Table of Content

10 February 2023, Volume 45 Issue 2

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Special Topic

Landscape and prospect of tuberculosis vaccine research and development in China

Zhang Mengxian, Wang Ni, Huang Fei, Zhou Liping, Zhao Yanlin

Chinese Journal of Antituberculosis. 2023, 45(2):  125-129.  doi:10.19982/j.issn.1000-6621.20220267

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BCG is currently only available vaccine for tuberculosis (TB) at global level. It can mainly reduce the occurrence of tuberculous meningitis and disseminated tuberculosis in children, however, the protection effect on adolescents and adults is limited. In order to achieve “The End TB Strategy”, it is essential to research and develop novel tuberculosis vaccines that are effective for all ages. Encouraging research and development of new tuberculosis vaccines and participating in multi-regional clinical trials, which will help stimulate internal vitality, shorten the research and development cycle of TB vaccine, and accelerate the marketing and promotion speed. The author sorted out the current status of TB vaccine which are in clinic trial, the relevant supportive policies, the basic requirements of the multi-regional clinical trials and TB vaccine landscape.

Interpretation of Standards

Interpretation of the Operation specification of Mycobacterium tuberculosis recombinant protein skin test

Guo Tonglei, Cao Xuefang, Gao Lei

Chinese Journal of Antituberculosis. 2023, 45(2):  130-133.  doi:10.19982/j.issn.1000-6621.20220407

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Operation specification of Mycobacterium tuberculosis recombinant protein skin test (T/CHATA 020—2022), one of the social organization standards issued by the Chinese Antituberculosis association, was put into force since February 24, 2022. The standard specifies the scope of application, contraindications, operating procedures, observation and treatment principles of common adverse reactions, and quality assurance of the Mycobacterium tuberculosis recombinant protein skin test. To help medical staff better understand and normatively apply the Mycobacterium tuberculosis recombinant protein skin test, this article explains the drafting process and major points of the content of this standard.

Interpretation of immune function status assessment in Expert consensus on immune function assessment and immunotherapy in patients with active tuberculosis (2021 edition)

Xue Yong, Wu Xueqiong

Chinese Journal of Antituberculosis. 2023, 45(2):  134-138.  doi:10.19982/j.issn.1000-6621.20220421

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More and more clinical evidence showed that tuberculosis is not only an infectious disease, but also an immune disease. Many patients with active tuberculosis have the low immune function, so it is important and necessary to evaluate their immune function status, which can provide a basis for clinical immune intervention. Expert consensus on immune function assessment and immunotherapy in patients with active tuberculosis (2021 edition) published in Issue 1 of 2022 in the Chinese Journal of Antituberculosis, provides recommendations for the evaluation of immune function status and immunotherapy in tuberculosis patients, and forms a consensus. This interpretation mainly focuses on the assessment of immune function status, introduces more new progress of immune evaluation beyond the consensus for the readers, and enriches readers’ understanding of immune function assessment in tuberculosis patients.

Original Articles

Diagnostic application of GeneXpert MTB/RIF in stool specimens for intestinal tuberculosis

Liu Rongmei, Lyu Zizheng, Ma Liping, Li Qiang, Song Yanhua, Chen Hongmei, Kong Zhongshun, Gao Mengqiu

Chinese Journal of Antituberculosis. 2023, 45(2):  139-143.  doi:10.19982/j.issn.1000-6621.20220381

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Objective: To evaluate the diagnostic value of rifampicin resistance real-time fluorescence quantitative nucleic acid amplification assay (GeneXpert MTB/RIF) in testing stool specimens for detecting intestinal tuberculosis. Methods: From January 2019 to December 2021, the stool samples of 538 patients with clinically suspected intestinal tuberculosis were collected from Beijing Chest Hospital, Capital Medical University. Fluorescent smear microscopy, BACTEC MGIT 960 liquid rapid growth culture, GeneXpert MTB/RIF detection were performed. At the same time, the whole blood T-cell spot test, enteroscopy and intestinal mucosal tissue pathology were performed to analyze the diagnostic efficacy of fecal samples in diagnosing intestinal tuberculosis by GeneXpert MTB/RIF. Results: Out of 538 patients suspected of intestinal tuberculosis, 189 were diagnosed as intestinal tuberculosis according to clinical diagnostic criteria, 349 were diagnosed as non intestinal tuberculosis (including ulcerative colitis, intestinal infection, gastrointestinal ulcer, malignant tumor, Crohn’s disease, etc.). With the clinical diagnostic criteria as the gold standard, the sensitivity and specificity of GeneXpert MTB/RIF test on stool samples were 77.2% (95%CI: 70.5%-82.9%) and 51.0% (95%CI: 45.6%-56.3%), respectively; The sensitivity and specificity of stool fluorescent smear microscopy were 23.3% (95%CI: 17.6%-30.1%) and 92.8% (95%CI: 89.5%-95.2%); The sensitivity and specificity of fecal liquid rapid growth culture were 29.1% (95%CI: 22.9%-36.2%) and 83.7% (95%CI: 79.3%-87.3%). Conclusion: In the diagnosis of intestinal tuberculosis, stool GeneXpert MTB/RIF test showed relatively high sensitivity for detecting Mycobacterium tuberculosis in clinical diagnosed patients who lack bacteriological diagnosis evidence, which could improve the diagnosis level of intestinal tuberculosis.

Clinical diagnostic value of combining four methods in detecting etiologically negative pulmonary tuberculosis

Tian Lili, Chen Shuangshuang, Fan Ruifang, Zhang Jie, Wang Nenhan, Chen Hao, Dai Xiaowei, Ren Yixuan, Zhao Yanfeng, Li Chuanyou, Ding Beichuan, Li Bo, Yu Lan, Yi Junli, Wang Pei, Yang Xinyu, Song Weiping

Chinese Journal of Antituberculosis. 2023, 45(2):  144-150.  doi:10.19982/j.issn.1000-6621.20220443

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Objective: To analyze the diagnostic value of combining T-cell spot test for tuberculosis infection (T-SPOT.TB), antibody (TB-Ab) test, erythrocyte sedimentation rate (ESR) test, and hypersensitive C-reactive protein (hs-CRP) test in detecting etiologically negative pulmonary tuberculosis(PTB). Methods: Data of 216 PTB patients who were initially treated and had negative etiological test results (etiologically negative PTB group) were collected from the Tuberculosis Clinic of the Beijing Center for Disease Prevention and Control from July 2020 to July 2022. Meanwhile 147 primary PTB patients with positive etiological test results and 455 patients with other pulmonary diseases who were admitted during the same period were classified as the etiologically positive PTB group and other lung disease group respectively. All of them were tested with T-SPOT.TB, TB-Ab, ESR, and hs-CRP to analyze the diagnostic performance of single test and combined tests with those four methods, based on clinical diagnosis. Results: The detection positive rate of T-SPOT.TB in etiologically negative PTB group was 82.4% (178/216), no statistically significant difference was observed comparing with the detection positive rate in etiologically positive PTB group (87.8% (129/147); χ²=1.917,P=0.166), but the difference was statistically significant (χ²=160.746,P=0.000), while comparing with the detection positive rate in other pulmonary disease group (28.6%, 130/455). The sensitivity, specificity, positive and negative predictive value and accuracy of T-SPOT.TB were 82.9% (178/216), 71.4% (325/455), 57.8% (178/308), 89.5% (325/363), 75.0% (503/671), respectively. While for combination of all four methods, they were 91.7% (198/216), 53.4% (243/455), 48.3% (198/410), 93.1% (243/261), 65.7% (441/671), respectively. The area under ROC curve (AUC) of T-SPOT.TB, TB-Ab, ESR and hs-CRP test were 0.764, 0.600, 0.529 and 0.515, respectively, and the AUC of combining those four tests was 0.804. Conclusion: The sensitivity, negative predictive value and accuracy of the T-SPOT.TB test for detecting etiologically negative PTB were relatively good, and the sensitivity, negative predictive value and AUC of combining four test methods were relatively high, which indicates that combining tests could improve the diagnostic efficacy for detecting etiologically negative pulmonary tuberculosis.

SLC22A12 gene polymorphism study on susceptibility to hyperuricemia induced by pyrazinamide

Peng Jiangli, Chen Jie, Chen Yonggang, Wang Lu, Li Na, Luo Ji, Han Yi, Yu Mingli, Zhu Jiangchun

Chinese Journal of Antituberculosis. 2023, 45(2):  151-158.  doi:10.19982/j.issn.1000-6621.20220315

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Objective: To investigate the correlation between SLC22A12 gene polymorphism and hyperuricemia induced by pyrazinamide in patients with pulmonary tuberculosis. Methods: A total of 514 patients with pulmonary tuberculosis who had received an intensive regimen containing pyrazinamide in the Third People’s Hospital of Kunming from January 2019 to March 2021 were collected. A total of 294 patients with hyperuricemia were selected as the elevated uric acid group and 220 patients without hyperuricemia were selected as the normal uric acid group. The SNP Sequenom MassARRAY genotyping was used to detect the polymorphisms of rs11602903, rs559946, rs475688 and rs476037 in SLC22A12 gene, and logistic regression model was used to analyze the correlation between the the polymorphisms of related loci and hyperuricemia induced by pyrazinamide. Results: After 4-week treatment with pyrazinamide, the serum uric acid in the elevated uric acid group ((648.32±109.23) μmol/L) was significantly higher than that in the normal uric acid group ((319.14±52.64) μmol/L), and the difference was statistically significant (t=-15.425,P=0.000). Logistic regression model was used to analyze the correlation between the genotypes and alleles of each locus and the occurrence of hyperuricemia in the elevated uric acid group and the normal uric acid group. The results showed that the rs475688 TC (50.3% (148/294) vs. 44.1% (97/220)), TT genotype (21.8% (64/294) vs. 6.4% (14/220)) and T allele (46.9% (276/588) vs. 28.4% (125/440)) of patients in the normal group had a significantly increased risk of hyperuricemia after taking pyrazinamide (OR (95%CI) were 2.028 (1.381-2.978), 6.077 (3.187-11.586), 2.229 (1.714-2.900)). The risk of hyperuricemia was significantly reduced in patients with TA (32.3% (95/294) vs. 50.0% (110/220)), TT genotype (4.1%(12/294) vs. 8.2% (18/220)) and T allele (20.2% (119/588) vs. 33.2% (146/440)) of rs11602903 and TC (32.7% (96/294) vs. 45.5% (100/220)), T allele (20.4% (120/588) vs. 26.4% (116/440)) of rs559946 (OR (95%CI) were 0.425 (0.293-0.616), 0.328 (0.152-0.710), 0.511 (0.385-0.678); 0.578 (0.401-0.833), 0.716 (0.535-0.959), respectively). Conclusion: The rs11602903 and rs559946 polymorphisms of SLC22A12 gene may be related to the reduction of pyrazinamide-induced hyperuricemia. The rs475688 polymorphism may increase the risk of pyrazinamide-induced hyperuricemia.

Analysis of atypical chest CT findings in AIDS patients complicated with pulmonary tuberculosis

Du Yanni, Xue Ming, Guan Chunshuang, Xing Yuxue, Chen Budong, Xie Ruming

Chinese Journal of Antituberculosis. 2023, 45(2):  159-164.  doi:10.19982/j.issn.1000-6621.20220401

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Objective: To analyze the chest CT features of AIDS patients complicated with pulmonary tuberculosis (PTB), so as to improve the diagnostic value of imaging. Methods: One hundred and seventy-one AIDS patients only complicated with PTB from Beijing Ditan Hospital, Capital Medical University were retrospectively collected. The diagnosis was confirmed by pathology, laboratory examination or clinical diagnosis from January 2017 to January 2020. The type, distribution, morphology and changes of chest CT were analyzed. Results: Among the 171 patients, 117 (68.4%) had multiple types of PTB, and the incidence of secondary PTB combined with intrathoracic lymph node PTB was the highest (n=74, 43.3%). Of the 117 secondary PTB patients, 37 cases (31.6%) were located at the predilection site, 25 cases (21.4%) were located at the non predilection and atypical sites, and 55 cases (47.0%) were located at both the predilection and non predilection sites. The imaging signs were mainly bronchial dissemination (n=85, 72.6%), consolidation (n=79, 67.5%) and multiple nodules (n=78, 66.7%); 31 cases (39.2%) showed exudative consolidation similar to pneumonia without satellite lesions around. Among 53 cases of hematogenous disseminated PTB, 45 cases (84.9%) showed “three homogeneous” miliary nodules. Among 107 cases of intrathoracic lymph node TB, 31 cases (29.0%) had ulceration and invasion of adjacent pulmonary parenchyma, 23 cases (21.5%) had focal fusion, and 5 cases (4.7%) had gas signs in the lymph nodes. The incidence of TB pleurisy and associated pericardial effusion was high (36.3%, 62/171). The average time of CT re-examination in 139 cases after anti-tuberculosis drug treatment was 17 days, PTB lesions were absorbed in 52 cases (37.4%), while 58 cases (41.7%) had progressed. Conclusion: AIDS complicated with PTB often showed multiple types of PTB. The lesions were extensive and had no dominant distribution; the proportion of consolidation lesions similar to pneumonia was high; intrathoracic lymph nodes TB might have rare signs of gas; non-“three homogeneous” hematogenous disseminated PTB was common; the lesions changed rapidly in a short time after anti-TB treatment.

Influence of linezolid blood concentration on hematological toxicity in drug-resistant tuberculosis patients

Wang Honghong, Guo Shaochen, Zhou Wenqiang, Liu Zhongquan, Zhu Hui, Lu Yu

Chinese Journal of Antituberculosis. 2023, 45(2):  165-171.  doi:10.19982/j.issn.1000-6621.20220301

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Objective: To analyze the influence of linezolid blood concentration on hematological toxicity in drug-resistant tuberculosis patients, as well as to explore other risk factors for hematopoietic toxicity. Methods: A prospective cohort study was conducted in 219 drug-resistant tuberculosis patients, all of them were continuously included and received chemotherapy treatment containing linezolid from January 2019 to February 2021 in Beijing Chest Hospital affiliated to Capital Medical University. Clinical data and blood samples 2 hours after administration were collected. A high performance liquid chromatography-mass spectrometry was used to measure the plasma concentrations of linezolid. The diagnostic value of blood drug concentration (peak concentration) on blood system toxicity was determined by drawing receiver operating characteristic curve (ROC curve), and the optimal diagnostic threshold was also determined. Multivariate logistic regression was used to analyze the influencing factors of blood system toxicity. Results: Among 219 subjects, 92 cases (42.0%) had hematological toxicity, including leukopenia (15.5%, 34/219), anemia (21.5%, 47/219), and thrombocytopenia (27.4%, 60/219), and the other 127 (58.0%) cases did not have any toxic reactions associated with linezolid. The peak plasma concentration of linezolid in patients with hematotoxicity was 17.1 (11.8, 22.8) μg/ml, significantly higher than that of non-occurrence (14.7 (10.4, 18.0) μg/ml)(Z=-3.206, P=0.001). Of patients without hematological toxicity, 29.1% (37/127) had serum albumin of <40 g/L, which was significantly lower than that of those with serum albumin ≥40 g/L (70.9%, 90/127)(χ²=7.998, P=0.005). Based on the ROC curve analysis, the linezolid’s peak concentration had predictive value on blood system toxicity (the area under the curve was 0.627), and 20.7 μg/ml of the linezolid’s peak concentration was the best diagnostic point. The multivariate logistic regression analysis showed that, the risk of hematotoxicity in patients with serum albumin <40 g/L was 2.622 times higher than that in patients with serum albumin ≥40 g/L (OR=2.622, 95%CI:1.344-5.117); the risk of blood system toxicity in patients with the peak plasma concentration of linezolid >20.7 μg/ml was 6.419 times higher than that in patients with the peak blood concentration≤20.7 μg/ml (OR=6.419, 95%CI:2.874-14.337). Conclusion: The proportion of hematological toxicity caused by linezolid is high. It is important to be aware of the possibility of blood system toxicity when administering linezolid to patients with serum albumin <40 g/L and linezolid peak plasma concentration >20.7 μg/ml.

Analysis of clinical characteristics of 15 household contacts of patients with drug-resistant pulmonary tuberculosis who developed active pulmonary tuberculosis

Yang Hong, Ma Jinbao, Ren Fei, Li Rong, Wu Yanqin, Zhang Yaohui

Chinese Journal of Antituberculosis. 2023, 45(2):  172-180.  doi:10.19982/j.issn.1000-6621.20220274

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Objective: To analyze the clinical characteristics of patients with pulmonary tuberculosis detected in household contacts of patients with drug-resistant pulmonary tuberculosis (DR-TB), and to provide evidence for the management of household contacts of patients with DR-TB. Methods: The clinical data of family contacts (1100 cases) of patients diagnosed with DR-TB (650 cases) who developed active pulmonary tuberculosis (referred to as TB patients) in Xi’an Chest Hospital from January 2019 to June 2021 were retrospectively analyzed. Demographic characteristics, contact with index cases, onset time, clinical characteristics, laboratory test results, etiological characteristics and treatment outcomes were summarized and analyzed. Results: Among 15 TB patients in the contacts, 11 were female (73.3%) and 4 were male (26.7%); they were aged 3-56 years, with an average age of (36.1±13.0) years. The number of wives and children of the index case was higher, accounting for 80.0% (12/15), and the others, such as mother-in-law, son-in-law, and brother-sister relationship, each had 1 case which accounted for 6.7% (1/15). Eight cases (53.3%, 8/15) developed TB within six months of exposure to the index case, 6 cases (40.0%, 6/15) developed TB at 6-12 months after exposure, and 1 case (6.7%, 1/15) developed TB at more than 1 year after exposure to the index case. Eight cases were detected through active screening, and 7 cases were detected during medical visits after symptoms showed. Twelve cases were detected by initial screening, and 3 cases were diagnosed with active TB after multiple screenings. Nine cases of all the TB patients were etiologically positive, the drug susceptibility results were consistent with the index cases. The other 6 cases were etiologically negative, and the drug susceptibility were unknown. All cases had less than 3 lung fields being infected, and 4 cases (26.7%, 4/15) had cavities. All 15 cases received standard anti-TB treatment, 11 cases were cured, 4 cases achieved bacteriological negative conversion after treatment, and were still under treatment. Conclusion: Most of the household contacts of DR-TB patients got DR-TB when they developed active TB. Active screening played a crucial role in the early detection of TB. The disease was relatively mild after progressing to active TB. Good therapeutic effect could be achieved with early detection and proactive treatment.

Analysis of trend in tuberculosis incidence among people aged 0-10 years in China based on an age-period-cohort model

Liu Simin, Li Qiaomei, Tang Jiayi, Li Tingting, Ding Guowu

Chinese Journal of Antituberculosis. 2023, 45(2):  181-187.  doi:10.19982/j.issn.1000-6621.20220376

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Objective: To analyze the changes in the incidence of pulmonary tuberculosis in China’s 0-10-year-old population in terms of age, period, and cohort. Methods: By collecting the incidence data of tuberculosis reported to the Chinese Public Health Science Data Center from 2004 to 2018, the age period cohort (APC) model was used to analyze the impact of age, period, and cohort on the incidence of tuberculosis among the 0-10 years old population in China. Results: From 2004 to 2018, the annual average reported incidence rate of pulmonary tuberculosis in the whole population of China and the incidence rate of pulmonary tuberculosis in people aged 0 to 10 years showed a downward trend, decreasing from 74.64/100000 and 8.14/100000 in 2004 to 59.27/100000 and 1.22/100000 in 2018, respectively (χ_trend²=211.469, P=0.001; χ_trend²=210.018, P=0.001). The APC model analysis showed that age-period-cohort had a significant impact on the tuberculosis incidence of 0-10 years old population. The cross-sectional age specific incidence rate of pulmonary tuberculosis decreased from 6.12/100000 to 1.06/100000 with the increase of age (χ_trend²=89.765, P=0.013); The incidence risk decreased with time, and the RR value decreased from 0.97 to 0.14; The later the birth cohort, the lower the risk of onset, and the RR value decreased from 6.38 to 0.15. Conclusion: The risk of tuberculosis incidence in the 0-10 age group was decreasing as the cross-sectional age, period, and cohort continued to advance, which showed that the effect of tuberculosis vaccination and preventive control was significant, but there is still a need to strengthen the dissemination of tuberculosis knowledge and enhance tuberculosis surveillance.

Effect of mindfulness level on mental health of middle-aged and elderly people with type 2 diabetes mellitus comorbidity latent tuberculosis infection in rural areas

Dai Zhenwei, Zhang Haoran, Jing Shu, Xiao Weijun, Wang Hao, Huang Yiman, Chen Xu, Fu Jiaqi, Wu Yijin, Gao Lei, Su Xiaoyou

Chinese Journal of Antituberculosis. 2023, 45(2):  188-194.  doi:10.19982/j.issn.1000-6621.20220341

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Objective: To investigate the prevalence of latent tuberculosis infection (LTBI) in the middle-aged and elderly type 2 diabetes mellitus (T2DM) patients in rural areas of China, and to explore the influence of mindfulness on depression and the mediation effect of anxiety in T2DM comorbidity with LTBI patients. Methods: From November 2 to November 12, 2021, using a convenient sampling method, 469 middle-aged and elderly patients T2DM in rural areas of Zhongmu County, Henan Province were selected as the research participants for questionnaire survey and LTBI detection. The questionnaire includes general information, Five-item Mindful Awareness Attention Scale, Generalized Anxiety Disorder Questionnaire, and Patient Health Questionnaire. LTBI was detected by interferon-gamma release assay (IGRA). Structural equation modeling was used to test the mediation effect of anxiety between mindfulness and depression. Results: Of the 469 participants, 74 were IGRA positive, accounting for 15.78%. The score of Five-item Mindful Awareness Attention Scale in the 74 T2DM participants with LTBI was 5.00 (5.00, 10.00). The score of Patient Health Questionnaire and Generalized Anxiety Disorder Questionnaire in female were higher than male (0.00 (0.00, 2.00) vs. 0.00 (0.00, 0.00) and 0.50 (0.00, 3.00) vs. 0.00 (0.00, 0.75), respectively); the score of Patient Health Questionnaire in those with an annual income of less than RMB 20000 yuan was higher than those with an annual income of more than RMB 20000 yuan (0.00 (0.00, 2.25) vs. 0.00 (0.00, 0.00)); the score of Generalized Anxiety Disorder Questionnaire in those did not drink in the past 12 months was higher than those drank in the past 12 months (0.00 (0.00, 3.00) vs. 0.00 (0.00, 0.00)); the score of Patient Health Questionnaire in those without hypertension was higher than those with hypertension (1.00 (0.00, 4.00) vs. 0.00 (0.00, 0.75), all the differences were statistically significant (Z values were 1.789, 2.509, 2.572, 2.133, and 2.018, respectively, all P<0.10). The prevalence of anxiety and depression in T2DM patients with LTBI were 8.10% (6/74) and 5.40% (4/74), respectively, and 3 (4.10%, 3/74) had both depression and anxiety simultaneously. We used mindfulness as independent variable, depression as dependent variable, anxiety as mediator, and gender, annual income, whether drink in the past 12 months, and whether had hypertension as covariates, to build structural equation model. The model had good reliability, convergence validity and discrimination validity. In the model, the effects of mindfulness on anxiety (β=-0.394 (95%CI:-0.778-0.115), P=0.036), and anxiety on depression (β=0.878 (95%CI:0.446-0.979), P<0.001) were both statistically significant. The mediating effect of mindfulness on depression was statistically significant (β=-0.346 (95%CI:-0.628-0.103), P=0.011). Conclusion: The conditions of anxiety and depression in middle-aged and elderly T2DM patients comorbidity with LTBI of rural areas in China should be paid attention, preventive intervention and psychological mindfulness is suggested to be carried out.

Analysis on transmission of multidrug-resistant pulmonary tuberculosis in family

Zhou Yan, Zhou Meng, Peng Jun, Duan Qionghong, Chen Jun, Zhou Meilan, Zhang Yunxia, Liang Jun

Chinese Journal of Antituberculosis. 2023, 45(2):  195-199.  doi:10.19982/j.issn.1000-6621.20220355

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Objective: To explore transmission characteristics of multidrug-resistant pulmonary tuberculosis (MDR-PTB) in family. Methods: A total of 282 household contacts of 166 MDR-PTB patients (first generation cases) registered in Wuhan Pulmonary Hospital from July 2018 to June 2020 (MDR-PTB patients found in them were second generation cases) were enrolled. All the subjects were treated with tuberculin skin test (TST), chest X-ray, mycobacterium culture and phenotypic drug sensitivity test. Genotypes of strains from the first and second generation patients were tested by DTM-PCR and standard 24-loci MIRU-VNTR. The infection rate of Mycobacterium tuberculosis and the number of cases of MDR-PTB in close family contacts were calculated. The drug-resistant phenotype of first and second generation cases were compared, and the MIRU minimum spanning tree of the isolated strain was drawn. Results: Among 282 family contacts, the negative rate, general positive rate, moderate positive rate and strong positive rate of TST were 53.90% (n=152), 8.51% (n=24), 10.64% (n=30) and 26.95% (n=76), respectively, the infection rate of Mycobacterium tuberculosis was 37.59% (n=106). Of the 282 subjects, 9 (3.19%) had suspected symptoms, and 8 (2.92%) had abnormal chest films among 274 subjects who underwent chest X-ray. Among 106 subjects who had performed bacteriological examination of sputum Mycobacterium tuberculosis, 4 (3.77%) were positive in etiology, and all of them were second generation MDR-PTB, with a incidence rate of 1.42%. In the second generation cases, 3 cases had the same drug resistance phenotype as the indicator case, and 1 case was different. The 24 locus MIRU-VNTR genotyping of 6 strains from 3 families showed that the 24 loci of MIRU genotyping of 2 families were identical, and only 1 locus of 1 family was different. DTM-PCR genotyping showed that all 6 strains were Beijing strains. Conclusion: Close family contacts of MDR-PTB patients are at risk of infection. The incidence rate of second generation MDR-PTB in families is higher than that of the general population. Therefore, publicity, education, screening and follow-up should be coducted for close family contacts to reduce the spread of MDR-PTB within families.

Awareness of core knowledge of tuberculosis prevention and treatment among adolescents in Fujian Province and its impact on the risk of delayed medical treatment

Chen Kun, Lin Shufang, Dai Zhisong, Chen Daiquan, Chen Jiangfen

Chinese Journal of Antituberculosis. 2023, 45(2):  200-207.  doi:10.19982/j.issn.1000-6621.20220305

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Objective: To explore the awareness of core knowledge of tuberculosis prevention and treatment among adolescents in Fujian Province, and its impact on the risk of patient delay. Methods: Stratified random cluster sampling method was used, 8624 students from 38 schools were selected in Xiamen, Zhangzhou, Quanzhou, Sanming, Putian, Nanping, Longyan, Ningde, and Pingtan in Fujian Province from October to December, 2021. The questionnaire was confirmed according to Technical Guide for Tuberculosis Prevention and Control in China and experts’ discussion, involved core knowledge of tuberculosis prevention and treatment and patient-delay risk. A total of 8624 questionnaires were distributed, of which 8557 were valid, and the efficiency was 99.22%. The awareness rate and score of core prevention knowledge of tuberculosis, risk of patient delay were collected and the influencing factors of the patient-delay risk was analyzed using logistic regression. Results: Among 8557 subjects, the total awareness rate of core knowledge of tuberculosis prevention and treatment was 77.94% (46684/59899), the awareness rate of pulmonary tuberculosis is a chronic infectious disease was the highest (89.55% (7663/8557)), and the awareness rate of have suspected tuberculosis symptoms or confirmed tuberculosis should actively report and take classes without illness was the lowest (65.57% (5611/8557)). About 533 (6.23%) subjects who had risk of patient delay chose more than 14 days when asked about how long it would take to see a doctor if coughing, sweating, fever, or weight loss occurred. The score of core knowledge of tuberculosis prevention and treatment (M(Q₁,Q₃)) of all subjects was 6 (5,6), the score of subjects who were at risk of patient delay was 6 (4,6), which was statistically lower that of those who without patient-delay risk (6 (5,6), Z=5.583, P<0.001). Multivariate logistic regression analysis showed that senior high school students were 1.663 times more likely to have patient-delay risk than junior high school students (OR=1.663, 95%CI:1.039-2.704), students who did not know that pulmonary tuberculosis is a chronic infectious disease, suspected tuberculosis should go to designated hospitals, or tuberculosis is mostly curable were 1.702 times (OR=1.702, 95%CI:1.328-2.161), 1.514 times (OR=1.514, 95%CI:1.251-1.827), and 1.405 times (OR=1.405, 95%CI:1.167-1.688) more likely to have patients delay risk than who did know that, respectively. Conclusion: The awareness of core knowledge of tuberculosis prevention and treatment among adolescents in Fujian Province was good, but still need to be further improved. The awareness of core knowledge of tuberculosis prevention and treatment among those who at risk of patient delay is poor. Strengthening education on tuberculosis prevention and treatment knowledge among adolescents, especially senior high school students, improving the awareness of tuberculosis, and guiding students with suspected symptoms to go to designated hospitals could help reduce the risk of patient delay.

Review Articles

Development and application of CRISPR assisted genome editing technology in Mycobacterium tuberculosis

Qu Yunmo, Ding Xinyuan, Yan Meiyi, Guo Xiaopeng, Sun Yicheng

Chinese Journal of Antituberculosis. 2023, 45(2):  208-214.  doi:10.19982/j.issn.1000-6621.20220481

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Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains a public health threat. To address this challenge, development of new anti-TB vaccines and drugs is urgent, which requires a more comprehensive understanding of gene function of MTB. CRISPR-Cas assisted genome editing has been widely used in prokaryotes and eukaryotes, whereas it was developed and applied in MTB until recently. Here, we reviewed recent advances in the development and the application of CRISPR assisted genome editing in MTB. This review particularly focused on the application of genome-wide CRISPR knockout and CRISPRi libraries for screening the genetic and chemical-genetic interaction profiling in MTB, aiming to deepen the understanding of gene editing in MTB and promote the basic research of MTB.