Table of Content

10 June 2019, Volume 41 Issue 6

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Expert Consensus

Expert consensus on the solutions of drug side effects during the treatment of drug resistance tuberculosis

Board of Chinese Journal of Antituberculosis Editorial

Chinese Journal of Antituberculosis. 2019, 41(6):  591-603.  doi:10.3969/j.issn.1000-6621.2019.06.003

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Drug-resistant tuberculosis (TB) has the characteristics of long treatment course, regimens with variety of drugs,high incidence rate of drug side-effect, how to treat drug side-effect correctly is one of essential factors of improving the outcome of drug-resistant tuberculosis. This expert consensus will elaborate in the treatment of side-effects from each drug and each system,treatment monitoring for drug side-effect and will provide the normative methods and principles for side-effects of drugs.

Expert Forum

Current knowledge and future prospects on the treatment of multidrug-resistant tuberculosis with second-line injectable agents

Guo-fang DENG,Pei-ze ZHANG,Min YANG,Liang FU

Chinese Journal of Antituberculosis. 2019, 41(6):  604-608.  doi:10.3969/j.issn.1000-6621.2019.06.004

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WHO Treatment guidelines for multidrug- and rifampicin-resistant tuberculosis (2018 update) was issued in late 2018 to improve MDR/RR-TB care, in which a new all-oral 20-month treatment regimen is now proposed, prioritising oral drugs over injectables. A shorter MDR-TB regimen of 9-12 months was recommended to use instead of the longer regimens under some specific circunstances, including the daily use of second-line injec-table agents for at least 4 months. Under the background, we review the drug resistance mechanism, clinical effectiveness, adverse reaction and role change of second-line injectable agents commonly used in the treatment of MDR-TB in China and address the rational use of second line injection.

Original Articles

Design of a next generation microsequencing gene microarray and preliminary study of its effect on drug resistance detection

Zhao-gang SUN,Hong-jing ZHANG,Zi-hui LI,Qi SUN,Lin-na LYU,Li-ping PAN,Gilbert Sandy,Zong-de ZHANG,Shao-fa XU,Xia James

Chinese Journal of Antituberculosis. 2019, 41(6):  609-615.  doi:10.3969/j.issn.1000-6621.2019.06.005

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Objective To design and evaluate the value of next generation of microsequencing gene microarray on detecting the drug resistance of Mycobacterium tuberculosis (MTB).Methods The standard laboratory strains of the MTB H37Rv and 109 clinical isolates selected from the Beijing tuberculosis data and clinical sample data base were tested the phenotypic drug susceptibility using the absolute concentration method, and the drug resistance-related gene mutation of MTB (including inhA, katG, rpsL, gyrA, rrs, eis, rpoB and embB) using the gene sequencing method. The fluorescent labeled probes were set as the fundamental testing principle to design and prepare the microsequencing gene microarray, and then the 109 MTB clinical isolates were detected to analyze the detection performance of the microsequencing gene microarray.Results Based on the results of phenotypic drug susceptibility test and gene sequencing test, the mutation sites and forms of drug resistance-related genes (inhA, katG, rpsL, gyrA, rrs, eis, rpoB and embB) in 109 clinical isolates were identified. The microsequencing gene microarray contained 220 probes of the mutations that had been reported in the above genes, and 67 predominant probes were identified. The microsequencing drug-resistance gene microarray containing 67 probes was used to detect the mutations in 109 clinical isolates. The results showed that, except for the two probes in embB gene, the remaining 65 probes had more than 95% coincidence rate in the base mutation pattern detection, compared with the sequencing results, even 42 probes of them reached a coincidence rate of 100.00%. Taking sequencing results as the reference, the sensitivity of gene microarray detection method for embB gene, gyrA gene, inhA gene, katG gene, rpoB gene, rpsL gene, eis gene and rrs gene were 64.21% (61/95), 80.00% (8/10), 95.83% (23/24), 98.55% (68/69), 92.63% (88/95), 93.85% (61/65), 75.00% (3/4) and 94.44% (17/18), respectively. The specificity of the above genes were 92.86% (13/14), 100.00% (99/99), 97.65% (83/85), 87.50% (35/40), 85.71% (12/14), 63.64% (28/44), 100.00% (105/105) and 98.90% (90/91), respectively. After statistical analysis (Kappa test), the Kappa values of the above genes were 0.29, 0.88, 0.92, 0.88, 0.68, 0.60, 0.85 and 0.93, respectively.Conclusion The microsequencing gene microarray for drug-resistance detection with a set of 67 probes had been designed and developed. After preliminary verification, it showed a good performance on the detection of MTB drug-resistant gene mutation. However, for the embB gene, the detection probes needs to be further optimized, to better fulfill the clinical requirement.

Analysis of drug resistance of clinical isolates of smear positive pulmonary tuberculosis patients in Shaanxi Province from 2017 to 2018

Jian YANG,Tian-hua ZHANG,Xiao-ping XIAN,Yan LI,Rui WANG

Chinese Journal of Antituberculosis. 2019, 41(6):  616-623.  doi:10.3969/j.issn.1000-6621.2019.06.006

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Objective To explore the drug resistance of Mycobacterium tuberculosis(MTB) isolated from smear-positive pulmonary tuberculosis (TB) patients in Shaanxi Province.Methods Twenty-six survey points in Shaanxi Province were extracted with stratified cluster random sampling. All the culture positive isolated strains from new smear positive pulmonary TB patients registered from January 2017 to December 2018 were collected. Twenty-two strains were identified as non-tuberculosis mycobacteria (NTM) which accounted for 2.23% (22/987), and 965 strains were identified as MTB which accounted for 97.77% (965/987). Drug susceptibility test of 6 anti-TB drugs (including isoniazid (INH), rifampicin (RFP), ethambutol (EMB), streptomycin (Sm), ofloxacin (Ofx), kanamycin (Km)) with proportional method were performed on 965 strains of MTB. SPSS 18.0 was used for statistical analysis, and the counting data were analyzed by Chi-square test or Fisher exact test. P<0.05 was considered statistically significant.Results The drug resistance rate of 965 MTB strains was 28.50% (275/965), 26.07% (219/840) for initially-treated patients and 44.80% (56/125) for re-treated patients. The mono-resistance rate was 14.30% (138/965), 14.76% (124/840) for initially-treated patients and 11.20% (14/125) for re-treated patients. The poly-drug resistance rate was 4.56% (44/965), 4.40% (37/840) for initially-treated patients and 5.60% (7/125) for re-treated patients. The multi-drug resistance rate was 6.53% (63/965), 4.40% (37/840) for initial patients and 20.80% (26/125) for re-treated patients. The extensive drug resistance rate was 0.62% (6/965), 0.24% (2/840) for initially-treated patients and 3.20% (4/125) for re-treated patients. The rifampicin resistance rate was 9.84% (95/965), 7.14% (60/840) for initially-treated patients and 28.00% (35/125) for re-treated patients. The drug resistance rate, multi-drug resistance rate and rifampicin resistance rate of re-treated patients were significantly higher than those of initially-treated patients (χ²=18.730, 47.930 and 53.331 respectively, all P=0.000). The drug resistance rate to 4 first-line and 2 second-line anti-TB drugs were 26.01% (251/965) and 8.50% (82/965), respectively. It showed the highest resistance to Sm (17.62%, 170/965), followed by INH (15.03%, 145/965), RFP (9.84%, 95/965), Ofx (6.84%, 66/965), EMB (5.08%, 49/965) and Km (2.59%, 25/965).There were 39 types of drug resistance spectrum, which included 6 mono-resistance, 5 poly-drug resistance, 13 multi-drug resistance and 15 kinds of poly-drug resistance of second-line drugs.Conclusion In recent years, some achievements have been made in the prevention and control of drug-resistant TB in Shaanxi Province, but the drug resistance spectrum presents polymorphism and complexity, and the epidemic of multi-drug resistance and rifampicin resistance is still severe.

Analysis of risk factors for recurrence of pulmonary tuberculosis after successful completion of treatment of relapsed smear positive tuberculosis

Jian DU,Xi-qin HAN,Wei SHU,Zi CHEN,Shi-heng XIE,Xiao-ya LYU,Qi-ping GE,Yan MA,Yu-hong LIU,Liang LI,Wei-wei GAO

Chinese Journal of Antituberculosis. 2019, 41(6):  624-631.  doi:10.3969/j.issn.1000-6621.2019.06.007

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Objective This study is to identify and analyze the risk factors of recurrence of pulmonary tuberculosis after successful completion of treatment of relapsed smear positive tuberculosis.Methods This was a multi-centered open-label randomized controlled prospective cohort study which recruited patients from 22 TB specialized clinical centers across China. From March 2013 to January 2019, 300 relapsed pulmonary TB patients after completion of anti-TB retreatment had been followed-up for 6 consecutive years. Twenty-three of those who had completed retreatment relapsed again formed the recurrent cohort, the rest 277 patients who remained clear of TB formed the control cohort. Indicators including past accumulated time of anti-TB medication including initial treatment and retreatment, the presence of drug resistance prior initiation of retreatment, retreatment chemo-regimens, dosages of rifampicin or rifapentine (in short rifamycins)of retreatment regimens as well as cavitation on chest X-ray after successful completion of retreatment were investigated and analyzed by using mono-factor or multi-factor analysis for further TB recurrence. SPSS 19.0 was used for statistical analysis, collected data were verified using χ² test; a logistical regression was utilized to analyze the correlation between clinical characteristics of both cohorts and TB recurrence, P<0.05 was considered statistically significant difference.Results 7.1%(1/14) of patient from recurrent cohort having his or hers lung cavity closed which was much lower than control with 49.2%(90/183)of patients having their lung cavities closed, the difference was statistically significant(χ²=9.246,P=0.002). Using mono-factor analysis, percentages of patients who received ≥7 months of past accumulated time of administration of first-line anti-TB drugs from both recurrent and control cohort were 60.9%(14/23)and 29.1% (80/275) respectively, difference between 2 cohorts was statistically significant (χ²=9.926, P=0.002). Presence of drug resistance prior to initiation of retreatment was found in 63.6% (14/22) of patients in the recurrent cohort and 35.8% (93/260) of patients in control, difference between 2 cohorts was statistically significant (χ²=6.690, P=0.010). Using multi-factor analysis, the odds ratios (OR) between further TB recurrence and past accumulated time of anti-TB medication as well as presence of drug resistance prior retreatment were 4.911 (95%CI, 1.885-12.792) and 3.085 (95%CI, 1.204-7.902) (P=0.001 and P=0.019) respectively. In the meantime, lower dosage of rifamycins in the retreatment regimen was found to be closely associated with further recurrence of TB after retreatment completion, OR was 3.499 (95%CI, 1.302-9.404) (P=0.013).Conclusion ≥7 months of past accumulated time of anti-TB medication, the presence of drug resistance prior to initiation of retreatment, lower dosage of rifamycins in the retreatment regimen as well as persistence of pulmonary cavitation on the chest X-ray at the end of retreatment have been identified as risk factors for further TB recurrence after completion of treatment of relapsed TB.

Analysis of prognostic factors in 164 tuberculous meningitis patients

Wei HUANG,Xue-mei AN,Xu-hui LIU,Ning PEI,Ping LIU,Lu XIA,Tao LI,Xiu-hong XI,Qin HUANG,Shui-hua LU

Chinese Journal of Antituberculosis. 2019, 41(6):  632-639.  doi:10.3969/j.issn.1000-6621.2019.06.008

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Objective To analyze the clinical characteristics and prognostic factors of tuberculous meningitis (TBM) patients.Methods The clinical data of 164 patients with TBM clinically diagnosed in the Shanghai Public Health Clinical Center from January 2014 to December 2017, including sex, age, BCG vaccination, temperature, meningeal syndrome, TBM stage, indexes of cerebrospinal fluid, brain MR/CT, lung CT, using mechanical ventilation or not, T-SPOT.TB assay, the number of TBM patients who receiving linezolid within two weeks after onset, and outcomes within 9 months after starting treatment, were retrospectively analyzed. According to the outcome within 9 months after starting treatment, patients were divided into good prognosis group and poor prognosis group (death or neurological sequelae). The clinical datas of patients in the two groups were compared, and the risk factors affecting the prognosis of patients were analyzed by conditional logistic stepwise regression.Results Incidencesin the poor prognosis group, including aged 0-15-year (36.2% (25/69)), MRC grade Ⅲ (58.0% (40/69)), cerebral infarction (45.2% (28/62)), cerebral hydrocephalus (54.8% (34/62)) and mechanical ventilation (19.4% (13/67)), were statistically higher than those in good prognosis group (17.9% (17/95), 20.0% (19/95), 4.3% (4/93), 11.8% (11/93) and 5.4% (5/92)) (χ ² values were 7.06, 25.02, 37.91, 33.40 and 7.53; all P<0.05); while the rate of TBM patients treated with linezolid at early stage in the poor prognosis group was lower than those in the good prognosis group (8.7% (6/69) vs. 21.1% (20/95)) and the differences were statistically significant (χ ²=4.58, P=0.032). Logistic regression analysis showed that 0-15 year old (OR (95%CI)=3.51 (1.09-11.22)), MRC grade Ⅲ (OR (95%CI)=3.95 (1.29-12.09)), cerebral infarction (OR (95%CI)=25.90 (6.81-98.40)), cerebral hydrocephalus (OR (95%CI)=10.00 (3.56-28.07)) were risk factors, whereas receiving linezolid at early stage (OR (95%CI)=0.14 (0.03-0.64)) was protective factor.Conclusion Young (0-15 years old), MRC grade Ⅲ, cerebral infarction and hydrocephalus are the main risk factors for poor prognosis in TBM patients. This study highlighted that the early use of linezolid could improve the prognosis.

Analysis of risk factors for poor outcome of treatment in patients with ulcerous necrotic type bronchial tuberculosis

Wen-ting LI,Hong-xia CHEN,Yan YANG

Chinese Journal of Antituberculosis. 2019, 41(6):  640-644.  doi:10. 3969/j.issn.1000-6621.2019.06.009

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Objective To analyze the factors affecting the efficacy in patients with ulcerous necrotic type bronchial tuberculosis.Methods A total of 105 cases who were first diagnosed with ulcerous necrotic type bronchial tuberculosis by bronchoscopy in the Department of Tuberculosis in Tongji University affiliated to Shanghai Pulmonary Hospital were successively collected from January 2016 to January 2018, and were set as subjects. The clinical data of the patients were collected, and the lesion involved airway sites and levels, the degree of lumen stenosis caused by necrotic materials and mucosal edema, and the imaging characteristics of the chest CT scan under bronchoscopy were recorded.Results Among the 105 patients with ulcerous necrotic type bronchial tuberculosis, 72 cases (68.6%) were effectively treated, and 33 (31.4%) were ineffectively treated. In the ineffective treatment group, 12 cases (36.4%) had a smoking history, 21 cases (63.7%) had a symptom duration (from onset to treatment) ≥ 4 weeks, 10 cases (30.3%) had cavity on chest CT scan, and 12 cases (36.4%) had a lesion involved airway level ≥3. In the effective treatment group, the case numbers of the above four outcomes were 12 (16.7%), 24 (33.3%), 8 (11.1%) and 10 (13.9%), respectively. The differences between the two groups were statistically significant (χ ²=4.98, 8.49, 5.87 and 6.90, respectively, all P values were <0.05). Multivariate logistic regression analysis showed that the smoking history (OR=2.87, 95%CI: 1.01-8.14), symptom duration ≥ 4 weeks (OR=3.48, 95%CI: 1.35-9.01), cavity on chest CT scan (OR=3.27, 95%CI: 1.02-10.55), the lesion involved airway levels ≥ 3 (OR=3.73, 95%CI: 1.23-11.31) were risk factors for the ineffective treatment of ulcerous necrotic type bronchial tuberculosis.Conclusion The strengthening smoking cessation education, enhancement of publicity and education on tuberculosis prevention, and early diagnosis and treatment may contribute to improve the treatment efficiency for the ulcerous necrotic type bronchial tuberculosis.

Analysis on the monitoring results of plasma-drug concentration of rifampicin in different dosage forms

Ming-wu LI,Ming-hong LAI,Meng MA,Rong WAN,Yuan XU,Chao-mei DU

Chinese Journal of Antituberculosis. 2019, 41(6):  645-649.  doi:10.3969/j.issn.1000-6621.2019.06.010

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Objective To analyze the monitoring results of plasma-drug concentration of rifampicin in two different dosage forms and provide guidance for clinical proper drug use.Methods A hundred and thirty patients with active pulmonary tuberculosis (PTB), who received treatment in the Second Department of Tuberculosis of the Third People’s Hospital of Kunming from May 2016 to June 2017 were selected. Based on the principle of random number table, the enrolled patients were divided into an injection group (65 cases, rifampicin was given by intravenous drip, 0.6 g per time, once a day, with 500 ml 5% glucose injection) and an oral group (65 cases, rifampicin was administered orally, 0.6 g per time, once a day). The minimum inhibitory concentration (MIC) of rifampicin was 0.39-1.56μg/ml and the patients who reached the MIC of 0.39μg/ml were counted in this study. In the oral group, 2 patients were excluded because of the omission of the blood concentration monitoring data at different time points. So the study eventually included 128 patients, including 65 cases in the injection group and 63 cases in the oral group. After seven days of medication, plasma samples of the patients in two groups were collected in different time periods and the plasma-drug concentration of rifampicin in the two groups was tested by using UPLC-MS/MS.Results For the injection group, the highest concentration of rifampicin occurred at one hour and a half after injection, with a Median (Quartiles) (M (Q₁, Q₃)) of 0.954 (0.210, 3.420)μg/ml; for the oral group, it occurred at two hours after taking the medicine, with a Median (Quartiles) (M (Q₁, Q₃)) of 1.253 (0.249, 2.501)μg/ml. The peak and mean plasma-drug concentrations of rifampicin in the injection group were 1.786 (0.704, 3.591)μg/ml and 0.688 (0.269, 1.087)μg/ml, which were higher than those in the oral group (1.468 (0.423, 3.748)μg/ml and 0.571 (0.149, 1.894)μg/ml), but there was no statistical difference between the two groups (Z=-0.90 and -0.02; P=0.366 and 0.980). The valley plasma-drug concentration in the injection group (0.004 (0.001, 0.038)μg/ml) was lower than that in the oral group (0.007 (0.001, 0.070)μg/ml), and the difference between the two groups was a statistically significant (Z=-8.74, P=0.000). The total rate that the plasma-drug concentration reached MIC in the injection group was 47.7% (248/520) while that was 49.4% (218/441) in the oral group, there was no statistical difference between the two groups (χ ²=0.29, P=0.591).Conclusion The rifampicin treatment is given to the PTB patients either by injection or oral, the plasma-drug concentration of rifampicin all remains low. It fails to reach MIC in more than half of the patients and the internationally recommended reference range cannot be met. It may be coursed by inadequate dose. So he monitoring to the plasma-drug concentration of rifampicin should be strengthened and the use of rifampicin injection should be regulated.

Curative effect of percutaneous pedicle screw internal fixation combined with small abdominal incision debridement for lumbar tuberculosis in old patients

Shi-yuan SHI,Zhen LAI,Jun FEI,Gui-he HAN,Sheng-ping HU

Chinese Journal of Antituberculosis. 2019, 41(6):  650-656.  doi:10.3969/j.issn.1000-6621.2019.06.011

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Objective To evaluate the curative effect of percutaneous pedicle screw internal fixation combined with small abdominal incision debridement for lumbar tuberculosis in old patients.Methods From March 2014 to March 2017, 56 old patients with lumbar tuberculosis in Zhejiang Integrated Traditional and Western Medicine Hospital met the inclusion criteria were divided into group A and group B. All patients were received the standard anti-tuberculosis chemotherapy. Patients in group A were underwent percutaneous pedicle screw internal fixation combined with small abdominal incision debridement and interbody fusion with bone grafting. Patients in group B were underwent pedicle screw internal fixation and anterior debridement and interbody fusion with bone grafting. The volume of surgical bleeding, operation time, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), segment kyphotic Cobb angle, accuracy of nailing and lumbar function were compared and analyzed between the two groups. SPSS 17.0 statistical software was used for data analysis, t test and χ ² test were used, and P<0.05 was the significant difference.Results Fifty-six patients were followed up for an average of 16.00±4.51 months ranged from 12 to 20 months. No mixed infection, relapse of tuberculosis, pedicle screw loosening and retreating were found. The bleeding volume in the group A was (154.37±11.28) ml and the group B was (297.28±30.73) ml. The operation time was (193.56±15.72) min in the group A and (205.07±19.80) min in the group B. The mean operation time and bleeding volume in group A were less than those in group B with significant difference (t=6.412,t=3.937,P=0.000). The accuracy of pedicle screw placement was 85.80% (151/176) in group A and 84.18% (149/177) in group A. There was no significant difference in the accuracy of pedicle screw placement between the two groups (χ ²=0.359, P=0.549). Postoperative complications occurred 16 cases (57.14%) in group A and 17 cases (60.71%) in group B without significant statistically difference between the two groups (χ ²=0.074,P=0.786). Japanese Orthopaedic Association Scores (JOA) score of lumbar function, preoperative follow-up was (6.37±0.51) scores in group A and (6.41±0.61) scores in group B, 1 month after operation was (16.82±2.75) scores in group A and (19.03±3.57) scores in group B. There was significant difference between the two groups (t=0.128, P=0.036), the last follow-up was (26.71±3.91) scores in group A and (27.23±5.23) scores in group B, there was no significant difference between the two groups (t=0.279, P=0.782).Conclusion The early curative effect of group A and group B was satisfactory,but the former had the advantages of less trauma, shorter operation time and less bleeding than the latter.

The clinical effect of thermo ablation and cryoablation treatment of lymph nodes fistula type of central airway tracheobronchial tuberculosis (TBTB) under flexible bronchoscopy

Fei TANG,Li-ping LYU

Chinese Journal of Antituberculosis. 2019, 41(6):  657-661.  doi:10.3969/j.issn.1000-6621.2019.06.012

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Objective To evaluate the efficacy of combined thermoablation and cryoablation treatment of lymph nodes fistula type of central airway tracheo-bronchial tuberculosis (TBTB) under flexible bronchoscopy (referred to as “bronchoscopy”).Methods A total of 78 patients with TBTB were enrolled in the Anhui Provincial Chest Hospital from January 2013 to January 2017. After approval by the Ethics Committee, 39 patients in the control group were treated with systemic anti-tuberculosis treatment and bronchoscopy which biopsy forceps were repeatedly cleaned and the isoniazid was injected through the catheter at the lesion. The observation group were treated with systemic anti-tuberculosis treatment and bronchoscopy which combined with cryo-thermo ablation and the isoniazid was injected through the catheter at the lesion. All of them were ended up with endoscopic treatment after stable lesions and followed up for 1 year. The average number of treatments was calculated, and the clinical symptoms and bronchoscopy findings were observed at 1, 3, 6, and 12 months after treatment, and the treatment efficiency was evaluated.Results The average number of interventional treatments in the observation group and the control group were (12.49±3.34) times and (17.28±3.64) times. The average number of treatments in the observation group was significantly lower than that in the control group. The difference was statistically significant (t=6.055, P<0.001); The effective rates of treatment in the observation group at 3 months, 6 months, and 12 months were 48.72% (19/39), 82.05% (32/39), and 92.31% (36/39) respectively, which were higher than that in the control group (20.51% (8/39), 53.85% (21/39), 71.79% (28/39)), the difference was statistically significant (χ ²=6.854, P=0.009; χ ²=7.123, P=0.008; χ ²=5.571, P=0.018). A total of 43 patients in the two groups were treated with a small amount of hemorrhage, which was improved after endoscopic spray of 1∶20000 adrenaline, ice physiological saline and Bothrops atrox hemocoagulase, and there were no serious complications such as major bleeding, perforation, and pneumothorax.Conclusion The combined thermoablation and cryoablation treatment of lymph nodes fistula type of central airway tracheo-bronchial tuberculosis under flexible bronchoscopy can reduce the average number of treatments and improve the patients’ treatment efficiency.

Epidemic trends and characteristics of pulmonary tuberculosis in students in China from 2014 to 2018

Hui CHEN,Yin-yin XIA,Can-you ZHANG,Jun CHENG,Hui ZHANG

Chinese Journal of Antituberculosis. 2019, 41(6):  662-668.  doi:10.3969/j.issn.1000-6621.2019.06.013

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Objective To analyze the epidemic trends and characteristics of pulmonary tuberculosis (PTB, except for tuberculous pleurisy) in the national students in mainland China (not including Hong Kong, Macao and Taiwan), in order to provide a reference for the effective epidemic control of PTB in students.Methods The PTB reporting data in students from the Infectious Diseases Reporting System (IDRS), Tuberculosis Information Management System (TBIMS) and China Statistical Yearbook were collected from 2014 to 2018 to analyze the spatial, temporal and population distribution of reported PTB in students and the patients with delayed treatment. The total number of the national students in China were 258000000 in 2014, 255810000 in 2015, 259270000 in 2016, 262750000 in 2017 and 268670000 in 2018, respectively.Results A total of 48289 student patients with PTB were reported in 2018 with the reported incidence of 17.97/100000 (48289/268670000), increased by 29.19% ((17.97-13.91)/13.91) in comparison with that in 2014 (13.91/100000, 35881/258000000). Annually, March and April were the peak periods for students to report PTB (the reported cases in the two months from 2014 to 2018 were 4506 and 4521, 4350 and 4252, 4802 and 4110, 4695 and 3810, and 5407 and 4851, respectively). The epidemic incidence of the two months was low in the eastern region (11.64/100000, 12391/106410000) and high in the central (15.82/100000, 13369/84500000) and western regions (28.97/100000, 22529/77760000). In the constituent ratio for all age groups in the reported cases in students in 2018, the highest proportion was at senior high school stage (16-18 age group) with an average of 43.90% (21186/48257), followed by college and junior college stage (19-22 age group) with 31.44% (15172/48257). In 2018, the median time interval (quartile) from the onset of symptoms to the first visit to a medical institution for the student patients with PTB was 13 (3, 33) days, which had no difference with that in 2017 (13 (3, 34) days, Z=-0.31, P=0.753). The delayed treatment rate of patients was 47.38% (20643/43572).Conclusion From 2014 to 2018, the epidemic PTB incidence in students had a rising trend, highly occurred in 16-18 ages, and the epidemic incidence was slightly higher in the western region. The students are still one of the important populations for TB prophylaxis. Therefore, health education should be further developed and the capacity for active monitoring should be enhanced.

Comparison of ARIMA model and Elman neural network along with ARIMA-Elman combination model in predicting incidence of tuberculosis in Beijing

Yin-suo YAN,Shan-hua SUN,Ya-min LI,Yan-yuan LI,Xin ZHAO,Li-ying TAO,Zhi-dong GAO

Chinese Journal of Antituberculosis. 2019, 41(6):  669-675.  doi:10.3969/j.issn.1000-6621.2019.06.014

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Objective To compare the predictive effects of Autoregressive Integrated Moving Average (ARIMA) model, Elman neural network model and their combination (ARIMA-Elman) model on the incidence of pulmonary tuberculosis in Beijing, and explore the best predictive model.Methods The data between 2010 to 2017 was used as training data to establish three models (ARIMA, Elman, ARIMA-Elman). Data of 2018 was used as testing data to evaluate the predictive effects of three models. The Mean Absolute Error and the Mean Absolute Percentage Errors were two predictive efficiency indicators.Results The Relative Errors of ARIMA model, Elman neural network and ARIMA-Elman model were mostly within ±10% in predicting the monthly incidence of tuberculosis in Beijing, there were 8, 8 and 9, respectively. Except for the parts within ±10%, the number of Relative Errors within ±(10%-20%) for ARIMA model was 3 and 1 over ±20%; the number of Relative Errors within ±(10%-20%) for Elman neural network was 2 and 2 over ±20%; while the number of ARIMA-Elman combination model was 3 within ±(10%-20%). The mean Absolute Errors of the three models above were 44.7 (536/12), 47.8 (574/12) and 43.8 (526/12), while the Mean Absolute Percentage Errors were 8.7% (1.039/12×100%), 8.2% (0.99/12×100%) and 7.9% (0.953/12×100%) respectively. Both the two indicators of ARIMA-Elman model were smaller than the other two models.Conclusion ARIMA-Elman combination model has higher prediction accuracy and more desirable effect on the prediction of the incidence of tuberculosis in Beijing.

The value of target management in improving the quality of sputum samples retention of initially treated pulmonary tuberculosis patients

Hua JIANG,Lin WANG,Ling-ling TANG,Xian-Lan ZENG

Chinese Journal of Antituberculosis. 2019, 41(6):  676-680.  doi:10.3969/j.issn.1000-6621.2019.06.015

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Objective To explore the application effect of target management in quality control of sputum specimens retention of initially treated pulmonary tuberculosis patients.Methods A total of 338 initially treated pulmonary tuberculosis patients were collected as subjects, who were hospitalized because of suspected tuberculosis and then were diagnosed and accepted the treatment in Tuberculosis Department of Shanghai Pulmonary Hospital from July 2017 to December 2017. They were divided into two groups: the observation group (N=165, patients hospitalized in the Ward 5 of Tuberculosis Department) and the control group (N=173, patients in the Ward 1). The patients in the control group received the routine nursing management in tuberculosis department, and the pro-paganda and education of sputum specimen retention. Meanwhile, sputum specimen retention and the standard inspections were supervised and inspected. In addition to these routine managements, patients in the observation group accepted other target management approaches for the sputum specimen retention, namely doctors, nurses and patients jointly involved and determined the overall target of sputum specimen retention, and decomposed the overall target into sub-targets, and finally reached the overall target by sub-target setting, target implementing, feedback processing, and implementation results checking. The completion rate, qualified rate and positive rate of Mycobacterium smear in sputum samples between the two groups were compared.Results In observation group, 502 sputum specimens were supposed to be retained, and 476 were actually remained, among them 432 were qualified and 312 were positive for Mycobacterium smear. In control group, 524 sputum specimens were supposed to be retained, and 431 were actually remained, among them, 307 were qualified and 172 were positive for Mycobacterium smear. In observation group, the completion rate of retention of sputum specimens was 94.82% (476/502), qualified rate was 90.76% (432/476), and positive rate of Mycobacterium smear was 72.22% (312/432). All of them were higher than that in control group (completion rate: 82.25% (431/524), qualified rate 71.23% (307/431), positive rate of Mycobacterium smear 56.03% (172/307)). The difference was statistically significant (χ ² were 39.50, 57.15, 20.83, P<0.01).Conclusion Target management can improve the initiative of sputum sample retention, the quality and positive rate of sputum samples, and is beneficial to the early diagnosis of suspected pulmonary tuberculosis.

The correlation between loneliness and social support of nurses in tuberculosis wards (Investigation and analysis of 91 tuberculosis nurses)

Bin WAN,Xia ZHAO,Li FU,Xu-jue XIAO,Yan JIN

Chinese Journal of Antituberculosis. 2019, 41(6):  681-686.  doi:10.3969/j.issn.1000-6621.2019.06.016

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Objective To investigate the status of loneliness and social support of nurses in tuberculosis wards, and to understand the correlation between loneliness and social support.Methods From September 5th to September 30th, 2018, 113 nurses in the tuberculosis wards of the Public Health Clinical Center of Chengdu were surveyed with UCLA Loneliness Scale (Version 3) and Social support rate scale (SSRS). A total of 91 valid questionnaires were collected with an effective response rate of 80.5%. Pearson correlation analysis was used to explore the correlation between them.Results The loneliness score of 91 nurses was 41.43±9.73. 25.3% (23/91) of nurses had mild loneliness, 58.2% (53/91) had moderate loneliness, and 13.2% (12/91) had moderately severe loneliness and 3.3% (3/91) had severe loneliness. The total score of social support was 44.75±8.32. The scores of subjective support, objective support and utilization rate of social support in three dimensions were 27.20±6.51, 9.45±2.99, and 8.10±2.12 respectively. 46.2% (42/91) of nurses had medium social support level, 53.8% (49/91) had high social support level. Pearson correlation analysis showed that there was significant correlation between loneliness and the score of social support (r=-0.61, P=0.000), subjective support (r=-0.58, P=0.000) and utilization of support (r=-0.50, P=0.000) among tuberculosis nurses.Conclusion Nurses in tuberculosis wards have a higher sense of loneliness with moderate and high level social support. Loneliness has a significant correlation with social support, and improving the social support of nurses can reduce their loneliness.

Analysis of health education channels for conveying key tuberculosis messages in different regions and age groups in China

Jing WANG,Yin-yin XIA,Tao LI,Can-you ZHANG,Ming-ting CHEN,Hui ZHANG,Qing-lin MENG

Chinese Journal of Antituberculosis. 2019, 41(6):  687-694.  doi:10.3969/j.issn.1000-6621.2019.06.017

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Objective To provide scientific evidence for health education activities on tuberculosis (TB) control, through the nationwide investigation of health education channels for conveying TB key messages among residents in China. Methods Multi-stage stratified cluster sampling method was applied to select 181 survey sites in 31 provinces, including 84 urban survey sites and 97 rural survey sites. Of all 33357 subjects who were 15 years and above, 18156 (54.43%) subjects and 15201 (45.57%) subjects were from urban and rural areas respectively. Subjects were divided into 12 population groups to compare their different preferences of health education channels and choice of propaganda materials. These 12 groups were population groups of 15-60 years old from eastern urban area (5311 subjects) and eastern rural area (3561 subjects), groups of 60 years old and above from eastern urban area (1618 subjects) and eastern rural area (1106 subjects); groups of 15-60 years old from central urban area (6055 subjects) and central rural area (4476 subjects), groups of 60 years old and above from central urban area (1560 subjects) and central rural area (974 subjects); and groups of 15-60 years old from western urban area (2791 subjects) and western rural area (3789 subjects), groups of 60 years old and above from western urban area (732 subjects) and western rural area (1218 subjects). All subjects were interviewed face to face using the awareness questionnaire of TB key messages designed by experts. General information on their socioeconomical characteristics and information about their channels of receiving health education were collected. Finally, 33191 questionnaires were calculated as valid, thus the retrieve rate was 99.50%. Among whom 21296 subjects (64.16%) confirmed they had received at least some sort of health education before this survey. Results Out of the 21296 subjects who had received health education from the 12 population groups, the first 3 mostly preferred media were television (17.46%, 11087/63510), broadcasting (14.54%, 9237/63510), and leaflet/flyer/poster (13.60%, 8635/63510). Group with highest preference for television and broadcasting was group of 60 years old and above from central urban area (23.07%, 314/1361 for TV and 19.62%, 267/1361 for broadcasting). As well, group of >60 years old from central rural area preferred leaflet/flyer/poster (14.97%, 299/1998) best. The group of 15-60 years old in eastern urban area had the highest preference rate (5.89%, 577/9792) for website/Mini-blog/WeChat, whereas the group of 60 years old and above from western rural area got the lowest (0.30%, 5/1639). The best 3 channels for all 33357 subjects as ideal channel for obtaining TB control information were broadcasting/television/film/internet/audio and video materials (26.76%, 15517/57978), doctor propaganda (18.21%, 10559/57978), and poster/bulletin board/blackboard newspaper/exhibition panel (16.06%, 9311/57978). For the choices of propaganda materials, they loved picture-oriented (25.76%, 9549/37074) and mainly text products (24.57%, 9110/37074) best. For the acceptance level about internet, the highest one (9.16%, 163/1779) was the group of 60 years old and above from eastern urban area, the lower ones (2.60%, 27/1037 and 2.71%, 25/923 respectively) were the ≥60 groups from central and western rural areas. The most favorable online consultation or enquiry approaches were “consulting a medical professional online” (27. 89%, 9653/34608), “viewing professional medical websites” (21.86%, 7563/34608), “searching by Baidu or Google” (15.74%, 5448/34608), etc. The way of online knowledge dissemination preferred by the public were mainly text + pictures (29.14%,11268/38672) and text + videos (26.20%,10131/38672). Conclusion Different health education channels and approaches should be taken as per the characteristics of different regions, areas and age group populations. Key TB control information should be effectively conveyed to specific targeted groups, especially to the elderly population and the western rural population with relatively low awareness rate.

Review Articles

γδ T cells in tuberculosis immunotherapy and future prospects

Liang FU,Juan LIANG,Guo-liang ZHANG,Yang-zhe WU,Guo-fang DENG

Chinese Journal of Antituberculosis. 2019, 41(6):  695-698.  doi:10.3969/j.issn.1000-6621.2019.06.019

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Traditional anti-tuberculosis drugs, directly targeting on the Mycobacterium tuberculosis, have played important roles on controlling tuberculosis. However, new strategies for treatment are needed to solve the remaining problems. In recent years, “host-directed therapy”,including new use of old drugs and cell immunotherapies, has been reported to have exciting efficacy. The γδ T cell immunotherapy attracted especial attention by immunologists and clinicians. The γδ T cells are a subset of T cells, quite different from αβ T cells. The safety and efficacy of γδ T cell immunotherapy for cancer treatment have been confirmed in clinical trials. At present, studies on animal and human with tuberculosis have demonstrated that γδ T cells play important roles in immune response against tuberculosis. This review introduces current implications of host-targeted therapy, especially γδ T cell immunotherapy in tuberculosis treatment, and recent progresses of the basic research and preclinical studies on this new therapy, and also proposes potential possibilities in anti-tuberculosis treatment.

Research and progress of PK/PD for anti-tuberculosis drugs

Jiao-jie ZHAO,Yu LU

Chinese Journal of Antituberculosis. 2019, 41(6):  700-704.  doi:10.3969/j.issn.1000-6621.2019.06.020

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Tuberculosis treatment requires a combination of multiple drugs and long-term treatment, therefore, it is urgent to develop new anti-tuberculosis drugs. The research and development of new anti-tuberculosis drugs are inadequate. Exploring the pharmacokinetic/pharmacodynamics (PK/PD) of existing drugs in vitro and in vivo and optimizing the use of anti-tuberculosis drugs are essential to improve treatment efficacy and reduce the occurrence of drug-resistant tuberculosis. This article reviewed the PK/PD research methods and characteristics of anti-tuberculosis drugs PK/PD, in order to provide reference for clinical optimization of anti-tuberculosis treatment.

Short Articles

Surgery join with anti-tuberculosis and anti-viral therapy to treat patient combined with cervical tuberculous lymphadenitis and AIDS (With 12 cases of clinical effect analysis)

Li-wei WANG,Chang-qing WU

Chinese Journal of Antituberculosis. 2019, 41(6):  704-708.  doi:10.3969/j.issn.1000-6621.2019.06.021

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The clinical data of 12 patients with cervical lymph node tuberculosis (CTL) complicated with AIDS who underwent surgical treatment were collected in the Infectious Diseases Hospital Affiliated to Soochow University from April 2012 to June 2018. There were 10 males and 2 females; They were 19-62(38.0±11.3)years old. Both the standard anti-tuberculosis and antiviral drugs were supplemented by surgical treatment, and the level of CD4 ⁺ T lymphocytes, the ratio of CD4 ⁺ T lymphocytes/CD8 ⁺ T lymphocytes and the rate of blood cell deposition (ESR) were compared and analyzed before and 3 months after operation. CD4 ⁺ T lymphocyte were (267.07±77.89)cells/μl after operation, preoperative level were (156.80±84.83)cells/μl, the ratio of CD4 ⁺/CD8 ⁺ T lymphocyte was 0.68±0.53, preoperative ratio was 0.47±0.32. The differences were statistically significant (t=28.30, P=0.019; t=20.37, P=0.033). The postoperative ESR was (15.88±11.08) mm/1 h, and the preoperative ESR was (52.32±17.12) mm/1 h. The difference was statistically significant (t=12.92, P=0.025). All the 12 patients were followed up, 11 patients had primary wound healing and CTL symptoms disappeared; 1 case had delayed wound healing and healed after 2 months of local dressing change; 3 cases had recurrence of CTL, and the wound healed well after operation; 1 case died in the course of treatment, the cause of death was late AIDS and complicated with refractory pneumocystis pneumonia. Normalized control of anti-tuberculosis and antiviral drugs, combined with reasonable and precise surgical intervention at appropriate time, has a better therapeutic effect on patients with cervical lymph node tuberculosis complicated with AIDS.