Table of Content

10 February 2019, Volume 41 Issue 2

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Expert Consensus

Expert consensus on detection of Mycobacterium tuberculosis drug resistance

Editorial Board of Chinese Journal of Antituberculosis,Basic and Clinical Groups of Tuberculosis Control Branch of China International Exchange and Promotive Association for Medical and Health Care

Chinese Journal of Antituberculosis. 2019, 41(2):  129-137.  doi:10.3969/j.issn.1000-6621.2019.02.003

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Drug-resistant tuberculosis (DR-TB) especially multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) are one of the most difficult problems to be solved in clinical practice. Anti-tuberculous drug susceptibility tests (DST) provide experimental basis for the diagnosis of DR-TB. This expert consensus briefly introduces the common M.tuberculosis (MTB) DST methods (including phenotypic DST and molecular DST) used in clinic, proposes the strategies of MTB drug resistance detection and correct interpretation of the results, points out the problems of DST detection technology and clinical application, and prospects the development of DST in the future.

Original Articles

Direct detection of rifampicin and isoniazid resistance-associated genes in clinical specimens from the patients with tuberculosis using gene chip

Xue-juan BAI,Yin-ping LIU,Jun-xian ZHANG,Jie WANG,Xue-qiong WU

Chinese Journal of Antituberculosis. 2019, 41(2):  138-144.  doi:10.3969/j.issn.1000-6621.2019.02.004

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Objective To study the clinical value of direct detection on Mycobacterium tuberculosis (MTB) rifampicin (RFP) and isoniazid (INH) resistance-related genes in clinical specimens from the patients with tuberculosis (TB) by gene chip. Methods A retrospective analysis of 125 clinical specimens identified as MTB by culture using the media with nitrobenzoic acid (PNB) and thiophene-carboxylic acid hydrazide (TCH) was carried out, including sputum specimens (n=90), bronchial lavage fluid (n=12), pus (n=12), pleural effusion (n=6), tissue specimens (n=3), peritoneal effusion (n=1) and urine specimen (n=1). RFP and INH susceptibility tests were performed simultaneously by absolute concentration method, and MTB rpoB, katG and inhA genotypes in clinical specimens were detected directly by gene chip. Using absolute concentration method as control, the sensitivities and specificities of gene chips for detecting RFP, INH resistance and multidrug resistance (MDR) were evaluated, and the consistency of the two methods was compared. Results Of 125 clinical specimens from TB patients, the results of absolute concentration method showed that RFP-, INH- and multidrug-resistant (MDR) rates were respectively 20.0% (25/125) (88.0% (22/25) high level resistance and 12.0% (3/25) low level resistance), 17.6% (22/125) (18.2% (4/22) high level resistance and 81.8% (18/22) low level resistance) and 16.8% (21/125). The detection rates of MDR-MTB were 7.6% (7/92) and 39.4% (13/33) in the clinical specimens from primary and recurrent TB patients, respectively. Compared with absolute concentration method, the sensitivities of detecting RFP-, INH-resistant and MDR-MTB were 72.0% (18/25), 63.6% (14/22) and 61.9% (13/21) by gene chip, respectively. The specificity was 91.0% (91/100), 86.4% (89/103) and 89.4% (93/104), respectively. The consistency rates of the two methods were 87.2% (109/125), 82.4% (103/125) and 84.8% (106/125), respectively. Conclusion MTB, RFP, and INH resistance-related gene mutation detection in clinical samples of TB patients have moderate sensitivities and high specificities by gene chip. It can be used to quickly detect RFP-, INH-resistant, and MDR-MTB to provide experimental basis for early effective chemotherapy.

Effectiveness analysis of new molecular detection techniques for diagnosing pulmonary tuberculosis in primary laboratory

Ying PENG,Xin SU,Qi JIANG,Chang-ming CHEN,Ran BIAN,Sheng ZHONG,Qian GAO,Fa-bin LI

Chinese Journal of Antituberculosis. 2019, 41(2):  145-148.  doi:10.3969/j.issn.1000-6621.2019.02.005

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Objective To analyze and compare the effectiveness of GeneXpert MTB/RIF (GeneXpert for short) and cross-primer amplification (CPA) in rapid diagnosis of tuberculosis in primary laboratories. Methods The sputum samples from suspected tuberculosis patients during April 2014 to July 2017 were collected continuously in TB Prevention and Control Institute of Wuchang City, Heilongjiang Province. L?wenstein-Jensen culture (referred to as “solid culture method”) and rapid molecular detection (787 cases detected by GeneXpert as group A, 501 cases detected by CPA as group B) were performed. The sensitivity and specificity of two molecular detection techniques were calculated according to solid culture method. Results Of 787 sputum specimens detected in group A, 229 specimens were positive by culture and 300 specimens were positive by GeneXpert. The sensitivity and specificity of GeneXpert were 99.1% (227/229) and 86.9% (485/558), respectively. Kappa value was 0.788. Of 501 sputum specimens detected in group B, 129 specimens were positive by culture and 125 specimens were positive by CPA. The sensitivity and specificity of CPA detection were 81.4% (105/129), 94.6% (352/372), respectively. Kappa value was 0.768. There was no significant difference in the concordance rate between two kinds of molecular techniques and solid culture methods (90.5% (712/787) vs 91.2% (457/501), χ ²=0.204, P=0.652). Conclusion The accuracy of CPA detection is comparable to that of GeneXpert, but its cost is lower than that of GeneXpert, and it does not need testing instruments. It allows a large number of samples to be operated simulta-neously per batch, which is more suitable for the early diagnosis of patients with pulmonary tuberculosis in primary laboratories.

The value of fluorescent PCR probe melting curve technique in detecting anti-tuberculosis drug resistance of Mycobacterium tuberculosis using sputum samples from smear-positive patients

Guo-lian ZHAO,Xiao-li CUI,Lei KANG,Yuan LIU,Li-yun DANG

Chinese Journal of Antituberculosis. 2019, 41(2):  149-155.  doi:10.3969/j.issn.1000-6621.2019.02.006

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Objective To evaluate the detection performance of the fluorescent PCR probe melting curve (MeltPro) technique in detecting anti-tuberculosis drug resistance using smear-positive sputum specimens. Methods Sputum specimens from 500 sputum-positive tuberculosis patients in Xi’an Chest Hospital from September 2016 to August 2018 were collected. Sputum smear microscopy, GeneXpert MTB /RIF, BECTEC MGIT 960 liquid culture, phenotypic drug susceptibility test and MeltPro technique were applied to detect the drug resistance to rifampicin, isoniazid, second-line injection drugs and fluoroquinolones. Phenotypic drug susceptibility test was used as the reference standard to assess the detection performance. Results The sensitivity and specificity of MeltPro technique for rifampicin resistance detection were 98.7% (76/77) and 94.2% (343/364), for isoniazid were 82.3% (102/124) and 96.2% (304/316), for amikacin were 8/9 and 99.5% (432/434), for capreomycin were 6/7 and 99.1% (432/436), for levofloxacin were 90.6% (48/53) and 99.2% (386/389), and for moxifloxacin were 88.1% (37/42) and 96.5% (386/400), respectively. The sensitivity and specificity of GeneXpert MTB/RIF for detection of M.tuberculosis rifampicin resistance were 94.8% (73/77) and 94.0% (342/364), respectively. The results of both GeneXpert-MTB/RIF and MeltPro methods were well consistent with the phenotypic susceptibility test (Kappa values were 0.81 and 0.84, respectively), but the MeltPro method was more consistent. Conclusion MeltPro technique shows a good capability in detecting the drug resistance of anti-tuberculosis drugs of MTB including rifampicin, isoniazid, second-line injection drugs and fluoroquinolone using smear-positive sputum specimen.

Detection of drug resistance mutations in Mycobacterium tuberculosis to five antitubercular drugs using the fluorescent PCR probe melting curve method

Zhi-hua CAO,Yue-zhu ZHAO,Shuang-shuang HU

Chinese Journal of Antituberculosis. 2019, 41(2):  156-161.  doi:10.3969/j.issn.1000-6621.2019.02.007

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Objective To detect rifampicin, isoniazid, ethambutol, streptomycin and fluoroquinolone drug resistance mutations in Mycobacterium tuberculosis using the fluorescent PCR probe melting curve method, and evaluate its potential for clinical application. Methods A total of 153 Mycobacterium tuberculosis clinical isolates from outpatients of the Fourth People’s Hospital of Fushun were collected from January 2018 to August 2018. Drug susceptibility testing was performed using the proportional method to evaluate the sensitivity, specificity and diagnostic consistency rate of the fluorescent PCR probe melting curve method. Results The sensitivity, specificity, diagnostic consistency rate and Kappa value of the fluorescent PCR probe melting curve method for detection of drug resistance mutations to rifampicin was 95.56%(43/45), 94.44% (102/108), 94.77% (145/153) and 0.88, respectively, while that for detection of drug resistance mutations to isoniazid was 90.57%(48/53), 96.00% (96/100), 94.12% (144/153) and 0.87, respectively, and 85.71%(18/21), 92.42% (122/132), 91.50% (140/153) and 0.69, respectively, for detection of drug resistance mutations to ethambutol. The sensitivity, specificity, diagnostic consistency rate and Kappa value for detection of drug resistance mutations to streptomycin was 89.66% (26/29), 92.74% (115/124), 92.16% (141/153) and 0.76, respectively, and that for detection of fluoroquinolone resistance mutations was 93.75%(15/16), 96.35% (132/137), 96.73%(147/153) and 0.81, respectively. Conclusion The fluorescent PCR probe melting curve method has good sensitivity and specificity for the detection of resistance mutations to rifampin, isoniazid, ethambutol, streptomycin and fluoroquinolone, and can thus be used as a clinical detection method for resistance mutations to the five most important anti-MTB drugs, providing important evidence for doctors when making decisions on which drug combinations to use in treatment regimens.

The value of MicroDST and GeneXpert MTB/RIF test in detecting Mycobacterium tuberculosis resistance to rifampicin

Jing LI,Ya-ping LIANG,Zhuo WANG,Ji-ping CHEN,Zhi-cun WANG,Qian-hong WU

Chinese Journal of Antituberculosis. 2019, 41(2):  162-168.  doi:10.3969/j.issn.1000-6621.2019.02.008

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Objective To compare the results of Mycobacterium tuberculosis (MTB) resistance to rifampicin (RFP) by Micropore-plate method (Microdrug sensitivity, MicroDST) and GeneXpert MTB/RIF test. Methods Among the 6893 suspected MTB patients who admitted to or visited Outpatient Department in Shaanxi Provincial Tuberculosis Control and Prevention Hospital, 6086 patients were diagnosed as MTB cases according to the clinical diagnostic criteria. A total of 425 clinical specimens were tested by BACTEC MGIT 960 liquid culture method and GeneXpert method, including 217 sputum specimens, 170 alveolar lavage specimens, and 38 extrapulmonary fluid specimens (such as pleural and peritoneal effusion, pus and cerebrospinal fluid). After excluding 3 specimens that reported errors or could not be interpreted and 2 specimens that were contaminated when cultured, there were 420 valid specimens. Three hundred and seventy-two clinical isolates with positive results by GeneXpert and MGIT 960 method were tested for drug resistance by MicroDST, GeneXpert MTB/RIF and MGIT 960 method, including 191 sputum specimens, 158 alveolar lavage specimens, and 23 extrapulmonary fluid specimens (such as pleural and peritoneal effusion, pus and cerebrospinal fluid). Taking MGIT 960 test as the gold standard, the performance of MicroDST and GeneXpert MTB/RIF in detecting MTB resistance to RFP were compared. Results The overall positive rates of RFP resistance by GeneXpert MTB/RIF, MicroDST and MGIT 960 method were 18.8% (70/372), 16.7% (62/372), and 16.7% (62/372), respectively. Taking MGIT 960 test as the gold standard, the sensitivity, specificity, coincidence rate and Kappa value of RFP resistance test were 91.9% (57/62), 98.4% (305/310), 97.3% (362/372) and 0.8 by MicroDST assay and 96.8% (60/62), 96.8% (300/310), 96.8% (360/372) and 0.8 by GeneXpert MTB/RIF assay. The sensitivity, specificity, coincidence rate and Kappa value using sputum, alveolar lavage and extrapulmonary specimens were 96.7% (29/30), 98.1% (158/161), 97.9% (187/191), 0.9; 93.3% (28/30), 96.3% (155/161), 95.8% (183/191), 0.9; and 91.7% (22/24), 98.5% (132/134), 97.5% (154/158), 0.9 by MicroDST assay and 100.0% (24/24), 97.0% (130/134), 97.5% (154/158), 0.9; 75.0% (6/8), 100.0% (15/15), 91.3% (21/23), 0.8; and 100.0% (8/8), 100.0% (15/15), 100.0% (23/23), 1.0 by GeneXpert MTB/RIF assay, respectively. Conclusion Taking MGIT 960 test as the gold standard, MicroDST and GeneXpert MTB/RIF assay have a good consistency in overall positive detection rate of RFP resistance, as well as in different samples.

Clinical diagnostic value of four laboratory techniques in detecting drug resistance to rifampicin and isoniazid

Peng-sen WANG,Gang ZHOU,Chang-ping MENG,Ming-ying JIANG,Qiang-zhong SUN,Si-kuan YE,Kan ZHOU,Zheng-gu HUANG,Chuan-yu LIAO,Hui-zheng ZHANG,Ming LUO,Guo-qiang YANG,Yu CHEN,Xiao-xu LI,Tong-xin LI

Chinese Journal of Antituberculosis. 2019, 41(2):  169-175.  doi:10.3969/j.issn.1000-6621.2019.02.009

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Objective To explore the clinical value of micropore-plate method, real-time fluorescent PCR melting curve technology (melting curve method), multicolor nested real-time fluorescence PCR detection technology (Xpert method) and Roche drug sensitivity test (L-J drug sensitivity test, referred to as proportional method) in rapid screening multidrug-resistant tuberculosis (MDR-TB). Methods From the hospital information system of Chongqing Public Health Medical Center during July 2014 to March 2018, patients who were diagnosed as TB and had the rifampicin and/or isoniazid resistance data by the Micropore-plate, melting curve, Xpert and/or proportional method were screened. The micropore-plate and proportional method were conducted by using positive isolates, and the melting curve and Xpert method were conducted using patient specimens. A total of 1488 patients with both micropore-plate and proportional drug resistance test results were included in the study. Among them, 341 patients underwent micropore-plate + proportional + Xpert methods to detect rifampicin resistance, and 87 patients underwent micropore-plate + proportional + melting curve methods to detect rifampicin resistance, and 66 cases were tested by micropore-plate + proportional + melting curve methods for isoniazid resistance. Taking the proportional method as the standard, SPSS 13.0 software was used to calculate the sensitivity, specificity, coincidence rate and Kappa value of rifampicin and/or isoniazid resistance by micropore-plate, melting curve and Xpert method. Results Taking the proportional method as the standard, the sensitivity, specificity, positive predictive value, negative predictive value, coincidence rate and Kappa value of rifampicin resistance test were 97.2% (731/752), 96.9% (713/736), 96.9% (731/754), 97.1% (713/734), 97.0% (1444/1488) and 0.94 by micropore-plate method, 97.2% (140/144), 94.9% (187/197), 93.3% (140/150), 97.9% (187/191), 95.9% (327/341) and 0.92 by Xpert method, and 97.1% (33/34), 84.9% (45/53), 80.5% (33/41), 97.8% (45/46), 89.7% (78/87) and 0.79 by melting curve method, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, coincidence rate and Kappa value of isoniazid resistance test were 94.8% (751/792), 95.7% (667/697), 96.3% (751/780), 94.2% (667/708), 97.9% (1418/1448) and 0.91 by micropore-plate method and 97.3% (36/37), 86.2% (25/29), 90.0% (36/40), 96.2% (25/26), 92.4% (61/66) and 0.84 by melting curve method. Conclusion Micropore-plate, melting curve and Xpert method have high sensitivity and specificity in detecting rifampicin and/or isoniazid resistance, which are suitable for rapid screening of MDR-TB. The Micropore-plate method also shows the minimum drug concentration of each drug, which provides a reference for the selection of clinical dosage.

The relationship between false-positive rifampicin resistant results of GeneXpert MTB/RIF and very low bacterial load in the clinical samples

Yuan LIU,Jun ZHOU,Xiao-li CUI,Jia-yuan LEI,Guo-lian ZHAO,Li-yun DANG

Chinese Journal of Antituberculosis. 2019, 41(2):  176-180.  doi:10.3969/j.issn.1000-6621.2019.02.010

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Objective To assess the performance of GeneXpert MTB/RIF (GeneXpert) assay in the detection of Mycobacterium tuberculosis (MTB) and its rifampicin resistance, and further analyze the relationship between the false-positive rifampicin-resistant results of GeneXpert assay and the low bacterial load in the clinical samples. Methods From April 2016 to September 2017, a total of 2707 clinical samples (1945 sputum specimens and 762 alveolar lavage fluid specimens) of suspected pulmonary tuberculosis cases from Xi’an Chest Hospital were collected for GeneXpert detection, BACTEC MGIT 960 liquid culture and drug susceptibility test. Among them, GeneXpert detected rifampicin-resistant samples were further tested by GenoType MTBDRplus assay. Results The positive rate of GeneXpert assay in detecting MTB was 39.8% (1077/2707). Seven cases had “indeterminate” rifampicin resistance results and “Very low” bacterial load level. Considering MGIT 960 drug susceptibility test as the gold standard, the sensitivity and specificity of GeneXpert test in detecting rifampicin resistance was 89.4% (135/151) and 94.7% (721/761), respectively. The inconsistent results of two methods were found in 56 cases. Among them, 40 cases were rifampicin-resistant detected by GeneXpert but were rifampicin-sensitive detected by MGIT 960. Of the 40 patients, 10, 6, 14 and 10 showed a MTB load level of “Very low”, “Low”, “Medium” and “High”, respectively. Taking MGIT 960 test result as gold standard, the false-positive rates of rifampicin-resistance by GeneXpert in the four MTB load levels were 58.8% (10/17), 16.7% (6/36), 19.2% (14/73) and 20.4% (10/49), respectively; the difference was statistically significant (χ ²=13.981, P<0.05). Among the 40 cases, 30 cases with Low, Medium and High level of MTB load were rifampicin-resistant when detected by the MTBDRplus test, which was consistent with the GeneXpert results. As to the 10 cases with Very low level of MTB load, 2 cases were negative and 8 were positive by MTBDRplus test, and in the cases with positive results, 5 cases were rifampicin-sensitivity and 3 rifampicin-resistance. Conclusion The detection of MTB rifampicin-resistance with GeneXpert assay has a higher sensitivity and specificity. However, when the tested load of MTB is Very low, false drug resistant results may occur.

The value of blood interferon-gamma-inducible protein 10 level in assessing the treatment efficacy of pulmonary tuberculosis patients

Lan WEI,Xue-bo QIN,Xiao-liang DUAN,Hui LI,Yu-zhuo LI,Xin-zhuan JIA,Lei ZHANG

Chinese Journal of Antituberculosis. 2019, 41(2):  181-185.  doi:10.3969/j.issn.1000-6621.2019.02.011

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Objective To investigate the changes of serum interferon-gamma-inducible protein 10 (IP-10) and IP-10 response against tuberculosis specific antigens in QuantiFERON Gold In-Tube (QFT-GIT) assay in patients with active pulmonary tuberculosis before and after treatment. Methods A total of 161 cases of active pulmonary tuberculosis who were improved after 6-9 months of regular antituberculosis treatment in Hebei Provincial Chest Hospital during January 2017 to March 2017 were enrolled in this study. Patients were divided into anti-acid staining (+) group (82 cases) and anti-acid staining (-) group (79 cases) according to the results of sputum smear anti-acid staining before treatment. Anti-acid staining (+) group was further divided into group A (anti-acid staining change (-) after 2 months of treatment, 31 cases) and group B (anti-acid staining still (+) after 2 months of treatment, 51 cases). Anti-acid staining (-) group was defined as the group C (79 cases). The levels of serum IP-10 and IP-10 response to antigen in QFT-GIT assay were measured and compared in all groups within 2 weeks, at the end of 2 months and after 6-9 months of treatment. Results The levels of serum IP-10 within 2 weeks, at the end of 2 months and after 6-9 months of treatment were (0.16±0.03)μg/L, (0.13±0.03)μg/L and (0.09±0.02)μg/L in group A, (0.16±0.03)μg/L, (0.15±0.03)μg/L and (0.09±0.02)μg/L in group B, and (0.16±0.03)μg/L, (0.13±0.03)μg/L and (0.09±0.02)μg/L in group C, respectively. The levels of IP-10 response to antigen in QFT-GIT assay within 2 weeks, at the end of 2 months and after 6-9 months of treatment were (21.60±3.07)μg/L, (19.94±3.05)μg/L and (11.01±2.16)μg/L in group A, (23.52±3.10)μg/L, (20.50±4.60)μg/L and (12.08±3.57)μg/L in group B, and (19.67±3.32)μg/L, (13.43±3.16)μg/L and (8.72±1.08)μg/L in group C, respectively. The differences in the levels of serum IP-10 and IP-10 response to antigen in QFT-GIT assay among the three treatment time points in group A, B and C were all statistically significant (F values were 72.84, 111.92, 107.52 and 75.01, 118.09, 138.98, respectively; Ps=0.000). The levels of serum IP-10 and IP-10 response to antigen in QFT-GIT assay after the course of treatment were lower than those within 2 weeks of treatment, and the differences were statistically significant (group A: q values were 71.42 and 138.42; group B: q values were 74.68 and 150.29; group C: q values were 68.76 and 129.83; Ps=0.000). Conclusion Serum IP-10 and IP-10 response to antigen in QFT-GIT assay can be used as potential biomarkers for monitoring the treatment effect of patients with active pulmonary tuberculosis.

Evaluation of three methods for early etiological diagnosis in patients with tuberculous meningitis

Li-heng ZHENG,Xiao-jin LIU,Jian-chun FENG,Zhi-hua ZHANG,Hong-yan HE,Yan-xin SHAO,Yan-qiang CHEN

Chinese Journal of Antituberculosis. 2019, 41(2):  186-189.  doi:10.3969/j.issn.1000-6621.2019.02.012

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Objective To evaluate the clinical value of three methods in early diagnosis of tuberculous meningitis (TBM). Methods The cerebrospinal fluid specimens (CSF) of 45 patients with TBM and the samples of 42 patients with non-TBM were collected from patients admitted to Hebei Chest Hospital and the Fifth Hospital of Shijiazhuang between August 2016 and June 2018. Three methods, including conventional acid fast stain, modified acid fast stain, and GeneXpert MTB/RIF assay were used to detect the mycobacterium in the CSF specimens for diagnosis of TBM. SPSS 19.0 software was used for statistical analysis. The comparison of the rates was made by χ ² test and corrected χ ² test, P<0.05 was statistically significant. Results Based on clinical diagnosis, the sensitivity was 4.44% (2/45), 88.89% (40/45), 35.56% (16/45) in the TBM group as tested by conventional acid fast stain, modified acid fast stain, and GeneXpert MTB/RIF assay respectively. There was significant difference between the three methods in the sensitivity (χ ²=64.46, 13.16, 27.23, P=0.000). No mycobacterium was detected in the samples of non-TBM group. The specificity of three detection techniques for mycobacterium was 100.00%. Conclusion The sensitivity of the modified acid fast staining method is higher than that of the conventional acid fast stain and GeneXpert MTB/RIF assay in detection of the mycobacterium in CSF. It is worthwhile for the early diagnosis of TBM.

Correlation between vitamin D level and LL-37 expression in peripheral blood of different forms of active pulmonary tuberculosis patients

Gui-hui WU,Tao HUANG,Mei LUO,Yang CAI,Wei HE,Lei CHEN

Chinese Journal of Antituberculosis. 2019, 41(2):  190-194.  doi:10.3969/j.issn.1000-6621.2019.02.013

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Objective To evaluate the difference in expression levels of 25-(OH)D₃ and LL-37 in patients with different types of active pulmonary tuberculosis (PTB). Methods One hundred and seventy-eight PTB patients admitted to Chengdu Public Health Clinical Medical Center from June 2017 to December 2017 were enrolled as case group. One hundred and seventy-eight patients included 81 PTB cases (Group B), 57 PTB cases with extrapulmonary tuberculosis (Group C) and 40 PTB cases complicated with diabetes (Group D). According to the severity of the disease, the patients were divided into severe PTB (79 cases) and mild PTB (99 cases). One hundred medical workers who had physical examination in our hospital during the same period were selected as the healthy control group (Group A). The levels of 25-(OH)D₃ and LL-37 were measured by ELISA. The difference of 25-(OH)D₃ and LL-37 expression between the groups, and the correlation between the severity of PTB and levels of 25-(OH)D₃ and LL-37 were analyzed. Results The concentrations of 25-(OH)D₃ in peripheral blood in Group B, Group C and Group D were (31.58±11.89) nmol/L, (25.68±13.57) nmol/L and (26.39±10.01) nmol/L respectively, which were significantly lower than that in Group A ((40.57±14.32) nmol/L) (respectively t=4.61, P=0.000; t=6.48, P=0.000; t=5.72, P=0.000). The levels of LL-37 in Group B, Group C and Group D were (26.97±10.29) μg/L, (30.75±10.16) μg/L and (31.84±11.36) μg/L respectively, which were significantly higher than that in Group A ((24.38±4.57) μg/L), the differences were statistically significant (respectively t=2.26, P=0.025; t=4.48, P=0.000; t=4.03, P=0.000). Compared with Group B, the concentrations of 25-(OH) decreased and LL-37 increased in Group C and Group D, with statistically significant differences (respectively t=2.64, P=0.008; t=2.52, P=0.011 and t=2.14, P=0.032; t=2.29, P=0.022). In patients with severe PTB, the concentration of 25-(OH)D₃ was (24.59±12.36) nmol/L, and the level of LL-37 was (31.97±11.43) μg/L, which was statistically significant compared with those with mild PTB ((33.79±15.47) nmol/L and (27.32±10.69) μg/L; t=4.41, P=0.000; t=2.77, P=0.006). Conclusion The serum levels of vitamin D in patients with active PTB are significantly lower than that in normal adults, and the levels of LL-37 in active PTB cases are significantly higher than that in normal adults, and there are differences in the expression levels of vitamin D and LL-37 of patients with different types of active PTB in blood.

The comparison of CT imaging features between Mycobacterium avium-intracellulare complex and Mycobacterium chelonei and abscessus pulmonary diseases combined with bronchiectasis

Hui-li REN,Pin-ru CHEN,Hua CHEN,Jin-xing HU,Wen LIU,Wei-jun FANG

Chinese Journal of Antituberculosis. 2019, 41(2):  195-201.  doi:10.3969/j.issn.1000-6621.2019.02.014

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Objective To discuss the CT imaging features of Mycobacterium avium intracellulare complex (MAC) lung disease and Mycobacterium chelonei and abscessus lung disease combined with bronchiectasis, and to improve the differential diagnosis of two diseases. Methods A retrospective analysis of the CT imaging data of 25 cases of MAC lung disease combined with bronchiectasis (Group A) and 26 cases of Mycobacterium chelonei and abscessus lung disease combined with bronchiectasis (Group B). All cases were treated in outpatient or inpatient and were diagnosed clinically in Guangzhou Chest Hospital from January 2017 to December 2017. CT imaging data of patients who were initial diagnosis or had not received anti-NTM treatment were collected. The CT findings and complications of the two groups were compared and analyzed, including bronchiectasis (CT classification, distribution), lung lesions (micronodule, tree in bud, nodules, consolidation, etc.), and cavities (type, distribution). Results There were bronchiectasis, micronodule, tree in bud and thin-walled cavities in two groups. The rates of bronchiectasis in the left lower lobe, micronodules in the left lower lobe, pulmonary consolidation in the right upper lobe and lung volume reduction of Mycobacterium chelonei and abscessus lung disease were 57.69% (15/26), 84.62% (22/26), and 61.54% (16/26) respectively, which was higher than that in MAC lung disease (28.00% (7/25), 56.00% (14/25), 32.00% (8/25)). There was significant statistical differences (χ ²=4.58, 5.03, 4.46, P=0.032, 0.025, 0.035). The cystic bronchiectasis (50.00%, 13/26) was common in Mycobacterium chelonei and abscessus lung disease and columnar bronchiectasis (52.00%, 13/25) often occurs in MAC lung disease. There was significant statistical differences (χ ²=7.69, 6.63, P=0.006, 0.010). Conclusion The incidence of bronchiectasis in left lower lobe, micronodule in left lower lobe and lung volume reduction in Mycobacterium chelonei and abscessus lung disease is higher than that in MAC lung disease. The cystic bronchiectasis often occurs in Mycobacterium chelonei and abscessus lung disease and columnar bronchiectasis is common in MAC lung disease. All these CT manifestations are meaningful for their differential diagnosis.

Analysis of CT image classification and clinical characteristics of nontuberculous mycobacterial pulmonary disease

Duo LI,Kun FANG,Jue WANG,Zhen ZHOU,Ping-xin LYU

Chinese Journal of Antituberculosis. 2019, 41(2):  202-209.  doi:10.3969/j.issn.1000-6621.2019.02.015

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Objective To analyze the CT image classification of non-tuberculosis mycobacterium(NTM) pulmonary disease and the clinical and CT features in patients with different CT image classifications. Methods The clinical and CT data of 132 patients with non-tuberculous mycobacterial pulmonary disease admitted in Beijing Chest Hospital, Capital Medical University from November 2011 to January 2018 were analyzed retrospectively. According to CT imaging features, there were four types of cavities in the upper lobe, nodular bronchiectasis, mixed and difficult to differentiate. The clinical and imaging characteristics of patients with different image classification were analyzed statistically using SPSS software with 17.0 version, and the enumeration data were analyzed by chi-square test or continuous correction chi-square test. Measurement data were analyzed by t test or variance analysis. The difference were considered statistically significant when P<0.05. When the clinical statistical data of 4 groups of patients with different types of patients were compared in pairs, P<0.008 was considered as the significant statistically difference. Results Of 132 cases with non-tuberculous mycobacterial pulmonary disease, there were 36 (27.3%) cases in the type of upper lobe cavitary 61 (46.2%) cases in the type of nodular bronchiectasis, 15 (11.4%) cases in the mixed type and 20 (15.2%) cases in unclassified type. The male ratio from high to low were upper lobe cavitary (86.1%, 31/36), unclassified type (70.0%, 14/20), mixed type (53.3%, 8/15) and nodular bronchiectasis (24.6%, 15/61) in all cases with significant statistically difference (χ ²=37.712,P<0.001).The average age of patients with upper lobe cavitary, nodular bronchiectasis, mixed type and unclassified type were 58.5±13.8, 58.1±13.3, 64.3±10.4 and 51.0±17.0 years old with no significant difference (F=1.875, P=0.140). The ratio of smoker in patients with upper lobe cavitary (64.7%,22/34) was significantly higher than that in patients with nodular bronchiectatic type (13%, 7/54)(χ ²=25.258, P<0.001). The incidence rate of emphysema (66.7%,24/36) and interstitial fibrosis (33.3%,12/36) in patients with upper lobe cavitary were significant higher than those (13.1%,8/61 and 0.0%,0/61) in patients with nodular bronchiectasis (χ ²=29.369,P<0.001;χ ²=23.204,P<0.001). The incidence rates of pleural thickening in upper lobe cavity type (61.1%, 22/36) and in mixed type (66.7%,10/15) were higher than that in nodular bronchiectasis (23.0%,14/61) (χ ²=10.649,P=0.001). Conclusion Nodular bronchiectasis type is the most common imaging features in NTM pulmonary disease. The upper lobe cavitary type is more common in male patients with emphysema and/or interstitial fibrosis. Nodular bronchiectatic type is frequently seen in female patients without underlying lung diseases.

Analysis of treatment outcomes in patients with multiple lumbar spinal tuberculosis by using approach of anterior debridement bone graft fusion and posterior long-segment fixation with short pedicle screw

Lin-ming YAO,Zhi-yuan WANG,Xin-liang ZHANG,Teng-fei GAO,Jian-hua LIU,Tao ZHAO,Qi-liang CHEN

Chinese Journal of Antituberculosis. 2019, 41(2):  210-216.  doi:10.3969/j.issn.1000-6621.2019.02.016

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Objective To explore the clinical efficacy of anterior debridement, bone graft fusion and posterior long-segment fixation with short pedicle screw method in treatment of patients with multiple lumbar spinal tuberculosis. Methods The clinic data of 17 multiple lumbar spinal tuberculosis patients who hospitalized and received surgery with the above mentioned operative method in Shaanxi Provincial Institute for Tuberculosis Control and Prevention from April 2013 to April 2015 were collected and analyzed. The clinical treatment outcomes of using the operative method was evaluated according to visual analog scale (VAS) and Oswestry dysfunction index (ODI), Cobb angle, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Frankel classification of neurological function, the status of bone fusion. SPSS 21.0 software was used for statistical analysis, matched t test was used to test the measurement data and P<0.05 was regarded as significant difference. Results The surgeries for all cases were successfully completed. All 17 patients were followed up 24-33 months after surgery and the average follow-up duration was (27.8±5.4) months. They were all cured. Of which, 2 patients developed paravertebral psoas abscess at 6 months after discharged from the hospital and was cured by excision of psoas abscess and adjustment of anti-tuberculosis treatment; the remaining 15 patients were normal during follow-up period. Before surgery, the VAS scores (7.9±1.4), ODI scores (72.5±7.9), Cobb angle (22.5±7.6)°, ESR (47.3±11.3) mm/1 h and CRP (32.6±9.4) mg/L in 17 patients were significantly higher than those at the last follow up ((2.1±0.9) scores, (30.3±6.6) scores, (10.8±4.4)°, (6.1±3.2) mm/1 h and (2.8±2.4) mg/L) and the differences had statistical significance (t=16.61, 4.18, 21.24, 2.44, 20.11; Ps<0.001). Among the 7 patients who had neurological symptoms before surgery, their Frankel Classification all reached E level at the last follow up after surgery. At 6 months follow-up after surgery, the fusion rate in the bone graft areas reached 94.1% (16/17) with grade Ⅰ in 14 cases, grade Ⅱ in 2 cases and grade Ⅲ in 1 case; at the last follow-up, the fusion rate reached grade Ⅰ with complete interbody fusion without recurrence or pseudoarthrosis in all patients. Conclusion The clinical treatment outcomes is good by using anterior debridement, bone graft fusion and posterior long-segment fixation with short pedicle screw in patients with multiple lumbar spinal tuberculosis.

Prevalence of nontuberculosis mycobacterium infection in Hunan Province between 2012 and 2017

Zhong-nan CHEN,Song-lin YI,Pei-lei HU,Jing-wei GUO,Yan-yan YU,Bin-bin LIU,Huan YI,Kun-yun YANG,Yun-hong TAN

Chinese Journal of Antituberculosis. 2019, 41(2):  217-221.  doi:10.3969/j.issn.1000-6621.2019.02.017

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Objective To investigate the infection trend, distribution characteristics and prevalence of non-tuberculosis mycobacteria (NTM) infection in Hunan Province from 2012 to 2017, and provide reference for the prevention and treatment of NTM disease. Methods A total of 15576 patients were collected from 14 cities who were diagnosed as mycobacterial infections in the Hunan Chest Hospital by BACTEC MGIT 960 from 2012 to 2017, including 11126 males and 4450 females. 15576 strains of mycobacteria isolated (1 strain per patient). M.tuberculosis complex and NTM were identified by MPB64 colloidal gold and p-nitrobenzoic acid (PNB) growth test. NTM strains were for further strains identification by 16S rRNA and Hsp65 sequencing. Clinical datas of NTM infected patients were also collected and analyzed. Results The overall prevalence of NTM infection was 10.17% (1584/15576) between 2012 and 2017. The prevalence of NTM infection among the male patients was 62.06% (983/1584)which was higher than that among the female patients (37.94%,601/1584).The age distribution was dominated by the patients aged 40- years, accounting for 39.02% (618/1584). Occupation distribution was dominated by farmers, accounting for 66.67% (1056/1584). Twenty-four species were identified and the top four species were M.intracellular (25.23%,84/333), M.abscessus (24.62%,82/333), M.gordonae (18.62%,62/333) and M.avium (16.82%,56/333) in 2016. Twenty-one species were identified and the top four species were also M.intracellular (27.15%,104/383), M.abscesus (22.46%,86/383), M.gordonae (21.15%,81/383) and M.avium (17.49%,67/383) in 2017. Conclusion The prevalence of NTM infection in Hunan Province is high, and majorities of patients with NTM infection are mainly attributed to groups such as male patients, middle-aged and elderly and farmers, and the pathogenic NTM take the main proportion.

Analysis of TB surveillance among entry-exit people in Xi’an port between 2015 and 2017

Lin ZHANG,Xi-zhuang XUE,Xiao-mou LI

Chinese Journal of Antituberculosis. 2019, 41(2):  222-226.  doi:10.3969/j.issn.1000-6621.2019.02.018

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Objective To understand the surveillance of active pulmonary tuberculosis among entry-exit people in Xi’an port, and to provide evidence for prevention and control of tuberculosis at ports. Methods A total of 63368 people were selected in the health examination at the Xi’an port from January 2015 to December 2017. The chest X-ray findings, PPD and laboratory sputum smears combined with GeneXpert MTB/RIF test results were used to diagnose tuberculosis in the screening of entry-exit people health examination. Analyzing the detection of tuberculosis under the characteristics of different time, personnel flow, gender, age, occupation or personnel category in Xi’an port for 3 years. Results A total of 106 active pulmonary tuberculosis patients were detected in 3 years, the detection rate was 167.28/100000 (106/63368). Fifty-six cases were positive for sputum smear combined with GeneXpert MTB/RIF, and the positive rate was 52.83% (56/106). The detection rate of male active pulmonary tuberculosis patients (191.21/100000 (92/48115))was higher than that of women (91.79/100000 (14/15253)), and the difference was statistically significant (χ ²=6.86,P<0.05); The detection rate in the 30- year-old group was the highest (227.06/100000 (46/20259)), and the lowest in the 20- years old group (68.55/100000 (4/5835)), the overall difference in all age groups was statistically significant (χ ²=10.11,P<0.05); The detection rate of exit personnels (184.79/100000 (95/51411)) was higher than that who were entry (92.00/100000 (11/11957)), and the difference was statistically significant (χ ²=5.00,P<0.05); In different occupations or personnel categories, the highest detection rate was among laborers (202.81/100000 (89/43883)), and the lowest was among students (75.30/100000 (7/9296)), the overall difference was statistically significant (Fisher exact probability test, P<0.05). Conclusion The condition of active pulmonary tuberculosis among entry-exit people in Xi’an port is relatively serious. It is necessary to take measures to strengthen the prevention and control of tuberculosis at the port, and the laborers around 30 years old are the key people under surveillance.

Review Articles

Advances in detection of drug resistance of Mycobacterium tuberculosis

Jun-xian ZHANG,Xue-qiong WU

Chinese Journal of Antituberculosis. 2019, 41(2):  227-232.  doi:10.3969/j.issn.1000-6621.2019.02.019

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Detection of drug-resistant genes of Mycobacterium tuberculosis is one of the difficult problems in diagnosis and treatment of tuberculosis. In recent years, many methods have been used to detect drug-resistant genes. The author summarized the research progress of drug-resistant detection methods of Mycobacterium tuberculosis in three respects as follows: the detection kits with registration certificates in China,the detection kits with registration certificates in the world that have not yet entered into China and new methods of preclinical research.

The applications and problems of mesenchymal stem cells for the treatment of tuberculosis

Bei-bei WU,Wei HUANG,Zhi-min WANG

Chinese Journal of Antituberculosis. 2019, 41(2):  233-235.  doi:10.3969/j.issn.1000-6621.2019.02.020

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Tuberculosis is one of the most serious infectious diseases in the world because of its high mortality and morbidity. Despite the robust immune response of human, Mycobacterium tuberculosis (MTB) evades host immunity and sets up a persistent infection. With the advances of medicine there have been some drugs to treat tuberculosis, but due to slow development of anti-tuberculosis drugs and the constant variation of MTB, prevention and management of tuberculosis is still a global health problem threatening thousands of lives. Recently, with the discovery and confirmation of its immunomodulatory property, the mesenchymal stem cells could give us new expectations for clinical management of tuberculosis. The authors summarize the applications and problems about mesenchymal stem cells for tuberculosis.

Short Articles

The expressions of peripheral blood interleukin-6 and C-reactive protein in patients with pulmonary tuberculosis complicated with type 2 diabetes mellitus

Jie CHEN,Hong-yang HAN,Zhi-song WU,Yi LIU,Nan-lan MA,Ya-ping ZHANG,Hui-juan MAO

Chinese Journal of Antituberculosis. 2019, 41(2):  236-238.  doi:10.3969/j.issn.1000-6621.2019.02.021

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A total of 186 cases with T2DM-PTB who were admitted to the Tuberculosis Department of Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine (The Second Hospital of Nanjing, Nanjing Public Health Medical Center) from January 2018 to June 2018. One hundred and sixty-five patients who met the inclusion criteria were numbered, and 55 of them were selected as the T2DM-PTB group by systematic sampling method. In addition, 815 age-matched patients with pulmonary tuberculosis in our hospital were screened, and 55 of them were selected as the PTB group by systematic sampling method. The serum levels of IL-6 and CRP were tested, and examination of sputum smear for acid-fast bacilli was conducted. The numbers of lesions were counted for statistical analysis. The results showed that media (quartile) M(Q₁,Q₃) levels of serum IL-6, CRP, and the lung lesion rang of T2DM-PTB group were (21.2 (21.2,44.4) ng/L, 31.2 (15.1,77.3) mg/L, and 4.0 (3.3,6.0)) respectively, which were higher than those of PTB group (8.6 (8.6,19.2) ng/L, 13.5 (4.5,37.4) mg/L, and 3.0 (3.0,4.0); there were significant differences among the two groups (U=3.78, 3.45, and 2.45; P=0.000, 0.001, and 0.014). The media (quartile) M(Q₁,Q₃) number of sputum examination positive cases in the T2DM-PTB group was higher than that in the PTB group (1.5 (0.0,5.8) vs 0.0 (0.0,2.0)), but the difference was not statistically significant (U=1.74, P=0.083). In conclusion, compared with PTB patients, T2DM-PTB patients had higher levels of IL-6 and CRP and wider lung lesion ranges, suggesting more active inflammatory state in the patients suffering PTB and T2DM.