Table of Content

10 May 2020, Volume 42 Issue 5

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Guideline·Standard·Consensus

Guideline for clinical application of clofazimine in the treatment of tuberculosis

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

Chinese Journal of Antituberculosis. 2020, 42(5):  409-417.  doi:10.3969/j.issn.1000-6621.2020.05.001

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Clofazimine, as one of the core drugs for the treatment of drug-resistant tuberculosis, lacks regulatory guideline. The Clinical Trial Branch of the Chinese Antituberculosis Association and the Editorial Board of Chinese Journal of Antituberculosis organized relevant experts to develop this guideline. This guideline formulated the molecular structure, mechanism of action, pharmacodynamics and pharmacokinetics, mechanism of drug resistance, indications and contraindications, dosage, chemotherapy regimen, adverse effect and precautions for clinical application to guide the clinical application for different population with clofazimine in practice.

Experts’ consensus on the diagnosis and treatment of patients with spinal tuberculosis complicated with HIV/AIDS

The Joint Tuberculosis Professional Branch of Chinese Antituberculosis Association, the Western China Bone Tuberculosis Alliance, the North China Bone Tuberculosis Alliance, Editorial Board of Chinese Journal of Antituberculosis

Chinese Journal of Antituberculosis. 2020, 42(5):  418-424.  doi:10.3969/j.issn.1000-6621.2020.05.002

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Patients with spinal tuberculosis complicated with HIV/AIDS have multiplied the difficulty of treatment due to low immune function. To standardize the procedures for diagnosis and treatment in patients with spinal tuberculosis complicated with HIV/AIDS, and to increase peer awareness of the details of the treatment of such diseases, and to have a reliable basis for their treatment, we organized the Professional Branch of Chinese Antituberculosis Association, the Western China Bone Tuberculosis Alliance, the North China Bone Tuberculosis Alliance and the Editorial Board of Chinese Journal of Antituberculosis to jointly develop the experts’ consensus on the diagnosis and treatment of patients with spinal tuberculosis complicated with HIV/AIDS. Some items including the epidemiological background, the common clinical manifestations, laboratory examination, diagnostic criteria, drugs usage, surgical treatment, occupational exposure during surgery,announcements and relative research have been formulated and discussed on these patients with spinal tuberculosis complicated with HIV/AIDS in this experts’ consensus.

Expert Forum

Overview situation and progress of diagnosis and treatment in patients with spinal tuberculosis and HIV/AIDS co-infection

PU Yu, HUAN Ming-cang

Chinese Journal of Antituberculosis. 2020, 42(5):  428-435.  doi:10.3969/j.issn.1000-6621.2020.05.004

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At present, the number of patients with spinal tuberculosis (TB) and HIV/AIDS co-infection is increasing year by year. However, the clinical health workers are lack of knowledge on the disease and the latest diagnosis and treatment methods of this disease. In view of this, the author reviewed the new diagnosis techniques, new anti-tuberculosis drugs and treatment regimens, the progress of the highly active antiretroviral therapy (HAART) and the new surgical methods, intraoperative protection of the patients with spinal tuberculosis complicated with HIV/AIDS, as well as the latest research directions, and then made a brief summary. It is hoped that, a certain extent, this paper would be helpful for the health workers to unify their understanding on the disease and improve their diagnosis and treatment level of the disease.

Expert Note

Current status and progress of surveillance and automated-alert for tuberculosis in school

CHENG Jun, LIU Jian-jun

Chinese Journal of Antituberculosis. 2020, 42(5):  436-441.  doi:10.3969/j.issn.1000-6621.2020.05.005

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Tuberculosis (TB) control in school is always a key point in China, and active surveillance and timely alert are very important for response. This article described the epidemic and characteristic of TB in students, outlined the requirements for TB surveillance and automated-alert systems,analyzed the performance and effect of China Infectious Disease Automated-alert System implementing for TB control in school, and put suggestions for data usage.

Current situation and prospect of laboratory diagnosis of tuberculous meningitis

LI Zi-hui, ZHANG Zong-de

Chinese Journal of Antituberculosis. 2020, 42(5):  442-448.  doi:10.3969/j.issn.1000-6621.2020.05.006

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Tuberculous meningitis (TBM) is the most serious and common form of central nervous system tuberculosis. Rapid diagnosis and timely treatment are the key to improve the prognosis and survival rate of patients. However, the definite diagnosis of TBM is still extremely difficult due to the lack of effective detection methods. This article discussed the current situation, the latest progress as well as the problems and challenges of TBM laboratory diagnosis, and called for cooperation to further strengthen the research on laboratory diagnosis of TBM.

Original Articles

Clinical characteristics of HIV-positive spinal tuberculosis patients and effect analysis of strengthening perioperative management

LI Bang-yin, PU Yu, HE Min, HE Lei, HUAN Ming-cang, CAI Yu-guo, LIU Lin, JIANG Xi

Chinese Journal of Antituberculosis. 2020, 42(5):  449-453.  doi:10.3969/j.issn.1000-6621.2020.05.007

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Objective To analyze the disease characteristics of HIV-positive spinal tuberculosis patients and the effect of strengthening perioperative management. Methods Using retrospective analysis, 23 cases of HIV-positive spinal tuberculosis treated in Chengdu Public Health Clinical Medical Center from January 2014 to January 2018 were enrolled as HIV-positive group, 316 cases of HIV-negative spinal tuberculosis treated in the same period were used as control group. Measurement data was expressed as “ \bar{x} ±s”, comparison between groups was tested by t test; categorical data was expressed as “rate (or composition ratio)”, comparison between groups was tested using χ ², statistically significance was set at P<0.05. Results HIV positive group, PPD test positive rate was 21.7% (5/23), tuberculosis infected T cell spot test positive rate was 47.8% (11/23), tuberculosis antibody test positive rate was 13.0% (3/23), sputum smear acid-fast bacillus test positive rate was 4.3% (1/23), the incidence of concurrent pulmonary tuberculosis was 21.7% (5/23), the typical imaging of spinal tuberculosis were 43.5% (10/23), and the incidence of typical tuberculosis symptoms was 13.0% (3/23), which were lower than the control group (81.0% (256/316), 84.8% (268/316), 28.2% (89/316), 21.2% (67/316), 60.8% (192/316), 82.0% (259/316), 58.9% (186/316)). Except for the positive rate of tuberculosis antibody and sputum smear showed no significant difference (χ ²=42.42, 21.75, P=0.115, 0.051), all others were statistically significant (χ ²=204.99, 232.23, 142.52, 220.68, 132.16, P=0.000). The percentage of patients with CD4 ⁺ T lymphocyte count <350 cells/μl among HIV-positive group was 82.6% (19/23), which was higher than the control group (20.6% (65/316)). The difference was statistically significant (χ ²=52.17, P=0.000). After intensive perioperative management in the HIV-positive group, CD4 ⁺ T lymphocyte counts and serum albumin quantifications, and hemoglobin amounts were (285.17±23.04)/μl, (40.44±0.37) g/L, (129.30±1.72) g/L, getting improved from before implementing intensive perioperative management ((219.83±26.56) pcs/μl, (29.51±0.94) g/L, (97.48±3.16) g/L),the difference was statistically significant (t=-6.804, -10.977, -8.318, P=0.000). The body mass index before and after enhancing perioperative management were 20.84±0.29, 20.85±0.29 respectively, the difference was not statistically significant (t=-0.541, P=0.594). In the HIV-positive group, the drug resistance rate, liver damage rate, tuberculosis unhealed rate, and long-term mortality were 30.4% (7/23), 65.2% (15/23), 8.7% (2/23), 8.7% (2/23), which were higher than the control group (13.0% (41/316), 34.5% (109/316), 0.9% (3/316), 0.6% (2/316)), the differences were statistically significant (χ ²=10.11, 37.71, 15.04, 17.39, P=0.020, 0.006, 0.003, 0.001). Conclusion Most of the clinical test results of HIV-positive spinal tuberculosis patients are worse than those of patients with HIV-negative spinal tuberculosis. By strengthening the perioperative management, the immunological and nutritional indicators of patients have improved.

Observation on the clinical effect of surgical treatment for 23 patients with spinal tuberculosis complicated with AIDS

HE Min, PU Yu, CAI Yu-guo, LI Bang-yin, HE Lei, HUAN Ming-cang

Chinese Journal of Antituberculosis. 2020, 42(5):  454-458.  doi:10.3969/j.issn.1000-6621.2020.05.008

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Objective To explore the clinical effect of surgical treatment for patients with spinal tuberculosis complicated with acquired immune deficiency syndrome (AIDS). Methods Retrospective analysis was used to collect clinical data of 23 patients with spinal tuberculosis complicated by AIDS who underwent surgical treatment from January 2014 to January 2018 in Chengdu Public Health Clinical Medical Center, including operation time, intraoperative blood loss, surgical complications, preoperative and final follow-up visual analogue score (VAS score), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), CD4 ⁺ T lymphocyte count, nerves functional status, as well as bone graft fusion at the last follow-up. The effects of surgical treatment for those study subjects were analyzed. Results All 23 patients successfully completed the operation, with the average operation time of (268.4±11.3) min and the average bleeding volume of (490.6±101.5) ml, and without surgical incision infection. All cases were followed up. The VAS score at the last follow-up was significantly lower than that before surgery (1.0±0.7 vs. 8.2±0.6, t=6.15, P=0.001), and the pain was distinctly improved compared with that before surgery. The nerve function of 4 patients with neurological impairment before surgery completely recovered to normal. After antituberculosis treatment and surgical treatment, the ESR and CRP of the patients at the last follow-up were (9.3±2.6) mm/1 h and (4.8±1.2) mg/L, respectively, which were obviously lower than those before surgery ((79.4±4.6) mm/1 h and (57.5±5.9) mg/L), with the statistically significant differences (t=64.66, P=0.000; t=47.73, P=0.000, respectively). After perioperative management and subsequent comprehensive treatment with highly active anti-retroviral therapy, the CD4 ⁺ T lymphocyte count ((267.5±38.5) cells/μl) was increased at the last follow-up compared with preoperative count ((233.3±41.1) cells/μl), with the statistically significant difference (t=-36.57, P=0.001). All patients with bone graft fusion conformed to the Bridwell Ⅰ-Ⅱ standards. The median time of bone graft fusion was 6 months, and no internal fixator rupture was observed during follow-up. Two patients developed epilepsy 1 day after operation, 5 patients had atelectasis and high fever after operation, 11 patients had abdominal distension after operation, and all of them returned to normal after symptomatic treatment. Conclusion By strengthening perioperative management and rationally choosing surgical timing, patients with spinal tuberculosis complicated by AIDS who received surgical treatment have the better clinical effects.

Analysis of CT features of spinal non-tuberculous mycobacterial disease

LIANG Rui-yun, LI Cheng-cheng, LUO Jie-qi, FANG Wei-jun, REN Hui-li, LI Hui-ru

Chinese Journal of Antituberculosis. 2020, 42(5):  459-464.  doi:10.3969/j.issn.1000-6621.2020.05.009

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Objective To explore the CT features of spinal non-tuberculous mycobacterial disease(spinal NTM disease),in order to improve the diagnosis of spinal NTM disease. Methods A retrospective analysis of 21 patients who diagnosed as spinal NTM disease(study group:11 patients in Guangzhou Chest Hospital and 10 patients in Shenzhen Third People’s Hospital)were collected from Guangzhou Chest Hospital and Shenzhen Third People’s Hospital from January 2015 to December 2018. At the same time,289 patients with spinal tuberculosis who were confirmed by laboratory strain identification and met the inclusion criteria were collected, among them, 53 patients (control group: 39 patients in Guangzhou Chest Hospital and 14 patients in Shenzhen Third People’s Hospital) were selected at the same sex and age to carry out a comparative study.The study compares the CT scanning signs between the two groups,in oder to analyze the CT features of spinal NTM disease. Results The incidence of lesions involving vertebral body ≥3 segments,multi-section (≥2 segments) of vertebral body with multiple forms of destruction without involving the intervertebral disc,osteogenic bone destruction in the study group were 76.19% (16/21), 52.38% (11/21), 57.14% (12/21),respectively,which were 43.40% (23/53), 7.55% (4/53), 9.43% (5/53) in the control group;There were statistically significant differences between the two groups (χ ²=6.489, 16.035, 16.744,respectively;P=0.011,<0.001,<0.001,respectively). The incidence of sequestrum in the area of bone destruction,vertebral collapse, disc destruction, paravertebral abscess, dura and spinal cord compression or invasion in the study group were 42.86% (9/21), 9.52% (2/21), 38.10% (8/21), 33.33% (7/21), 33.33% (7/21),respectively,which were 77.36% (41/53), 49.06% (26/53), 79.25% (42/53), 81.13% (43/53), 75.47% (40/53) in the control group;There were statistically significant differences between the two groups(χ ²=8.170,9.994,11.622,15.681,11.524,respectively;P=0.004,0.002,0.001,<0.001,0.001,respectively). Conclusion The CT scan of spinal NTM disease patients is more likely to see lesions involving vertebral body ≥3 segments,osteogenic bone destruction,multi-section (≥2 segments) of vertebral body with multiple forms of destruction without involving the intervertebral disc;Its CT features are different from those of spinal tuberculosis patients,which can make a contribution for early clinical diagnosis and treatment.

Clinical analysis of hypothyroidism after anti-tuberculosis treatment in patients with multidrug-resistant tuberculosis

ZHAO Ben-nan, LIU Da-feng, LIU Ya-ling, YANG Ming, LAN Li-juan, DU Qing

Chinese Journal of Antituberculosis. 2020, 42(5):  465-471.  doi:10.3969/j.issn.1000-6621.2020.05.010

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Objective To analyze the occurrence and characteristics of hypothyroidism in patients with multidrug-resistant tuberculosis (MDR-TB) after anti-tuberculosis treatment with prothionamide (Pto) and/or para-aminosalicylic acid (PAS). Methods According to the selection criteria, 336 MDR-TB patients both from outpatient and hospitalized in Department of Tuberculosis, the Public and Health Clinic Centre of Chengdu between October 1, 2017 and June 30, 2019 were selected. They were divided into Pto group (n=91, treated only with Pto) and Pto+PAS group (n=245, treated with Pto and PAS). Their thyroid function were tested before anti-tuberculosis treatment and 1, 3, 6, 9, 12, 18, 24 months after anti-tuberculosis treatment. The occurrence rate and time of hypothyroidism, and when treat with Levothyroxine Sodium Tablets, the rate of treantment, treatment effect and the dosage were compared. Results Of the 336 MDR-TB patients, incidence of drug-induced hypothyroidism was 28.87% (97/336); among the 97 patients, myxedema was found in 4, fatigue with hair loss was found in 2, and the other 91 were without any obvious symptoms. The occurrence rate of hypothyroidism was 19.78% (18/91) in Pto group, which was statistically different from that in Pto+PAS group (32.24% (79/245), χ ²=5.020, P=0.025). Hypothyroidism incidence in male group was significantly lower than that in female group (24.07% (52/216) vs. 37.50% (45/120), χ ²=6.772, P=0.009). Occurrence rate of drug-induced hypothyroidism decreased with the treatment duration, rates were 40.20% (39/97), 24.74% (24/97), 17.53% (17/97) and 17.53% (17/97), respectively, 1.5 months, 3 months, 3-6 months, and 6 months after treatment. Occurrence rate of drug-induced hypothyroidism in Pto+PAS group within 1.5 months after treatment was significantly higher than that in Pto group (46.83% (37/79) vs. 11.11% (2/18), Fisher, P=0.018). A total of 78 drug-induced hypothyroidism patients needed to be treat with Levothyroxine Sodium Tablets, and the number of cases from Pto+PAS group was significantly more than that from Pto group (84.81% (67/79) vs. 61.11% (11/18), χ ²=5.227,P=0.022). The dosage of Levothyroxine Sodium Tablets were ≤50 μg/d for 49 patients (62.82%), 51-75 μg/d for 20 patients (25.64%), >75 μg/d for 9 patients (11.54%). Four patients in Pto+PAS group were treated with the dosage of over 125 μg/d, but the effect was little, therefore, the Pto and PAS were discontinued; however, the other 74 patients had better prognosis. Conclusion Hypothyroidism are more likely to occur in MDR-TB patients treated with Pto+PAS than those treated with Pto alone. The incidence of hypothyroidism is high within 3 months after anti-tuberculosis treatment, and thyroid function needs to be closely monitored. If patients with drug-induced hypothyroidism have better prognosis when treated with Levothyroxine Sodium at different dosages, the Pto and PAS could be continued.

Establishment of modified propidium monoazide (PMAxx)-quantitative PCR assay and its application for identification of antituberculosis drug activity

ZHANG Jing, CHEN Xi, WANG Bin, FU Lei, LU Yu, CHEN Xiao-you

Chinese Journal of Antituberculosis. 2020, 42(5):  472-480.  doi:10.3969/j.issn.1000-6621.2020.05.011

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Objective To establish the method of modified propidium monoazide (PMAxx)-quantitative PCR (qPCR) for identifying live and heat-inactivated Mycobacterium tuberculosis (MTB), and evaluate the value of PMAxx-qPCR assay to detect activity of antituberculosis drugs in vitro. Methods The pre-treatment conditions of PMAxx including light-exposure time, dark-incubation time, PMAxx concentration and DNA amplification size were optimized with live and heat-inactivated MTB (H37Rv). Through plotting the dose-effect curve and establishing the standard curve of the quantification cycle (Cq) value and bacterial load, the antibacterial activity of isoniazid (INH) and rifampin (RFP) in vitro were calculated by this assay, the detection sensitivity was evaluated, and comparing it to Microplate Alamar Blue assay (MABA) and colony forming unit (CFU) method, the colony count was analyzed by independent sample t-test, and the difference was statistically significant (P<0.05). Results When the bacterial load was set as 10 ⁷ CFU/ml, the dead and living bacteria could be identified effectively (ΔCq_dead-live=6.772±0.453) under the condition of the concentration of PMAxx with 10 μmol/L, dark incubation for 10 min and light-exposure for 15 min. The difference of the dead and living bacteria could be confirmed more effectively by using the >200 bp target DNA fragments. PMAxx-qPCR method obtained good MIC results comparing to MABA method in three days (INH: 0.049-0.076 μg/ml vs. 0.032-0.064 μg/ml, t=0.782, P=0.491; RFP: 0.102-0.145 μg/ml vs. 0.051-0.079 μg/ml, t=2.828,P=0.066). The Cq value of the quantitative standard curve showed a good linear relationship with the CFU (lgCFU/ml) (R ²=0.9863), and the limit number of detection was 10 ²CFU/ml. Meanwhile, the antibacterial counts of 16×, 8×, 4×, 2× and 1×MIC concentrations of INH by the PMAxx-qPCR method and CFU method were (4.376±0.344) and (4.325±0.318) CFU/ml, (4.232±0.106) and (3.936±0.194) CFU/ml, (4.122±0.277) and (3.874±0.105) CFU/ml, (3.950±0.113) and (3.675±0.250) CFU/ml, (3.770±0.228) and (3.618±0.257) CFU/ml, respectively. The antibacterial counts of 16×, 8×, 4×, 2× and 1×MIC concentrations of RFP by the PMAxx-qPCR method and CFU method were (4.577±0.216) and (4.675±0.250) CFU/ml, (4.445±0.054) and (4.374±0.675) CFU/ml, (3.627±0.173) and (3.154±0.076) CFU/ml, (1.946±0.359) and (2.159±0.083) CFU/ml, (1.552±0.423) and (0.960±0.202) CFU/ml respectively, all differences were not statistically significant ((t=0.165, P=0.880; t=1.894, P=0.199; t=1.186, P=0.357; t=1.419, P=0.292; t=0.626, P=0.595) and (t=0.469,P=0.671; t=0.199,P=0.855; t=3.535,P=0.071; t=0.784,P=0.490; t=1.777,P=0.174)). Conclusion The established PMAxx-qPCR method in this study is stable. It can be used to detect the activity of the first-line antituberculous drugs including INH and RFP with high sensitivity, rapid and accuracy.

Application value of probe-directed recombinase amplification assay in detecting MTB rpoB gene mutation

LI Xin-na, SHEN Xin-xin, WANG Rui-bai, DUAN Su-xia, ZHANG Rui-qing, WANG Rui-huan, BAI Xue-ding, FAN Guo-hao, WANG Jin-rong, GAO Yuan, CHEN Zi-wei, MA Xue-jun

Chinese Journal of Antituberculosis. 2020, 42(5):  481-488.  doi:10.3969/j.issn.1000-6621.2020.05.012

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Objective To establish a probe-directed recombinase amplification (PDRA) assay for rapid detection of 516 mutations in Mycobacterium tuberculosis (MTB) rpoB gene. Methods Four probes including one wild-type (P-W) probe and three mutant-type probes (P-GGC, P-GTC, P-TAC) and a common downstream primer were designed to construct four detection systems (TB-516-W, TB-516-GGC, TB-516-GTC, and TB-516-TAC), respectively. The isothermal amplification was performed at 39 ℃ for 40 min. The positive threshold time was used to determine the occurrence and type of mutation at 516 locus of the MTB rpoB gene. The sensitivity of the detection system was assessed by detecting the corresponding recombinant plasmid with the same probe. The specificity of the detection system was assessed by detecting the same recombinant plasmid with different probes. The established PDRA assay was used to detect 6 MTB rifampicin-resistant strains and 35 MTB culture-positive sputum specimens, and compared with the results of Sanger sequencing. Results The sensitivity of the four detection systems for corresponding recombinant plasmids was 1000 copies/μl. When the probe and the target sequence were completely matched, the positive threshold time was short; otherwise, the positive threshold time was long, with a stable difference in positive threshold time, suggesting the good specificity of the four detection systems. The positive threshold time differences of the systems TB-516-W, TB-516-GGC, TB-516-GTC and TB-516-TAC were 7.0, 5.8, 10.0 and 7.0 min, respectively. The PDRA detection results of 6 MTB-resistant strains and 35 MTB culture-positive sputum samples were consistent with the sequencing results. Conclusion This study has preliminarily established a PDRA assay that can be applied to detect the 516 mutations in rpoB gene of MTB. It has high detection sensitivity and good specificity, and therefore has certain laboratory application value.

Exploration of the expression level of lipoxin A4 and its influence mechanism in process of tuberculous pleural fibrosis

ZHU Jian-kun, MENG Qian, JIN Feng

Chinese Journal of Antituberculosis. 2020, 42(5):  489-492.  doi:10.3969/j.issn.1000-6621.2020.05.013

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Objective To analyze the expression level of lipoxin A4 (LXA4) and its influence mechanism in the process of pleural fibrosis in the patients with tuberculous pleurisy. Methods The clinical data of 61 patients with tuberculous pleural effusion and 15 patients with cancerous pleural effusion, who were treated at Shandong Provincial Chest Hospital Affiliated to Shandong University from July 2017 to December 2018, were collected. According to presence or absence of pleural fibrosis, the enrolled patients were divided into three groups: tuberculous pleural fibrosis group (27 cases), tuberculous without pleural fibrosis group (34 cases) and cancerous without pleural fibrosis group (15 cases). The LXA4 concentration in the pleural effusion of the patients in each group was tested and compared; the correlation between LXA4 and TGF-β in the tuberculous pleural effusion was analyzed. Results The median (quartile) of LXA4 concentration was 7.74 (4.69, 10.55) ng/L in the patients of tuberculous without pleural fibrosis group, which was statistically significant lower than that in the patients of tuberculous pleural fibrosis group (12.50 (11.60, 14.83) ng/L; Z=-3.830, P<0.001). The concentration of LXA4 was 7.88 (5.91, 15.02) ng/L in the patients of cancerous without pleural fibrosis group, there was no significant difference compared with the tuberculosis patients without pleural fibrosis (Z=-0.586, P=0.558). The concentrations of LXA4 (10.23 (5.14, 13.15) ng/L) and TGF-β (46.30 (41.04, 60.85) ng/L) were negative correlation in 61 tuberculosis patients with pleural effusion (Spearman correlation coefficient, r_s=-0.519, P<0.001). Conclusion The LXA4 concentration is highly expressed in tuberculous pleurisy patients with pleural fibrosis, and has a significant negative correlation with the concentration of TGF-β. It may play an anti pleural fibrosis role by inhibiting TGF-β.

Study of the serum concentration at two time points after taking rifampicin

ZHANG Pei-ze, ZHENG Jun-feng, CAO Wei-peng, WANG Yu-xiang, CHEN Tao, FU Liang, DENG Guo-fang

Chinese Journal of Antituberculosis. 2020, 42(5):  493-497.  doi:10.3969/j.issn.1000-6621.2020.05.014

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Objective To evaluate the application of the peak plasma concentration, which were plasma concentrations of rifampicin (RFP) at 2 h (C_{2 h}) and 6 h (C_{6 h}) post-dose in newly diagnosed active tuberculosis patients, in guidance for clinical management. Methods According to the inclusion criteria, 148 active tuberculosis patients from the Third People’s Hospital of Shenzhen between November 2016 and November 2017 were included, and their C_{2 h} and C_{6 h} were monitored by HPLC one week after taking rifampicin. Based on international rifampicin plasma C_max (8-24 μg/ml), plasma concentration, malabsorption and delayed absorption of the two time points were analyzed using SPSS 19.0. Gender, age, BMI, rifampicin dosage, concurrent diabetes, concurrent hepatitis B virus and serum albumin levels etc. of the low C_max group (those who were below the standard range) and the normal C_max group (those who in the standard range) were described as “ \bar{x} ±s” and compared by t test. Categorical variables were compared by χ ² test and P<0.05 was considered statistically significant. Results C_{2 h} was below the standard range in 24.3% (36/148) of all the patients;however, among them, 36.1% (13/36) patients reached target C_max (8-24 μg/ml) at C_{6 h}; totally, C_{6 h} of 84.5% (125/148) patients reached the target C_max, the rate of delayed absorption was 10.4% (13/125). There were no statistical differences between low C_max group and the normal C_max group in gender (male, 60.9% (14/23) vs. 68.8% (86/125), χ ²=0.558, P=0.455), age ((36.9±4.2) years vs. (38.2±3.5) years, t=-1.585, P=0.115), BMI ((21.5±4.0) vs. (22.9±3.7), t=-1.647, P=0.102), rifampicin dosage of 450 mg/d (60.9% (14/23) vs. 43.2% (54/125), χ ²=2.442, P=0.118), concurrent diabetes (8.7% (2/23) vs. 22.4% (28/125), χ ²=2.257, P=0.166), complicated with hepatitis B virus (4.3% (1/23) vs. 9.6% (12/125), χ ²=0.669, P=0.694), and serum albumin levels ((42.3±4.4) g/L vs. (40.9±3.2) g/L, t=1.457, P=0.157). Conclusion Monitoring rifampicin C_max at two time points could reflect the absorption of rifampicin in the body more accurately. However, there was no influence factors been found, and expanded sample for further research would be warranted in the future.

Analysis of the epidemiological characteristics of tuberculosis students in Shanghai from 2009 to 2017

XIAO Xiao, CHEN Jing, LI Xiang-qun, XIA Zhen, LUAN Rui-rong, RAO Li-xin, SHEN Xin

Chinese Journal of Antituberculosis. 2020, 42(5):  498-502.  doi:10.3969/j.issn.1000-6621.2020.05.015

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Objective To investigate the epidemic trend of tuberculosis of students in Shanghai from 2009 to 2017, to improve the tuberculosis control management. Methods The reported data of tuberculosis were collected from Tuberculosis Information Management System, including general conditions, medical information, and diagnosis results, etc. And data of student population were collected from Shanghai Statistical Yearbook 2018. The characteristics of student tuberculosis epidemic in Shanghai from 2009 to 2017 were described by indicators such as the reported incidence of student tuberculosis, the sequence of reported student cases in population, and the trend of incidence (calculated by linear regression analysis method of annual change percentage (APC)). Results From 2009 to 2017, the reported incidence of tuberculosis among students were between 15/100000 and 20/100000 in Shanghai, the incidence decreased from 19.70/100000 (386/1959700) in 2009 to 15.31/100000 (301/1966300) in 2017 (Y=58.562-0.030X, APC=-2.96, t=-5.158, P=0.001). The reported cases were increased by age with the peak at 19 years old and above (when at college) (61.94% (1963/3169)), and male cases were significantly more than female cases (63.27% (2005/3169) vs. 36.73% (1164/3169), χ ²=18.226, P=0.020). The local cases decreased from 64.77% (250/386) in 2009 to 45.85% (138/301) in 2017 (Y=83.109-0.042X, APC=-4.11, t=-7.897, P<0.001), while the immigrant cases increased from 35.23% (136/386) in 2009 to 54.15% (163/301) in 2017 (Y=-108.161+0.053X, APC=5.44, t=7.653, P<0.001). It was found that the ratio of severe patients decreased from the peak of 47.35% (170/359) in 2011 to 3.65% (11/301) in 2017 (Y=339.673-0.170X, APC=-15.63, t=-2.243, P=0.060), the ratio of severe patients in immigrant cases decreased from the peak of 48.34% (73/151) in 2011 to 6.13% (10/163) in 2017, also showing (Y=293.665-0.147X, APC=-13.67, t=-2.616, P=0.035). Conclusion The reported incidence of tuberculosis in students was decreasing, cases were mainly from college. The reported number of immigrant cases was increased, but the ratio of severe patients was decreased significantly.

Acceptability of preventive treatment with 12-week regimen among close contacts of tuberculosis

REN Zhe-wen, ZHANG Guo-long, GONG De-hua, LEI Rong-rong, ZU Xiao-wen, XU Cai-hong, XIA Yin-yin, ZHANG Can-you, CHEN Hui, CHENG Jun, ZHANG Hui

Chinese Journal of Antituberculosis. 2020, 42(5):  503-509.  doi:10.3969/j.issn.1000-6621.2020.05.016

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Objective To understand the acceptability and influencing factors for 12-week preventative treatment for close contacts with latent tuberculosis infection (LTBI), and to provide more evidence for the progressive promotion of preventive treatment measures in close contacts of tuberculosis (TB) patients in China. Methods A total of 1, 087 etiologically positive TB patients enrolled in the “Thirteenth Five-Year Plan” National Science and Technology Major Project (intervention on latent infected close contacts of TB patients) from Jan 1st, 2018 to Jan 15th, 2020 were selected, among whom 1033 cases aged 5 to 65 with LTBI were enrolled in this study. Informed consent and questionnaires were conducted to understand the acceptance rate and influencing factors for the 12-week preventative treatment regimen in these 1033 cases. The main contents of the questionnaire included the social demographic information of the close contacts with LTBI, the awareness of the knowledge of TB control and prevention, the history of TB exposure, the symptoms of the index cases, and whether they were willing to take preventive medicine. A total of 1033 questionnaires were valid with the effectively response rate of 100%. Acceptability of the 1033 cases was analyzed with Chi-square test and unconditional dichotomous logistic regression test. Results Among 1033 latent infected close contacts, 788 (76.28%) were willing to take preventive medicine. The risk factor was the family’s average annual income ≥16000 yuan (OR=0.42, 95%CI:0.27-0.67), and the protective factor was not living with the index case (OR=1.89, 95%CI:1.32-2.67). Conclusion Close contacts with LTBI are much willing to accept the 12-week preventive treatment regimen, which is affected by the family’s economic level and the degree of exposure to the index cases.

Influencing factors of pulmonary tuberculosis patient delay in Guangzhou, 2008—2018

SHEN Hong-cheng, DU Yu-hua, ZHANG Guang-chuan, WU Gui-feng, LIU Jian-xiong, LI Tie-gang

Chinese Journal of Antituberculosis. 2020, 42(5):  510-517.  doi:10.3969/j.issn.1000-6621.2020.05.017

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Objective To analyze the trend and influencing factors of pulmonary tuberculosis (PTB) patient delay in Guangzhou from 2008 to 2018, and to provide scientific evidence for the development of prevention and control measures. Methods Data of 125201 PTB cases registered and treated in Guangzhou from 2008 to 2018 were collected from TB Management Information System of China Information System for Disease Control and Prevention, including residence, gender, age, ethnicity, occupation, cases source, cases classification and complication. Influencing factors of PTB patient delay were analyzed by univariate and multivariate logistic regression. Results Median of days (quartiles) from symptom onset to seeking health care was 13 (2, 38) days in Guangzhou from 2008 to 20l8, with 49.25% (61656/125201) of PTB patients delayed in seeking health care. Univariate analysis showed that patient delay rates of female, aged ≥65, ethnic minorities, children, cases from tracing, extrapulmonary tuberculosis, with complications were significantly higher than those of male (49.98% (19951/39919) vs 48.90% (41705/85282)) (χ ²=12.60, P<0.001), aged <25 (53.60% (8323/15528) vs 43.99% (11493/26129)) (χ ²=664.34, P<0.001), ethnic HAN (52.05% (1128/2167) vs 49.20% (60528/123034)) (χ ²=6.96, P=0.008), teacher or doctor or cadre (64.66% (161/249) vs 46.49% (1848/3975)) (χ ²=878.51, P<0.001), health check (53.06% (5347/10078) vs 23.94% (643/2686)) (χ ²=940.21, P<0.001), PTB (56.27% (3465/6158) vs 48.88% (58191/119043)) (χ ²=127.79, P<0.001) and without complications (63.80% (1202/1884) vs 49.02% (60454/123317)) (χ ²=162.12, P<0.001), respectively. Multivariate logistic regression analysis showed those with the following characteristics were more likely to delay in seeking health care: female (male as reference, OR (95%CI)=1.11 (1.08-1.13)), aged 25-, 45-, ≥65 (aged <25 as reference, OR (95%CI)=1.13 (1.09-1.16), 1.37 (1.32-1.42) and 1.40 (1.33-1.47), respectively), ethnic minorities (ethnic HAN as reference, OR (95%CI)=1.22 (1.12-1.33)), children, worker/civilian worker, farmer, others (teacher or doctor or cadre as reference, OR (95%CI)=2.38 (1.80-3.15), 1.17 (1.10-1.26), 1.38 (1.28-1.48) and 1.17 (1.10-1.25), respectively), clinical consultation, recommendation, referral, tracing (health check as reference, OR (95%CI)=3.06 (2.79-3.35), 3.27 (2.83-3.77), 2.78 (2.54-3.05) and 3.35 (3.04-3.70), respectively), extrapulmonary tuberculosis (pulmonary tuberculosis as reference, OR (95%CI)=1.41 (1.33-1.49)), with complications (without complications as reference, OR (95%CI)=1.62(1.47-1.78)). Conclusion Patient delay is rather common in pulmonary tuberculosis patients in Guangzhou from 2008 to 2018. The influencing factors mentioned above for patient delay should be paid more attention.

Study on the distribution and epidemiological characteristics of non-tuberculous mycobacterium strains in Fujian Province

LIN Jian, LIN Shu-fang, DAI Zhi-song, ZHAO Yong, WEI Shu-zhen, ZHOU Yin-fa

Chinese Journal of Antituberculosis. 2020, 42(5):  518-522.  doi:10.3969/j.issn.1000-6621.2020.05.018

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Objective To understand the distribution and epidemiological characteristics of non-tuberculous mycobacterium (NTM) strains in Fujian Province and provide references for development of the provincial NTM control strategies. Methods The strain specimens were collected from 190 suspects with NTM infection, who were detected by sputum culture examination in the 11 drug-resistant tuberculosis (TB) surveillance sites, and the fluorescence PCR melting curve method was performed to do the strain identification. Excel 2016 and SPSS 24.0 software were used to manage and analyze the data. Nonparametric test was used to analyze the distribution of NTM strain in patients with different demographic characteristics and Chi square test was performed to compare the characteristics differences between the patients infected with M.intracellular and noncellular NTM. P value <0.05 was considered statistically significant. Results A total of 161 patients were confirmed to be infected by NTM, including 153 patients were infected by 8 kinds of strains and the strains were not identified in the other 8 patients. Most of patients were infected with M.intracellular (60.9%, 98/161), followed by M.abscessus (19.9%, 32/161). The average age of the patients infected with NTM was (57.3±13.0) years old, and most of them were male (70.2%,113/161), local resident (87.0%, 140/161), migrant workers (72.7%, 117/161), Han nationality (97.5%, 157/161) and living in coastal cities (77.6%, 125/161). In the patients infected with either M.intracellular or noncellular NTM, the highest proportions of the infection were in the 45-60 age groups respectively (63.3% (62/98) and 57.2% (36/63)), and were male (71.4% (70/98) and 68.3% (43/63)], migrant workers (76.5% (75/98) and 66.7% (42/63)), local residents (88.8% (87/98) and 84.1% (53/63)) and living along the coast (74.5% (73/98) and 82.5% (52/63)); those proportions did not have significate differences between the patients infected with M.intracellular or noncellular NTM (χ ²=4.202, 0.185, 1.879, 0.731, 1.431 respectively and all P values were >0.05). The proportion of Han nationality was significant difference between the patients infected with M.intracellular (100.0% (98/98)] and noncellular NTM (93.7% (59/63)) (χ ²=4.029, P<0.05)). Conclusion The patients infected with NTM in Fujian were mainly Han nationality, local resident, male, middle aged and old people, and migrant workers; most of the them were infected with M.intracellular, followed by M.abscess. Except for nationality, the social-demographic characteristics did not have significant differences between the patients infected with M.intracellular and noncellular NTM.

Short Articles

Observation on the effects of bronchoscopy diagnosis and interventional treatment in 11 children with tracheobronchial tuberculosis

BIN Song-tao, WANG Ji, TAN Li, WU Cheng-qing, WANG Yan-chun, LI Ming

Chinese Journal of Antituberculosis. 2020, 42(5):  523-526.  doi:10.3969/j.issn.1000-6621.2020.05.019

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In order to observe the effects of electronic bronchoscopy diagnosis and interventional treatment in children with tracheobronchial tuberculosis (TBTB), the author collected 11 children with TBTB as the research subjects who were admitted to Kunming Children’s Hospital from January 2018 to October 2019 and underwent bronchoscopy diagnosis and interventional treatment. The subjects were examined by imaging, tuberculin skin test, γ-interferon release test, sputum culture, sputum and gastric juice detection for Mycobacterium tuberculosis and culture. Then the suspicious subjects were finally confirmed by bronchoscopy, observing the specific changes under the microscope, and pathological examination of the biopsy tissue. Subjects received bronchoscopy interventional therapy 2 weeks after antituberculosis drug treatment in non-emergency cases. Among them, 10 cases were treated by electronic bronchoscopy forceps and cryotherapy, and 1 case was treated by balloon dilatation, holmium laser and cryotherapy. The bronchoscopy revealed granulation proliferative change in 3 cases, and caseous necrotic ulceration change in 8 cases, including 1 case complicated by cicatricial stricture. The 11 cases were treated by bronchoscopy for 2-6 times/case, and the obstructed and narrowed lumen recovered unobstructed. After follow-up review, all the children were effective in interventional treatment, and there were no complications such as airway spasm, massive hemorrhage, pneumothorax, secondary pulmonary infection, and tuberculosis spread. The results showed that TBTB, on the basis of antituberculosis drug treatment, could effectively remove caseous necrosis, reduce granulation hyperplasia, relieve respiratory tract obstruction, and promote lesion absorption through bronchoscopic interventional therapy, which was conducive to the recovery of atelectasis and was safe and reliable.

Clinical analysis of delayed diagnosis of 5 cases of tuberculous perianal abscess

LIU Xin, WANG Zhi-chao

Chinese Journal of Antituberculosis. 2020, 42(5):  527-528.  doi:10.3969/j.issn.1000-6621.2020.05.020

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From December 2015 to December 2017, among the 320 patients with perianal abscess treated in the department of general surgery of Aviation General Hospital, 5 patients’ incisions failed to heal within 30 days after surgery. They were finally diagnosed as tuberculous perianal abscess among whom 3 cases got pulmonary tuberculosis too. After 2R-H-E-Z/4R-H-E anti-tuberculosis treatment, all incisions were healed, with an average healing time (25.5±3.6) d, and no recurrence. Main reasons for the delayed diagnosis were: tuberculous perianal abscess was relatively rare clinically; lack of specificity in clinical manifestations; lack of understanding of the disease among medical staff; no detailed analysis of patients’ medical history; no examination of acid-fast bacilli in pus secretion and histopathological examination of perianal lesions. For patients with perianal abscess, we should inquire about the patient’s medical history carefully, and undertake routine examination of acid-fast bacilli in pus secretion and histopathological biopsies. Standard anti-tuberculosis treatment should be given for 0.5 to 1 year after diagnosis of tuberculous perianal abscess.