Table of Content

10 June 2013, Volume 35 Issue 6

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Annual report on clinical diagnosis and treatment progress of tuberculosis(2012) (Part 1 clinical diagnosis)

Chinese Antituberculosis Association of Clinic Society

Chinese Journal of Antituberculosis. 2013, 35(6):  405-426. 

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In the recent 1 year, much progress has been made on the clinical diagnosis of tuberculosis (TB), and some new diagnostic methods and techniques have already been employed in clinical practice. In the bacteriological diagnosis, the combination of 2 new techniques isothermal microcalorimetry, detonation nanodiamonds with traditional culture is more rapid and could improve the detection rate, sensitivity and specificity. Molecular imaging in the diagnosis of pulmonary and extrapulmonary TB has made great progress. Interferon-gamma release assays have the superiority in the diagnosis of sputum-negative pulmonary TB and extrapulmonary TB. Molecular biology diagnosis for TB still focused on testing technology with a core of nucleic acid amplification. Among those methods, Xpert Mtb/RIF is most compelling, it not only achieved fruitful results in the diagnosis of TB and drug-resistant TB, but also played an important role in pediatric TB and Mtb/HIV coinfection. RNA simultaneous amplification and testing have been used for the diagnosis of TB and the surveillance of therapeutic effect. The episode for endoscopic intervention gave an introduction of its application in pulmonary TB, tracheal/bronchial TB, mediastinal lymph node TB and pleural TB. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has drawn great attentions of scholars both at home and abroad. Being characterized by simple procedure, minimally invasive, accurate positioning with high sensitivity, specificity and repeatability, EBUS-TBNA has become more and more important in the diagnosis of mediastinal and hilar lymph node TB.

The dynamic change of Th17 cells and regulatory T cells in PBMC during the anti-tuberculosis treatment of the patients with pulmonary tuberculosis

ZHANG Ying，LU Jian，HOU Zhi-ping，ZHANG Ming-xia，CHEN Xin-chun，ZHANG Xing-shu，QIU Zhen-gang

Chinese Journal of Antituberculosis. 2013, 35(6):  427-432. 

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Objective To study the relationship between the numbers of Th17 cells, CD4⁺CD25⁺CD127^low Tregs and the tuberculosis (TB) and outcome of anti-TB.  Methods Intracellular staining and flow cytometry  analysis were used to evaluate IL-17 cytokine secreted by Th17 cells and the responses of CD4⁺CD25⁺CD127^low Treg cells in peripheral blood samples collected from 25 individuals with LTBI, 45 healthy donors (HD), 32 patients with active pulmonary TB. The results were showed as x±s，all data were analyzed by software Prism 4.0. Two groups were compared by t-test，the comparison between groups used ANOVA. There is statistical significance if P<0.05. Results The percentage of IL-17 in TB group ［（3.25±1.68）%］was significantly lower than that in HD group ［（4.62±1.46）%］（F=6.633，P<0.0001）before treatment. The dynamic variation of IL-17 percentage was monitored at different time points: before treatment［（3.25±1.68）%］, at 3 months［（4.17±2.27）%］, and at  6 months after treatment［（5.58±1.66）%］. The percentage of Th17 cells from TB group at 3 months after treatment was higher than that before treatment, but there was no significant difference（F=12.244，P=0.057）. The percentage of Th17 cells at 6 months after treatment was significantly higher than those before treatment（F=12.244，P<0.0001） and at 3 months after treatment（F=12.244，P=0.004）. The percentage of CD4⁺CD25⁺CD127^low treg cells in LTBI group ［（5.00±1.08）%］ was higher than that in HD group ［（4.97±1.60）%］, but there was no significant difference （F=11.986，P=0.937）. The percentage of CD4+CD25+CD127low treg cells in TB group ［（6.59±1.73）%］ was significantly higher than that in HD group and LTBI group (F=11.986，P<0.0001). The Treg cells at 3 months after treatment were significantly higher than that before treatment（F=6.458，P=0.001）. But the Treg cells at 6 months after treatment were lower than that at 3 months after treatment（F=6.458，P=0.085）. There was no significant difference between before treatment and at 6 months after treatment（F=6.458，P=0.068）. The Treg cells at 6 months after treatment were significantly higher than HD group（t=6.255，P<0.0001）.  Conclusion The Th17 cells in TB group were low, gradually increased after effective anti-TB treatment, which suggested that Th17 cells play a protective role in the anti-TB immunity. The CD4⁺CD25⁺CD127^low treg cells in TB group were higher, and gradually reduced after effective anti-TB treatment, which suggested that CD4⁺CD25⁺CD127^low treg cells play a supressive role in the anti-TB immunity.

The anti-mycobacterial efficacy of sulfamethoxazole combined with trimethoprim and the interaction with other anti-tuberculosis drugs in vitro

YU Xia, ZHAO Li-ping, JIANG Guang-lu, MA Yi-feng, HUANG Hai-rong

Chinese Journal of Antituberculosis. 2013, 35(6):  433-438. 

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Objective  To evaluate the anti-mycobacterial efficacy of sulfamethoxazole（SMX）and trimethoprim（TMP） on Mycobacterium tuberculosis and analyze the interaction between SMX and other anti-TB drugs in vitro.  Methods The minimum inhibition concentrations (MICs) of TMP/SMX in 121 Mycobacterium tuberculosis (Mtb) strains were tested by microplate alamar blue assay(MABA). Eighteen clinical isolates were chosen by the stratified cluster sample method, and determined the interactions between SMX and rifampicin, isoniazid, streptomycin, ethambutol, kanamycin, ofloxacin, rifabutin in vitro by fractional inhibitory concentration index (FICI) method. Meanwhile, Mtb H37Rv strain was used as reference. The data were analyzed using SPSS software-version 13.0, nonparametric rank sum text was adopted for comparing the MIC of 3 groups, statistically significant difference was P<0.05.  Results  90.08% (109/121) isolates of Mtb could be inhibited by 1/19 μg/ml TMP/SMX. The MIC of TMP/SMX(1∶19) in 5 isolates was 2/38 μg/ml, 7 strains including 5 drug-sensitive strains and 2 MDR strains with MIC≥2/38 μg/ml. The MICs of TMP/SMX(1∶19) had no statistical significance among drug-sensitive strains, MDR strains and other drug-resistant strains (χ²=0.111，P=0.946). Drug combination testing did not display synergy between SMX and 7 other anti-TB drugs on H37Rv strain, except for with rifabutin（FICI 0.281）. Among 18 clinical isolates, 14（14/18，77.78%） exhibited synergy between SMX and rifabutin, in which FICI ranged from 0.205 to 1.063.  Conclusion TMP/SMX showed great anti-mycobacterical efficacy on Mtb clinical isolates in vitro, regardless of drug-resistant patterns. There were no synergy between SMX and 7 other anti-TB drugs in vitro, except for rifabutin.

Research on synchronously screening the rifampin-dependent M. tuberculosis during Mycobacterium culture

LI Tong-xin,CHEN Tian-gang,LIAO Chuan-yu,WANG Jing,LI Huan,NIE Xiao-ping,YI Xue-jun,ZHOU Gang, ZHONG Min

Chinese Journal of Antituberculosis. 2013, 35(6):  439-442. 

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Objective  To study practical value of synchronously screening the rifampin-dependent (R-dependent) M. tuberculosis (Mtb) strains during routine Mycobacterium culture, to early diagnose R-dependent infection in a clinical setting.  Methods Based on the typical growth conditions for R-dependent strains from clinical specimens in Lowenstein-Jensen medium (L-J) which contained rifampicin at concentration of 100μg/ml (L-J R100), a primary screening model was established. In routine BD960 fast liquid culture process, clinical specimens were also simultaneously inoculated in L-J culture medium without and with rifampin (L-J R100). A R-resistant Mtb is defined as culture-positive bacterium which grew better in L-J R100 than that in L-J (R-dependent), and an absolute R-dependent Mtb is defined as positive culture only in L-J R100 but negative culture in L-J. A total of 5362 specimens were examined during the period of March 7, 2011 to February, 15, 2012 in Chongqing Public Health Medical Center, and results were analyzed with LIS software system (Ruimei, Shanghai, China). Results Of 5362 cases, the total positive rate of the combined three methods of BD960, L-J and L-J R100 was 43.92% (2355/5362), the positive rates of BD960 and L-J culture were 39.56% (2121/5362) and 25.57% (1371/5362) respectively. 234 specimens were L-J positive and BD960 negative. Of 2355 culture-positive specimens, 703 (29.85%,703/2355) were L-J R100 positive, in which 258 isolates from 221 cases were R-dependent and 14 isolates were absolute R-dependent. The R-dependent phenomenon was also observed repeatedly twice in 33 isolates, 3 times in 1 isolate and 4 times in 3 isolates.  Conclusion The synchronously screening the rifampin-dependent Mtb strains during routine Mycobacterium culture is a simple method for early diagnosing the TB patients infected by the rifampin-dependent or rifampin-resistant strains of M. tuberculosis. It also improves the positive rate of Mycobacterium culture.

Investigation and intervention of treatment compliance of MDR-TB cases

LI Yi-fen，LI Pei-zhu，DENG Hong，HE Qing-qiu，LIN Yin，GAO Cui-nan

Chinese Journal of Antituberculosis. 2013, 35(6):  443-446. 

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Objective To understand the influencing factors of treatment compliance of multi-drug resistant tuberculosis (MDR-TB) patients, and to explore new measures in order to improve TB patients’ treatment compliance. Methods  Seventy-eight MDR-TB cases were interviewed by the self-designed questionnaire, 78 questionnaires were distributed and 78 valid questionnaires were received. The study subjects were divided randomly into experimental group and control group with 39 patients in each group. The average ages were（34.6±14.5） years for experimental group and （35.3±14.7） years for control group. The routine supervision measure was adopted in control group, while the hierarchical supervision based on routine supervision was taken in experimental group. Results There were 28 MDR-TB cases taking anti-TB drugs according to the doctor’s advice completely in experimental group, higher than that of the control group (19 cases). Four cases in experimental group did not fulfill the doctor’s instructions, which was less than that of the control group (11 cases). The treatment compliance of experimental group was higher than control group (Z=－2.234, P<0.05). Conclusion Different nursing intervention measures should be developed according to the patient’s social condition and adverse reactions, so that to improve the treatment compliance of MDR-TB patients and increase the cure rate eventually.

Current status of human resource in county level TB institutions of China, 2010

LIU Xiao-qiu, JIANG Shi-wen, WANG Li-xia, QU Yan

Chinese Journal of Antituberculosis. 2013, 35(6):  447-450. 

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Objective  To identify the current status of human resources in county level TB institutions of China, and provide the reference for county level human resources development. Methods Data were sourced from the 2001—2010 national TB program final evaluation database, the human resource situation of 2709 TB institutions nationwide were analyzed. In terms of staffing level, the proportion of TB institutions reaching the standards set by ‘the national tuberculosis prevention and control norms’ were analyzed and evaluated. Results There were a total of 24 646 full-time TB control personnel at county level nationally in 2010. Majority of them had college qualifications (including post-secondary and secondary), accounting for 73.7% (18 172/24 646). 59.5% (14 659/24 646) personnel had junior titles or below. In terms of the average number of TB personnel in TB institutions, the independent TB dispensaries had the highest of 22.1（6708/303）, much higher than the least of 4.7（2456/519） in non-independent TB institution subordinate to CDC. As for the proportion of personnel with senior title, the highest was 13.9% （444/3203）of designated hospitals, lowest was 4.8%（467/9834）of TB institutions under CDC. The designated hospitals also had the highest proportion of staff with above bachelor degree, 40.1% （1285/3203） versus the lowest of 13.5% （903/6708）in independent TB dispensaries. In eastern part of China, 33.3%（272/817）TB institutions reached the criteria of staffing level set by the ‘norms’, significantly higher than that in middle part (27.4%, 224/818) and western part (11.8%, 127/1074) （χ²=133.49，P<0.0001）.  Conclusion The human resources in county level is insufficient, we should address this problem in conjunction with the local health resources.

Investigation of the current situation of patients with sputum smear positive pulmonary tuberculosis under implementation of home quarantine in Xiaolan Town

LU Hui-lin, LIU Ben-jian, LEI Zhi-ming, LIU Wen-fu

Chinese Journal of Antituberculosis. 2013, 35(6):  451-455. 

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Objective To explore the implementation of home quarantine for patients with sputum smear positive pulmonary tuberculosis (PTB) in Xiaolan Town, so as to provide scientific evidence for TB control and prevention. Methods Cross-sectional investigation was applied. Patients aged 15 years and above diagnosed as sputum smear positive PTB in Xiaolan Town registered from 2011 to 2012 were investigated. Among the 195 cases who met the requirement, there were 59 cases with local Hukou and 136 cases with non-local Hukou. There were 130 male cases and 65 female cases. The average age was 39.47±16.88 years. One hundred and forty-one cases were 45 years old or below. Seventy-two cases had primary school or lower education experience, 86 cases graduated at junior high school and 37 cases had diploma of senior high school or above. Every patient was guided by a TB control doctor on the core information of TB control and prevention, and home quarantine implementation. A questionnaire survey was conducted face-to-face after a month. The questionnaire was designed according to Guidelines on Implementation of Chinese Tuberculosis Control Program, which covered the awareness of core information on TB and home quarantine implementation. One hundred and ninety-five questionnaires were delivered, and 195 valid questionnaires were collected，the effective rate was 100.00%. The data were input by Excel software package and analyzed by SPSS 13.0 software package. χ² test were adopted in the statistical analysis, P<0.05 was set as the criteria of statistical significance.  Results The awareness rate of core information was 42.56%（83/195）, 50.35% (71/141) for those 45 years and below and 22.22% (12/54) for those above 45 years. The difference between two different age groups was statistical significant（χ²=12.641，P<0.001）. The awareness rate for those had primary school and below education level was 16.67%（12/72）, 45.35%（39/86）for junior high school level and 86.49%（32/37）for senior high school and above. There was a statistical significance among different educational level groups（χ²=49.223，P<0.001）. 83.08%（162/195）patients didn’t wear mask in public place, 97.22%（70/72）for the group with primary school or below education level, 83.72%（72/86）for junior high school level, and 54.05%（20/37）for senior high school and above. There was a statistical significance among different educational level groups（χ²=32.440，P<0.001）. 87.69%（171/195） patients didn’t disinfect their daily necessities, the rates of different education level were 95.83%（69/72）, 90.70%（78/86）and 64.86%（24/37）respectively. The difference was statistical significant among different educational level groups（χ²=23.005，P<0.001）. Conclusion The awareness rate of core information of tuberculosis and the implementation rate of home quarantine were relative to the age and the level of education. The older the patients are, and the lower education level the patients have, the less core information of tuberculosis the patients know, which result in poor implementation of home quarantine. These groups should be the most important targets in the future.

Effect analysis of application of the clinical nursing pathway on health education in patients with multidrug-resistant pulmonary tuberculosis（MDR-TB）

SU Li-fang, LI Jin-sheng, CHEN En-tai

Chinese Journal of Antituberculosis. 2013, 35(6):  456-459. 

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Objective To explore the effect of application of the clinical nursing pathway on health education in patients with MDR-TB.  Methods One hundred and five patients with MDR-TB were assigned to clinical pathway group(55 cases) and control group(50 cases). The clinical pathway group included 35 male and 20 female, the average age was（51±13.8）years old. The control group included 31 male and 19 female,the average age was（52±11.9）years old. Patients in clinical pathway group received health education with clinical nursing pathway and those in control group received health education with conventional care program. Change of life behavior, nursing satisfaction and compliance of taking anti-tuberculosis drugs were compared between the clinical pathway group and the control group. Data were analyzed with chi-square test. P-value＜0.05 was considered to be statistically significant. Results In terms of the score of treatment compliance, in the clinical pathway group, 50 cases got 4 scores, 5 cases got 3 scores, no case got 2 scores, no case got 1 score. In contrast, in the control group, 25 cases got 4 scores, 10 cases got 3 scores, 5 cases got 2 scores, 10 cases got 1 score. In terms of the cognitive behavior change, in the clinical pathway group, 40 cases had general understanding, 12 cases had partial understanding and 3 cases could not understand. In the control group, 19 cases had general understanding, 18 cases had partial understanding and 13 cases could not understand. In terms of the nursing satisfaction, in the clinical pathway group, 47 cases were satisfied with the health education, 5 cases felt partly satisfaction, 3 cases felt basic satisfaction and no case felt unsatisfactory. In the control group, 30 cases were satisfied with the health education, 8 cases felt partly satisfaction, 7 cases felt basic satisfaction and 5 cases felt unsatisfactory. Three above assessment indicators between the clinical pathway group and the control were significantly different. The chi-square value were 26.52，8.56 and 6.95 respectively. The indicator in the clinical pathway group was higher than those in the control(all P<0.01）. Conclusion Management of clinical pathway can improves treatment compliance,nursing care satisfaction and cognitive behavior change in patients with MDR-TB.

Risk assessment and control for clinical trial of new tuberculosis intradermal diagnostic reagents

XU Miao, PU Jiang, YANG Lei, LU Jin-biao, TAO Li-feng, ZHONG Zai-xin, CHEN Bao-wen, DU Wei-xin, WANG Guo-zhi

Chinese Journal of Antituberculosis. 2013, 35(6):  460-462. 

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In order to reduce the risk of clinical trial for new tuberculosis intradermal diagnostic reagents in China, we made the risk assessment and provided the corresponding prevention and control measures for their clinical trial under the normal usage of qualified products. During the risk assessment, we took the Chinese laws and regulations on clinical trials as the guideline and referring to the evaluation of reported adverse events of OT and TB/BCG PPD close to such products in function and applicable people.

Research progress of phenotype detection of Mycobacterium tuberculosis drug susceptibility

SHEN Xiao-na, ZHAO Yan-lin, XIAO He-ping

Chinese Journal of Antituberculosis. 2013, 35(6):  463-467. 

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The epidemic situation of global drug-resistant tuberculosis is still severe, particularly in China. The phenotype detection of Mycobacterium tuberculosis drug susceptibility still plays an important role in the diagnosis of drug-resistant tuberculosis. This paper discussed the research progress of various phenotypic drug susceptibility testing methods at home and abroad in recent years, summarized the sensitivities, specificities of various methods and their advantages and disadvantages, which will provide a basis for selecting drug susceptibility test methods in clinical laboratories according to the different demand.

Research of anti-tuberculosis drugs’  hepatotoxicity

JIA Zhong，WU Jing，MA Jian-jun，LIANG Yun，LIU Yuan，WANG Xing-gang

Chinese Journal of Antituberculosis. 2013, 35(6):  468-471. 

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Hepatotoxicity is one of the side effects of rifampin, isoniazid, pyrazinamide and ethambutol hydrochloride, and it was particularly more serious in antituberculosis drugs combination. This review summarized the pathogenic mechanism and risk factors of hepatotoxicity caused by anti-tuberculosis drugs, and emphasized the importance of clinical monitor of hepatotoxicity. The occurrence of hepatotoxicity is related to the factors such as age, gender, nutrition status, alcohol, slow acetylation genotype and hepatitis B carriers. The administration and monitor of anti-tuberculosis therapy should be strengthened, so that the hepatotoxicity induced by drugs can be controlled.