Table of Content

10 November 2022, Volume 44 Issue 11

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Special Topic

Immunologically active substances: novel treatment options for tuberculosis and nontuberculous mycobacteriosis

Gong Wenping, Mi Jie, Wu Xueqiong

Chinese Journal of Antituberculosis. 2022, 44(11):  1107-1121.  doi:10.19982/j.issn.1000-6621.20220239

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Tuberculosis (TB) is not only an infectious disease, but also an immune disease. As a new potential treatment for diseases caused by the Mycobacterium tuberculosis (MTB) and nontuberculous mycobacteria (NTM), immunotherapy can inhibit or even eliminate MTB and NTM by influencing and regulating the immune system of the human body. In this article, we summarized the research progress of immunologically active substances such as cytokines, antibodies, small molecule active peptides, lysozyme, and immunoblockers in the treatment of MTB and NTM infections. This study will provide new ideas for TB and NTM treatment.

Interpretation of Standards

Interpretation of WHO consolidated guidelines on tuberculosis Module 4: Treatment of drug-susceptible tuberculosis

Yuan Yuan, Lu Shuihua

Chinese Journal of Antituberculosis. 2022, 44(11):  1122-1125.  doi:10.19982/j.issn.1000-6621.20220330

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In 2010, World Health Organization (WHO) issued recommendations for the treatment of drug susceptible tuberculosis (DS-TB). This treatment regimen is widely used, but in clinical practice, it is found that many patients fail to complete the 6-month treatment due to the long treatment time. Based on two phase Ⅲ trials, for the first time, the 2022 WHO guidelines add to the evidence-based recommendations of the most recent 2021 guideline development panel, which recommended a 4-month regimen for DS-TB. In this article, the author interprets the treatment of DS-TB according to the latest 2022 guidelines.

Original Articles

Analysis on characteristic of drug resistance-associated gene mutations and the correlation with genotypes among Mycobacterium tuberculosis isolates in Zhejiang Province

Wu Kunyang, Lu Yewei, Zhang Mingwu, Zhu Yelei, Li Xiangchen, Pan Junhang, Wang Xiaomeng, Wang Wei, Jiang Minmin, Peng Xiaojun, Wang Weixin, Gao Junshun, Liu Zhengwei

Chinese Journal of Antituberculosis. 2022, 44(11):  1126-1134.  doi:10.19982/j.issn.1000-6621.20220224

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Objective: To evaluate the drug resistance analysis and detection performance of whole-genome sequencing (WGS) on the characteristic of drug resistance-associated gene mutations and its correlation with genotypes among Mycobacterium tuberculosis (MTB) isolates in Zhejiang Province. Methods: WGS analysis of 14 drugs was performed on 808 MTB strains collected from the fifth tuberculosis drug resistance surveillance project in Zhejiang Province from 2018 and 2019. MTB genotypes and drug resistance-related gene mutations were identified, meanwhile, their relationship and the consistency of WGS drug susceptibility test results and phenotypic drug susceptibility test results of isoniazid were analyzed. Results: Of the 808 MTB strains, 153 were identified with drug-resistant gene mutations related to 11 anti-tuberculosis drugs (isoniazid, rifampicin, ethambutol, pyrazinamide, streptomycin, fluoroquinolones, amikacin, kanamycin, capreomycin, ethionamide, para-aminosalicylic acid) and the overall mutation rate was 18.9%. The major drug resistance-associated gene mutation types were katG-315-S/T (isoniazid, 60.0% (45/75)), rpoB-450-S/L (rifampicin, 57.1% (16/28)), embB-306-M/V (ethambutol, 43.8% (7/16)), rpsL-43-K/R (streptomycin, 65.5% (36/55)), gyrA-94-D/G (fluoroquinolones, 36.6% (15/41)), rrs-1402-C/A (amikacin, 3/3), rrs-1402-C/A (kanamycin, 3/4), rrs-1402-C/A (capreomycin, 3/3), inhA-15-C/T (ethionamide, 65.0% (13/20)) and thyA-75-H/N (para-aminosalicylic acid, 7/8). Drug resistance-associated mutations on rpsL gene were detected only in Beijing genotype strains (6.8% (40/586) vs. 0.0% (0/222), χ²=15.943, P=0.000). The mutation rate of katG-315 was higher in Beijing genotype strains (6.8% (40/586)) than non-Beijing genotype strains (3.2% (7/222)) and the difference was statistically significant (χ²=3.964, P=0.046). The sensitivity, specificity, positive predictive value, negative predictive value, consistency rate and Kappa value of the WGS drug resistance profiling method for isoniazid were 87.5% (49/56), 98.0% (680/694), 77.8% (49/63), 99.0% (680/687), 97.2% (729/750) and 0.808, respectively. Conclusion: The major drug resistance-associated gene mutations of 11 drugs were on katG, rpoB, embB, pncA, rpsL, gyrA, rrs, thyA and inhA among Zhejiang Province MTB strains. Mutations on rpsL, katG-315 and rpsL-43 were related with Beijing genotypes. The WGS drug resistance profiling method has comprehensive detection performance for isoniazid, but the performance of some drug-resistant gene mutations is poor.

Diagnostic value of metagenomic next-generation sequencing in nontuberculous mycobacterial pulmonary disease

Kong Jiao, Chen Yuanyuan, Cai Qingshan, Zhao Yafang, Yu Yihang

Chinese Journal of Antituberculosis. 2022, 44(11):  1135-1140.  doi:10.19982/j.issn.1000-6621.20220298

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Objective: To investigate the diagnostic value of metagenomic next-generation sequencing (mNGS) in nontuberculous mycobacterial pulmonary disease (NTM-PD). Methods: The data of 123 patients with suspected NTM-PD admitted to the Tuberculosis Diagnosis and Treatment Center of Hangzhou Chest Hospital, Zhejiang University School of Medicine from January 2020 to February 2022 were retrospectively selected. According to the diagnostic criteria, 123 suspected NTM-PD patients were finally diagnosed as NTM-PD patients (NTM-PD group; n=74) and non-NTM-PD patients (non-NTM-PD group; n=49). All the patients underwent mNGS, PCR-fluorescence probe and mycobacterial culture in alveolar lavage fluid, sputum and lung tissue simultaneously. The sensitivity and specificity of the three methods were compared. Results: Based on the final clinical diagnosis, the sensitivities of mNGS, liquid culture and PCR fluorescence probe for NTM-PD detection were 83.8% (62/74), 78.4% (58/74) and 67.6% (50/74), respectively, the specificities were 65.3% (32/49), 91.8% (45/49) and 87.8% (43/49), respectively, the consistencies in diagnosis were 76.4% (94/123), 83.7% (103/123) and 75.6% (93/123), respectively, with Kappa values of 0.524, 0.647 and 0.521, respectively. Using liquid culture results as the standard, of mNGS and PCR fluorescence probe for NTM-PD detection, the sensitivities were 87.1% (54/62) and 75.8% (47/62), and specificities were 59.0% (36/61) and 85.2% (52/61), respectively, the consistencies in diagnosis were 73.2% (90/123) and 80.5% (99/123), and the Kappa values were 0.462 and 0.587, respectively. The strains of 74 NTM-PD patients were identified by mNGS and gene chip method, and the concordance rate of two detecting methods was 63.8% (37/58) with gene chip method as the standard for strain identification. Conclusion: For the diagnosis of NTM-PD, of mNGS detection, the sensitivity is high, it can directly identify the strains; however, the specificity is low, the specificity should be focused on improving, to better serve the clinic.

Prevalence of drug resistant tuberculosis in China: data from national drug resistant tuberculosis survey in 2018

Wang Shengfen, Zhou Yang, Ou Xichao, Xia Hui, Zhao Bing, Song Yuanyuan, Zheng Yang, Du Xin, Zhao Yanlin

Chinese Journal of Antituberculosis. 2022, 44(11):  1141-1147.  doi:10.19982/j.issn.1000-6621.20220268

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Objective: The aim of this study is to analyze prevalence of drug resistant tuberculosis in China in 2018, and provide evidence for formulating policies about treatment and prevention of tuberculosis. Methods: The 70 clusters selected by the National Drug Resistant Tuberculosis Baseline Survey during 2007—2008 were used as survey sites, newly diagnosed smear positive pulmonary tuberculosis patients were recruited in this study in 2018. Standardized questionnaire was used to collect socio-demographic features, disease histories and medical treatment histories of these patients. Sputum samples were collected from presumptive pulmonary tuberculosis patients visiting the surveysites for smear and culture. Positive isolates were transferred to provincial or municipal Centers for Disease Control and Prevention or tuberculosis institutes for bacteria identification and drug susceptibility test. Survey procedures of SAS 9.4 software were used to calculate the weighted drug resistant prevalence considering the complex sampling design and sampling weight. Logistic regression model was used to assess changes in prevalence. Results: 3820 new smear positive pulmonary tuberculosis patients and 643 retreated smear positive patients were included in the survey. Prevalence of rifampicin resistant tuberculosis (RR-TB) was 5.08% (95%CI: 4.39%-5.77%) and 23.31% (95%CI: 20.14%-26.48%) in new cases and retreated patients, respectively. Multidrug resistant tuberculosis (MDR-TB) accounted for 3.52% (95%CI: 2.94%-4.11%) of new cases, and 18.01% (95%CI: 15.36%-20.67%) of retreated patients. Compared with the 2007—2008 baseline survey, the RR-TB prevalence in new cases (OR(95%CI): 0.71 (0.58-0.87);P<0.001) and retreated patients (OR(95%CI): 0.53 (0.41-0.68);P<0.001) decreased significantly. The MDR-TB prevalence of new cases (OR(95%CI): 0.53 (0.42-0.67);P<0.001) and retreated patients (OR(95%CI): 0.47 (0.36-0.61);P<0.001) also decreased significantly. It was estimated that the numbers of RR-TB patients were 12662 (95%CI: 10942-14382) and 8156 (95%CI: 7047-9265) among bacteriologically confirmed new cases and retreated patients nationwide in 2018. Conclusion: The prevalence of RR-TB and MDR-TB among new cases and retreated patients in 2018 decreased significantly while compared with that of the 2007—2008 baseline survey. However, due to the large number of population, China is still a country with high burden of drug resistant tuberculosis. It is suggested that comprehensive measures should be taken to reduce the emergence and spread of drug resistant tuberculosis, and then to reduce the overall burden of drug resistant tuberculosis in China.

Analysis of influencing factors of recurrence after successful treatment in new pulmonary tuberculosis patients in Kashgar Prefecture, Xinjiang Uygur Autonomous Region

Maiweilanjiang·Abulimiti , Diermulati·Tusun , Keyoumu·Wubulikasimu , Musa·Aihaiti , Liu Zhenjiang, Li Bin, Xirizhati·Mamuti , Chen Jinou, Li Tao, Su Wei, Zhao Yanlin, Ou Xichao

Chinese Journal of Antituberculosis. 2022, 44(11):  1148-1153.  doi:10.19982/j.issn.1000-6621.20220299

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Objective: To analyze the influencing factors of recurrence after successful treatment in new pulmonary tuberculosis (PTB) patients in Kashgar Prefecture, and to provide scientific basis for formulating intervention measures to reduce the recurrence of PTB in Kashgar Prefecture. Methods: Using the stratified cluster sampling method, as of December 31, 2021, 216 recurrent and 216 non-recurrent new PTB patients registered and successfully treated in Kashgar Prefecture in 2015 were selected as the survey objects and were matched 1∶1 according to gender and age. A questionnaire survey was conducted on those 432 patients, and multivariate logistic regression was used to analyze the main influencing factors of PTB recurrence after successful treatment. Results: Multivariate logistic analysis indicated: body mass index>24.00 (OR=4.235, 95%CI: 1.277-7.877), education level being new school (OR=3.434, 95%CI: 1.861-6.337), middle-income (OR=2.240,95%CI: 1.256-3.993), unstandardized anti-TB treatment (OR=3.436, 95%CI: 1.788-6.606), smoking (OR=3.970, 95%CI: 1.419-11.113) were independent risk factors for TB recurrence. Patients with no history of close contact with other TB patients (OR=0.256, 95%CI: 0.137-0.477) and patients receiving centralized medication (OR=0.103, 95%CI: 0.026-0.413) were less likely to recurrent. Conclusion: Implementing centralized medication management for tuberculosis patients in Kashgar Prefecture, and timely implementation of targeted interventions for smokers and people with a history of close contact with other TB patients, can effectively reduce the recurrence of PTB.

Effects of meteorological factors and air pollutants on the incidence of pulmonary tuberculosis in Yulin from 2017 to 2021

Cao Fu, Ma Xiaohong, Ma Tian, Luo Jian, Zhong Xinxin, Feng Junlan, Li Xiaojuan, Liang Zhengen, Zhang Qizhen

Chinese Journal of Antituberculosis. 2022, 44(11):  1154-1161.  doi:10.19982/j.issn.1000-6621.20220254

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Objective: To analyze the influence of air pollutants and meteorological factors on the incidence of pulmonary tuberculosis and the interaction of them in Yulin. Methods: The case data of 11251 patients with newly diagnosed pulmonary tuberculosis in Yulin, Guangxi Zhuang Autonomous Region from January 1, 2017 to December 31, 2021 were collected, and the meteorological data of air pollutants and meteorological factors in Yulin were also collected. Spearman correlation analysis was used to analyze the correlation between air pollutants and meteorological factors and the incidence of pulmonary tuberculosis. Bivariate response surface model and single pollutant-air temperature interaction model were used to analyze the interaction between air pollutants and air temperature on the risk of pulmonary tuberculosis. Results: The incidence of pulmonary tuberculosis in Yulin had obvious seasonal fluctuation from 2017 to 2021, and the peak was concentrated in spring (27.57%, 3102/11251) and summer (27.89%, 3138/11251). The incidence rates of males and farmers were higher (74.70% (8405/11251) and 87.74% (9872/11252), respectively). The daily concentrations (median (quartile)) of PM_2.5, PM₁₀, SO₂, NO₂, CO and O₃ in Yulin from 2017 to 2021 were 27.00 (19.00, 41.00) μg/m³, 44.00 (32.00, 64.00) μg/m³, 13.00 (8.00, 21.00) μg/m³, 15.00 (12.00, 21.00) μg/m³, 0.82 (0.69, 0.99) mg/m³ and 53.00 (39.00, 69.00) μg/m³, respectively. The daily average temperature (median (quartile)) was 24.50 (19.00, 29.00) ℃. The average daily incidence of pulmonary tuberculosis was 6 cases (11251/1825). When high temperature (37.00 ℃) lasted for 0-4 days, the incidence of pulmonary tuberculosis in Yulin increased. Compared with the median of daily temperature (24.50 ℃, RR value was 1.00), the RR value was 1.20 when 37.00 ℃ lasted for 0-4 days. Low temperature (3.00 ℃) lasting for 0-2 days could also increase the incidence of tuberculosis in Yulin. Compared with the median of daily temperature (24.50 ℃, RR value was 1.00), the RR value of was 1.22 when 3.00 ℃ lasted for 0-2 days. At low temperature (3.00 ℃), PM_2.5, PM₁₀, NO₂ and CO had a strong effect on the incidence of pulmonary tuberculosis, while at high temperature (37.00 ℃), PM_2.5, PM₁₀, SO₂, NO₂, CO and O₃ had a weak effect on the incidence of pulmonary tuberculosis. Conclusion: High or low temperature exposure can increase the risk of tuberculosis in Yulin, there is no synergistic effect between meteorological factors and air pollutants on the risk of tuberculosis in Yulin.

Study on the application effect of ultrasonic dispersion technique in the reprocessing of contaminated mycobacterium liquid cultures

Tian Peng, Deng Yunfeng, Wang Junling, Ling Xiaojie, Zhang Zhenjin, Wang Lin

Chinese Journal of Antituberculosis. 2022, 44(11):  1162-1166.  doi:10.19982/j.issn.1000-6621.20220217

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Objective: Study on the application effect of ultrasonic dispersion technique in the reprocessing of mycobacterium liquid culture contaminated specimens. Methods: Sputum samples of 4490 suspected tuberculosis patients and 795 confirmed tuberculosis patients admitted to the Outpatient and Inpatient Departments of Shandong Public Health Clinical Center were subjected to initial liquid culture, and the positive rate, contamination rate and reporting time of contamination were observed. Among them, there were 259 cases of culture contamination. The liquid culture of every contaminated specimen was thoroughly mixed and divided into two samples, one was reprocessed directly, and the other was reprocessed by ultrasound dispersion method. The positive rate and contamination rate in groups using the two methods were observed, and the detection rate of Mycobacterium tuberculosis complex (MTBC) and nontuberculous mycobacteria (NTM) were compared. Results: The positive rate of primary culture of 5285 sputum specimens was 17.7% (935/5285), and the contamination rate was 4.9% (259/5285). Among the 259 contaminated samples, 157 cases (60.6%) reported contamination time within 1-3 days, 100 cases (38.6%) within 4-10 days, 2 cases (0.8%) within 11-20 days. The positive rates of direct group and ultrasonic group were 7.3% (19/259) and 13.9% (36/259), respectively; contamination rates were 26.6% (69/259) and 21.2% (55/259); MTBC detection rates were 4.2% (11/259) and 5.0% (13/259); NTM detection rates were 3.1% (8/259) and 8.9% (23/259), respectively. Comparing the culture positive rate between the two groups, the ultrasound group was statistically higher than the direct group (χ²=5.879, P=0.015). The detection rate of NTM in the ultrasound group was statistically higher than that in the direct group too (χ²=7.720, P=0.005), while no statistical difference was observed for detection rate of MTBC between the two groups (χ²=0.175,P=0.676). Conclusion: The ultrasonic dispersion method can better detect mycobacteria and especially for NTM while controlling the contamination, indicating that it has great application potential in the reprocessing of mycobacterial liquid culture contaminated specimens.

Application of isothermal amplification fluorescence method for rapid detection of Mycobacterium tuberculosis complex

Li Jing, Wu Zheyuan, Yang Jinghui, Yang Liyuan, Wang Lili, Yuan Feng, Shen Xin, Jiang Yuan

Chinese Journal of Antituberculosis. 2022, 44(11):  1167-1173.  doi:10.19982/j.issn.1000-6621.20220221

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Objective: To evaluate the clinical application value of isothermal amplification fluorescence method for detection of Mycobacterium tuberculosis complex (MTBC) in sputum samples. Methods: Between January and November 2020, a total of 1848 sputum samples from suspected pulmonary tuberculosis patients in Shanghai 6 designated tuberculosis hospitals were respectively tests by isothermal amplification fluorescence, sputum smear, BACTEC MGIT 960 liquid culture and GeneXpert MTB/RIF (GeneXpert). Test effectiveness of isothermal amplification fluorescence, sputum smear and GeneXpert were compared according to liquid culture method. Results: Of all the 1848 sputum samples, the positive detection rates of isothermal amplification fluorescence, sputum smear, liquid culture and GeneXpert were 16.7% (309/1848), 14.4% (266/1848), 25.4% (470/1848) and 28.7% (530/1848), respectively. Based on liquid culture, the sensitivity of isothermal amplification fluorescence, sputum smear and GeneXpert were 58.94% (277/470), 52.77% (248/470) and 80.43% (378/470), respectively. The specificity of isothermal amplification fluorescence, sputum smear and GeneXpert were 97.68% (1346/1378), 98.69% (1360/1378) and 88.97% (1226/1378), respectively. The concordance rate of the isothermal amplification fluorescence, sputum smear and GeneXpert were 87.82% (1623/1848), 87.01% (1608/1848) and 86.80% (1604/1848), respectively. The Kappa value were 0.638, 0.600 and 0.666, respectively. Among the four sputum samples with different characteristics (mucoid sputum, salivary sputum, caseous sputum and blood sputum), the highest detection rate was by GeneXpert with 51.5% (308/598), 66.7% (28/42) and 64.0% (16/25) respectively, and the highest detection rate in salivary sputum was liquid culture with 38.8% (59/152). Conclusion: The isothermal amplification fluorescence detection method showed good specificity for detecting MTBC in sputum samples, and the result was general consistent with the liquid culture for detecting MTBC. Multiple detection methods should be considered according to laboratory and patient’s condition to improve the pathogenic diagnosis rate of pulmonary tuberculosis.

Predictive value of MRI combined with diffusion-weighted imaging on the effectiveness of drug therapy for cervical lymph node tuberculosis

Wen Xiaojian, Yin Quhua, Ling Jie, Yao Qineng

Chinese Journal of Antituberculosis. 2022, 44(11):  1174-1179.  doi:10.19982/j.issn.1000-6621.20220169

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Objective: To investigate the predictive value of MRI combined with diffusion-weighted imaging (DWI) on the effectiveness of drug therapy for cervical lymph node tuberculosis. Methods: A total of 160 cases of newly-treated patients with cervical lymph node tuberculosis who were admitted to Hunan Chest Hospital and received standardized anti-tuberculosis drug treatment from January 2017 to December 2021 were enrolled in the study.Their MRI data were collected for clinical classification. According to the re-examination results, the patients were divided into the good curative effect group (119 cases) and the poor curative effect group(41 cases).The differences of clinical classifications and MRI imaging data of the two groups were compared. Results: There were 20 cases (12.50%) with nodular hyperplasia, 79 cases (49.38%) with nodular necrosis, 46 cases (28.75%) with peri-lymph node inflammation, and 15 cases (9.37%) with peripheral abscess among 160 patients. The number (proportion) of nodular hyperplasia type, nodular necrosis type, peri-lymph node inflammation type and peripheral abscess type were 19 (15.97%), 67 (56.30%), 30 (25.21%) and 3 (2.52%) in the good curative effect group respectively, while the number (proportion) of corresponding subtypes were 1 (2.44%), 12 (29.27%), 16 (39.02%) and 12 (29.27%) in the poor curative effect group.There were statistical differences between the two groups (χ²=34.272, P<0.01). The lesions did not break through the capsule accounted for 72.27% (86/119) in the good curative effect group, which was significantly higher than that in the poor curative effect group (31.71%, 13/41), and the difference was statistically significant (χ²=21.267, P<0.01). The patients whose apparent diffusion coefficient (ADC) map showed mixed signals dominated by high signal (96.3%,77/80) usually got better curative effect, while the 39 cases whose ADC map showed obvious low signal had poor prognosis. The average ADC values of the good curative effect group and the poor curative effect group were (1.49±0.21)× 10^-3mm²/s and (1.06±0.19)×10^-3mm²/s respectively, and the difference was statistically significant (t=11.576, P<0.01). Conclusion: MRI combined with DWI had a certain predictive value for the effectiveness of anti-tuberculosis drug therapy in patients with cervical lymph node tuberculosis. Lesions that brook through the lymph node capsule or had limited diffusion were often indicative of poor prognosis.

Diagnostic value of spectral images derived from dual-layer spectral detector CT in bronchial-pulmonary shunts in patients with hemoptysis

Qu Huifang, Wang Wuzhang, Wang Liming, Deng Weiwei, Liu Xiaomin, Yang Jisheng, Guo Xiaowen, Zhang Yunzeng, Lu Yinan, Jin Feng

Chinese Journal of Antituberculosis. 2022, 44(11):  1180-1186.  doi:10.19982/j.issn.1000-6621.20220190

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Objective: To explore the diagnostic value of spectral images derived from dual-layer spectral detector CT (DLCT) in bronchial-pulmonary shunts (BPS). Methods: Conventional and spectral images (monoenergetic images and iodine density images) of spectral CT body arterial phase reconstruction of 28 patients with hemoptysis diagnosed as BPS by digital subtraction angiography (DSA) in Shandong Provincial Chest Hospital from December 2019 to December 2020 were retrospectively analyzed. Using DSA as the standard, the positive rates of spectral single level image and conventional image in the diagnosis of BPS were compared. The CT attenuation value or iodine density of the main pulmonary artery trunk (ROI1), the abnormally developed pulmonary artery lumen (ROI2) and the most obvious pulmonary artery enhancement area (ROI3) at the root of the lobe in the three groups of images were measured respectively, and the change trend was analyzed. Besides, of the same level and location of ROI2 and ROI3, the pulmonary artery lumen (ROI4) and lobar root lumen (ROI5) in the contralateral normal and diseased pulmonary artery were examined, and the measured values and differences with the contralateral changes were analyzed. Results: A total of 39 BPS positive pulmonary arteries were diagnosed by DSA images. Staggered development of pulmonary artery branches by 40 keV virtual monoenergetic images (VMI 40 keV) showed that the positive rates of BPS were 76.9% (30/39) and 69.2% (27/39), respectively. In the three groups of images on the abnormal side, the measured value of ROI3 ((539.00±152.09) HU) was significantly higher than those of ROI1 ((398.10±102.31) HU) and RO2 ((441.40±115.52) HU) (F=9.990, P <0.001). Compared with the pulmonary artery in the contralateral normal lung tissue, the measured value of ROI1 ((393.95±120.03) HU) was slightly greater than those of ROI4 ((396.40±146.01) HU) and ROI5 ((361.00±135.40) HU). There was no statistically significant difference (F=0.290, P=0.753). Compared with the pulmonary artery in the contralateral normal pulmonary tissue, the enhancement degree of pulmonary artery distribution along the blood flow in the three images showed a certain trend: the contrast agent concentration in the pulmonary artery lumen of the BPS positive side increased gradually along the blood flow direction, with the average value rising from (398.10±102.31) HU to (539.00±152.09) HU; however, the contrast agent concentration of normal pulmonary vessels changes little, increased from (361.00±135.40) HU to (393.95±120.03) HU. Conclusion: Spectral images based on DLCT could improve the diagnosis of BPS responsible vessels in patients with hemoptysis, which is helpful to predict the abnormal blood vessels of BPS before DSA.

Clinical effect on the treatment of long tunnelled external ventricular drainage for tuberculous meningitis complicated with hydrocephalus

Chen Qifu, Zhang Shengkun, Liao Guangsheng, Tang Zhong, Zhan Shenlin, Deng Guofang, Zhang Peize, Chu Ming

Chinese Journal of Antituberculosis. 2022, 44(11):  1187-1192.  doi:10.19982/j.issn.1000-6621.20220264

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Objective: To investigate the effect of long tunnelled external ventricular drainage (LTEVD) for tuberculous meningitis complicated with hydrocephalus. Methods: The clinical data of 43 tuberculous meningitis patients with hydrocephalus were retrospectively collected. All of them were treated with external ventricular drainage (EVD) in the Department of Neurosurgery, The Third People’s Hospital of Shenzhen from January 2018 to May 2021. Of them, 26 were treated with traditional EVD (traditional EVD group) and 17 were treated with LTEVD (LTEVD group). The therapeutic effect and complications were compared between the two groups. Results: Seventeen patients’s drainage time was 16-67 days in the LTEVD group, with an average of (28.12±13.86) days. Among them, 5 patients (29.4%) had aggravated hydrocephalus after the removal of the long-distance external drainage tube and was treated with ventriculoperitoneal shunt surgery. The 26 patients’s single drainage time did not exceed 14 days in the traditional EVD group. Among them, 16 patients (61.5%) had recurrence of hydrocephalus after extubation and then underwent ventriculoperitoneal shunt surgery. The hospital stay of patients in LTEVD group was 30.00 (33.50, 24.00) d, which was lower than that in traditional EVD group (30.50 (39.25, 26.00) d), the difference was not statistically significant (Z=0.847, P=0.397). However, the rate of unexpected extubation, cerebrospinal fluid leakage and intracranial infection, the incidences of catheterization and secondary shunt surgery in LTEVD group were all significantly lower or less than those in traditional EVD group (0.0% (0/17) vs. 30.8% (8/26), χ²=6.426, P=0.014; 0.0% (0/17) vs. 30.8% (8/26), χ²=6.426, P=0.014; 0.0% (0/17) vs. 26.9% (7/26), χ²=5.467, P=0.031; 100.0% (17/17) vs. 180.8% (47/26), χ²=5.932, P=0.000; 29.4% (5/17) vs. 61.5% (16/26), χ²=4.246, P=0.039; respectively). Patients in both groups were followed up for 1-2 years after discharge. The total effective rate was 82.4% (14/17) in LTEVD group, and was 69.2% (18/26) in the traditional EVD group, there was no significant difference between the two groups (χ²=0.368, P=0.544). Conclusion: LTEVD is a safe and effective technology for tuberculous hydrocephalus, which with longer drainage time and fewer complications compared to the traditional EVD.

Review Articles

Progress and application of whole genome sequencing data analysis of Mycobacterium tuberculosis

Li Xiangchen, Liu Zhengwei, Lu Yewei, Zhu Yelei, Zhang Mingwu, Jiang Jinqin, Peng Xiaojun, Wang Weixin, Gao Junshun, Wang Xiaomeng

Chinese Journal of Antituberculosis. 2022, 44(11):  1193-1198.  doi:10.19982/j.issn.1000-6621.20220219

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Whole genome sequencing technology has been widely used in Mycobacterium tuberculosis research, including lineage identification, microevolution, drug resistance prediction, transmission monitoring and mixed infection detection, etc. Bioinformatics in genomics research runs through all stages from data processing, analysis and visualization, and plays a crucial role in the application of whole genome sequencing. Current mainstream bioinformatics software and platforms commonly used in the whole genome sequencing of Mycobacterium tuberculosis were mainly reviewed, and the newly developed bioinformatics methods in recent years from the aspects of availability, software selection and application were summarized, to provide a reference for researchers in the same field to improve the data analysis more conveniently and flexibly, and quickly select research tools.

Updates on the application of whole-genome sequencing for within-host heterogeneity of Mycobacterium tuberculosis

Zhang Rui, Liu Yanping, Qian Jun, Fang Qianglin, Yang Chongguang

Chinese Journal of Antituberculosis. 2022, 44(11):  1199-1204.  doi:10.19982/j.issn.1000-6621.20220250

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Tuberculosis (TB) is an infectious disease caused by the Mycobacterium tuberculosis (MTB). The genetic polymorphism of the MTB complex is relatively conservative. With the impressive progress in the field of next generation sequencing (NGS) and the whole-genome sequencing (WGS) analysis, vast genetic heterogeneity has been observed in MTB isolates from different hosts and even within the same host. The reasons for this phenomenon are complex, at least including multiple or mixed infections of different strains and microevolution of the same strain within the host. Still, its mechanism and role in drug resistance, transmission, diagnosis and treatment of TB are not fully understood. This article reviews the identification and current research progress of the within-host genetic heterogeneity of MTB.

Structure and function of lipoarabinomannan and its application in tuberculosis diagnosis

Tang Minghui, Li Hao

Chinese Journal of Antituberculosis. 2022, 44(11):  1205-1212.  doi:10.19982/j.issn.1000-6621.20220276

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Tuberculosis is a significant zoonosis caused by Mycobacterium tuberculosis complex. Mannose-capped-lipoarabinomannan (ManLAM), an essential glycolipid component of the cell wall, has immunomodulatory effects and is recognized by intrinsic cells and adaptive cells. ManLAM in body fluids is a biomarker with good specificity for the diagnosis of tuberculosis, and has the potential ability to differentiate the latent tuberculosis infection and active tuberculosis. It also plays a certain role in detecting tuberculosis patients whose sputum could not be obtained. This article mainly introduces the structure, biosynthesis, and the related antibodies of ManLAM and summarizes the research progress in the diagnosis of tuberculosis, in order to provide reference for the development of tuberculosis diagnostic technology.

Short Articles

Investigation on the core knowledge of tuberculosis prevention and control among students in two middle school in Beijing

Ma Qianhui, Shang Xiyu, Ji Xinyu, Guo Yang, Xie Na, Jin Aning, Ma Yan

Chinese Journal of Antituberculosis. 2022, 44(11):  1213-1217.  doi:10.19982/j.issn.1000-6621.20220320

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To explore the core knowledge of tuberculosis prevention and control among students in middle school in Beijing. From May 17 to 31, 2019, a questionnaire survey on the core knowledge of tuberculosis prevention and control was conducted among 867 students in two middle schools in Fengtai District, Beijing. The results showed that the total awareness rate of the 8 core information of tuberculosis control was 66.41% (4606/6936), the awareness rate of all the core knowledge was 16.03% (139/867), and the awareness rate of none of the core knowledge was 10.96% (95/867). Among the 8 core information of the tuberculosis prevention and control in schools, “to develop the habit of frequently opening windows for ventilation” (82.47% (715/867)), while the lowest awareness rate was “After experiencing suspicious symptoms of tuberculosis or being diagnosed as tuberculosis, you should actively report to the school, not concealing the illness” (43.94% (381/867)). The total awareness rate of senior high school students was significantly higher than that of junior high school students (68.12% (3259/4784) vs. 62.59% (1347/2152); χ²=23.020, P<0.001). The awareness rate of none of the core knowledge of senior high school students was significantly lower than that of junior high school students (9.53% (57/598) vs.14.13% (38/269); χ²=4.014, P=0.045). The total awareness rate among females was higher than that of males (69.03% (2380/3448) vs.63.82% (2226/3488)), and the difference was statistically significant (χ²=20.840, P<0.001). Of the respondents, 1.85% (16/867) chose not to interact with their neighbors or classmates with tuberculosis, 77.51% (672/867) expressed willingness to participate in tuberculosis prevention campaigns. Only 35.29% (306/867) had received tuberculosis education. Schools (including publicity board, wall newspaper, blackboard newspaper, etc.), the Internet and Radio and Television were the most popular publicity channels among students (accounted for 87.08% (755/867)). Therefore, middle school students in Beijing have low awareness of core knowledge of tuberculosis prevention and uneven mastery of different core knowledge. Health promotion and publicity and education of tuberculosis prevention and control should be carried out for different target groups.