Table of Content

10 February 2014, Volume 36 Issue 2

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The effect of patient delay and diagnosis delay on drug-resistance in new smear positive tuberculosis

WANG Ni，ZHOU Lin，BAI Li-qiong, XU Wei-guo, HE Jin-ge, XU Xiao-yu, CHENG Shi-ming

Chinese Journal of Antituberculosis. 2014, 36(2):  81-85.  doi:10.3969/j.issn-1000.6621.2014.02.001

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Objective To understand the effect of patient delay and diagnosis delay of new smear positive tuberculosis (TB) cases and drug-resistance, and to provide scientific evidence for the development of drug-resistant TB control and prevention strategies.  Methods The typical survey method was adopted and 3 counties were selected from 3 provinces located in the eastern, middle and western areas in China. Three hundred and twenty-nine new smear positive TB patients registered during May 2010 to September 2010 were investigated with the questionnaire of the process of diagnosis and treatment of new smear positive patients designed by the research group, and 329 questionnaires were received with 100.0% effective rate. Sputum culture examination was applied for the sputum samples from 329 patients, drug susceptibility test of INH, RFP, EMB and S was used for those with positive sputum culture samples. Non-parametric test was used to compare the delay between drug-resistant patients and non-drug resistant patients. 0.05 was set as the criteria of statistical significance. Results The positive rate of sputum culture was 88.8%(292/329),the total drug-resistance rate was 12.7%(37/292), and the multidrug-resistance (MDR) rate was 2.8%(8/292). Total delay, patient delay and diagnosis delay for drug-resistant patients were 37 d (8-465 d), 15 d (0-462 d) and 12 d (0-218 d) respectively, and 38 d (1-597 d), 16 d (0-594 d) and 10 d (0-429 d) for non-resistant patients.There was no significant difference between drug-resistance and non-drug resistance on 3 kinds of delay (Z=0.377, 0.142, 0.069, P<0.05). Conclusion There is no inevitable relationship between delay and drug-resistance.

Analysis of TB screening results among applicants for immigration to the United States in Beijing

XIAO Li-li, WU Si-yuan, HE Ping-ping, WANG Jin, CAO Shan-shan

Chinese Journal of Antituberculosis. 2014, 36(2):  86-92.  doi:10.3969/j.issn.1000-6621.2014.02.001

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Objective To investigate the situation of tuberculosis (TB) morbidity and infection among applicants for living abroad in Beijing, and to fill this knowledge gap which will be used for establishing an effective monitoring and management system at the ports, thereby preventing TB transmission across national boundaries. Methods A retrospective analysis was conducted. The data used for analysis were from 15 598 immigration applicants to the United States (US) who received TB screening at Beijing International Travel Health Care Center from July 2008 to June 2013. Tuberculin skin testing (TST) or interferon gamma release assays (IGRAs) was performed on 2488 children aged 2-<15 years; chest X-ray (CXR) was taken on 13 110 applicants aged 15 years and older, sputum smear and culture were performed on 401 applicants with a CXR result suggesting pulmonary TB (PTB) or suspected PTB, strain identification of Mycobacterium tuberculosis (Mtb) and drug susceptibility testing (DST) were done using the strains isolated by culture. Results Accordance to the updated guidelines for using IGRAs to detect Mtb infection issued by US CDC in 2010 and the Chinese diagnostic criteria for PTB, the following results were obtained: (1) Active PTB: among 401 applicants with abnormal CXRs who were identified from 13 110 applicants aged 15 years and older, 15 PTB cases were detected (114.42 per 100 000), including 11 bacteriologically confirmed cases and 4 bacteriologically-negative cases (83.91 and 30.51 per 100 000, respectively). (2) Inactive TB: 386 inactive TB were found among applicants aged 15 years and older, the rate was 2944.32 per 100 000. (3) Latent TB infection (LTBI) in children: among 2488 children aged 2-<15 years, 444 children were diagnosed as LTBI with normal CXRs, including 423 were TST≥10 mm and 21 were IGRAs positive. The rate of LTBI among children was 17 845.66 per 100 000. (4) There were 2 close contacts of TB patients among the applicants aged 15 years and older. (5) Bacteriological examinations: 3 sputum specimens were collected from each of 401 applicants with abnormal CXRs and aged 15 years and older, smear and culture were performed, of which were detected: 4 cases were smear-positive and culture-positive (S+C+), 7 cases were smear-negative but culture-positive (S-C+) and 390 cases were smear-negative and culture-negative (S-C-). All of the 11 culture-positive cases were identified as Mtb, 9 of them were confirmed by DST as susceptible TB while other 2 were drug-resistant TB (1 was multidrug-resistant TB and 1 was poly drug-resistant TB). (6) The active TB prevalence reached a peak for the age group 60 years and older (371.52 per 100 000), followed by the age group 15-<30 years (145.88 per 100 000).  Conclusion People with abnormal CXRs and aged 15 years and older should be considered as the target populations of TB control in the immigration health check-up, and those with TST≥10 mm or IGRAs positive and aged 2-<15 years should not be neglected either.

Analysis on epidemic and relevant factors for drug-resistant tuberculosis in Xiamen city

KE Ran，ZHENG Rong-rong，ZHANG Xiang-dong, YANG Yi-ming，LIN Xiang-lian，HUANG Cheng-ji，HUANG Qiao-jun

Chinese Journal of Antituberculosis. 2014, 36(2):  93-97.  doi:10.3969/j.issn.1000-6621.2014.02.003

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Objective To understand the epidemic status of drug-resistant tuberculosis (TB) in Xiamen city in the recent years, to identify the risk factors for drug-resistance and to provide scientific evidences for developing effective local policies and measures on TB control. Methods A cross-sectional study was carried out. All smear-positive TB patients notified in the designated TB hospitals of Xiamen from July 1st, 2011 to Jun 30th, 2012 were enrolled in this study. The basic information, relevant medical information and sputum specimens were collected on every enrolled patient. Culture was performed on all subjects; drug susceptibility testing (DST) of 4 first-line anti-TB drugs (INH, RFP, Sm, EMB) was performed using proportion method; Mycobacterium tuberculosis (Mtb) identification was done using p-nitrobenzoic acid (PNB) cultivation. Unconditional logistic regression model was used with SPSS 18.0 to identify the potential risk factors for drug-resistance. Results The total number of the subjects was 776 cases. The overall drug-resistant TB (DR-TB) rate in Xiamen was 27.2%（198/729）and the overall multidrug-resistant TB (MDR-TB) rate was 9.7% (71/729). The drug-resistance rates for initial treatment TB patients and retreatment TB patients were 23.4% (134/573) and 41.0% (64/156) respectively. The multidrug-resistance rate for initial treatment TB patients was 7.3% (42/573) and it was 18.6% (29/156) for retreatment TB patients. Of 4 first-line anti-TB drugs tested in this study, the INH-resistance rate was 16.5% (120/729), ranking the first; the lowest drug-resistance rate was EMB (6.9%, 50/729). The drug-resistance rate among retreatment TB patients was significantly higher than that among initial treatment TB patients (χ²=19.286, P<0.01). Previous treatment was identified as the major risk factor of drug resistance (OR=2.154, 95%CI=1.467-3.163, Waldχ²=15.319, P<0.001). Conclusion The situation of drug-resistant TB in Xiamen is not optimistic and a history of previous TB treatment is associated with drug-resistance.

Factors affecting the economic burden of patients with pulmonary tuberculosis in Zhangjiagang county

JIANG Wei, QIU Sang-sang, LU Hui, WANG Qun-gang, HUANG Li-fang, QIN Rong, FENG Yan, LV Jie-qiong, WANG Jian-ming

Chinese Journal of Antituberculosis. 2014, 36(2):  98-103.  doi:10.3969/j.issn.1000-6621.2014.02.004

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Objective To explore the economic burden of patients with pulmonary tuberculosis and risk factors, in order to provide evidences for development of tuberculosis control strategies and improving patients’ treatment adherence and treatment success rate. Methods We chose Zhangjiagang, a relatively rich county in Jiangsu province, as the study area. Twenty-three villages were selected as the study sites based on a cluster sampling me-thod. Three hundred and forty patients who were diagnosed as pulmonary tuberculosis during January 2010 and March 2013 and had already completed the standard anti-tuberculosis treatment before March 31, 2013 were invited for the investigation. We used a self-designed questionnaire to collect data on patient’s healthcare seeking experience and costs of illness. Patient’s economic burden due to the disease was analyzed and the influencing factors were explored. Eventually 274 patients accepted the investigation with the response rate of 80.6% and the questionnaire efficiency rate of 100.0%. The economic burden included two parts: direct costs and indirect costs. Direct costs included medical costs related to tuberculosis diagnosis and treatment (clinical and hospitalization expenses), transportation costs, accommodation costs and food costs. Indirect costs were calculated as loss of income due to inability to work following tuberculosis diagnosis and treatment. Considering the distribution of data, we used the mean toge-ther with the median (P25,P75) to describe the costs. We used the rank sum test (Mann-Whitney U) to compare the costs between groups. Results The average annual income of patients was 19 159.9 yuan and the median income was 15 000 yuan. The average total cost was 18 793.3 yuan and the median (P25,P75) cost was 9965 (3200-24 400) yuan. Per capita direct cost was 11 936.9 (median: 4590) yuan. After excluding costs covered by health insurance, the per capita out-of-pocket cost was 7448.0 yuan, with the median of 3315 yuan. The per capita indirect cost was 6856.4 (median: 1575) yuan. Factors associated with the economic burden included hospitalization (the average (median) out-of-pocket cost was 8512.9 (3800) yuan for patients without hospitalization history, and 24 381.4 (15 500) yuan for patients with hospitalization history, respectively. Z=－8.119, P<0.001); taking li-ver protective drugs (the average (median) out-of-pocket cost was 9911.8 (5900) yuan for patients not taking liver protective drugs, and 17 075.9 (8150) yuan for patients taking liver protective drugs, respectively. Z=－2.645, P=0.008); using the second-line anti-tuberculosis drugs (the average (median) out-of-pocket cost was 13 294.5 (6785) yuan for patients not taking second line drugs, and 18 065.3 (10 325) yuan for patients taking second line drugs, respectively. Z=－2.327, P=0.020); and diagnosis delay (the average (median) out-of-pocket cost was 12 656.5 (6110) yuan for patients with the diagnosis delay less than 14 days, and 17 457.7 (11 065) yuan for patients with the diagnosis delay over 14 days, Z=－2.970, P=0.003) etc.  Conclusion The economic burden of patients with tuberculosis in Zhangjiagang was relatively high. The costs were related to hospitalization, taking liver protective drugs and the second-line anti-tuberculosis drugs, and diagnosis delay, etc.

Clinical analysis of lamivudine combined with anti-tuberculosis drugs in treating pulmonary tuberculosis complicated with hepatitis B virus carriers

DENG Guo-fang, SUN Li-zhen, LEI Jian-ping, WU Yu-qing, YE Hong

Chinese Journal of Antituberculosis. 2014, 36(2):  104-108.  doi:10.3969/j.issn.1000-6621.2014.02.005

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Objective To explore the effect of lamivudine therapy on pulmonary tuberculosis patients with hepatitis B virus carriers based on anti-TB treatment, including the incidence of liver injury, the treatment time and long-term effects.  Methods One hundred and forty-two new pulmonary tuberculosis patients with chronic hepatitis B virus carriers who had normal liver function were randomly divided into lamivudine group (73 patients, 4 cases were lost to follow-up) and control group (69 patients, 6 cases were lost to follow-up). By the end of 18-month treatment, lamivudine would be stopped, but anti-tuberculosis drugs were not stopped until the treatment ended. All the patients of both groups were followed up for 24 months, liver injury rate within 4 weeks,the total liver injury rate, HBV-DNA negative rate, mortality, TB cure rate, failure rate were analyzed by Chi-square test or Fisher’s exact probability method. Results Patients treated with lamivudine significantly reduced liver injury. Liver injury rate within 4 weeks, the total liver injury rate and mortality of the lamivudine group were lower than the control group. There were significant differences between lamivudine group （4.3%（3/69）,20.3%（14/69）,0.0%（0/69）; P=0.007, 0.0001, 0.023, χ²=7.064，15.176) and control group （19.0% (12/63)，49.2% (31/63)，7.9% (5/63)）. At the end of TB treatment and the end of follow-up period, the HBV-DNA negative rate of lamivudine group （24.6%（17/69），21.7%（15/69）） was higher than control group （3.2%（2/63），3.2%（2/63））, the dif-ference was statistically significant (χ²=12.311，P=0.0005；andχ²=10.115，P=0.001). TB cure rate of lamivudine group was higher than control group (89.9% vs 73.0%) and the failure rate lamivudine group were lower than the control group (4.3% vs 17.5%), There were significant differences between 2 groups.   Conclusion Using lamivudine within 18 months is relatively safe for reducing the incidence of hepatitis B, which has a long-term effect. Our findings can provide a clinic basis for prophylactic lamivudine therapy on pulmonary tuberculosis patients with HBV infection.

Analysis on clinical characteristics of 70 patients with bacteriologically-negative tracheobronchial tuberculosis

CHEN Hua, CHEN Pin-ru, SU Duo-hua, XIAO Peng

Chinese Journal of Antituberculosis. 2014, 36(2):  109-111.  doi:10.3969/j.issn.1000-6621.2014.02.006

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Objective To investigate the clinical characteristics of bacteriologically-negative tracheobronchial tuberculosis (TBTB). Methods A retrospective study was conducted to analyze the clinical features of 70 bacteriologically-negative tracheobronchial TB patients registered in Guangzhou Chest Hospital from July 2006 to June 2012, who had completed medical records and their diagnosis were pathologically confirmed. At the same time, 97 bacteriologically-positive tracheobronchial TB patients registered in the same hospital and in the same period were rando-mized enrolled as a control group. The following clinical characteristics were compared between 2 groups: clinical symptoms, imaging, signs and bronchoscopic features; Chi-square test was used for statistics analysis (P<0.05 was considered statistically significant). Results (1) In the bacteriologically-negative tracheobronchial TB group, the proportion of patients with dry rales detected by lung auscultation was 51.43% (36/70), which was higher than the rate in the bacteriologically-positive group (34.02%, 33/97). A significant difference was showed between 2 groups (χ²=5.082, P<0.05); The proportion of patients with moist rales was lower in the bacteriologically-negative group (15.71%, 11/70) than that in the bacteriologically-positive group (32.99%,32/97). It also showed a significant difference between 2 groups (χ²=6.347, P<0.05). (2) The main bronchoscopic features of the bacteriologically-negative tracheobronchial TB patients were inflammatory infiltration (type Ⅰ, 40.00%, 28/70) and scar stenosis (type Ⅳ, 52.86%, 37/70), which were significantly higher than the rates of type Ⅰ (23.71%, 23/97) and type Ⅳ (19.59%, 19/97) among bacteriologically-positive patients (χ²=45.817, P<0.01).   Conclusion Tracheobronchial TB with bacteriologically-negative is lack of specific clinical symptoms and imaging, its bronchoscopic features are mainly inflammatory infiltration (type Ⅰ) and scar stenosis (type Ⅳ). We should keep alert to tracheobronchial TB when the decreased breath sounds or dry rales are detected by auscultation.

A case-control study on the relationship between the HLA-DRB1 genetic polymorphisms and susceptibility to pulmonary tuberculosis

JI Chun-mei, WANG Yu-hua, AN Ya-chen, WANG Jing, LI Lin-xu, ZHANG Shu-wen

Chinese Journal of Antituberculosis. 2014, 36(2):  112-120.  doi:10.3969/j.issn.1000-6621.2014.02.007

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Objective To investigate the relationship between the HLA-DRB1 gene polymorphisms and susceptibility to pulmonary tuberculosis (PTB) in Han nationality of Tangshan city. Methods 1∶1 matched case-control study was adopted (in March to early June in 2010 in Tangshan TB hospitals), 124 new adult TB patients of Han nationality (age 18 and above) were enrolled consecutively as case group. Three hundred and sixty-one health people infected with Mycobacterium tuberculosis confirmed by the unified tuberculin test (PPD) in the physical examination, with the same nationality, same sex, similar age (age difference was less than 3 years), and same residence matching conditions, were selected at the same period. Each case had at least 2 people matched, in which 1 was randomly selected to match the case. One hundred and twenty-four people were randomly selected among 361 people as control group. Polymerase chain reaction-sequence-specific primers technique (PCR-SSP) and restriction fragment length polymorphism (RFLP) were used to type polymorphisms (DR15, DR16, DR1 and DR11). Information on environmental-related risk factors and pathological changes of TB was collected using a pre-tested standard questionnaire. Univariate and multivariate conditional logistic analysis were conducted using SPSS 12.0. Results DR11 wild type accounted for 85.5% (106/124) in case group and 87.1% (108/124) in control group, without statistical significance (P=0.712, OR=1.146, 95%CI＝0.555-2.366). Cases with DR16 wild type was 75.0% (93/124), and was 83.1% (103/124) in control group, there was no statistical significance (P=0.119, OR=1.635, 95%CI＝0.879-3.042)). Cases with DR15 wild type accounted for 85.3% (81/124), and 82.2% (102/124) in control group had this wild type, which was statistically lower than that in case group (P=0.002, OR=2.461, 95%CI＝1.363-4.444). According to the above results, DR15 gene mutation might be the susceptible genotype of PTB. If DR15 genetic mutation and DR16 genetic mutation occurred together, the risk of PTB increased (P=0.007, OR=4.904, 95%CI=1.554-15.476), which was significantly higher than any mutation, so that DR15 and DR16 has synergistic effects on PTB susceptibility. Univariate analysis was conducted for 17 environmental factors. In multivariate analysis, associations of TB and DR15 genotype still remained adjusting for scar of BCG, BMI, per capita living space and family history (Waldχ²=9.844,P=0.002, OR=2.996, 95%CI=1.510-5.945). Conclusion DR15 gene mutant might affect the susceptibility to TB in Han nationality in Tangshan city.

Comparison and analysis of TST and IGRAs for testing tuberculosis infection of health care workers

GENG Meng-jie, SONG Yu-dan, XIONG Yong-chao, ZHAO Fei, HU Dong-mei, LI Meng, HOU Yue-yun, CHENG Jun, HE Guang-xue

Chinese Journal of Antituberculosis. 2014, 36(2):  121-125.  doi:10.3969/j.issn.1000-6621.2014.02.008

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Objective To compare and analyze the agreement of tuberculosis (TB) infection results of health care workers with tuberculin skin test (TST) and interferon γ release assays (IGRAs). Methods Between April to August 2010, 1005 health care workers in an infectious disease hospital and a general medical hospital in Inner Mongolia were enrolled. Questionnaire was used to get the general demographic information, the history of BCG vaccination and so on. 1005 questionnaires were sent out, and 952 qualified questionnaires were taken back (the number of medical staff completed questionnaires, received TST and QFT - GIT test was 952, 924 and 999 respectively),923 subjects completes all of the three inquiries, excluding 6 with not-sure QFT-GIT results, there were 917 health care workers in the analysis. We applied TST and one of IGRAs namely QuantiFERON-TB Gold In-Tube (QFT-GIT) assay to test tuberculosis infection of health care workers, and assessed the agreement of the two tests with Kappa coefficients with the 5 mm, 10 mm and 15 mm as the positive cut-off of TST. Results Of the 917 health care wor-kers included in the analysis, the TST positive rates were 68.92% (632/917), 47.87% (439/917) and 25.08% (230/917) respectively with the different positive cut-off of 5 mm, 10 mm and 15 mm. With 5 mm as the positive cut-off, there were 483 medical staff got positive results and 130 got negative results of the two tests, and the agreement rate was 66.85% (613/917). With 10 mm as the positive cut-off, there were 350 medical staff got positive results and 190 got negative results of the two tests, and the agreement rate was 58.89% (540/917). With 15 mm as the positive cut-off, there were 181 medical staff got positive results and 230 got negative results of the two tests, and the agreement rate was 44.82% (411/917).The Kappa value (95%CI) between the tests were 0.22 (0.16-0.29), 0.19(0.13-0.25) and 0.08 (0.04-0.12) respectively, the agreement was poor. Conclusion The agreement between TST and QFT-GIT was low.

Progress in chemotherapy of MDR-TB during pregnancy

HAN Dan, DUAN Qiong-hong, CHEN Zi, ZHOU Mei-lan, LU Lan-ying, RUAN Han-li

Chinese Journal of Antituberculosis. 2014, 36(2):  126-130.  doi:10.3969/j.issn.1000-6621.2014.02.009

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Treatment of MDR-TB during pregnancy has long been regarded as a clinical difficulty, currently there is no uniform chemical regimen as a standard. In a hope to provide some relevant references for the treatment of multidrug-resistant tuberculosis (MDR-TB) during pregnancy, the author makes a systematic review regarding the progress in research of the epidemiology, anti-MDR-TB drugs and reported chemical regimens of MDR-TB during pregnancy in recent years.