Table of Content

10 March 2013, Volume 35 Issue 3

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Analysis of the clinical characteristics of hypothyroidism caused by anti-MDR-TB regimen containing prothionamide(Pto) and p-aminosalicylic acid granule(PAS)

ZHOU Mei-lan, ZHANG He-wu, WANG Wei-hua, CHEN Zi, CHEN Cong,WANG Jian-jie, PAN Hong, WANG Feng-hua, LIANG Jun, JIAO Xin-guang

Chinese Journal of Antituberculosis. 2013, 35(3):  157-161. 

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Objective To investigate the incidence and the clinical characteristics induced by chemotherapy regimen containing prothionamide (Pto) and p-aminosalicylic acid granule (PAS) in anti-multi drug-resistant tuberculosis (MDR-TB)treatment and to develop preventive measures and treatment methods for hypothyroidism induced by Pto and PAS. Methods We analyzed 106 cases with MDR-TB who received standard chemotherapy regimen containing Pto and PAS(6 PZA Km(Cm) Lfx (Mfx) Pto PAS/18 PZA Lfx(Mfx) Pto PAS) from the research project supported by the 5^th round of the global funds projects during August 1, 2008 and April 1,2010 in Wuhan city. Thirty two cases experienced hypothyroidism were monitored by thyroid functions during treatment.The treatment outcomes were analyzed in 106 cases. There were 32 cases with hypothyroidism treated with levothyrocine(L-T₄) in 19 cases and without levothyrocine in 13 cases and 74 cases without hypothyroidism.  Results There were 32 cases experienced hypothyroidism in 106 cases. Thirty one cases with hypothyroidism were recovered after treatment and 1 cases died due to respiratory failure.The cure rates for MDR-TB with and without hypothyroidism were 68.8%（22/32）and 68.9%（51/74）respectively. The difference was insignificant statistically（χ²=0.19，P=0.66）. The cure rates for MDR-TB with hypothyroidism treated with L-T₄ and without L-T₄ were 68.4%（13/19）and 76.9%（10/13） respectively.The difference was insignificant statistically (χ²=0.28, P=0.60).  Conclusion The incidence of hypothyroidism tends to increase in MDR-TB patients treated with chemotherapy regimen containing Pto and PAS. Hypothyroidism can be controlled by taking the drug of L-T₄.The thyroid functions can be recovered after chemotherapy teatment.

Analysis of tuberculosis aggregation in schools of Shaanxi province

ZHANG Tian-hua

Chinese Journal of Antituberculosis. 2013, 35(3):  162-167. 

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Objective To investigate the reason and the appropriateness of emergency response measures on tuberculosis（TB）aggregation in school.  Methods Data of 10 TB aggregations in school of Shaanxi province since 2006 to 2012 were collected, which were from epidemic situation report, case diagnosis, individual basic information, close contactors screening, protection of infected students, healthy education, emergency response situation, the final report, the occurrence of subsequent cases, et al.  Results The shortest patient delay of the first visit case was 15 days in Chang’an College, and the longest was 64 days in the high school of Cheng country. The average patient delay was 26.7（267/10）days. The shortest diagnostic delay was 20 days in the high school of Cheng country, and the longest was 156 days in the junior high school of Xun’yi country. The average diagnostic delay was 31.2（312/10）days. After the diagnosis, the interval for close contacts screening lasted from 2 days to 403 days with an average of 121.1（1211/10） days. The lowest PPD positive rate of close contacts in these ten epidemics was 49.5%（229/463）in the junior high school of Tibet, and the highest was 100.0%（43/43）in Chang’an College, with an average of 59.2%（1128/1906）. The lowest PPD positive rate of general contacts was 9.5%（18/189） in the junior high school of Xun’yi country, and the highest was 56.4%（1055/1871）in Chang’an College, with an average of 34.2%（3861/11 282）. The difference between the average PPD positive rates of close contact and general contact was statistical significant（χ²=431.9，P＜0.001）. The lowest attack rate of close contacts was 3.6%（25/698）in the high school of Cheng country, and the highest was 37.2%（16/43）in Chang’an College, with an average of 8.9%（174/1963）.  Conclusion Lack of timely detection, isolation and treatment for the sources of infection and no timely and effective screening of exposed population are the main reasons of TB aggregation.

Atypical CT manifestations of pulmonary tuberculosis

SONG Min, LIU Wen, FANG Wei-jun, FENG Hui-yong, LI Hui-ru, ZHANG Hui

Chinese Journal of Antituberculosis. 2013, 35(3):  168-172. 

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Objective To investigate and analyze the features of atypical CT image of pulmonary tuberculosis. Methods  A retrospective analysis of 73 cases of tuberculosis with atypical CT image of our hospital from January 2010 to September 2012 was done to classify all cases into various types due to their image characteristics.  Results According to the image characteristics, all cases were divided into 6 types including: type of multiple cavitates, 7 cases, showed multiple pulmonary cavitates without tuberculosis disseminated lesions; type of interstitial lesions, 20 cases, showed intrapulmonary large fine mesh weave-like higher density shadows with clear boundary, consolidation in it and multiple thickening interlobular septa perpendicular to the pleural were also seen; type of snowflake, 16 patients(4 with interstitial change), showed that multiple acinar nodules distributed around the small bronchi and its branches, and formed feeding bronchus sign, multiple “tree-in-bud” and lobular consolidation in it; type of mass, 29 cases, showed that the edge was found smooth, lobulation, long burr, pleural indentation signs, no short glitches sign, intermediate density was seen in all masses on CT plain scan, 3 cases with rim enhancement, 7 with homogeneous enhancement; type of hilar and mediastinal lymphoid tuberculosis with pseudoaneurysm, 1 cases, showed pseudoaneurysm in rim enhancement lymph node; type of consolidation, 4 cases, showed multiple segment, lobe consolidation with normal endobronchial sign.  Conclusion Type of interstitial lesions, snowflake, hilar and mediastinal lymphoid tuberculosis with pseudoaneurysm of these 6 types of atypical CT image of pulmonary tuberculosis have a certain degree of specificity to be diagnosed, but clinical and laboratory tests are still needed to be combined with in all types.

Quantitative proteomic analyses of isoniazid- and streptomycin-resistant and sensitive clinical isolates and H37Rv of Mycobacterium tuberculosis

HE Xiu-yun，ZHU Chuan-zhi, PANG Yu, HUANG Xiang-yu, JIANG Li-qi, ZHAO Yan-lin, ZHUANG Yu-hui

Chinese Journal of Antituberculosis. 2013, 35(3):  173-178. 

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Objective To identify the proteins differentially expressed in isoniazid- and streptomycin-resistant Mycobacterium tuberculosis clinical isolate (INH/S^r isolate) compared with drug-sensitive clinical isolate (INH/S^s isolate) and H37Rv. Methods Whole cellular proteins were extracted from the INH/S^r isolate 02166, the INH/S^s isolate 01105 and H37Rv of M. tuberculosis, respectively. The proteins were digested with trypsin. The peptides were labeled, separated and identified by isobaric tags for relative and absolute quantitation (iTRAQ) combined with Nano LC-MS-MS technology. The bioinformatics were used to identify and quantify the proteins. Results One hundred and fifty three and 130 proteins were found differential expression in 02166 strain compared with 01105 strain and H37Rv, respectively, including 86 proteins in 02166 strain compared with both 01105 strain and H37Rv. The theoretical molecular weight and isoelectric point of differentially expressed proteins ranged from 7.63 to 326.22 and from 3.74 to 12.48, respectively. Differentially expressed proteins were mainly associated with intermediary metabolism, respiration, and lipid metabolism. Nine ribosomal proteins (Rv0056, Rv0651, Rv0652, Rv0701, Rv0719, Rv1630, Rv2785c, Rv2909c and Rv3458c) were commonly down-regulated in 02166 strain compared with both 01105 and H37Rv. Succinate-semialdehyde dehydrogenase (Rv0234c) and putative uncharacterized protein (Rv2466c) were common up-regulation (the ratios>1.2), and probable DNA-binding protein HU homolog hupB （Rv2986c） and putative uncharacterized protein (Rv2626c and Rv3118) were down-regulation (the ratios <0.5) in 02166 strain compared with both 01105 strain and H37Rv. Conclusion Differentially expressed proteins were identified in INH/S^r isolate compared with INH/S^s isolate and H37Rv using iTRAQ. Further study will focus on the above proteins playing role in INH or S resistance.

The relationship between N-acetyltransferase 2 genotypes and the concentration of isoniazid in human plasma

LIU Cheng-cheng, JIN Hai-xia, XU Jian, LI Hua, ZHU Hui, FU Lei, WANG Bin, LU Yu

Chinese Journal of Antituberculosis. 2013, 35(3):  179-182. 

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Objective To study the correlation between N-acetyltransferase 2 (NAT2) genotypes and the concentration of isoniazid (INH) in the plasma, and provide a theoretical basis for the individualized medication of tuberculosis (TB) patients by NAT2 genotyping. Methods The NAT2 genotypes of 121 TB patients were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). INH concentration in the plasma was detected by the liquid chromatography-tandem mass spectrometry (LC/MS-MS) at 2 hours after treatment. The differences between the groups were tested by using single factor analysis of variance, and then the differences of every two groups were tested by using Tamhane’s T2, P＜0.05 was considered statistically significant.  Results Of 121 TB patients, 55 were NAT2 rapid acetylation (RA) type，and their average concentration of INH in plasma was（1.86±1.28）μg/ml; 17 were slow acetylation (SA) type (homozygous mutant), their INH concentration was（5.86±2.10）μg/ml; 49 were intermediate acetylation (IA) type (heterozygous mutant), and the INH concentration was（3.49±2.60）μg/ml. INH concentration of hospitalized TB patients in plasma was（3.08±2.42）μg/ml. INH concentration among the three groups have statistically significant differences (RA with IA, P＝0.001；RA with SA，P＝0.002; IA with SA，P＝0.000，P＜0.05).  Conclusion There were significant differences among the TB patients with different NAT2 genotypes. NAT2 genotyping has important guiding significance for the INH treatment in the TB patients.

The comparison of different wall-breaking method for extracting total RNA of Mycobacterium tuberculosis

LUO Ying-shu, GAO Wen-feng, HUANG Ruo-ying, LIU Heng-chuan

Chinese Journal of Antituberculosis. 2013, 35(3):  183-186. 

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Objective  To establish a simple and effective total RNA extraction method of Mycobacterium tuberculosis.  Methods  Cell wall of Mycobacterium tuberculosis were treated by ultrasonic and glass-bead associated with Trizol method respectively, the total RNA was extracted and the influence of different total RNA extraction methods of Mtb were evaluated through fluorescent quantitative RT-PCR. The negative control is ultrapure water instead of template. Each method were extracted from 3 samples for testing. The final result is the average of 3 specimen.  Results  The Ct and △Rn value of glass-bead group is 20.67 and 0.644, 400 W ultrasonic group is 22.09 and 0.571, 240 W ultrasonic group is 21.86 and 0.503, 160 W ultrasonic group is 25.21 and 0.411, bead absent group is 28.40 and 0.299, negative control is 40.00 and 0.000. Conclusion  The wall-breaking effection of glass-bead method is better than that of ultrasonic method.

Cost comparison analysis of line probe assay and conventional drug susceptibility testing for diagnosis of drug resistance of Mycobacteria tuberculosis

LI Qiang, XIA Hui, OU Xi-chao, ZHAO Bing, PANG Yu, ZHAO Yan-lin

Chinese Journal of Antituberculosis. 2013, 35(3):  187-190. 

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Objective  To compare the costs of line probe assay (LPA) and conventional drug susceptibility testing (DST) for detecting the drug resistance of Mycobacteria tuberculosis  in prefectural TB hospitals.  Methods  The full costs related to LPA and conventional DST including management, building, equipment, reagent, consumables and staff were collected from the Fourth People’s Hospital of Inner Mongolia, the Fourth People’s Hospital of Lianyungang City, Kaifeng Lung Hospital and the Second People’s Hospital of Yongchuan District. The average costs of LPA and DST were analyzed by t test, and the level of significance was set to P<0.05.  Results  The average costs for testing one case by LPA and DST were 201.0 Yuan and 365.8 Yuan respectively. The difference was significant (t=32.28, P<0.01). The unit costs for identifying one MDR-TB case by LPA and DST were 2794.4 Yuan and 4689.7 Yuan respectively. Compared to conventional DST, 1895.3 Yuan could be saved by LPA for detecting one MDR-TB case, and the testing cost was significantly reduced.  Conclusion  The cost of LPA for detecting drug resistant TB patient was lower than that of DST. It can be applied in prefectural TB laboratory.

Arrival situation and influencing factors of pulmonary tuberculosis patients reported in Guangdong province in internet-based reporting system

LI Jian-wei, JIANG Li, LIAN Yong’e, ZHOU Lin, ZHONG Qiu

Chinese Journal of Antituberculosis. 2013, 35(3):  191-196. 

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Objective To analyze the arrival situation and influencing factors of pulmonary tuberculosis （PTB） cases/suspects reported in internetbased system by general hospital in Guangdong province. Methods Referring and tracing TB patients have been implemented by using the information of internetbased reporting system. The arrival rate of 106669 local PTB cases/suspects, reported by local general hospital in 2011, were analyzed with logistic regression analysis method. Results There were 89825 PTB patients/suspects arrived at TB dispensary for seeking medical advice in 2011 in Gunagdong province. The overall arrival rate was 84.2% (89825/106669) and 42.5% （38179/89825） of arrivals were the cases by tracing. Referral（OR＝7.993；95%CI：7.611-8.395）, ID number recorded （OR＝1.049；95%CI：1.006-1.094）, telephone number recorded（OR＝1.534；95%CI：1.467-1.603）, organization name recorded（OR＝1.222；95%CI：1.165-1.282）and detailed address recorded（OR＝1.360；95%CI：1.297-1.425） were the factors helping patients seek medical advice in TB dispensary. The overall arrival rate in Western Guangdong was the lowest （OR＝0.903；95%CI：0.847-0.963）. The overall arrival rate of township hospital/community service center was higher than that of county level and above（OR＝1.562；95%CI：1.465-1.666）. The overall arrival rate of suspects was lower than those of laboratory diagnosed cases（OR＝10.006；95%CI：9.219-10.861） and clinic diagnosed cases（OR＝2.458；95%CI：2.349-2.571）. The overall arrival rates of 15- age group（OR＝0.338；95%CI：0.285-0.400）, 35- age group（OR＝0.282；95%CI：0.238-0.334） and 55- age group（OR＝0.243；95%CI：0.205-0.288）were lower than that in <15 age group. Conclusion It has large development space in the work of referring and tracing in Guangdong province. Integrated management approaches need to be taken to consolidate and improve the overall arrival rate. Pressing the general hospital for referring PTB cases/suspects, filling in complete and accurate reporting information and improving the diagnostic capabilities of the general hospital are the keys to increase arrival.

Analysis on referral and tracing of pulmonary tuberculosis patients reported by non-TB control institutions in Heihe city in 2009 to 2011

LI Gang, ZHAO Chun-li, SUN Chang-jiang, LI Bai-xiang

Chinese Journal of Antituberculosis. 2013, 35(3):  197-200. 

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Objective  To understand the status of referral and follow-up of pulmonary tuberculosis (PTB) patients reported in internet-based surveillance system by non-TB control institutions in Heihe city in 2009 to 2011 in order to improve case detection.  Methods  The referral, tracing and checking report forms of PTB patients reported by non-TB control institutions in Tuberculosis Management Information System of Heihe in 2009 to 2011 was used. The referral arrival rate, tracing arrival rate, total arrival rate, detection rate and the contribution rate on TB case detection by non-TB institutions of 4991 cases that needed referral were analyzed.  Results  For the patients reported in internet-based surveillance system by non-TB control institutions in 2009 to 2011, the referral arrival rates was 45.4% (870/1918), 47.8% (762/1594) and 61.1% (904/1479) respectively, with a rising trend year by year(χ²_trend=78.711, P=0.000). The tracing arrival rate was 91.7% (961/1048), 94.2% (784/832) and 86.6% (498/575). The total arrival rate was 95.6% (1834/1918), 97.1% (1547/1594) and 94.8% (1402/1479) respectively. Among arrival patients, the detection rate of active PTB was 43.0% (2057/4783) and that of smear positive PTB was 23.9% (1144/4783). The contribution rate on active PTB case detection by non-TB institutions was 50.1% (2057/4107) and that of smear positive PTB was 46.8% (1144/2446).  Conclusion  The referral arrival rate was increasing year by year in Heihe city from 2009 to 2011, and the tracing arrival rate and the total arrival rate maintained at a high level.

Comparative study of intervention treatment plus drugs and drug treatment for new smear positive bronchial tuberculosis patients

CHEN Zhen-hua, XI Zhao, WANG Yu-mei, LUO Dan-lin

Chinese Journal of Antituberculosis. 2013, 35(3):  201-203. 

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Objective  To explore the treatment effect of new smear positive endobronchial tuberculosis cases by fiberoptic bronchoscopic interventional therapy combined with oral anti-TB drugs.  Methods  80 new smear positive endobronchial tuberculosis cases admitted to the Department of Respiratory Medicine from February 2010 to August 2011 was divided randomly (queue law) into two groups, the intervention group received fiberoptic bronchoscopic interventional therapy and oral anti-TB drugs, while the control group received oral anti-TB drugs. There were 40 cases in each group, with 11 male and 29 female in intervention group and 17 male and 23 female in control group. The average age of the intervention group was (35.6±8.5), while that of the control group was (35.2±6.8). The sex (χ²=1.978, P=0.241) and age (t=0.218,  P=0.828) of the two groups were comparable with each other. Related treatment prescriptions were informed before signed informed consent provided. Excel software was used for data entry. SPSS 13.0 was used for analysis. P<0.05 was defined as the criteria for statistically significant difference.   Results  After treatment, 37 cases acquired remarkable effect or normal effect in the intervention group, and the total effective rate was 92.5% (37/40). While in the control group, 28 cases acquired remarkable effect or normal effect with 70.0% (28/40) total effective rate.   Conclusion  The effect of fiberoptic bronchoscopic interventional therapy combined with oral anti-TB drug therapy was better than that of oral anti-TB drugs.

The relationship between the adaptor molecule caspase recruitment domain-containing protein 9 and anti-tuberculosis immunity

SUN Lei, ZHENG Jin-hui，WANG Cui, FEI Si-ping，ZHAO Zhuo

Chinese Journal of Antituberculosis. 2013, 35(3):  204-206. 

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Tuberculosis(TB) is a chronic infectious disease, globally 1.7 million people die from TB annually.The number of TB patients in China ranks the second in the world. China is one of the countries  with high prevalence of multi-drug resistance TB (MDR-TB). The number of TB deaths exceeds the sum of the number of deaths caused by other infectious diseases. Therefore, the development of effective anti-TB drugs and new vaccines is imminent. This requires the in-depth understanding of the interaction mechanism between the host and Mtb, and the internal signaling mechanisms and the key molecules of antigen presenting cell(APC). When the pathogen-associated molecular patterns(PAMPs) of Mtb is recognized by pattern recognition receptors (PRRs), the signal is transmitted to the adaptor molecule which starts the downstream signaling cascade reaction, induces innate immune cells to synthesize cytokines, and activates the host immune mechanisms. This review briefly elaborated the correlation between caspase recruitment domain-containing protein 9 (CARD9) and anti-TB immunity, and provided a reference for the TB treatment and the development of vaccine.