Table of Content

10 February 2021, Volume 43 Issue 2

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Original Articles

The analysis of national tuberculosis reported incidence and mortality, 2015—2019

WANG Qian, LI Tao, DU Xin, NI Ni, ZHAO Yan-lin, ZHANG Hui

Chinese Journal of Antituberculosis. 2021, 43(2):  107-112.  doi:10.3969/j.issn.1000-6621.2021.02.002

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Objective To understand main trends of reported case number of tuberculosis (TB) in China from 2015 to 2019. Methods By using TB incident case data (clinical diagnosed and laboratory confirmed) reported and recorded in the National Infectious Disease Reporting and Management System between 2015 and 2019, to analyze the national TB reported incidence and mortality, and TB reported incidence in different provinces,TB reported case numbers in different sex, age groups, occupations and their respective proportions. Results In 2015, the TB reported incidence nationwide was 63.42/100000 (864015/1362470000) which decreased to 55.55/100000 (775764/1396540000) in 2019, 12.41% lower than that in 2015. From 2015 to 2018, the reported incidence of Xinjiang Autonomous Region ranked first among all provinces, which were 184.56/100000 (42413/22980000), 185.66/100000 (43816/2360000), 202.59/100000 (48581/23980000), and 304.90/100000 (74549/24450000). In 2019, the Tibet Autonomous Region became the province with the highest reported incidence which was 182.38/100000 (6274/3440000). In terms of the sex distribution of reported cases in 2015 and 2019, males accounted for 68.97% (595939/864015) and 68.83% (533981/775764) respectively; females accounted for 31.03% (268076/864015) and 31.17% (241783/775764) respectively. In terms of occupational distribution, the proportion of farmers was the highest in 2015-2019, accounting for 64.42% (556643/864015), 63.81% (533637/836236), 62.26% (520003/835193), 61.42% (505664/823342), 60.06% (465945/775764), respectively. Conclusion From 2015 to 2019, the TB reported incidence in China showed a steady downward trend. Attention should be paid to the prevention and control of TB in key occupations and regions such as farmers, Tibet and Xinjiang Autonomous Region.

Analysis on the effect of management strategies for multidrug-resistant tuberculosis in Guangzhou from 2014-2019

KUANG Hao-bin, XIE Yu-hong, FENG Zhi-yu, QIN Hong-juan, LIAO Ya-yi, WANG Min, ZHANG Hong, YUANG Yuan, WU Di, CHEN Ze-ying, TAN Shou-yong

Chinese Journal of Antituberculosis. 2021, 43(2):  113-118.  doi:10.3969/j.issn.1000-6621.2021.02.003

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Objective To evaluate the effect of the management strategies for multidrug-resistant tuberculosis (MDR-TB) in Guangzhou, to provide the basis for the prevention and treatment of tuberculosis. Methods A total of 2417 high-risk patients of MDR-TB screened in Guangzhou Chest Hospital from July 1, 2014 to December 31, 2019 were selected. Their demographic characteristics and clinical data were collected; 671 cases were diagnosed of MDR-TB, and of them, 352 had treatment outcomes until December 31, 2019. The treatment plan of patients registered in Guangzhou were determined by the expert group, hospitalized in designated departments and followed-up in multidrug-resistant clinics, while the other patients chose hospitals and doctors freely. The medical costs of 162 patients from January to May, 2018 were collected. The treatment and outcome of the subjects, as well as the factors affecting the outcome of treatment, and the financial burden of medical care were analyzed. Results Of the 671 MDR-TB patients, 303 were registered in Guangzhou and the detection rate was 21.37% (303/1418), which was significantly lower than that of non-local registered patients (36.84% (368/999); χ²=69.93, P<0.01). Among the 352 patients with treatment outcomes, 200 patients (56.82%) were successfully treated, and 152 (43.18%) had adverse outcomes. Single factor analysis showed that the rate of successful treatment of patients registered in Guangzhou was significantly higher than that of non-local registered patients (69.23% (108/156) vs. 46.94% (92/196), χ²=17.59, P<0.01). The ratios of adverse outcomes in patients aged 41-60 years and ≥61 years were both significantly higher than that in successfully treated patients (52.00% (78/150) vs. 48.00% (72/150), 56.82% (25/44) vs. 43.18% (19/44), χ²=18.45, P<0.01). The rate of successful treatment in patients treated since and after January 1, 2016 was significantly higher than that in patients treated before January 1, 2016 (61.71% (166/269) vs. 40.96% (34/83), χ²=11.13, P<0.01). According to the multivariate regression analysis, the risk factors for adverse outcomes were non-local registration (OR(95%CI)=4.01(2.37-6.79)), aged >40 years (41-60 years old: OR(95%CI)=4.08(1.05-15.96); ≥61 years old: OR(95%CI)=6.51(1.48-28.60)). Treatment started after January 1, 2016 was a protective factor (OR(95%CI)=0.30(0.17-0.52)). The total economic burden of patients registered in Guangzhou was significantly lower that of non-local registered patients (M(Q₁,Q₃), RMB 24674 (17466, 49920) yuan vs. RMB 100215 (63858, 133720) yuan, Z=-7.80, P<0.01). Conclusion The management strategy of MDR-TB in Guangzhou could increase the rate of successful treatment in patients registered in Guangzhou, and reduce the financial burden. The management strategy of MDR-TB patients by the expert group, hospitalized and followed-up in designated departments, and reduction of medical costs should be promoted.

Analysis of epidemiological characteristics of smear-positive tuberculosis patients in Guangzhou from 2014 to 2019

ZHANG Guang-chuan, LAI Keng, DU Yu-hua, WU Gui-feng, LEI Yu, SHEN Hong-cheng, YANG Jie-ying, LIN Ying, ZHONG Min-er, ZHONG Zhi-qing, LIU Li, LI Tie-gang

Chinese Journal of Antituberculosis. 2021, 43(2):  119-125.  doi:10.3969/j.issn.1000-6621.2021.02.004

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Objective To analyze the epidemiological characteristics of smear-positive pulmonary tuberculosis patients in Guangzhou from 2014 to 2019, and to provide scientific evidence for development of pulmonary tuberculosis prevention and control measures. Methods The information of 24344 smear-positive pulmonary tuberculosis patients registered in Guangzhou from 2014 to 2019 was collected through the subsystem “Tuberculosis Information Management System” of the “China Disease Prevention and Control Information System”, including household registration, gender, occupation, case detection channel and treatment category, etc. Seasonal index was applied to analyze the seasonal effect of time series, and Moran index was applied to analyze the global spatial autocorrelation of geographic information. Results The average annual registration rate of smear-positive tuberculosis in Guangzhou from 2014 to 2019 was 28.53/100000 (24344/85.3338 million), and the average annual registration rate in each district was 20.49/100000 to 43.74/100000. The average registration rate performed “high in the west and low in the east”. The annual average registration rate of smear-positive tuberculosis in Yuexiu District was the highest (43.74/100000 (3069/7.0168 million)). The total registration rate decreased from 38.39/100000 (5022/13.0805 million) in 2014 to 21.39/100000 (3274/15.3059 million) in 2019 with a significant trend ($x^{2}_{trend}$=1110.440, P<0.01). Among the smear-positive pulmonary tuberculosis patients, there were 17331 male patients and 7013 female patients, with a male-female ratio of 2.47∶1; the proportion of the transient population increased year by year ($x^{2}_{trend}$=12.197, P<0.01), from 30.19% (1516/5022) in 2014 to 47.62% (1559/3274) in 2019; domestic workers accounted for the highest proportion of occupations, which was 36.59% (8908/24344); medical consultation was the main way to find smear-positive tuberculosis patients, accounting for 48.66% (11846/24344); the smear-positive rate of retreated patients reached 68.16% (2894/4246). The prevalence of smear-positive pulmonary tuberculosis was January (with the seasonal index 110.40) and March to August (seasonal indexes were 108.00, 105.70, 112.90, 104.50, 110.40 and 106.90 respectively) each year; global spatial autocorrelation analysis showed that there was no spatial clustering of smear-positive pulmonary tuberculosis patients in Guangzhou as a whole (Moran I values from 2014 to 2019 were -0.180, -0.160, 0.180, 0.141, -0.097 and -0.095, Z values were -0.440, -0.391, 1.382, 1.038, -0.006 and 0.032, P values were 0.374, 0.393, 0.101, 0.158, 0.472 and 0.463, respectively). Conclusion The overall prevalence of smear-positive pulmonary tuberculosis in Guangzhou is on a downward trend, and smear-positive pulmonary tuberculosis registration presents a seasonal variation. The prevalence of smear-positive pulmonary tuberculosis in different regions is different, and the transient population should be regarded as the key population for tuberculosis control.

Analysis of influencing factors of death in TB patients complicated with AIDS during anti-tuberculosis treatment in Yunnan, 2011-2019

YE Jin-xin, XU Lin, CHEN Jin-ou, QIU Yu-bing, LYU Tong

Chinese Journal of Antituberculosis. 2021, 43(2):  126-131.  doi:10.3969/j.issn.1000-6621.2021.02.005

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Objective To investigate the influencing factors for deaths of tuberculosis (TB) patients complicated with acquired immune deficiency syndrome(AIDS) during anti-tuberculosis treatment in Yunnan province from 2011 to 2019, so as to provide a reference for the prevention and treatment of TB patients complicated with AIDS. Methods Treatment information about 3329 TB patients complicated with AIDS receiving anti-tuberculosis treatment in Yunnan province from January 2011 to December 2019 was collected via the “Tuberculosis Management Information System”. The demographic characteristics, clinical characteristics, and antiviral treatment of 246 patients (7.39%, 246/3329) who died during anti-tuberculosis treatment were described. Kaplan-Meier method, Log-rank test and Cox proportional hazard regression model were used to analyze the influencing factors of death. Results Among the 246 patients, 98 (39.84%,98/246) died during intensive phase of anti-tuberculosis treatment. The majority of death cases were males (81.71%,201/246);the median age (M(Q₁,Q₃)) of them was 40 (33, 48) years. Cox regression model showed that patients over 60 years old (aHR=2.00, 95%CI=1.27-3.15), with a CD4⁺T lymphocyte level of 50-<400 cells/μl (aHR=3.23, 95%CI=1.63-6.42), CD4⁺T lymphocyte level <50 cells/μl (aHR=8.96, 95%CI=4.37-18.38), only taking anti-tuberculosis treatment (aHR=1.74, 95%CI=1.13-2.67), patients treated in designated TB hospitals (aHR=1.58, 95%CI=1.19-2.10) had a higher risk of death. Conclusion TB patients complicated with AIDS had a relatively high risk of death during anti-tuberculosis treatment. We should especially focus on patients in the intensive phase of anti-tuberculosis treatment, and those over 60 years old. In addition, tuberculosis prevention and treatment training should be strengthened for doctors in TB designated hospitals to improve diagnostic and therapeutic capabilities, so as to reduce the fatality rate of those patients.

Comparison of the clinical application between fluorescence PCR probe melting curve and Micropore-plate method in determining the drug resistance of Mycobacterium tuberculosis

WANG Pei, ZHAO Guo-lian, LEI Qian, ZHENG Dan, CUI Xiao-li, ZHOU Jun

Chinese Journal of Antituberculosis. 2021, 43(2):  132-138.  doi:10.3969/j.issn.1000-6621.2021.02.006

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Objective To analyze the consistency between fluorescence PCR probe melting curve and Micropore-plate drug sensitivity tests (MicroDST) in determining the drug resistance of Mycobacterium tuberculosis (MTB), as well as the correlation between MTB gene mutation and drug resistance, in order to provide reference for optimization of clinical diagnosis and treatment. Methods From January to December, 2019, a total of 343 MTB clinical isolates from patients in Xi’an Chest Hospital were collected, all the specimens were tested using fluorescence PCR probe melting curve and MicroDST. Based on the results of MicroDST, the detection efficiency of fluorescence PCR probe melting curve in MTB resistance of isoniazid, rifampin, streptomycin, ethambutol, moxifloxacin and levofloxacin were evaluated. And the correlation between the gene mutation of MTB detected by fluorescence PCR probe melting curve and the minimum inhibitory concentration (MIC) of MicroDST was analyzed. Results With reference of the results of MicroDST, the sensitivity, specificity, and Kappa value of fluorescence PCR probe melting curve for isoniazid, rifampin, streptomycin, ethambutol, moxifloxacin and levofloxacin were 96.20% (76/79), 95.28% (242/254), 0.88; 93.62% (44/47), 94.58% (279/295), 0.79; 96.88% (62/64), 94.96% (264/278), 0.86; 93.33% (14/15), 95.37% (309/324), 0.61; 92.31% (24/26), 97.16% (308/317), 0.80; 91.18% (31/34), 99.35% (307/309), 0.92. Among the isolates, results of which by the fluorescence PCR probe melting curve were inconsistent with the phenotypic drug sensitivity, the lower phenotype drug sensitivity rates were found in those with the mutation of AhpC promoter region (-44--30 and -15-3) of isoniazid, the rpoB 507-512 of rifampin, the rrs 905-908 of streptomycin and the embB 406 of ethambutol, and the rates were 1/5, 1/5, 1/10 and 1/5, respectively. However, the phenotype drug sensitivity rates were higher in the isolates with mutation of the KatG 315 of isoniazid, the rpoB 529-533 of rifampin and the rpsL 43 of streptomycin, the rates were 92.42% (61/66), 92.31% (36/39) and 95.74% (45/47), respectively. Conclusion It has showed a good consistency in detection of drug resistance of MTB by fluorescence PCR probe melting curve and MicroDST. The drug resistance of MTB to isoniazid, rifampin and streptomycin was correlated with some gene mutations.

Application value of ESAT-6 combined with MMP-9 in assessing the severity of tuberculosis destroyed lung

LU Ni-hong, SUN Ya-ping, JIN Yuan, XIA Jia-wei, YANG Yong-rui

Chinese Journal of Antituberculosis. 2021, 43(2):  139-142.  doi:10.3969/j.issn.1000-6621.2021.02.007

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Objective To explore the application value of early secretory antigen target-6 (ESAT-6) and matrix metalloproteinase-9 (MMP-9) in evaluating the severity of tuberculous damage to the lung. Methods From January 2018 to January 2019, 55 patients with tuberculosis-destroyed lung (group A), 40 patients with secondry tuberculosis pulmonary (group B) and 20 healthy volunteers with physical examination (group C) were selected from the Third People’s Hospital of Kunming. The clinical data and laboratory examination results were collected, and the level (M(Q₁,Q₃)) of ESAT-6, MMP-9 and immune function were compared among the groups. Results The expression level of ESAT-6 were 28.83 (19.26, 38.20) pg/ml in group A, 22.26 (17.85, 25.01) pg/ml in group B, which were both significantly higher than that in group C (0.06 (0.03, 1.50) pg/ml; U=63.155, P<0.01; U=49.725, P<0.01). The expression level of MMP-9 in group A was 12.54 (9.01, 18.11) μg/ml, which was significantly higher than those in group B (6.80 (4.10, 12.29) μg/ml) and group C (1.14 (0.72, 1.29) μg/ml; U=26.097, P<0.01; U=66.309, P<0.01). The expression level of ESAT-6 in pulmonary tuberculosis patients (group A and group B) was 24.05 (18.54, 34.89) pg/ml, which was negatively correlated with the count of CD4⁺ T lymphocytes (476.00 (312.00, 647.00) cells/μl and CD3⁺ T lymphocytes (599.00 (456.00, 762.00) cells/μl; r=-0.462, P<0.01; r=-0.275, P=0.003). The expression of MMP-9 was 11.05 (6.30, 14.28) μg/ml, which was negatively correlated with the count of CD4⁺ and CD3⁺ T lymphocytes (r=-0.499, P<0.01; r=-0.341, P<0.01). In group A, the expression of MMP-9 (10.79 (7.10, 12.54) μg/ml) in moderate and severe ventilatory dysfunction patients (52.7%, 29/55) was significantly lower than that in very severe ventilatory dysfunction patients (47.3% (26/55); 17.39 (12.47, 33.30) μg/ml; U=150.000, P<0.01). Conclusion The expression of ESAT-6 and MMP-9 increased in pulmonary tuberculosis patients, which was related to immune function. The level of MMP-9 was related to the severity of tuberculous damage to the destroyed lung.

Value of molecular diagnosis and liquid culture methods in improving the pathogenic diagnosis of pulmonary tuberculosis in general hospitals

CUI Xiao-jing, WEI Dong, WANG Chun-lei, CAO Bin

Chinese Journal of Antituberculosis. 2021, 43(2):  143-146.  doi:10.3969/j.issn.1000-6621.2021.02.008

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Objective To analyze the value of applying molecular diagnosis and liquid culture methods in improving the diagnostic capabilities of tuberculosis in general hospitals. Methods Data of diagnostic basis, etiological test and the results, submitting time of specimen and result returning time, admission time and discharge time of 1438 inpatients diagnosed with pulmonary tuberculosis and reported with infectious disease cards in China-Japan Friendship Hospital from March 2014 to December 2018 in the medical record system were collected. The changes in the pathogenic diagnosis ability and time of diagnosis of tuberculosis were analyzed, between 2014-2016 when the hospital only carried out acid-fast staining and solid culture method of mycobacteria (Roche culture method), and 2017-2018 when the hospital carried out molecular diagnosis technique (GeneXpert MTB/RIF test) and liquid culture method (BACTEC MGIT 960 mycobacterium rapid liquid culture). Results The positive rate of pathogenic detection of pulmonary tuberculosis increased from 19.83% (24/121) in 2014 to 53.89% (256/475) in 2018. The difference of positive rate of pathogenic detection of pulmonary tuberculosis before and after the use of molecular diagnosis technique and liquid culture method was significant (22.68% (132/582) vs. 49.65% (425/856), χ²=106.184, P=0.000). After carrying out the GeneXpert MTB/RIF test (2017-2018), the rate of rifampin-resistant was found to be 7.45% (28/376), while drug resistant tuberculosis couldn’t be diagnosed before the use of the test. After carrying out molecular diagnosis technique and liquid culture method (2017-2018), the diagnosis time of tuberculosis was 7.00 (3.00, 12.00) d, which was significantly shorter than before (2014-2016)(10.00 (6.00, 14.00) d; Z=-7.815, P=0.000). Conclusion The application of molecular diagnosis technique and liquid culture method in general hospital can improve the diagnosis of tuberculosis and shorten the diagnosis time.

Subspecies and in vitro drug sensitivity analysis of Mycobacterium intracellular clinical isolates

LI Yuan-chun, ZHANG Yue, ZENG Xiang-jie, HE Wen-cong, QIU Qian, ZHAO Yan-lin, LI Yan-ming

Chinese Journal of Antituberculosis. 2021, 43(2):  147-152.  doi:10.3969/j.issn.1000-6621.2021.02.009

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Objective To analyze the subspecies composition and drug resistance profiles of Mycobacterium intracellular clinical isolates in Shenzhen, providing scientific basis for the treatment of Mycobacterium intracellular pulmonary disease. Methods A total of 97 Mycobacterium intracellular clinical strains stored in National Tuberculosis Reference Laboratory of Chinese Center for Disease Control and Prevention were finally included. All strains were isolated from respiratory specimens of suspected tuberculosis or NTM patients in Shenzhen Third People’s Hospital in 2018. Multi-target sequencing was applied to subspecies identification and minimum inhibitory concentrations (MIC) of strains to 13 drugs (clarithromycin, amikacin, moxifloxacin, linezolid, rifampin, rifabutin, ethambutol, streptomycin, doxycycline, ciprofloxacin, isoniazid, ethionamide and trimethoprim/sulfamethoxazole) was tested by Sensititre^? SLOWMYCO plate. Results The majority subspecies of Mycobacterium intracellular was Mycobacterium intracellular subsp,accounting for 63.92% (62/97), followed by Mycobacterium intracellular subsp.chimaera (18.56% (18/97)) and Mycobacterium intracellular subsp.paraintracellulare (17.53% (17/97)). Drug susceptibility testing (DST) indicated that the lowest values of MIC₅₀ and MIC₉₀ were 0.5 and 8 μg/ml (rifabutin); and the highest were 32 and 64 μg/ml (streptomycin) in Mycobacterium intracellular. The value of MIC₉₀ of clarithromycin in Mycobacterium intracellular and Mycobacterium paraintracellular both was 2 μg/ml while that in Mycobacterium chimaera was 64 μg/ml. The drug resistant rates of Mycobacterium intracellular to clarithromycin, ethambutol, rifampicin, rifabutin, streptomycin, amikacin, linezolid and moxifloxacin were 9.28% (9/97), 44.33% (43/97), 42.27% (41/97), 15.46% (15/97), 36.08% (35/97), 11.34% (11/97), 38.14% (37/97) and 46.39% (45/97), respectively. The resistance of Mycobacterium chimaera to clarithromycin was significantly higher than that of Mycobacterium paraintracellulare (27.78% (5/18) vs. 4.84% (3/62), χ²=8.156, P=0.012). Conclusion The dominant subspecies was Mycobacterium intracellular subsp. in Mycobacterium intracellular. Drug resistance profiles varied a lot within subspecies to different drugs, thus subspecies identification and DST should be conducted to guide tailored therapy.

The study of in vitro synergistic activities of GSK656 with clarithromycin or azithromycin against Mycobacterium abscessus

GUO Hai-Ping, CHEN Lei, HUO Feng-min, PANG Yu, LI Shan-Shan

Chinese Journal of Antituberculosis. 2021, 43(2):  153-158.  doi:10.3969/j.issn.1000-6621.2021.02.010

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Objective The purpose of this study was to assess in vitro drug susceptibility of M.abscessus against the combinations of the 3-aminomethyl 4-halogen benzoxaboroles compound GSK656 with macrolides, including clarithromycin (Clr) and azithromycin (Azm). Methods Eighty nontuberculous mycobacteria isolates were stored the biobank of Beijing Chest Hospital, Capital Medical University between 2016 and 2018, consisting of 30 isolates of M.abscessus, 7 isolates of Mycobacterium kansasii,37 isolates of Mycobacterium intracellulare, 5 isolates of Mycobacterium avium and 1 isolates of Mycobacterium fortuitum. The minimal inhibitory concentrations (MICs) were determined using Microporous Alamar-Blue Assay (MABA). Additionally, the checkerboard titration method was used to determine the synergistic effect between GSK656 and other antimicrobial agents. Results For Clr, the MIC values of M.abscessus isolates ranged from 0.031 mg/L to 16 mg/L. The proportion of Clr resistance was 10.0% (3/30) for M.abscessus. For Azm, the MIC values of M.abscessus isolates ranged from 0.125 to 64 mg/L. The Azm resistance was noted in 30.0% (9/30) of M.abscessus isolates. Additionally, GSK656 also exhibited the potent activity against M.abscessus isolates, the MIC₅₀ and MIC₉₀ of which were 0.25 and 2 mg/L, respectively. In the GSK656-Clr combination, 6 (20.0%,6/30) were synergistic, 23 (76.7%,23/30) were indifferent,1 (3.3%,1/30) was antagonistic. For the GSK656-Azm combination, 3 (10.0%,3/30) was synergistic, 18 (60.0%,18/30) were indifferent, and 9(30.0%,9/30)were antagonistic. Chi-square test results revealed that there was a statistically significant difference in synergistic distribution between GSK-Clr and GSK-Azm group (χ²=8.010,P=0.018). Conclusion Our data demonstrate that GSK656 has promising activity against M.abscessus in vitro. The synergistic distribution between GSK-Clr group and GSK-Azm group is statistically significant. The antagonistic effect is more frequent for GSK-Azm combination than GSK-Clr combination.

Study on plasma proteomics of patients with secondary pulmonary tuberculosis based on label-free quantitative technology

WANG Xiu-jun, LIU Qiu-yue, CHEN Xiao-feng, YU Lei, MA Yan, HAN Fen

Chinese Journal of Antituberculosis. 2021, 43(2):  159-165.  doi:10.3969/j.issn.1000-6621.2021.02.011

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Objective To study the plasma proteomics of specific protein markers in patients with secondary pulmonary tuberculosis, to explore specific protein markers of secondary pulmonary tuberculosis. Methods Blood samples were obtained from 30 secondary pulmonary tuberculosis (tuberculosis group) and 30 healthy controls and a certain protein mass spectrometry was detected using label-free quantitative technology. If the protein abundance of the tuberculosis group more than 2 (up-regulated) or <0.5 (down-regulated) compared with that of the control group, and P<0.05 using t test, it was considered to be a differential protein bioinformatics analysis of differential proteins was performed using GO and KEGG. The difference in the average protein abundance between the two groups was analyzed by t test and P<0.05 was considered statistically significant. Results A total of 518 differential proteins were found in the two groups. Of them, 256 proteins were up-regulated and 262 were down-regulated. Bioinformatics analysis showed that the main functions of differential proteins were binding (29.79%, 406/1363) and protein binding (24.80%, 338/1363), and cell process (14.75%, 467/3167) and metabolic process (11.11%, 352/3167) were the main processes biological they involved.By cell location analysis, it was found that most of the proteins were located within the cell (22.07%, 389/1763) and cell (22.01%, 388/1763). KEGG analysis showed that 17 up-regulated pathways (such as dorsal ventral axis pathway and focal adhesion pathway) and 1 down regulated pathway were different between tuberculosis group and control group. Conclusion The plasma protein of patients with secondary pulmonary tuberculosis may have changed significantly, which provides valuable clues for exploring the mechanism of the secondary pulmonary tuberculosis.

Whole-genome sequencing for drug resistance profile prediction in multidrug-resistant Mycobacterium tuberculosis in Shenzhen

JI Le-cai, ZHANG Le-ping, LYU Jian-wen, LI Xiao-ding, ZOU Xiao-fei, PIAO Wei

Chinese Journal of Antituberculosis. 2021, 43(2):  166-170.  doi:10.3969/j.issn.1000-6621.2021.02.012

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Objective To analyze the drug resistance spectrum of the clinical multidrug-resistant Mycobacterium tuberculosis (MDR-MTB) isolates in Shenzhen using whole-genome sequencing data, to provide scientific basis for the treatment and prevention of MDR-TB patients. Methods A total of 420 MDR-MTB strains were successfully recovered from all strains stored in the tuberculosis laboratory of Shenzhen Center for Chronic Disease Control from 2013 to 2017. Whole-genome sequencing were conducted for the genomic DNA extracted from these strains. The sequencing data were analyzed using an in-house pipeline. Drug-resistance to isoniazid, rifampicin, streptomycin, ethambutol, fluoroquinolones, pyrazinamide, ethionamide, p-aminosalicylic acid, kanamycin, amikacin, capreomycin, linezolid, bedaquiline, and clofazimine were determined based on MTB drug resistance gene database and drug resistance determining and harmless mutations database. Simultaneously, a string diagram of bacterial resistance and a heat map were used to visualize drug resistance spectrum of all strains and pre-XDR-MTB/XDR-MTB strains, respectively. Results Among the 420 clinical MDR-MTB strains, 23 (5.48%) were XDR-MTB strains and 97 (23.10%) were pre-XDR-MTB strains; except for isoniazid and rifampicin resistance, the frequency of streptomycin resistance was the highest with 67.86% (285/420), followed by ethambutol (66.19%, 278/420), fluoroquinolones (28.57%, 120/420), pyrazinamide (28.33%, 119/420), ethionamide (13.33%, 56/420), p-aminosalicylic acid (7.38%, 31/420), kanamycin (6.67%, 28/420), amikacin (5.48%, 23/420), capreomycin (5.48%, 23/420), and linezolid (0.24%, 1/420). No strain was resistant to bedaquiline or clofazimine. A total of 212 drug-resistance mutation types were revealed using the whole genome sequencing data, and the most common mutations were katG-315-S/T (81.43%, 342/420), rpoB-450-S/L (58.57%, 246/420), rpsL-43-K/R (65.96%, 188/285), and embB-306-M/V (32.37%, 90/278). Conclusion It was found that, among clinical MDR-MTB isolates in Shenzhen, the proportion of pre-XDR-MTB and the resistance rates to the first-line anti-tuberculosis drugs and fluoroquinolones were high, indicating that the use of these drugs in the clinic should be combined with the results of drug sensitivity tests; while the drug resistance rates to the second-line anti-tuberculosis drugs such as ethionamide, clofazimine, and aminosalicylic acid were low, suggesting that these drugs can be used in the treatment plan for MDR-TB patients.

Biomechanical study of cortical bone trajectory screw in lumbar spine tuberculosis intervertebral fixation

FEI Jun, SHI Shi-yuan, HU Sheng-ping, HU De-xin, ZHANG Chen-wei

Chinese Journal of Antituberculosis. 2021, 43(2):  171-177.  doi:10.3969/j.issn.1000-6621.2021.02.013

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Objective To explore the biomechanical stability and advantages of cortical bone trajectory (CBT) screws in the treatment of lumbar spine tuberculosis and provide biomechanical evidence for the choice of clinical fixation methods. Methods Sixteen pig spine specimens (T₁₂-L₅) were selected to simulate the in vitro (L₂-L₃) lumbar spine tuberculosis bone destruction. The 16 specimens were randomly divided into 4 groups (short-segment (vertebra pedicle screw) fixation (group A), short-segment (spine CBT screw) fixation (group B), intervertebral pedicle screw fixation (group C), vertebrae fixation with CBT screw (group D)), 4 specimens in each group, each specimen in each group was subjected to biomechanical testing in the state of complete specimen (state 1) and L₂-L₃ spinal tuberculosis model bone graft fusion and internal fixation (state 2). We loaded each specimen on the spine 3D exercise machine, applied moments of 2 N·m, 2.5 N·m, 1 N·m, 3 N·m, respectively, then recorded the range of movement (ROM) of the specimens in the four directions of flexion, extension, lateral bending and torsion, compared and analyzed each group of ROM. Results The ROMs of flexion, extension, lateral bending, and torsion in group A in state 1 and state 2 modes were (8.47±1.76)°, (7.01±1.10)°, (5.03±0.92)°, (4.48±0.41)° and (4.78±0.07)°, (2.91±0.16)°, (2.66±0.09)°, (2.23±0.05)°; the ROMs of flexion, extension, lateral bending and torsion in group B in state 1 and state 2 modes were (7.32±0.75)°, (5.35±0.69)°, (3.44±0.51)°, (3.36±1.02)° and (3.51±0.29)°, (1.74±0.04)°, (1.53±0.31)°, (1.23±0.08)°; the ROMs of flexion, extension, lateral bending, and torsion in group C in state 1 and state 2 modes were (10.01±0.39)°, (9.05±0.25)°, (7.42±1.06)°, (6.92±1.15)° and (7.21±0.17)°, (5.07±0.02)°, (5.12±0.74)°, (4.58±0.01)°; the ROMs of flexion, extension, lateral bending, and torsion in group D in state 1 and state 2 modes were (9.20±1.37)°, (7.38±0.88)°, (6.89±1.22)°, (6.00±0.52)° and (6.06±0.16)°, (3.99±0.02)°, (3.85±0.08)°, (3.47±0.10)°. The ROM value of each fixed mode group under the state of bone graft fusion and internal fixation (state 2) was lower than that of the intact state (state 1), and the difference was statistically significant (group A: t values were 4.531, 5.346, 6.008, 4.149, P values were 0.020, 0.013, 0.009, 0.025; group B: t values were 9.481, 16.181, 11.814, 4.769, P values were 0.002, 0.001, 0.001, 0.018; group C: t values were 4.349, 8.002, 4.473, 4.800, P values were 0.022, 0.004, 0.021, 0.017; group D: t values were 5.041, 4.146, 12.232, 10.583, P values were 0.015, 0.025, 0.001, 0.002). Conclusion The state 2 of the 4 groups of fixation modes all have stronger mechanical support than state 1. CBT screw intervertebral fixation can not only provide sufficient mechanical stability, but also provide stronger stability when using the same fixed segment, thus could minimize number of segments for fixation.

Review Articles

The research progress of lymphocyte subsets detection in diagnosis and treatment of tuberculosis

MI Jie, XUE Yong, BAI Xue-juan, WU Xue-qiong

Chinese Journal of Antituberculosis. 2021, 43(2):  178-185.  doi:10.3969/j.issn.1000-6621.2021.02.014

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Tuberculosis is a chronic infectious disease caused by M.tuberculosis. When the amount and virulence of M.tuberculosis invading the body are greater than the defense ability of the immune system, the tuberculosis will occur. Those with low immune function are more susceptible to be infected. At present, lymphocyte subsets detection has become one of the methods to analyze the immune status of tuberculosis patients, but its significance in the diagnosis and treatment of tuberculosis has not been recognized. This paper summarized the application progress of lymphocyte subsets percentage and absolute count in the peripheral blood of tuberculosis patients in diagnosis and treatment of tuberculosis, so as to judge its clinical value and provide the basis for immunodiagnosis and immunotherapy of tuberculosis patients.

Research progress of stem cells in Mycobacterium tuberculosis infection

GUO Qian, SHEN Chen, SHEN A-dong

Chinese Journal of Antituberculosis. 2021, 43(2):  186-189.  doi:10.3969/j.issn.1000-6621.2021.02.015

Abstract ( 473 )   HTML ( 13 )   PDF (700KB) ( 214 )   Save

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Tuberculosis is mainly caused by an intracellular pathogen—Mycobacterium tuberculosis, which can lurk or proliferate in host cells. It can also invade stem cells such as hematopoietic stem cells and mesenchymal stem cells. Stem cells are capable of self-replication, pluripotent differentiation, high migration and immune regulation, thus the role of them in the occurrence and development of tuberculosis can not be ignored. We mainly reviewed the pathogenesis and prevention and treatment strategies of tuberculosis through the interaction between Mycobacterium tuberculosis and stem cells.

Research progress on susceptibility genes of anti-tuberculous drug-induced liver injury

CAO Xin-yu, XUE Miao, WEN Yan, LIU Li

Chinese Journal of Antituberculosis. 2021, 43(2):  190-193.  doi:10.3969/j.issn.1000-6621.2021.02.016

Abstract ( 431 )   HTML ( 31 )   PDF (702KB) ( 268 )   Save

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The course of tuberculosis chemotherapy is a long, and the first-line anti tuberculosis drugs commonly used (such as isoniazid and rifampicin) are potentially hepatotoxic and easily cause anti-tuberculosis drug-induced liver injury (ATLI), which leads to low treatment efficacy and ineffective drug use, and then induces drug-resistant tuberculosis, increasing the difficulty of treatment and the burden of patients. ATLI has obviously individual difference, which is mainly caused by genes. However, there is no relevant review on the progress of ATLI susceptibility genes research in China, the authors provide a reference for clinical treatment and prevention by reviewing the relevant research progress of ATLI susceptibility genes at home and abroad.