Table of Content

10 July 2023, Volume 45 Issue 7

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Special Topic

Development process of setting of critical concentrations for phenotypic drug susceptibility testing of Mycobacterium tuberculosis

Song Yuanyuan, Xia Hui, Zhao Yanlin

Chinese Journal of Antituberculosis. 2023, 45(7):  631-638.  doi:10.19982/j.issn.1000-6621.20230153

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Phenotypic drug susceptibility testing of Mycobacterium tuberculosis remains a crucial method for detecting drug resistance. However, the accuracy and reproducibility of certain drugs are sub-optimal with critical concentration being one of the key factors affecting results. This article provides a systematic summary and introduction on establishing and revising critical concentrations for anti-tuberculosis drug susceptibility testing, and offered valuable guidance to laboratory technicians and clinicians for accurately interpreting drug susceptibility testing methods and results, as well as to facilitate critical concentration research.

Interpretation of Standards

Interpretation of WHO consolidated guidelines on tuberculosis: Module 3: diagnosis: tests for tuberculosis infection

Xin Henan, Gao Lei

Chinese Journal of Antituberculosis. 2023, 45(7):  639-643.  doi:10.19982/j.issn.1000-6621.20230128

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On September 30, 2022, the World Health Organization (WHO) published the WHO consolidated guidelines on tuberculosis: Module 3: diagnosis: tests for tuberculosis infection. The medical evidence-based guideline systematically evaluated the performance of different tests and recommended using of Mycobacterium tuberculosis antigen-based skin tests for the diagnosis of tuberculosis infection for the first time. The author now introduces the development of the new guideline and interprets the three key recommendations hoping to provide evidence-based reference for tuberculosis infection test and control.

Epidemiology and Statistical Methods

Application of regression discontinuity in public health

Yu Shengnan, Gao Qi, Zheng Liang, Shi Yuan, Chen Yijin, Li Xiujun

Chinese Journal of Antituberculosis. 2023, 45(7):  644-650.  doi:10.19982/j.issn.1000-6621.20230130

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Regression discontinuity (RD) is a kind of statistical method for making causal inferences based on counterfactuals composed of both sides of the cutoff. In recent years, the application of RD has gradually increased in public health, especially in the fields of factors influencing air quality and the effects of related policy interventions, as well as vaccine effectiveness. Since the outbreak of the COVID-19, RD has also been increasingly applied to investigate the impact of the epidemic on public health and individual behavior. The application conditions of RD are relatively simple, and RD can reduce the effect of confounding and reflect the causal relationship between variables more realistically. In this study, based on the introduction of the idea and application of RD, the current status of its application in public health is reviewed.

Original Articles

Analysis of death related factors in tuberculosis destroyed lung patients undergoing invasive mechanical ventilation

Cheng Yao, Chen Hongde, Wu Guihui, Lai Min, Luo Haixia, Cui Kunping, Li Yuke

Chinese Journal of Antituberculosis. 2023, 45(7):  651-657.  doi:10.19982/j.issn.1000-6621.20230054

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Objective: To explore the clinical characteristics and death-related factors of patients with tuberculosis-destroyed lung (TDL) undergoing invasive mechanical ventilation (IMV). Methods: A retrospective study was conducted in 107 TDL-IMV patients admitted to the intensive care unit of Chengdu Public Health Clinical Center from January 2017 to December 2021.The epidemiological data, complications, comorbidities, acute physiology and chronic health status scores (APACHE Ⅱ score), sequential organ failure scores (SOFA score), causes of IMV, laboratory test results, and clinical outcomes, etc., of the patients were collected. The above indicators in patients with different clinical outcomes were compared and analyzed, and unconditional multivariate logistic regression was used to analyze the influencing factors of death in TDL-IMV patients. Results: Of the 107 subjects, 42 (39.3%) died and 65 (60.7%) survived. Univariate analysis showed that 52.4% (22/42) of the patients in the death group were complicated with chronic obstructive pulmonary disease, which was significantly higher than that in the survival group (20.0%, 13/65, χ²=12.154, P=0.000); IMV for acute respiratory failure accounted for 52.4% (22/42), which was significantly higher than that of survival group (23.1%, 15/65, χ²=9.685, P=0.002); the albumin level ((25.34±4.22) g/L) was significantly lower than that in the survival group ((28.71±6.26) g/L, t=3.065, P=0.002); N-terminal pro-B-type natriuretic peptide level (median (quartile): 993.45 (869.32, 1096.61) ng/L) was significantly higher than that of survival group (649.26 (528.40, 789.82) ng/L, U=-7.085, P=0.000). Further multivariate logistic regression analysis showed that comorbidities with chronic obstructive pulmonary disease (OR=4.999, 95%CI: 1.253-19.937), IMV treatment for acute respiratory failure (OR=8.548, 95%CI: 2.045-35.729), hypoproteinemia (OR=13.069, 95%CI: 2.662-64.156) and high levels of N-terminal pro-B-type natriuretic peptide (OR=11.354, 95%CI: 2.809-45.888) were independent risk factors for the death of patients with TDL-IMV. Conclusion: Patients with TDL-IMV have a high risk of death, especially those who complicated with chronic obstructive pulmonary disease, undergoing IMV treatment due to acute respiratory failure, hypoproteinemia and high level of N-terminal pro-B-type natriuretic peptide.

Meta-analysis of effectiveness and safety of the cycloserine-containing treatment for multidrug-resistant pulmonary tuberculosis in China

Zheng Rui, Zhao Mingrui, Yang Yuanzheng

Chinese Journal of Antituberculosis. 2023, 45(7):  658-668.  doi:10.19982/j.issn.1000-6621.20230057

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Objective: The purpose of this study was to provide evidence for clinical treatment of multidrug-resistant pulmonary tuberculosis (MDR-PTB) by assessing the effectiveness and safety of using cycloserine (Cs)-containing anti-tuberculosis regimens in China. Methods: A search for “cycloserine”“multi-drug resistant pulmonary tuberculosis”“treatment effect” and “adverse effects” was conducted in database of China National Knowledge Infrastructure, Wanfang Data, VIP, China Biomedical Literature Service System, PubMed, Embase, and Cochrane Library for literature published from January 2011 to September 2022. Randomized controlled trials (RCT) of Cs-containing anti-tuberculosis regimens for the treatment of MDR-PTB in China were targeted. The literature was screened by two researchers and the Cochrane 5.1.0 bias risk assessment tool was used to evaluate the methodological quality of the included studies. Stata 17.0 MP software was used to analyze the outcome indicators. Results: A total of 35 included literature was divided into: Cs+conventional treatment compared with conventional treatment group, 1128 cases; thymosin+Cs+conventional treatment group compared with the conventional treatment group, 791 cases; Cs+conventional treatment group compared with para aminosalicylic acid+conventional treatment group, 433 cases; Cs+conventional treatment compared with ethambutol+conventional treatment, 419 cases. The results of Meta-analysis indicated that compared with conventional anti-tuberculosis treatment, Cs-containing regimens showed superior effectiveness in treating MDR-PTB (RR=2.191, 95%CI: 1.847-2.599), including the rate of sputum conversion (RR=2.002, 95%CI: 1.696-2.364), lesion absorption (RR=2.259, 95%CI: 1.836-2.779), and cavity shrinkage (RR=1.812, 95%CI: 1.482-2.217). The incidence of adverse reactions in mental and nervous system was higher in Cs-containing regimens (RR=1.696, 95%CI: 1.493-1.927). Conclusion: The results suggested that the Cs-containing regimens were more effective in treating MDR-PTB, but caution should be taken for adverse reactions in the central nervous system.

Application value of ultrasound guided percutaneous biopsy in the diagnosis of hip joint tuberculosis

Cao Bingsheng, Zhang Gengchen, Fu Liyuan, Wang Jinshan

Chinese Journal of Antituberculosis. 2023, 45(7):  669-672.  doi:10.19982/j.issn.1000-6621.20230101

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Objective: To investigate the application value of ultrasound guided percutaneous biopsy in the diagnosis of hip joint tuberculosis. Methods: Forty-five patients with hip joint tuberculosis admitted to the Eighth Medical Centre of General Hospital of PLA from December 2012 to December 2022, were collected. Their hip ultrasound examination imaging data and ultrasound guided hip biopsy results were analyzed, and the ultrasound imaging characteristics of hip tuberculosis were summarized. The diagnostic rate of ultrasound guided puncture biopsy for hip joint tuberculosis and the impact of different ultrasound manifestations on the diagnostic rate of puncture biopsy for hip joint tuberculosis were analyzed. Results: Depending on the progression of the lesion, ultrasound manifestations of tuberculosis of hip joint can be divided into three categories. There were 10 patients of type Ⅰ, characterized by swollen synovial membrane or joint cavity accumulation, 22 patients of type Ⅱ, characterized by bone destruction on the joint surface and unevenness, and 13 patients of type Ⅲ, characterized by joint structure destruction and fusion into mixed echogenic masses. The success rate of ultrasound-guided puncture biopsy was 97.8% (44/45), and the overall diagnostic rate of puncture biopsy was 66.7% (30/45). Diagnostic rates of type Ⅰ, type Ⅱ and type Ⅲ were 30.0% (3/10), 72.7% (16/22) and 84.6% (11/13), respectively. Diagnostic rate of type Ⅰ was significantly lower than those of type Ⅱ and type Ⅲ (χ²=5.203, P=0.049; χ²=7.078, P=0.013). Conclusion: Conventional ultrasound can demonstrate the pathological morphologic change of hip joint tuberculosis and ultrasound guide biopsy has important value in the diagnosis of tuberculosis hip joint.

Comparison of therapeutic effects between calcium sulfate incorporated with rifamycin sodium and autologous bone grafting in the treatment of thoraco-lumbar tuberculosis

Wu Yunbiao, Pu Xingyu, Qi Yang, Kou Xianshuai, Xie Wendong, Luo Wenyuan, Liu Shengfen

Chinese Journal of Antituberculosis. 2023, 45(7):  673-680.  doi:10.19982/j.issn.1000-6621.20230094

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Objective: To evaluate the efficacy and safety of calcium sulfate incorporated with rifamycin sodium in the treatment of thoraco-lumbar spinal tuberculosis through posterior approach lesion clearance and internal fixation surgery. Methods: A retrospective study was conducted in patients with thoraco-lumbar tuberculosis admitted to the Orthopedics, Cadre Ward of Gansu Provincial Hospital from June 2019 to August 2022. According to whether or not to implant rifamycin sodium calcium sulfate, the patients were divided into drug-loading group (simple posterior approach lesion removal combined with rifamycin sodium sulfate implantation) and bone graft group (simple posterior approach lesion removal combined with autologous bone implantation). Of the 54 cases initially included (26 cases in the drug-loading group and 28 cases in the bone graft group), 4 were lost to follow-up, and 50 cases were finally included (25 cases in the drug-loading group and 25 cases in the bone graft group). Lesion segments: 28 cases in the thoracic spine, 7 cases in the thoraco-lumbar spine, and 15 cases in the lumbar spine. The operation time, blood loss, hospital stay, postoperative complications, levels of ESR and CRP preoperative, 3 months postoperative and in the last follow-up were recorded, as well as the Cobb angles preoperative, 3 day, 3 months and 6 months postoperative and in the last follow-up. Results: All the 50 patients were followed up for 7-16 months. There was no significant difference in operation time ((168.04±17.22) min vs. (163.96±16.07) min, t=0.750, P=0.282), blood loss (911.20±93.38) ml vs. (904.40±90.74) ml, t=0.068, P=0.795) and hospital stay ((15.96±1.21) d vs. (15.28±1.31) d, t=3.651, P=0.062) between the two groups. The levels of ESR and CRP 3 months postoperative, in the drug-loaded group were significantly lower than those in the bone graft group ((26.48±2.76) mm/1 h vs. (28.64±3.03) mm/1 h, t=2.639, P=0.011; (3.45±0.79) mg/L vs. (4.41±1.15) mg/L, t=3.454, P=0.001). The Cobb angles in the bone graft group 6 months postoperative and in the last follow-up were significantly lower than those in the bone graft group ((12.32±0.68)° vs. (12.84±1.02)°, t=2.115, P=0.034; (12.43±0.76)° vs. (12.94±0.81)°, t=2.278, P=0.027). Conclusion: Simple posterior approach lesion removal combined with rifamycin sodium sulfate implantation for the treatment of thoraco-lumbar tuberculosis could achieve the goal of complete removal of lesions and reconstruction of spinal stability.

Value of DNA real-time fluorescence isothermal amplification method and combined testing in early diagnosis of tuberculous pleurisy

Zhao Guolian, Lei Qian, Wang Pei, Ren Yunxia, Guan Jing

Chinese Journal of Antituberculosis. 2023, 45(7):  681-686.  doi:10.19982/j.issn.1000-6621.20230055

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Objective: To investigate the value of DNA real-time fluorescence isothermal amplification method (abbreviated as “constant temperature amplification method”), combined with adenosine deaminase (ADA) and peripheral blood tuberculosis infection T cell spot test (T-SPOT. TB) detection in the early diagnosis of tuberculous pleurisy. Methods: Using retrospective research method, 427 patients with pleural effusion of unknown causes admitted to Xi’an Chest Hospital from January 2020 to December 2021 were selected as the research objects. All patients underwent pleural effusion isothermal amplification, ADA, Mycobacterium tuberculosis culture, and peripheral blood T-SPOT.TB testing. Based on clinical comprehensive diagnostic criteria as a reference, the early diagnostic value of pleural effusion DNA constant temperature amplification combined with ADA and peripheral blood T-SPOT.TB for tuberculous pleurisy was analyzed. Results: Among 427 subjects, 279 cases (65.3%) were diagnosed as tuberculous pleurisy (tuberculous pleurisy group) and 148 cases were diagnosed as non-tuberculous pleurisy (non-tuberculous pleurisy group). The optimal threshold of ADA was 19.5 U/L. Among the single detection methods, the specificity and sensitivity of the constant temperature amplification method were 100.00% and 31.54%, which were similar to those of Mycobacterium tuberculosis culture (100.00% and 30.11%, respectively). The sensitivity of ADA and T-SPOT.TB in peripheral blood was 74.91% and 84.95%,respectively, and the specificity was 87.16% and 74.91%, respectively. ADA+T-SPOT.TB could obtain high sensitivity (94.27%) and specificity (99.32%) in parallel and series, respectively. The parallel detection efficiency of isothermal amplification method, ADA and T-SPOT.TB got the same value as that with the Mycobacterium tuberculosis culture method in parallel. Among the joint detection methods, ADA+T-SPOT.TB detection in series had the highest cost-effectiveness, with a cost effectiveness ratio (C/E) of 669.23. Conclusion: The constant temperature amplification method with rapid detection protocols such as ADA and peripheral blood T-SPOT.TB could provide strong evidence for the early diagnosis and treatment of tuberculous pleurisy patients.

Analysis of drug resistance characteristics of pulmonary tuberculosis in children in Guangdong, 2014—2020

Zhuo Wenji, Zhang Chenchen, Chen Xunxun, Wei Wenjing, Yu Meiling, Peng Kehao, Xu Liuyue, Chen Yanmei

Chinese Journal of Antituberculosis. 2023, 45(7):  687-692.  doi:10.19982/j.issn.1000-6621.20230109

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Objective: To investigate the drug resistance characteristics of Mycobacterium tuberculosis (MTB) isolates from children with pulmonary tuberculosis (PTB) in Guangdong Province from 2014 to 2020. Methods: According to the enrollment standard, 1274 (3.3%) MTB isolates from children aged 0 to 18 were collected from 32 sentinel sites of PTB resistance surveillance (39046 MTB isolates) in Guangdong Province from January 1, 2014 to December 30, 2020. Analysed the data of drug resistance of MTB isolates for first- and second-line of anti-TB drugs (including isoniazid (INH), streptomycin (Sm), ethambutol (EMB), rifampicin (RFP), kanamycin (Km), propylthioisoniacin (Pto), capreomycin (Cm), ofloxacin (Ofx), and sodium p-aminosalicylate (PAS)) and summarized the drug resistance characteristics. Results: The proportion of PTB children was dropped from 4.3% (123/2856) in 2014 to 3.1% (177/5760) in 2020, showing a downward trend of year by year ($X_{trend}^{2}$=25.864, P<0.001). The resistance rates of the isolates to anti-TB drugs from high to low were Sm (14.8% (189/1274))>INH (7.7% (98/1274))>RFP (6.3% (80/1274))>EMB (6.0% (77/1274))>Ofx (3.5% (44/1274))=PAS (3.5% (44/1274))>Pto (2.9% (37/1274))>Km (2.5% (32/1274))>Cm (2.2% (28/1274)), and the drug resistance rate, mono-resistance rate, poly-resistance rate, multidrug-resistance rate (MDR) and extensively drug resistance rate (XDR) of MTB of the 1274 isolates was 26.0% (331/1274), 15.4% (196/1274), 4.2% (54/1274), 3.1% (39/1274), and 0.8% (10/1274), respectively. The XDR of MTB in children aged 0 to 12 was significantly higher than that in children aged 13 to 18 (3.0% (3/100) vs. 0.6% (7/1174); χ²=6.837, P=0.038). In addition, the XDR of MTB in boys was significantly higher than that in girls (1.3% (10/749) vs. 0.0% (0/525); χ²=10.679, P=0.007), and the resistance rate of MTB in the Pearl River Delta was significantly higher than that in eastern and northwestern Guangdong (28.1% (213/758) vs. 22.9% (118/516); χ²=4.370, P=0.037). Conclusion: The prevalence of PTB in children in Guangdong Province is serious. The drug resistance in PTB children aged 0-12 years, who were boys, and who lived in Pearl River Delta should be paid special attention.

Review Articles

Recent advances in the source and biological function of bacterial DNA in extracellular vesicles

Liu Dingyi, Sun Hong, Sheng Gang, Sun Zhaogang

Chinese Journal of Antituberculosis. 2023, 45(7):  693-698.  doi:10.19982/j.issn.1000-6621.20230060

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Cells can release their own substances or metabolites outside the cell through extracellular vesicles, which is also known as EV (exosomes). As research progressed, it is discovered that bacteria can also produce exosomes that encapsulate many macromolecules (including proteins, lipids, DNA and RNA) and that bacterial exosomes are closely linked to a variety of biological activities, including bacterial survival and development, as well as bacterial-mediated intra- and inter-species interactions. Researchers have also found that both Gram-negative and Gram-positive bacteria can produce exosomes containing DNA, and that bacterial exosomes DNA can perform biological functions such as mediating horizontal gene transfer, assisting in biofilm formation, and stimulating immunomodulatory mechanisms. In this paper, the production mode and biological functions of bacterial extracellular DNA have been elucidated, so that readers can have deeper understanding of bacterial exosomes DNA and promote further research and development of bacterial exosome DNA.

Research progress on the correlation between intestinal microbiota short chain fatty acids and pulmonary tuberculosis

Zhang Xiaomeng, Li Min, Chai Yinghui, Zhou Jing, Lei Hong

Chinese Journal of Antituberculosis. 2023, 45(7):  699-706.  doi:10.19982/j.issn.1000-6621.20230079

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Short chain fatty acids (SCFA) are the main metabolites of the gut microbiota, mainly including formic acid, acetic acid, propionic acid, butyric acid and their branched chain fatty acids, and some salts. Research has shown that there is a significant direct correlation between SCFA and the occurrence and development of pulmonary tuberculosis. Pulmonary tuberculosis leads to imbalance of gut microbiota, thereby reducing the abundance of SCFA, which affects the host immune system and the response of inflammatory factors; the disorder of host immune system and inflammatory factor will promote the occurrence and development of pulmonary tuberculosis.The author reviewed the correlation between SCFA and pulmonary tuberculosis, the possible regulatory mechanism between them, and whether it was possible to improve the abundance of SCFA in the body by regulating intestinal flora to achieve the purpose of treatment or adjuvant treatment of pulmonary tuberculosis.

Research progress on application of local drug delivery and sustained-release system in spinal tuberculosis

Yang Jun, Deng Qiang, Li Junjie, Wang Yurong, Du Jianqiang, Chen Bo, Zhang Lijuan

Chinese Journal of Antituberculosis. 2023, 45(7):  707-713.  doi:10.19982/j.issn.1000-6621.20230064

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As a new method for the treatment of spinal tuberculosis, the local drug delivery and sustained-release system has been found in the experimental stage to inhibit the growth of local Mycobacterium tuberculosis and facilitate lesion recovery, providing an effective means for treating bone defects caused by spinal tuberculosis. The authors reviewed relevant literature to discuss the commonly used drug loading methods and drug carrier materials in current research, deeply analyzed the application value of local drug delivery and sustained-release system as a new drug delivery strategy in the repair of spinal tuberculosis bone defects, and summarized the challenges in existing research, in order to provide a basis and direction for the application of drug delivery and sustained-release system in spinal tuberculosis surgical treatment and future research.