Table of Content

10 April 2021, Volume 43 Issue 4

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Expert Note

Pay attention to the reasonable treatment of retreatment tuberculosis:today is not what it used to be

MA Yan*, GAO Wei-wei

Chinese Journal of Antituberculosis. 2021, 43(4):  313-317.  doi:10.3969/j.issn.1000-6621.2021.04.003

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Timely and reasonable anti-tuberculosis treatment is a key measure to effectively cure tuberculosis patients, eliminate infectivity and stop the spread of the disease. The implementation of standardized retreatment regimens has played a significant role in improving the success rate of retreatment pulmonary tuberculosis patients. But Mycobacterium tuberculosis is constantly evolving, and the individual conditions of patients are also constantly changing. In addition to the current status of poor anti-tuberculosis drug treatment, the standardized retreatment regimens should be adjusted and updated accordingly. In this article, the target of retreatment pulmonary tuberculosis, the evolution of the retreatment regimens and its rational application will be discussed by the author in combination with literature and clinical experience.

Special Articles

Interpretation of Expert consensus on treatment and management of tuberculosis-diabetes mellitus comorbidity

DENG Guo-fang

Chinese Journal of Antituberculosis. 2021, 43(4):  318-321.  doi:10.3969/j.issn.1000-6621.2021.04.004

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The comorbidity of tuberculosis (TB) and diabetes (DM) is becoming a big clinical challenge. It requires physicians from TB and DM teams to work together to decide treatment plans and conduct follow-up management in order to further increase cure rate and reduce mortality. The Expert consensus on treatment and management of tuberculosis-diabetes mellitus comorbidity was published on the first issue of 2021 in the Chinese Journal of Antituberculosis. This consensus offered management recommendations for frequently met problems during the treatment of TB-DM. We hereby further interpret the concept of TB-DM comorbidity, the management of diabetes, adverse drug reactions and precautions during treatment for clinicians in our country when taking care of patients with TB-DM.

Original Articles

Analysis of treatment outcomes of retreated pulmonary tuberculosis patients with isoniazid-resistance and rifampin-resistance

SHU Wei, GE Qi-ping, HUANG Xue-rui, MA Li-ping, JI Bin-ying, CHEN Yu-hui, CHEN Xiao-you, JIANG Guang-lu, XIE Li, LI Bo, CHEN Sheng-yu, CHEN Sen-lin, YAN Jun-ping, SHI Lian, CHEN Ling, LI You-lun, XI Xiu-e, LIU Qian-ying, YAN Xing-lu, WANG Fei, WANG Fu-rong, WU Xiang, ZHANG Peng, LENG Xue-yan, CAO Wen-li, ZHANG Hai-qing, CUI Hong-zhe, YANG Cheng-qing, WU Chao, LI Juan, LI Hua, SUN Yu-xian, ZHANG Li-jie, XIE Shi-heng, NING Yu-jia, TIAN Xi-zhong, DU Jian, LI Liang, GAO Wei-wei

Chinese Journal of Antituberculosis. 2021, 43(4):  322-327.  doi:10.3969/j.issn.1000-6621.2021.04.005

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Objective To analyze the treatment outcomes of retreated pulmonary tuberculosis patients (PTB) with isoniazid resistance, rifampicin resistance, and drug sensitive PTB patients, and explore the prognosis of patients with isoniazid resistance. Methods From July 2009 to July 2019, a retrospective investigation was adopted to select 922 retreated bacteriologically positive PTB patients with complete data and treatment outcomes from Beijing Chest Hospital of Capital Medical University and other more than 20 domestic tuberculosis prevention and control institutions. Two hundred and nineteen MDR or XDR cases, and 100 non-rifampicin and non-isoniazid resistance cases were excluded, a total of 603 retreated bacteriologically positive PTB patients were enrolled in this study. The standard retreatment regimen was used for the sensitive and not drug-resistant group while an individualized treatment regimen was used for the isoniazid-resistant or rifampicin-resistant group. The treatment outcomes were compared among 485 patients in “drug-sensitive group”, 73 patients in “isoniazid-resistant group” (including isoniazid mono-drug resistance and poly-drug resistance), and 45 patients in “rifampicin-resistant group” (including rifampicin mono-drug resistance and poly-drug resistance). Results At the end of 2nd month’s treatment, the sputum smear negative conversion rate (63.6%, 42/66) and sputum culture negative conversion rate (63.6%, 35/55) in isoniazid-resistant group were lower than those in rifampicin-resistant group (84.6%, 33/39; 70.6%, 24/34) and drug-sensitive group (84.2%, 388/461; 80.0%, 343429) (χ²=16.567, 8.500; P<0.001, 0.014), respectively. At the end of 6th month’s treatment, the sputum smear negative conversion rate (79.7%, 47/59) and sputum culture negative conversion rate (76.5%, 39/51) in isoniazid-resistant group were lower than those in rifampicin-resistant group (89.2%, 33/37 and 93.5%, 29/31) and drug-sensitive group (91.5%, 398/435 and 90.8%, 367/404) (χ²=8.127, 10.533; P=0.017, 0.005), respectively. The cure rate of isoniazid-resistant group (53.4%, 39/73) was lower than that of rifampicin-resistant group (60.0%, 27/45) and drug-sensitive group (69.5%, 337/485) (χ²=8.407, P=0.015); the treatment success rate of isoniazid-resistant group (64.4%, 47/73) was lower than that of rifampicin-resistant group (75.6%, 34/45) and drug-sensitive group (82.1%, 398/485) (χ²=12.587, P=0.002). Conclusion The negative conversion rates and success rates of treatment in retreated PTB patients with isoniazid resistance were lower than that of rifampicin-resistant group and drug-sensitive group. It is suggested that attention should be paid to the drug resistance of every bactericide, especially for those medicines clinically used for a long period.

Treatment effect analysis of the optimized regimen for re-treated drug-susceptible pulmonary tuberculosis patients

GE Qi-ping*, DU Jian, SHU Wei, MA Yan, MA Li-ping, ZHAO Cai-yan, CHEN Yu-hui, ZHANG Li-jie, HUANG Xue-rui, HAN Xi-qin, CHEN Sheng-yu, WANG Fei, LI Bo, CAO Wen-li, LIU Qian-ying, CHEN Dong-jin, SHI Lian, WANG Xin, LI You-lun, YANG Shang-peng, PENG Zhang-li, WU Chao, OUYANG Bing, WANG Fu-rong, LI Po, WU Xiang, XI Xiu-e, LENG Xue-yan, ZHANG Hai-qing, LI Hua, LI Juan, YANG Cheng-qing, ZHANG Peng, CUI Hong-zhe, XIE Li, LIU Yu-hong, LI Liang, GAO Wei-wei

Chinese Journal of Antituberculosis. 2021, 43(4):  328-334.  doi:10.3969/j.issn.1000-6621.2021.04.006

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Objective To analyze the treatment efficacy and safety of optimized regimen for re-treated patients with drug-susceptibility pulmonary tuberculosis. Methods This was a multi-center, randomized, open, parallel, controlled prospective cohort study for retreated drug-susceptible pulmonary tuberculosis. All of 381 subjects with either positive smear and positive culture, or with negative smear but culture positive were enrolled in the study. Two hundred and forty-four cases were randomly enrolled in the optimized regimen group and 137 cases in the standard regimen. SPSS 19.0 software was used for data statistics, and chi square test was used for data analysis. When the theoretical frequency is less than 1, Fisher exact probability test was used. The difference is statistically significant (P<0.05). Treatment outcome and side effect during treatment were compared between the two groups. Results At the end of treatment, the success rate was 84.0% (205/244, 175 cases cured and 30 cases completed treatment) in the optimized regimen group and 74.5% (102/137, 92 cases cured and 10 cases completed treatment) in the standard treatment group. The treatment success rate of optimized regimen group was significantly higher than that of the standard regimen group (χ²=5.128, P=0.024). There was no significant difference between the two groups in the incidence of both side effects (25.8% (63/244) in optimized regimen group and 21.2% (29/137) in standard regimen group respectively; χ ²=1.037,P=0.309);and severe side effects (2.5% (6/244) vs. 4.4% (6/137); χ²=0.525, P=0.469). Conclusion The optimized regimen can increase treatment success patients with re-treated drug-susceptible pulmonary TB without increasing the side effects.

The relationship between bacterial load and treatment failure and recurrence of sputum positive retreatment pulmonary tuberculosis patients

ZHANG Li-jie*, HAN Xi-qin, WANG Jing-ping, CHEN Yu-hui, CHEN Sheng-yu, CHEN Ling, LI Bo, LIN Ming-gui, LI You-lun, SHI Lian, XI Xiu-e, MA Li-ping, WANG Xin, WANG Fei, ZHAO Cai-yan, WANG Fu-rong, CHEN Sen-lin, WU Xiang, LI Po, ZHANG Peng, LENG Xue-yan, ZHANG Hai-qing, CAO Wen-li, SHU Wei, SUN Yu-xian, XIE Shi-heng, TIAN Xi-zhong, HUANG Xue-rui, DU Jian, GAO Wei-wei

Chinese Journal of Antituberculosis. 2021, 43(4):  335-340.  doi:10.3969/j.issn.1000-6621.2021.04.007

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Objective To analyze the relationship between bacterial load and treatment failure and recurrence of sputum positive retreatment pulmonary tuberculosis patients, providing reference for the diagnosis and treatment of retreatment tuberculosis. Methods A retrospective cohort study including 400 patients of sputum positive retreatment pulmonary tuberculosis except multidrug-resistant and extensive drug-resistant in 22 tuberculosis designated institutions from July 2009 to July 2012 were conducted. New treatment regimen and standard treatment regimen for retreatment tuberculosis patients were adopted. All patients with successful treatment were followed up to July 2019 (a total of 7 years). Fifty-one cases of retreatment failure were selected as failure group and 23 cases of recurrence after successful treatment were selected as recurrence group. Clinical data between failure group and recurrence group were analyzed. Results The previous dosage of rifampicin drugs (low dosage 70.2% (33/47) and 52.2% (12/23), normal dosage 29.8% (14/47) and 47.8% (11/23)), retreatment types (recurrence 51.0% (26/51) and 56.6% (13/23), initial treatment failure 23.5% (12/51) and 21.7% (5/23), other retreatment 25.5% (13/51) and 21.7% (5/23)), drug susceptibility test result before treatment (sensitive 34.0% (17/50) and 31.8% (7/22), isoniazid resistance 32.0% (16/50) and 31.8% (7/22), rifampicin resistance 12.0% (6/50) and 13.7% (3/22), other drugs resistance 22.0% (11/50) and 22.7% (5/22)), previous accumulated treatment duration (<6 month 24.0% (12/50) and 21.7% (5/23), ≥6 month 76.0% (38/50) and 78.3% (18/23)) and the number of retreatment (1 time 78.4% (40/51) and 87.0% (20/23), ≥2 times 21.6% (11/51) and 13.0% (3/23)) were all compared between failure and recurrence group and there were no statistical significance (χ²=2.189,P=0.139;χ²=0.206,P=0.902;Fisher exact probability test,P>0.999;χ²=0.045,P=0.832;χ²=0.298,P=0.585). The proportions of Mycobacterium tuberculosis load >2+ in sputum smear testing and culture testing before treatment in failure group (44.9% (22/49) and 63.9% (23/36)) were higher than in recurrence group (8.7% (2/23) and 12.5% (2/16)) and the differences between the two groups were statistically significant (χ² values were 9.232 and 11.718,P values were 0.002 and 0.001) respectively. Conclusion The failure rate of sputum positive retreatment pulmonary tuberculosis patients with high bacterial load was higher than the recurrence rate, and it should be paid more attention when designing the new retreatment regimen.

Analysis of CT features of drug-resistant pulmonary tuberculosis with cavity

LIANG Rui-yun, FANG Wei-jun, REN Hui-li, LI Hui-ru, ZHANG Hui, LI Cheng-cheng

Chinese Journal of Antituberculosis. 2021, 43(4):  341-345.  doi:10.3969/j.issn.1000-6621.2021.04.008

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Objective To explore the CT features of drug-resistant tuberculosis (DR-TB) patients with cavity,in order to improve diagnosis for DR-TB with cavity. Methods A retrospective analysis of 56 cases of pulmonary DR-TB with cavity (group A) confirmed by drug susceptibility test(proportional method) in Guangzhou Chest Hospital from January 2018 to December 2019.At the same time, 56 cases of drug-sensitive pulmonary tuberculosis with cavity (group B) were collected for comparative analysis, matching each Group A patient with the same gender and age ±2 years. By comparing CT scanning findings of the two groups,we analyzed the CT features of DR-TB with cavity. Results In group A, the detection rates of number of cavities ≥3, cavities located in ≥3 lung lobes were 55.36% (31/56) and 46.43% (26/56) respectively. In group B, they were 32.14% (18/56) and 26.79% (15/56) respectively.The differences between the two groups were statistically significant (χ ²=6.132 and 4.655,P=0.013 and 0.031, respectively). In group A, the detection rates of thick wall cavity and destroyed lungs were 61.44% (94/153) and 32.14% (18/56) respectively,while in group B, they were 49.21% (62/126) and 14.29% (8/56) respectively. The differences between the two groups were statistically significant (χ²=4.194 and 5.009, P=0.041 and 0.025, respectively). The detection rates of thin-walled cavity, drainage bronchus and tree bud sign in group B were 30.16% (38/126), 40.48% (51/126), 51.79% (29/56) respectively.In group A,they were 14.38% (22/153), 28.10% (43/153), 32.14% (18/56) respectively. There were significant differences between the two groups (χ ²=10.192, 4.734, 4.436, P=0.001, 0.030, 0.035, respectively). Conclusion The CT scan of DR-TB with cavity is more likely to have number of cavities ≥3, cavities located in ≥3 lung lobes, thick wall cavity and destroyed lung. The CT scan of drug-sensitive pulmonary tuberculosis with cavity is more likely to show thin-walled cavity, drainage bronchus and tree bud sign.They have their own CT features which can provide help for early clinical diagnosis and treatment。

Analysis of risk factors associated with false negative results of interferon-gamma release assays on peripheral blood from tuberculosis patients

YU Shan, LI Zhi-ming, XU Chun-xia, WANG Tao

Chinese Journal of Antituberculosis. 2021, 43(4):  346-351.  doi:10.3969/j.issn.1000-6621.2021.04.009

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Objective To analyse the risk factors associated with false negative results of interferon-gamma release assays (IGRA) of peripheral blood from tuberculosis patients. Methods We performed a retrospective analysis using data from tuberculosis patients at TB Department 4 of the 8th Medical Center of the Chinese People’s Liberation Army General Hospital from January 2018 to March 2020 who had peripheral blood IGRA assay results. They were divided into IGRA negative (38 patients) and IGRA positive (119 patients) groups. General information, medical history, serum biochemical indexes and peripheral T lymphocyte subpopulation data were collected. Single factor analysis and multivariate logistic regression analysis were performed to analyze risk factors associated with false negative IGRA results in tuberculosis patients. Results The M(Q₁,Q₃) of lymphocyte count, T cell count, CD4 ⁺ T cell count, CD8⁺ T cell count and NKT cell count for the negative group were 1.15 (0.77, 1.58)×10⁹ cells/L, 867.50 (508.75, 1135.50) cells/μl, 493.00 (256.00, 673.75) cells/μl, 254.50 (170.25, 429.25) cells/μl and 38.50 (16.50, 88.25) cells/μl respectively, and were significantly lower than that of the positive group: 1.46 (0.99, 1.88)×10⁹ cells/L, 1013.00 (667.00, 1394.00) cells/μl, 590.00 (386.00, 850.00) cells/μl, 335.00 (232.00, 561.00) cells/μl and 57.00 (30.00, 121.00) cells/μl (the Z values were -2.512, -2.143, -2.092, -2.303 and -2.338, and the P values were 0.012, 0.032, 0.036, 0.021 and 0.019 respectively). Logistic regression analysis indicated that patients with NKT cell counts that were lower than normal (<40 cells/μl) had a 2.440 times higher risk (95%CI: 1.159-5.134) than those with a normal NKT cell count of having a false negative IGRA result. Conclusion Lowered NKT cell counts may be a contributing factor leading to false negative peripheral blood IGRA results.

The study on the anti-tuberculosis activity of polymorphonuclear cell from peripheral blood of patients with multidrug-resistant pulmonary tuberculosis

LIU Ting*, WANG Liang, YANG Mei

Chinese Journal of Antituberculosis. 2021, 43(4):  352-356.  doi:10.3969/j.issn.1000-6621.2021.04.010

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Objective To investigate whether the drug resistance of Mycobacterium tuberculosis (MTB) is related to the impaired ability to induce apoptosis of human peripheral blood polymorphonuclear cell (PMN),thereby avoiding immune killing. Methods A total of 10 MDR-TB (multidrug-resistant tuberculosis) patients (MDR-group) and 10 drug-sensitive tuberculosis patients (non-drug-resistant group) who were diagnosed by Bao’an Hospital of Chronic Diseases Control and Prevention,Shenzhen from May 2017 to September 2018 were collected. MTB clinical isolates were obtained and frozen. All the strains were confirmed by drug sensitivity test using proportional method. 6 ml of peripheral blood was extracted from patients and PMN was isolated, meanwhile, MTB antigen was prepared. The isolated PMN (R_PMN and S_PMN) and MTB (R_MTB and S_MTB) were co-cultured in vitro, and 6 groups of detection specimens were obtained, including R_PMN, R_PMN+R_MTB, R_PMN+S_MTB, S_PMN, S_PMN+R_MTB, S_PMN+S_MTB. The apoptotic rate of PMN was observed by fluorescence inversion microscopy. The level of Toll-like receptor 2 (TLR2) and the activation degree of Caspase-3 in PMN were detected by ELISA and spectrophotometry, respectively. Results The apoptosis rate of the R_PMN group without MTB antigen stimulation ((30.67±3.03) %) was significantly lower than that of the S_PMN group ((36.54±2.49) %), but higher than that of the R_PMN+R_MTB group ((21.74±3.35) %), with statistical significance (t=4.728 and 6.254, respectively, P values were 0.000); R_PMN+R_MTB group was significantly lower than S_PMN+S_MTB group ((50.84±3.38) %) and R_PMN+S_MTB group ((34.66±3.05) %), and the differences were statistically significant (t=16.699 and 9.018, respectively, P values were 0.000).The S_PMN+S_MTB group was significantly higher than the S_PMN+R_MTB group ((33.56±2.94) %) and the S_PMN group, the differences were statistically significant (t=12.200 and 8.974, respectively, P values were 0.000).TLR2 ((24.94±1.77) ng/ml) and Caspase-3 (6.77±0.73) levels of PMN in S_PMN group without MTB antigen stimulation were significantly higher than those in R_PMN group ((13.46±1.67) ng/ml and 4.85±0.91), with statistical significance (t=14.931 and 5.224, respectively, P values were 0.000); TLR2 ((28.32±3.00) ng/ml) and Caspase-3 (6.33±0.93) levels of PMN in S_PMN+S_MTB group were significantly higher than those in R_PMN+R_MTB group ((15.25±2.10) ng/ml and 4.95±1.07), with statistical significance (t=11.297 and 3.063, P=0.000 and 0.007, respectively).TLR2 level in S_PMN group was significantly higher than that in S_PMN+R_MTB group ((22.23±1.90) ng/ml), but significantly lower than that in S_PMN+S_MTB group (LSD-test,Ps<0.05,respectively). Conclusion The apoptosis rate, degree of caspase-3 activation and TLR2 level of PMN stimulated by MDR-TB were lower than those of PMN without MTB antigen stimulation,suggesting that PMN of MDR-TB patients may have apoptosis inhibition related to the down-regulation of TLR2 level and the decrease of caspase-3 activation.

The effect of Mycobacterium tuberculosis infection on sputum flora structure

ZHANG Chen-chen*, TAN Wei-guo, GUO Hui-xin, HUANG Xin-chun, CHEN Yan-mei, WEI Wen-jing

Chinese Journal of Antituberculosis. 2021, 43(4):  357-363.  doi:10.3969/j.issn.1000-6621.2021.04.011

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Objective To explore the difference of sputum flora in healthy population, latent tuberculosis infection (LTBI) and active pulmonary tuberculosis patients. Methods From November 2016 to December 2017, 53 healthy subjects from Shenzhen Center of Chronic Diseases Prevention and Control were enrolled as group A, 41 registered patients with confirmed LTBI were enrolled as group B, and 54 patients with newly treated active tuberculosis were enrolled as group C. The 148 sputum samples of the lower respiratory tract (cheese sputum and mucus sputum were preferred) were collected from all the subjects in the morning when limosis. Total DNA was extracted from sputum samples, and 16S rRNA V4-V5 region genes were sequenced by high-throughput sequencing, the sequencing results were analyzed by bioinformatics. Results Through high-throughput sequencing analysis of the 148 sputum samples, 14136502.0 effective sequences and 21712.00 operational taxonomic units (OTU) were obtained. Alpha diversity analysis showed that the Pielou_e index of group A was 0.85 (0.82, 0.88), which was significantly higher than that of group C (0.83 (0.78, 0.86), H=4.462, P=0.035). Beta diversity analysis showed that there were differences in sputum flora composition among the three groups (H=2.027, P=0.002). Species analysis of different bacterial groups showed significant differences in levels of different Phylum (Firmicutes, Fusobacteria, Spirochaetes), Class (Flavobacteriia, Fusobacteriia, Spirochaetes), Order (Flavobacteriales, Lactobacillales, Fusobacteriales, Burkholderiales, Spirochaetales), Family (Porphyromonadaceae, Flavobacteriaceae, Fusobacteriaceae, Leptotrichiaceae, Burkholderiaceae, Spirochaetaceae), Genus (Capnocytophaga, Porphyromonas, Fusobacterium, Leptotrichia, Treponema) and Species (Nanceiensis,Parvula) among the three groups. Of them, the richness of Burkholderiales (0.01 (0.00, 0.02)) and Burkholderiaceae (0.01 (0.00, 0.01)) in group C was significantly higher than those in group A (0.00 (0.00, 0.01) and 0.00 (0.00, 0.00), respectively) and group B (0.00 (0.00, 0.01) and 0.00 (0.00, 0.00), respectively) (group C vs. group A: H values were 9.733 and 4.799, P values were 0.002 and 0.028, respectively; group C vs. group B: H values were 12.134 and 8.152, respectively, P values were both <0.01). Conclusion Mycobacterium tuberculosis infection did not change the richness of human sputum bacteria, however, it caused differences in the composition of the bacterial community.

Analysis of drug resistance surveillance results of Mycobacterium tuberculosis in Hu’nan Province from 2014 to 2018

BAI Hua, GUO Jing-wei, HU Pei-lei, YI Song-lin, WEN Jia, LIU Feng-ping, TAN Yun-hong, BAI Li-qiong

Chinese Journal of Antituberculosis. 2021, 43(4):  364-369.  doi:10.3969/j.issn.1000-6621.2021.04.012

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Objective To explore the drug resistance spectrum of Mycobacterium tuberculosis isolated from the drug-resistance surveillance sites in Hu’nan Province from 2014 to 2018, and to analyze the change trend of drug resistance. Methods A total of 1463 strains of Mycobacterium tuberculosis complex were isolated from sputum smear-positive tuberculosis cases registered in 5 national tuberculosis drug resistance monitoring sites in Hu’nan Province from 2014 to 2018. Drug sensitivity test was carried out on Mycobacterium tuberculosis complex strains. The tested drugs included isoniazid (INH), rifampicin (RFP), ethambutol (EMB), streptomycin (Sm), kanamycin (Km) and ofloxacin (Ofx). The drug resistance spectrum of the strains was described and the changes of characteristics of drug resistance were analyzed. Results Among the 1463 strains, 1244 (85.0%) were isolated from new tuberculosis patients and 219 (15.0%) were isolated from retreated tuberculosis patients. A total of 252 strains were resistant to at least one drug, and the rate of total drug resistance was 17.2% (252/1463), the rate of mono-drug resistance was 9.0% (131/1463), the rate of multi-drug resistance was 5.1% (74/1463) and the poly-drug resistance rate was 3.2% (47/1463). The drug resistance spectrum of the six anti-tuberculosis drugs consisted of 30 different types of drug resistance. Resistance rate of the six drugs were INH 9.9% (145/1463), Sm 8.2% (120/1463), RFP 7.0% (103/1463), Ofx 5.2% (76/1463), EMB 2.3% (34/1463) and Km 0.8% (12/1463), respectively, the difference was statistically significant (χ²=318.838, P=0.001). From 2014 to 2018, the drug resistance rates of isolates to RFP were 48.4% (15/31), 45.3% (34/75), 40.0% (20/50), 46.3% (19/41), and 27.3% (15/55), respectively, showing a downward trend ( {\chi }_{\mathrm{trend}}^2 =7.028, P=0.008); the drug resistance rates were 15.7% (31/198), 20.2% (75/371), 21.5% (50/233), 17.3% (41/237) and 13.0% (55/424), respectively, which also showed a downward trend ( {\chi }_{\mathrm{trend}}^2 =3.850, P<0.05). The drug resistance rate and multi-drug resistance rate in strains isolated from retreatment tuberculosis cases were significantly higher than those of the strains isolated from new tuberculosis cases (28.8% (63/219) vs. 15.2% (189/1244), χ²=24.065, P<0.01; 12.8% (28/219) vs. 3.7% (46/1244), χ²=32.024, P<0.01). Conclusion The drug resistance of Mycobacterium tuberculosis in Hu’nan Province was at a medium level and the drug resistance rate showed a decreasing trend year by year. The rates of drug resistance and multi-drug resistance in the re-treated patients were higher than those in the newly treated patients.

Analysis of the epidemiological characteristics of pulmonary tuberculosis among migrants in Shanghai from 2008 to 2019

WANG Huan*, SHEN Xin, CHEN Jing, XIA Zhen, XU Biao, YUAN Zheng-an

Chinese Journal of Antituberculosis. 2021, 43(4):  370-377.  doi:10.3969/j.issn.1000-6621.2021.04.013

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Objective To improve the tuberculosis control management of migrants by analyzing the epidemiological characteristics and incidence trend of pulmonary tuberculosis (PTB) of migrants in Shanghai during 2008—2019. Methods The data of PTB incidence and population were calculated from the Infectious Disease Reporting Information Management System. Joinpoint Regression Analysis was performed to analyze chronological trends, Annual Percentage Changes (APC) and Average Annual Percent Change (AAPC) were also estimated. Results A total of 36748 cases of PTB in migrants were reported in Shanghai from 2008 to 2019, accounting for 44.79% (36748/82047) of the reported cases in the whole population, the overall reported incidence rate decreased from 43.66/100000 (3273 cases) in 2008 to 26.70/100000 (2563 cases) in 2019, with APC=-3.42% (t=-9.838, P<0.01), the average reported incidence of PTB was 33.02/100000 (36748 cases). Of the reported PTB cases 23685 were males, with an average reported incidence of 39.28/100000 (23685 cases), and 13063 were female with an average reported incidence of 25.61/100000 (13063 cases), the difference were statistically significant (χ²=68.742, P<0.01). The reported incidences in male and female both decreased from 2008 to 2019 (APC=-3.27%, t=-7.444, P<0.01 and APC=-3.74%, t=-9.791, P<0.01, respectively). In different age groups, the number of patients aged 15-29 years was the most (52.69% (19364/36748)). The peak in average reported incidence of the total population was 104.67/100000 (365 cases) in the 75-104 years, there were significant differences in the incidences of PTB among different age groups (χ²=486.537, P<0.01). The reported incidence of PTB increased in the 60-74 years from 50.44/100000 (104 cases) in 2010 to 69.24/100000 (154 cases) in 2019 (APC=3.94%, t=3.443, P<0.01). The reported incidence of PTB in urban districts showed a significant decrease trend from 2008 to 2010 with APC=-7.99% (t=-2.758, P<0.01) and a stable decrease trend from 2010 to 2019 with APC=-1.28% (t=-4.726, P<0.01); while the reported incidence of PTB in rural districts showed a decrease trend from 2008 to 2019 with APC=-6.04% (t=-12.173, P<0.01). Both the reported incidence of smear-positive PTB and smear-negative PTB showed a decrease trend from 2008 to 2019 with APC=-7.26% (t=-28.533, P<0.01), APC=-1.67% (t=-3.852, P<0.01). Conclusion The epidemic of PTB of migrants in Shanghai steadily declined from 2008 to 2019, and the reported incidence rate of males was higher than that of females; the reported incidence of PTB showed a increase trend in the 60-74 years from 2010 to 2019. A better strategy especially for migrants should be developed to rapidly reduce the incidence rate.

The research on psychological status of pulmonary tuberculosis patients and influencing factors in Baoshan District, Shanghai

MA Zhi-tao, WANG Na, LYU Yang, HU Wei-hong, CHEN Chang, HE Fan, SHEN Xin, LIU Xiao-feng

Chinese Journal of Antituberculosis. 2021, 43(4):  378-384.  doi:10.3969/j.issn.1000-6621.2021.04.014

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Objective To analyze the main factors of depression and anxiety among pulmonary tuberculosis (PTB) patients in Baoshan District of Shanghai, so as to provide evidence for targeted interventions. Methods Four hundred and eighty-seven patients with PTB registered in Baoshan District of Shanghai from January 1 to December 31, 2018, those who refused or unable to complete the investigate were excluded, a total of 356 patients with PTB were selected. We used Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder (GAD-7), Social Support Rate Score (SSRS) for investigation. A total of 356 questionnaires were distributed, all the questionnaires were collected and valid, with an effective rate of 100.0%. Results The detection rate of depression and anxiety among PTB patients were 14.6% (52/356) and 6.2% (22/356) respectively. Univariate analysis showed that 48.1% (25/52) of middle social supporters had depression, which was significantly higher than the high social supporters (9.6%, 5/52; χ²=14.405, P=0.001). The detection rates of anxiety within junior high school education, income under 2000 yuan and low/middle social supporters were 36.4% (8/22), 59.1% (13/22) and 50.0% (11/22) respectively, which were significantly higher than those with senior high school education (13.6%, 3/22), income above 5000 yuan (9.1%, 2/22) and high social supporters (0.0%, 0/22), the difference was statistically significant (χ²=10.010, 21.884, 12.327, P=0.018, <0.001, 0.002). Multivariate logistic regression analysis showed that medium social support (high social support as reference, OR=3.782, 95%CI: 1.332-10.738) was the risk factor for depression, income <2000 yuan (income >5000 as reference, OR=8.415, 95%CI: 1.800-39.334) were the risk factors for anxiety. Conclusion The abnormal rate of anxiety and depression of PTB patients in Baoshan District of Shanghai is relatively high. The improvement of social support is helpful to alleviate the depression of patients and the income incense could attribute to relieve the anxiety of patients.

Analysis of screening of close contacts of a tuberculosis patient in a kindergarten in downtown Shanghai

LI Zhi-hong, GU Kan-kai, YAO Jing, ZHANG Huai-qing, HAN Zhi-ying, SHEN Xin, CHEN Jing, SHEN Bing

Chinese Journal of Antituberculosis. 2021, 43(4):  385-390.  doi:10.3969/j.issn.1000-6621.2021.04.015

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Objective To analyze the screening close contacts of a tuberculosis patient in a kindergarten in the downtown area of Shanghai, and to provide references for improving the prevention and control of tuberculosis in nurseries and kindergartens. Methods Epidemiological screening, including suspected symptoms screening, latent Mycobacterium tuberculosis infection (IGRA), chest X-rays or CT scans, and sputum smears and cultures were conducted on February 15, 2019 and March 14, 2019 among 128 close contacts of a staff member who was diagnosed as tuberculosis on January 14, 2019 in a kindergarten in downtown Shanghai. The latent infection status of close contacts with different characteristics (gender, BCG vaccination status, suspected pulmonary tuberculosis symptoms, recent medical history of respiratory disease, and exposure level) was analyzed. Results Among the 128 close contacts, 107 (83.59%) were children and 21 (16.41%) were faculty. The positive rate of suspected tuberculosis symptoms was 5.47% (7/128), which were 5.61% (6/107) in children and 4.76% (1/21) in faculty. In the two screening tests, 125 close contacts (3 children refused to be tested) were tested for IGRA, and 11 cases (8.80%) were positive, including 4 children (3.20%) and 7 teaching staff (5.60%). The detection rate of tuberculosis was 0.78% (1/128), and the total latent infection rate was 8.06% (10/124, excluding 1 case confirmed and 3 children without IGRA test). The latent infection rate of children (2.91%, 3/103) was significantly lower than that of teaching staff (33.33%, 7/21), and the difference was statistically significant (χ²=21.773, P=0.000). Seven teaching staffs of latent infection were followed up by chest film at the end of 3, 6 and 12 months, and 3 children of latent infection were treated with prophylactic anti-tuberculosis drug intervention for 3 months. After one year follow-up observation, there was no patient with secondary tuberculosis. Univariate analysis showed that the latent infection rate of BCG vaccinated patients (5.13%, 6/117) was statistically significant compared with that of non-vaccinated patients (4/7) (Fisher’s exact probability method, P=0.001). The latent infection rate of high exposure level persons (17.07%, 7/41) was significantly higher than that of medium exposure level persons (3.61%, 3/83), and the difference was statistically significant (χ²=5.012, P=0.025). Conclusion Health examination of staff in nurseries and nursery institutions should be strengthened, and IGRA testing should be actively carried out to screen close contacts of tuberculosis patients, especially those without BCG vaccination history and high exposure. It is of great significance to take preventive therapy or follow up with radiography in the patients with latent Mycobacterium tuberculosis infection for the prevention of secondary tuberculosis.

Analysis on the therapeutic effect and influencing factors of initial treated smear-positive pulmonary tuberculosis patients in Kashgar Prefecture from 2016 to 2018

Maiweilanjiang· Abulimiti, Diermulati· Tusun, LIU Zhen-jiang, Xirizhati· Mamuti, LI Guan-zhen, OU Xi-chao

Chinese Journal of Antituberculosis. 2021, 43(4):  391-397.  doi:10.3969/j.issn.1000-6621.2021.04.016

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Objective To explore the treatment effect and influencing factors of initial treated smear-positive pulmonary tuberculosis patients in Kashgar Prefecture, and to improve the treatment success rate and provide references for formulating appropriate intervention measures. Methods With stratified cluster sampling method, 240 out of 4970 initial treated smear-positive pulmonary tuberculosis patients who were registered at tuberculosis designated hospitals in Kashgar Prefecture from 2016 to 2018 and completed treatment were selected as the research objects, 231 patients completed questionnaire survey, on-site interview and case investigation analysis. General demographic data, medication management, treatment outcomes and adverse reactions were collected. Univariate and multivariate logistic regression models were used to analyze the treatment effect and its influencing factors of the enrolled patients. Results Among the 231 cases who completed the survey, 179 cases were successfully treated (77.49%, 179/231). Multivariate logistic regression analysis showed that BMI 18.50-24.00 (OR=0.036, 95%CI: 0.002-0.700), sputum smear negative after two months treatment (OR=0.054, 95%CI: 0.003-0.930), sputum smear negative after five months treatment (OR=0.003, 95%CI: 0.000-0.057), taking medication according to the dose (OR=0.013, 95%CI: 0.001-0.107), regular medication (OR=0.077, 95%CI: 0.022-0.268), knowing the route of transmission of tuberculosis (OR=0.076, 95%CI: 0.008-0.768) and when the treatment can be stopped (OR=0.254, 95%CI: 0.074-0.875) were the protective factors for the treatment effect of patients. Conclusion The treatment success rate of initial treated smear-positive pulmonary tuberculosis patients in Kashgar Prefecture is relatively low, which is related to the nutritional status of patients, follow-up sputum examination results, medication according to the dose and schedule, and the patients’ awareness of prevention and treatment. The treatment management, nutritional support and health education of initial treated smear-positive pulmonary tuberculosis patients in Kashgar Prefecture should be further strengthened to improve the treatment success rate of the initial treated smear-positive pulmonary tuberculosis patients.

Investigation of the experience of tuberculosis patients for follow up using the internet platform

ZHOU Shuang, CHEN Nan, ZHU Kun, JIANG Hui, YANG Lei, DU Jian

Chinese Journal of Antituberculosis. 2021, 43(4):  398-403.  doi:10.3969/j.issn.1000-6621.2021.04.017

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Objective To analyze the tuberculosis (TB) patients’ experience of the follow-up medical treatment online during the COVID-19 epidemic. Methods A questionnaire survey was conducted among 131 TB patients partcipated in the online consultation of Beijing Chest Hosipital, Capital Medical University and completed the whole process of internet diagnosis and treatment and drug delivery. The effective recovery rate was 96.9% (127/131). Likert 5-level scoring system was used to evaluate patients’ satisfaction before, during and after visit. Results The results showed that the satisfaction of patients was 93.7% (119/127). The satisfaction of patients who older than 45 years, around Beijing and other areas, and disease course over 6 months were significantly higher than those of younger than 30 years, Beijing local, and disease course less than 6 months (97.3% (36/37) vs. 90.0% (45/50), χ²=3.650, P=0.004; 95.9% (94/98) vs. 86.2% (25/29),χ²=3.243, P=0.008; 95.1% (98/103) vs. 87.5% (21/24), χ²=3.233, P=0.008; respectively). For patients around Beijing and other areas, “ Recommendation of attending doctors”was the main way to obtain information (54.7% (35/64)). However, obtaining information mainly “after going to the hospital”was the main way for Beijing patients (44.8% (13/29)), the rate was significantly higher than that in the patients from other areas (1.6% (1/64),χ²=36.015, P<0.01). “Unable to go out because of epidemic” (81.1% (103/127)) was the main reason for choosing internet diagnosis and treatment. The rate of “out-patient number not available” in Beijing was significantly higher than that in other areas (51.7% (15/29) vs. 18.8% (12/64),χ²=10.764, P=0.005); 48.8% (62/127) of patients “had no concerns” before receive treatment on the internet, however, the rate of “the inaccurate diagnosis online” in patients around Beijing was significantly higher than that in patients from other areas (50.0% (17/34) vs. 25.0% (16/64), χ²=6.647, P=0.036); 78.0% (99/127) of the patients considered that internet diagnosis and treatment reduced the infection risk caused by going out, they hope to solve the problems of “follow-up consultation” (55.9% (71/127)) and “prescription and drug delivery” (57.5% (73/127)) mainly through internet in the future. In the patients older than 45, the willingness of “reduce the risk of going out” was significantly lower than those younger than 30 years (62.2% (23/37) vs. 84.0% (42/50), χ²=7.588, P=0.023), while the willingness of “follow up consultation” was significantly higher than those younger than 30 years (73.0% (27/37) vs. 50.0% (25/50), χ²=6.226, P=0.044). However, only 26.0% (33/127) of the patients would “prefer online diagnosis and treatment”. Conclusion Patients’ satisfaction of internet diagnosis and treatment was high in this survey, but the willingness was greatly affected by the epidemic. The normalization of internet diagnosis and treatment needs to find new ways.

Review Articles

Progress in pharmacodynamic screening of anti-tuberculosis drug combination

LIU Hai-ting, LU Yu

Chinese Journal of Antituberculosis. 2021, 43(4):  404-408.  doi:10.3969/j.issn.1000-6621.2021.04.018

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Tuberculosis remains a global health concern. Because anti-tuberculosis treatment need drug combination, it is urgent to develop effective regimen with drug combination to improve the therapeutic effect and shorten the course of treatment. The determination of the best drug combination regimen must first be screened in vitro and then verified by in vivo experiments. This article reviews the anti-tuberculosis drug combinations and screening methods in vivo and in vitro in recent years, in order to provide a rapid and effective drug combination regimen for the treatment of clinical tuberculosis in the practice.

Short Articles

Analysis of the effect of flurbiprofen axetil on postoperative fever in patients with spinal tuberculosis

CAO Xiao-man, LIU Wei, LIU Tao, WANG Chun, GAO Guang-kuo, ZHAI Wen-ting, CHEN Fen, WU Chun-yu

Chinese Journal of Antituberculosis. 2021, 43(4):  409-412.  doi:10.3969/j.issn.1000-6621.2021.04.019

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This is a retrospective study to analyze the effect of postoperative analgesia with flurbiprofen axetil on postoperative fever in spinal tuberculosis patients.The clinical data (operation time, number of incisions, operation site, intraoperative blood transfusion, intraoperative use of glucocorticoid, the use of flurbiprofen axetil as postoperative analgesia, and fever 2 days after operation) of 255 spinal tuberculosis patients undergoing surgery in Beijing Chest Hospital from January 2017 to January 2019 were analyzed. The results showed that the fever rate was 44.7% (114/255) on the first day after operation, and 77.3% (109/141) of the patients who used flurbiprofen axetil for analgesia had no fever, which was significantly higher than that of the patients who did not use flurbiprofen axetil for analgesia (22.7% (32/141), χ²=11.970, P=0.001). The fever rate was 28.6% (73/255) on the second day after operation, and 72.5% (132/182) of the patients who used flurbiprofen axetil for analgesia had no fever, which was significantly higher than that of the patients who did not use flurbiprofen axetil for analgesia (27.5% (50/182), χ²=5.400, P=0.020). Multivariate logistic analysis showed that on the first and second day after spinal tuberculosis surgery, the risk of fever was reduced values (OR (95%CI) were 0.319 (0.178-0.570) and 0.412 (0.222-0.764), respectively). According to the results, postoperative analgesia with flurbiprofen axetil could reduce the risk of postoperative fever in patients with spinal tuberculosis.

A case of severe myelosuppression caused by anti-tuberculosis drugs and literature review on this issue

LIU Xin, GUO Le, WU Qian-hong

Chinese Journal of Antituberculosis. 2021, 43(4):  413-418.  doi:10.3969/j.issn.1000-6621.2021.04.020

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Anti-tuberculosis drug is a risk factor for causing bone marrow suppression, which can lead to death in severe cases. This article reported a patient who got bone marrow suppression caused by the use of anti-tuberculosis drugs and died. The authors also did a literature review regarding to this issue. The patient was female, 24 years old. She was found to have bilateral neck masses for more than 1 month and diagnosed as cervical lymph node tuberculosis by puncture biopsy in another hospital before she came to our hospital. After admission, she was confirmed as multidrug-resistant tuberculosis (MDR-TB) by Mycobacterium tuberculosis drug susceptible test (MTB-DST) using the pus obtained from her neck mass. The routine blood examinations were performed for her and the results were normal, and then the initial treatment regimen of anti-tuberculosis (3H-R-Z-E/12H-R) was given to this patient. After she received the treatment, the granulocyte cells were starting to drop slightly and gradually progressed to severe reduction, and then further progressed to severe reductions of the erythroid, granulocyte and megakaryocyte cells. The patient eventually died of infectious shock and failure to resuscitate. By reviewing the relevant publications, the authors did discussions on pathogenesis, clinical manifestations, diagnosis and treatment of bone marrow suppression caused by anti-tuberculosis drugs in this article, aimed to remind clinicians to understand the adverse reactions in blood system caused by anti-tuberculosis drugs and their severity, and to emphasize that the causes of the abnormal blood test results should be identified as soon as possible and the effective intervention measures should be taken soon.