety and effectiveness of these treatment were analyzed. Results Of the 130 children, 88 were male (67.7%) and 42 were female (32.3%). The age ranged from 1 month to 12 years, with 86.9% (113/130) <5 years old. A total of 281 lymph node fistula lesions were involved and mainly located on right and upper lobe bronchus. The median (quartile) of lesions number in children aged ≤1 year old was 2.0 (1.0, 4.0), which was significantly higher than that in children aged >1 year old (2.0 (1.0, 2.0), U=1514.000, P=0.004). The overall effective rate of bronchoscope clamp combined with lavage and local spray was 95.4% (124/130). The number of interventions (median (quartile)) was 6.0 (3.8, 9.0). The number of interventions (median (quartile)) in children with single lesion was 3.0 (2.0, 5.0) times, which was significantly lower than that in children with multiple lesions (8.0 (5.0, 10.0), U=581.500, P<0.01). There were no serious complications during or after the treatment. All the children were followed up more than 6 months, and no recurrence was observed. Conclusion Bronchoscope clamp combined with lavage and local spray was of good effect and safety for lymph node fistula TBTB in children.

    Endovascular embolization for pulmonary artery pseudoaneurysms associated with pulmonary tuberculosis with massive hemoptysis:three case reports and literature review
    CHEN Shan-shan, TANG Xiao-jun, TANG Xiao-li, DAI Guang-chuan, ZENG Yi, ZHANG Xia
    Chinese Journal of Antituberculosis. 2021, 43(8):  832-837.  doi:10.3969/j.issn.1000-6621.2021.08.015
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    Objective To summarize and analyze the clinical characteristics of pulmonary tuberculosis-associated pulmonary artery pseudoaneurysms (PAP) with massive hemoptysis in the treatment of arterial embolization intervention. Methods The clinical manifestations, treatment and prognosis of 3 patients with PAP complicated with pulmonary tuberculosis and massive hemoptysis who underwent interventional embolization in Nanjing Second Hospital were reported. PubMed database was searched with key words of “pulmonary tuberculosis” and “pulmonary artery pseudoaneurysms” or “Rasmussen’s aneurym” from January 2011 to December 2020. Reviews, repeated publications and articles with incomplete data were excluded, and researches with complete clinical data of patients with tuberculosis complicated with PAP were included. The clinical features, imaging manifestations, PAP typing, methods of diagnosis and treatment, and prognosis of the patients were collected to review the literature. Results Three cases were diagnosed with pulmonary tuberculosis complicated with massive hemoptysis. Radiology suggested cavity lesion of pulmonary tuberculosis, and chest CT angiography (CTA) and pulmonary angiography showed that PAP were secondary to pulmonary artery vessels on the pulmonary cavity wall of tuberculosis. Case 1, male, 24 years old, with blood in sputum for 7 days and aggravation for 3 days (hemoptysis volume >500 ml/d, unconscious) as the main manifestations. The patient had massive hemoptysis again after bronchial artery embolization and hemoptysis was stopped after embolization of left internal thoracic artery, left lateral thoracic artery and left pulmonary artery. Case 2, female, 65 years old, with hemoptysis for 5 days (100 ml/time, twice/day) and chest tipiness as the main presentation. Massive hemoptysis was relapsed after bronchial artery embolization and was stopped until right pulmonary artery embolization surgery. Case 3, male, 58 years old, presented with cough, chest tiresomy and night sweats for 4 months and hemoptysis for 3 days (300 ml). Hemoptysis still occurred after bilateral bronchial artery embolization, and was stopped after embolization of left and right bronchial arteries and right upper pulmonary artery. Through PubMed database searching, a total of 21 literatures were obtained, of which 42 patients with tuberculosis complicated with PAP. A total of 45 patients were included with the 3 patients in this paper, including 36 males and 9 females, with a median age of 52.0 (35.0,63.0) years. CTA was performed in all patients, and the detection rate of PAP was 100.0%. Pulmonary arteriography was performed in 41 cases and the detection rate of PAP was 75.6% (31/41). Forty-one patients received vascular interventional therapy, including 26 cases of pulmonary artery embolization, 7 cases of bronchial artery embolization, 8 cases of bronchial artery embolization and pulmonary artery embolization. Forty cases were of effective hemostasis after surgery and 1 patient died of asphyxia due to massive hemoptysis. Forty cases were followed up after surgery, of which 2 patients relapsed and were cured by surgical resection and bronchial artery embolization. Conclusion PAP is one of the main causes of massive hemoptysis in pulmonary tuberculosis, and pulmonary vascular interventional embolization is still the preferred intervention for PAP complicated with massive hemoptysis. When bronchial artery embolization is not effective or hemoptysis recedes recently, chest CTA examination should be performed in time to rule out the possibility of PAP.

    Analysis of surgical effect of cervical lymph node tuberculosis patients at different imaging stages
    REN Hang-kong, HUANG Guang-hong, ZHAO Jian, ZHOU Jie, NIU Jing-jing
    Chinese Journal of Antituberculosis. 2021, 43(8):  838-842.  doi:10.3969/j.issn.1000-6621.2021.08.016
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    Objective To explore the surgical effect of cervical lymph node tuberculosis patients at different imaging stages, in order to find the most suitable stage for surgical treatment. Methods A total of 201 cervical lymph node tuberculosis patients admitted to Xi ’an Chest Hospital and confirmed by pathology were collected from Xi’an Chest Hospital between January 2019 and January 2021. According to results of neck enhanced CT, patients were divided into 4 groups of different stages, which were stage Ⅰ group (nodular type, n=48), stage Ⅱ group (infiltrative type, n=62), stage Ⅲ group (abscess type, n=56), stage Ⅳ group (ulcerative type or ulcerative fistula type, n=35). The final length of scar, the healing time and the recurrence rate of cervical lymph node tuberculosis after wound healing in these 4 groups were observed. Results The wound healing time, the length of scar and the recurrence rate in stage Ⅰ group were 5.00 (5.00, 5.00) d, (3.79±0.53) cm and 10.4% (5/48); 10.00 (8.75, 12.00) d, (4.43±0.44) cm and 11.3% (7/62) in stage Ⅱ group, 16.00 (12.25, 19.75) d, (5.09±0.65) cm and 26.8% (15/56) in stage Ⅲ group, 19.00 (16.00, 22.00) d, (4.86±0.51) cm and 28.6% (10/35) in stage Ⅳ group. Comparison of the 4 groups showed that the postoperative healing time in stageⅡgroup was higher than that in stage Ⅰ group, the postoperative healing time in stage Ⅲ group was higher than that in stage Ⅱ group, and the postoperative healing time in stage Ⅳ group was higher than that in stage Ⅲ group, all the differences were statistically significant (Z=152.435, P<0.001), the scar length in stage Ⅱ group was longer than that in stage Ⅰ group, the scar length in stage Ⅲ group was longer than that in stage Ⅱ group, both the differences were statistically significant (F=55.887, P<0.001). The recurrence rates after postoperative healing in stage Ⅲ and stage Ⅳ groups were significantly higher than those in stageⅠand stage Ⅱ groups (χ2=9.165, P=0.027). Conclusion Of the cervical lymph node tuberculosis, the wound healing time, the length of scar and the recurrence rate increased as the stage progressed. Therefore, surgical treatment was recommended to perform as soon as possible for cervical lymph node tuberculosis patients whose lesion did not change after drug treatment.

    Review Articles
    Application progress of Xpert MTB/RIF Ultra assay in tuberculosis diagnosis in children
    WANG Ya-cui, SUN Lin, SHEN A-dong
    Chinese Journal of Antituberculosis. 2021, 43(8):  843-846.  doi:10.3969/j.issn.1000-6621.2021.08.017
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    Accurate diagnosis of tuberculosis timely is challenging in children because of the nonspecific clinical manifestations, low load of Mycobacterium tuberculosis in specimens, and insensitive and time-consuming characteristics of traditional diagnostic methods. Xpert MTB/RIF Ultra (Xpert Ultra), a new generation assay of Xpert, is gradually attract the attention of researchers and clinicians due to its superior performance and shorter turnaround time. In this review, the application of Xpert Ultra technology in pediatric tuberculosis was summarized to provide assistant for the diagnosis and treatment.

    Immunomodulatory effect of Mycobacterium tuberculosis lipoarabinomannan and its value on tuberculosis diagnosis
    FAN Yu-xin, LIU Mei-xiao, CHEN Jing-jing, XU Xin, ZHANG Yu, YUE Peng, CAO Wen-jing, BAO Fu-kai, LIU Ai-hua
    Chinese Journal of Antituberculosis. 2021, 43(8):  847-852.  doi:10.3969/j.issn.1000-6621.2021.08.018
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    Mycobacterium tuberculosis (MTB) cell wall contains rich lipids, which helps to maintain its own virulence and the long-term latent in the host. Lipoarabinomannan (LAM) is an important component in the cell wall of MTB, and its complex and unique structure is crucial for the growth, survival and virulence of MTB. In this review, we summarized the structure, biosynthetic pathway of LAM and its role in immune response as well as its application value in tuberculosis diagnosis. It could provide a new vision and ideas for its potential as a new biomarker for tuberculosis diagnosis.

    Short Articles
    Temporal-spatial distribution of pulmonary tuberculosis in Fujian Province during 2011—2020
    ZHOU Yin-fa, LIN Shu-fang, DAI Zhi-song, Wei Shu-zhen, CHEN Dai-quan
    Chinese Journal of Antituberculosis. 2021, 43(8):  853-856.  doi:10.3969/j.issn.1000-6621.2021.08.019
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    In order to analyze the temporal-spatial distribution of pulmonary tuberculosis (PTB) in Fujian Province, the information of patients diagnosed with active PTB and tuberculous pleurisy in Fujian Province from 2011 to 2020 were collected from the Infectious Disease Surveillance System, a subsystem of China Disease Control and Prevention Information System. The incidence of the PTB, global and local spatial autocorrelation analysis (Moran’s I index, Getis-Ord G and Getis-Ord Gi* index), visual hotspot analysis and temporal-spatial scanning analysis were implemented by SPSS 24.0, ArcGIS 10.2, local indicators of spatial association (LISA) cluster diagram and SaTScan 9.6 software. The incidence of PTB reported in Fujian decreased from 60.6/100000 (22374/36900000) in 2011 to 45.0/100000 in 2020 (17860/39730000) (χ2trend=1496.216, P<0.05). Annual Global Moran’s I (I=0.292, Z=3.936, P<0.01) and Getis-Ord General G (G=0.000, Z=2.124, P=0.034) index indicated that the incidence of PTB reported in Fujian was somehow clustered. Twenty-two local spatial cluster areas were showed in the LISA cluster diagram, including 11 high-high, 8 low-low, 2 low-high and 1 high-low cluster areas. Local Getis-Ord Gi* index presented that there were 24 “hot spots” regions, including 6 “negative hot spots” and 18 “positive hot spots”. The temporal-spatial scanning analysis showed that the cluster areas and classification were reduced, but the spatial cluster was still obvious. In addition, there were 5 levels of cluster areas in 2011 and 2012, involving 28 counties; while only 3 levels were found in 2018, involving 18 counties.

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

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