Table of Content

10 September 2018, Volume 40 Issue 9

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Expert Forum

Present status and problems of diagnosis and treatment of tuberculosis in children

Lin SUN,A-dong SHEN

Chinese Journal of Antituberculosis. 2018, 40(9):  912-916.  doi:10.3969/j.issn.1000-6621.2018.09.002

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Tuberculosis (TB) remains a global public health problem. Despite substantial progress on the dia-gnosis and treatment of this disease duing to the global commitment to TB, it is still far from goals of ending TB and no death in childhood TB. This article reviewed TB epidemic data, problems and the trends of TB diagnosis and treatment of children in our contry and worldwide.

Original Articles

Clinical and bronchoscopic characteristics of tracheobronchial tuberculosis in children

Fang LIU,Chen SHEN,Lin SUN,Xiao-chun RAO,Yu-yan MA,Chen-fang MENG,Yue-na PAN,Gan LI,An-xia JIAO

Chinese Journal of Antituberculosis. 2018, 40(9):  917-923.  doi:10.3969/j.issn.1000-6621.2018.09.003

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Objective We analyzed the associated clinical factors and bronchoscopic characteristics of children with Tracheobronchial tuberculosis (TBTB) to provide clues for the early diagnosis of tracheobronchial tuberculosis.Methods We retrospectively analyzed 240 cases of tuberculosis patients who had gone through bronchoscopy and been hospitalized in Beijing Children’s Hospital, Capital Medical University between July 2006 and December 2014. In the end, 130 cases of TBTB (“TBTB group”) and 110 cases of non-TBTB tuberculosis (“non-TBTB group”) were confirmed according to the results of bronchoscopy. The general information, clinical symptoms, imaging features, and characteristics under bronchoscopy of the two groups were analyzed and compared. We used SPSS 22.0 statistical software for a Chi-square test and Spearman rank correlation test, with statistical significance of P<0.05. Results The median age of the TBTB group (1.6 years old (Quartile: 0.8 years old, 5.5 years old)) was significantly lower than the non-TBTB group (4.5 years old (Quartile: 1.1 years old, 10.1 years old)) (U=5309.500,P=0.001). The proportion of children younger than 2 years old in the TBTB group (75 cases, 57.7%) was significantly higher than in the non-TBTB group (38 cases, 34.5%) (χ²=12.813, P=0.000). The incidence of wheezing and tachypnea in the TBTB group (23.1%, 30/130) was significantly higher than non-TBTB group (5.5%, 6/110) (χ²=14.513, P=0.000). The positive rate of Mycobacterium tuberculosis culture in the TBTB group(21.5%, 28/130)was significantly higher than non-TBTB group(7.3%, 8/110) (χ²=9.510, P=0.002). Among the TBTB group, 22.3% (29/130) had airway obstruction on chest CT, which was significantly higher than non-TBTB group (4.5%, 5/110) (χ²=15.460, P=0.000). Results from the bronchoscopy showed that lymph node erosion (LNE) happened in 95.4% (124/130) of the TBTB group, and caseous pneumonia erosion (CPE) happened in 6.2% (8/130) of the TBTB group. At the first bronchoscopy, 77.7% (101/130) of the TBTB group was in the burst stage of LNE, and 17.7% (23/130) were in the early stage of LNE. The most common sites of TBTB were in the right main bronchus (33 cases), the middle right bronchus (32 cases) and the right upper lobe bronchus (30 cases). The median age of single bronchus involved (2.2 years old (Quartile: 1.0 years old, 6.1 years old)) was significantly higher than the median age of those with multi-bronchus involved (1.0 years old (Quartile: 0.5 years old, 1.8 years old)) in the TBTB group (U=1176.500,P=0.002).The number of bronchial involvement showed a negative correlation (Pearson correlation coefficien t=-0.222, P=0.001) with the ages of the children.Conclusion TBTB is highly suspected in children with pulmonary tuberculosis with wheezing and tachypnea, with chest images indicating obstructed ventilation. Bronchoscopy needs to be operated as early as possible to confirm the diagnosis.

Analysis of the results of two detection methods for screening latent tuberculosis infection in children with different risk levels

Xue QI,Ya-cui WANG,Ya-jie GUO,Qi MA,Yu-ying CHEN,Lin SUN,A-dong SHEN

Chinese Journal of Antituberculosis. 2018, 40(9):  924-931.  doi:10.3969/j.issn.1000-6621.2018.09.004

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Objective Evaluate the value of tuberculin skin test (TST) and interferon-gamma release assay test (IGRA) in screening latent tuberculosis infection (LTBI) among children with different risk levels.Methods Collection of information on 965 children with a history of contact with active tuberculosis (ATB) patients enrolled at Beijing Children’s Hospital from 2013 to 2015, excluding 451 children diagnosed by etiology or clinically as ATB and 31 children diagnosed as inactive tuberculosis based on medical history and imaging examination, 483 children were finally included for the study and analysis of LTBI screening by TST and IGRA. Close contact history, children aged <5 years and no BCG scar were defined as risk factors, and the risk level was classified according to the number of risk factors. Those without the above risk factors were grouped as Grade Ⅰ (218 cases), those with 1, 2 and 3 risk factors were grouped as Ⅱ (210 cases), Ⅲ (54 cases) and Ⅳ (1 case, incorporate Ⅲ), respectively. Chi-square test was used to analyze the positive rates of TST and IGRA, and the univariate analysis related to positive results was conducted, P<0.05 was considered to be statistically significant. Kappa test was used for consistency analysis of the two laboratory techniques.Results All of the 483 children were tested by IGRA, the positive rate was 2.48% (12/483). The positive rates of IGRA in the Ⅰ-Ⅲ group were 2.29% (5/218), 2.38% (5/210), and 3.64% (2/55), respectively, and the difference was not statistically significant (χ ²=0.459, P=0.795). TST was performed in 369 children, the positive rate was 11.38% (42/369), and the positive rates of TST in the Ⅰ-Ⅲ group were 9.36% (16/171), 12.74% (20/157) and 14.63% (6/41), the difference was not statistically significant (χ ²=1.412,P=0.494). The combined detection of the two methods (TST+IGRA) means that the positive rate of either method was 9.11% (44/483), and the positive rates of TST+IGRA in the Ⅰ-Ⅲ group were 7.34% (16/218), 9.52% (20/210), 14.55% (8/55), and the difference was not statistically significant (χ ²=2.832,P=0.243). The positive rates of the three screening methods were statistically significant in the risk grades Ⅰ and Ⅱ (χ ²=7.861,P=0.020;χ ²=13.318,P=0.001). The close contact history with tuberculosis patients had the most significant correlation with the positive results of TST and IGRA. The positive rate of TST (25.26%, 24/95) or IGRA (5.00%, 6/120) in children with close contact with ATB patients was higher than that in non-intimate patients (6.57% (18/274), 1.65% (6/363)), the difference was statistically significant (χ ²=21.131,P=0.000, OR (95%CI)=4.329(2.232-8.396); χ ²=4.291,P=0.038,OR (95%CI)=3.186(1.006-10.096)).The consistency of the two tests was poor and the Kappa value was 0.346.Conclusion Among children with history of exposure to tuberculosis, those at the higher risk levels have the higher risk to develop LTBI, which is a high risk factor for LTBI in children. Due to the poor consistency of the two tests, in order to avoid missed diagnosis, combination use of TST and IGRA for screening LTBI in high-risk children is recommended.

The evaluation of tuberculous meningitis scoring system in the diagnose of tuberculous meningitis in children

Tong-qiang ZHANG,Lin SUN,Wei GUO,Cai-li ZHOU,Li-xin REN,Zhuo FU,Shu-jing LI,A-dong SHEN,Yong-sheng XU

Chinese Journal of Antituberculosis. 2018, 40(9):  932-939.  doi:10.3969/j.issn.1000-6621.2018.09.005

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Objective The purpose of this study was to evaluate the value of tuberculous meningitis (TBM) scoring system in differentiating TBM from viral meningitis.Methods This was a retrospective analysis on 102 TBM children who admitted to the Department of Respiration, Children’s Hospital of Tianjin between January 1, 2010 and December 31, 2017 (defined as the TBM group) and 125 children with viral encephalitis in the same period (defined as the viral encephalitis control group). TBM was diagnosed using a comprehensive scoring system that included clinical manifestations, cerebrospinal fluid (CSF) test results, imaging findings, and other manifestations of pulmonary tuberculosis/extrapulmonary tuberculosis. The higher the score, the more TBM diagnosis was supported. TBM could be clinically diagnosed if the score was greater than or equal to 12. In this case-control study, the sensitivity and specificity of the scoring system in the diagnosis of TBM were analyzed. At the same time, the difference in test sensitivity among the scoring system and the tuberculin skin test (TST), the tests for release of interferon (IGRA) and the CSF etiology was compared.Results Among the children in the TBM group, 16 (15.69%, 16/102) of them were positive in the CSF etiology test and were confirmed as definite TBM by the scoring system. The score of the remaining 86 (84.31%, 86/102) patients with TBM was (13.25±2.22), which was higher than that of the children with viral encephalitis (3.79±2.48). The difference was statistically significant (t=29.97, P<0.001). Seventy-six of the 86 cases had a TBM score of ≥12, and thus were clinically diagnosed as TBM. The sensitivity of the TBM scoring system for the diagnosis of TBM was 90.20% (92/102) and the specificity was 100.00% (102/102). In the examination of CSF etiology, the sensitivity of anti-acid staining of Mycobacterium tuberculosis was 15.69% (16/102), the sensitivity of culture was 10.78% (11/102), and the sensitivity of DNA testing was 16.47% (14/85), which were significantly lower than that of TBM scoring system (χ ²=113.65, 128.66, 100.64, Ps<0.001). In the immunological examination, the sensitivity of TST test was 50.00% (51/102) and the specificity was 99.20% (124/125). IGRA had a sensitivity of 72.55% (74/102) and a specificity of 99.20% (124/125). The sensitivities were significantly lower than that of the TBM scoring system (χ ²=39.31, 10.48, Ps<0.001).Conclusion The TBM scoring system has a good diagnostic value for TBM, and its sensitivity is significantly higher than those of CSF acid stain, CSF culture, CSF DNA test, TST and IGRA detection methods.

Analysis of clinical characteristics of pediatric pulmonary tuberculosis based on CT classification

Yan WANG,Shun-ying ZHAO,Tong YU,Hong ZHANG,Zhi-min LIU,Ji-hang SUN,Jin-jin ZENG,Yun PENG

Chinese Journal of Antituberculosis. 2018, 40(9):  940-943.  doi:10.3969/j.issn.1000-6621.2018.09.006

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Objective To study the clinical features of CT characteristics of pediatric pulmonary tuberculosis.Methods The clinical and imaging data (including age, sex, clinical manifestations, vaccination history, contact history and laboratory examination) of 734 children with pulmonary tuberculosis diagnosed in Beijing Children Hospital affiliated to Capital Medical University from July 2006 to December 2014 were retrospectively analyzed. The CT characteristics and clinical features were analyzed based on CT typing.Results Among the 734 children, 159 (21.7%) were diagnosed by pathogeny or biopsy. Primary pulmonary tuberculosis and tracheobronchial tuberculosis were the most common (365 cases, 50.4%), followed by two or more kinds of CT typing (199 cases, 27.3%). For infants and young children less than 3 years old, primary pulmonary tuberculosis and tracheobronchial tuberculosis (189 cases, 26.1%) were the most common, while tuberculous pleurisy (94 cases, 13.0%) was common in adolescent children aged 7-14 years. Tuberculous meningitis (109 cases, 34.5%) and extrapulmonary dissemination involving two or more sites (103 cases, 32.6%) were common among the cases with extrapulmonary tuberculosis. 192 (26.2%) cases were complicated with other diseases.Conclusion Pediatric pulmonary tuberculosis cases with different ages have different CT typing and are often complicated with extrapulmonary dissemination. The CT manifestations of pediatric pulmonary tuberculosis have their own characteristics and age distribution characteristics.

Clinical characteristics of new pulmonary tuberculosis cases complicated with pulmonary other infection in tuberculosis clinic

Shou-yong TAN,Fang GONG,Guo-biao LIU,Yan-qiong LI

Chinese Journal of Antituberculosis. 2018, 40(9):  944-947.  doi:10.3969/j.issn.1000-6621.2018.09.007

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Objective To understand the present situation of the pulmonary tuberculosis cases with pulmonary other infection (PTB&PIN), and to explore the patients’ clinical characteristics for PTB&PIN in TB clinic.Methods A retrospective analysis was carried out on 506 new bacteriological positive PTB patients with the complete clinical data from January 2015 to June 2016 in a TB prevention and treatment center in Yuexiu district of Guangzhou. The patients were divided into the infection group (n=200) and the control group (n=306), according to whether they had complicated pulmonary infection or not at the time of visit. SPSS 19.0 software was used for statistical analysis, the counting data were analyzed by Chi-square test, which was statistical significance with P<0.05.Results (1) Of the 506 patients with PTB, 200 cases (39.53%) were complicated with PIN. There were 24.50% (49/200) patients aged over 60 years in the infection group, which was significantly higher than that in the control group (16.01%, 49/306) (χ ²=6.583, P=0.037). (2) In the infection group, there were 83.00% (166/200) patients with cough or expectoration symptoms, which was same as 76.47% (234/306)(χ ²=3.510, P=0.319) in the control group. (3) And there were 49.00% (98/200) patients with the lung involvement over 3 lesions in the infection group, which was significantly higher than that in the control group (31.70%,97/306)(χ ²=6.965, P=0.008).(4) In the infected group, there were 42.50% (85/200) patients with cavities in the focus, which were significantly higher than that in the control group (26.80%, 82/306)(χ ²=13.487, P=0.000).Conclusion Among the new bacteriological positive PTB patients who combined with other pulmonary infections in the tuberculosis specialist outpatient clinic, the proportion of the elderly patients is higher. The pulmonary lesions are more extensive and often accompanied with cavity formation.

Short-time efficacy of regimen containing rifabutin in patients with slowly growing mycobacterium lung disease

Wen-wen SUN,Hai LOU,Qin SUN

Chinese Journal of Antituberculosis. 2018, 40(9):  948-953.  doi:10.3969/j.issn.1000-6621.2018.09.008

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Objective To observe the short-time efficacy and safety of regimen containing rifabutin (Rfb) in patients with slowly growing mycobacterium (SGM) lung disease.Methods One hundred and twenty-four inpatients with SGM lung disease treated with standard regimen and regular management who hospitalized in shanghai pulmonary hospital from January 2013 to December 2014 were enrolled in this retrospective study. Fifty-six patients were treated with Rfb regimen as observation group and 68 patients were treated without Rfb regimen as control group. The treatment outcome and drug adverse reaction rates were compared between the two groups.Results (1) The sputum negative conversion rate in the end of 12 months in the observation group was (78.57%,44/56) significantly higher than that in the control group (69.12%,47/68) (χ ²=3.098, P=0.008). There were no statistic significance of the sputum negative conversion rates in the end of 3 months and 6 months between the two groups (all P value >0.05). (2) The focal absorption rate (75.00%,42/56)in the observation group was significantly higher than that (60.29%,41/68) in the control group (χ ²=4.523, P=0.009). There was no statistic significance of the lung cavity closure rate between the two groups (χ ²=1.952, P=0.094). Compared with the control group on the focus absoption rate (60.29%, 41/68), the observation group (73.21%, 41/56) had a better efficacy (χ ²=3.412, P=0.012).Conclusion Regimen containing Rfb shows a better short-time efficacy in the treatment of patients with SGM lung disease. However, the drug adverse reaction rates in observation group are higher than those in control group.

Diagnostic value of T-SPOT.TB method in detection of pulmonary tuberculosis in patients receiving immuno-suppression

Yi-gang TAN,Yan-hong LI,Min-li ZHENG

Chinese Journal of Antituberculosis. 2018, 40(9):  954-958.  doi:10.3969/j.issn.1000-6621.2018.09.009

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Objective To explore the diagnostic value of T-SPOT.TB test in detection of pulmonary tuberculosis (PTB) among the patients receiving immuno-suppressive agents.Methods A total of 197 patients, who stayed at the inpatients department of Guangzhou Chest Hospital for receiving immunosuppressive agents treatment from Jul. 2013 to Dec. 2015 and were also diagnosed to be complicated with PTB, were enrolled in this study as the “Observation group”, while 200 PTB cases who stayed at the inpatients department of the same hospital at the same period were enrolled as the “Control group”. All enrolled patients were acid-fast bacillus (AFB) smear microscopy or culture positive with the specimens of their sputum or bronchoalveolar lavage fluid (BALF); in order to exclude NTB, the identification of Mycobacterium tuberculosis (MTB) was performed to culture positive isolates; the images of their chest X-rays were also consistent with the features of active PTB. The diagnosis of PTB for all enrolled patients was consistent with the standards of the Guideline for Pulmonary Tuberculosis Diagnosis and Treatment. The following test results (positive rate) between the two groups were compared: T-SPOT.TB test, AFB fluorescence stain microscopy of Auramine O, BACTEC MGIT 960 liquid culture (MGIT 960) and purified protein derivate (PPD) skin test. SPSS 19.0 software was used for calculation of χ ² test and P<0.05 was regarded as statistical significance. Results The positive rate of T-SPOT.TB was 85.28% (168/197) in the Observation group and 96.00% (192/200) in the Control group respectively; which was significantly higher than that of AFB fluorescence stain microscopy of Auramine O (36.55% (72/197) in the Observation group and 35.50% (71/200) in the Control group; χ ² was 98.24 in the Observation group and 162.53 in the Control group respectively (Ps=0.000)). The positive rates of T-SPOT.TB in the two groups were significantly higher than those of MGIT 960 culture (53.81% (106/197) in the Observation group and 57.50% (115/200) in the Control group; χ ² was 46.06 in the Observation group and 83.06 in the Control group respectively (P=0.000 in both groups). The positive rates of T-SPOT.TB test in both groups were significantly higher than those of PPD skin test (34.52% (68/197) in the Observation group and 63.50% (127/200) in the Control group; χ ² was 105.66 in the Observation group and 65.40 in the Control group respectively (P=0.000 in both groups)). The positive rates of T-SPOT.TB and PPD skin test in the Observation group were significantly lower than those in the Control group (the former χ ² was 13.50 (P=0.000) and the later χ ² was 33.36 (P=0.000)).Conclusion The positive rate of T-SPOT.TB test in those patients receiving immunosuppressive agents and are complicated with PTB is high. The T-SPOT.TB test, as an auxiliary diagnostic method of PTB, is more valuable than those traditional methods.

Results analysis on detection of drug resistance gene of Mycobacterium tuberculosis by using fluorescence PCR melting curve method

Yan LIU,Mulati Gulibike·,Abulitifu Maliyamu·,Xing YI,Jun-lian LI,Yong-huan SHI,Tian-jian LIU

Chinese Journal of Antituberculosis. 2018, 40(9):  959-963.  doi:10.3969/j.issn.1000-6621.2018.09.010

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Objective To evaluate the value of fluorescence PCR melting curve analysis in Mycobacterium tuberculosis (MTB) identification and drug-resistant TB detection.Methods The sputum specimens from 976 suspected TB patients were collected during September 2015 to December 2016 in Chest Hospital of Xinjiang Uyghur Autonomous Region. MTB and its drug resistance to rifampicin and isoniazid were detected by fluorescence PCR melting curve analysis. The results of MGIT 960 liquid culture method and liquid drug resistance test were stipulated as criterion to evaluate the sensitivity, specificity, agreement rate and Kappa value of melting curve analysis in MTB identification and drug-resistant TB detection.Results The sensitivity, specificity, Kappa value and diagnostic coincidence rate of the melting curve analysis for MTB DNA identification were 85.44% (135/158), 94.01% (769/818), 0.75 and 92.62% (904/976), respectively, taking the result of MGIT 960 liquid culture as gold standard. Taking MGIT 960 liquid drug resistance test as gold standard, the sensitivity, specificity, Kappa value and diagnostic coincidence rate of the melting curve analysis for isoniazid-resistant mutation detection were 83.33% (20/24), 94.59% (105/111), 0.76 and 92.59% (125/135), respectively. Meanwhile, the sensitivity, specificity, Kappa value and diagnostic coincidence rate of the melting curve analysis for rifampin-resistant mutation detection were 95.83% (23/24), 95.50% (106/111), 0.86 and 95.56% (129/135), respectively.Conclusion The probe based melting curve analysis can detect rifampicin-resistant and isoniazid-resistant mutation rapidly and accurately, which can be used for the rapid detection of the multi-drug resistant mutations of MTB.

Analysis of distribution and drug resistance of pulmonary TB patients with concurrent extrapulmonary TB

Su-ting CHEN,Yu-hong FU,Li-ping ZHAO,Yi XUE,Hai-rong HUANG

Chinese Journal of Antituberculosis. 2018, 40(9):  964-968.  doi:10.3969/j.issn.1000-6621.2018.09.011

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Objective To explore the distribution and drug resistance of pulmonary TB patients combined with extra-pulmonary TB.Methods A total of 347 PTB patients (male: 199, female: 148) with concurrent EPTB were recruited from Beijing Chest Hospital Capital Medical University between Jan 2013 and Dec 2015, of which the clinical data such as age, gender and co-infection sites were retrospectively reviewed, and drug resistance patterns were analyzed.Results The median age of the cases was 33 (24-52) years, and most patients were of 20-39 years old (41.8% (145/347)). Of the patients with concurrent EPTB, the types of TB disease included bone joint tuberculosis (n=112, 32.3%), lymph node tuberculosis (n=96, 27.7%), tuberculous meningitis (n=82, 23.6%) and tuberculous peritonitis (n=23, 6.6%), tuberculous pericarditis (n=9, 2.6%), intestinal tuberculosis (n=8, 2.3%), urinary tuberculosis (n=5, 1.4%), polyserositis tuberculousis (n=5, 1.4%), renal tuberculosis (n=2, 0.6%), splenic tuberculosis (n=1, 0.3%), pelvic tuberculosis (n=1, 0.3%), liver tuberculosis (n=1, 0.3%), epididymal tuberculosis (n=1, 0.3%) and nasal tuberculosis (n=1, 0.3%), respectively. The median ages of each group were 47 (26-60) years, 26 (20-42) years, 34 (25-50) years, 26 (20-46) years and 47 (31-66) years, respectively; there was significant difference among these groups (χ ²=36.25, P=0.000). The drug resistance patterns were analyzed in a total of 70 patients who had positive bacterial cultures. And 31 isolates were defined drug resistant, including 8 single-drug resistant, 2 poly-drug resistant and 21 multidrug resistant (MDR) isolates according to the drug susceptibility test outcomes. The overall resistant ratio was 44.3% (31/70), while the ratios of single drug resistance, poly-drug resistance and multi-drug resistance were 11.4% (8/70), 2.9% (2/70) and 30.0% (21/70), respectively.Conclusion Concurrent EPTB in PTB patients involves a wide range of types, of which the most common types are bone joint, lymph node and nervous system. The overall drug resistance ratio of PTB patients with concurrent EPTB is high.

Comparative analysis of the adjustment success ratio of plasma drug concentration of three anti-tubercular drugs

Jun ZHOU,Xiao-hui LYU,Xiu-qi ZHENG,Chao-gang XIONG,Yuan ZHAO,Li-yun DANG

Chinese Journal of Antituberculosis. 2018, 40(9):  969-972.  doi:10.3969/j.issn.1000-6621.2018.09.012

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Objective Based on therapeutic drug monitoring (TDM), the adjustment results of plasma drug concentration of the anti-tubercular drugs isoniazid (INH), rifampicin (RFP) and pyrazinamide (PZA) were analyzed.Methods Using the information management system of Xi’an Chest Hospital to collect and analyze blood drug concentration monitoring data of 132 cases that had applied plasma drug concentration monitoring for two or more times and adjusted the oral dosages to meet the need of clinical treatment from November 2016 to November 2017. Among them, there were 50 and 19 INH-treated cases, 47 and 9 RFP-treated cases, and 35 and 11 PZA-treated cases who performed TDM for two or more times and dose adjustment, respectively. The drug dose adjustment of each treatment group was analyzed.Results The plasma concentration adjustment rates of the INH, RFP, and PZA groups were 38.0% (19/50), 19.1% (9/47), and 31.4% (11/35), respectively. The dose adjustment success rate of plasma drug concentration in the INH group was only 31.6% (6/19), and that of the RFP and PZA groups were 7/9 and 81.8% (9/11), respectively. The result of precise probability test indicated that there was a significant difference in the adjustment success rate of plasma drug concentrations among the three drug groups. The adjustment success rate of INH plasma drug concentration was significantly lower than that of RFP and PZA (Fisher’s exact probability method, P=0.013).Conclusion The blood concentrations of the three first-line anti-tubercular drugs were all not nicely within the clinical therapeutic range after once dose adjustment, and the plasma concentration of INH was even less controllable than that of RFP and PZA. This analysis suggests that the drug regimens adjustment based on TDM for one time can not be perfectly implemented, and for specific individuals and drugs it is also necessary to practise further TDM monitoring and dosage adjustment.

Molecular epidemiologic characteristics of Mycobacterium tuberculosis complex at Guangdong port

Pei-feng WU,Ying WEN,Jia CHEN,Ying-long GAO,Jing BAI,Xiang-yang WANG,Jian WU

Chinese Journal of Antituberculosis. 2018, 40(9):  973-978.  doi:10.3969/j.issn.1000-6621.2018.09.013

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Objective To study the molecular epidemiologic characteristics of the main epidemic strains and the imported strains of M.tuberculosis complex (MTBC) at Guangdong port.Methods Five hundred and fifty-eight MTBC strains preserved at Guangdong port were genotyped by melting curve spoligotyping (McSpoligotyping). The spoligotype patterns were compared with SITVITWEB database to obtain spoligotype international type (SIT) number and clustered by BioNumerics 7.6 version.Results Five hundred and fifty-eight MTBC strains were divided into 107 spoligotype patterns, among which 66 patterns belonged to 8 families and 4 lineages. Lineage 2 and lineage 4 were accounted for 86.38% (482/558) of the total strains. SIT1, SIT53, SIT52, SIT50, SIT190 and SIT19 were the six main epidemic clusters, among which SIT1 was the biggest one. The 17 imported MTBC contained Beijing, Latin American and Mediterranean (LAM), East African Indian (EAI), T, Africanum (AFRI) as well as undefined gene family, including 23.53% (4/17) new genotypes. No significant difference was observed between Beijing family strains (27.25%, 106/389) and non-Beijing family strains (23.81%, 40/168) in drug resistance (χ ²=0.72, P=0.40). Nevertheless, the drug resistant rate of atypical Beijing family strains (45.83%, 11/24) was higher than that of typical Beijing family strains (26.03%, 95/365), and the differences were significant (χ ²=4.46, P=0.03).Conclusion Lineage 2 and lineage 4 of MTBC are the main epidemic strains at Guangdong port. The imported strains are dominated by gene families prevalent in the source areas and new genotypes. It’s necessary to strengthen the molecular epidemiologic surveillance of the main epidemic strains and the imported strains. There is a correlation between atypical Beijing family strains and drug resistance.

Analysis of tuberculosis patients detection situation in extremely severe or severe disaster areas of Mianyang city during ten years after Wenchuan earthquake

Hong-ying SUN,Jin-chao DUAN,Zhao ZHANG,Lei LUO,Qi-wen HE,Chang-wu YAN,Xiao-rong YANG

Chinese Journal of Antituberculosis. 2018, 40(9):  979-982.  doi:10.3969/j.issn.1000-6621.2018.09.014

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Objective To analyze the case-detection trend of tuberculosis (TB) patients in the extremely severe or severe disaster areas in Mianyang City, Sichuan Province in the past 10 years since the 2008 Sichuan Earthquake.Methods The related data and information of the TB patients, who were registered in the TB facilities in 9 counties or districts of Mianyang city (including 5 severe disaster areas: Fucheng, Youxian, Santai, Zitong and Yanting; and 4 extremely severe disaster areas: Pingwu, Beichuan, An County and Jiangyou) from 2008 to 2017, were collected and analyzed retrospectively. The following indicators were analyzed and compared by extremely severe disaster areas and severe disaster areas: the reported incidence of pulmonary TB, the source of active TB patients, and the long-term changing trend.Results In 2008, the reported incidence of pulmonary TB was 83.10/10000 (1380/1660700) and 86.47/10000 (3122/3610500) respectively in the extremely severe disaster areas and severe disaster areas. The difference of the incidence between the two areas was not statistically significant (χ ²=1.52, P=0.223). After earthquake, in the extremely severe disaster areas, the reported incidence of pulmonary TB was 91.24/10000 (1516/1661500), 86.33/10000 (1439/1666900), 95.30/10000 (1466/1538300), 89.36/10000 (1341/1500700), 86.20/10000 (1295/1502300), 84.22/10000 (1271/1509100), 85.01/10000 (1288/1515100) and 77.57/10000 (1202/1549500) respectively from 2009 to 2016; which were all significantly higher than those in the severe disaster areas: 83.79/10000 (3050/3639900), 76.30/10000 (2780/3643400), 84.48/10000 (2724/3224500), 74.99/10000 (2494/3225800), 80.50/10000 (2514/3122900), 76.14/10000 (2419/3177000), 75.20/10000 (2369/3150100) and 72.00/10000 (2320/3222400); χ ² was 7.36, 14.15, 13.87, 26.88, 4.00, 8.49, 12.56 and 4.41 respectively, and P values were all<0.05. In 2017, the reported incidence of pulmonary TB in the extremely severe disaster areas was 77.45/10000 (1210/1562200), which was close to that in the severe disaster areas (72.68/10000, 2361/3248700), and χ ²=3.25, P=0.073.Conclusion The incidence of TB in Mianyang city is high, and earthquake has a long-term impact on case-detection of TB. The role of the three-level network (county, township and village levels) on TB prevention and control should be restored and strengthened as soon as possible; the active and effective TB screening and prevention work should be carried out.

Analysis of the tuberculosis detection among students in Xidian University in Xi’an from 2006 to 2017

Min-ling LU,Ya-li DENG,Xiao-xia LI,Xian-zhen HU,Wu-lu LIU

Chinese Journal of Antituberculosis. 2018, 40(9):  983-988.  doi:10.3969/j.issn.1000-6621.2018.09.015

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Objective To analyze the tuberculosis (TB) detection among students in Xidian University from 2006 to 2017, and to evaluate the effect of prevention and treatment.Methods The data on pulmonary TB patients registered in the school from 2006 to 2017 were collected. Descriptive epidemiological methods were used to analyze the incidence, detection methods and detection rates during the 12 years.Results Seeking health care with symptoms was the most common way of TB detection, accounting for 52.29% (137/262), followed by medical examinations for new students with 29.77% (78/262). The TB incidence from 2006 to 2017 respectively were 86.44/100000 (22/25452), 97.94/100000 (28/28590), 42.38/100000 (12/28316), 34.75/100000 (10/28776), 48.38/100000 (14/28935), 33.87/100000 (10/29527), 63.71/100000 (19/29821), 60.43/100000 (18/29787), 43.23/100000 (13/30070), 30.21/100000 (10/33102), 43.12/100000 (13/30146), and 49.27/100000 (15/30442), and the difference in TB incidence during the 12 years was statistically significant (χ ²=26.60, P=0.005), showing a decreasing trend ($\chi^{2}_{trend}$=7.15, P=0.008). The detection rates of medical examinations for new students from 2006 to 2017 respectively were 76.37/100000 (6/7857), 89.40/100000 (7/7830), 104.14/100000 (8/7682), 135.17/100000 (11/8138), 124.08//100000 (10/8059), 48.89/100000 (4/8182), 131.59/100000 (11/8359), 133.06/100000 (11/8267), 48.13/100000 (4/8310), 48.95/100000 (4/8171), 0.00/100000 (0/8452), and 23.13/100000 (2/8647). There was a statistically significant difference in the TB detection rate of medical examinations for new students (χ ²=24.83, P=0.010), and the incidence was decreasing ($\chi^{2}_{trend}$=8.29, P=0.004). The TB detection rates by seeking health care with symptoms from 2006 to 2017 respectively were 185.51/100000 (19/10242), 173.84/100000 (20/11505), 51.81/100000 (6/11580), 69.91/100000 (8/11443), 111.65/100000 (13/11644), 68.13/100000 (8/11742), 110.73/100000 (14/12643), 102.94/100000 (13/12629), 72.75/100000 (11/15120), 85.46/100000 (9/10531), 78.91/100000 (9/11406), and 57.82/100000 (7/12106). There was a statistically significant difference in the TB detection rate by seeking health care with symptoms (χ ²=23.73, P=0.014), which showed a decreasing trend ($\chi^{2}_{trend}$=7.86, P=0.005). The detection rates by screening for close contacts with TB from 2006 to 2017 respectively were 0.00/100000 (0/854), 690.85/100000 (4/579), 235.29/100000 (5/2125), 86.06/100000 (1/1162), 0.00/100000 (0/515), 66.53/100000 (1/1503), 591.72/100000 (5/845), 217.27/100000 (4/1841), 53.08/100000 (1/1884), 108.34/100000 (1/923), 286.53/100000 (3/1047), and 852.62/100000 (7/821). The detection rate by screening for close contacts with TB was statistically different (χ ²=25.33, P=0.001), but there was no statistical difference according to the trend test ($\chi^{2}_{trend}$=1.94, P=0.171). The detection rates of graduates’ medical exa-minations from 2006 to 2017 respectively were 61.00/100000 (3/4910), 82.36/100000 (4/4857), 19.34/100000 (1/5171), 22.42/100000 (1/4460), 35.79/100000 (1/2794), 30.70/100000 (1/3257), 0.00/100000 (0/3805), 25.71/100000 (1/3889), 29.49/100000 (1/3391), 0.00/100000 (0/3602), 28.93/100000 (1/3457), and 30.18/100000 (1/3313). There was no statistical difference in the detection rate of graduates’ medical examinations (χ ²=6.69, P=0.805) and no statistical difference according to the trend test ($\chi^{2}_{trend}$=2.53, P=0.115).Conclusion The TB incidence in the university during the past 12 years was declining, but there were still fluctuations. Thus, the TB prevention and control work still need to be strengthened. The combination of medical examination for new students and graduates, seeking health care with symptoms, and screening for close contacts with TB is an important means for the early detection of TB patients to prevent the spread of the disease.

Review Articles

Burden and detriment of drug-resistant tuberculosis in children

Jie-qiong LI,A-dong SHEN

Chinese Journal of Antituberculosis. 2018, 40(9):  989-992.  doi:10.3969/j.issn.1000-6621.2018.09.016

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Drug-resistant tuberculosis is one of the major health problems in children. Due to the difficulties in diagnosis, low detection rate, low cure rate and high transmission rate, drug-resistant tuberculosis is a critical problem for pediatricians and tuberculosis prevention and control experts. The authors collected and reviewed domestic and international data on the burden and danger of drug-resistant tuberculosis in children to understand status of drug-resistant tuberculosis in children and timely solve the current problems.

Research progress on pharmacogenomics of anti-tuberculosis drugs

Chen SHEN,A-dong SHEN

Chinese Journal of Antituberculosis. 2018, 40(9):  993-998.  doi:10.3969/j.issn.1000-6621.2018.09.017

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Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB) infection, and the treatment of TB are mainly by chemical drugs. The researches on pharmacogenomics of anti-TB drugs focus on the application of pharmacogenomics in anti-TB treatment. Intensive researches in the field of genomics of anti-TB drugs will be helpful for paving the way of individual anti-TB treatment. This literature review study mainly introduced the current progress in the field of anti-TB pharmacogenomics research, including research methods for human genomics, pharmacogenomics and anti-TB drug metabolism, pharmacogenomics and anti-TB drug-induced liver damage, as well as pharmacogenomics and MTB resistance; the challenges of researches on anti-TB drug genomics were also explored.

Effect of diabetes mellitus on multidrug-resistant pulmonary tuberculosis and the countermeasures

Long JIN,Wei-hua HU,Shui-hua LU

Chinese Journal of Antituberculosis. 2018, 40(9):  999-1002.  doi:10.3969/j.issn.1000-6621.2018.09.018

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With the increasing prevalence of diabetes mellitus (DM) and multidrug-resistant pulmonary tuberculosis (MDR-PTB), the effect of DM on MDR-PTB has aroused people’s concern. The authors analyzed the effects of DM on MDR-PTB by summarizing the incidence, clinical features, imaging features, other bacterial infections, selection and application of anti-tuberculosis drugs, and treatment outcome of MDR-PTB patients complicated with DM in the domestic and foreign literatures. The results suggest that DM is an important risk factor for MDR-PTB. Effective control of blood glucose as soon as possible, reasonable selection of effective anti-tuberculosis drugs, timely detection and management of adverse drug reactions during treatment, and treatment of DM complications are the key to improve the success rate of MDR-PTB with diabetes.

Short Articles

Analysis of CT images of secondary pulmonary tuberculosis in children

Dan XIN,Jun XIN

Chinese Journal of Antituberculosis. 2018, 40(9):  1003-1006.  doi:10.3969/j.issn.1000-6621.2018.09.019

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The clinical data/information and CT findings of 75 children with secondary pulmonary tuberculosis, who were diagnosed at Shenyang Tenth People Hospital from August 2012 to September 2017, were retrospectively analyzed. Among 75 cases, their lesions mainly occurred in the posterior or apical segment of the upper lobe of the lung (proportion occurred in the posterior segment of the right upper lobe was 64.0% (48/75), in the posterior or apical segment of the left upper lobe was 62.7% (47/75), in the apical segment of the right upper lobe was 56.0% (42/75)) and the back segment of the lower lobe of the lung (proportion occurred in the back segment of the right lower lobe was 61.3% (46/75), in the back segment of the left lower lobe was 42.7% (32/75)). The lesions in the lungs were in a variety of forms. The most common images of the lesions included fibrous strips (92.0% (69/75)), acinar-like nodules in the lobules & nodular fusion (91.7% (68/75)), patchy shadow (86.7% (65/75)) and light film (80.0% (60/75)); the incidence of tuberculoma was very low (5.3% (4/75)). In the changes of lesion density, the incidence of calcification (58.7% (44/75)) was slightly higher; the most cavities were thick-walled (22.7% (17/75))) or wall-less (10.7% (8/75)). The rate complicated with tuberculous pleurisy (77.3% (58/75)) or bronchial tuberculosis (36.0% (27/75)) was high.

Dose adjustment of Immunosuppressants in anti-tuberculosis regimen containing rifampins (Report of three cases)

Tao JIN

Chinese Journal of Antituberculosis. 2018, 40(9):  1007-1011.  doi:10.3969/j.issn.1000-6621.2018.09.020

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Patients who use immunosuppressants are more likely to be infected with tuberculosis than the general population. Rifampin can accelerate the metabolism of immunosuppressive agents (especially calcium phosphatase inhibitors and glucocorticoids) and decrease the serum concentration of immunosuppressants. This will course the aggravation or recurrence of the primary disease in some patients. It is suggested that the dosage of tacrolimus or ciclosporin should be adjusted to 1.5-3 times and glucocorticoid to 2 times of the original dose for keeping the effective blood concentration when the rifampicin(or rifapentine) be used for anti-tuberculosis treatment. Furthermore, the medicines mentioned above have to be adjusted to the initial measurement after going off rifampin (or rifapentine). Wuzhi tablet or wuzhi capsule as an adjuvant drug for anti-tuberculosis treatment, not only has an effect of protecting liver and ensure the efficacy and safety of standard treatment regimens including rifampicin, but also keep the plasma concentration of calcium phosphatase inhibitor and reduce the dose of immunosuppressant. Wuzhi tablet or wuzhi capsule has good economic efficiency..

Application of information technology in home quarantine of patients with sputum smear positive pulmonary tuberculosis

Sheng-yuan LIU,Ya-rui YANG,Liang CHEN,Xu-jun GUO,Tao ZHONG,Min-min ZHU,Jian WANG,Sheng-bin LI,Jie ZHANG,Chun-fa SONG,Nan-sen YANG,Jian-ping MA

Chinese Journal of Antituberculosis. 2018, 40(9):  1012-1018.  doi:10.3969/j.issn.1000-6621.2018.09.021

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To explore the application of global positioning system (GPS) technology and mobile terminals application (APP) to monitor the activity trajectory and medication of tuberculosis (TB) patients during their home quarantine, 10 smear-positive mild TB patients with voluntary signing the informed consent of home quarantine, who were newly treated and managed at Nanshan Center for Chronic Disease Control from August 2017 to November 2017, were selected as the research subjects. The ten patients were managed by the doctors with “Jian xiang hu lian” APP. After two weeks of quarantine (one home quarantine cycle), the patients went to Nanshan Center for Chronic Disease Control for sputum smear examination. According to the results of sputum smear, the doctors decided to cease or continue the quarantine. In the end, 7 cases carried out 1 home quarantine cycle, and 3 cases performed 2 home quarantine cycles. Eight patients’ medication video upload rates were above 95%. Three patients were at home during the whole period of quarantine, while 7 patients were unable to stay at home during the whole period of quarantine, but the trajectories were clear. Among the 7 patients who were out of their homes, 2 patients went to see a doctor 5 times with reporting to the doctor. Two patients respectively went out 3 times and 4 times due to illness and other matters without reporting to the doctor. One patient went to see a doctor 4 times with reporting to the doctor, but went out 1 time for moving house without reporting to the doctor. One patient went out 2 times for medical examination with reporting to the doctor, but went out 3 times due to other matters without reporting to the doctor. One patient went out 5 times for medical examination with reporting to the doctor, but went out 1 times for purchasing daily necessities without reporting to the doctor. The results showed that the home quarantine model based on GPS technology could provide control and supervision basis for the precise and effective quarantine of smear-positive TB patients and reducing the transmission of TB.