Table of Content

10 December 2022, Volume 44 Issue 12

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Guideline·Standard·Consensus

Expert consensus on clinical differential diagnosis and treatment of intrathoracic sarcoidosis and pulmonary tuberculosis under the background of tuberculosis epidemic

Multidisciplinary Diagnosis and Treatment Committee of the Chinese Anti-tuberculosis Association, Editorial Board of Chinese Journal of Antituberculosis, Clinical Multidisciplinary Cooperation Working Group of the Radiology Branch of the Chinese Medical Association

Chinese Journal of Antituberculosis. 2022, 44(12):  1227-1241.  doi:10.19982/j.issn.1000-6621.20220361

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Common pathological features of both intrathoracic sarcoidosis and pulmonary tuberculosis are epithelioid granulomas, and the clinical manifestations of the two diseases are similar to some extent, which may lead to misdiagnosis and mistreatment. It is necessary to establish standardized identification and management procedures for the two diseases, especially in tuberculosis endemic areas. Therefore, the Multidisciplinary Diagnosis and Treatment Committee of the Chinese Antituberculosis Association, Editorial Board of Chinese Journal of Antituberculosis and Clinical Multidisciplinary Cooperation Working Group of the Radiology Branch of the Chinese Medical Association organized multidisciplinary experts to develop an Expert consensus on clinical differential diagnosis and treatment of intrathoracic sarcoidosis and pulmonary tuberculosis under the background of tuberculosis epidemic after combining clinical experiences and summarizing worldwide research results. The consensus provides the differentiation of the two diseases in terms of clinical manifestations, imaging characteristics, bronchoscopy, pathological and etiological examinations. It also proposes a specific framework of confirming the diagnosis of challenging cases through multidisciplinary cooperation with specific procedures and steps. Meanwhile, target population for the screening of potential tuberculosis infection amongst sarcoidosis patients are determined. Additionally, recommendations are given on the treatment and management of latent tuberculosis infection, so as to provide accurate treatment and improve the prognosis of patients.

Interpretation of Standards

Interpretation of Expert consensus on clinical differential diagnosis and treatment of intrathoracic sarcoidosis and pulmonary tuberculosis under the background of tuberculosis epidemic

Zeng Yi, Hu Hongling, Li Zhiyong, Zhou Hui, Chen Yu, Zhang Peize, Fang Fang, Lai Xiaoyu, Lu Xiwei

Chinese Journal of Antituberculosis. 2022, 44(12):  1242-1248.  doi:10.19982/j.issn.1000-6621.20220359

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Intrathoracic sarcoidosis and tuberculosis are similar in clinical characteristics, pathological manifestations and imaging signs. It is particularly important to establish a standardized differential diagnosis process to avoid misdiagnosis and mistreatment, especially in tuberculosis endemic areas. Therefore, the Multidisciplinary Diagnosis and Treatment Committee of the Chinese Antituberculosis Association, Editorial Board of Chinese Journal of Antituberculosis and Clinical Multidisciplinary Cooperation Working Group of the Radiology Branch of the Chinese Medical Association organized multidisciplinary experts from the national tuberculosis department, respiratory department, pathology department, imaging department and related disciplines to develop an Expert consensus on clinical differential diagnosis and treatment of intrathoracic sarcoidosis and pulmonary tuberculosis under the background of tuberculosis epidemic. As a participant in the consensus compilation, the author interprets the difficulties and recommendations in the differential diagnosis of the two diseases for clinical reference.

Interpretation of WHO Guidelines on tuberculosis care and support

Liu Eryong, Meng Qinglin, Wang Qian, Wang Jing, Zhou Lin

Chinese Journal of Antituberculosis. 2022, 44(12):  1249-1252.  doi:10.19982/j.issn.1000-6621.20220409

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In July 2022, the World Health Organization (WHO) published Guidelines on tuberculosis care and support. The patient centered care activities were introduced from various interventions such as social support, treatment management and digital health technology. Through the interpretation of the guideline, to introduce the contents to the readers and provide reference to patients’ care activities in China.

Special Topic

Strengthen the screening of close contacts to improve the detection of tuberculosis patient

Li Meng, Chen Chuang, Gao Qian

Chinese Journal of Antituberculosis. 2022, 44(12):  1253-1255.  doi:10.19982/j.issn.1000-6621.20220384

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Screening of close contacts of tuberculosis (TB) patients is a routine work of actively finding patients in TB control tuberculosis control measures in China, but the effect is not satisfactory. In this article, we summarized the current status of incidence risk and screening among close contacts of TB patients at home and abroad, and described the results of recent research. Meanwhile, we found that the proportion of TB patients from close contacts in the rural TB epidemic in China is greatly underestimated. Therefore, strengthen the screening of close contacts plays an essential role in actively finding TB patients is an urgent problem to be solved.

Original Articles

Surveillance and analysis of tuberculosis in Inner Mongolia from 2011 to 2020

Zhang Xin, Lang Shengli, Bai Guohui, Gao Yulong, Xu Lijuan

Chinese Journal of Antituberculosis. 2022, 44(12):  1256-1261.  doi:10.19982/j.issn.1000-6621.20220211

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Objective: To analyze the epidemiological characteristics of tuberculosis (TB) epidemic in Inner Mongolia from 2011 to 2020, and to provide scientific evidence for the development of TB control and prevention strategy. Methods: Data of patients with pulmonary tuberculosis registered in Inner Mongolia from Jan. 1st, 2011 to Dec. 31st, 2020 were collected from the tuberculosis information management system, a subsystem of the infectious disease surveillance system of China CDC. Demographic data came from the Inner Mongolia. A descriptive epidemiological method was used to describe the epidemiological characteristics of the Inner Mongolia tuberculosis epidemic. Results: From 2011 to 2020, a total of 118599 cases of tuberculosis were registered in Inner Mongolia, with an average annual registered incidence of 47.42/100000, the registered incidence rate decreased from 67.47/100000 (16743/24817100) in 2011 to 35.39/100000 (8510/24049200) in 2020. The overall trend was downward ( {\chi }_{\mathrm{t}\mathrm{r}\mathrm{e}\mathrm{n}\mathrm{d}}^2=3442.167, P<0.001), There were 44548 cases with positive pathogen. The positive rate of pathogen decreased from 53.15% (8899/16743) in 2011 to 24.74% (2498/10095) in 2017, ( {\chi }_{\mathrm{t}\mathrm{r}\mathrm{e}\mathrm{n}\mathrm{d}}^2=18281.481, P<0.001), and from 2018 to 2020, the positive rate of pathogens increased year by year, which was from 36.29% (4703/12958) to 52.26% (4447/8510) ( {\chi }_{\mathrm{t}\mathrm{r}\mathrm{e}\mathrm{n}\mathrm{d}}^2=8077.724, P<0.001). The epidemic situation of pulmonary tuberculosis showed obvious seasonal and periodic fluctuation, with a high incidence in spring and summer. The number of patients in March was 12571, accounting for 10.60% (12571/118599) of all registered patients. The average annual registration rate of pulmonary tuberculosis patients ranged from 25.70/100000 to 66.49/100000. The peak of the average registered incidence rate was in eastern region. Leagues (prefectures) with relatively high registered incidence were Xing’an League (66.49/100000, 10547/15862600), Tongliao (64.86/100000, 20131/31038100), and those with relatively low incidence were Ordos City (25.79/100000, 5299/20544600), Hohhot City (25.68/100000, 7925/30864800). The incidence rate of male (61.22/100000, 79090/129194300) was significantly higher than that of female (32.67/100000, 39509/120927500)(χ²=10739.668, P<0.001).The highest incidence rate was in the 45-54 age group (9.49/100000, 23726/250121800), the next was in the 55-64 age group (9.32/100000, 23315/250121800).The patients were mainly farmers (61.58%, 73032/118599), followed by the patients with housekeeping/housework/unemployment, accounting for 13.32% (15794/118599). Conclusion: From 2011 to 2020,the registered incidence rate of pulmonary tuberculosis in Inner Mongolia was decreasing year by year. More attention should be paid to men, the middle-aged and the elderly, farmers and people in eastern region. Further measures should be taken to improve the quality of work in key areas and among high-risk groups in order to end the epidemic of tuberculosis.

Incidence and risk factors of catastrophic expenditure for multidrug-resistant tuberculosis in Guangdong Province

Yu Meiling, Liang Hongdi, Zhou Fangjing, Chen Liang, Wu Ya, Gao Lijie, Wen Wenpei, Zhu Sui, Wu Huizhong

Chinese Journal of Antituberculosis. 2022, 44(12):  1262-1272.  doi:10.19982/j.issn.1000-6621.20220235

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Objective: To investigate the incidence and risk factors of catastrophic expenditure among patients with multidrug-resistant tuberculosis (MDR-TB) in Guangdong Province. Methods: The MDR-TB patients diagnosed in 11 designated medical institutions in 9 prefecture-level cities in Guangdong Province from 2018 to 2019 were selected. Questionnaires for surveying basic characteristics, patients’ disease and medical visit history, financial burden, and health insurance policies of medical institutions, individuals and cities were collected. A two-level logistic regression model was used to explore the risk factors of catastrophic expenditure in MDR-TB patients. Results: A total of 398 patients were included in this study. The median direct medical expenses was 51100 (22600, 98200) yuan; the median direct non-medical expenses was 14600 (7100, 33300) yuan; the median indirect costs was 5100 (3100, 7300) yuan; the median total costs was 84300 (42900, 147600) yuan; and the median total out-of-pocket expenses was 58400 (29700, 111800) per case. A total of 259 MDR-TB patients suffered with catastrophic expenditure, with an incidence of 65.08%. The two-level logistic regression model showed that the risk of catastrophic expenditure for households with debt was 2.57 times of that for households without debt (95%CI: 1.43-4.62). The incidence of catastrophic expenditure increased gradually with the patients’ hospitalization length, and the incidence for patients hospitalized for 1 month and ≥2 months were 4.38 (95%CI:2.38-8.06) times and 31.37 (95%CI: 11.09-88.74) times of that for non-hospitalized patients. Conclusion: A high incidence of catastrophic expenditure for MDR-TB patients was found in Guangdong Province. Debt and length of hospitalization were the risk factors for incidence of catastrophic expenditure. Multiple measures should be taken to reduce the incidence of catastrophic expenditure in MDR-TB patients.

Investigation and analysis on awareness rate of core knowledge of tuberculosis prevention and control among residents in pastoral areas of Qinghai Province

Wang Chaocai, Song Jiahui, Liu Yan, Wei Yujia, Chao Xiuzhen, Li Erchen, Jiang Mingxia

Chinese Journal of Antituberculosis. 2022, 44(12):  1273-1278.  doi:10.19982/j.issn.1000-6621.20220230

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Objective: To explore the core knowledge of tuberculosis prevention and control among residents in pastoral areas of Qinghai,so as to provide a basis for targeted health education in the future. Methods: From March to August 2021, the herdsmen in 32 counties of 6 Tibetan autonomous prefectures in Qinghai were investigated using the method of multi-stage stratified cluster sampling. A face-to-face interview survey was conducted using the questionnaire designed by the special expert group after literature search and expert consultation. A total of 3310 questionnaires were distributed and 3241 valid questionnaires were collected, with an effective rate of 97.92%. The questionnaire includede the basic demographic characteristics, the awareness rate of the core knowledge of tuberculosis prevention and control and the main way for getting tuberculosis knowledge and information. Results: The total awareness rate of tuberculosis prevention and control knowledge among residents in pastoral areas of Qinghai was 81.49% (13206/16205). Among the single item knowledge awareness rates, the awareness rate of “coughing or coughing up sputum for more than 2 weeks or with blood in sputum, should be suspected of having tuberculosis” was the highest (91.11%, 2953/3241); while the awareness rate of “as long as regular treatment is adhered to, most tuberculosis patients can be cured” was the lowest (71.52%, 2318/3241). Of the 3241 subjects, 91.48% (2965/3241) had received health education, those without health education accounted for 8.52% (276/3241). The top three ways for residents to receive education were television (68.80%, 2040/2965), flyers/folds/posters (63.61%, 1886/2965), and billboards/wall newspapers/blackboard newspapers (61.42%, 1821/2965). The most desirable way for pastoral residents to receive health education was radio/television/film/audio-visual materials (73.71%, 2389/3241), followed by posters/billboards/billboards/display boards/wall slogans (59.80%, 1938/3241) and doctor publicity (56.56%, 1833/3241). Conclusion: The awareness rate of core knowledge of tuberculosis prevention and control among residents in pastoral areas of Qinghai is lower than the requirement of the National Tuberculosis Control Program. It is necessary to strengthen the propaganda and education of tuberculosis prevention and control knowledge in pastoral areas, and targeted propaganda and education measures suitable for pastoral areas should be carried out.

Analysis of drug resistance situation and influencing factors among high-risk group of drug-resistant tuberculosis in Guangzhou, 2014—2019

Shen Hongcheng, Du Yuhua, Zhang Danni, Wu Guifeng, Lei Yu, Xiao Xincai, Liu Jianxiong

Chinese Journal of Antituberculosis. 2022, 44(12):  1279-1287.  doi:10.19982/j.issn.1000-6621.20220284

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Objective: To analyze the status and characteristics of drug resistance and influencing factors among high-risk group of drug resistant tuberculosis in Guangzhou. Methods: Information of 2155 high-risk group of drug-resistant tuberculosis in Guangzhou from January 1, 2014 to December 31, 2019 was collected from “Tuberculosis Management Information System of China Information System for Disease Control and Prevention”, including sociodemographic characteristics, drug resistance screening results and so on, relevant information of 2155 subjects was finally included. Drug resistance status, sequence, spectrum and influencing factors of five anti-tuberculosis drugs including isoniazid (INH), rifampicin (RFP), ethambutol (EMB), ofloxacin (Ofx) and kanamycin (Km) were analyzed. Results: Among 2155 subjects, 768 were drug resistant cases, with the total drug resistance rate of 35.64%. The rates of single drug resistance, multi-drug resistance, and extensively drug resistance were 10.39% (224/2155), 24.36% (525/2155), and 0.88% (19/2155), respectively. The drug resistance rates of INH, RFP, EMB, Ofx, Km were 31.97% (689/2155), 29.05% (626/2155), 10.72% (231/2155), 7.75% (167/2155), 2.55% (55/2155), respectively. The percentages of drug resistance including 1 to 5 anti-tuberculosis drugs were 24.22% (186/768), 39.97% (307/768), 24.87% (191/768), 9.38% (72/768) and 1.56% (12/768), respectively. Among the single drug resistance subjects, INH was the most common, accounting for 15.23% (117/768); among those who resistant to 2 anti-tuberculosis drugs, INH+RFP was the most common, accounting for 35.94% (276/768); among those who resistant to 3 anti-tuberculosis drugs, INH+RFP+EMB resistance was the most common, accounting for 16.80% (129/768); among those who resistant to 4 anti-tuberculosis drugs, INH+RFP+EMB+Ofx was the most common, accounting for 6.51% (50/768). Multivariate logistic regression analysis showed that the risk of drug resistance in patients ≥65 years old was 37.9% of the patients <25 years old (OR=0.379, 95%CI: 0.226-0.634); as to the occupational classification, the risk of drug resistance in business service, teachers, medical staff and cadres, farmers, and others was 2.419 times (95%CI: 1.429-4.096), 2.541 times (95%CI: 1.325-4.873), 1.479 times (95%CI: 1.028-2.127), and 6.452 times (95%CI: 4.624-9.003) that of retirees, respectively; as to the classification of patients, the risk of drug resistance of initial treatment failure, retreatment failure/chronic patients, relapse and others was 9.443 times (95%CI: 6.009-14.621), 7.504 times (95%CI: 4.634-12.151), 2.567 times (95%CI: 1.968-3.348) and 3.091 times (95%CI: 1.969-4.854) that of sputum smear positive patients at the end of 2 and 3 months after initial treatment, respectively. Conclusion: In recent years, more than 1/3 of the high-risk group of drug resistant tuberculosis in Guangzhou has developed drug resistance, and the situation of drug resistance cannot be ignored. Among the high-risk group of drug resistant tuberculosis, we should focus on young and middle-aged people, business services, teachers, doctors, employees of enterprises and institutions, farmers and other practitioners, as well as people who have failed initial treatment, failed retreatment/chronic patients, and relapsed.

Analysis of the efficacy of regimen containing bedaquiline in the treatment of twelve adolescent rifampicin-resistant pulmonary tuberculosis patients

Xue Yu, Zhang Jing, Chen Yanqin, Li Wensheng, Lei Xuan, Zhou Kun, Jiao Yan, Nie Wenjuan, Chu Naihui

Chinese Journal of Antituberculosis. 2022, 44(12):  1288-1293.  doi:10.19982/j.issn.1000-6621.20220288

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Objective: To retrospectively analyze the efficacy of regimen containing bedaquiline in the treatment of 12 adolescent drug-resistant pulmonary tuberculosis (TB) patients. Methods: From April 2020 to January 2021, 12 adolescent patients under 18 years old with drug-resistant TB who used bedaquiline regimen in Beijing Chest Hospital were enrolled, of them, 3 with rifampicin-resistant (RR), 5 with multidrug-resistant (MDR), and 4 with pre-extensively drug-resistant (pre-XDR). TB culture conversion rate and lesions absorption after 24 weeks were analyzed to assess the treatment efficacy. The adverse effects such as changes of QTc in ECG were recorded to assess the treatment safety. Results: All the 12 cases completed the 24-week treatment and the culture achieved negative conversion. Chest CT scan showed significant effect in 8 cases and effective in 4 cases. Among 6 patients with lung cavities, cavity in the lung became smaller or the number reduced in 4 cases, and 2 showed cavity closure. Adverse effects included prolonged QT interval (n=1), peripheral neuropathy (n=3), damaged optic nerve (n=2), headache (n=1), shaking hands (n=1), tinnitus (n=1), anemia (n=2), gastrointestinal reaction (n=3), elevated transaminase (n=3), and hyperuricemia (n=2), however, all of the patients did not stop using bedaquiline. Conclusion: The negative conversion rates of culture in adolescent patients with drug-resistant TB was relatively high after receiving 24 weeks regimen containing bedaquiline, and the tolerance was relatively good.

Retrospective analysis of clinical intervention and follow-up of patients with systemic lupus erythematosus complicated with tuberculosis infection

Zhou Qian, Deng Guofang, Wang Qingwen

Chinese Journal of Antituberculosis. 2022, 44(12):  1294-1302.  doi:10.19982/j.issn.1000-6621.20220244

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Objective: To analyze the clinical intervention and follow-up of patients with systemic lupus erythematosus (SLE) complicated with tuberculosis infection, and to provide a reference for the prevention and treatment of tuberculosis in SLE patients. Methods: A retrospective study was conducted to collect 486 SLE patients, who admitted to the Rheumatology and Immunology Department of Peking University Shenzhen Hospital from November 2014 to March 2020. All subjects underwent tuberculin skin test (TST), interferon-gamma release assays (IGRA) and imaging examination after SLE diagnosis, and were followed up for more than two years. The clinical data of the subjects were collected, including gender, age, duration of SLE, laboratory examination, imaging examination and drug treatment, etc. The tuberculosis infection status, possible influencing factors and follow-up results of SLE patients were analyzed. Results: Among these 486 SLE patients, the incidence of tuberculosis was 20.8% (101/486), including 15 (3.1%) active tuberculosis and 86 (17.7%) inactive tuberculosis patients; of the inactive tuberculosis patients, 74 (15.2%) were latent tuberculosis infection (LTBI), and 12 (2.5%) were obsolete tuberculosis infection (OTBI). Of the LTBI patients, 12.2% (9/74) received preventive anti-tuberculosis treatment, while 87.8% (65/74) didn’t. The course of SLE in SLE with active tuberculosis group (median (quartile)) was 108.0 (84.0, 180.0) months, significantly longer than that in SLE with inactive tuberculosis group (54.0 (13.5, 108.0) months, Z=-3.151, P=0.002). The proportion of use of hormone shock, leflunomide and cyclophosphamide in SLE with active tuberculosis group were significantly higher than those in SLE with inactive tuberculosis group (33.3% (5/15) vs. 7.0% (6/86), χ²=9.142, P=0.010; 20.0% (3/15) vs. 1.2% (1/86), Fisher’s exact probability method, P=0.010; 40.0% (6/15) vs.19.8% (17/86), χ²=10.815, P=0.002). In SLE patients with LTBI undergoing prophylactic antituberculosis therapy, the average daily dose of glucocorticoids (50.0 (40.0, 60.0) mg) was significantly higher than that in the untreated group (20.0 (5.0, 47.5) mg; Z=-2.951, P=0.003), the proportions of usage of cyclophosphamide (5/9) and methotrexate (6/9) were also significantly higher than those in the untreated group (18.5% (12/65) and 13.8% (9/65); Fisher’s exact probability method, P=0.026 and 0.020, respectively). After follow-up for 2 years or more, two cases (3.1%) of SLE combined with LTBI and without prophylactic anti-tuberculosis treatment developed into active tuberculosis, while no such case was found in anti-tuberculosis treatment group, and the difference was not statistically significant (Fisher’s exact probability method, P=1.000). Conclusion: Active tuberculosis is the most common disease in SLE patients with tuberculosis infection. The long course of SLE would lead to an increased probability of tuberculosis infection. The use of high-dose hormone, leflunomide and cyclophosphamide could cause the SLE patients to be susceptible to tuberculosis. Therefore, preventive anti-tuberculosis therapy should be actively carried out for SLE patients with LTBI.

Influencing factors of getting unfavorable treatment outcomes of patients with multidrug-resistant pulmonary tuberculosis in China: a Meta-analysis

Li Shuolan, Li Mingwu, Li Guangmei, Wang Lin, Wan Rong, Ma Meng

Chinese Journal of Antituberculosis. 2022, 44(12):  1303-1313.  doi:10.19982/j.issn.1000-6621.20220212

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Objective: To systematically review the influencing factors of unfavorable treatment outcomes of multidrug-resistant pulmonary tuberculosis (MDR-PTB) in China. Methods: Chinese databases (CNKI, WanFang Data, VIP, CBM) and English databases (PubMed, Embase, Web of Science) were electronically searched to collect studies about factors of unfavorable treatment outcomes of MDR-PTB. The time was limited as from inception of those databases to December 2021. Two researchers independently screened literatures, extracted information and evaluated the risk of bias. RevMan 5.3 was used to conduct Meta-analysis. Results: A total of 21 studies involving 4663 patients were included. Meta-analysis results showed that re-treatment (OR=2.63, 95%CI:1.54-4.47), complications (OR=4.28, 95%CI:2.61-7.03), adverse reactions (OR=2.71, 95%CI:1.87-3.93), cavity (OR=2.79, 95%CI:1.82-4.28), unreasonable chemotherapy (OR=5.80, 95%CI:2.05-16.41) and irregular treatment (OR=6.05, 95%CI:1.91-19.18) were associated with MDR-PTB treatment outcomes in multivariable analysis. Conclusion: The existing evidence suggested that re-treatment, complications, cavity, adverse reactions, unreasonable chemotherapy as well as irregular treatment were risk factors for unfavorable outcomes of MDR-PTB. In order to reduce the failure rate of MDR-PTB treatment, patients with these risk factors should receive strengthened medical managements and be cautious about the occurrence of adverse reactions.

Meta-analysis of operation combined with irrigation and drainage of focus lesion in the treatment of spinal tuberculosis

Muradil·Mardan , Parhat·Yasin , Xu Tao, Cai Xiaoyu, Yakup·Abliz , Xun Chuanhui, Sheng Weibin, Mardan·Mamat

Chinese Journal of Antituberculosis. 2022, 44(12):  1314-1320.  doi:10.19982/j.issn.1000-6621.20220245

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Objective: To systematically analyze the therapeutic effect of operation combined with irrigation and drainage of focus lesion in the treatment of spinal tuberculosis. Methods: Two researchers independently conducted a literature search in China National Knowledge Infrastructure, Wanfang Date, VIP, PubMed, EMbase and Cochrane Library, and collected randomized controlled trials (RCTs) and retrospective studies on the treatment of spinal tuberculosis by surgery combined with catheter irrigation and drainage. The language was limited to Chinese and English. The two researchers independently evaluated the quality of each study, and extracted the preoperative and postoperative data of visual analogue score (VAS), Cobb angle, Erythrocyte sedimentation rate (ESR), C-reactive protein into an electronic baseline table which were analyzed and synthesized by Review Manager 5.4 software to evaluate the effectiveness of this surgical technique in the treatment of spinal tuberculosis. Results: A total of 7 studies with 191 patients were eventually included in the analysis. Meta-analysis results showed that: the mean difference between postoperative VAS scores and preoperative VAS scores was 5.33 (95%CI: 4.11-6.55); The mean difference between Cobb angle after operation and Cobb angle before operation was 14.47° (95%CI: 11.32°-17.61°); The difference between postoperative ESR and preoperative ESR was 40.20 mm/1 h (95%CI: 27.80-52.60); The mean difference between postoperative C-reactive protein and preoperative C-reactive protein was 30.44 mg/L (95%CI: 12.12-48.76). Conclusion: Operation combined with irrigation and drainage had a good therapeutic effect in the treatment of spinal tuberculosis, could effectively reduce the pain level of patients and improve the physical deformity and physical condition of patients, thus to improve the cure rate.

Efficacy and safety of modified all-oral short course chemotherapy in the treatment of multidrug-resistant pulmonary tuberculosis

Jin Long, Wang Lihua, Zhang Xiaolei, Jiang Huailong, Li Xiaonan, Liu Yuqin

Chinese Journal of Antituberculosis. 2022, 44(12):  1321-1326.  doi:10.19982/j.issn.1000-6621.20220318

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Objective: To analyze the effectiveness and safety of modified all-oral short course chemotherapy in the treatment of multidrug-resistant pulmonary tuberculosis (MDR-PTB). Methods: A prospective study was conducted in 22 MDR-PTB patients diagnosed in the Infectious Disease Hospital of Heilongjiang Province from April 2020 to April 2021 according to the inclusion criteria. The patients were treated with a modified short all-oral course chemotherapy regimen (6Lfx(Mfx)-Bdq-Lzd-Cfz-Cs/3Lfx(Mfx)-Lzd-Cfz-Cs). The changes of sputum smear, sputum culture, chest CT and adverse events were assessed during treatment. The main outcome indicators were culture negative conversion rate and treatment success rate and the secondary outcome indicator was the time of sputum culture negative conversion. Results: Of the 22 enrolled patients, 15 patients (68.2%) were male and the average age was (40±11) years old. All of the patients completed the 9-month therapy. The total success rate of treatment was 100.0% with no failure, lost to follow up or death at the end of treatment. During treatment, the cumulative sputum smear negative conversion rate, culture negative conversion rate, effective rate of chest lesions absorption and the improvement rate of cavities all increased gradually with the extension of treatment time. The effective rate of chest lesions absorption and the improvement rate of cavities both reached 100.0% (22/22 and 10/10, respectively) after 12-week treatment; the sputum smear negative conversion rate reached 100.0% (22/22) after 16-week treatment; the culture negative conversion rate reached 100.0% (22/22) after 20-week treatment. A total of 61 adverse events were reported in 21 patients (95.5%). However, no serious adverse event was observed and the treatment outcomes were not influenced. The most frequently reported adverse events were peripheral neuropathy (18 patients, 81.8%), gastrointestinal discomfort (15 patients, 68.2%) and QTc prolongation (14 patients, 63.6%). Conclusion: The modified short all-oral course chemotherapy regimen achieved a high treatment success rate with shortened treatment course and satisfactory safety, and it is worthy to be promoted in clinic.

Meta-analysis of the diagnostic value of metagenomic next-generation sequencing and GeneXpert MTB/RIF in tuberculosis

Wang Yajuan, Cao Xinyi, Liu Shengming

Chinese Journal of Antituberculosis. 2022, 44(12):  1327-1337.  doi:10.19982/j.issn.1000-6621.20220303

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Objective: To compare the diagnostic efficacy of metagenomic next-generation sequencing (mNGS) and GeneXpert MTB/RIF (Xpert) for tuberculosis using meta-analysis. Methods: Literatures about the diagnostic accuracy of mNGS and Xpert for tuberculosis were systematically searched in PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (CBM), Wanfang and VIP databases from the establishment to July 5, 2022. According to the inclusion and exclusion criteria, two reviewers independently conducted the screening and inclusion of literatures, data extraction, risk of bias evaluation, as well as analysis for the diagnostic performance of mNGS and Xpert. Results: Twelve literatures with a total of 1344 samples were ultimately included. As the meta-analysis showed, the pooled sensitivity, specificity, diagnostic odds ratio and AUC of mNGS in tuberculosis diagnosis were 63.4%, 99.8%, 58.6 and 0.931, respectively, which of Xpert were 50.3%, 99.9%, 23.8 and 0.860, respectively, while those of the parallel diagnosis of mNGS and Xpert were 68.7%, 99.8%, 91.2 and 0.978, respectively. Meanwhile, the sensitivities of mNGS on cerebrospinal fluid and other extra-pulmonary or multi-site specimens were 64.6% and 60.8%, respectively, and those of Xpert were 41.8% and 50.8%, respectively. Conclusion: Both mNGS and Xpert performed well in the diagnosis of tuberculosis. The sensitivities of mNGS single detection and detection combined with Xpert were higher than that of Xpert single detection, but there is no difference in the specificities. The combined detection with mNGS is expected to improve the detection rate of Xpert negative but clinically suspected tuberculosis infection, especially the pathogen of extrapulmonary tuberculosis.

Dynamic changes and significance of biomarkers of cerebral injury in pediatric tuberculous meningitis

Shi Jiayun, Wang Manzhi, Zhou Haiyi, Zhang Xiaofo, Wei Songqing

Chinese Journal of Antituberculosis. 2022, 44(12):  1338-1344.  doi:10.19982/j.issn.1000-6621.20220304

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Objective: To analyze the dynamic changes of expression of neuron specific enolase (NSE), S100B protein and glial fibrillary acidic protein (GFAP) in serum and cerebrospinal fluid of children with tuberculous meningitis (TBM) and their prognostic value. Methods: A prospective study was conducted in 72 children with TBM admitted to the Department of Pediatric Tuberculosis, Changsha Central Hospital affiliated to South China University from January 1, 2018 to December 31, 2021 (TBM group). And 20 hospitalized children diagnosed with pulmonary tuberculosis and excluded TBM in the corresponding period were collected as pulmonary tuberculosis group. Children in TBM group were divided into complete recovery group (n=47) and poor prognosis group (n=25) according to the prognosis after 6-month treatment. Enzyme-linked immunosorbent assay (ELISA) was used to determine the NSE, S100B and GFAP levels in serum and cerebrospinal fluid of TBM group within 48 h after admission and after treatment (1,2 and 3 weeks) and of pulmonary tuberculosis group within 48 h after admission, the results were compared. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to analyze NSE, S100B and GFAP levels in cerebrospinal fluid of TBM children at admission to predict the threshold, sensitivity and specificity of the poor prognosis. Results: NSE, S100B and GFAP levels (median (quartile)) in serum and cerebrospinal fluid at admission were 15.12 (3.22, 26.90) μg/L, 1.11 (0.40, 3.20) μg/L, 15.34 (3.44, 45.82) μg/L and 37.90 (6.50,142.70) μg/L, 2.31 (1.02, 10.20) μg/L, 65.31 (10.87, 252.60) μg/L, respectively in TBM group, which were all significantly higher than those in pulmonary tuberculosis group (7.03 (2.48, 13.23) μg/L, 0.25 (0.12, 0.36) μg/L, 10.38 (2.41,19.00) μg/L, 7.56 (2.12, 12.79) μg/L, 0.35 (0.05, 0.51) μg/L and 7.86 (2.41, 13.80) μg/L, respectively)(serum levels: Z values were -5.064, -6.817 and -2.693, respectively; P values were 0.000, 0.000 and 0.007, respectively) (cerebrospinal fluid level: Z values were -6.465, -6.816 and -6.778, respectively, all P=0.000). The levels of NSE, S100B and GFAP in cerebrospinal fluid of patients in the poor prognosis group were significantly higher than those in the complete recovery group (60.16 (24.90,142.70) μg/L vs. 29.37 (6.50, 68.82) μg/L, Z=-4.855, P=0.000; 2.59 (1.32, 10.20) μg/L vs. 1.97 (1.02,6.10) μg/L, Z=-3.212, P=0.001; 118.74 (58.83, 252.60) μg/L vs. 45.39 (10.87, 84.93) μg/L, Z=-6.334, P=0.000, respectively). In the poor prognosis group, at the 1st, 2nd and 3rd week after treatment, NSE levels of cerebrospinal fluid were 49.58 (15.38, 87.56) μg/L, 41.53 (9.60, 82.00) μg/L and 25.97 (5.56,58.49) μg/L, respectively; S100B levels were 10.15 (3.63, 15.72) μg/L, 1.60 (0.41, 3.28) μg/L and 0.75 (0.41, 1.60) μg/L, respectively; GFAP levels were 99.75 (65.79, 180.84) μg/L, 63.94 (13.65, 120.59) μg/L and 38.03(10.87,85.40) μg/L, respectively; which were all significantly higher than those in the complete recovery group (NSE: 18.49 (4.87,36.12) μg/L, 14.51 (4.87, 35.70) μg/L and 8.53 (2.12, 21.70) μg/L, Z=-2.496, -3.815, -4.041, P=0.015, 0.000, 0.000, respectively; S100B: 5.34 (2.19, 10.08) μg/L, 0.66 (0.19, 1.56) μg/L and 0.40 (0.11, 0.74) μg/L, Z=-3.331, -4.745, -1.207, P=0.047, 0.000, 0.036, respectively; GFAP: 45.39 (10.87, 84.93) μg/L, 17.77 (5.66, 38.15) μg/L and 12.82 (5.04, 26.90) μg/L, Z=-4.940, -2.337, -3.745, P=0.000, 0.016 and 0.012, respectively). ROC curve analysis showed that the predictive thresholds of NSE, S100B and GFAP levels in cerebrospinal fluid for poor prognosis of TBM children at admission were 51.92 μg/L, 2.75 μg/L, and 77.54 μg/L, respectively under the maximum Youden index. Conclusion: The levels of NSE, S100B and GFAP in serum and cerebrospinal fluid of TBM children were significantly increased, and after treatment, the levels of NSE, S100B and GFAP in serum quickly decreased to normal, while those in cerebrospinal fluid decreased slowly. In cerebrospinal fluid of TBM children, NSE ≥51.92 μg/L, S100B ≥ 2.75 μg/L, or GFAP ≥77.54 μg/L at admission and the levels decreased slowly after treatment, indicating the possibility of poor prognosis.

Bioinformatic analysis of the structure and function of Mycobacterium tuberculosis epitope-tandem protein W541

Li Pengchuan, Liang Yan, Zhang Linxi, Wu Xueqiong

Chinese Journal of Antituberculosis. 2022, 44(12):  1345-1357.  doi:10.19982/j.issn.1000-6621.20220309

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Objective: To predict and analyze the structure and function of Mycobacterium tuberculosis (MTB) epitope-tandem protein W541 by bioinformatics method. Methods: W541 protein constructed in our laboratory was encoded by a novel multi-antigen epitope-tandem DNA vaccine composed of the epitopes of MTB proliferative antigens Ag85A, Ag85B, latent-related antigens Rv3407 and Rv1733c. Its amino acid sequence of physicochemical properties, hydrophilic (hydrophobic), transmembrane helix, secondary and tertiary structures, subcellular localization, signal peptide, glycosylation and phosphorylation sites, B cell, helper T (Th) and cytotoxic T lymphocyte (CTL) epitopes, the protein interaction network, the homology between W541 protein and human protein was analyzed using bioinformatics softwares ProtParam, Protscale, TMHMM, SOPMA, SWISS-MODEL, PSORT, SignalP, NetNGlyc, NetPhos, SYFPEITHI, RANKPEP, IEDB, NetMHC, STRING, and EXPASY, respectively. Results: W541 protein was composed of 704 amino acids, with the molecular formula of C₃₃₂₉H₅₀₃₅N₉₂₃O₉₉₃S₂₄, the instability index of 45.37, which was hydrophilic unstable protein. The proportions of α-helix, β-fold, β-corner and irregular crimp in its secondary structure were 26.99%, 19.03%, 11.51% and 42.47%, respectively. It had no transmembrane helix region or signal peptides, which was an intracellular membrane protein. W541 protein had 6 glycosylation sites, and 62 phosphorylation sites, including 15 threonine, 35 serine and 12 tyrosine phosphorylation sites, respectively. W541 protein had multiple potential T cell and B cell epitopes. W541 protein interacted with 10 proteins. The amino acid sequence of W541 protein had less than 3.27% homology with the human protein. Conclusion: MTB epitope-tandem protein W541 has multiple potential T-cell and B-cell epitopes. Among them, T-cell epitopes were dominant, which may have better immunogenicity, play an important regulatory role and lay a foundation for further animal experimental evaluation.

Review Articles

Research progress of non-coding RNA tuberculosis

Zhu Yinyin, Zhang Hongying

Chinese Journal of Antituberculosis. 2022, 44(12):  1358-1362.  doi:10.19982/j.issn.1000-6621.20220282

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Tuberculosis, a chronic infectious disease caused by Mycobacterium tuberculosis, is one of the most serious infectious disease in the world. Despite significant advances in detection techniques and therapeutic approaches for tuberculosis, there is still lack of early screening methods and targeted treatment. Non-coding RNA (ncRNA) widely participate in various biological processes, including Mycobacterium tuberculosis infection, and play critical roles. In view of the interaction of the host with Mycobacterium tuberculosis, the author reviewed research progress and regulation mechanism of host ncRNA in the tuberculosis infection process in human and regulation mechanism, to bring potential clinical prospects for tuberculosis diagnosis and the development of new anti-tuberculosis therapies.

Progress in the identification of Mycobacterium tuberculosis antigenic proteins in clinical specimens

Sheng Gang, Chu Hongqian, Liu Dingyi, Sun Zhaogang

Chinese Journal of Antituberculosis. 2022, 44(12):  1363-1368.  doi:10.19982/j.issn.1000-6621.20220312

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Tuberculosis (TB) is a serious respiratory disease caused by Mycobacterium tuberculosis (MTB) infection. The spread of TB is hidden, and it is difficult to prevent and control. The current rapid detection technology of TB has certain shortcomings and new diagnostic technology is urgently needed. Antigen detection technology of TB is widely applicable, simple, rapid and accurate. However, no target with good and stable detection effect has been found, and even for the same antigen target, the detection efficiency of different studies varies greatly. Therefore, we reviewed the detection status of antigenic proteins in various clinical specimens confirmed by different identification methods and experimental studies, to reconsider the status and content of MTB antigens in clinical specimens, and improve the method of antigen discovery and identification, so as to provide the theoretical reference for the development of diagnostic technology for tuberculosis antigens.