Table of Content

10 August 2018, Volume 40 Issue 8

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Expert Forum

Management of latent tuberculosis infection: moving forward to prevention first

Lei GAO,Qi. JIN

Chinese Journal of Antituberculosis. 2018, 40(8):  791-795.  doi:10.3969/j.issn.1000-6621.2018.08.003

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It was estimated that about a quarter of the global population were latently infected with Mycobacterium tuberculosis, and millions of active tuberculosis (TB) diseases will occur from this reservoir. World Health Organization released guidelines in 2015 and in 2018 respectively, to provide updated consolidated guidance for expanding latent tuberculosis infection (LTBI) management in high-income or upper middle-income countries with an estimated TB incidence rate of less than 100 per 100000 population (including China). The development of the national guidelines should adapt to local epidemiology of TB, the availability of resources, and other determinants. Identifying at-risk populations, exploring appropriate intervention tools, and establishing systematic management system all require technical supports by means of strengthening basic research and clinical research. LTBI management is one of the important tools for moving TB control forward to prevention first.

Epidemiology and Statistical Methods

How to conduct a high-quality study on a tuberculosis diagnostic research

Shao-wen TANG,Bi-lin TAO,Qi-qi WANG,Hong-yan. YAO

Chinese Journal of Antituberculosis. 2018, 40(8):  796-799.  doi:10.3969/j.issn.1000-6621.2018.08.004

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Tuberculosis diagnosis often involved a variety of methods or examinations that makes it possible to conduct tuberculosis diagnostic accuracy studies based on routine work. However, most of the current diagnostic accuracy of tuberculosis research still have quality problems, such as patients’ selection, gold standard verification, blind evaluation, and so on. All these requires researchers to rigorous design, standardized report. So, this paper systematically introduces the design of diagnostic accuracy, indicators analysis and some problems need to pay attention, and help researchers to carry out high-quality original research.

Original Articles

Analysis of clinical characteristics in drug-resistant tuberculosis patients with drug-induced liver injury caused by chemotherapy

Yan-ping GE,Shao-jun ZHANG,Lan YAO,Ya HE,Lin FAN

Chinese Journal of Antituberculosis. 2018, 40(8):  800-804.  doi:10.3969/j.issn.1000-6621.2018.08.005

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Objective To analyze the clinical characteristics in drug-resistant pulmonary tuberculosis (PTB) patients with drug-induced liver injury (DILI) caused by chemotherapy.Methods A retrospective study was conducted on 2767 drug-resistant PTB patients in Shanghai Pulmonary Hospital during the period from January 1, 2008 to December 31, 2014. Of them, 387 cases occurred DILI (13.99% (387/2767)). To analyze some problems about the 387 cases. Composition of all kinds of drug-resistant PTB, the time distribution of DILI occurrence, the effect on the outcome of treatment, and whether concomitant viral hepatitis would affect the outcome of treatment or not.Results Of all the 387 patients, mono-resistance tuberculosis (MR-TB), polydrug-resistance tuberculosis (PDR-TB), multidrug-resistance tuberculosis (MDR-TB), extensive drug-resistance tuberculosis (XDR-TB) accounted for 11.63% (45/387), 27.65% (107/387), 35.14% (136/387), 25.58% (99/387), respectively. The incidences of DILI happened in ≤1 month, >1 month and ≤2 months, >2 months and ≤3 months and >3 months after anti-TB treatment were 258 (66.67%), 83 (21.45%), 17 (4.39%) and 29 (7.49%), respectively. After DILI, 68.99% (267/387) of the cases continued their anti-TB chemotherapy, the continued rate were 73.33% (33/45), 66.36% (71/107), 69.85%(95/136), 68.69% (68/99) in MR-TB, PDR-TB, MDR-TB and XDR-TB, respectively. There was no statistical difference among the four groups (χ ²=0.80, P=0.851). Of drug-resistant PTB cases with DILI, the success rate of chemotherapy was 47.03% (182/387), and the rates were 53.33% (24/45), 61.68% (66/107), 47.79% (65/136), 27.27% (27/99) in MR-TB, PDR-TB, MDR-TB and XDR-TB, respectively. Statistical difference was found among the four groups (χ ²=25.48, P<0.01). The treatment success rates of cases with and without viral hepatitis were 38.52% (47/122) and 50.94%(135/265), respectively. The difference was statistically significant (χ ²=5.17, P=0.023). Conclusion PDR-TB, MDR-TB and XDR-TB accounted for a high proportion of drug-resistant PTB with DILI cases. The majority of DILI occurred in one to two months after anti-TB treatment.DILI had little effect on the outcome of treatment. The success rate of drug-resis-tant treatment was low in concomitant viral hepatitis, therefore the anti-virus treatment should be took in time while anti-tuberculosis treatment get started.

Analysis on adverse drug reactions and treatment outcomes of different chemotherapy regimens for multidrug-resistant tuberculosis

Feng-li LI,Xiao-hong KAN,Qi LI,Yun-ling ZHNAG,Dong-fang LI,Yun ZHOU,Wen JIANG,Xiao-guo HUA,Cheng-yang HU,Min PAN,Xiu-jun ZHANG

Chinese Journal of Antituberculosis. 2018, 40(8):  805-809.  doi:10.3969/j.issn.1000-6621.2018.08.006

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Objective This study aims to analyze the adverse drug reactions and treatment outcomes of multidrug-resistant tuberculosis (MDR-TB) patients who received different chemotherapy regimens.Methods A prospective study was conducted from October 2009 to May 2014 in Anhui Provincial Chest Hospital. A total of 102 MDR-TB cases (including outpatients and inpatients) who met the inclusion criteria and received treatment were enrolled in this study. The cases were continuously and randomly assigned to regimen One (54 patients) and regimen Two (48 patients) group, according to their time of enrollment. Regimen One: 3Clr-Z-Am-Mfx+XY/3Clr-Z-Am3-Mfx+XY/12Clr-Z-Mfx+X, Regimen Two: 3Z-Am-Lfx+XY/3Z-Am3-Lfx+XY/18Z-Lfx+XY. In the regimens, Clr represented clarithromycin, Z represented pyrazinamide, Am represented amikacin, Lfx represented levofloxacin, Mfx represented moxifloxacin, and XY represented selecting two sensitive drugs according to the drug sensitivity test and drug tolerance results (could choose from protionamide (Pto), P-aminosalicylicacid (PAS), and ethambutol (E)). Adverse drug reactions and treatment outcomes of MDR-TB cases in the two groups were analyzed.Results The treatment success rates of the two regimens were 59.3% (32/54) and 64.6% (31/48), and there was no significant difference (χ ²=0.31, P=0.581). The adverse drug reactions rates of two treatment regimens were 66.7% (36/54) and 62.5% (30/48), and there was no significant difference (χ ²=0. 41,P=0.815). The top three adverse drug reactions for Regimen One were gastrointestinal reactions (41.7%, 15/36), simple uric acid increase (41.7%, 15/36) and blood system influence (25.0%, 9/36). And for the Regimen Two, the top three adverse drug reactions were gastrointestinal reactions (36.7%, 11/30), simple uric acid increase (33.3%, 10/30) and liver dysfunction (20.0%, 6/30). There were 12 (22.2%) patients in Regimen One and 3 (6.3%) patients in Regimen Two appeared QT interval prolongation. The difference between the two regimens was statistically significant (χ ²=3.97, P=0.046). In Regimen One, the treatment compliance rates between patients with (83.3% (30/36)) and without adverse reactions (88.9% (16/18)) were not statistically significant (χ ²=0.02, P=0.892). For the patients treated with Regimen Two, the treatment compliance rates of with and without adverse reactions was 83.3% (25/30) and 88.9% (16/18), respectively, with no statistically significant difference (χ ²=0.01, P=0.916). In Regimen One, there was no significant difference in the treatment success rate between patients with (55.6% (20/36)) and without adverse reactions (66.7% (12/18)) (χ ²=0.61, P=0.433); in Regimen Two, the difference in treatment success rate between the patients with adverse drug reactions (60.0% (18/30)) and without adverse drug reactions (72.2% (13/18)) was not statistically significant (χ ²=0.74,P=0.391). Conclusion The two treatment regimens achieved good results. And the treatment outcomes and compliance rates were not affected by adverse drug reactions.

Analysis on the adverse events among multidrug-resistant pulmonary tuberculosis patients receiving cycloserine-containing regimen

Jing WANG,Wei JING,Wei CHEN,Ru GUO,Xi-qin HAN,li-min WU,Guang-xu YANG,Kun-yun YANG,Cong CHEN,Lin JIANG,Chun-kui CAI,Zhi DOU,Li-juan DIAO,Hong-qiu PAN,Jian-yun WANG,Fei-fei DU,Li-xia WANG,Ren-zhong LI,Nai-hui CHU

Chinese Journal of Antituberculosis. 2018, 40(8):  810-814.  doi:10.3969/j.issn.1000-6621.2018.08.007

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Objective To analyze the adverse events in multidrug-resistant pulmonary tuberculosis patients treated with cycloserine-containing chemotherapy regimen.Methods A total of 623 multidrug-resistant pulmonary tuberculosis patients who were eligible for inclusion in the Global Fund’s fifth round of multidrug-resistance control program during January 2013 to June 2016 from 11 hospitals in China were selected. All patients used a standardized treatment regimen: 6PZA-Am(Cm)-Lfx(Mfx)-Pto-Cs/18PZA-Lfx(Mfx)-Pto-Cs; alternatives: PAS instead of Pto, Cm instead of Am, Mfx replacement Lfx (PZA: pyrazinamide, Am: amikacin, Cm: capreomycin, Lfx: levofloxacin, Mfx: moxifloxacin, Pto: prothionamide, Cs: cycloserine, PAS: p-aminosalicylide sodium). The adverse events during treatment were collected, their clinical characteristics, severity, occurring time, duration, treatment method and prognosis were analyzed, and the correlation between the drugs and adverse events were determined.Results Of the 623 multidrug-resistant pulmonary tuberculosis patients treated with cycloserine-containing regimen, 316 (50.7%) patients had at least one adverse event, and 36 (5.8%) patients discontinued the treatment or changed the treatment regimen due to adverse reactions. The most common adverse reactions were hyperuricemia (22.8%, 142/623) and abnormal liver function (18.8%, 117/623). Twenty-seven (4.3%, 27/623) patients developed central nervous system or psychiatric symptoms that were likely to be associated with cycloserine, and the median (interquartile range) time of occurrence was 3 (2, 6) months. After drug discontinuance or psychological counseling, the symptoms disappeared.Conclusion In multidrug-resistant pulmonary tuberculosis patients who received cycloserine-containing regimen, the occurrence of nervous system or psychiatric symptoms was mainly related to cycloserine. Patients need to be closely monitored for these symptoms during treatment that includes cycloserine.

Observation and comparative analysis on the adverse drug reactions of amikacin and capreomycin in treating multidrug resistant tuberculosis patients

Fei REN,You XU,Li-yun DANG,Yan-qin WU,Jin-bao MA,Si-si. ZHENG

Chinese Journal of Antituberculosis. 2018, 40(8):  815-820.  doi:10.3969/j.issn.1000-6621.2018.08.008

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Objective To observe and compare the adverse drug reactions (ADR) of amikacin and capreomycin in treating multidrug resistant tuberculosis (MDR-TB) patients and their impact on therapeutic regimen, and to provide references for the selection of second-line injectable anti-tuberculosis agents in MDR-TB patients.Methods This study retrospectively analyzed the data of 112 MDR-TB patients who were diagnosed and received individualized treatment over 1 year in Xi’an Chest Hospital from January 2015 to December 2016. According to the used second-line injectable anti-tuberculosis agents, the patients were divided into two groups, Group amikacin (n=43) and Group capreomycin (n=69). The negative conversion rate of Mycobacterium tuberculosis sputum cultivation and lesions absorption rate at the end of 6 and 12 months after treatment, the incidence and severity of hearing loss, tinnitus, nephrotoxicity and hypokalemia, and the impact of these ADR on treatment were observed in the two groups.Results The negative conversion rate at the end of 6 months after treatment in the Group amikacin and Group capreomycin was 65.1% (28/43) and 82.6% (57/69), respectively; the difference was statistically significant (χ ²=4.43, P<0.05). The negative conversion rate in the two groups at the end of 12 months after treatment was 69.8% (30/43) and 82.6% (57/69), and the lesions absorption rate were 53.5% (23/43) and 60.9% (42/69) at the end of 6 months and 65.1% (28/43) and 71.0% (49/69) at the end of 12 months, respectively; however, the differences were not statistically significant (χ ² values were 2.52, 0.59 and 0.43, P values were >0.05). In the Group amikacin and Group capreomycin, the incidence of hearing loss was 20.9% (9/43) and 5.8% (4/69), and the incidence of hypokalemia was 4.7% (2/43) and 30.4% (21/69); the differences were statistically significant (χ ² values were 4.53 and 10.79, P values were <0.05). The incidence of tinnitus in the two groups was 46.5% (20/43) and 30.4% (21/69), and the incidence of nephrotoxicity was 4.7% (2/43) and 10.1% (7/69), respectively; the differences were not statistically significant (χ ² values were 2.95 and 1.08, P values were >0.05). The overall incidence of ADR in the two groups was 60.5% (26/43) and 53.6% (37/69), respectively, and the difference was not statistically significant (χ ²=0.50, P>0.05). There were no serious ADR in the two groups. The mild ADR in the patients with ADR accounted for 65.4% (17/26) and 81.1% (30/37), respectively, and the difference was not statistically significant (χ ²=1.99, P>0.05). The occurrence rate of drug discontinuation caused by ADR within 4 months was 20.9% (9/43) and 5.8% (4/69) in the Group amikacin and Group capreomycin, respectively, and the difference was statistically significant (χ ²=4.53, P<0.05).Conclusion The incidence of ADR of second-line injectable anti-tuberculosis agents is high. Considering the occurrence of ADR and the therapeutic efficacy, capreomycin is recommended in MDR-TB patients as a second-line injectable agent.

Correlation analysis between inhA gene mutation and protionamide-resistance in multidrug resistance and extensively drug-resistant Mycobacterium tuberculosis

Yan-hua SONG,Gui-rong WANG,Feng-min HUO,Rong-mei LIU,Meng-qiu GAO,Qi. LI

Chinese Journal of Antituberculosis. 2018, 40(8):  821-824.  doi:10.3969/j.issn.1000-6621.2018.08.009

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Objective To investigate the characteristics of mutations in genes katG and inhA and their association with resistance to protionamide (PTH) in the clinical strains of multidrug resistance Mycobacterium tuberculosis (MDR-MTB) and extensively drug-resistant Mycobacterium tuberculosis (XDR-MTB).Methods A total of 132 patients with MDR-TB or XDR-TB diagnosed in Beijing Chest Hospital, Capital Medical University from February 2016 to February 2017 were selected as the subjects of this study. The clinical isolates of these subjects were culture-positive and identified as MTB. The results of drug sensitivity test for isoniazid (INH), rifampicin (RFP), levofloxacin (Lfx), amikacin (Am), capreomycin (Cm) and PTH and the data of mutations in katG and inhA were available. The characteristics of katG and inhA mutations in MTB clinical isolates and their correlation with resis-tance to PTH were analyzed.Results Among the 132 clinical isolates, 89 (67.4%) were MDR-MTB, 26 (19.7%) were pre-XDR-MTB and 17 (12.9%) were XDR-MTB. The total resistance rate of PTH was 22.7% (30/132), and the rates were 11.2% (10/89), 30.8% (8/26) and 70.6% (12/17) in MDR-MTB, pre-XDR-MTB and XDR-MTB, respectively. The resistance rate of XDR-MTB to PTH was significantly higher than that of MDR-MTB (χ ²=30.57, P<0.01) and pre-XDR-MTB (χ ²=6.55, P<0.05). The mutation rate of inhA (with or without katG mutation) was 19.1% (17/89), 23.1% (6/26) and 17.6% (3/17) in MDR-MTB, pre-XDR-MTB and XDR-MTB strains, respectively. In PTH resistant strains of MDR-MTB, pre-XDR-MTB and XDR-MTB, only 5/10, 4/8 and 3/12 had inhA gene mutation. Conclusion From MDR-MTB to XDR-MTB clinical strains, the proportion of PTH resistance was increased significantly, and the mutation rate of inhA gene was decreased. The mutation in inhA gene may not be the main molecular mechanism of PTH resistance in XDR-MTB, and the strains without inhA mutation are not sure to be sensitive to PTH.

Analysis of drug resistance baseline in smear positive pulmonary tuberculosis patients in Anhui province

Qing WANG,Dong-chun MA,Jie LIU,Song YAO,Xiao-hong KAN,Fang-jin BAO,Ai-min WANG,Si-jiu SHI,Xiao-min XU,Xue-hui FANG,Gen-you ZHANG,Yun-sheng DING,Xun-di BAO

Chinese Journal of Antituberculosis. 2018, 40(8):  825-833.  doi:10.3969/j.issn.1000-6621.2018.08.010

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Objective To analyze the drug resistance and distribution of smear positive pulmonary tuberculosis patients in Anhui province.Methods Using stratified cluster sampling method, 42 sampling survey points in Anhui province were extracted. A total of 3047 patients with smear-positive pulmonary tuberculosis was collected from September 15, 2015 to August 31, 2016, and were cultured by Roche solid (101 were polluted (3.31%), 275 were negative (9.03%), 2671 were positive (87.66%)) and anti-drug sensitivity test of 6 anti-TB drugs (including isoniazid (INH), rifampin (RFP), ethambutol (EMB), streptomycin (Sm), ofloxacin (Ofx) and kanamycin (Km)). Finally 141 cases were identified as non-tuberculosis mycobacteria (NTM), and results of drug sensitivity test were acquired from 2530 cases. SPSS 19.0 was used for statistical analysis, and the counting data were analyzed by the χ ² test. P<0.05 was considered statistically significant. Results A total of 1861 strains (73.56%) were all sensitive of INH, RFP, EMB, Sm, Ofx, Km in 2530 strains of Mycobacterium tuberculosis isolates, 669 strains (26.44%) were resistant to one or more anti-TB drugs. All of them (2530 strains), clinical isolates from initial (84.31%, 2133/2530) and re-treat patients (15.69%, 397/2530) had the highest percentages in INH (13.32%, 337/2530), Sm (10.97%, 234/2133), RFP (31.74%, 126/397), respectively. The resistant rates of INH (10.45%, 223/2133), RFP (7.64%, 163/2133), Sm (10.97%, 234/2133), EMB (1.88%, 40/2133) and Ofx (6.52%, 139/2133) in initial patients were significantly lower than those in re-treat patients (28.72% (114/397), 31.74% (126/397), 21.91% (87/397), 8.56% (34/397) and 21.66% (86/397); χ ²=96.66, 192.07, 36.19, 52.74, 94.76, respectively, all P=0.000). The multidrug resistance rates were 7.63% (193/2530), 4.97% (106/2133) and 21.91% (87/397) for all, initial and re-treat patients, respectively. The poly-resistance rates were 12.41% (314/2530), 8.95% (191/2133) and 30.98% (123/397), respectively. The extensively drug-resistant rates were 0.91% (23/2530), 0.61% (13/2133) and 2.52% (10/397), respectively. Conclusion The drug resistance rate of patients with smear positive pulmonary tuberculosis in Anhui province is relatively high for any drug resistance, and the drug resistance rate of INH is the highest. The resistance rate of Sm was the highest in the initial treatment patients, and RFP is the highest in the retreatment patients. The epidemic of drug-resistant tuberculosis in Anhui province cannot be ignored.

The diagnostic value of sputum PCR-reverse dot blot hybridization in the diagnosis of suspected NTM pulmonary disease

Li-ping CHENG,Xiao-yan ZHANG,Wei SHA

Chinese Journal of Antituberculosis. 2018, 40(8):  834-839.  doi:10.3969/j.issn.1000-6621.2018.08.011

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Objective To investigate the diagnostic value of sputum PCR-reverse dot blot (RDB) hybridization in the diagnosis of suspected NTM pulmonary disease.Methods Three hundred and thirty four cases of suspected NTM pulmonary disease were selected from January 2014 to October 2017 at the Shanghai Pulmonary Hospital Affiliated to Tongji University School of Medicine based on respiratory symptoms and thoracic CT findings. Sputum samples were collected and underwent PCR-RDB hybridization Mycobacterium species identification, and traditional PNB-TCH growth culture, 218 patients were diagnosed with NTM pulmonary disease (NTM pulmonary disease group), 42 with tuberculosis (TB group), and 74 with other lung diseases (excluded from the study). The sensitivity, specificity, positive predictive values and conformity rate of PCR-RDB were calculated.Results The positive culture detection rate for the 334 cases of suspected NTM pulmonary disease was 67.66% (226/334), while the PCR-RDB detection rate was 64.67% (216/334). Differences in the results for the two methods were not statistically significant (χ ²=0.67, P=0.231). The sensitivity of PCR-RDB and culture for the 218 cases of NTM pulmonary disease was 82.57% (180/218) and 87.61% (191/218), respectively, and no statistically significant difference between the two methods was found (χ ²=1.20, P=0.169). The positive predictive values for PCR-RDB and culture were 98.36% (180/183) and 100.00% (191/191), respectively. The specificity of PCR-RDB and culture for the 42 cases of TB was 78.57% (33/42) and 83.33% (35/42), respectively, and no statistically significant difference was found (χ ²=0.31, P=0.391).The positive predictive values of PCR-RDB and culture for diagnosing TB were 100.00% (33/33) and 100.00% (35/35), respectively. The conformity rate of PCR-RDB was 83.08% (216/260), and that of culture was 86.92% (226/260), and no statistically significant difference was found (χ ²=1.51, P=0.134). Conclusion Sputum PCR-RDB hybridization has high sensitivity and specificity and is a simple and rapid method that can be used to identify bacteria directly. It is a helpful guide for clinicians during diagnosis and may lead to more rapid and accurate treatment.

The diagnostic value of GeneXpert MTB/RIF of the lapping suspension of the thoracoscopic biopsy tissue in tuberculous pleural effusions

Cheng-jun LI,Bing-qi SUN,Jiao SUN,Wei ZHANG,Yang WANG,Li JI,Fang. MA

Chinese Journal of Antituberculosis. 2018, 40(8):  840-845.  doi:10.3969/j.issn.1000-6621.2018.08.012

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Objective To assess the diagnostic value of GeneXpert MTB/RIF assay using the lapping suspension of thoracoscopic biopsy tissue in detecting tuberculous pleurisy.Methods From January 1, 2017 to December 31, 2017 in the pleurisy ward of Shenyang Chest Hospital, 51 cases who showed unexplained pleural effusion under medical thoracoscopy and were not treated by any anti-tuberculous therapy were selected as the subjects of this study. A routine pathological examination of the pleural biopsy specimen was conducted for each patient. Also, BACTEC MGIT 960 liquid culture system and GeneXpert MTB/RIF detections were conducted using the suspension of the other part of specimen after grinding. The diagnosis accuracy of GeneXpert MTB/RIF assay using biopsy tissue suspension in detecting tuberculous pleurisy was evaluated, taking BACTEC MGIT 960 positive results (stain identification as Mycobacterium tuberculosis) and pleural tissue biopsy results (granulomatous inflammation and anti-acid staining positive) as diagnostic criteria.Results Of the 51 patients, 34 were diagnosed with tuberculous pleurisy. MGIT 960 positive culture and strain identification confirmed 20 cases (39.2%, 20/51), and 17 cases (33.3%, 17/51) were pleural biopsy pathological positive. Among them, 3 cases were confirmed by the two detection me-thods. Seventeen (33.3%, 17/51) patients were diagnosed with non-tuberculous pleural effusion. Taking the finial diagnosis as the gold standard, the sensitivity and specificity of GeneXpert MTB/RIF, MGIT 960 culture system and pathological diagnosis were 64.7% (22/34) and 100.0% (17/17), 58.8% (20/34) and 100.0% (17/17), and 50.0% (17/34) and 100.0% (17/17), respectively. The sensitivity of GeneXpert MTB/RIF was superior to the MGIT 960 culture system and pathological diagnosis; however, the difference was not statistically significant (χ ²=1.53, P=0.466).Conclusion The sensitivity and specificity of GeneXpert MTB/RIF assay using the lapping suspension of thoracoscopic biopsy tissue taken under thoracoscopy is high. It is of great significance for the diagnosis of tuberculous pleurisy.

The diagnostic value of T cell enzyme-linked immunospot tuberculosis assay in diabetes complicated with pulmonary tuberculosis

Ya WANG,Mei-ying WU,Kun-yun YANG, ,Shu-cai WU,Shu-jun GENG,Zhi-hui LI,Ming-wu LI,Wan-li KANG,Shen-jie TANG

Chinese Journal of Antituberculosis. 2018, 40(8):  846-853.  doi:10.3969/j.issn.1000-6621.2018.08.013

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Objective To investigate the diagnostic value of T cell enzyme-linked immunospot tuberculosis assay (T-SPOT.TB) in diabetic patients complicated with pulmonary tuberculosis.Methods From December 2012 to November 2015, 207 cases of diabetes mellitus complicated with pulmonary tuberculosis and 95 cases of diabetes in Beijing Chest Hospital, Suzhou Fifth People’s Hospital, Hunan Thoracic Hospital, the Xinjiang Uygur Autonomous Region Thoracic Hospital, Hebei Provincial Chest Hospital, and Kunming Third People’s Hospital tuberculosis department were retrospectively analyzed. Among them, there were 141 cases of diabetes complicated with positive culture pulmonary tuberculosis (group Ⅰ) and 66 cases of diabetes complicated with culture-negative pulmonary tuberculosis (group Ⅱ), and the 95 cases of diabetes were defined as (group Ⅲ). Whole blood T-SPOT.TB kit was used to detect the immune response of peripheral blood lymphocytes to early secretory target antigen 6 (ESAT-6) and secretory protein 10 (CFP-10) of MTB strain.Results The positive rates of T-SPOT.TB in group Ⅰ, Ⅱ and Ⅲ were 92.9% (131/141) (95%CI: 87.3%-96.5%), 86.4% (57/66) (95%CI: 75.7%-93.6%) and 48.4% (46/95) (95%CI: 38.0%-58.9%), respectively. The positive rate of T-SPOT.TB in group Ⅰ was significantly higher than that in group Ⅲ, and the difference was statistically significant (χ ²=59.91 P<0.01); the positive rate of T-SPOT.TB in group Ⅱ was significantly higher than that in group Ⅲ, and the difference was statistically significant (χ ²=24.33, P<0.01); the positive rate of T-SPOT.TB in group Ⅰ was similar to that in group Ⅱ (χ ²=2.31, P=0.129). Taking the clinical diagnosis of pulmonary tuberculosis as the gold standard, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of T-SPOT.TB test to diagnose pulmonary tuberculosis in patients who were complicated with diabetes were 90.8% (188/207) (95%CI: 86.0%-94.3%), 51.6% (49/95) (95%CI: 41.1%-62.0%), 80.3% (188/234) (95%CI: 74.7%-85.2%), 72.1% (49/68) (95%CI: 59.9%-82.3%), and 78.5% (237/302) (95%CI: 73.4%-83.0%), respectively.Conclusion T-SPOT.TB has a high positive rate, sensitivity and specificity in the diagnosis of tuberculosis in diabetes patients complicated with pulmonary tuberculosis. It can be used as an auxiliary diagnostic method for diabetes complicated with pulmonary tuberculosis.

Study on the infection risk and model of students in close contact with senile tuberculosis patients

Da-jie ZHANG,Jia-yu HUANG,Xu-hui LI,Meng-yu LI,Yan-shu CHEN,Ying ZHANG,Yi-hua XU

Chinese Journal of Antituberculosis. 2018, 40(8):  854-859.  doi:10.3969/j.issn.1000-6621.2018.08.014

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Objective To provide scientific basis for the early detection of tuberculosis (TB) infection in close contacts though investigating the infection risk and model of students (the high-risk and susceptible family members) who were in close contact with elderly TB cases (referred to as indicator cases).Methods A total of 244 newly diagnosed elderly TB patients were registered in the Tuberculosis Prevention and Treatment Center in Wuhan from May 2016 to November 2017. By self-recommendation and according to the inclusion and exclusion criteria, 209 student close contacts were enrolled. A questionnaire survey and a purified protein derivative (PPD) test were conducted. Univariate analysis and multivariate logistic regression models were used to screen the risk factors for TB infection in student close contacts of senile tuberculosis and to study the key risk factors and establish a decision tree model.Results The positive rate of PPD test among the 209 student close contacts was 77.51% (162/209). Logistic stepwise regression analysis showed that the duration of contact with the indicator cases (OR=29.17, 95%CI: 4.65-183.04), site ventilation (OR=5.79, 95%CI: 2.14-15.67), and self-protection awareness (OR=3.56, 95%CI: 1.24-10.22) had statistically significant differences between the students with positive and negative PPD test results. Using the results of logistic regression analysis, the decision tree model was built with 3 layers and 7 nodes. The duration of exposure to the indicator cases had the greatest impact on the risk of TB infection in close contacts. The positive rate of student with a contact time of ≥2 h was 97.30% (72/74), which was higher than that of students with a contact time of <2 h (66.67% (90/135)). The self-protection awareness of close contacts was a secondary influence factor when exposed to indicator cases. Under the contact time <2 h node, the positive rate of close contacts without self-protection awareness was 94.12% (48/51), which was higher than that of contacts with self-protection consciousness (50.00% (42/84)). In the self-protection awareness node, the positive rate of contacts in good ventilation condition at the site of exposure was 25.00% (12/48), lower than that of contacts in moderate or poor ventilation condition at the site of exposure (83.33% (30/36)).Conclusion The decision tree model indicates the duration of contact with the indicator cases, the ventilation at the contact sites and the self-protection awareness as important influencing factors of TB infection among students close contacts. The degree of influence of each factor was as follows: contact time > self-protection awareness > contact point ventilation.

Plasma oxidative stress in patients with pulmonary tuberculosis complicated with diabetes mellitus

Chun-ling LI,Liang-fei NIU,Hai-cong LI,Kang WU,Shui-hua LU,Xiao-yong FAN

Chinese Journal of Antituberculosis. 2018, 40(8):  860-865.  doi:10.3969/j.issn.1000-6621.2018.08.015

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Objective To explore the profile of oxidative stress in plasma of patients with pulmonary tuberculosis complicated with type 2 diabetes mellitus.Methods Forty five cases of tuberculosis patients (group PTB), 28 cases of tuberculosis and type 2 diabetes (group PTB-DM2), and 24 healthy volunteers (group HC) were collected from February 2016 to January 2017 in the Shanghai Public Health Clinical Center. The content of total antioxidant capacity (T-AOC), catalase (CAT), heme oxygenase-1 (HO-1), glutathione (GSH), superoxide dismutase (SOD) and lipid malondialdehyde (MDA) in the 3 groups were measured, respectively, with the median (quartile) (M (P₂₅, P₇₅)). SPSS 23.0 software was used to analyze the data of 3 groups, and GraphPad Prism 7.0 software was used to map, the difference was statistically significant in P<0.05.Results The biochemical indexes of group HC, group PTB, and group PTB-DM2 were T-AOC (4.65 (4.16, 5.15), 2.70 (3.50, 4.30), 2.55 (2.03,3.48) U/ml), CAT (54.20 (35.46,81.30), 23.49 (9.49, 44.72), 5.66 (-14.00, 31.98) U/ml), HO-1 (16.12 (11.84, 24.09), 11.44 (7.95, 15.53), 8.19 (7.53, 11.58) ng/ml), GSH (5.14 (3.98, 7.33), 4.69 (3.02, 6.47), 2.90 (1.90, 6.14) μmol/ml), SOD (14.31 (10.63, 17.33), 14.28 (11.86, 15.69), 13.78 (12.26, 18.00) U/ml), MDA (3.60 (2.62, 4.40), 5.11 (4.26, 7.23), 12.77 (9.47, 14.89) nmol/ml), there were significant differences between the three groups (χ ²=35.28,P<0.01;χ ²=28.94,P<0.01;χ ²=23.00,P<0.01;χ ²=9.24,P=0.010;χ ²=15.53,P<0.01;χ ²=59.46,P<0.01). The plasma levels of T-AOC, CAT and HO-1 in the PTB group were significantly lower than those in the HC group, and the MDA level was significantly higher than that in the HC group (Z=-3.88,P<0.01; Z=-3.82,P<0.01;Z=-3.21,P=0.005;Z=-3.94,P=0.008, respectively). The levels of T-AOC, CAT, HO-1, GSH and SOD in the PTB-DM2 group were all significantly lower than those of the PTB patients, and the MDA level was significantly higher than those of the PTB patients (Z=-3.08, P=0.047; Z=-2.44, P=0.046; Z=-2.27, P=0.023; Z=-2.45, P=0.096; Z=-3.50, P=0.002; Z=-6.01, P<0.01). Conclusion After infection of MTB, the anti-oxidant ability of PTB patients is lower and the lipid oxidation damage is present. While combined type 2 diabetes, the oxidative stress of PTB patients can be aggravated, the patient’s antioxidant capacity is lower, and the lipid oxidation damage is aggravated.

Establishment of a rabbit model of brucellar spondylitis

Chuan-hui XUN,Xiao-yu CAI,Chuan-feng WANG,

Chinese Journal of Antituberculosis. 2018, 40(8):  866-871.  doi:10.3969/j.issn.1000-6621.2018.08.016

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Objective To explore the feasibility of establishing a New Zealand rabbit Brucellosis spondylitis animal model based on the method used in constructing a rabbit spinal tuberculosis model.Methods Forty-eight New Zealand rabbits were randomly divided into an experimental group (16), a control group (16) and a blank group (16). In the experimental group, a gelatin sponge containing 0.1 ml of a M5 suspension of an attenuated sheep Brucella vaccine (3×10 ⁸ CFU/ml) was inserted in a hole drilled under the endplate of L6. In the control group, the gelatin sponge was immersed in 0.1 ml of a 0.9% NaCl solution. The blank group did not receive any treatment. Results Eight weeks after surgery, the survival rate of the rabbits in the experimental group was 75.0% (12/16), that in the control group was 87.5% (14/16), and that in the blank group was 100.0% (16/16). Four weeks after surgery, X-ray and CT 3D reconstruction results showed the intervertebral space in 5 rabbits from the experimental group became narrowed, and MRI examination showed that 7 rabbits had paravertebral soft tissue abscess formation. There was no paravertebral soft tissue abscess formation in the control group and the intervertebral disc showed no change. Eight weeks after surgery, X-ray and CT 3D reconstruction showed narrowing of the intervertebral space in 8 rabbits, and MRI examination showed paravertebral soft tissue abscess formation and disc signal change in 10 rabbits. Paravertebral soft tissue abscess formation and disc signal change was not observed in the control group. Histopathology analysis at 8 weeks after surgery showed pathological changes in the paravertebral soft tissue in the experimental group and the infiltration of inflammatory cells (predominantly lymphocytes). No changes in cell proliferation and inflammatory cell infiltration were found in the control group nor the blank group.Conclusion A new animal model of Brucellosis spondylitis can be established by drilling a hole in the upper endplate of the lumbar vertebrae, applying a gelatin sponge injected with an M5 suspension of the attenuated sheep Brucella vaccine and sealing the whole with paraffin wax.

Treatment of spinal tuberculosis using one-stage anterior debridement combined with rib grafting and internal fixation of diseased vertebrae (report of 30 cases)

Hui-jun ZHANG,Zeng-hui LU,Li-ming DUAN,Chang-sheng. ZHU

Chinese Journal of Antituberculosis. 2018, 40(8):  872-877.  doi:10.3969/j.issn.1000-6621.2018.08.017

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Objective To investigate the clinical efficacy of one-stage anterior debridement combined with rib graft fusion and anterior internal fixation with nail for diseased vertebrae.Methods Thirty patients with spinal tuberculosis who were admitted in Xi’an Chest Hospital and performed one-stage anterior debridement combined with rib grafting and anterior internal fixation during Jan. 2013 to Dec. 2015. There were 11 males and 19 females with average age (44.2±12.4) years old ranged from 23 to 70.The lesion segments were involved from T5 to L1 (no more than 2 segments in all cases). Operative time, intraoperative bleeding volume, incision healing, postoperative complication, and toxic symptoms of tuberculosis were recorded in all cases. The visual analogue scales (VAS) were observed before operation and two weeks and two years after operation in all cases. The neurological function Frankel grade according to the American Spinal injury Association (ASIA) were observed after operation. There were grade A in 3 cases, grade B in 2 cases, grade C in 5 cases, grade D in 12 cases and grade E in 8 cases before operation. The Cobb angles were compared before operation, two weeks and two years after operation in all cases.Results The average operative time was (178.0±33.6) min ranged from 120 to 240 min and average intraoperative bleeding volume was (507.5±148.9) ml ranged from 300 to 800 ml. No relapse cases, no incision healing poor, no complication with sinus and screw loosening occurred during average follow-up (25.9±6.6) months ranged from 24 to 36 months. The toxic symptoms of tuberculosis and spinal pain disappeared in all patients. The average VAS in the group after operation (1.4±0.5) was significantly lower than that before operation (6.5±1.5) at the last follow-up (2 years after operation) with significant difference statistically (t=15.759,P=0.000). The Frankel grades were no cases with grade A, grade B and grade C in each one case, grade D in 2 cases and grade E in 26 cases at the last follow-up (2 years after operation). The Cobb angle was average (19.1±7.4)° before operation and (13.6±3.9)° at the last follow-up. The improvement of Cobb angle before and after operation was significant difference statistically (t=5.003,P=0.000). The lesions of spinal vertebrae were basically healed and bone nonunion and pseudoarthrosis were not found in the patients. There were no screws of internal fixation loosened and broken and no bone graft absorbed and disappeared.Conclusion It is feasible for the treatment of spinal tuberculosis using one stage anterior debridement with rib graft fusion and anterior internal fixation with nails for diseased vertebrae. The operation is safe and reliable, and the efficacy of short-term follow-up is satisfactory.

One-stage anterior debridement with titanium cage bone graft and system internal fixation with screw rod in the treatment of thoracic spinal tuberculosis

Jian LIU,Ming-xia LIN,Ke CHEN,Xian-an WANG,Ming-dong. LI

Chinese Journal of Antituberculosis. 2018, 40(8):  878-883.  doi:10.3969/j.issn.1000-6621.2018.08.018

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Objective To analyzed the clinical efficacy of one-stage anterior debridement with titanium cage bone graft and system internal fixation with screw rod in the treatment of thoracic spinal tuberculosis.Methods Twenty eight patients with thoracic spinal tuberculosis who were underwent surgery of one-stage anterior debridement with titanium cage bone graft and system internal fixation with screw rod in our hospital during Sep. 2009 to Dec. 2016. Twenty one patients were followed up including male in 14 cases and female in 7 cases. There was one patient with the fifth and sixth thoracic spinal involved, three patients with the sixth and seventh thoracic spinal involved, three patients with the seventh and eighth thoracic spinal involved, two patients with the ninth and tenth thoracic spinal involved, four patients with the tenth and eleventh thoracic spinal involved, two patients with the eleventh and twelfth thoracic spinal involved, one patient with the sixth, seventh and eighth thoracic spinal involved, three patients with the seventh, eighth and ninth thoracic spinal involved, and two patients with the ninth, tenth and eleventh thoracic spinal involved. According to the results of preoperative and postoperative follow-up of Frankel spinal cord injury grade, visual analogue score (VAS), Cobb angle correction of kyphosis and bone graft fusion, the clinical efficay was assessed.Results There were grade B in one case, grade C in five cases, grade D in six cases, grade E in nine cases according to preoperative Frankel grade assessment, and grade D in four cases, grade E in seventeen cases according to Frankel grade assessment in the last follow-up ranged from 10 months to seven years. The VAS was average 6.29±1.27 scores before operation, average 2.81±0.87 scores at one week after operation and average 1.24±0.89 scores at the last follow-up. The Cobb angle was average 19.81±11.08 degrees before operation, average 3.81±2.77 degrees at one week after operation and average 4.52±3.23 degrees at the last follow-up. Bone fusion was achieved in all 21 patients. The fusion time was 6.93±1.33 months ranged from 5 to 11 months. No case was found loosening, shedding and fracture of the internal fixation system at the last follow-up.Conclusion One-stage anterior debridement with titanium cage bone graft and system internal fixation with screw rod can achieve good clinical effect including effective debridement, nerve compression relieved, kyphosis correction and spinal stability reconstruction in the treatment of thoracic spinal tuberculosis.

Clinical effects of total knee resurface arthroplasty in treatment of patients with tuberculous knee joint stiffness or rigidity

Sheng-ping HU,Shi-yuan SHI,Jun FEI,Zhen LAI,Peng-fei. MA

Chinese Journal of Antituberculosis. 2018, 40(8):  884-889.  doi:10.3969/j.issn.1000-6621.2018.08.019

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Objective To explore the clinical feasibility of total knee resurface arthroplasty (TKR) in treatment of the patients with tuberculous knee joint stiffness.Methods A retrospective analysis was used. A total of 10 cases with tuberculous knee joint stiffness, who hospitalized at our hospital from October 2011 to July 2015 and were treated with TKR, were enrolled into this study. Before the operation of TKR, a comprehensive assessment was given to each patient, including the function of the knee joint and the situation of tuberculosis (TB) disease. The laboratory examinations, magnetic resonance imaging (MRI) of knee joint, X-ray and CT scan, as well as the correct anti-TB chemotherapy were given to the patients. The total knee resurface arthroplasty was performed to the patients whose knee joint TB had been well controlled, bone defects did not influence the stability of joint prostheses and had no sinus tract and mixed infections. After the operation, the correct anti-TB chemotherapy was continued, and the joint prosthesis stability, the knee joint functions (Hospital for Special Surgery Knee Score (HSS) was used), the range of motion and the relapse of knee joint TB were evaluated.Results Before the operation, among 10 patients, 3 cases had rigidity knee while 7 cases had stiff knee; 4 cases had active knee joint TB with the disease course of 4-9 months, and the remaining 6 patients had old lesions of knee joint TB with the disease course of 20-41 month. All patients were followed up till 24-41 months after surgery, and the average follow-up time was (35.4±9.6) months. The time of operation ranged from 90 minutes to 118 minutes, and the average time was (102.0±8.5) minutes. The preoperative knee joint stiffness angle of the patients ranged from 15.0° to 55.0°; at the end of follow-up, the flexion angle of the patients’ knee ranged from 95.0°to 120.0°(mean (105.0±14.8)°) and the extensor angle ranged from -5.0°to 10.0°(mean (0.5±7.0)°). The score of HSS had improved from 46.6±16.2 before the operation to 79.6±9.6 after the operation. At the end of follow-up, no loosening of joint prostheses and no relapse of TB were found.Conclusion Under the premise of individual and correct anti-TB chemotherapy, the clinical treatment to the patients with tuberculous knee joint stiffness by using total knee resurface arthroplasty is effective and feasible. However, the surgical indications should be strictly assessed and followed.

A case report of eyelid tuberculosis and literatures review on ocular tuberculosis

Ke XIAO,Ying PENG,Lin YU,Fu-li HUANG,Li ZHONG

Chinese Journal of Antituberculosis. 2018, 40(8):  890-893.  doi:10.3969/j.issn.1000-6621.2018.08.020

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Objective The clinical features of ocular tuberculosis patients were summarized and analyzed in order to improve clinical diagnosis and treatment.Methods The clinical manifestations, laboratory findings, treatment and prognosis of one case with eyelid tuberculosis were reported, and the corresponding domestic and foreign literatures were reviewed and analyzed. The PubMed, Wanfang, Weipu, and CNKI databases were searched by using “ocular tuberculosis” and “eye; tuberculosis” as search terms and the date of retrieval was set from January 2000 to December 2017. The patients’ general condition, duration of disease, ocular tuberculosis involving site, clinical manifestations, basal status and complications, tuberculosis infections on other sites, major diagnostic methods, treatment, and outcomes were collected. The literatures with complete clinical data were included in this analysis, while the review literatures, duplicate publications, and literatures having incomplete data were excluded. A total of 57 articles were obtained through screening and 61 cases of ocular tuberculosis were reported in these articles.Results The 36-year-old male patient showed painless masses of the right lower eyelid and ulcerated suppurative pus as the main manifestations. No concurrent other parts of tuberculosis infection was found. The secretions were checked by acid-fast staining and real-time quantitative PCR to confirm the presence of Mycobacterium tuberculosis infection. The prognosis was good after anti-tuberculosis and local dressing treatment. Through literatures review, data on 61 patients with ocular tuberculosis were obtained. The total number of subjects was 62 cases including the case reported in this study. There were 27 males and 35 females, who aged from 3-83 years. 35 cases were complicated with tuberculosis in other sites. 9 cases were binocular tuberculosis and 53 cases were monocular tuberculosis. There were 41 cases with intraocular tuberculosis, mainly manifested as changes in vision; among them, 19 cases improved, 9 were blind, 5 had impaired vision, and 5 were cured after treatment. As for the 23 cases with orbital and ocular adnexal tuberculosis, local mass and abnormal secretions were the main manifestations; among them, 8 cases were cured, and 7 cases improved.Conclusion The clinical manifestations of ocular tuberculosis are not typical. The prognosis of orbital and ocular adnexal tuberculosis is good. The intraocular tuberculosis has a great impact on visual acuity. Clinicians should be alert to ocular tuberculosis so as to avoid missed diagnosis and misdiagnosis.

Review Articles

Progress in nutritional status evaluation of elderly pulmonary tuberculosis patients

Dan-ping CHEN,Min LI

Chinese Journal of Antituberculosis. 2018, 40(8):  894-897.  doi:10.3969/j.issn.1000-6621.2018.08.021

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Tuberculosis is a chronic consumptive infectious disease that has a two-way relationship with the body’s nutritional status and affects each other. Elder patients with pulmonary tuberculosis are a special group. Due to their age and weak resistance, they often coexist with multiple diseases, and their nutritional status is not ideal, which is affected by many factors. Correct assessment of the nutritional status of elder tuberculosis patients is the basis for improving their nutritional intake. At present, there are many researches on the evaluation indicators of nutritional status of elderly pulmonary tuberculosis patients, but there is no unified evaluation index. This review contains the related researches on the nutritional status of elder pulmonary tuberculosis patients both domestic and international to provide help and support for the clinical evaluation of nutritional status of elder pulmonary tuberculosis patients.

Short Articles

A survey and analysis on the incidence of tuberculosis in an enterprise in Xiaogan, Hubei province in recent years

Shuang-chu LI,Yu-xia GUO,Long-ling YE,Zhi CHENG,Jun WANG,Hong-zhang. CHEN

Chinese Journal of Antituberculosis. 2018, 40(8):  898-904.  doi:10.3969/j.issn.1000-6621.2018.08.022

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This paper reports a survey on the tuberculosis (TB) morbidity in an enterprise in recent years, which was conducted by Xiaogan Antituberculosis Institute in August, 2017. The results showed that 13 TB patients were diagnosed in 2242 employees, 12 of whom had an attack within one year; of the 224 employees in the work group where the first onset patient operated, the strongly positive rate of PPD test was 63.8% (143/224), and a definite diagnosis was confirmed in 7 patients; of the 36 employees on the dormitory floor where the first onset patient lived, the strongly positive rate of PPD test was 75.0% (27/36), and a definite diagnosis was confirmed in 4 patients. It was analyzed that two outbreaks in this epidemic were resulted from the same source; the primary causes were the absence of timely quarantine and normative therapy and management, as well as the poor ventilation of workshops and buildings. In order to avoid similar epidemic, it was proposed that every medical and health institution should strictly enforce Measures for the Management of TB Prevention and Control, perform well in the report and referral of TB patients and suspected patients, treatment and management of TB patients, and also in the examination of the close contacts of infectious TB patients according to their respective functions, and guide the enterprises to promote the propaganda and education of TB prevention and treatment knowledges to their employees.