Table of Content

10 October 2022, Volume 44 Issue 10

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Guideline·Standard·Consensus

Evidence-based guidelines for active screening of pulmonary tuberculosis in Chinese communities

Tuberculosis Control Branch of Chinese Antituberculosis Association, Elderly Tuberculosis Control Branch of Chinese Antituberculosis Association, Editorial Board of Chinese Journal of Antituberculosis

Chinese Journal of Antituberculosis. 2022, 44(10):  987-997.  doi:10.19982/j.issn.1000-6621.20220321

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To achieve the goals of the End Tuberculosis Strategy, stronger measures are urgently needed to improve the detection and treatment of tuberculosis, and active screening is an important part of achieving the goals to ensure early diagnosis of tuberculosis. Tuberculosis Control Branch and Elderly Tuberculosis Control Branch of Chinese Antituberculosis Association, and Editorial Board of Chinese Journal of Antituberculosis organized experts to develop the Chinese guidelines for active screening of pulmonary tuberculosis in communities based on the evidence and recommendations of the latest World Health Organization guidelines in 2021. The guidelines also supplemented follow-up newly published literature and relevant literature and research evidence in China. The guidelines systematically summarized the characteristics of active screening techniques such as symptom screening, chest imaging and C-reactive protein, and proposed to conduct pulmonary tuberculosis active screening among close contacts of pulmonary tuberculosis patients, former tuberculosis patients, HIV/AIDS patients, the elderly, diabetic patients, and the general population in epidemic areas. It would provide a basis for the country and localities to improve and optimize the active tuberculosis screening strategy of key populations.

Interpretation of Standards

Interpretation of the application of TB antigen-based skin tests for the diagnosis of TB infection

Zhu Limei

Chinese Journal of Antituberculosis. 2022, 44(10):  998-1001.  doi:10.19982/j.issn.1000-6621.20220247

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The World Health Organization published a rapid communication “TB antigen-based skin tests for the diagnosis of TB infection” in January 2022. Based on the interpretation and analysis of this rapid communication, and combined the status of latent tuberculosis infection and prevention and control in China, the significance of the application of tuberculosis antigen-based skin tests for the prevention and control of latent tuberculosis infection in China was described, and how to better use tuberculosis antigen-based skin tests were also suggested.

Original Article

Meta-analysis on clinical effectiveness of combination regimens with interferon-γ in treatment of pulmonary tuberculosis

An Huiru, Han Yiran, Yan Mengdie, Wu Xueqiong

Chinese Journal of Antituberculosis. 2022, 44(10):  1002-1009.  doi:10.19982/j.issn.1000-6621.20220205

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Objective:To evaluate the clinical effectiveness and safety of interferon-γ(IFN-γ) combined with anti-tuberculosis drugs in treating pulmonary tuberculosis (PTB) through Meta-analysis and to provide reliable evidence for using IFN-γ in the treatment of PTB. Methods:Searching PubMed, Embase, Chinese Bio Medical Literature Database (CBM), China Knowledge Network (CNKI), and Wanfang Database, the publicly published clinical randomized controlled trials (RCTs) in the treatment of PTB using IFN-γ combined with anti-tuberculosis drugs were included. According to the Cochrane manual, Review Manager 5.4 software was used to evaluate the quality of those included papers. All the studies were analyzed with STATA 12.0 software, patients treated with IFN-γ combined with anti-tuberculosis drugs were regarded as the observation group, while patients treated only with anti-tuberculosis drugs were regarded as the control group. The evaluation indicators included the absorption rate of lung lesions, the closure rate of cavities, the sputum negative conversion rate after 2-3 months’ and 6-9 months’ treatment, and the percentage of CD4⁺T cell and the CD8⁺T cell in peripheral blood after treatment. Results:Eighteen RCT studies with a total of 1341 patients were included. The Meta-analysis showed that compared with the control group, after 2-3 months’ and 6-9 months’ treatment, the RR (95%CI) of sputum negative conversion rate of the observation group were 1.40 (1.26-1.56) and 1.41 (1.12-1.76), respectively; the RR (95%CI) of lesion absorption rate were 1.43 (1.09-1.88) and 2.84 (1.65-5.00), respectively; the RR (95%CI) of cavity closure rate were 2.07 (1.47-2.92) and 1.56 (1.28-1.91), respectively. These indicators were all significantly increased in the observation group (Ps<0.05). Comparing the observation group with the control group, the percentage of peripheral blood CD4⁺ T cells was significantly increased (P<0.05), and the percentage of CD8⁺ T cells was significantly decreased (P<0.05), the WMD (95%CI) were 5.18 (2.53-7.84) and -3.16 (-6.08--0.23), respectively. The RR (95%CI) of side effect incidence was 1.07 (0.72-1.60), RR (95%CI) of abnormal liver function, skin allergy, and gastrointestinal reactions were 1.02 (0.95-1.11), 1.03 (0.95-1.11) and 1.01 (0.93-1.11), respectively. All differences were not statistically significant (Ps>0.05). Conclusion:IFN-γ combined with anti-tuberculosis drugs in treating PTB can promote the absorption of lung lesions, the closure of cavities, the negative conversion of sputum, and meanwhile improve the immunological indicators of PTB patients.

Treatment containing interleukin-2 may improve the early sputum culture negative conversion rate in newly diagnosed and drug-susceptible pulmonary tuberculosis patients

Nie Wenjuan, Yang Yang, Shi Wenhui, Wang Jun, Liu Peiying, Wang Qingfeng, Chu Naihui

Chinese Journal of Antituberculosis. 2022, 44(10):  1010-1015.  doi:10.19982/j.issn.1000-6621.20220176

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Objective:To evaluate the efficacy and safety of interleukin-2 (IL-2) in the treatment of newly diagnosed drug-susceptible tuberculosis. Methods:A prospective, randomized, controlled and multi-center clinical research was conducted. From December 2017 to June 2019, newly diagnosed drug-sensitive pulmonary tuberculosis patients were continuously included from 17 research centers in 15 provinces (cities) of China, and 1264 cases were finally included and divided into the test group (n=619) and the control group (n=645) using computer-generated randomization sequence. In the test group, 560 cases completed the protocol treatment, and 591 cases in the control group completed the protocol treatment. The test group was treated with a background treatment regimen containing IL-2 (5×10⁵ U/d subcutaneous injection in the first month of the treatment), isoniazid, rifampicin, pyrazinamide and ethambutol; the control group was treated with isoniazid, rifampicin, pyrazinamide and ethambutol only. During the 6-month treatment and within 12 months after the end of treatment, the treatment effectiveness including sputum culture and imaging evaluation, and the treatment safety including adverse drug reactions were evaluated. Results:The treatment success rate of the test group was 99.8% (559/560), and that of the control group was 99.3% (587/591). There was no statistical difference between the two groups (χ²=1.650, P=0.125). One case (0.2%) in the test group had an adverse outcome (death); in the control group, 4 patients (0.7%) had adverse outcomes, and there were no deaths. The difference between the two groups was not statistically significant (χ²=1.650, P=0.125). After 2 months of treatment, the cavity closure rate of the test group was 28.4% (60/211), which was significantly higher than that of the control group (18.5% (46/248), and the difference was statistically significant (χ²=6.276, P=0.001). The sputum culture negative conversion rate of the test group was 96.3% (539/560), which was significantly higher than that of the control group (93.2% (551/591), and the difference was statistically significant (χ²=5.219, P=0.025). At the end of the treatment, the cavity closure rate was 61.6% (130/211) in the test group and 57.3% (142/248) in the control group, with no statistical difference (χ²=0.118, P=0.391). Within 12 months after the end of treatment, 15 patients (2.7%) in the test group relapsed, and 19 patients (3.2%) in the control group relapsed, with no statistical difference (χ²=0.298, P=0.607). Except for skin induration at the injection site, there was no significant difference in the occurrence of adverse drug reactions between the two groups. In the test group, the incidence of skin induration at the injection site was 14.8% (83/560). The most common adverse drug reactions in the two groups were hyperuricemia (the incidence rates were 23.2% (130/560) in the test group and 23.3% (138/591) in the control group). Conclusion:IL-2 containing regimen as an adjunctive treatment for newly diagnosed drug-sensitive pulmonary tuberculosis may promote the negative conversion of sputum culture and cavity closure in the early stage of treatment.

Efficacy comparison of two molecular drug sensitivity methods and phenotypic drug sensitivity testindetecting drug resistance of Mycobacterium tuberculosis

Sun Wenna, Zhang Junxian, Zhang Xiushuang, Wang Xiaomeng, Lin Wen, Liang Yan, Wang Jie, Wu Xueqiong

Chinese Journal of Antituberculosis. 2022, 44(10):  1016-1021.  doi:10.19982/j.issn.1000-6621.20220259

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Objective:To evaluate the value of the gene chip method and fluorescence quantitative PCR-probe melting curve method in the direct detection of Mycobacterium tuberculosis (MTB) drug resistance in clinical specimens of tuberculosis patients. Methods:Forty-four clinical specimens of hospitalized tuberculosis patients in the Senior Department of Tuberculosis, the 8th Medical Center of Chinese PLA General Hospital were selected. Using the absolute concentration method of the traditional drug susceptibility test as the control, the drug resistance of MTB to rifampicin and isoniazid in clinical samples was directly detected by the gene chip method, and the drug resistance of MTB to rifampicin, isoniazid, and levofloxacin in the clinical specimens was directly detected by fluorescence quantitative PCR-probe melting curve method, to evaluate the sensitivity, specificity, and consistency of these two molecular drug susceptibility test methods. Results:The traditional drug susceptibility test was used as the standard, the sensitivity, specificity, consistency, and Kappa value of MTB to rifampicin resistance in 44 clinical samples directly detected by the gene chip method were 87.5% (14/16), 96.4% (27/28), 93.2% (41/44) and 0.851, respectively; for the isoniazid resistance were 85.7% (12/14), 96.7% (29/30), 93.2% (41/44) and 0.758, respectively. The sensitivity, specificity, consistency, and Kappa value of MTB to rifampin resistance in 44 clinical samples directly detected by the probe melting curve method were 87.5% (14/16), 89.3% (25/28), 88.6% (39/44), and 0.840, respectively; for isoniazid resistance were 85.7% (12/14), 83.3% (25/30), 84.1% (37/44), and 0.653, respectively; for the levofloxacin resistance were 85.0% (17/20), 100.0% (24/24), 93.2% (41/44), and 0.861, respectively. Conclusion:The gene chip method and probe melthing curve method have a high consistency with the absolute concentration method in detecting the drug resistant of MTB to rifampicin, isoniazid (and levofloxain) in clinical specimens,which can be used as a reference for clinical chemotherapy.

Serum cytokine TNF-α, IL-4, sIL-2R and IFN-γ progress in monitoring bacterial load and anti-tuberculosis treatment

Nie Wenjuan, Shi Wenhui, Liu Peiying, Yang Yang, Wang Jun, Wang Qingfeng, Chu Naihui

Chinese Journal of Antituberculosis. 2022, 44(10):  1022-1027.  doi:10.19982/j.issn.1000-6621.20220167

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Objective:To explore the predictive value of serum cytokines TNF-α, IL-4, sIL-2R and IFN-γ for antituberculosis treatment in patients with pulmonary tuberculosis. Methods:By a prospective cohort study method, 67 patients diagnosed active pulmonary tuberculosis admitted to Beijing Chest Hospital Affiliated to Capital Medical University from December 2017 to June 2019 were enrolled according to the enrollment criteria. Serum cytokine levels of TNF-α, IL-4, sIL-2R and IFN-γ were measured by enzyme-linked immunosorbent assay (ELISA) from patients before treatment, 1-2 months and 6 months after treatment. ROC curve analysis was performed to determine the best cut-off value, and treatment progress were predicted with this as the cut-off value. Results:The levels of SIL-2R (14.1 (11.2,19.1) pg/ml) after 1-2 months of treatment, TNF-α (686.6 (226.9,1030.5) pg/ml) after 6 months of treatment, IFN-γ (357.0 (273.4,431.0) pg/ml) after 1-2 months of treatment were significantly lower than that before treatment (16.7 (12.9, 23.9), 848.3 (345.2, 1201.6), 490.0 (303.6,607.9) pg/ml, respectively), with the statistically difference (χ²=15.276, P=0.036; χ²=33.421, P=0.002; χ²=31.111, P=0.000). ROC analysis showed that when serum TNF-α at 845.2 pg/ml and IFN-γ at 393.3 pg/ml,the AUC of therapeutic effectiveness were 0.594 (P=0.013) and 0.651 (P=0.017). With the best cut-off value as the reference standard, serum IFN-γ and TNF-α level above the cut-off value before treatment were 43 cases (64.2%) and 34 cases (50.7%), respectively. In 1-2 months after treatment, 14 cases (20.9%) were positive with the serum IFN-γ significantly lower than that before treatment (χ²=34.634, P=0.000). In 6 months after treatment, 19 cases (28.4%) were positive with the serum TNF-α significantly lower than that before treatment (χ²=53.181, P=0.013). Conclusion:Both serum TNF-α and IFN-γ levels might be useful biomarkers for monitoring treatment progress.

Analysis of influencing factors of recurrence in cured patients with multidrug-resistant pulmonary tuberculosis

Yang Xiaoyu, Qiu Lei, Zhang Shunxian, Zhang Shaoyan, Zhou Wei, Wu Xianwei, Wu Dingzhong, Zhang Huiyong, Xiao Heping, Lu Zhenhui

Chinese Journal of Antituberculosis. 2022, 44(10):  1028-1036.  doi:10.19982/j.issn.1000-6621.20220195

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Objective:To analyze the risk factors of recurrence in cured patients with multidrug-resistant pulmonary tuberculosis (MDR-PTB). Methods:A retrospective study was conducted in 600 MDR-PTB patients who were cured by long-term (18-24 months) chemotherapy (6Am-Lfx-P-Z-Pto/18Lfx-P-Z-Pto; Am: amikacin, Lfx: levofloxacin, P: sodium p-aminosalicylate, Z: pyrazinamide, Pto: prothionamide) and followed up for 3 years from 18 hospitals in 15 provinces between January 2013 and December 2017. The basic information, clinical information and laboratory test results of the subjects were collected, including gender, age, body mass index, history of chronic disease, history of tuberculosis (before receiving this long-term chemotherapy regimen), treatment and medication status, as well as sputum smear, sputum culture, drug sensitivity test, chest CT scan, routine blood test, erythrocyte sedimentation rate, routine urine test, liver and kidney function, etc. The risk factors of recurrence in cured MDR-PTB patients were analyzed, and the predictive value of recurrence risk factors for MDR-PTB recurrence was evaluated by receiver operating characteristic curve. Results:The 3-year recurrence rate of the 600 MDR-PTB patients was 6.7% (40/600; 95%CI: 4.9%-9.1%). Logistic multivariate regression analysis showed that elevated erythrocyte sedimentation rate (OR (95%CI)=2.705 (1.136-6.444)), elevated total bilirubin (OR (95%CI)=5.329 (1.408-20.170)), elevated urinary protein (OR (95%CI)=5.642 (1.650-19.292)), elevated urine glucose (OR (95%CI)=5.333 (1.357-20.954)), usage of cycloserine (OR (95%CI)=11.771 (3.920-35.347)), the time from the initial diagnosis of pulmonary tuberculosis to the initial diagnosis of MDR-PTB ≥1 year (OR (95%CI)=8.730 (2.710-28.119)), and cavity (OR (95%CI)=32.806 (6.096-176.557)) were independent risk factors for MDR-PTB recurrence. The receiver operating characteristic curve analysis showed that when the logistic regression analysis overall model was used as the test variable, the area under the curve was the largest (0.932). Conclusion:Attention should be paid to the erythrocyte sedimentation rate, total bilirubin level, urine protein level and urine sugar level when they higher than the normal levels, as well as the treatment and follow up of MDR-PTB patients with the initial diagnosis of PTB to the initial diagnosis of MDR-PTB ≥1 year, and MDR-PTB patients with cavities, furthermore, the use of cycloserine should be reasonable and standardized.

Study on clinical efficacy of integrated traditional Chinese and western medicine in the treatment of pulmonary tuberculosis

He Meiyan, Zhang Zunjing, Liu Zhongda

Chinese Journal of Antituberculosis. 2022, 44(10):  1037-1042.  doi:10.19982/j.issn.1000-6621.20220131

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Objective:To evaluate the clinical efficacy of conventional chemotherapy combined with traditional Chinese medicine (TCM) anti-tuberculosis mixture and appropriate traditional Chinese medicine technology in the treatment of pulmonary tuberculosis (PTB). Methods:Using the approach of a prospective study, 300 primary diagnosed and treated TB patients in the Tuberculosis Department of Lishui Hospital of Traditional Chinese Medicine Affiliated to Zhejiang University of Traditional Chinese Medicine were continuously collected from January 2017 to December 2019. According to the random number table, patients were equally divided into 3 groups, the conventional western medicine anti-TB treatment group (group A), conventional western medicine anti-TB treatment combined with TCM anti-TB mixture group (group B), and conventional western medicine anti-TB treatment combined with TCM anti-TB mixture and TCM appropriate technology group (Group C). After excluding 24 patients due to diagnosis changes, treatment interruption and adverse reactions, 276 patients were finally included in group A (n=97), group B (n=93) and group C (n=86). The improvement of TCM symptoms, absorption of pulmonary lesions, changes of T lymphocyte subsets and treatment outcomes were observed and compared among the three groups. Results:After 6 months of treatment, in group B and group C, the effective rate of TCM syndromes improvement (92.5% (86/93) and 94.2% (81/86)), the effective rate of pulmonary lesions absorption (92.5% (86/93) and 94.2% (81/86)), the percentage of CD3⁺T cells ((65.76±5.42) % and (67.06±5.95) %), the percentage of CD4⁺T cells ((44.97±5.35) % and (46.51±5.26) %), and the effective rate of treatment (94.6% (88/93) and 97.7% (84/86)) were significantly better than those in group A (82.5% (80/97), 76.3% (74/97), (63.80±4.57) %, (42.72±4.82) %, 80.4% (78/97)), the differences were statistically significant (χ²=2.000, P=0.046; χ²=2.999, P=0.003; χ²=2.427, P=0.015; χ²=2.886, P=0.004; t=2.699, P=0.008; t=4.186, P=0.005; t=3.048,P=0.003; t=6.428, P<0.001; χ²=2.069, P=0.039; χ²=2.192, P=0.028, respectively). The percentages of CD8⁺T cells in group B and C ((27.12±2.32) % and (26.35±3.17) %) were significantly lower than that in group A ((29.12±2.21) %), and the difference was statistically significant (t=5.051, P<0.001; t=9.231, P<0.001, respectively). Conclusion:The traditional Chinese and western medicine combined with anti-TB regimen can significantly reduce the clinical symptoms of PTB patients, promote the absorption of pulmonary lesions, improve the immunity of PTB patients, and effectively improve the clinical efficacy, however, the application effect of TCM appropriate technology has not been confirmed.

Burden and challenge of TB and TB/HIV co-infection: a case study of Nigeria

Zhao Yaxin, Olabi Onikepe, Zhou Zhongliang, Wei Xiaolin

Chinese Journal of Antituberculosis. 2022, 44(10):  1043-1049.  doi:10.19982/j.issn.1000-6621.20220251

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Objective: To explore the burden of tuberculosis (TB) and TB/HIV co-infection and the implementation of integrated TB control measures in Nigeria, to identify the challenge for TB control and to provide reference for TB elimination in Nigeria. Methods: The World Health Organization’s TB data between 2010 and 2020 were used to depict the trend of TB and TB/HIV burden in Nigeria. Results: Nigeria is a country with high burden of infection of tuberculosis and TB/HIV. The incidence rate of tuberculosis among HIV infected people decreased from 54/100000 in 2010 to 17/100000 in 2020; In 2020, the number of confirmed tuberculosis patients was 135000, and the estimated number of cases will be 452000, however, the detection rate of tuberculosis was only 30%. The antiretroviral treatment coverage rate of TB/HIV co-infection increased from 6.9% in 2010 to 26.0% in 2020; The successful treatment rate of tuberculosis increased from 81% in 2010 to 88% in 2019, and the successful treatment rate of TB/HIV double infection patients increased from 78.9% in 2012 to 81.1% in 2019. The total funds of tuberculosis in Nigeria increased, while the TB/HIV project funds little changed, from US $4.5 million in 2010 to US $5.4 million in 2020. Conclusion: The situation in Nigeria is far from the goal of the 2020 End TB Strategy. To reduce and eliminate the burden of TB and TB/HIV, priority must be given to implement integrated TB control measures, increasing necessary resources and funds for TB control, and strengthening diagnostic ability of TB.

Analysis on the adoption rate and influencing factors of electronic medication monitors in tuberculosis patients in Jilin Province

Yang Fan, Ma Jianjun, Gao Ying, Gao Zhihui, Yuan Yanli

Chinese Journal of Antituberculosis. 2022, 44(10):  1050-1056.  doi:10.19982/j.issn.1000-6621.20220080

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Objective:According to the acceptance of electronic medication monitors (EMM) after its comprehensive promotion in Jilin Province, analyze the relevant factors affecting the adoption rate of EMM. Methods:Collect the medical record data about adoption of EMM among tuberculosis patients registered in Jilin Province in 2019 at different times, in different regions and with different characteristics. Univariable and multivariable logistic regression models were used to analyze the current status and influencing factors of EMM usage in tuberculosis patients. Results:In 2019, 8435 tuberculosis patients were registered in the EMM promotion regions, and 5231 patients accepted EMM management, the adoption rate of EMM was 62.02%. Multivariable logistic regression analysis showed that patients being 20-39 years old (OR=1.264, 95%CI: 1.026-1.558) or 40-59 years old (OR=1.280, 95%CI: 1.045-1.567), non-Han ethnic groups (OR=2.176, 95%CI: 1.691-2.801), with an occupation farmer or herdsman (OR=1.189, 95%CI: 1.081-1.308), local patients (OR=3.425, 95%CI: 2.968-3.952), patient coming from referral or tracking (OR=1.747, 95%CI: 1.588-1.921), etiologically positive (OR=3.437,95%CI:2.779-4.250) or negative (OR=3.454,95%CI:2.790-4.278) patients, newly treated patients(OR=3.024, 95%CI: 2.511-3.642) got a higher rate of using EMM. Conclusion:As a tool for supervision of medication for patients, EMM can be popularized and used in Jilin Province, especially for patients aged 20-59, farmers and herdsmen, local registered residence patients, patients coming from referral and tracking, etiologically positive and negative patients and newly treated patients.

Analysis of drug compliance and influencing factors of patients with multidrug-resistant pulmonary tuberculosis in Huai’an, Jiangsu Province

Wang Chunlei, Jin Tao, Zhao Pengpeng, Ding Shouhua, Zhou Jin, Hu Jinliu

Chinese Journal of Antituberculosis. 2022, 44(10):  1057-1062.  doi:10.19982/j.issn.1000-6621.20220214

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Objective:To investigate the current situation and influencing factors of drug compliance of patients with multidrug-resistant pulmonary tuberculosis (MDR-PTB) in Huai ’an, Jiangsu Province. Methods:A total of 235 MDR-PTB patients diagnosed and treated in the designated tuberculosis hospital in Huai’an, Jiangsu Province from January 2017 to June 2019 were selected, and the Morisky medication adherence scale (MMAS-8) was used for investigation to analyze the current status and influencing factors of drug compliance of MDR-PTB patients. Results:Among the 235 patients, 197 patients (83.8%) had good drug compliance, and 38 patients (16.2%) had poor drug compliance. The results of logistic multivariate analysis showed that male (OR=2.526, 95%CI: 1.217-4.524), aged ≥60 years (OR=1.521, 95%CI: 1.025-2.693), adverse drug reactions (OR=3.892, 95%CI: 1.793-6.822), self-taking medicine (OR=2.635, 95%CI: 1.466-6.107), duration of disease ≥2 years (OR=1.529, 95%CI: 1.112-2.453), floating population (OR=2.868, 95%CI: 1.559-5.234), education background of junior high school or below (OR=1.297, 95%CI: 1.009-1.615), family monthly income <RMB 5000 yuan (OR=1.493, 95%CI: 1.265-5.392) were risk factors of drug compliance. Conclusion:Targeted health education and medication guidance should be carried out for MDR-PTB patients who were male and aged ≥60 years old, with adverse drug reactions and self-administration, and the disease duration ≥2 years, furthermore, those who were floating population, with education background of junior high school or below, and monthly household income <RMB 5000 yuan.

Survey on burnout and influencing factors of medical staff for tuberculosis control in Beijing

Zhang Hongwei, Sun Shanhua, Xu Yan, Gao Zhidong, Li Yanyuan, Tao Liying, Zhao Yao, Zhao Xin, Chen Xi

Chinese Journal of Antituberculosis. 2022, 44(10):  1063-1070.  doi:10.19982/j.issn.1000-6621.20220231

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Objective:To overview burnout of medical staff for tuberculosis control in Beijing and explore the risk factors of the three different dimensions which are reduced personal accomplishment, depersonalization and emotional exhaustion. Thus to make recommendations to reduce burnout, then to improve the quality of tuberculosis prevention and control. Methods:Cross-sectional surveys were conducted during April 25 to May 10, 2021. All the medical staff in Beijing Institute of Tuberculosis Control and prevention and tuberculosis control agencies in 16 districts of Beijing completed the anonymous online structured self-filled questionnaire. The questionnaire included the Maslach Burnout Survey Generalized Scale (MBI-GS) and general information. Logistic stepwise regression was used to analyze the influencing factors of its three dimensions of burnout. Results:A total of 313 questionnaires were distributed, and 311 were valid, with an effective rate of 99.36%. Among 311 practitioners, 81 (26.05%) were male and 230 (73.95%) were female, with an average of (41.12±9.84) years old, 195 (62.70%) positive cases of burnout, 202 (64.95%) cases of reduced personal accomplishment, 144 (46.30%) cases of depersonalization, 192 (61.74%) cases of emotional exhaustion. The logistic multiple regression analysis of three dimensions of burnout among the practitioners showed that medical staff in prevention and control positions (OR=2.12, 95%CI: 1.26-3.55) were more likely to experience reduced personal accomplishment in their work; medical staff who working in TB for ≥10 years (OR=2.21,95%CI:1.34-3.64), exercising less than 3 hours per week (OR=1.71, 95%CI:1.04-2.82), not meeting expectations for promotion (OR=3.09,95%CI:1.79-5.33), and not getting along well with colleagues (OR=2.70, 95%CI:1.43-5.08) were more likely to experience depersonalization; those who sleep <6 hours per day (OR=1.85, 95%CI: 1.02-3.37), did not meet expectations for title promotion (OR=1.84, 95%CI: 1.11-3.05), did not get along with colleagues (OR=2.68, 95%CI: 1.34-5.35) more likely to experience emotional exhaustion among medical staff. Conclusion:High burnout rate was detected in medical stall for tuberculosis control in Beijing. Those in prevention and control positions are more likely to have reduced personal accomplishment. It is necessary to increase the opportunities for the promotion, carry out group psychological construction, create a good working atmosphere, and various measures should be taken to improve the sense of work achievement, and to reduce the occurrence of burnout.

Interrupted time series analysis of hospitalization costs of tuberculosis patients before and after the abolition of the drug markup policy

Li Gaiyun, Wu Yanghaotian, Ding Mingfeng, Li Yilun, Zhang Jiawen, Luo Xiaolei, Jiang Jingwen, Han Xuemei

Chinese Journal of Antituberculosis. 2022, 44(10):  1071-1078.  doi:10.19982/j.issn.1000-6621.20220220

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Objective:To analyze the changes in hospitalization costs of tuberculosis inpatients before and after the implementation of the drug markup abolition policy. Methods:This study was a retrospective study with data obtained from the medical insurance settlement system of Luzhou City, Sichuan Province. The billing data of tuberculosis inpatients hospitalized from February 1, 2015 to November 20, 2018 in two Grade A tertiary tuberculosis designated hospitals (Affiliated Hospital of Southwest Medical University and Luzhou People’s Hospital) were obtained, and a total of 3749 cases were included. Interrupted time series (ITS) model was used to analyze the changes in the level and trend of the average total hospitalization cost and costs under different categories before and after the implementation of the drug markup abolition policy. Results:The average age of 3749 tuberculosis inpatients was (48.23±18.90) years, and the largest number of tuberculosis patients had a total single hospitalization cost of RMB 10000-14999 yuan per patient which accounted for 26.25% (984/3749) of all patients. After the implementation of the abolition of the drug markup policy, the median total cost of a single hospitalization was decreased by RMB 1150.13 yuan, and the median cost of a single western medicine was decreased by RMB 643.16 yuan. ITS analysis showed that before the implementation of the abolition of the drug markup policy, the average traditional Chinese medicine cost and average material cost increased by 5.34% (β₁=0.052, t=2.941, P<0.05) and 1.92% (β₁=0.019, t=3.987, P<0.05) per month on average. At the time of policy implementation, the average anesthesia, material and traditional Chinese medicine costs immediately increased by 83.31% (β₂=0.606, t=3.311, P<0.05), 24.48% (β₂=0.219, t=2.477, P<0.05), and 99.57% (β₂=-0.691, t=-2.187, P<0.05) respectively. After the implementation of the drug markup abolition policy, the average monthly decrease in the average traditional Chinese medicine, material, western medicine, examination, anesthesia, surgical costs, and the average total hospitalization cost were 0.60% (β₁=0.052, β₃=-0.058, t=-2.193, P<0.05), 4.81% (β₁=0.019, β₃=-0.066, t=-10.051, P<0.05), 1.51% (β₁=0.003, β₃=-0.018, t=-2.223, P<0.05), 2.53% (β₁=0.009, β₃=-0.034, t=-4.552, P<0.05), 4.39% (β₁=0.003, β₃=-0.046, t=-3.373, P<0.05), 4.92% (β₁=0.009, β₃=-0.057, t=-3.057, P<0.05) and 1.31% (β₁=0.006, β₃=-0.019, t=-4.432, P<0.05), respectively. Conclusion:After the implementation of the abolition of the drug markup policy, the total hospitalization cost and drug cost of tuberculosis inpatient showed a decreasing trend, indicating that the policy of abolishing drug markup had made a significant influence in reducing drug costs and controlling total hospitalization cost of tuberculosis patients.

Review Articles

Research progress in immunotherapy of tuberculosis

Wang Li, Yang Enzhuo, Sha Wei, Shen Hongbo

Chinese Journal of Antituberculosis. 2022, 44(10):  1079-1084.  doi:10.19982/j.issn.1000-6621.20220194

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At present, the treatment of tuberculosis, especially multidrug-resistant tuberculosis (MDR-TB) faces many challenges. Immunotherapy can improve the protective immunological response to Mycobacterium tuberculosis infection, thus is an important beneficial supplement to conventional chemotherapy. In this paper, we summarize the research progress of cytokines, immunological cells and immunomodulatory drugs that have the potential to be used in the immunotherapy of tuberculosis and analyze their clinical application prospects, to provide ideas for future clinical researches and mechanism exploration of tuberculosis.

Research progress of programmed cell death protein 1/programmed cell death ligands signaling pathway in immune regulation of tuberculosis

Liu Qi, Liang Jianqin

Chinese Journal of Antituberculosis. 2022, 44(10):  1085-1090.  doi:10.19982/j.issn.1000-6621.20220127

Abstract ( 285 )   HTML ( 10 )   PDF (881KB) ( 171 )   Save

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Programmed cell death protein 1 (PD-1) and programmed cell death ligands (including programmed cell death ligand 1 (PD-L1) and PD-L2) are inhibitory costimulatory molecules, which plays an important role in the immune response of tuberculosis. This article reviewed the structure and function of PD-1/PD-L1, PD-L2 and its immune-regulatory role in pulmonary alveolar macrophage and T cell subsets, different types of tuberculosis and different treatment stages of tuberculosis, in order to provide new ideas for the diagnosis and treatment of tuberculosis.

Development and challenges of Mycobacterium tuberculosis cfDNA in the diagnosis of tuberculosis

Peng Lijun, Fang Tingting, Cai Long

Chinese Journal of Antituberculosis. 2022, 44(10):  1091-1095.  doi:10.19982/j.issn.1000-6621.20220228

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In order to achieve the goal of “End Tuberculosis by 2035”, it is urgent to develop new detection methods. Mycobacterium tuberculosis cfDNA (MTB-cfDNA) can indicate the presence of pathogens and is an attractive biomarker for tuberculosis (TB) diagnosis and treatment monitoring. Easily accessible MTB-cfDNA in urine and/or blood can be used to detect both pulmonary and extrapulmonary TB in any age group. The diagnostic performance of MTB-cfDNA in fluid samples such as pleural effusion, ascites and cerebrospinal fluid is higher than that of genomic DNA assays such as GeneXpert MTB/RIF. Research on cfDNA as a TB biomarker is still in its infancy, larger and clinical studies including more comprehensive patient types are needed to evaluate the utility of cfDNA in TB diagnosis. With further optimization of detection methods, cfDNA testing may improve TB diagnosis and become a “game changer”.

Short Articles

Meta analysis of the differences between BCG-PPD and TB-PPD in tuberculosis screening

Ding Xiaojuan, Wang Dan, Zhang Yaozhi, He Jianqing

Chinese Journal of Antituberculosis. 2022, 44(10):  1096-1099.  doi:10.19982/j.issn.1000-6621.20220156

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To investigate the differences between pure protein derivative of BCG (BCG-PPD) and pure protein derivative of tuberculin (TB-PPD) in tuberculosis screening. Relevant literatures published from the establishment of the databases to February 2022 were searched from PubMed, Embase, Medline, Cochrane Library, CNKI and Wanfang. Open Meta Analyst software was used for meta-analysis of the included literatures. Cochrane Risk of Bias Assessment tool with Rev Man 5.3 software was used to evaluate the quality of the literature. Finally, 7 articles were included, with a total of 36131 participants, including 18314 participants in BCG-PPD group and 17817 participants in TB-PPD group. Dichotomous random effect model was used to analyzed. The combined OR (95%CI) value was 2.072 (1.683-2.550), I²=78.73%, P<0.001, indicating high heterogeneity, and the source of heterogeneity should be further analyzed. The results of subgroup analysis showed that the OR (95%CI) value of students and newborns was 2.393 (2.132-2.686), I²=50.15%, P=0.091, and I² value decreased significantly. The OR (95%CI) value of tuberculosis patients in the subgroup was 0.481 (0.236-0.978), I²=0, P=0.043, and the fixed-effect model was used. Differences in the positive detection rate of TB-PPD and BCG-PPD in different populations were found. The positive detection rate of BCG-PPD is higher than that of TB-PPD in students and neonates, and the positive detection rate of TB-PPD was higher than that of BCG-PPD in tuberculosis patients.

CT imaging of 56 cases of epididymal tuberculosis

Li Xiang, Ma Zhongxu, Fu Xuwen, Qi Min, Xu Yanling, Shen Lingjun

Chinese Journal of Antituberculosis. 2022, 44(10):  1100-1103.  doi:10.19982/j.issn.1000-6621.20220208

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To understand the CT imaging features of epididymal tuberculosis, the author analyzed 56 patients with epididymal tuberculosis admitted to Kunming Third People’s Hospital from September 1, 2020 to October 31, 2021, who were diagnosed with pathology, bacteriology or effective with anti-tuberculosis treatment.The results revealed the median age of 56 patients with epididymal tuberculosis was found to be 42 years old, and 37 cases (66.1%) had symptoms of scrotal swelling and pain. Among them, 9 cases (16.1%) were combined with scrotal skin sinus tract formation. The number of cases with combined pulmonary tuberculosis, renal tuberculosis, syringomyelia and testicular involvement were 29 (51.8%), 26 (46.4%), 24 (42.9%) and 15 (26.8%).CT showed the epididymis was thickened in 56 cases (100.0%), multiple lesions in 34 cases (60.7%).The epididymis was involved unilaterally in 32 cases (57.1%), and the epididymis was calcified in 8 cases (14.3%). The number of cases with only nodular enhancement, only rim enhancement and both were 23 (41.1%), 19 (33.9%) and 14 (25.0%), respectively, on CT-enhanced scans of epididymal lesions in the portal vein phase. It is believed that patients with epididymal tuberculosis mostly have scrotal swelling and pain, and can be combined with pulmonary and renal tuberculosis. CT scans mostly show unilateral epididymal involvement with multiple lesions and nodular or rim enhancement on enhancement CT scans, which have certain CT imaging characteristics.