Table of Content

10 June 2020, Volume 42 Issue 6

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Guideline·Standard·Consensus

Guideline for clinical application of cycloserine in the treatment of tuberculosis

Beijing Chest Hospital, Capital Medical University, Clinical Trial Branch of the Chinese Antituberculosis Association, Editorial Board of Chinese Journal of Antituberculosis

Chinese Journal of Antituberculosis. 2020, 42(6):  533-540.  doi:10.3969/j.issn.1000-6621.2020.06.001

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Recently, the tuberculosis epidemic is serious. Cycloserine, as the core drug in the treatment of drug-resistant tuberculosis, lacks the relevant guidance. The Clinical Trial Branch of the Chinese Antituberculosis Association and the Editorial Board of the Chinese Journal of Antituberculosis organized relevant experts to discuss deeply and to develop this guideline. This guideline introduces the molecular structure and mechanism of action, pharmacodynamics, pharmacokinetics, drug interaction, drug resistance mechanism, efficacy and safety, usage of special population, indications and contraindications, dosage and usage, drug adverse effect and clinical attentions, so as to help medical staff to standardize and reasonably use cycloserine.

Expert Forum

Impact of coronavirus disease 2019 (COVID-19) on tuberculosis control and countermeasures in China

SHEN Xin, SHA Wei, LIU Jian-jun

Chinese Journal of Antituberculosis. 2020, 42(6):  544-548.  doi:10.3969/j.issn.1000-6621.2020.06.003

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The pandemic of coronavirus disease 2019 (COVID-19)(named by WHO in 2020-02-11) has brought heavy disease burden and huge economic loss to almost all countries in the world. COVID-19 also has a huge impact on global public health. We analyzed the impact of COVID-19 epidemic on tuberculosis prevention and control in China, and put forward countermeasures and suggestions for tuberculosis case detection, treatment and management, as well as improvement of tuberculosis control network during normalized prevention and control for the pandemic of COVID-19 in future.

Original Articles

Retrospective study of CT imaging evolution of treatment failure patients with multidrug-resistant tuberculosis

XU Yan, LU Xi-wei, CAI Chun-kui, SUN Shi-xue, GU Xiao-feng, YU Yang, LI Gang, WANG Ying

Chinese Journal of Antituberculosis. 2020, 42(6):  549-557.  doi:10.3969/j.issn.1000-6621.2020.06.004

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Objective To investigate imaging evolution of treatment failure patients with multidrug-resistant tuberculosis, and provide the evidence for the evaluation. Methods Fifty-six cases of MDR-PTB patients who failed to be treated in Dalian tuberculosis hospital were collected. CT examination was carried out every 3 months in the course of treatment. The evolution and outcome of lung CT signs of 56 MDR-PTB patients were observed. According to CT signs, the course of disease can be divided into three types: absorption progressive type in 21 cases (37.5%, 21/56); absorption transforming type in 20 cases (35.7%, 20/56); intermittent progressive type in 15 cases (26.8%, 15/56). χ ² test was used to count the data, with a statistical significance of P<0.05. Results (1) At the 3rd, 6th and 24th month, the negative rate of sputum bacteria was 81.0% (17/21), 61.9% (13/21), 28.6% (6/21) in the absorption progressive type, 90.0% (18/20), 85.0% (17/20), 60.0% (12/20) in the absorption transformation type, and 40.0% (6/15), 26.7% (4/15), 20.0% (3/15) in the intermittent progressive type. There were significant differences in the sputum negative rate of the 3rd, 6th and 24th month among three types (χ ²=11.953,12.248,6.994, P=0.003,0.002,0.030). (2) In 56 patients, the detection rates of tree bud sign, ground glass shadow and nodular shadow were 67.9% (38/56), 21.4% (12/56) and 80.4% (45/56) before treatment, and 8.9% (5/56), 1.8% (1/56) and 60.7% (34/56) after treatment, there were statistically significant differences between before and after treatment (χ ²=41.108,10.530,5.198, P=0.000,0.001,0.023). After treatment, the number of bronchus clustered, fibrosis, damaged lung and bronchiectasis increased significantly, which were 21.4% (12/56), 5.4% (3/56), 5.4% (3/56) and 8.9% (5/56) before treatment, 41.1% (23/56), 17.9% (10/56), 23.2% (13/56) and 37.5% (21/56) after treatment, there were significant differences between before and after treatment.(χ ²=5.029,4.264,7.292,12.823, P=0.025,0.039,0.007,0.000).(3) In the inherent lesions, cavity 37.8% (108/286),nodule 25.9% (74/286),consolidation 16.4% (47/286) and tree in bud 10.8% (31/286) were common; in the new lesions, tree in bud 46.9% (23/49) and nodule 40.8% (20/49) were common. The detection rate of caseous consolidation with cavities in tree in bud cases was 47.4% (9/19) and that in non-tree in bud cases was 18.9% (7/37),which was statistically significant (χ ²=4.979, P=0.026). Conclusion Through continuous observation of CT imaging, treatment failure can be predicted, which suggests that clinical chemotherapy should be adjusted in time to reduce the incidence of irreversible lung injury.

CT imaging characteristics of cured multidrug-resistant pulmonary tuberculosis

ZHANG Pei-ze, FU Liang, TAN Jie, WANG Yu-xiang, CHEN Tao, DENG Guo-fang

Chinese Journal of Antituberculosis. 2020, 42(6):  558-562.  doi:10.3969/j.issn.1000-6621.2020.06.005

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Objective To evaluate the characteristics of lung CT image in patients with cured multidrug-resistant pulmonary tuberculosis (MDR-PTB). Methods Forty-two patients who were diagnosed with MDR-TB from March 2012 to March 2018 in the Third People’s Hospital of Shenzhen and cured and no relapse occurred in two years were enrolled. Eighteen patients were divided into newly treated group and 24 patients were retreated groups. Consecutive lung CT images of 42 cured MDR-PTB patients were retrieved. The dynamic CT sign change at the time point of cure, 12 and 24 months after cure were analyzed. Results Respectively, 57.1% (24/42), 42.9% (18/42), and 31.0% (13/42) patients had active signs of PTB at the time point of cure, 12 months after cure, and 24 months after cure. Stable signs were observed in 69.0% (29/42), 81.0% (34/42), and 83.3% (35/42) patients at these time points. Uncertain signs were found in 40.5% (17/42) patients. At the time of cure, active signs were observed in 33.3% (6/18) newly treated group, and 75.0% (18/24) retreated group, and stable signs in 50.0% (9/18) newly treated and 83.3% (20/24) in retreated. The differences between two groups were statistically significant (χ ²=7.292, P=0.007; χ ²=5.347, P=0.021). At 12 months after cure, active signs were observed in 27.8% (5/18) newly treated, and 54.2% (13/24) in retreated, and stable signs in 83.3% (15/18) newly treated and in 79.2% (19/24) retreated. The differences between two groups were not statistically significant (χ ²=2.925, P=0.087; χ ²=0.116, P=1.000). At 24 months after cure, active signs were found in 22.2% (4/18) newly treated, and 37.5% (9/24) retreated, and stable signs in 88.9% (16/18) newly treated, and 79.2% (19/24) in retreated, and no statistical differences were found (χ ²=1.123, P=0.289; χ ²=0.700, P=0.679). At these different time points, uncertain signs were observed in 16.7% (3/18) newly treated, and 58.3% (14/24) retreated, and there was a statistical significance between the two groups (χ ²=7.412, P=0.006; χ ²=7.412, P=0.006; χ ²=7.412, P=0.006). Conclusion CT images showed signs of delayed repairment of pulmonary damage in most MDR-PTB patients after cure. Retreated MDR-PTB patients had more uncertain signs than newly treated MDR-PTB patients.

A multicenter investigation of pulmonary tuberculosis with concurrent extrapulmonary tuberculosis and its correlation with gender and age

YU Jia-jia, LI Liang, DU Jian, CHEN Hong-yan, LIU Jian-xiong, MA Jin-shan, LI Ming-wu, QIN Jing-min, SHU Wei, ZONG Pei-lan, YAN Xiao-feng, ZHANG Yi, DONG Yong-kang, YANG Zhi-yi, MEI Zao-xian, DENG Qun-yi, WANG Pu, HAN Wen-ge, WU Mei-ying, CHEN Ling, ZHAO Xin-guo, TAN Lei, LI Fu-jian, ZHENG Chao, LIU Hong-wei, LI Xin-jie, , DU Ying-rong, LIU Feng-lin, YANG Song, CUI Wen-yu, WANG Quan-hong, CHEN Xiao-hong, HAN Jun-feng, XIE Qing-yao, FENG Yan-mei, LIU Wen-yu, TANG Pei-jun, ZHANG Jian-yong, ZHENG Jian, CHEN Da-wei, YAO Xiang-yang, REN Tong, LI Yan, LI Yuan-yuan, WU Lei, SONG Qiang, YANG Mei, ZHANG Jian, LIU Yuan-yuan, GUO Shu-liang, YAN Kun, SHEN Xing-hua, LEI Dan, ZHANG Yan-li, KANG Wan-li, TANG Shen-jie

Chinese Journal of Antituberculosis. 2020, 42(6):  563-569.  doi:10.3969/j.issn.1000-6621.2020.06.006

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Objective To investigate the incidence of pulmonary tuberculosis concurrent with extrapulmonary tuberculosis and its relationship with gender and age group. Methods Using observational research method, 360187 hospitalized tuberculosis patients’ gender, age and the involved position of tuberculosis were collected from hospital information management system (HIS) of 21 medical institutions in 15 provinces in China from January 1, 2011 to December 31, 2017 by investigators with unified training. The incidence of extrapulmonary tuberculosis and its relationship with gender and age were analyzed. Results Among 360187 patients with tuberculosis, 238910 (66.33%) were male, 121277 (33.67%) were female, and the median age (quartile) (M(Q₁,Q₃)) was 47 (28, 62) years old; 42987 (11.93%) cases were concurrent with extrapulmonary tuberculosis, the highest incidence was tuberculous meningitis (2.72% (9809 cases), followed by cervical lymph node tuberculosis (1.93% (6966 cases)), tuberculous peritonitis (1.59% (5733 cases)), tuberculous pericarditis (0.94% (3399 cases)) and intestinal tuberculosis (0.94% (3380 cases)) etc. The incidence of tuberculous meningitis, cervical lymph node tuberculosis, tuberculous peritonitis, tuberculous pericarditis, tuberculous polyserositis, lumbar tuberculosis, thoracic tuberculosis and chest wall tuberculosis in male tuberculosis patients were respectively 2.44% (5829 cases), 1.44% (3429 cases), 1.41% (3376 cases), 0.90% (2138 cases), 0.75% (1791 cases), 0.67% (1604 cases), 0.64% (1522 cases), 0.60% (1438 cases), and significantly lower than that of female (respectively 3.28% (3980 cases),2.92% (3537 cases),1.94% (2357 cases),1.04% (1261 cases),0.90% (1093 cases),0.79% (960 cases),0.76% (924 cases),0.66% (805 cases))(χ ²=215.235,930.541,144.480,18.061,23.272,16.442,18.585,4.976;Ps<0.05). The differences of incidences of tuberculous meningitis, cervical lymph node tuberculosis, tuberculous peritonitis, intestinal tuberculosis, tuberculous pericarditis, tuberculous polyserositis, lumbar tuberculosis, thoracic tuberculosis, chest wall tuberculosis and throat tuberculosis between different age (1- to ≥65 year) groups were statistically significant (χ ²=3870.549,2939.502, 1830.620, 673.372,115.428, 319.078, 52.512, 19.308, 439.177, 136.619;Ps<0.05). Except that the incidence of thoracic tuberculosis did not change with age ($\chi^{2}_{trend}$=0.814, P=0.367) and that of tuberculous pericarditis increased with increase of age ($\chi^{2}_{trend}$=62.087, P<0.001), the incidence of other tuberculosis decreased with increase of age (Ps<0.001).Multivariate logistic regression analysis showed that the risk of pulmonary tuberculosis concurrent with extrapulmonary tuberculosis in female was significantly higher than that in male (OR (95%CI): 1.325 (1.297-1.353)), and the risk of other age groups was higher than that in the age group ≥65 years old (1-,15-,25-, 35-, 45-, 55- years old; OR (95%CI)=4.995 (4.655-5.360), 2.481 (2.397-2.568), 2.053 (1.982-2.126), 1.683 (1.619-1.749), 1.276 (1.228-1.326), 1.109 (1.067-1.153).The risk of pulmonary tuberculosis concurrent with extrapulmonary tuberculosis decreased with increase of age after controlling the influence of gender (OR (95%CI)=0.817 (0.812-0.821)). Conclusion The common extrapulmonary tuberculosis concurrent with pulmonary tuberculosis are tuberculous meningitis, cervical lymph node tuberculosis, tuberculous peritonitis, tuberculous pericarditis and intestinal tuberculosis, and the risk of extrapulmonary tuberculosis in female is higher than that in male, and its trends decrease with the increase of age.

Efficacy and safety of thymopentin in adjuvant treatment of retreatment positive pulmonary tuberculosis: a Meta-analysis

HUANG Guo-jun, GAO Yuan, TANG Xi-liang, GAO Xiao, BAI Li-qiong

Chinese Journal of Antituberculosis. 2020, 42(6):  570-577.  doi:10.3969/j.issn.1000-6621.2020.06.007

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Objective To systematically assess the efficacy and safety of thymopentin in adjuvant treatment of retreatment pulmonary tuberculosis. Methods The PubMed, the Cochrane Library, Sinomed, CNKI, Wanfang and VPCS database were retrieved online from the establishment of database to Aug 1st 2019. Both Chinese and English retrieval words were thymopentin and pulmonary tuberculosis. According to the retrieval strategies, a total of 326 related literatures were initially retrieved, including 322 in Chinese, and 4 in English. Finally, 18 studies were included in this study. The RevMan 5.3 was adopted in analysis on the sputum conversion rate of the treatment after 2 months and 6 months, the foci absorption rate, the cavity closure rate, the incidence of adverse events, the CD4 ⁺ level and CD8 ⁺ level of the retreatment positive pulmonary tuberculosis. Results Meta-analysis showed that compared with conventional treatments, thymopentin in adjuvant treatment of retreatment positive pulmonary tuberculosis could significantly enhance the sputum conversion rate after 2 months of treatment (RR (95%CI)=1.28 (1.17-1.40)), and 6 months of treatment (RR (95%CI)=1.24 (1.18-1.29)). The foci absorption rate (RR (95%CI)=1.27 (1.19-1.37)) and the cavity closure rate (RR (95%CI)=1.39 (1.26-1.54)) were also improved. There was no statistical significance in incidence of adverse events (RR (95%CI)=0.82 (0.63-1.07)). Analysis also indicated that CD4 ⁺ level (WMD (95%CI)=11.03 (8.79-13.27)) and CD4 ⁺/CD8 ⁺ level (WMD (95%CI)=0.51 (0.26-0.75)) were improved, while CD8 ⁺ level (WMD (95%CI)=-8.34 (-12.54--4.14)) decreased. Conclusion The current evidence shows that thymopentin is safe and effective in adjuvant treatment of retreatment positive pulmonary tuberculosis.

Drug resistance and genotypic characteristics of multidrug-resistant Mycobacterium tuberculosis in Guangxi Zhuang Autonomous Region

LIANG Xiao-yan, LIN Mei, LIANG Da-bin, LAN Ru-shu, QIN Hui-fang, YE Jing, HUANG Li-wen

Chinese Journal of Antituberculosis. 2020, 42(6):  578-582.  doi:10.3969/j.issn.1000-6621.2020.06.008

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Objective To understand the drug resistance situation, genotype composition and the correlation between genotype and drug-resistant of multidrug-resistant Mycobacterium tuberculosis (MDR-MTB) in Guangxi Zhuang Autonomous Region (referred to as Guangxi), thereby providing a theoretical basis for the prevention and control of MDR-MTB. Methods Using continuous monitoring methods, 5 cities including Guigang, Baise, Chongzuo, Guilin, and Fangchenggang on East, West, South, North, and Central of Guangxi were selected as monitoring points, and random number table method was used to extract 21 counties (cities, districts) from 5 cities. A total of 1514 culture-positive MTB strains which registered and treated in the local tuberculosis prevention and treatment institution were collected from 2016 to 2017. The drug susceptibility test to isoniazid (INH), rifampin (RFP), ethambutol (EMB), streptomycin (Sm), Ofloxacin (Ofx) and kanamycin (Km) was performed using the ratio method recommended by WHO. Finally, 51 strains were identified as MDR-MTB strains. Genotyping was performed by melting curve analysis-based spoligotyping (McSpoligotyping), and then the results were compared with the SpolDB 4.0 database. Results The drug resistance rates to EMB, Sm, Ofx and Km of 51 MDR-MTB strains were 41.18% (21/51), 31.37% (16/51), 9.80% (5/51) and 1.96% (1/51), respectively. Beijing genotype strains accounted for 56.86% (29/51) and non-Beijing genotype strains accounted for 43.14% (22/51). Among the strains resistant to EMB, there were 14 Beijing genotype strains, accounting for 66.67% (14/21) and 7 non-Beijing genotype strains, accounting for 33.33% (7/21), the difference was not statistically significant (χ ²=1.399, P=0.237). Among the strains resistant to Sm, there were 11 Beijing genotype strains, accounting for 68.75% (11/16) and 5 non-Beijing genotype strains, accounting for 31.25% (5/16), the difference was not statistically significant (χ ²=1.343, P=0.246). Among the strains resistant to Ofx, there were 9 Beijing genotype strains, accounting for 60.00% (9/15) and 6 non-Beijing genotype strains, accounting for 40.00%(6/15), the difference was not statistically significant (χ ²=0.085, P=0.770). Among the strains resistant to Km, there was 1 Beijing genotype strain, accounting for 100.00% (1/1), and no non-Beijing genotype strain, accounting for 0.00% (0/1), the difference was not statistically significant (P=1.000). Conclusion We should pay attention to the resistance of MDR-MTB strains to EMB, Sm, Ofx and Km in Guangxi. MDR-MTB strains are mainly Beijing genotype. There are no significant differences in the resistance rates of Beijing and non-Beijing genotypes to EMB, Sm, Ofx and Km.

Analysis of characteristic of resistant gene mutations among multidrug-resistant Mycobacterium tuberculosis in Shenzhen

HONG Chuang-yue, YANG Ting-ting, LI Jin-li, LI Shuang-jun, WU Li-kai, YANG Zheng, TAN Wei-guo

Chinese Journal of Antituberculosis. 2020, 42(6):  583-589.  doi:10.3969/j.issn.1000-6621.2020.06.009

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Objective To analyze the characteristics of gene mutations of MDR-MTB in Shenzhen using the whole-genome sequencing (WGS) data, providing basement for rapid molecular detection of drug-resistant tuberculosis. Methods WGS was performed on 449 MDR-MTB clinical isolates collected from Shenzhen Center for Chronic Disease Control and Chronic Disease Control of districts of Shenzhen among 2013-2017. Among them, 447 strains were enrolled after sequence alignment with the standard strain of Mycobacterium tuberculosis (H37RV) genome template sequence. After being identified by single nucleotide polymorphism (SNP), each strain was aligned with the specific mutation of genotype or subtype of H37Rv and the drug-resistant gene mutation of 11 anti-TB drugs, to explore the genotype or subtype and drug-resistant gene mutation of each strain, and analyze the correlation of main mutation types from different drugs resistance genes in genotype or subtype. Results The WGS results of 447 MDR-MTB showed that 432 strains (96.6%) had gene mutation. The major resistant mutation types to 11 drugs were katG-315-S/T (INH,81.7% (353/432)), rpoB-450-S/L (RFP, 59.7% (258/432)), rpsL-43-K/R (Sm, 66.0% (198/300)), embB-306-M/V (EMB, 35.5% (94/265)), pncA promoter -11-T/C (PZA,8.9% (11/123)), gyrA-90-A/V (Ofx,31.5% (39/124)), rrs-1401-A/G (Am,48.1% (25/52)), rrs-1401-A/G (Cm, 100.0% (27/27)), rrs-1401-A/G (Km, 84.4% (27/32)), inhA-15-C/T (Eto, 84.2% (48/57)), and thyA-75-H/N (PAS, 31.3% (10/32)). Among mutation types, two or more mutations were found in INH, RFP, EMB and Sm. The 3 genotypes of MDR strains in Shenzhen were lineage 1 (L1) (0.4% (2/447)), lineage 2 (L2) (84.6% (378/447)) and lineage 4 (L4) (15.0% (67/447)) in Shenzhen. The L2 was further divided into three subtypes: L2.1 (1.9% (7/378)), L2.2 (37.0% (140/378)) and L2.3 (61.1% (231/378)). katG-315-S/T, rpsL-43-K/R and embB-306-M/V in L2 (79.6% (301/378), 50.5%(191/378), 23.0%(87/378)) were significantly higher than those in L4 (61.2% (41/67), 10.4% (7/67), 10.4% (7/67)) (χ ² were 10.874, 37.021 and 5.396, respectively; P values were 0.001, 0.000, and 0.020, respectively). However, the PAS resistant mutations, folC-43-I/T and thyA-75-H/N, were only found in L2. The mutation frequency of katG-315-S/T in L2.2 (88.6% (124/140)) was significantly higher than in L2.3 (74.5%(172/231)) (χ ²=10.764, P=0.000), while the mutation frequencies of inhA-15-C/T (INH), rpoB-450-S/L, rpsL-43-K/R and inhA-15-C/T (Eto) in L2.3 (8.2% (19/231), 61.9% (143/231), 59.3% (137/231), 15.6% (36/231)) were higher than those in L2.2 (2.9% (4/140), 49.3% (69/140), 37.9% (53/140), 3.6% (5/140)(χ ² were 4.319, 5.668, 16.053 and 12.797, respectively;P values were 0.038, 0.017, 0.000 and 0.000, respectively). Conclusion The major resistant mutation types of 11 drugs in MDR-MTB of Shenzhen were katG-315-S/T, rpoB-450-S/L, rpsL-43-K/R, embB-306-M/V, pncA promoter -11-T/C, gyrA-90-A/V, rrs-1401-A/G, inhA-15-C/T and thyA-75-H/N; and the genotypes were L1, L2 and L4, of which the main types were L2.2, L2.3 and L4.

Spatial-temporal analysis on tuberculosis among students in Guangzhou City during 2014-2018

LAI Keng, LEI Yu, DU Yu-hua, WU Gui-feng, XIE Wei, SHEN Hong-cheng, ZHONG Zhi-qing, LI Tie-gang

Chinese Journal of Antituberculosis. 2020, 42(6):  590-596.  doi:10.3969/j.issn.1000-6621.2020.06.010

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Objective To analyze the spatial-temporal characteristics of tuberculosis (TB) affected students at the township level in Guangzhou from 2014 to 2018 and provide evidence for the prevention and control of TB in schools. Methods The information of TB patients who were students was collected by “China Disease Prevention and Control Information System and Infective Diseases Management Information System”. We obtained data of 2755 cases in Guangzhou City with date of onset from January 1, 2014 to December 31, 2018. Global and local spatial auto-correlation analysis and Kulldorff’s Scan Statistics were applied to map the spatial distribution and detect the space-time cluster of those cases during 2014-2018. Result The TB incidence rates among students in Guangzhou City from 2014 to 2018 were 17.14/100000, 16.42/100000, 15.64/100000, 16.57/100000 and 17.22/100000 respectively which presented a trend of decreasing at the beginning and then rising. There were two peaks of monthly incidence during the study period: March to April and September in year 2014 to 2016; December to January and September in year 2017 to 2018. Global spatial auto-correlation analysis found that the incidence among students in Guangzhou from 2014 to 2015 showed a random distribution at the street/township level (Moran I: -0.004 and 0.023, Z: 0.098 and 1.238, respectively). From 2016 to 2018, it showed that there were obvious clustering (Moran I: 0.059, 0.172, 0.088; Z: 2.954, 6.706, 3.565; P: 0.012, 0.001, 0.005). Local indicators of spatial association analysis found 7 high-high clusters as follows: Xiaoguwei and Xinzao in Panyu District, Pazhou and Guanzhou in Haizhu District, Yuangang and Changxing in Tianhe District. Spatiotemporal scan showed that the primary cluster was located in Panyu district, including 2 streets/townships: Xiaoguwei and Xinzao, during March 2016 to July 2018 (log likelihood ratio=360.04, relative risk=29.28, and P=0.000). Conclusion Incidence rates of TB among students displayed spatial clusters at the township level in Guangzhou during 2016 to 2018, with high risk areas relatively concentrated in Xiaoguwei and Yuexiu District with high density of colleges and universities.

Spatial-temporal analysis of smear-positive pulmonary tuberculosis in Xinjiang Uygur Autonomous Region from 2011 to 2015

YIN Zhe, HE Xiang-yan, LI Qi-feng, LIU Ya-jie, ZHANG Yan, LI De-yang, Jiayina· Lazibieke, Gulinazhaer· Aikebaier, CAO Ming-qin

Chinese Journal of Antituberculosis. 2020, 42(6):  597-603.  doi:10.3969/j.issn.1000-6621.2020.06.011

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Objective Based on the data of the standardized incidence ratio (SMR) of smear-positive pulmonary tuberculosis (PTB) in 98 districts (counties) in Xinjiang Uygur Autonomous Region (Xinjiang) from 2011 to 2015, the spatial and temporal distribution pattern of PTB risk was explored using spatial epidemiological methods. Methods The information of 57 700 cases of smear-positive PTB in Xinjiang from 2011 to 2015 was obtained through the ‘China Disease Prevention and Control Information System and Infective Diseases Management Information System’. ArcGIS 10.2 software was used for geospatial analysis to create a TB SMR distribution map, the global Moran I index was calculated to explore the spatial autocorrelation effect of smear-positive PTB. The Kriging interpolation method was used to construct the prediction model. Results The SMR of smear-positive PTB in Xinjiang showed spatial autocorrelation. From 2011 to 2015, the values of Moran I were 0.261, 0.372, 0.376, 0.248 and 0.297, respectively, and Z values were 10.188, 14.424, 14.798, 9.762 and 11.594, respectively, with all P values <0.001. The Ordinary Kriging model and the Bayesian Kriging model predicted the distribution in line with the actual distribution law. After cross-validation, the fitting effect of the two models was ideal. The Bayesian Kriging model (RMSE ranged 0.382-0.484) was slightly higher than the Ordinary Kriging model (RMSE ranged 0.379-0.522). Conclusion The SMR of smear-positive PTB in Xinjiang from 2011 to 2015 showed spatial clustering at the district (county) level, and SMR showed a downward trend in volatility. Kriging interpolation analysis is helpful in estimating the risk of active PTB in Xinjiang.

Study on the influencing factors of perceived social support in patients with drug-resistant tuberculosis

TANG Ling-ling, CHEN Dan-ping, FANG Xue-e, SHI Ting, CAI Li-ping, LI Ce

Chinese Journal of Antituberculosis. 2020, 42(6):  604-608.  doi:10.3969/j.issn.1000-6621.2020.06.012

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Objective The aim of the study is to explore the influencing factors of perceived social support in patients with drug-resistant tuberculosis. Methods From January 2018 to August 2019, 160 patients with drug-resistant tuberculosis admitted to the tuberculosis Department of Shanghai Pulmonary Hospital were selected as the study object. The perceived social support scale was used to evaluate the degree of social support of patients, and according to the total score of perceived social support scale (mainly including family support, friend support, and other supports) with the threshold point of 50 scores, patients were divided into high group (68 cases) and low group (92 cases). The influencing factors of perceived social support of patients with drug-resistant tuberculosis were analyzed by logistic multivariate regression analysis. Results Logistic multivariate regression analysis showed that age >60 years (OR=6.900; 95%CI: 2.984-15.953; P=0.005), junior high school and below (OR=2.870;95%CI: 1.236-6.665; P<0.001), unmarried (OR=1.257; 95%CI: 0.545-2.899; P=0.045) or divorced (OR=3.960;95%CI: 1.742-9.001; P=0.030), mild depression (OR=6.325; 95%CI: 2.910-13.750; P=0.022) or moderate or above depression (OR=10.733; 95%CI: 3.847-29.950; P<0.001), rural area (OR=2.294; 95%CI: 1.209-4.353; P=0.040), family monthly income per capita <2500 yuan (OR=5.881; 95%CI: 2.348-14.733; P<0.001), retreatment (OR=2.030; 95%CI: 1.074-3.838; P=0.013), and multi-drug resistance (OR=1.860; 95%CI: 0.854-4.048; P<0.001) or extensive drug resistance (OR=3.409; 95%CI: 1.533-7.581; P<0.001) were risk factors of perceived social support for patients with drug-resistant tuberculosis. Conclusion Age >60 years old, junior high school or below, unmarried or divorced, depression, rural areas, monthly income per family <2500 yuan, retreatment and multi-drug or extensive drug resistance are risk factors of perceived social support for patients with drug-resistant tuberculosis.

Analysis of drug susceptibility of 680 patients with multidrug-resistant tuberculosis in Xi’an City from 2015 to 2019

MA Jin-bao, REN Fei, ZENG Ling-cheng, CHEN Ming-wei

Chinese Journal of Antituberculosis. 2020, 42(6):  609-613.  doi:10.3969/j.issn.1000-6621.2020.06.013

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Objective A retrospective analysis of drug susceptibility test (DST) results of multidrug-resistant tuberculosis(MDR-TB) patients was carried out to provide evidence for guiding clinical drug administration for MDR-TB patients. Methods All of 680 MDR-TB patients in Xi’an City from 2015 to 2019 were selected as study subjects. The DST results of ethambutol (EMB), streptomycin (Sm), protionamide (Pto), amikacin (Am), capreomycin (Cm), P-aminosalicylic acid (PAS), levofloxacin (Lfx) and moxifloxacin (Mfx) were collected and analyzed. Results (1)The rates of resistance to different drugs could be listed from high to low as: Sm (85.7% (583/680)), Lfx (40.1% (273/680)), EMB (37.5% (255/680)), Mfx (31.3% (213/680)), PAS (14.4% (98/680)), Pto (4.6% (31/680)), Am (4.4% (30/680)), and Cm (4.3% (29/680));(2)The rates of resistance to several second-line anti-tuberculosis drugs decreased from 2015 to 2019:Am (from 6.9% decreased to 3.0%,$\chi^{2}_{trends}$=2.78,P=0.096), Cm (10.3%/3.0%,$\chi^{2}_{trends}$=6.96,P=0.008), Lfx (55.2%/28.4%,$\chi^{2}_{trends}$=24.97,P=0.000), Mfx (43.1%/22.9%,$\chi^{2}_{trends}$=16.45,P=0.000), Pto (6.9%/6.0%,$\chi^{2}_{trends}$=0.44,P=0.506), Pas (20.7%/8.0%,$\chi^{2}_{trends}$=7.79,P=0.005).(3)Cross resistance of second-line anti-tuberculosis drugs: among 30 cases resistant to Am, 21 (70.0%) cases were resistant to Cm; in 29 cases resistant to Cm, 21 (72.4%) cases were resistant to Am; 205 (75.1%) cases were resistant to Mfx in 273 Lfx-resistant cases, 205 (96.2%) cases were resistant to Lfx in 213 Mfx-resistant cases. Conclusion In these 5 years, MDR-TB patients in Xi’an City kept a high resistance rate to EMB and Sm. The drug resistance rates of second-line anti-tuberculosis drugs decreased, but we still need to pay attention to the high resistance rate of quinolone. Those resistance rates to different drug and high cross-resistance rate among second-line anti-tuberculosis drugs should be considered when selecting drugs.

A study of prediction effect of autoregressive integrated moving average model on the monthly reported pulmonary tuberculosis cases in China

ZHANG Shun-xian, QIU Lei, ZHANG Shao-yan, LI Cui, HU Jun, TIAN Li-ming, LU Zhen-hui

Chinese Journal of Antituberculosis. 2020, 42(6):  614-620.  doi:10.3969/j.issn.1000-6621.2020.06.014

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Objective An autoregressive integrated moving average (ARIMA) model was used to predict the monthly pulmonary tuberculosis cases in China(excluding Hong Kong, Macao and Taiwan regions) to provide a reference for pulmonary tuberculosis prevention and control. Methods Monthly pulmonary tuberculosis cases number in China from January 2006 to December 2018 reported on Disease Surveillance sponsored by CDC were collected. Based on these data, time series, preliminary identification and ordering of ARIMA model types were conducted using SPSS 26.0. Several ARIMA models were selected according to that both the simplicity of the model and the parameters of the ARIMA model (including autoregressive method (AR), average moving method (MA), seasonal autoregressive method (SAR), seasonal moving average method (SMA)) were statistically significant (Ps<0.05), as well as the overall test index (Ljung-Box Q value), maximum stationary coefficient (R ²) of the model, standardized Bayesian information criterion value (NBIC) of the smallest overall model, and minimum root mean square error (RMSE). Numbers of reported cases from January to August 2019 were used as verification, and the model with the smallest relative error was selected as the optimal model according to that the smaller the relative error of the predicted value, the better the model; finally, the model was used to predict monthly reported numbers of tuberculosis patients from September 2019 to December 2020 in China. Results Time series were based on cases from January 2006 to December 2018, the fitted model was ARIMA (p, d, q) or ARIMA (p, d, q)×(P, D, Q). Twelve models were selected according to P value (which is relative to Ljung-Box Q)>0.05,the simplicity of the model, and parameters of the model were statistically significant (all P<0.05); and models with the maximum R ² (ARIMA (1, 0, 1) (0, 1, 1)₁₂, R ²=0.707)), or with the minimum RMSE (ARIMA (0, 1, 2) (0, 1, 1)₁₂, RMSE=9147.85), or with the minimum NBIC (ARIMA (0, 1, 1) (0, 1, 1)₁₂, NBIC=18.355)), or with the minimum Ljung-Box Q (ARIMA (1, 1, 1) (0, 1,1)₁₂, Ljung-Box Q=8.797)) were taken as alternatve models, to predict numbers of reported cases from January to August 2019, which were then compared with the actual data, to determine the optimal ARIMA model (ARIMA (0, 1, 1) (0, 1, 1)₁₂ model), with the relative error was the smallest (0.55%), MA (1)=0.875 (t=19.243, P<0.001), SMA (1)=0.876 (t=7.596, P<0.001), Ljung-Box Q=9.876 (df=16, P=0.873). The ARIMA (0, 1, 1) (0, 1, 1)₁₂ model was used to predict numbers of monthly reported tuberculosis cases in China from September 2019 to December 2020; in 2020 year, there will be 1025863 cases totally with average of 85489 cases monthly. Conclusion ARIMA (0, 1, 1) (0, 1, 1)₁₂ model is the better model to predict the monthly pulmonary tuberculosis cases in China. However, in order to improve accuracy of the prediction, the establishment and prediction of the model is a dynamic process needed to be adjusted continuously according to accumulated data.

Review Articles

Progress and prospect of positron emission computed tomography applied in clinical research of pulmonary tuberculosis

SONG Qi-sheng, LU Xi-wei

Chinese Journal of Antituberculosis. 2020, 42(6):  621-625.  doi:10.3969/j.issn.1000-6621.2020.06.015

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Positron emission computed tomography-CT (PET-CT) scan can be used for evaluating the latent tuberculosis (TB) infection/subclinical TB infection in early stage, identifying the potential infectious lesions, finding the etiological factors in patients with unexplained fever, comprehending the inflammatory reaction of lesions by observing the uptake of fluorodeoxyglucose ( ¹⁸F-FDG), and making an objective evaluation of TB activity. During the course of anti-TB treatment, the success of the treatment can be predicted by observing the series of changes of ¹⁸-FDG uptake of the lesion. However, due to the high price and other issues, the widespread clinical application of PET-CT is limited. Nevertheless, based on the technical advantages of PET-CT, it is still expected to play an important role in clinical and scientific research of TB.

Review on the progress of laboratory tests for activity judgment of pulmonary tuberculosis

FU Liang, DENG Guo-fang

Chinese Journal of Antituberculosis. 2020, 42(6):  626-629.  doi:10.3969/j.issn.1000-6621.2020.06.016

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The epidemic situation of pulmonary tuberculosis in China is challenging. The pathogenic test of Mycobacterium tuberculosis is the “golden indicator” for the diagnosis of pulmonary tuberculosis, but the diagnosis becomes difficult when the test results are negative. This review introduces the current evaluation methods of laboratory tests for activity judgment of pulmonary tuberculosis, such as Mycobacterium tuberculosis antigens, inflammatory and acute-phase reaction markers, immunological indicators, and blood transcription markers; points out the problems of current laboratory tests for activity judgment and clinical implementation; and discusses its future development.

Short Articles

Spectrum and drug resistance analysis of 339 strains of nontuberculous mycobacterium isolated from clinical practice

QIN Zhong-hua, JING Ye, DU Yan-qing, SONG Xiao-mei, ZHANG Li-xia

Chinese Journal of Antituberculosis. 2020, 42(6):  630-633.  doi:10.3969/j.issn.1000-6621.2020.06.017

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From March 2014 to March 2019, 339 strains were identified as nontuberculous mycobacterium (NTM) by Roche culture and DNA microarray technology in Tianjin Haihe Hospital. Drug sensitivity test (DST) were performed. Among 339 NTM clinical isolates, the top three were M.intracellulare (38.6%, 131/339), M.cheloni-abscessus (21.2%, 72/339) and M.kansas (18.3%, 62/339). In vitro DST showed that the drug resistance rates of M.intracellular, M.Kansas an M.cheloni-abscessus to 8 antituberculosis drugs (isoniazid, rifampin, streptomycin, ethambutol, p-aminosalicylic acid, kanamycin, capreomycin, ofloxacin) were: 95.6% (108/113), 82.3% (93/113), 94.7% (107/113), 54.0% (61/113), 92.0% (69/75), 81.3% (61/75), 85.3% (64/75), 87.5% (49/56) for M.intracellulare; 100.0% (54/54),3.7% (2/54),98.1% (53/54),11.1% (6/54),95.0% (38/40),90.0% (36/40),27.5% (11/40),13.8% (4/29) for M.kansas; 96.9% (62/64),93.8% (60/64),95.3% (61/64),92.2% (59/64),88.4% (38/43),86.0% (37/43), 88.4% (38/43), 87.1% (27/31) for M.cheloni-abscessus. The clinical isolates of NTM were mainly M.intracellulare, M.cheloni-abscess and M.Kansas, of which M.intracellulare and M.cheloni-abscess had high resistance to common first-line and second-line anti tuberculosis drugs, while M.Kansas had low resistance to rifampin, ethambutol, ofloxacin and capreomycin.

Clinical characteristics of 15 pregnant women with tuberculosis

JIANG Ling, ZENG Wei-feng, TANG Na, LUO Ting-ru, MENG Chang-ping, PENG Yu-jing, QIAN Chun-fang

Chinese Journal of Antituberculosis. 2020, 42(6):  634-637.  doi:10.3969/j.issn.1000-6621.2020.06.018

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The clinical data of 15 pregnant women with tuberculosis who admitted to the tuberculosis Department of Chongqing Public Health Medical Treatment Center from January 1, 2017 to September 30, 2019 were collected. The clinical manifestations, treatment delays, imaging manifestations, immune response status, therapeutic effect and fetal outcome of pregnant women with tuberculosis were summarized. The main clinical manifestations of pregnant women with tuberculosis were fever, fatigue and cough, and the main clinical manifestations of tuberculous meningitis were headache. For treatment delays, 12 pregnant women had different degrees of delayed treatment with the shortest delayed days of 20 days, the longest of 252 days, and the median delayed days of 78 days. Chest CT scan showed 4 patients with multi-lobal patchy of both lungs with exudative shadows or cavities, 12 patients with diffuse miliary nodules in the lungs, and 10 patients with unilateral or bilateral pleural effusions or pleura thickening. Eleven patients with tuberculous meningitis underwent head MRI, which showed 9 cases of cerebral parenchymal nodules and patchy lesions, 8 cases of thickened meninges, 2 cases of cerebral edema, and 1 case of thickened spinal membrane.. Immune response results showed that the values of CD4 ⁺T cells decreased in 10 pregnant women, CD8 ⁺T cells decreased in 9 pregnant women, and CD4 ⁺ T/CD8 ⁺ T ratio decreased in 11 pregnant women. After treatment, 14 patients improved after treatment with anti-tuberculosis drugs, and 1 patient was hospitalized for severe tuberculous meningitis. In terms of fetal outcome, there were 10 naturally conceived fetuses, 1 abortion, 1 stillbirth, and 8 deliveries (including 2 children died of tuberculous meningitis and 6 healthy fetuses); as well as 7 fetuses conceived by assisted reproductive technology, 2 abortions, and 5 deliveries (including 3 healthy fetuses and 2 died of tuberculous meningitis). In summary, pregnant women with tuberculosis have a low immune response and more blood-borne disseminated pulmonary tuberculosis. Mycobacterium tuberculosis is prone to cause extrapulmonary tuberculosis by blood dissemination, and tuberculosis meningitis is common. The delay of medical treatment of pregnant women with tuberculosis is serious, and timely and standardized treatment can benefit pregnant women and fetuses.

The clinical features and prognostic analysis of 30 pregnant or parturient women with severe tuberculosis

CHEN Juan, MAO Yi, CHEN Hong-de

Chinese Journal of Antituberculosis. 2020, 42(6):  638-640.  doi:10.3969/j.issn.1000-6621.2020.06.019

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To investigate the clinical features and prognosis of the pregnant or parturient women with severe tuberculosis, the clinical data of 30 patients (21 pregnant women and 9 parturients) with severe tuberculosis admitted to the tuberculosis department of the Urban Public Health Clinical Medical Center from January 2013 to June 2018 were collected and analyzed in this study. The results showed that the symptoms of patients were fever (90.0%, 27/30), shortness of breath (86.7%, 26/30), and cough (76.7%, 23/30). Hematogenous pulmonary tuberculosis was the most common form (73.3%, 22/30) of tuberculosis, and 33.3% (10/30) of the patients were complicated with extrapulmonary tuberculosis. Of the 30 patients, 11 (36.7%) patients underwent in vitro fertilization-embryo transfer (IVF-ET); 4 patients died in the hospital, 2 patients died by phone follow-up after being discharged; 9 parturients gave birth to live babies outside the hospital, 14 cases of pregnant women induced labor or abortion, 4 cases of pregnant women delivered successfully in our hospital, and 3 cases of pregnant women continued pregnancy. In conclusion, the pregnant or parturient women in severe tuberculosis are lack of typical clinical manifestations, mainly with hematogenous pulmonary tuberculosis. Timely diagnosis and standardized treatment should be made to improve the prognosis. Meanwhile, tuberculosis screening is recommended for women who plan to undergo IVF-ET.

Application effect of individual case management model during the process of taking bedaquiline in patients with MDR-PTB

FANG Xue-e, CHEN Dan-ping, TANG Ling-ling, FAN Lin, CHEN Wei, JI Hai-ming, MAO Yan-jun

Chinese Journal of Antituberculosis. 2020, 42(6):  641-644.  doi:10.3969/j.issn.1000-6621.2020.06.020

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A total of 50 patients with multidrug-resistant pulmonary tuberculosis (MDR-PTB), who received bedaquiline treatment in the Shanghai Pulmonary Hospital Affilicated to Tongji University from November 2018 to October 2019, were enrolled into this study. A individual case management model was used to all enrolled patients, and the medication adherence of those MDR-PTB patients was evaluated with the Morisky Medication Adherence Scale (MMAS, Chinese version) at 2 weeks, 1 month, 3 months and 6 months respectively after taking bedaquiline and their self-efficacy was evaluated with the General Self-efficacy Scale (GSE, Chinese version). The MMAS score of the patients was (5.25±0.15) before the intervention; after the intervention, it increased to (7.29±0.12), (7.68±0.07), (7.76±0.06) and (7.96±0.03) respectively at 2 weeks, 1 month, 3 months and 6 months of bedaquiline treatment, which was statistically significant higher than that before the intervention (F=88.925, P<0.001). The GSE score was (24.32±8.36) before the intervention; after the intervention, it was (25.20±7.94), (27.28±9.58), (36.48±5.81) and (36.76±5.90) respectively at 2 weeks, 1 month, 3 months and 6 months of bedaquiline treatment, which was statistically significant higher than that before the intervention (F=15.532, P<0.001). The study suggested that the application of the individual case management model in the management of MDR-PTB patients taking bedaquiline can significantly improve their treatment compliance and self-efficacy.

Experience Introduction

Analysis of surgical treatment characteristics in patients with spinal tuberculosis and HIV co-infection

BAO Rui, LIU Xiao-yang, REN Peng, ZHANG Feng, LIANG Hai-yan, WANG Ru, FU Ling, GAN Di-shou

Chinese Journal of Antituberculosis. 2020, 42(6):  645-648.  doi:10.3969/j.issn.1000-6621.2020.06.021

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A total of 5 patients with spinal tuberculosis (TB) and HIV co-infection (observation group) and 5 patients with spinal TB only (control group), who received surgical treatment in the Guiyang City Public Health Treatment Center of Guizhou Province from 2013 to 2018 and met the admission criteria, were enrolled into this study. The sex, age and operation methods of the patients in the observation group and control group were matched. The author compared the clinical data of the patients in both groups and to explore the surgical treatment strategy of the patients with spinal TB and HIV co-infection. It was found that, when the CD4 ⁺ T-lymphocyte count of the patients in the observation group was evaluated and corrected before the operation and the standardized disinfection and isolation procedures and the three-level occupational exposure protection principles (all surgical medical staff wore masks with protective glasses, double-layer latex gloves, disposable waterproof surgical clothes, sleeves and boots) were strictly adhered during the operation, there was no significant difference between the two groups in the selection of surgical methods, age, intraoperative hemorrhage, postoperative drainage, and VAS score (Ps>0.05). However, the average operation time in the observation group ((3.0±0. 9) h) was significant higher than that in the control group ((2.7±0. 6) h) (t=-0. 424, P=0. 004). One patient in the observation group appeared the drainage sinus in one week after discharged from the hospital and it gradually healed in 3 months of debridement, dressing change and control of CD4 ⁺ T-lymphocyte count.