Table of Content

10 October 2020, Volume 42 Issue 10

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Guideline·Standard·Consensus

Expert consensus on detection and clinical application of peripheral blood lymphocyte subsets in patients with tuberculosis

Editorial Board of Chinese Journal of Antituberculosis

Chinese Journal of Antituberculosis. 2020, 42(10):  1009-1016.  doi:10.3969/j.issn.1000-6621.2020.10.001

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The occurrence, development and prognosis of tuberculosis (TB) depend on the quantity and virulence of MTB and immune resistance. The analysis of lymphocyte subsets in peripheral blood of TB patients by flow cytometry can help to evaluate the immune status, immune function and immune balance of TB patients, and provide experimental basis for clinical development of immune intervention measures, observation of curative effect and judgment of prognosis. This expert consensus briefly introduces lymphocyte subsets analysis items (including percentage and absolute count) commonly used in clinic; puts forward the suggestions for the detection of lymphocyte subsets in TB patients and the correct interpretation of the results; introduces the use of lymphocyte subsets analysis in the clinical diagnosis and treatment of TB patients, and prospects the development of lymphocyte subsets detection in the future.

Expert Forum

Current status and thinking of clinical practice guidelines of tuberculosis in children

WANG Ze-ming, SUN Lin, SHEN A-dong

Chinese Journal of Antituberculosis. 2020, 42(10):  1025-1028.  doi:10.3969/j.issn.1000-6621.2020.10.004

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Tuberculosis (TB) remains a infection disease which causes relatively higher morbidity and mortality in children. In order to reduce childhood TB, a number of clinical practice guidelines for the management of tuberculosis in children with variable qualities have been published by different countries or organizations, only these wtih high qualities provide a better guidance. In order to promote the application of these clinical practice guidelines in children and improve the standardization, science and transparency of the formulation of the clinical practice guidelines in the further, this article analyzed the current status of the characteristics, quality and recommendations of published clinical practice guidelines, pointed out the existing limitations and propose improvement strategies.

Original Articles

Analysis of characteristics and related factors of tuberculosis resistance in children

FAN Li-chao, WU Hao-yu, CHENG Mo-xin, YANG Yi-fan, WANG Xiao-hong, YU Yan-hong, CHEN Yu

Chinese Journal of Antituberculosis. 2020, 42(10):  1029-1035.  doi:10.3969/j.issn.1000-6621.2020.10.005

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Objective To understand the status of drug resistance in children with tuberculosis and to identify risk factors associated with drug resistance. Methods Information of 314 tuberculosis patients under 18 years old admitted to Shenyang Tenth People’s Hospital from January 31, 2017 to December 31, 2019 were collected. 178 cases were male, and 136 cases were female. The age ranged from 1 to 18 years old, median age (M(Q₁,Q₃)) was 17 (15,18). There were 253 primary treated cases and 61 retreated cases. Drug susceptibility test results of positive culture isolates from those 314 patients were analyzed. Risk factors for multidrug-resistant tuberculosis (MDR-TB) in children were analyzed using multivariate logistic regression. Results The overall drug resistance rate, primary treated drug resistance rate and retreatment drug resistance rate of 314 clinical isolates of Mycobacterium tuberculosis (MTB) were 27.1% (85/314), 20.9% (53/253) and 52.5% (32/61) respectively, and the retreatment drug resistance rate was significantly higher than the primary treated drug resistance rate (χ²=24.771,P=0.000). The overall,primary treated and retreatment multidrug-resistance rate were 10.8% (34/314), 6.3% (16/253) and 29.5% (18/61) respectively. The retreatment multidrug-resistance rate was significantly higher than that of primary treated multidrug-resistance rate (χ²=27.360, P=0.000). Logistic multivariate regression analysis showed that retreatment (OR=5.671, 95%CI=2.228-14.435, P=0.000), 14-18 years old (OR=2.235, 95%CI=1.568-3.562, P=0.032), complicated with malnutrition (OR=1.908, 95%CI=1.337-2.447, P=0.034), smoking (OR=1.225, 95%CI=1.013-2.740, P=0.046) were risk factors related to MDR-TB in children. Conclusion The current situation of tuberculosis drug resistance in children is severe. Retreatment, 14-18 years old, malnutrition and smoking history are risk factors of MDR-TB in children.

Study on intrapleural injection of urokinase to prevent pleural thickening and adhesive encapsulation in children with tuberculous pleurisy

TIAN Yao, WU Hao-yu, LI Ran, CHENG Mo-xin, WANG Xiao-dan, CHEN Yu

Chinese Journal of Antituberculosis. 2020, 42(10):  1036-1041.  doi:10.3969/j.issn.1000-6621.2020.10.006

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Objective To investigate the effect of early intrapleural injection of urokinase on pleural thickening and adhesive encapsulation in children with tuberculous exudative pleurisy. Methods Seventy children with tuberculous pleurisy diagnosed in Shenyang Tenth people’s Hospital from January 1, 2019 to December 31, 2019 were included in the study. According to the random number table, patients were randomly enrolled into treatment group or control group. It was estimated that the data will be discontinued when 35 patients per group were reached according to the variability of the cohort design rate. A total of 70 patients were included, 53 males and 17 females, aged 4-14 years (27 patients) and 15-18 years (43 patients).On the basis of standard anti-tuberculosis treatment (2H-R-Z-E/10H-R-Z) assisted by pleural catheterization, the control group was treated with simple pleural drainage. The treatment group was treated with intrapleural injection of urokinase and pleural drainage. Pleural thickening, adhesive encapsulation, and whether needed operation after treating for 12 weeks were compared between those two groups. At the same time, length of hospital stay, drainage time, disappearance time of pleural effusion, levels of plasminogen activator inhibitor-1 (PAI-1), tissue-plasminogen activator (t-PA) and procollagen type Ⅲ (PCⅢ) in pleural effusion before and after drainage were compared. Results The incidences of pleural thickening, adhesive encapsulation and operation (12 weeks) in the treatment group were 28.6% (10/35), 8.6% (3/35) and 2.9% (1/35) respectively, which were significantly lower than those in the control group (62.9% (22/35), 31.4% (11/35), 22.9% (8/35); χ²=8.289, 5.714, 4.590; P=0.004, 0.017, 0.032). Median (Q₁,Q₃) of hospital stay,the average drainage time and the disappearance time of pleural effusion in the treatment group were 21 (14,32) d,20 (13,30) d and 19 (12,29) d respectively, which were significantly shorter than those in the control group (30 (18,39) d, 29 (16,36) d, 28 (14,35) d respectively). The differences were statistically significant (Z values were 2.475, 2.382 and 2.164 respectively, P=0.013, 0.017, 0.030). The median (Q₁,Q₃) level of t-PA/PAI-1 (0.43 (0.38,0.53)) in pleural effusion after urokinase intervention in the treatment group was significantly higher than that in the control group (0.22 (0.19,0.32)), and the difference was statistically significant (Z=5.733,P=0.000). The concentration of PCⅢ ((35.09±6.26) μg/L) in pleural effusion after urokinase intervention in the treatment group was significantly lower than that in the control group ((51.73±10.27) μg/L), and the difference was statistically significant (t=8.188,P=0.000). Conclusion Early intrapleural injection of urokinase on the basis of thoracic drainage is helpful to prevent pleural thickening and adhesive encapsulation in children with tuberculous pleurisy.

Clinical characteristics and therapeutic effect analysis of 23 cases of disseminated BCG disease after BCG vaccination caused by primary immunodeficiency disease

WANG Zhen-long, WU Xiao-ying, XU Hong-mei

Chinese Journal of Antituberculosis. 2020, 42(10):  1042-1047.  doi:10.3969/j.issn.1000-6621.2020.10.007

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Objective To investigate the clinical characteristics, immunological characteristics and therapeutic effects of disseminated BCG complicated with primary immunodeficiency disease. Methods Twenty-three patients with disseminated BCG complicated with primary immunodeficiency disease were retrospectively collected from January 2015 to December 2019 in Children’s Hospital Affiliated to Chongqing Medical University. Among them, there were 18 males and 5 females with disseminated BCG disease within 6 months after inoculation. The clinical data and immunological characteristics were analyzed, and the therapeutic effect was followed up. Results Among the 23 children with disseminated BCG disease after BCG vaccination, there were 16 cases of chronic granulomatosis, 3 cases of primary immunodeficiency disease, 2 cases of severe combined immunodeficiency disease, 1 case of X-linked severe combined immunodeficiency disease and 1 case of X-linked high IgM syndrome. Among the 23 cases, 23 cases had pulmonary dissemination, 3 cases had liver spread, 1 case had abdominal dissemination, 1 case had left femur spread and 1 case had intracranial spread. Sixteen cases of children with chronic granulomatosis were abnormal in leukocyte phagocytosis test. One case of X-linked high IgM syndrome had significantly increased IgM level and decreased complement C3 level; two cases of severe combined immunodeficiency disease showed that CD3⁺ CD4⁺ T cells and CD3⁺ CD8⁺ T cells were significantly decreased, with the decrease of immunoglobulin level. Among the 23 cases, 6 cases died, the mortality rate was 26.1%; seventeen cases of survival children were followed up for 1.0-2.8 years and were in intermittent hospitalization. Conclusion Disseminated BCG complicated with primary immunodeficiency has an early onset, and chronic granulomatous disease is more common in these children; this disease has a high mortality rate and poor prognosis, so it is necessary to clarify the type of immunodeficiency and carry out targeted treatment as early as possible.

Analysis of clinical efficacy of stageⅠanterior-posterior approach surgery for lumbar tuberculosis in children

BAI Yun-song, ZHANG Xue-jun, CAO Jun, FENG Lei, QI Xin-yu, GUO Dong, YAO Zi-ming, LI Cheng-xin

Chinese Journal of Antituberculosis. 2020, 42(10):  1048-1052.  doi:10.3969/j.issn.1000-6621.2020.10.008

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Objective To analyze the clinical effect of stageⅠanterior-posterior approach surgery for lumbar tuberculosis in children. Methods Clinical data of 68 lumbar tuberculosis children (male: 38, female: 30) who received stageⅠ anterior-posterior approach surgery in Beijing Children’s Hospital from February 2009 to February 2017 were retrospectively analyzed. They aged between 3 and 12 years with mean of (7.6±2.3) years, and the course of disease ranged from 3 to 10 months with mean of (5.6±1.5) months, with follow up of 36-48 months (mean, (41.2±3.4) months). Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Cobb angle, local kyphosis and function changes of spinal nerve cord before and after the operation, as well as fusion of bone graft the complications postoperative were observed. Results Three months after the operation, the ESR, CRP, Cobb angle and local kyphosis in patients were all significantly improved than those before the operation (20.2±5.8) mm/1 h vs. (50.2±13.3) mm/1 h, t=16.668, P<0.01; 8 (2, 10) mg/L vs. 20 (4, 30) mg/L, Z=-6.742, P<0.01; (11.6±3.7)° vs. (25.2±6.7)°, t=10.334. P<0.01; (35.6±5.4)° vs. (15.2±4.7)°, t=23.500, P<0.01). Change of spinal cord nerve function before the operation were found in 54 children (79.4%), however, the number was significantly decreased to 8 (11.8%) at the last visit (χ²=62.724, P<0.01). The bone graft fusion of all the 68 children reached the BridwellⅠ, and the fusion rate was 100% with duration of 3 to 11 months (mean, (6.6±2.1) months). Until the last follow-up, there were totally 4 cases (5.9%) suffering postoperative complications and getting better after receiving treatment. Conclusion Based on the usage of effective anti-tuberculosis medicines, stage Ⅰ anterior-posterior approach surgery could effectively improve the lumbar kyphosis deformity and nerve function of the tuberculosis children. The rate of bone graft fusion was high and occurrence of postoperative complications is rare, the clinical effect is significant.

Analysis of clinical features and influencing factors of prognosis in 222 children with tuberculous meningitis

YANG Ru-ling, LONG Xiao-ru, ZHANG Zhen-zhen, ZHEN Gai-huan, ZHAO Rui-qiu, XU Hong-mei

Chinese Journal of Antituberculosis. 2020, 42(10):  1053-1060.  doi:10.3969/j.issn.1000-6621.2020.10.009

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Objective To explore clinical features and influencing factors of prognosis in children with tuberculosis meningitis (TBM). Methods According to the diagnostic criteria, 222 TBM children from the Children’s Hospital affiliated to Chongqing Medical University from January 2015 to January 2019 were included. Univariate analysis and multivariate logistic regression analysis were used to evaluate the clinical indicators and influencing factors of prognosis in TBM children. Results Of the 222 cases, 129 (58.11%) had good prognosis, while 93 had bad prognosis, of whom 7 died; 117 (52.70%) were boys, 107 (48.20%) aged <5 years with the median of 6 years; 108 (48.65%) cases had a history of close contact with TB patients, duration of the diagnosis were over 21 days in 110 cases (49.55%) and 137 (61.71%) cases suffered malnutrition;in 205 cases (92.34%), tuberculosis lesions were found in 2 or more parts or organs, and pulmonary tuberculosis were the most common complication (n=200, 90.01%); 144 cases (64.87%) were at stage Ⅱ and stage Ⅲ TBM (according to GCS score). By multivariate logistic regression analysis, it was found that high cerebrospinal fluid (CSF) glucose and chloride were protective factor of the prognosis of TBM children (OR (95%CI)=0.444 (0.257-0.769);OR (95%CI)=0.914 (0.854-0.980)),the higher the CSF glucose and chloride, the better the prognosis. High incidence rates of consciousness disturbance, personality change,hydrocephalus and obstructive hydrocephalus were the risk factors of prognosis (OR (95%CI)=6.969 (2.283-21.277);OR (95%CI)=2.531 (1.105-5.796);OR (95%CI)=3.429 (1.546-7.604);OR (95%CI)=10.233 (1.059-98.886)). Conclusion Both the poor prognosis and mortality were high in TBM children. The detection of history of close contact with TB patients and tuberculosis in some other organs would help to diagnosis at early stage. Improvement of malnutrition and decreasement of cerebral effusion were good for prognosis.

Analysis of clinical characteristics and curative effect in 17 urinary tuberculosis children

ZHANG Feng, WANG Man-zhi, WEI Song-qing, ZHANG Xiao-fo, ZHOU Hai-yi

Chinese Journal of Antituberculosis. 2020, 42(10):  1061-1067.  doi:10.3969/j.issn.1000-6621.2020.10.010

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Objective To explore the clinical characteristics and curative effect in urinary tuberculosis children, and to improve pediatricians’ awareness of this disease. Methods Clinical data of 17 urinary tuberculosis children, who were admitted to Department of Pediatric Tuberculosis, Changsha Central Hospital, University of South China from January 2015 to January 2020 and met the diagnostic criteria, were collected for descriptive statistical analysis. Results The 17 cases were from all parts of Hu’nan Province, 15 were rural cases, and 11 were boys. The median age (quartile) was 11.0 (8.5, 16.5) years. Sixteen cases had been vaccinated with BCG, and 6 cases had a clear history of exposure to pulmonary TB. Numbers of cases who complicated with pulmonary tuberculosis, tuberculous meningoencephalitis, tuberculous spinal meningitis, or abdominal tuberculosis were 14, 8, and 7, respectively. 12 cases had urinary system symptoms, including 11 cases of frequent urination, urgency, and painful urination; night sweats were found in 9 cases and 8 cases suffered fever. The abnormal urine routine were found in 12 cases, the PPD test and T-SPOT.TB were positive in 9 and 12 cases, respectively. CT scans of the urinary system showed typical manifestations of tuberculosis, urinary system involvement, and bladder wall thickening in 15, 15 and 9 cases, respectively. All children were delayed in diagnosis, and the delay time was 15 days to 9 months; they were all treated with the H-R-Z-E anti-tuberculosis as basic plan (intensive period of 3 to 6 months and consolidation period of 12 to 15 months), only 1 case who complicated with primary epilepsy changed isoniazid to pasiniazid, and used the first- and second-line anti-tuberculosis drugs (such as prothionamide, streptomycin, levofloxacin, linezolid) in combination according to the condition or effect. Finally, 6 cases were cured, 9 cases improved and continued treatment, 2 cases died. Conclusion Children with urinary tuberculosis in this province are more common in rural areas, and mainly are boys, and elder children. BCG vaccination is not protective to them. Obvious history of close contact with tuberculosis, urinary system symptoms and tuberculosis of other organs, positive in PPD test and T-SPOT.TB, CT scan with suspicious typical lesion changes are helpful to diagnosis. The curative effect is good after active treatment.

A cross-sectional survey of the awareness of pediatric medical personnel on tuberculosis prevention and control in Zhejiang province

YU Gang, HU Xiao-guang, LIN Li, LYU Fang-fang, LI Chang-chong, ZHANG Hai-lin

Chinese Journal of Antituberculosis. 2020, 42(10):  1068-1074.  doi:10.3969/j.issn.1000-6621.2020.10.011

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Objective To investigate the awareness of pediatric medical personnel on tuberculosis prevention and control in Zhejiang province, and provide basement for formulating the strategy for prevention and treatment of pediatric tuberculosis and the tuberculosis training plan. Methods The anonymous online questionnaire of “The status of diagnosis and treatment of tuberculosis in childhood” includes three parts, the status of the diagnosis and treatment of tuberculosis in children in medical institutions, the awareness of the new theory of tuberculosis, and the prevention and control of tuberculosis in students. A total of 1609 pediatric doctors and nursesfrom the general hospitals with pediatrics, children’s hospitals, maternal and child health hospitals, public health centers and community health service centers at all levels in zhejiang province were selected between March 31 to April 8, 2020. Of the 1609 questionnaires, 1199 were valid, the effective rate was 74.52%. Results Among the 1199 respondents, 524 (43.70%) had received tuberculosis knowledge training; 1148 (95.75%) considered that it was necessary to receive tuberculosis knowledge training, while 51 (4.25%) considered that it was unnecessary or irrelevant. “World Tuberculosis Day” was best known (73.31%, 879/1199), while the number of respondents who know “Tuberculosis classification (WS 196-2017)” was smallest (48.79%, 585/1199). The correct ratios of answers to the five questions including tuberculosis classification, pulmonary tuberculosis classification, diagnosis methods of tuberculosis, criteria of tuberculosis infection, as well as latent tuberculosis infection and the prevention and treatment for it were 17.76% (213/1199), 9.92% (119/1199), 36.78% (441/1199), 43.62% (523/1199) and 57.46% (689/1199), respectively. Of the respondents, only 134 (11.18%) knew “key points of student tuberculosis management”. There were 90.43% (737/815), 95.83% (781/815) and 94.11% (767/815) of the pediatricians supported whether new students need tuberculosis screening, whether close contact classmates need to be screened by tuberculin purified protein derivative (PPD), and whether pediatricians need to participate in prevention and control of tuberculosis in studentswhile the rates in nurses were 92.71% (356/384), 95.83% (368/384) and 94.27% (362/384), respectively. Conclusionediatric medical personnel had high awareness of prevention and treatment of tuberculosis in students; however, the awareness of tuberculosis prevention and treatment policies and the knowledge of tuberculosis diagnosis and treatment were not satisfactory. Pediatric medical personnel should strengthen the training of tuberculosis prevention and control, improve the diagnosis and treatment level, and actively participate the prevention and control of tuberculosis in children.

Analyses of clinical features and lymphocyte subsets in patients with pulmonary tuberculosis complicated with diabetes mellitus

LIANG Jian-qin, BAI Xue-juan, WANG Jin-he, CHEN Zhi, GUO Dong-lin, WU Xue-qiong

Chinese Journal of Antituberculosis. 2020, 42(10):  1075-1079.  doi:10.3969/j.issn.1000-6621.2020.10.012

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Objective To investigate the clinical features and lymphocyte subsets in patients with pulmonary tuberculosis complicated with diabetes mellitus (PTB-DM). Methods A total of 85 PTB-DM patients who were hospitalized from April 1, 2018 to May 31, 2019 were enrolled as the PTB-DM group, and 96 PTB patients hospitalized at the same time were selected as the PTB group. Clinical features including gender, age, treatment history, chest CT examination, and lymphocyte subsets absolute counts and Mycobacterium tuberculosis-specific T cells response were compared between the two groups. Results Males and females were 76.4% (65/85) and 23.6% (20/85) respectively in PTB-DM group, while those were 57.3% (55/96) and 42.7% (41/96) respectively in PTB group (χ ²=7.42, P=0.006).2.4% (2/85), 68.2%(58/85) and 29.4% (25/85) of the patients were <25, 25-60 and >60 years old in PTB-DM group, respectively, while 25.0% (24/96), 63.5%(61/96) and 11.5% (11/96) were in PTB group, respectively, with significant difference (χ ²=23.55, P=0.000). The rate of initial- and retreatment patients were 74.1% (63/85) and 25.9% (22/85) in PTB-DM group, and those were 84.4% (81/96) and 15.6% (15/96) in PTB group, respectively, with no significant statistical difference (χ ²=2.92, P=0.088). In PTB-DM group, the rate of no cavity, cavity, lesion area <3 lobes and ≥3 lobes in chest CT were 23.5% (20/85), 76.5% (65/85), 31.8% (27/85) and 68.2% (58/85), respectively, while those were 53.1% (51/96), 46.9% (45/96), 54.2% (52/96) and 45.8% (44/96) respectively in PTB group. The patients with cavity and lesions ≥3 lobes in chest CT in PTB-DM group was significantly higher than those in PTB group (χ ²=16.56, P=0.000 and χ ²=9.20, P=0.002). The positive rate of Mycobacterium tuberculosis-specific T cell reaction was 81.3% (65/80) in PTB-DM group, and that was 74.2%(66/89)in PTB group, with no significant difference (χ ²=1.22,P=0.270).The median of absolute counts of total T lymphocytes, CD4⁺, CD8⁺, NK-like T lymphocytes, natural killer cells (NK cells) and total B lymphocytes in the PTB-DM group were 1069.00(753.50,2372.50), 548.00(381.00,787.50), 380.00(270.50,574.50), 60.00(36.00,120.50), 184.00(111.00,294.50) and 162.00(80.50,244.00)/μl, respectively, while those in PTB group were 1161.50(858.50,1601.00), 628.00(472.75,860.50), 457.50(286.00,614.75), 65.50(34.50,119.50), 191.50(115.75,315.75)and 184.50(112.25,301.00)/μl, respectively. There were no significantly statistical difference in the six indexes between the two groups(Z=-1.80,P=0.073;Z=-1.47,P=0.142;Z=-1.46,P=0.144;Z=-0.09,P=0.931;Z=-0.57,P=0.568;Z=-1.93,P=0.053). Conclusion There were more middle-aged and elderly men, and extensive, serious lesions in PTB-DM group. PTB with or without DM had no significant effect on the detection results of lymphocyte subsets.

Correlation analysis between clinical characteristics and flow cytometry cells subsets in peripheral blood of patients with pulmonary tuberculosis

MAO Yi, ZENG Yi-lan, WU Gui-hui, JIANG Zhi-hao, FAN Lin

Chinese Journal of Antituberculosis. 2020, 42(10):  1080-1086.  doi:10.3969/j.issn.1000-6621.2020.10.013

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Objective To understand the correlations between clinical characteristics of patients with pulmonary tuberculosis (PTB) and flow cytometry subsets of T cells and natural killer (NK) cells. Methods One thousand continuously admitted patients diagnosed as PTB in Shanghai Pulmonary Hospital from January 1, 2019 to May 25, 2019 were retrospective enrolled for analysis. Multiple linear stepwise regression models were established with Eviews 8.0 software to determine the correlations between clinical characteristics and values of flow cytometry cell subsets in peripheral blood. Results (1) The degree of lung lesion range and acid-fast staining smear from respiratory specimens in patients with PTB were positively related with the frequency of CD3⁺ T cells: the larger lung lesion range and the higher the positive degree of acid-fast staining smear, the lower the frequency of CD3⁺ T cells was(regression coefficient was -0.255 and -0.499 respectively, P value was 0.021 and 0.027 respectively). (2) Age, gender and tuberculosis molecular biological detection results of patients were related to the frequency of CD4⁺ T cells: the number of CD4⁺ T cells in patients aged less than 20 years was lower than that in patients with older age groups (regression coefficient -4.710, P=0.031). The frequency of CD4⁺ T cells in male patients was lower than that in female patients (regression coefficient -2.150, P=0.001). The frequency of CD4⁺ T cells in patients with positive PCR test was higher than that in patients with negative PCR test (regression coefficient 1.433, P=0.030). (3) The frequency of CD8⁺ T cells in patients with initial treatment was higher than that in patients with retreatment (regression coefficient 1.247, P=0.029). The higher the positive degree of acid-fast staining smear, the higher the frequency of CD8⁺ T cells was (regression coefficient 0.442, P=0.033). (4) The frequency of NK cells of patients with extrapulmonary tuberculosis (EPTB) was lower than those without EPTB (regression coefficient 0.375, P=0.030). Conclusion The degree of pulmonary lesions and positive acid-fast staining from respiratory tract specimens in patients with PTB were correlated with frequency of CD3⁺ T cells. Age, sex and tuberculosis molecular biological detection results were correlated with the frequency of CD4⁺ T cells. CD8⁺ T cells was correlated with initial treatment and positive acid-fast staining. There was a correlation between frequency of NK cells and patients with PTB coexisted with EPTB.

Analysis of three immunological indicators in rheumatic patients complicated with pulmonary tuberculosis

SHI Qian, CHEN Zhi

Chinese Journal of Antituberculosis. 2020, 42(10):  1087-1091.  doi:10.3969/j.issn.1000-6621.2020.10.014

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Objective To investigate the characteristics of immunological indicators of rheumatic patients complicated with pulmonary tuberculosis. Methods A total of 117 rheumatic patients complicated with pulmonary tuberculosis from PLA Institute of Tuberculosis, the 8th Medical Center of Chinese PLA Hospital between July 2017 and July 2019 were selected as the observation group, and 117 patients with pulmonary tuberculosis alone during the same period were randomly selected by systematic sampling method as the control group. The positive rate of TB antibody test, the positive rate of IGRA and the count of T lymphocyte subsets of the two groups were compared. Results The positive rates of TB antibody (38 kD+16 kD)(1 kD=1000 relative molecular mass) and TB antibody 38 kD in the observation group were significantly lower than those in the control group (6.84% (8/117) vs. 33.33% (39/117), χ ²=25.59, P=0.000;21.37% (25/117) vs. 71.79% (84/117), χ ²=59.78, P=0.000). The difference of positive rate of IGRA in two groups was not significant (57.26% (67/117) in the observation group and 55.56% (65/117) in the control group, χ ²=0.70, P=0.792). As to the detection of lymphocyte subsets, peripheral blood CD4 ⁺ cell count (median (quartiles)) and CD4⁺/CD8⁺ value (median (quartiles)) in the observation group were significantly higher than those in the control group (513.00 (339.75, 844.50)/μl vs. 380.00 (320.00, 503.00)/μl, Z=2.11, P=0.035; 0.96 (0.74, 1.53) vs. 0.91 (0.74, 0.96), Z=4.90, P=0.000). However, peripheral blood CD8⁺ cell count (median (quartile)) in the observation group was significantly lower than that in the control group (377.50 (193.00,528.50)/μl vs. 475.00 (410.00,524.00)/μl, Z=2.27, P=0.023). Conclusion Compared to those of patients with pulmonary tuberculosis alone, the positive rate of TB antibody and CD8⁺ cell count in peripheral blood in rheumatic patients complicated with pulmonary tuberculosis were lower, while the CD4⁺ cell count in peripheral blood of rheumatic patients complicated with pulmonary tuberculosis was higher. The difference of positive rate of IGRA between rheumatic patients complicated with pulmonary tuberculosis and patients with tuberculosis alone was not significant.

Evaluation of treatment effect and safety of rifampicin capsule (Ⅱ) on pulmonary tuberculosis

LIU Er-yong, ZHOU Lin, XUE Xiao, LIU Chun-fa, BAI Li-qiong, LU Wei, ZHANG Tian-hua, CHENG Shi-ming

Chinese Journal of Antituberculosis. 2020, 42(10):  1092-1099.  doi:10.3969/j.issn.1000-6621.2020.10.015

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Objective Our aim was to evaluate the clinical efficacy and safety of rifampicin capsule (Ⅱ) (rifampicin capsules embedded by fatty acid matrix) in treatment of pulmonary tuberculosis. Methods In March 2017, Chinese Anti-tuberculosis Association selected 8 designated TB hospitals in 6 provinces from Jiangsu, Shandong, Liaoning, Hunan, Hebei and Shaanxi as the field study implementation units through the method of random number table according to the regions from east, middle or west. From June to December in 2017, each implementing unit enrolled 644 patients in accordance with the inclusion criteria and adopted the continuous inclusion method. Ultimately newly discovered TB patients were assigned into two groups after eliminated invalid data: observated group 330 cases (the rifampicin capsules (Ⅱ) (0.45 g/d, empty stomach, one suit))and the control group 314 cases(the rifampicin capsules (0.6 g/d, empty stomach, one suit)) according to the method of random number table. The two groups all were treated with 2H-R-Z-E/4H-R chemotherapy regimens, all other drugs were the same except rifampicin. During the implementation of the project, if patients fail to complete treatment due to rifampicin resistance or multi-drug resistance or other reasons such as diagnostic changes, they will be included in the withdrawal group. The outcomes of anti-tuberculosis treatment, improvements of tuberculosis-related symptoms, imaging changes of pulmonary lesions, changes of sputum smear, liver and kidney function injury, hemocytopenia and total adverse events in the two groups were observed. SPSS 19.0 software was used for statistical analysis of the data. Chi-square test, Fisher exact probability method or rank sum test were used for enumeration data, and P<0.05 was considered as statistically significant. Results No statistically significant differences between observed group in the outcomes of treatment success (77.6% (256/330)), failure (0.6% (2/330)), loss or death (10.3% (34/330)), withdrawal (11.5% (38/330)) and control group (77.1% (242/314), 0.6% (2/314), 8.9% (28/314), 13.4% (42/314), respectively)(Fisher’s exact probability method, P=0.874). After finishing treatment, in the observed group and the control group, there were no statistically significant differences in cough (91.4%(267/292)and 88.2%(240/272)), fatigue (99.3% (290/292) and 98.2% (267/272)), body mass reduction (100.0% (292/292) and 99.3% (270/272)), fever (100.0% (293/293) and 99.6% (277/278)), the absorption efficiency of TB foci (87.6% (212/242) and 84.1% (196/233)), the cavity improvement rate (57.0% (138/242) and 49.4% (115/233)), and sputum smear positive rate (0.5%(1/210) and 1.0%(2/192)) (χ²=1.590, P=0.207; χ ²=0.732, P=0.392; Fisher’s exact probability method, P=0.234; Fisher’s exact probability method, P=0.487; χ ²=1.189,P=0.276;χ²=2.804,P=0.094; χ²=0.006, P=0.938). The incidence of total adverse events, liver injury and renal function injury in the observed group and the control group (43.3% (143/330) and 44.9% (141/314), 16.7% (55/330) and 18.5% (58/314), 23.6% (78/330) and 24.8% (78/314), respectively)were no statistically significant (χ ²=0.161, 0.362, 0.127, P=0.688, 0.547, 0.721). However, the incidence of reduced blood routine indicators in the control group (26.4% (83/314)) was higher than that in the observed group (17.9% (59/330)) (χ ²=6.850,P=0.009). Conclusion The anti-tuberculosis efficacy and safety of rifampicin capsule (Ⅱ) are not lower than rifampicin capsule, but with a lower dose. This drug provides a new direction for the selection of anti-tuberculosis drugs in China.

Metagenomic analysis of respiratory tract microbial flora distribution characteristics in pulmonary tuberculosis patients

QIU Qian, LIU Dong-xin, LIU Chun-fa, QIU Jie, YAN Xiao-feng, ZHAO Yan-lin

Chinese Journal of Antituberculosis. 2020, 42(10):  1100-1108.  doi:10.3969/j.issn.1000-6621.2020.10.016

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Objective To investigate changes in respiratory microbial flora composition in pulmonary tuberculosis patients and healthy individuals. Methods Multiple Chinese and English databases were searched with keywords “tuberculosis” and “respiratory tract flora”. Publications between 2010 and 2019 were selected according to literature screening procedure and then included. All available next-generation sequencing data were collected, parameters unified, data pre-processed and then used for metagenomic analysis and statistical processing. Results Nine English literatures were included. Species analysis suggested that the top 10 most abundant bacterial groups in both tuberculosis group and healthy control group were: Firmicutes, OD1, Proteobacteria, Bacteroidetes, Actinobacteria, and Fusobacteria, Cyanobacteria. However, there were significant differences in the composition of respiratory bacterial flora between the two groups. α diversity analysis showed that the number of OTUs (286.60±22.82), Faith ‘s PD index (13.57±2.58), and Shannon index (7.17±0.24) observed in tuberculosis group were significantly higher than those of healthy control group (42.88±2.49, 6.52±0.22, 4.42±0.07, respectively), which was statistically significant (P=0.00016,0.00056,0.00016). Chao1 index of tuberculosis group was higher than healthy control group (266.50±92.71 vs. 38.44±2.86), without statistical significance (P>0.05). Six phyla were found to have different abundance in the two groups, 5 of which were clustered in healthy controls: Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria and Fusobacteria, the other one-OD1 clustered in tuberculosis group. F16 family, Gammaproteobacteria, Firmicutes phylum, Leuconostocaceae family and Bacilillaceae family were found to be tuberculosis-specific. Conclusion Compared with healthy people, there are significant changes in respiratory tract flora diversity and species composition in tuberculosis patients, with presence of unique flora.

Effect of full-time health education nurses in the tuberculosis ward

CHEN Xiao-feng, PENG Le, LIU Ji-xing, YU Lei, WANG Xiu-hua

Chinese Journal of Antituberculosis. 2020, 42(10):  1109-1114.  doi:10.3969/j.issn.1000-6621.2020.10.017

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Objective To explore a health education model with low investment and high benefit by analyzing the intervention effect of full-time health education nurses on tuberculosis patients. Methods To collect 340 TB patients from June to December 2018 and 300 TB patients January to June 2019, which were hospitalized in the Tuberculosis Department of Beijing Chest Hospital and of them 12 and 4 deaf mute, foreign and invalid patients were excluded respectively. Finally, 328 cases (control group, health education provided by responsible nurses) and 296 cases (cohort group, health education provided by full-time health education nurses) were finally included. The data were collected by questionnaires and follow-up after discharge(return visit). Questionnaires included health education knowledge evaluation form (including 20 choice questions with tuberculosis prevention and control core information and key points, among of them 5 points for correct answer and 0 points for wrong answer; 100 points for full score) and health education satisfaction questionnaire (including 15 questions with admission propaganda and education, disease knowledge, discharge guidance and service attitude; select very satisfied, general and dissatisfied for 3 points, 2 points and 1 point respectively; 45 points for full score).And then to compare the awareness of health education knowledge (including awareness rate and average score of evaluation), and patient satisfaction and follow-up compliance (including timely return visit, late return visit and never return visit; the rate of timely return visit as the good follow-up compliance). Results The average score of health education knowledge evaluation (92.42±5.64) and total awareness rate (92.41% (5471/5920)) for cohort group were significantly higher than control group (67.52±9.14,67.74% (4444/6560))(t=-41.004,P<0.001;χ²=2520.110,P<0.001). The scores of health education satisfaction (7.70±0.86), disease knowledge (17.53±1.25), discharge guidance (7.70±0.84) and service attitude (5.07±0.73) for cohort group were higher than those in control group (7.02±0.80, 16.14±1.25, 7.06±0.85 and 4.30±0.55,respectively) (t=-9.700,-13.364,-9.531,-15.387, all P<0.001). The compliance of follow up on time strictly for cohort group(86.82%(257/296)) was significantly higher than control group (55.79%(183/328))(χ²=73.760,P<0.001). Conclusion The full-time health education nurses can improve the awareness rate of health education, health education quality, nursing satisfaction and treatment compliance of patients, which is worthy of promotion in tuberculosis ward.

Prediction of usage and mechanism of Traditional Chinese Medicine in treating pulmonary tuberculosis

LI Ting-ting, LIU Huan-qing, DU Qiao-ying

Chinese Journal of Antituberculosis. 2020, 42(10):  1115-1120.  doi:10.3969/j.issn.1000-6621.2020.10.018

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Objective To explore the usage of Traditional Chinese Medicine (TCM) in treating pulmonary tuberculosis and the mechanism of frequently used TCM. Methods The relevant Chinese literatures were collected from CNKI database and Wanfang Med Online with the keywords of “pulmonary tuberculosis” and “traditional Chinese medicine”; the foreign literature was collected from PubMed database with the keywords of “tuberculosis” and “traditional Chinese medicine”; the published time was limited from January 1, 1998 to December 31, 2018. A total of 512 related articles were retrieved (405 Chinese literatures, 107 foreign literatures), and 363 articles were included (352 Chinese literatures, 11 foreign literatures) finally. Rapidminer software was used to extracted the information, to explore the key TCM and the common combination for treating tuberculosis, the usage and combination of drugs were analyzed. BATMAN-TCM database was used to obtain the potential active ingredients and targets of frequently used TCM, and the DisGeNET database, Therapeutic Target Database (TTD) and Gene Cards database were used to predict and screen the targets of key TCM for the treatment of tuberculosis, and the drug targets and disease targets were matched. DAVID database was used to analyze the GO (Gene Ontology) biological function and Kyoto Encyclopedia of Genes and Genomes (KEGG). Results Tonic (663 times), activating blood circulation (403 times) and heat-clearing medicines (325 times) were mainly used to treat pulmonary tuberculosis. The most frequently used medicines were liquorice (122 times), chiretta (102 times), rehmanniae praeparatum (99 times) and paeoniae alba (74 times). The most frequently used two-drug pair compatibility were liquorice-chiretta (70 times) and liquorice-rehmanniae praeparatum (52 times). The liquorice-chiretta-rehmanniae praeparatum was the most frequently used three-drug pair (37 times), and liquorice-chiretta-rehmanniae praeparatum-paeoniae alba was used most as four-drug pair (24 times). When rehmanniae praeparatum compatible with paeoniae alba, the usage rate of chiretta was 95.0%. A total of screened 92 key targets against tuberculosis of 4 frequently used TCM (liquorice, chiretta, rehmanniae praeparatum, paeoniae alba) were found, which may play the role of anti-tuberculosis through cancer pathways (14 targets), leukocyte trans-endothelial migration (13 targets), natural killer cell mediated cytotoxicity (10 targets), and ErbB signaling pathway (10 targets). Conclusion The treatment of tuberculosis mainly use consists of tonic, activating blood circulation and heat-clearing medicines. Liquorice, chiretta, rehmanniae praeparatum and paeoniae alba could be used in clinical treatment. The mechanism of these 4 frequently used TCM in treating tuberculosis may be act through cancer pathway, leukocyte trans-endothelial migration pathway, natural killer cell mediated cytotoxicity pathway and ErbB signaling pathway.

Establishment and effect evaluation of polymerase spiral reaction for detection of Mycobacterium tuberculosis

MA Xiao-guang, SHI Jie, XU Xing-yong, ZHU Yan-kun, WANG Shao-hua, ZHENG Dan-wei, SUN Guo-qing, SUN Ding-yong, SU Ru-yue

Chinese Journal of Antituberculosis. 2020, 42(10):  1121-1127.  doi:10.3969/j.issn.1000-6621.2020.10.019

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Objective Establishment of polymerase spiral reaction (PSR) assay for detection of Mycobacterium tuberculosis (MTB) and evaluate its effect. Methods The PSR primers targeting the specific genes IS 6110 of MTB were designed. The genomic DNA of MTB was extracted and added into RM2 × reaction solution containing Bst DNA polymerase. The reaction was carried out at 63℃ for 45 min and detected by fluorescence quantitative PCR. By optimizing the primer sequence, the best one was selected, and its specificity and minimum detection limit were evaluated. A total of 200 sputum samples were collected from Zhengzhou Sixth Peoples Hospital during May 2019 to August 2019, and three copies were collected from the same patient. Sputum smear and sputum culture, as well as PSR detection were performed on sputum samples. Sputum culture was used as the gold standard to evaluate the effectiveness of PSR in detecting tuberculosis patients. Results A set of PSR primers for detection of MTB was screened by optimizing the primer sequence, the limit detection of PSR application to MTB was 10 ³ CFU/ml. The detection specificity experiment showed that the method had no cross-reactivity with 15 strains of non-tuberculous mycobacteria. Among 200 pulmonary tuberculosis patients, 48 cases were positive in sputum smears, and the positive detection rate was 24.0% (48/200); 83 cases were positive in sputum culture test, and the positive detection rate was 41.5% (83/200); 87 cases were positive in PSR test, and the positive detection rate was 43.5% (87/200). Compared with the gold standard method, the results of 200 clinical samples test showed that the sensitivity, specificity and positive predictive value, negative predictive value were 96.4%(80/83),94.0%(110/117),92.0%(80/87),97.3%(110/113), respectively, which were consistency to sputum culture detection method (Kappa value was 0.898). Conclusion PSR detection is suitable for the rapid diagnosis of MTB.

Review Articles

Research progress on the non-specific protective effect of BCG

CHEN Ning, SUN Lin, SHEN A-dong, HE Qiu-shui

Chinese Journal of Antituberculosis. 2020, 42(10):  1128-1133.  doi:10.3969/j.issn.1000-6621.2020.10.020

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In addition to the protection against tuberculosis, bacillus Calmette-Guérin (BCG) can induce non-specific protective effect (NSE). The results obtained by various epidemiological studies showed that BCG can provide certain protection against other pathogen infections and can effectively improve the survival rate of children. Some of those results had been verified by randomized clinical trials. In this review, the author will summarize the related epidemiological research results and the mechanisms of the NSE.

Interpretation of Standards

Interpretation of the Employees Health Examination Specification-Tuberculosis Examination

XU Cai-hong, ZHANG Hui, LIU Jian-jun

Chinese Journal of Antituberculosis. 2020, 42(10):  1134-1136.  doi:10.3969/j.issn.1000-6621.2020.10.021

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In order to standardize the tuberculosis health examination of employees, the Chinese Anti-tuberculosis Association issued Employees Health Examination Specification-Tuberculosis Examination (T/CHATA002-2020) on July 7th, 2020. The specification stipulates the agency qualification, examination items, examination algorithm, handing of inspection results and file management of employee’s tuberculosis examination, and integrates the concept of health management. This specification is the first released standardization in this field, it will guild and further standardize the employee’s tuberculosis examination, move forward the prevention and control threshold of tuberculosis, reduce the risk of infection and transmission of tuberculosis among employees, thus effectively reduce the probability of public health emergencies among employees.