Table of Content

10 October 2018, Volume 40 Issue 10

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Editorial

New TruArray technology for detection of Mycobacterium tuberculosis and drug resistance from sputum specimen

Dan SU,Qiang LI,Nan-ying CHE,Xi-chao OU,Bing ZHAO,Yan-lin ZHAO,Hai-rong HUANG

Chinese Journal of Antituberculosis. 2018, 40(10):  1034-1039.  doi:10.3969/j.issn.1000-6621.2018.10.002

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Objective To evaluate the performance of a new gel element arrays gel-drop (TruArray) chip for the detection of Mycobacterium tuberculosis (MTB) and rifampicin (RFP) and isoniazid (INH) resistance from sputum specimen. A total of 149 samples provided by pulmonary tuberculosis suspected patients from Capital Medical University Affiliated Beijing Chest Hospital were selected for smear microscopy, MGIT 960 liquid culture, TruArray and GeneXpert MTB/RIF (GeneXpert) test, and perform identification sequencing, MGIT 960 drug susceptibility test and drug resistance-related gene sequencing for liquid culture positive strains. Analyze the performance of TruArray test for MTB and its drug resistance detection in sputum samples. The detection rates of MTB in liquid culture, GeneXpert and TruArray test were 32.2% (48/149), 53.7% (80/149) and 57.0% (85/149), respectively. There was no statistical difference in the detection rates of TruArray and GeneXpert (χ ²=0.34, P=0.560), but the positive rate of TruArray test was significantly higher than that of liquid culture (χ ²=18.59, P<0.01). With the MGIT 960 liquid culture result as standard, the sensitivity and specificity of TruArray test for MTB detection in sputum samples were 97.9% (47/48) and 61.4% (62/101), respectively. Compared with GeneXpert result, the sensitivity and specificity of TruArray test for MTB detection were 97.5% (78/80) and 88.4% (61/69), respectively. Based on the results of MGIT 960 drug susceptibility test, the sensitivity and specificity of TruArray test for RFP resistance detection were 91.7% (11/12) and 96.8% (30/31), respectively. Compared with GeneXpert assay, the sensitivity and specificity of the TruArray test for RFP resistance detection were 85.0% (17/20) and 97.9% (47/48), respectively. Based on the sequencing results of drug resistance genes, the sensitivity and specificity of TruArray test for RFP resistance detection was 92.3% (12/13) and 100.0% (30/30), respectively. Based on the results of MGIT 960 liquid susceptibility test, the sensitivity and specificity of the TruArray test for INH resistance detection were 78.6% (11/14) and 93.8% (30/32), respectively. Using the sequencing results of drug resistance genes as the criterion, the sensitivity and specificity of TruArray test for INH resistance detection were 100.0% (11/11) and 94.3% (33/35), respectively. TruArray test is a rapid and reliable diagnostic method, it has a very good application prospect in tuberculosis and multidrug resistance tuberculosis detection.

The value of cross priming amplification test in clinical diagnosis of suspected pulmonary tuberculosis patients

Xi-chao OU,Hai-yan DONG,Hui XIA,Sheng-fen WANG,Yan QU,Bing ZHAO,Zhi-ying ZHANG,Yan-lin ZHAO

Chinese Journal of Antituberculosis. 2018, 40(10):  1040-1045.  doi:10.3969/j.issn.1000-6621.2018.10.003

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Objective To evaluate the application value of cross priming amplification (CPA) test in the early clinical diagnosis of pulmonary tuberculosis (PTB). TB suspected patients who went to the 7 TB dispensaries at county or district level in Foshan and Jiangmen cities of Guangdong province from January 2016 to October 2016 were enrolled, a total of 6507 suspected PTB patients were included. All of the recruited patients completed chest X-ray examination and provided sputum samples to perform smear microscopy, solid culture and CPA test, and species identification were performed for culture positive strains. The clinician made diagnosis combining laboratory and clinical examination results, and clinical experts at national level reviewed the initial clinical diagnosis on-site. The proportion of pathogenic positive patients in active PTB was analyzed. Comparison with reviewed clinical diagnosis results was conducted to analyze the sensitivity and specificity of smear microscopy, solid culture and CPA. The positive rates of smear microscopy, solid culture and CPA were 18.2% (1187/6507), 25.0% (1629/6507) and 23.9% (1555/6507) respectively. Among 3199 clinically diagnosed patients with active PTB, the positive detection rate of smear combined culture was 48.5% (1550/3199), the positive rate of smear combined with CPA was 47.9% (1531/3199), and that of smear combine culture and CPA was 54.4% (1740/3199). Compared with clinical diagnosis results as the standard, the sensitivities of smear microscopy, solid culture and CPA test for TB detection were 35.0% (1120/3199), 46.4% (1485/3199) and 44.6% (1428/3199) respectively, and the specificities were 98.0% (3241/3308), 95.7% (3164/3308) and 96.2% (3181/3308), respectively. TB dispensary at county (district) level can apply CPA test for rapid diagnosis of suspected PTB patients. The combination of multiple diagnostic techniques can significantly increase the pathogen positive rate of active TB patients.

Differential expression and diagnostic value of three cytokines in pleural effusion between pulmonary tuberculosis and lung cancer

Hao-ran LIU,Ya-li ZHANG,Wei-cong REN,Ling-juan ZHAO,Chuan-you LI,Wei WANG,Meng-qiu GAO

Chinese Journal of Antituberculosis. 2018, 40(10):  1046-1050.  doi:10.3969/j.issn.1000-6621.2018.10.004

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Objective To analyze the difference of macrophage migration inhibitory factor (MIF), retinoid acid related orphan receptor alpha (RORα) and retinoid acid related orphan receptor gamma (RORγ) in the pleural effusion of patients with pulmonary tuberculosis (TB) and lung cancer, and to explore their values in the differential diagnosis. By simple random sampling, the frozen pleural effusion samples of pulmonary tuberculosis and lung cancer were numbered, and 80 samples were collected, the basic information of the subjects was summarized. The levels of MIF, RORα and RORγ in the pleural effusion were detected by enzyme-linked immunosorbent assay (ELISA). The application software SPSS 20.0 was used for comparison and analysis, and the measurement data in this study do not conform to normal distribution, so the Mann-Whitney U test has been used, the difference was statistically significant when P<0.05. The medians of MIF level (quartile) [M (Q₁,Q₃)] in the pleural effusion of the tuberculosis group and lung cancer group were 5.83 (2.41, 16.43) and 2.79 (0.91, 11.12) ng/L respectively, there was significant difference between the groups (U=2314.50,P<0.01). The RORα levels [M (Q₁, Q₃)] in the pleural effusion of the tuberculosis group and lung cancer group were 0.63 (0.37, 1.66) and 0.63 (0.57, 2.16) ng/L respectively, there was no significant difference between the two groups (U=3525.00, P>0.05); the levels of RORγ in the pleural effusion of the tuberculosis group and lung cancer group were 3.23 (1.82, 5.26) and 3.44 (1.94, 7.11) ng/L respectively, with no significant difference (U=3431.50, P>0.05). The level of MIF in the pleural effusion of patients with tuberculosis is higher than the patients with lung cance, the detection of MIF level in pleural effusion is certainly diagnostically valuable in differentiating pulmonary tuberculosis from lung cancer. And the diagnostic value of RORα and RORγ in pleural effusion remains to be verified.

Association of cytokine genetic polymorphisms with susceptibility to diabetic pulmonary tuberculosis

Si-jia DONG,Li YUAN,Cheng CHEN,Wei-li JIANG,Qi ZHAO

Chinese Journal of Antituberculosis. 2018, 40(10):  1051-1059.  doi:10.3969/j.issn.1000-6621.2018.10.005

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This study aims to reveal the associations among IFN-γ +874 A/T, IL-10 -592 A/C, -1082 G/A SNPs and risk of diabetic pulmonary tuberculosis, and consequently provide further evidence for research on pathogenesis of diabetic pulmonary tuberculosis (PTB-DM) and the screening for diabetic pulmonary tuberculosis patients.

A case-control study based on the screening of DM in PTB patients (142 cases) was carried out in 3 counties in Jiangsu Province from 1 April, 2013 to 31 March, 2014. Cases in this study were all diagnosed diabetic pulmonary tuberculosis patients, whereas control groups were PTB patients (147 cases) and DM patients (141 cases) matching with gender and age. Social demographic information was collected by a questionnaire and DNA was extracted from the blood sample collected.The polymorphisms of IFN-γ +874 A/T, IL-10 -592 A/C and -1082 G/A were detected by PCR-RFLF methods and followed by direct sequencing. Statistical analyses were conducted using the EpiData and SPSS software version 16.0. Pearson chi-square and logistic regression were used to estimate the associations among IFN-γ+874 A/T, IL-10 -592 A/C, -1082 G/A SNPs and risk of diabetic pulmonary tuberculosis.

In the study on IL-10 -1082 G/A, statistical differences were discovered between PTB-DM patients and DM controls (A allele, 92.61% (263/284) versus 87.59% (247/282)(χ²=3.995, P=0.046); AA genotype, 85.21% (121/142) versus 75.18% (106/141). The AA genotype of IL-10 had a 1.970 fold increased risk for diabetic pulmonary tuberculosis individuals (OR=1.970, 95%CI=1.066-3.643, respectively). Linkage disequilibrium was found between IL-10 -592 and IL-10 -1082 (D'=0.959,r²=0.181,P<0.001) and statistical significance was also found in IL-10 -592C/-1082A haplotype between diabetic pulmonary tuberculosis patients and DM controls (25.90% versus 17.60%, P=0.026); IL-10 -592C/-1082A haplotype had a 1.590 fold increased risk for diabetic pulmonary tuberculosis individuals (OR=1.590, 95%CI=1.056-2.396, respectively).

Our results indicated an association between IL-10 -1082G/A polymorphism and susceptibility to diabetic pulmonary tuberculosis. Novel risk haplotype of IL-10 has been identified, of which -592C/-1082A haplotype was found to be strongly linked to diabetic pulmonary tuberculosis susceptibility. However, no association was found between IL-10 -592 or IFN-γ +874 and the risk of diabetic pulmonary tuberculosis.

Prevalence and molecular characterization of multidrug-resistant Mycobacterium tuberculosis isolates resistant to fluoroquinolones in Chongqing

Yan HU,Jie LIU,Jing SHEN,Da-mian ZHU,Xin FENG,Lin CHEN,Jian ZHAN,Xi-chao OU,Yang ZHOU,Yan-lin ZHAO

Chinese Journal of Antituberculosis. 2018, 40(10):  1060-1065.  doi:10.3969/j.issn.1000-6621.2018.10.006

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Objective To analyze the molecular characteristics of fluoroquinolones (FQs) resistance-associated gene mutations and the correlation with the different genotypes among the MDR-TB strains in Chongqing. Two hundred and twenty-nine MDR-TB clinical strains were tested for susceptibility to ofloxacin, levofloxacin, moxifloxacin, and gatifloxacin using microplate alamar blue assay (MABA). PCR and sequencing were conducted for gyrA and gyrB genes conferring FQs resistance. The Beijing genotypes were identified with real-time polymerase chain reaction (PCR) melting curve assay. Among the 229 MDR-TB strains, 94 strains (41.0%, 94/229) were resistant to any FQ. The prevalence of FQs resistance in Chongqing were highest for ofloxacin (41.0%, 94/229), intermediate for levofloxacin (31.4%,72/229) and moxifloxacin (30.6%, 70/229), and lowest for gatifloxacin (20.1%, 46/229).The 94 strains resistant to FQs contained 81 gyrA mutation strains (86.2%, 81/94), and the highest mutation frequency was at codon 94 (60.6%,57/94). Mutations with gyrB were observed in 10 FQ-resistant strains (10.6%, 10/94). Seven strains with double mutations in gyrA, and 2 of the 9 strains with Asp94Gly and Ala504Thr/Ala504Val double mutations in gyrA and gyrB respectively, showed high-level FQ resistance. The proportion of Beijing genotype strains was 85.1% (80/94) among FQ-resistant strains in Chongqing. Of these, 60.0% (48/80) were modern-Beijing sublineage strains. Modern-Beijing sublineage strains accounts for the majority of FQ-resistant strains and the resistant related mutations mainly occur in gyrA gene.

Clinical value of simultaneous amplification and testing in the auxiliary diagnosis of extrapulmonary tuberculosis

Xiao-ping NIE,Huan LI,Hong-ying YANG,Ming LUO,Guo-qiang YANG,Kan ZHOU,Zheng-gu HUANG,Peng-sen WANG,Chuan-yu LIAO,Hui-zhen ZHANG,Gang ZHOU,Yu CHEN,Yao-kai CHEN,Tao SHI,Tong-xin LI

Chinese Journal of Antituberculosis. 2018, 40(10):  1066-1070.  doi:10.3969/j.issn.1000-6621.2018.10.007

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Objective To explore the clinical value of simultaneous amplification and testing (SAT) in the auxiliary diagnosis of extrapulmonary tuberculosis (TB). We collected abscess fluid or surgical removal tissue samples at the lesion site of inpatients in Department of Tuberculosis, General Surgery and Orthopaedic Surgery of Chongqing Public Health Medical Center between Jan. 2016 and Dec. 2017. Based on the medical records regarding the results of extrapulmonary TB diagnosis, the extrapulmonary TB samples were set as experimental group, and nontuberculous samples as control group. All samples were pretreated by kit manufacturer’s instruction then cultured on solid Lowenstein-Jensen slants and in BACTEC MGIT 960 liquid, and were detected with SAT method. Identification of strains were conducted for specimens with culture-positive and SAT-negative results. The sensitivity, specificity and clinical value of SAT detection for extrapulmonary TB were analyzed, taking the culture method and clinical diagnosis as standards, respectively. The analyses were performed using SPSS 13.0 software. The categorical data were analyzed by χ ² test, and the difference was statistically significant at P<0.05. Among the 127 culture-positive specimens in the experimental group, 107 were positive and 20 were negative by TB-SAT detection. For the 306 culture-negative specimens in the experimental group, 73 were positive and 233 were negative by TB-SAT detection. In the control group, one specimen was positive by culture method and negative by TB-SAT test; the remaining 48 specimens were negative for both culture and TB-SAT method. Compared with the culture method, the sensitivity and specificity of the TB-SAT method were 83.6% (107/128) and 79.4% (281/354), respectively. Meanwhile, compared with the clinical diagnosis of patients, the sensitivity and specificity of the culture method were 29.3% (127/433) and 98.0% (48/49), respectively; and the sensitivity and specificity of the TB-SAT test were 41.6% (180/433) and 100.0% (49/49). The positive rate of culture method was 29.3% (127/433), and the positive rate of SAT method was 41.6% (180/433); the difference was statistically significant (χ ²=14.17, P<0.05). Compared with other methods used in this article, TB-SAT has the advantage of higher detection rate, sensitivity, and specificity as well as more convenient and rapid in diagnosis of extrapulmonary TB.

Application of isothermal amplification fluorescence in peripheral tuberculosis laboratory

Xiao-guang MA,Dan-wei ZHENG,Yan-kun ZHU,Jie SHI,Shao-hua WANG,Hui LI

Chinese Journal of Antituberculosis. 2018, 40(10):  1071-1074.  doi:10.3969/j.issn.1000-6621.2018.10.008

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Objective To evaluate the isothermal amplification fluorescence technique in detecting Mycobacterium tuberculosis in sputum of suspects in peripheral tuberculosis laboratory. Smear microscopy, L?wenstein-Jensen culture and isothermal amplification fluorescence tests were respectively performed to 4242 sputum samples from suspicious pulmonary tuberculosis patients in four county level laboratries in Henan province during 2014 to 2015, the sensitivity, specificity and detection time were compared with each method using Chi square test and the P value was set as <0.05. Of 4242 TB suspects’ samples, the number of smear positive cases 351 (8.21%), the number of culture positive was 576 (13.47%), the number of isothermal amplification fluorescence 733 (17.14%). The sensitivity of three detection methods were statistically significantly different, χ ²=153.412,P<0.001. The reporting time of the isothermal amplification fluorescence method was about 2 hours. Compared with culture as the standard, the sensitivity and specificity of the isothermal amplification fluorescence method were 86.81% (500/576) and 93.64% (3433/3666) respectively. Positive predictive value (PPV) and negative predictive value (NPV) of the isothermal amplification fluorescence method were 68.21% (500/733) and 97.83 (3433/3509) respectively. The sensitivity, specificity, PPV and NPV of sputum smear microscopy were 57.29% (330/576), 99.43% (3645/3666),94.02% (330/351),93.68% (3645/3891)respectively. The results of the isothermal amplification fluorescence method and sputum smear microscopy was consistent with L?wenstein-Jensen culture (Kappa values were 0.722 and 0.679). There was a statistically significantly difference in sensitivity between the isothermal amplification fluorescence method and sputum smear microscopy (χ ²=153.336,P<0.001). The isothermal amplification fluorescence method shows more sensitivity and specificity than the traditional methods, and is a rapid, sensitive, simple and specific method for the detection of Mycobacterium tuberculosis, then play an important role in diagnosing tuberculosis in peripheral laboratories .

Clinical value of automatic fluorescence mycob.T stainer and scanner for detecting tuberculosis

Qiang LI,Hong-guo YANG,Yun-feng DENG,Xi-chao OU,Hui XIA,Yan-lin ZHAO

Chinese Journal of Antituberculosis. 2018, 40(10):  1075-1078.  doi:10.3969/j.issn.1000-6621.2018.10.009

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Objective To observe the clinic value of automatic fluorescence Mycob.T Stainer and Scanner (AFSS) for detecting tuberculosis. A total of 2243 sputum specimens from 748 suspected TB patients were tested at Linyi People’s Hospital from September to December in 2016. Each specimen was subjected to 2 direct smear slides. One slide was stained by fluorescence method and read with conventional fluorescence microscopy (FM) manually. Another slide was stained and scanned by AFSS. All the specimens were decontaminated by 4% NaOH and then inoculated into Lowenstein-Jensen (L-J) media for comparison. The performance of AFSS was analyzed compared with culture. All discrepancy slides between AFSS and conventional FM were rechecked by Ziehl-Neelsen microscopy. The average positive rate of AFSS was 32.1% while the average positive rate of conventional FM was 31.92%. No significant difference was observed (χ ²=0.016,P>0.05). Compared to culture, the sensitivity and specificity of AFSS for detecting Mycobacteria was 83.4% and 95.9%, respectively. The positive predictive value and negative predictive value was 91.6% and 91.4%, respectively. AFSS can detect Tuberculosis with high sensitivity, specificity and automation, and deserve to be promoted.

Comparative study on the efficacy of three detection techniques in diagnosis of senile pulmonary tuberculosis

Fa-xiang JIN,Wen-fang XU,Xiao-meng WANG,Zheng-wei LIU,Hua-yun WANG,Xue-fang CHEN,Xiao-jun. SUN

Chinese Journal of Antituberculosis. 2018, 40(10):  1079-1082.  doi:10.3969/j.issn.1000-6621.2018.10.010

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Objective To investigate the diagnostic value of Mycobacterium tuberculosis and rifampicin resis-tance real-time fluorescence quantitative nucleic acid amplification (GeneXpert MTB/RIF), light emitting diode (LED) fluorescence staining and BACTEC MGIT 960 system liquid culture (MGIT liquid culture) in elderly patients with pulmonary tuberculosis. A total of 250 elderly patients with pulmonary tuberculosis admitted to the Department of Pulmonary and Respiratory Infections of Shaoxing Municipal Hospital from 2013 to 2015 were collected. Among them, there were 159 males and 91 females, aged 65-89 years, with an average of (70.3±6.2) years. All of 250 sputum specimens were detected by LED fluorescence staining, MGIT liquid culture and GeneXpert MTB/RIF technique. The chi square test was used to compare between each group, and P<0.05 was considered statistically significant. The positive rates of LED fluorescence staining, MGIT liquid culture and GeneXpert MTB/RIF were 36.00% (90/250), 48.40% (121/250) and 50.40% (126/250) respectively. The positive rate of GeneXpert MTB/RIF (50.40%) was higher than that of LED fluorescence staining (36.00%) and the difference was statistically significant (χ²=10.56, P<0.01); and higher than that of MGIT liquid culture (48.40%), but the difference was not statistically significant (χ²=0.20, P>0.05); the positive rate of MGIT liquid culture (48.40%) was higher than that of LED fluorescence staining (36.00%). The difference was statistically significant (χ²=7.88, P<0.01). The sensitivity, specificity, positive predictive value and negative predictive value of GeneXpert MTB/RIF were 95.93% (118/123), 93.70% (119/127), 93.65% (118/126) and 95.97% (119/124) respectively, and the results of the two tests have excellent consistency (Kappa value was 0.90). Among the three detection technologies in this study, GeneXpert MTB/RIF has a higher detection efficiency, which is highly consistent with the results of MGIT liquid culture, and has a good clinical application and promotion value.

The study of clinical application value of DNA microarray chip in detection of drug-resistant Mycobacterium tubercu-losis

Yong-mei SHAN,Wei-bing WANG,Jian-mei WANG

Chinese Journal of Antituberculosis. 2018, 40(10):  1083-1088.  doi:10.3969/j.issn.1000-6621.2018.10.011

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Objective To evaluate the performance of DNA microarray chip to detect Mycobacterium tuberculosis (MTB) and determine the susceptibility to isoniazid (INH) and rifampicin (RFP). A total of 814 specimens of sputum smear-positive (SS+) pulmonary tuberculosis cases registered in Guanyun County Center for Disease Control and Prevention between January 2011 and May 2017 were collected. Proportion method using L?wenstein-Jensen culture medium, drug susceptibility testing (DST) and DNA microarray chip were performed to detect MTB and to test the susceptibility to INH and RFP of the sputum specimens. The detection value of DNA microarray chip was assessed by using proportion method and DST as standard, respectively. DNA microarray chip showed a significant difference (χ ²=6.81, P<0.05) in the detection of MTB in SS+ cases with a detection rate of 86.1% (701/814), which was higher than that of proportion method (82.4%, 671/814). Taking proportion method as standard, the sensitivity and specificity of DNA microarray chip in detecting MTB were 92.4% (620/671) and 43.4% (62/143), Kappa value was 0.39, and positive predictive value (PPV) and negative predictive value (NPV) were 88.4% (620/701) and 54.9% (62/113), respectively. Taking DST as standard, analysis of 620 patients with complete results of INH- and RFP-resistance showed that the sensitivity of DNA microarray method for detecting INH and RFP resistance in new SS+ cases was 78.7% (37/47) and 84.6% (22/26), and the PPV was 69.8% (37/53) and 73.3% (22/30), respectively. The sensitivity of DNA microarray method for detecting INH and RFP resistance in relapse SS+ cases was 71.9% (23/32) and 89.3% (25/28), and the PPV were 85.2% (23/27) and 89.3% (25/28), respectively. Compared with proportion method, the detection rate of DNA microarray chip for MTB is higher. The testing performance of DNA microarray chip to detect INH- and RFP-resistance are sound regarding its high validity and reliability, which may be of great value in prevention and control of tuberculosis.

Spatial analysis on smear-positive pulmonary tuberculosis in Zhejiang province between year 2015 and 2017

Jian-mei WANG,Yu ZHANG,Nan QIN,Yue WANG,Lin ZHOU,Wei-bing WANG

Chinese Journal of Antituberculosis. 2018, 40(10):  1089-1094.  doi:10.3969/j.issn.1000-6621.2018.10.012

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Objective To analyze the spatial distribution pattern of smear-positive pulmonary tuberculosis patients registered in Zhejiang province, and determine the gathered areas, providing theoretical basis for further study of the risk factors of tuberculosis and prevention and control strategies. The registration data of smear-positive pulmonary tuberculosis in 89 counties in Zhejiang province from 2015 to 2017 was collected and was merged with a vector map to build spatial databases by ArcGIS (version 10.0). Global Moran’s I and local Moran’s I were calculated by GeoDa (version 1.6.0) software respectively, as well as spatial-temporal analysis were studied by SaTScan (version 9.3)software to detect the spatial autocorrelation and cluster range of the distribution of smear-positive pulmonary tuberculosis in Zhejiang province. From 2015 to 2017, a total of 30292 cases of smear-positive pulmonary tuberculosis were registered in Zhejiang province, and the mean annual registered incidence rate of each region was 20.69/100000 (range: 4.73 to 45.61/100000). The distribution of smear-positive pulmonary tuberculosis of each region in Zhejiang province showed global spatial autocorrelation (Moran’s I=0.429,Z=5.834,P=0.001). While at the local scale, 25 regions (P<0.05) with positive local spatial correlation (high-high pattern and low-low pattern) and negative local spatial correlation (low-high pattern and high-low pattern) were sort out for analysis, in which 12 regions showed high-high pattern and 11 regions showed low-low pattern, accounting for 92.0% (23/25), indicating the main result of local spatial autocorrelation analysis was positive. Spatial-temporal analysis using SaTScan software detected four cluster areas including 18 regions, and each cluster area showed statistical significance (P<0.001) with log likelihood ratio (LLR) of 211.54,57.66,51.70,44.47, respectively. There are apparent spatial autocorrelation and relative strong spatial heterogeneity existed in the distribution of smear-positive pulmonary tuberculosis in Zhejiang province.

Clinical efficacy of urokinase combined with ozone sequential irrigation in the treatment of tuberculous encapsulated pleural effusion

Ling CHEN,Li-hong LU,Jun-hong SUN

Chinese Journal of Antituberculosis. 2018, 40(10):  1095-1098.  doi:10.3969/j.issn.1000-6621.2018.10.013

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Objective To investigate the efficacy and safety of urokinase washout uses alone and ozone + urokinase sequential drug washout program in the treatment of patients with tuberculous encapsulated pleural effusion. One hundred patients with tuberculous encapsulated pleural effusion were chosen in the period from January 2016 to December 2017 in Beijing Ditan Hospital affiliated to Capital Medical University and randomly divided into two groups including control group (n=50) and observation group (n=50). Patients in the control group were given urokinase washout program and those in the observation group were given ozone + urokinase sequential drug washout program assisted with thoracic drainage. The short-term efficacy, drainage time, disappearance time of pleural effusion, hospitalization time, pleural thickness and the levels of pleural effusion protein and WBC count before and after treatment and the frequency of adverse reactions of both groups were compared. The overall effective rate of the observation group after treatment was significant higher than that of the control group (92.0% (46/50) vs 74.0% (37/50); χ ²=9.78, P=0.01). The drainage time, disappearance time of pleural effusion and hospitalization time of the observation group after treatment were significant shorter than those of the control group ((8.42±1.04)d vs (32.35±4.50)d, (8.15±1.86)d vs (14.09±2.59)d, and (11.82±2.39)d vs (16.31±3.64)d, respectively; t=3.14, 3.90, and 4.11, respectively; all Ps<0.05). The pleural thickness and the levels of pleural effusion protein and WBC count after treatment of observation group were significant less than those of the control group ((1.78±0.35) mm vs (2.31±0.52) mm, (37.84±3.72) g/L vs (49.42±5.98) g/L, and (1.38±0.27)×10 ³/L vs (2.03±0.42)×10 ³/L, respectively; t=2.89, 3.12, and 3.50, respectively; all Ps<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (10.0% (5/50) vs 6.0% (3/50); χ ²=1.33, P=0.490). Compared with urokinase washout uses alone, ozone + urokinase sequential drug washout program in the treatment of patients with tuberculous encapsulated pleural effusion possess the better clinical efficacy.

Investigations on willingness of anti-tuberculosis treatment in the cases diagnosed by active finding and impacts after interventions in provinces of China with a high prevalence of tuberculosis

Jie XU,Zhao-cai WANG,Yin-yin XIA,Can-you ZHANG,Jin-ming ZHAO,Hui-juan CHEN,Xiao DONG,Guo-feng YANG,Hui-hui LIU,Jun CHENG

Chinese Journal of Antituberculosis. 2018, 40(10):  1099-1109.  doi:10.3969/j.issn.1000-6621.2018.10.014

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Objective To understand the willingness of anti-tuberculosis treatment and explore the influence of health education on the rate of anti-tuberculosis treatment among tuberculosis cases diagnosed by active finding. Using a cross-sectional study method, 149 cases of tuberculosis patients found in the active screening program for tuberculosis were selected in one of the five provinces (or autonomous regions) with the highest tuberculosis incidence in Qinghai, Guizhou, Guangxi, Tibet, and Xinjiang from September to December in 2017. A 10-minute health education was conducted after the diagnosis, and a face-to-face interview questionnaire was conducted before and after the health education intervention. The questionnaire survey included personal basic information, family income, medical expenses, transportation costs to the designated hospital, treatment intention after diagnosis and after ten minutes’ health education, and the reasons not willing to accept treatment. Before and after intervention, 149 questionnaires were both sent out and 149 questionnaires were returned with 149 valid questionnaires. The treatment rate before and after health education were analyzed. Univariate analysis and multivariate logistic regression analysis were used to analyze the factors influencing the treatment willing of patients after health education. After health education, the rate of willing to receive treatment was raised from 78.52% (117/149) to 85.23% (127/149).After 10-minutes health education, the results of univariate analysis showed that compared with Guizhou (0, 0/39), the tuberculosis patients from Qinghai (29.41%, 10/34), Guangxi (26.09%, 6/23) and Xinjiang (15.62%, 5/32) were more reluctant to be treated (χ ²=18.13, P<0.001). Compared with patients younger than 65 years old (2.44%, 1/41), patients older than 65 years old (19.44%, 21/108) had less willing to be treated (χ ²=6.83, P=0.009). Compared with patients who had been going back and forth to the designated hospital for less than 30 minutes (8.43%, 7/83), patients who had been going back and forth for more than 30 minutes (22.73%, 15/66) had a higher rate of unwilling to be treated (χ ²=5.97, P=0.015). The multivariate analysis showed that the rates of unwillingness to be treated among cases ≥65 years (OR=10.18, 95%CI: 1.31-79.38; Wald χ ²=4.91, P=0.030) and cases who take more than 30 minutes from home to hospital (OR=3.36, 95%CI:1.25-9.02; Wald χ ²=5.78, P=0.020) were significantly higher. Health education can improve the rate of willing to receive treatment. The effect of village doctors’ home education is more obvious. Patients over 65 years old and far from designated hospitals should be paid more attention.

CT features and prognosis of tuberculous lymphatic ruptures in mediastinum and lung in adults

Min SONG,Wei-jun FANG,Hui-ru LI,Hui-li REN,Hui ZHANG,Hui-yong. FENG

Chinese Journal of Antituberculosis. 2018, 40(10):  1110-1117.  doi:10.3969/j.issn.1000-6621.2018.10.015

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Objective To investigate the CT features and prognosis of tuberculous lymphatic ruptures in mediastinum and lung in adults. We retrospectively analyzed 52 adult patients with tuberculous lymphatic ruptures in mediastinum and lung in Guangzhou Chest Hospital from January 2009 to December 2017. According to the location of ruptures, the patients were divided into 3 groups:tracheobronchial group with lymph nodes only ruptured to tracheobronchial airway, lung group with lymph nodes only ruptured to the lung, and tracheobronchial-lung group with lymph nodes ruptured into both tracheobronchial airways and lungs. Each group’s CT manifestations and all lymphatic ruptures’ prognosis were summarized and analyzed. There were 84 ruptured lymph nodes in 52 patients. Among them, 19 patients with 23 ruptured lymph nodes were in the tracheobronchial group, 14 of these 23 lymph nodes were with thickened mucous membrane and granulation of the corresponding bronchoedema made nodular protrusion in the airway cavity at the side of the rupture. In the CT enhancement, extension of the necrotic region to the airway could be seen in 13 of them, and 1 was homogeneous enhanced, and among the other 9 lymph nodes in this group, the airway wall close to the fistula was not smooth but with no nodular sign. There were 13 patients with 13 ruptured lymph nodes in the lung group, swollen lymph nodes crossed mediastinum or hilum to pulmonary tissue and formed nodules or masses, with halo sign or patchy shadows surrounding. and with necrotic region extended to the lung tissue in 12 of those lymph nodes after enhanced, and homogeneous enhancement was seen in the other 1. There were 20 patients with 48 lymph nodes ruptured in the tracheobronchial-lung group, which had multiple lymph nodes obviously enlarged in multiple regions in mediastinum and pulmonary hilum, 11 of which ruptured into airway, and 20 ruptured into lung. Under CT enhancement, these lymph nodes had the extension of the necrotic region to the side of fistulas except one homogeneous enhanced, and the airway walls corresponding to the fistula of the other 16 lymph nodes were not smooth but with no nodular sign in this group. After anti-tuberculosis treatment, and treatment under bronchoscope towards the lymph nodes ruptured into airway including taking out the granuloma with forceps, and suction of the necrosis, 33 patients had bronchostenosis at the fistula related remained, and 18 patients had some pulmonary fibrosis at the fistula related in the lung field remained after treatment. TB tuberculous lymphatic ruptures of adults in mediastinum and lung are mostly ruptured to trachea, bronchus and lung. CT plain scan and enhancement is helpful for their early diagnosis. Some therapeutic effect could be found after tuberculosis treatment on most of the ruptured lymph nodes, but some cases will leave bronchial cicatricial stenosis behind.

Study on correlation between care burden and life quality of family caregivers of children with tuberculosis

Lei SHEN,Lin ZHANG,Yong-hong TAO,Yong-jun TANG,Mei-juan BAO,Hong-zhou. LU

Chinese Journal of Antituberculosis. 2018, 40(10):  1118-1124.  doi:10.3969/j.issn.1000-6621.2018.10.016

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Objective To investigate the status of care burden and quality of life of family caregivers living with tuberculosis (TB) children, and to explore the correlation between the two, so as to provide a reference for formulating the systematic family intervention measures. Zarit Burden Interview (ZBI) and Family Caregiver-Specific Quality of Life Scale (FAMQOL) were used to investigate the family caregivers of 76 children with TB who hospitalized in Shanghai Public Health Clinical Center from September 2017 to March 2018. The total score of Zarit Burden Interview was 0-88, the higher the score was, the heavier the caregiver’s burden was. The ZBI score 0-19 indicated that there was no or little burden, the ZBI score 20-39 meant light burden, the ZBI score 40-59 meant mild burden, and the ZBI score above 60 means heavy burden. The total score of Family Caregiver-Specific Quality of Life Scale was 16-80, the higher the score was, the higher the quality of life was. T test, one-way ANOVA, rank-sum test were used to compare the data among groups, and Pearson correlation analysis or Spearman correlation analysis were used to test the correlation of care burden and quality of life of family caregivers living with TB children. The total score of care burden was 41.39±14.86, and the personal burden and responsibility burden scores were 22.58±9.10 and 10.79±4.88 respectively. The total FAMQOL score was 50.46±14.25, in which spiritual status (SS) was 11.61±4.53, mental status (MS) was 12.70±4.40, social concerns (SC) was 13.01±3.62 and physical status (PS) was 13.14±3.72.There was significantly negative correlation between the score of care burden and that of quality of life in the family caregivers of TB children (r=-0.726, P<0.001). The family caregivers of TB children have care burdens in different degrees, which influence on the quality of their lives.

Expert Forum

Comparison of BCG vaccine quality standards of domestic and foreign

Ai-hua ZHAO,Guo-zhi WANG,Li-li FU,Miao. XU

Chinese Journal of Antituberculosis. 2018, 40(10):  1125-1128.  doi:10.3969/j.issn.1000-6621.2018.10.017

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BCG vaccine is of great significance in preventing tuberculosis.China adopts the strategy of vaccinating newborns with BCG vaccine at birth.In this paper, the author discussed the quality control standards of BCG vaccine of domestic and foreign, the general situation of BCG vaccine strains in China, the induced immune response and adverse reactions of BCG vaccine in China, so as to provide basic information for understanding BCG vaccines in China.

Review Articles

Research progress of Mycobacterium tuberculosis exosome

Xin-yang WANG,Ying-me FU,Yan-lin ZHAO,Feng-min ZHANG

Chinese Journal of Antituberculosis. 2018, 40(10):  1129-1133.  doi:10.3969/j.issn.1000-6621.2018.10.018

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Since exosomes have been discovered in 1983, research on exosomes has been deepening, and their functions have been discovered constantly, such as diagnosing the occurrence of diseases as molecular markers and affecting the body’s immune function. Exosomes also exist in bacteria, which can affect the host immunity. When bacteria infect the host, the exosomes produced by the host also play a very important role in the host immunity. The function of exosomes of Mycobacterium tuberculosis is reviewed. In addition, the function of bacteria exosomes, represented by mycobacterium, is described.

The progress of establishing animal model of spinal tuberculosis

Ze-cheng CAI,He MA,Zhao-hui GE

Chinese Journal of Antituberculosis. 2018, 40(10):  1134-1137.  doi:10.3969/j.issn.1000-6621.2018.10.019

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Bone and joint tuberculosis is one of the most common extrapulmonary tuberculosis. In more than 50% of the patients with bone and joint tuberculosis, infection is located in the spinal column. In recent years, scholars at home and abroad have gradually increased the study of drug release, surgical methods, and internal substances for spinal tuberculosis. These studies are mainly based on the establishment of animal models similar to human spinal tuberculosis. The authors reviewed the important content of the animal model of spinal tuberculosis in recent years, in order to make the relevant researchers understand the characteristics of the establishment of the animal model of spinal tuberculosis.

Short Articles

Analysis of curative effect of combined treatment of traditional Chinese medicine and Western medicine in treatment of tuberculous peritonitis

Hong-yan XU,Zhao-ping GAN,Qian-hong WU,Jin-cheng LIU,Yi ZHOU,Lin-ming YAO,Qi-yuan WANG,Yan. ZHANG

Chinese Journal of Antituberculosis. 2018, 40(10):  1138-1140.  doi:10.3969/j.issn.1000-6621.2018.10.020

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The patients with tuberculous peritonitis who were hospitalized in Tuberculosis Hospital of Shaanxi Province from January 2013 to January 2015 were collected in this study. According to the different medication regimens, 42 cases were randomly selected by random digital table method as control group from 86 cases who were treated with simple Western medicine (drug regimen: 3H-R-Z-E/15H-R-E), and 42 cases were randomly selected as observational group from 94 cases who were treated with traditional Chinese medicine in combination with Western medicine (drug regimen: 3H-R-Z-E/15H-R-E combined with Tingli Dazao Xiefei Soup, in which the soup was took for 3 months). The efficacy, liver injury and recurrence rate after treatment of the two groups were statistically analyzed. After 3 months of treatment, the total effective rate of the observational group was 92.9% (39/42), significantly higher than that of the control group (76.2% (32/42); the difference was statistically signi-ficant (Z=1.93, P=0.013). The incidence of liver injury in the observational group (4.8%, 2/42) was lower than that in the control group (28.6%, 12/42), and the difference was statistically significant (χ ²=8.57, P=0.002). All 84 patients completed the course of treatment and were followed up for one year after the end of treatment. The rate of recurrence in the observational group (6.7%, 2/30) was lower than that in the control group (32.0%, 8/25), and the difference was statistically significant (χ ²=6.12, P=0.013). The combination of Chinese and western medicine in the treatment of tuberculous peritonitis has the advantages of high cure, low recurrence rate and small liver injury.

Study on mutations of rrs and eis genes in Mycobacterium tuberculosis resistant to amikacin and kanamycin

Ke-wei LI,Wei ZHAO,Si-jie LIU,Xiu-jun YANG,Li SHEN,Xin LIU,Peng QI

Chinese Journal of Antituberculosis. 2018, 40(10):  1141-1143.  doi:10.3969/j.issn.1000-6621.2018.10.021

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1357 Mycobacterium tuberculosis (MTB) isolates were collected from tuberculosis medical institutions in nine prefectures of Jilin Province from 2014 to 2017. Amikacin (Am) and kanamycin (Km) susceptibility tests were performed by proportional method, and rrs and eis genes were analyzed by PCR and sequencing. Twenty-eight strains were resistant to both Km and Am, and 2 strains were resistant to Km alone. rrs gene mutation occurred in 26 strains resistant to Am and Km, and the mutation rate was 92.86%. eis gene mutation occurred in 6 strains, and the mutation rate was 21.43%. No mutation was found in 60 control strains. MTB had high cross resistance to Am and Km in Jilin Province. The mutation of rrs gene can be used as a molecular marker of cross resistance, which can provide molecular basis for the establishment of rapid detection technology for tuberculosis resistant to Am and/or Km.