Table of Content

10 January 2015, Volume 37 Issue 1

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It’s the key that the measures for the three major challenges to deal with tuberculosis are in place

ZHONG Qiu

Chinese Journal of Antituberculosis. 2015, 37(1):  7-8.  doi:10.3969/j.issn.1000-6621.2015.01.002

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The effect of HIV screening in TB patients in different HIV epidemic area

LAI Yu-ji，CHENG Shi-ming，ZHOU Lin，LIU Er-yong，WANG Dong-mei，LI Tao

Chinese Journal of Antituberculosis. 2015, 37(1):  9-13.  doi:10.3969/j.issn.1000-6621.2015.01.003

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Objective To compare the effects of HIV screening for TB patients in different HIV epidemic area.  Methods Three hundred and thirty-three counties in 31 provinces (cities, districts) were sampled with stratified cluster sampling method. The survey was divided into two stages. New registered TB patients were offered HIV antibody testing during September 1st to December 31st in 2007 and 2008 respectively. A total of 45 675 TB patients were surveyed. Results The new HIV detection rate in TB patients was 0.3% (133/43 998). Of new diagnosed HIV-positive cases, 70.7% (94/133) came from nine southwest provinces, 20.3% (27/133) came from seven central provinces. It was more likely to detect new HIV-positive cases in TB patients in provinces with the cumulative reporting number of HIV/AIDS cases more than or equal to 6000 than in provinces with that less than 2000 (0.6%（98/15 872） vs 0.1%（13/13 302），OR=6.35，95%CI=3.56－11.33), in counties with that more than or equal to 200 than in counties with that less than 50 (0.6%（70/11 521） vs 0.1%（20/22 656），OR=6.92，95%CI=4.21－11.38), and in counties with that more than or equal to 50 but less than 200 than in counties with that less than 50 (0.4%（43/9821） vs 0.1%（20/22 656），OR=4.98，95%CI=2.93－8.47). Conclusion HIV screening strategy for TB patients should be developed according to the severity and characteristics of local HIV epidemic. Routine HIV testing for TB patients should be implemented in counties with the cumulative reporting number of HIV/AIDS cases more than or equal to 200 in central China where HIV transmission route was mainly through illegal blood transfusion, and in counties with that more than or equal to 50 in other area.

Epidemiological features of students’ pulmonary tuberculosis in Chongqing from 2009 to 2013

PANG Yan, ZHANG Shun, HU Dai-yu, LIN Hui

Chinese Journal of Antituberculosis. 2015, 37(1):  14-18.  doi:10.3969/j.issn.1000-6621.2015.01.004

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Objective To understand the epidemiological characteristics of pulmonary tuberculosis (TB) in students in Chongqing and provide evidence for the pulmonary TB prevention and control in schools. Methods We collected the pulmonary (PTB) reporting data from the infectious Diseases Reporting System, and refered to the Statistical Yearbooks Chongqing, the total number of students in Chongqing were 5 595 500 in 2009, 5 588 500 in 2010, 5 646 200 in 2011, 6 081 100 in 2012 and 6 128 800 in 2013 respectively. The reported incidence of pulmonary tuberculosis was calculated, statistical analysis was made on the student registration rate, and the situation of the population was described, the Chi-square value was calculated. 0.05 was set as the significance level. Results The total PTB cases of students were 2169 in 2009, 2045 in 2010, 1960 in 2011, 1782 in 2012 and 1777 in 2013 respectively. The smear-positive pulmonary cases of students were 809 in 2009, 806 in 2010, 624 in 2011, 439 in 2012 and 331 in 2013 respectively. The average registration rate of pulmonary TB and smear-positive pulmonary tuberculosis among students was 33.52/100 000(9733/29 040 100) and 10.36/100 000(3009/29 040 100) respectively. The proportion of smear negative pulmonary tuberculosis was 57.08%（1238/2169） in 2009, 54.52%（1115/2045） in 2010, 63.42%（1243/1960） in 2011, 71.04%（1266/1782） in 2012 and 78.05%（1387/1777） in 2013 respectively, the proportion rose by year(χ²_trend=280.51，P<0.01). The proportion of health examination was 4.47%（97/2169） in 2009, 6.99%（143/2045） in 2010, 8.01%（157/1960） in 2011, 7.18%（128/1782） in 2012 and 11.25%（200/1777） in 2013 respectively, the proportion rose by year(χ²_trend=53.82，P<0.01). The number of male student PTB were much higher than female(1.24∶1, 5396/4337). Most of them were between 15 and 19 age group,the proportion of PTB dropped in this group was 66.62%（1445/2169） in 2009, 68.26%（1396/2045） in 2010, 67.65%（1326/1960）in 2011, 68.69%（1224/1782） in 2012 and 72.04%（1280/1777） in 2013 respectively, the proportion rose by year(χ²_trend=11.06，P<0.01). The proportion of student PTB peaked in March, which was 21.48%（466/2169） in 2009, 18.63%（381/2045） in 2010, 17.70%（347/1960）in 2011, 23.46%（418/1782） in 2012 and 16.49%（293/1777） in 2013 respectively. The top three school PTB incidence county were Wuxi(137.84/100 000，102/73 999), Pengshui(81.61/100 000，102/124 980), Wulong(64.69/100 000，42/64 925), which were national poverty county.  Conclusion The epidemic situation of tuberculosis in Chongqing city among students is serious. The proportion of student PTB detected by health examination rose by year.The majority are smear negative. More PTB patients were male, mainly detected from the middle and high school. The PTB cases peaks in March, and the national poverty county was more serious.

Analysis of epidemic characteristics of tuberculosis among students from 2008 to 2013 in Shaanxi province

DENG Ya-li, ZHANG Tian-hua, MA Yu, LIU Wei-ping, ZHAO Yan

Chinese Journal of Antituberculosis. 2015, 37(1):  19-23.  doi:10.3969/j.issn.1000-6621.2015.01.005

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Objective To analyze epidemic characteristics of tuberculosis among students, and to provide the evidence for TB prevention and control strategy.  Methods We collected the students’ pulmonary TB reporting data from the Infectious Diseases Reporting System (IDRS) from 2008 to 2013. The number of students were 7 813 134, 7 618 213, 7 438 600, 7 200 128, 6 778 025 and 6 465 627 respectively from 2008 to 2013 in Shaanxi province. We implemented a descriptive statistics method to analyze epidemic characteristics of students TB, and used Chi-square and trend Chi-square test to compare rates.P<0.05 is considered significant difference.  Results The reported numbers of students TB from 2008 to 2013 were 3947, 3205, 2418, 1637, 1631 and 1410 respectively. The incidence of students TB from 2008 to 2013 were 50.52/100 000, 42.07/100 000, 32.51/100 000, 22.74/100 000, 24.06/100 000, and 21.81/100 000 respectively, which were declined by an average of 15.47% annually (χ²_trend=1382.68，P<0.05)；At the same time，the reported number of smear positive students PTB were 764, 500, 413, 269, 193 and 138 respectively with the incidence of 9.78/100 000, 6.56/100 000, 5.55/100 000, 3.74/100 000, 2.85/100 000 and 2.13/100 000 respectively, declining by annual average of 26.28% (χ² _trend=520.61，P<0.05). The proportion of students TB in the whole patients decreased from 12.07%（3947/32 702）in 2008 to 6.17%（1410/22 869）in 2013（χ²=1023.15，P<0.05）. The number of reported students TB was highest in each spring, especially in March with an average of 312 cases, a little rise in autumn and reported the least in December, July and August each year with an average of 147 monthly. The top three students TB incidence city was Yulin (103.38/100 000), Yan’an (52.21/100 000), Tongchuan (51.48/100 000) from 2008 to 2013. A total of 5696 cases of student PTB were reported in 18 to 20 years old group, accounting for 39.98% in the whole TB patients. The male to female sex ratio was 1.43∶1.  Conclusion The incidence of reported students TB had a declining trend from 2008 to 2013 in Shaanxi province. The number of reported students TB peaked in spring. The incidence of reported students TB in northern part of Shaanxi was highest, male higher than female. Students in 18 to 20 years old were the key population for TB prevention.

Retrospective study of epidemic features of registered pulmonary tuberculosis students in school in Sichuan province from 2009 to 2013

LI Ting, ZHANG Pei-ru, XIA Yong, WANG Dan-xia, LI Yun-kui, HE Jin-ge

Chinese Journal of Antituberculosis. 2015, 37(1):  24-29.  doi:10.3969/j.issn.1000-6621.2015.01.006

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Objective To understand the epidemic features of tuberculosis(TB)in students in Sichuan province and provide evidences for implementing TB control strategies and measures in students.  Methods We used data mining methods to analyze data obtained from Chinese Tuberculosis Information Management System and Sichuan Statistical Yearbook. The total number of students of Sichuan Province from 2009 to 2013 were 12 196 438, 13 307 748, 13 123 102, 12 788 048 and 12 788 048 respectively. Excel 2013 and SPSS 19.0 were used to analyze characteristics of TB students, trend Chi-square test was used to compare the sources of TB cases, diagnosis and therapeutic category of students among different years. Chi-square test was used to compare the characteristics like gender, nationality, diagnosis category, initial treatment and retreatment constitution and treatment outcome between students and the whole population. The delay time was analyzed by variance analysis. The significance level was 0.05.  Results The registered TB in students declined from 33.5/100 000(4085/12 196 438) in 2009 to 20.7/100 000 (2652/12 788 048) in 2013(χ²=495.675, P<0.05). Between 2009 and 2013, 39.1% (6222/15 905) of patients concentrated in northeast of Sichuan. Proportion of student TB patients detected by passive identification had a decline from 40.6%(1688/4149) in 2009 to 30.5%(801/2626) in 2013 (χ²=135.446, P<0.05),while referral tracking constituent ratio rose from 53.4%(2214/4149) in 2009 to 64.5%(1694/2626) in 2013 (χ²=135.446, P<0.05). In 2012, the proportion of smear-positive in student patients (21.9%(629/2876)) was lower than that of the whole population (32.2%(19 325/60 101)) (χ²=183.457, P<0.05), while patients with TB pleurisy in students (3.6%(104/2876)) was higher than that in the whole population (1.7%(1010/60 101)) (χ²=183.457, P<0.05). The proportion of retreatment smear-positive patients in students(4.9%(31/630)) was significantly lower than that of the whole population (16.3%(3155/19 325)) (χ²=59.153, P<0.05). Treatment delay time (46.37±130.449 days) of student patients was shorter than the whole population (75.29±317.071 days) (F=23.810, P<0.05).  Conclusion The students TB has a declining trend, but students TB control need strengthening in certain areas like northeast of Sichuan and minority concentrated areas and TB workers should be on the alert for the increase in student patients with tuberculous pleurisy.

Analysis of national tuberculosis control work mode with patients detection and treatment

LI Tao, CHENG Shi-ming, DU Xin

Chinese Journal of Antituberculosis. 2015, 37(1):  30-34.  doi:10.3969/j.issn.1000-6621.2015.01.007

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Objective Analyze patients detection and treatment in groups of counties with different TB control work mode, in order to enhance new TB control system.  Methods Collect the data of patients detection and treatment in 2012 and 2013 in county level from TB Management Information System, then divide the counties into different groups by work mode, and analyze their performance and trends. In the total 2627 counties, 1523 counties are defined as “tuberculosis (TB) control center mode”, 750 as “public-public mix (PPM) Mode”, 283 as “PPM transition mode”, and 71 as “TB control center transition mode”.  Results There are 39.3% (1033/2627) of counties in China have already changed their work mode to the new PPM TB control work mode (Collaboration of TB control center, designated hospitals and primary public health institutions) till end of 2013. Compared to 2012, in the four different type of counties with different work mode (“tuberculosis (TB) control center mode”, “PPM mode”, “PPM transition mode”, “TB control center transition mode”), the number of new smear positive patients (S+) registered have declined 13.5%(24 032/178 033, 178 033 patients registered in 2012,154 001 registered in 2013, similarly hereinafter), 9.2%(89 866,81 590,8276/89 866), 22.3%(30 044,23 346, 6698/30 044) and 2.2%(7297, 7133, 164/7297), the proportion of S+ accounted for patients with active pulmonary tuberculosis have declined 3.3%(37.4% in 2012, 34.1% in 2013, similarly hereinafter), 2.0%(33.1%, 31.1%), 5.9%(34.6%, 28.7%) and －0.3%(34.1%, 34.4%). The cure rate of new S+ registered in the first half year of 2012 in 4 types of counties above-mentioned are 94.0%(89 088/94 786), 93.1%(43 185/46 394), 94.1%(14 512/15 421) and 93.7%(3702/3943). The corresponding rate for S+ registered in the first half year of 2013 are 93.1%(72 180/77 521), 91.7%(36 622/39 950), 90.4%(10 565/11 683) and 91.8%(3187/3470). The cure rate of 2012 in “PPM transition mode” counties (94.1%, 14 512/15 421) have no difference with “TB control center mode” counties (94.0%, 89 088/94 786, χ²=0.321, P=0.571), but, when these counties changed their work mode in 2013, the cure rate have changed into 90.4%(10 565/11 683) and 93.1%(72 180/77 521), the significant differences appeared(χ²=108.550, P<0.0001).  Conclusion There have already much counties changed their work mode to PPM mode. The TB control work, such as the number of patients detection and the cure rate, in “PPM transition mode” counties may be weakened in the transition period, the relative departments must enhance their management and supervision work.

The induction of type Ⅰ interferon by different M. tuberculosis strains and its expression in the peripheral blood of the patients with tuberculosis

ZHAN Sen-lin, ZHANG Guo-liang, ZHONG Hong-jian, JIN Xiao-fei, LIN Qiao, ZHANG Ming-xia, CHEN Xin-chun, ZHOU Bo-ping

Chinese Journal of Antituberculosis. 2015, 37(1):  35-39.  doi:10.3969/j.issn.1000-6621.2015.01.008

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Objective To study the induction of type I interferon (IFN) by different M. tuberculosis (Mtb) strains and its expression in the peripheral blood of the patients with tuberculosis.  Methods CD14⁺ cells were isolated from the peripheral blood mononuclear cells of 30 healthy people from Feb 2012 to Aug 2012, and were stimulated by the recombinant human macrophage colony stimulating factor (M-CFS) for 7 days, and differentiated into human macrophages. These macrophages were infected with Mtb strains H37Ra and H37Rv, respectively. The expression levels of type Ⅰ IFN genes IFNB and IFNA in the macrophages were detected with real-time PCR assay. We also observed the gene expression of type Ⅰ IFN in different population (15 healthy controls, 15 persons with latent Mtb infection and 15 patients with tuberculosis). Using GraphPad 4.0 software for statistical analysis, P<0.05 was considered statistically significant.  Results After Mtb H37Rv infection, IFNB gene expression in human macrophages was significantly higher than that in the control group (10.38±2.24 vs 6.26±3.42; t=2.47, P=0.026). There were no significant differences in IFNB gene expression between Mtb H37Ra infection group and control group (8.92±0.85 vs 6.26±3.42;t=1.84, P=0.09). There were no significant differences in IFNA gene expression among Mtb H37Rv infection group, H37Ra infection group and control group (5.11±2.31 vs 5.17±3.40 vs 4.41±1.69; F=0.16，P=0.85). The IFNB gene expressions in TB patients (4.32±1.22) were significantly higher than that in healthy controls (2.73±1.23; t=3.55, P=0.0014). There were no significant differences in IFNA gene expression among healthy controls, the persons with latent Mtb infection and the patients with tuberculosis (3.91±0.75 vs 4.25±1.03 vs 4.73±1.44；F=1.93，P=0.064).  Conclusion Virulent Mycobacterium tuberculosis infection can induce type Ⅰ IFN gene expression. Up-regulated expression of IFNB gene can be used as a potential molecular marker in the diagnosis of tuberculosis.

The application value of T-SPOT.TB in the diagnosis of tuberculous pleurisy

CHEN Xi, LI Xiao-yuan, LI Ling, MENG Ping, ZHANG Ting-jun, ZHAO Hong-mei, LI Yun-peng

Chinese Journal of Antituberculosis. 2015, 37(1):  40-46.  doi:10.3969/j.issn.1000-6621.2015.01.009

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Objective To evaluate the clinical application value of Mycobacterium tuberculosis T cell enzyme-linked immunospot tuberculous test (T-SPOT.TB test) in the diagnosis and differential diagnosis of tuberculous pleurisy. Methods Ninety-three patients with pleural effusion who were hospitalized in Shenyang Chest Hospital from August 2012 to June 2013 were enrolled in this study. According to the diagnostic criteria of tuberculous pleurisy in clinical guidelines for the diagnosis and treatment of tuberculosis, 48 patients with tuberculous pleurisy and 45 cases of non-tuberculous pleurisy were divided into study group and control group. The number of T lymphocytes (namely spots forming cells, SFC) to early secretary antigenic target 6 (ESAT-6) and/or culture filtrate protein (CFP-10) sensitive in peripheral blood mononuclear cell (PBMC) of participants were determined by T-SPOT.TB test. The positive rates of SFC in two groups were compared. The results were compared with other related indicators (adenosine deaminase (ADA), serum tuberculosis antibody (TB-AB), and tuberculosis bacterium culture (Mtb culture) of pleural effusion. SPSS 17.0 was used for statistical analysis. Pearson Chi-square test was used to compare rates and P value less than 0.05 was considered statistically significant. Results The positive rate of tuberculous pleurisy group (91.67%, 44/48) by T-SPOT.TB test was significantly higher than that of control group (8.89%, 4/45). The difference χ² was statistically significant (χ²=63.73, P<0.05). The sensitivity of T-SPOT.TB test in detection of ESAT-6 and CFP-10 (91.67%, 44/48) was higher than that in detection of ESAT-6 (85.42%, 41/48) or CFP-10 (75.00%, 36/48). The difference had no statistical significance (compared with ESAT-6, χ²=0.92, P>0.05; compared with CFP-10, χ²=4.8, P>0.05). The sensitivities of T-SPOT.TB, ADA detection, TB-AB detection and Mtb culture were 91.67% (44/48), 70.83% (34/48), 62.50% (30/48) and 14.58% (7/48) respectively. The specificities were 91.11% (41/45), 55.56% (25/45), 62.22% (28/45) and 100.00% (45/45). The diagnostic accuracy rates were 94.62% (88/93), 63.44% (59/93), 62.37% (58/93) and 55.91% (52/93). Except the specificity of Mtb culture which was higher than T-SPOT.TB test, the sensitivity and specificity of T-SPOT.TB test were higher than those of other test methods, and the difference was statistically significant (compared with ADA-sensitivity χ²=6.84, P<0.05, specificity χ²=14.55, P<0.05; compared with TB-AB-sensitivity χ²=11.56, P<0.05, specificity χ²=10.49, P<0.05; compared with Mtb culture-specificity χ²=57.27, P<0.05, specificity χ²=4.18，P<0.05).  Conclusion T-SPOT.TB test has high sensitivity, specificity and diagnostic accuracy in the diagnosis of tuberculous pleurisy. Therefore, it is worth in the clinical extension and application.

The retrospective investigation on death rate of tuberculosis among rural residents in Xiangtan county from 2005 to 2010

GONG De-hua，BAI Li-qiong, CHEN Tian-zhu, ZENG Zheng-biao, ZHAO Pei-an, ZHANG Chuan-fang，LI Yan-hong

Chinese Journal of Antituberculosis. 2015, 37(1):  47-51.  doi:10.3969/j.issn.1000-6621.2015.01.010

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Objective To know TB death characteristics of the rural residents and assess the TB disease burden and the TB control effect in Xiangtan county，and to provide scientific basis for decreasing TB mortality.  Methods A retrospectively survey was conducted using the stratified cluster sampling method and death case card designed by “TB early warning model research” of “the 11th five-year” state’s major science and technology projects. The case card was mainly consists of three parts: the first was the basic information, including the name, the sex, the occupation, the marital status and the educational level etc.; and the second was the death condition, including the time of death, the age of death, the category of death cause and the diagnosis of death cause etc.; and the third was the condition of TB deaths, including the TB diagnosis and treatment, the death cause of TB patients and the direct death cause of the tuberculosis. Of 2880 case cards were sent out in the baseline survey in 2009 and the terminal survey in 2010, 2873 effective questionnaires were taken back, and the effective rate was 99.8%. We used the collected death case data and population data to analyze TB death feature of rural residents in Xiangtan county, which mainly includes the TB mortality, the composition of death cause, the order of death cause, the death rate of different gender, year, villages and towns. The data is analyzed by the SPSS 13.0 statistical software. The measurement data is described by the median, the minimum value, the maximum value et al. The count data is described by the rate and the composition et al. The difference of mortality is compared in different sex, in different villages and towns, and in years.  Results The total mortality of all kinds of diseases of in 2005—2010 was 568.3/100 000(2873/505 582). The TB mortality in 2005—2010 was 13.4/100 000 (68/505 582),the order TB death cause was 11th;. In 2005—2010 years,the male TB mortality rate was 21.1/100 000 (56/264 924). The women TB mortality rate was 5.0/100 000 (12/240 658), the difference was statistically significant (χ²=24.463, P<0.001). Among 2005—2010, TB mortality respectively was 10.7/100 000(9/83 752), 10.7/100 000(9/83 962), 8.3/100 000(7/84 155), 24.9/100 000 (21/84 389), 20.1/100 000(17/84 633) and 5.9/100 000(5/84 691), the difference was statistically significant (χ²=17.132, P<0.05). The TB mortality in 2010 compared with 2009 and 2008 respectively was statistically significant (χ²=6.555, P<0.05, χ²=9.905, P<0.05). The pulmonary tuberculosis mortality rate in 2005—2010 was 9.7/100 000(49/505 582).The median death was 68 years old, and 44 cases was more than 60 years old. Among 68 death cases of tuberculosis, 60 cases (88.2%) were known as TB patients, 34 were registered in the local CDC, accounting for 56.7%. Among 49 cases dead of pulmonary tuberculosis, 16 cases died of chronic incomplete cardiopulmonary function, accounting for 32.7% (16/49), 14 cases died of the whole body failure, accounting for 28.6% (14/49), 12 cases died of haemoptysis, accounting for 24.5% (12/49).  Conclusion The pulmonary tuberculosis mortality of the rural residents has declined in Xiangtan. TB prevention and control effect is remarkable. But, the TB mortality is still high and the disease burden of TB is heavy.

Prediction of epitopes of Mycobacterium tuberculosis Rv1419 protein

LIU Yin-ping, WANG Quan-li，ZHANG Jun-xian, LIANG Yan, YANG You-rong, BAI Xue-juan, WU Xue-qiong

Chinese Journal of Antituberculosis. 2015, 37(1):  52-55.  doi:10.3969/j.issn.1000-6621.2015.01.011

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Objective To predict the epitopes of Mycobacterium tuberculosis Rv1419 protein. Methods The amino acid sequence of Rv1419 protein was input and predicted B cell and T cell epitopes using multi-parameters including the secondary structure, hydrophilicity, antigenicity, accessibility, flexibility, charge distribution by Protean software of DNAStar software package. Results The Rv1419 protein has rich secondary structure and multiple sections with higher antigenicity. There were a few potential B cell epitopes at 67－70, 72－82, 142－154, 131－137 amino acid residues or nearby, these epitopes had better antigenicity, contained beta angle and irregular coil structure, present in the surface probability and had larger flexibility. There also were more potential T cell epitopes of the protein containing at 5－15, 18－22, 29－32, 43－55, 58－62, 64－68, 86－97, 99－109, 110－114, 117－123, 126－128, 136－140 amino acid residues or nearby. Conclusion Mycobacterium tuberculosis Rv1419 protein is a T-cell-epitope dominant antigen, B cell epitopes also exists, which will lay the foundation for its further study and application.

Diagnostic accuracy of gene chip in identifying rifampicin resistance Mycobacterium tuberculosis: a Meta-analysis

RAN Bing, CAI Lin

Chinese Journal of Antituberculosis. 2015, 37(1):  56-65.  doi:10.3969/j.issn.1000-6621.2015.01.012

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Objective To systematically review the diagnostic accuracy of gene chip in identifying rifampicin (RFP) resistance Mycobacterium tuberculosis (Mtb)，and to provide the evidence for the clinical use of gene chip in detection of RFP-resistance Mtb. Methods We electronically searched The Cochrane Library (Issue 1, 2014), PubMed, EMbase, Wanfang Data, CNKI from the date that the database was established to February 2014. In order to find any publications which are related to detection of RFP-resistance Mtb by using gene chip, the search key terms in English and Chinese were designed as follows: tuberculosis, tuberculosis and drug resistance, tuberculosis and drug resistance and gene chip, tuberculosis and drug resistance and gene chip and rifampicin. Two reviewers independently screened literatures according to the inclusion and exclusion criteria, extracted data and assessed the quality of methodology of the included studies according to the QUADAS items. The Meta-DiSc software (version 1.4) was used to conduct pooling on sensitivity (SEN), specificity (SPE), positive likelihood ratio (+LR), and negative likelihood ratio (-LR). Heterogeneity test was performed and the summary receiver operating characteristic (SROC) curve was drawn and area under curve (AUC) was calculated. Results A total of 223 publications were found. Finally, 22 articles (including one article from multicenter study) and 25 studies were included into the review，which involved 4879 Mtb isolates (including 1314 RFP-resistant strains, 3565 susceptible strains and the standard strain H37Rv). The results of Meta-analysis showed that, compared with the traditional drug sensitivity test, SEN of gene chip in detection of RFP-resistance Mtb was 0.89 (95%CI (0.87－0.91)), SPE was 0.98 (95%CI (0.97－0.98)), +LR was 30.89 (95%CI (22.15－43.06)), -LR was 0.10 (95%CI (0.07－0.15)), diagnostic OR was 354.06 (95%CI (212.09－591.07)), AUC was 0.9833. Conclusion Gene chip has a good value in detection of RFP-resistance Mtb. If the traditional drug sensitivity test is regarded as a gold standard, gene chip has high sensitivity, high specificity and high diagnostic OR value. It can be used as a clinical supplementary method of drug sensitivity test.

Identification of Mycobacterium tuberculosis and its drug resistance with gene chip

SHI Guo-min, YU Rong, PENG Xue-feng, SHI Yan, NIE Ying, QI Zhi-qiang, CHEN Yong-jun, XIANG Yan-gen,LIU Zhong-quan

Chinese Journal of Antituberculosis. 2015, 37(1):  66-73.  doi:10.3969/j.issn.1000-6621.2015.01.013

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Objective Study on gene chip technique in detection of drug resistance of Mycobacterium tuberculosis and its clinical value.  Methods (1) One hundred and thirty-seven strain identification of Mycobacterium clinical isolates from Changsha Central Hospital by gene chip and Spoligotyping technology from 2011-01 to 2012-12. (2)Drug-susceptibility test of rifampin and isoniazid to Mycobacterium tuberculosis clinical isolates by absolute concentration method. (3) Drug-susceptibility test of rifampin and isoniazid to Mycobacterium tuberculosis clinical isolates by DNA chips for rpoB, KatG, inhA. Rifampin resistant is one or a plurality of site mutation of rpoB gene, isoniazid resistance is one or a plurality of site mutation of KatG gene and inhA gene. Compared Spoligotyping with gene chip method of species identification by Kappa test, Compared the absolute concentration method with gene chip method of drug sensitivity by χ² test and Kappa test.  Results （1）For 45 rifampin sensitive (under 50 μg/ml) and isoniazid sensitive(under 1 μg/ml) isolates tested by absolute concentration method, 42 are wild type for rpoB gene with the sensitivity of 93.3%(1 for 511T-C mutations, 1 for 531C-T mutations, 1 for 516A-T mutations), 45 are wild type for KatG gene with the sensitivity of 100.0% and 43 are wild type for inhA gene with the sensitivity of 95.6%(2 for15C-T mutation) by DNA chip method, respectively. （2）For 18 rifampin-resistant (50－250 μg/ml) isolates tested by absolute concentration method, 16 has mutation in rpoB gene with the sensitivity of 88.9% by DNA chip method. Those mutations happened at 531, 516, 526, 511 amino acid sites of rpoB. For 19 rifampin-resistant (above 250 μg/ml) isolates tested by absolute concentration method, 19 has mutation in rpoB gene with the sensitivity of 100% by DNA chip method. Those mutations happened at 531, 516, 526, 511 amino acid sites of rpoB.（3）Compare the DNA chips with the absolute concentration method, for 13 isoniazid-resistance(1－10 μg/ml) isolates, 12 has mutation in KatG gene with the sensitivity of 92.3% by DNA chip method, which mainly happened at 315 site. No mutation related to the drug resistance was found in inhA gene. Compare the DNA chips with the absolute Concentration method, For 9 isoniazid-resistance(above 10 μg/ml) isolates, 9 has mutation in KatG gene with the sensitivity of 100% by DNA chip method, which mainly happened at 315 site. No mutation related to the drug resistance was found in inhA gene. （4）For 137 clinical isolates tested by Spoligotyping, 104 are Mycobacterium tuberculosis with the sensitivity of 100.0%(104/104), 7 are Mycobacterium avium complex with the sensitivity of 77.8%(7/9), 15 are Mycobacterium intracellulare with the sensitivity of 93.8%(15/16), 1 are Mycobacterium fortuitum with the sensitivity of 0.0%(0/0), 10 are Mycobacterium chelonei with the sensibility of 100.0%(8/8) by DNA chip method, respectively. Kappa=0.95, U=30.6, P<0.05. Conclusion The drug-sensitive test by DNA chips method matched the absolute concentration method very well. RFP-resistance was related to the mutations at the sites of 531, 516, 526, 511 for rpoB gene, and INH-resistance was related to the mutations at the site of 315 for KatG gene. No mutation was found in inhA gene in INH-resistant isolates. DNA chip method might be a rapid and effective method for the detection of Mtb drug-resistant isolates and mycobacterium species.

Risk factors associated with sputum culture status after two months’ treatment of multidrug-resistant tuberculosis

ZHOU Yang, XU Wei-guo, DING Xiao-yan, ZHU Li-mei, YU Hao, CHEN Cheng, SHAO Yan, LU Wei

Chinese Journal of Antituberculosis. 2015, 37(1):  74-79.  doi:10.3969/j.issn.1000-6621.2015.01.014

Abstract ( 2020 )   PDF (787KB) ( 816 )   Save

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Objective To explore the situation of sputum culture conversion, and to evaluate the risk factors of sputum culture conversion for patients with multidrug-resistant TB.  Methods In Xuzhou, Nantong and Zhenjiang, tuberculosis culture and strains identification were carried out on the sputum smear-positive patients, and then drug susceptibility test(DST) was carried out with proportion method. Standardized treatment regimen and individualized regimen were given to MDR-TB patients registered from 1 January 2009 to 30 June 2012. Surveillane and DOTS were implemented to each patient during the treatment. Bacteriologic, treatment outcome and risk factors of sputum culture conversion were evaluated. Three hundred and seventy-six MDR-TB patients had been analyzed, including 278 male, and 98 female. The average age was (49.33±15.36) years old. Data was analyzed using SPSS 13.0, Chi-squared test and logistic regression were used for univariate and multivariate statistics. P value less than 0.05 was considered statistically significant.  Results 58.78% (221/376), 61.97% (233/376) and 61.17% (230/376) patients got culture conversion at 2, 4 and 6 months’ treatment, which had no significant differences between them (χ²=0.807, P>0.05). The treatment success rates of patients got culture conversion at 2, 4 and 6 months were 69.68% (154/221), 71.24% (166/233) and 73.48% (169/230) respectively, which were all higher than patients with culture positive results or without culture results (χ²=60.804，82.619，101.047, P<0.01). The treatment success rate of patients with positive culture at 2 months’ treatment was 31.33% (26/83), and was higher than that at 6 months’ (16.36%, 9/55)(χ²=3.912, P<0.05). In a multivariate analysis, previous TB treatment (P<0.01, OR=0.205; 95%CI: 0.070－0.598), resistance to second line drugs (P<0.05, OR=2.609; 95%CI: 1.097－6.206) and resistance to kanamycin (P<0.05, OR=10.008; 95%CI: 1.101－90.974) had statistically significant negative association with culture conversion at 2 months.  Conclusion About 60% MDR-TB patients get culture conversion at 2 months’ treatment. Previous TB treatment, resistance to second line drugs and resistance to kanamycin are associated with culture conversion at 2 months.

Advances in the preventive treatment of latent tuberculosis infection

AI Jing-wen，RUAN Qiao-ling，ZHANG Wen-hong

Chinese Journal of Antituberculosis. 2015, 37(1):  80-85.  doi:10.3969/j.issn.1000-6621.2015.01.015

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The prophylactic treatment of latent tuberculosis infection plays an important role in the prevention and treatment of tuberculosis. In recent years, studies have reported that HIV-infected patients, close contacts of active tuberculosis, and patients who use tumor necrosis factor antagonists should take the prophylactic treatment for latent tuberculosis infection. The currently preferred treatment is 9 months of isoniazid therapy (9INH), other regimens includes 6 months of isoniazid therapy (6INH), 4 months of rifampicin therapy (4RFP), 3 months of rifampin + isoniazid program (3（RFP+INH）), 3 months rifapentine + isoniazid program (3（Rft+INH)）. In China, due to the large number of latent tuberculosis infection, it is of great importance to launch the preventive treatment. However, the number of drug resistant patients ranked the first in the world, careful evaluation should be conducted in order to avoid the further increase in drug resistance.

The progress of combined drug susceptibility test with Mycobacterium tuberculosis

ZHANG Lin-lin, YANG Hua, XIAO He-ping

Chinese Journal of Antituberculosis. 2015, 37(1):  86-89.  doi:10.3969/j.issn.1000-6621.2015.01.016

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Tuberculosis remains a threat to global pandemic, it becomes more difficult to control TB due to the emergence of multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis. Preventing the resistance to a paticular drug, WHO has recommended the combined modality therapy with several drugs as the main method in the treatment of TB. Individualized treatment plan, based on the drug susceptibility results, should be taken in the treatment of drug-resistant TB. So far, the drug susceptibility test is mostly carried out for monotherapy. However, in some cases, even the single drug susceptibility results are resistant, the combined modality therapy still performances better therapeutic effect, which reminds us that the combination of several drugs used in treatment may enhance its antibacterial activity. At present, because of the severe drug resistance of first-line drugs and the shortcoming of second-line drugs (such as price，toxicity and so on), we urgently need to find a new anti-TB chemotherapy to control the prevalence of drug-resistant. Before creating a new chemistry program, it is important to conduct quantified experiments repeatedly to evaluate the antimicrobial activity of the combined modality therapy.

Advance in anti-tuberculous activity of clofazimine

ZUO Xiao-shu, LU Yu

Chinese Journal of Antituberculosis. 2015, 37(1):  90-94.  doi:10.3969/j.issn.1000-6621.2015.01.017

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Clofazimine, a phenazine derivative possessing antimicrobial activity, was originally used to cure leprosy. Recently it has been found that clofazimine has potency against Mycobacterium tuberculosis, especially for multidrug-resistant strains. Related studies showed clofazimine has good potency in the treatment of multidrug and extensively multidrug-resistant tuberculosis. Thereby, study on the new targets and mechanisms of clofazimine have become the research hotspot in recent years. This review aims to introduce the latest advancement of clofazimine in terms of pharmacological properties and clinical applications, focusing on the mechanisms of anti-tuberculous action.