1 Application of ARIMA model in predicting the incidence of tuberculosis in Tianjin City based on Python language

ZHANG Xiao-hui , YAO Ting-ting , CHEN Yang , ZHANG Tian-tian , MA Jun

2020, 19(7):634-642. DOI: 10.12138/j.issn.1671-9638.20205807

[Abstract](103) [HTML](227) [PDF 1.91 K](264)

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Objective To evaluate feasibility of autoregressive integrated moving average (ARIMA) model in predicting the incidence of tuberculosis (TB). Methods Using statsmodels module-based Python language, incidence of TB in Tianjin City from January 2004 to December 2015 was as training set, the optimal seasonal ARIMA (SARIMA) model was established, data from January to December 2016 were used to evaluate the efficacy of SARIMA model, and monthly incidence of TB in Tianjin City from January 2017 to December 2019 was predicted. Results Epidemiological results showed that monthly incidence of TB in Tianjin showed a overall downward trend from January 2004 to December 2015. There was a of peak disease incidence in 2005-2008, which dropped sharply after 2009 and then stabilized. From January 2017 to December 2019, monthly incidence of TB in Tianjin City declined steadily compared with previous years. The established optimal model was SARIMA(1,1,1)×(3,1,1)₁₂, residual BOX-Ljung statistic of the model was P=0.493, which indicated that the residual was a white noise sequence and the model fitted well. The actual value of predicted results was within 95% confidence interval of predicted value. Conclusion SARIMA (1,1,1)×(3,1,1)₁₂ model can accurately predict the monthly incidence of tuberculosis in Tianjin City.

2 Diagnostic value of fever, blood sodium combined with neutrophil percen-tage in tuberculous meningitis secondary to pulmonary tuberculosis

ZHU Wen-fang , ZHAO Hui , ZHANG Yi-wen

2020, 19(7):630-633. DOI: 10.12138/j.issn.1671-9638.20205768

[Abstract](133) [HTML](177) [PDF 834.00 Byte](254)

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Objective To explore the diagnostic value of fever, blood sodium combined with neutrophil prcentage in tuberculous meningitis (TBM) secondary to pulmonary tuberculosis(PTB). Methods Clinical data of PTB patients who were admitted in a hospital from October 2015 to October 2018 were collected, 146 patients with TBM secondary to PTB were selected as study group, 584 patients of PTB patients without secondary TBM were as control group according to the proportion of 1:4 of admission time, diagnostic efficiency of blood sodium, neutrophil percentage, clinical fever symptom and their combination in TBM secondary to PTB were compared, area under the curve (AUC) was calculated, and critical point was determined. Results The critical points of blood sodium and neutrophil prcentage for the diagnosis of TBM secondary to PTB were 135.30mmol/L and 73.40% respectively. The AUC (95% CI) of fever, blood sodium, neutrophil percentage and their combination in diagnosis for TBM secondary to PTB were 0.732 (0.688-0.776), 0.768 (0.719-0.818), 0.727 (0.679-0.776) and 0.845 (0.807-0.882) respectively, with statistical significance (all P<0.05); sensitivity were 80.82%, 56.85%, 65.07% and 63.70% respectively, specificity were 65.58%, 87.50%, 73.46% and 89.38% respectively, there was no significant difference in AUC among the three, diagnostic efficacy of three combination was higher. Conclusion Fever, blood sodium<135.30 mmol/L or neutrophil percentage>73.40% have diagnostic significance for TBM secondary to PTB, there was no difference among the three, but the combination of the three has higher diagnostic value for TBM secondary to PTB.

3 Drug resistance of Mycobacterium tuberculosis and risk factors of multidrug-resistant tuberculosis in patients with pulmonary tuberculosis

YU Hai-juan , ZHAO Mei , WANG Jia-yue , FU Ting

2020, 19(1):58-62. DOI: 10.12138/j.issn.1671-9638.20205260

[Abstract](162) [HTML](233) [PDF 817.00 Byte](263)

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Objective To clarify the drug resistance of patients with pulmonary tuberculosis, explore the risk factors for multidrug-resistant tuberculosis(MDR-TB), and provide basis for the prevention and treatment of MDR-TB. Methods 468 patients with pulmonary tuberculosis were collected, including 365 newly treated patients and 103 retreated patients. Susceptibility of Mycobacterium tuberculosis to antituberculous drugs was detected by proportion method. Univariate analysis and multivariate logistic regression analysis were adopted to analyze the risk factors for MDR-TB. Results The overall drug resistance rate, multidrug resistance rate and extensive drug resis-tance rate of 468 patients were 25.85%, 11.97%, and 3.21%, respectively. The overall drug resistance rate, multi-drug resistance rate and extensive drug resistance rate in retreated patients were all significantly higher than those in newly treated patients (49.51% vs 19.18%; 34.95% vs 5.48%; 10.68% vs 1.10%, respectively, all P<0.05). The overall drug resistance from high to low was as follows:isoniazide(INH)>rifampicin(RFP)> oxfloxacin(OFX)>ethambutol (EMB)> streptomycin (SM)>kanamycin (KM). Univariate and multivariate logistic regression analysis showed that living in rural areas (OR=2.316,95% CI:1.604-5.118), retreatment (OR=6.150,95% CI:4.728-13.824), tuberculosis cavity (OR=3.219, 95% CI:2.405-8.627), treatment interruption (OR=5.826,95% CI:4.610-12.507) and initial treatment without combined medication (OR=2.508,95% CI:1.813-5.646) were risk factors for the occurrence of MDR-TB. Conclusion Drug resistance rate of pulmonary tuberculosis patients is high, and there are multiple risk factors affecting the occurrence of MDR-TB, active intervention mea-sures should be taken to control the occurrence of MDR-TB.

4 Prediction of pulmonary tuberculosis incidence in Zhejiang Province from 2011 to 2021: based on trinity model and trinity forecasting method

Run-ping LOU , Yi-fei PAN , Di-nan WANG , Yun-xin ZHANG

2024, 23(7):806-811. DOI: 10.12138/j.issn.1671-9638.20245245

[Abstract](62) [HTML](634) [PDF 994.75 K](574)

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Objective To study the application of the trinity model and trinity forecasting method in predicting the incidence trend of pulmonary tuberculosis (PTB). Methods By applying the monthly PTB incidence data in Zhejiang Province from 2011 to 2021, a prediction model was constructed based on the trinity model and trinity forecasting method. Predictive performance of the model was evaluated. Results The mean relative prediction errors of model 1 and model 2 based on trinity model and trinity forecasting method were 7.94% and 8.43%, respectively. The mean relative prediction error obtained by adopting autoregressive integrated moving average (ARIMA) model was 8.87%, and the above mean relative prediction error were all in the range of 7.9%-8.9%, which presented an excellent performance of the forecasting model. Conclusion The trinity model is an excellent time series forecasting model, and the trinity forecasting method is an excellent time series forecasting method, with high application value.

5 Spatial-temporal distribution characteristics and influencing factors of incidences of tuberculosis in Chinese mainland, 2017-2022

Jie XIONG , Hui-guo ZHANG , Xi-jian HU , Sen-lu WANG

2024, 23(7):812-818. DOI: 10.12138/j.issn.1671-9638.20246033

[Abstract](84) [HTML](622) [PDF 1.25 M](614)

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Objective To analyze the spatial-temporal distribution characteristics and influencing factors of the incidence of tuberculosis (TB) in Chinese mainland, and provide scientific basis for relevant departments to formulate policies and guidelines. Methods TB incidence in Chinese mainland from 2017 to 2022 was as the research object, and data of relevant influencing factors were collected. The spatial autocorrelation analysis method was adopted to establish a spatial lag model to explore the spatial-temporal distribution characteristics of TB incidence, and the important influencing factors of TB incidence were screened. Results From 2017 to 2022, TB incidence reported in 31 provinces and cities in Chinese mainland were 60.53/100 000, 59.27/100 000, 55.55/100 000, 47.76/100 000, 45.37/100 000 and 39.76/100 000, respectively, showing a yearly downward trend. Global Moran's Ⅰ analysis showed that TB incidence presented spatial-temporal aggregation. The spatial distribution map and the local indicators of spatial association (LISA) aggregation diagram analysis results for the incidence of reported TB showed a decreasing trend from west to east in TB incidence. In the spatial lag model, the coefficients of 6 insignificant factors shrank to 0, and 6 important factors were screened out: gross domestic product (GDP) per capita (coefficient -0.259), urban unemployment rate (coefficient -0.198), annual sunshine duration (coefficient -0.332), annual mean relative humidity (coefficient -0.433), annual mean NO₂ concentration (coefficient -0.263), and annual mean PM₁₀ concentration (coefficient -0.336). Conclusion From 2017 to 2022, TB incidences in Chinese mainland declined year by year, and presented spatial difference and spatial aggregation: high in the east, low in the west, and stable in the middle area. Social economy, climate and air pollution have strong effects on the incidence of TB. Relevant departments should pay more attention to the prevention and treatment of TB in the western region and take targeted preventive measures.

6 Preliminary study on the treatment of severe tuberculous meningitis with refractory hydrocephalus by modified extraventricular drainage

Dong-cheng XIE , Hong-wei CHEN , Sheng-jie WANG , Xiao-chuan GUO

2021(8):720-724. DOI: 10.12138/j.issn.1671-9638.20218138

[Abstract](102) [HTML](229) [PDF 865.16 K](205)

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Objective To explore the clinical effect of modified extraventricular drainage on severe tuberculous meningitis (TBM) and refractory hydrocephalus. Methods Clinical data of patients with severe TBM and refractory hydrocephalus in a hospital from 2013 to 2017 were analyzed, the modified extraventricular drainage was adopted, ventricular segment was punctured, then connected to the linear connector and abdominal segment shunt, pass through a subcutaneous incision in the abdomen, and continue to drain and purify the cerebrospinal fluid, after disease condition was stable, cerebrospinal fluid drainage device was removed or ventricular-abdominal shunt treatment was performed. The Evan's index, GCS score and GOS prognostic score of patients before and after treatment were compared. Results A total of 15 patients with severe TBM and refractory hydrocephalus were treated, aged from 19 to 64 years. Compared with before treatment, Evan's index and GCS score of patient after treatment were improved, differences were statistically significant (all P < 0.05). One case was removed extraventricular drainage tube after inflammation was controlled, and the other 14 cases underwent ventricular-abdominal shunt. According to the GOS classification at discharge, 13 cases (86.7%) recovered well (4-5 points), and 2 cases (13.3%) reco-vered poorly (3 points). Drainage time was 59-335 days, with an average of 173.3 days. There was no intracranial infection and shunt blockage complication during drainage. Patients were followed up for 2-5 years, with an ave-rage of 4.5 years, one case of ventricular segment of shunt tube was placed in the transparent septum space, which caused the ventricle to expand again, after fistulation through transparent septum and shunting again, it was cured, and the remaining cases were free of complications. Conclusion Modified extraventricular drainage can significantly improve the success rate of final shunt, especially for patients with severe TBM and refractory hydrocephalus after repeated treatment failure.

7 Susceptibility detection of multidrug-resistant Mycobacterium tuberculosis by broth microdilution method

Ye-teng ZHONG , Jie-ying WANG , Zhuo-lin CHEN , Yu-ni XU , Wen-hua QIU , Hua PEI

2024, 23(7):840-846. DOI: 10.12138/j.issn.1671-9638.20244901

[Abstract](46) [HTML](595) [PDF 999.48 K](574)

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Objective To evaluate the application effect of broth microdilution (BMD) method in susceptibility testing of multidrug-resistant Mycobacterium tuberculosis (MDR-MTB). Methods The Roche's proportion method and BMD method were adopted in drug susceptibility testing on 108 MDR-MTB strains and 11 non-MDR-MTB strains in Hainan Province. Whole genome sequencing (WGS) was performed on strains with inconsistent results by the above two methods. Results The average time to acquire drug susceptibility testing results by Roche's proportional method and BMD method were 28.0 and 8.5 days, respectively. Roche's proportional method showed higher resistance rates to isoniazid (INH), rifampicin (RFP), ethambutol (EMB), kanamycin (KM), and capreomycin (CPM) than BMD method (all P < 0.001). BMD method showed higher resistance rates to protionamide (PTO) and para-aminosalicylic acid (PAS) than Roche's proportional method (both P < 0.001). Taking Roche's proportional method as the gold standard, the sensitivity and specificity of BMD method for testing drug resistance were 50.00%-100% and 95.69%-100%, respectively. Except EMB (87.39%) and INH (94.96%), the consistency rates of the BMD method in testing drug resistance of other drugs were all ≥95.00%. The overall consistency rate between Roche's proportional method and WGS was 76.19% (32/42), while the consistency rate between BMD method and WGS was 23.81% (10/42), difference was statistically significant (χ²=23.048, P < 0.001). 34 MTB strains showed inconsistent results by two drug susceptibility testing methods. Among the 26 MTB strains that were resis-tant in Roche's proportion method but sensitive in BMD method, 22 strains (84.62%) had mutations in relevant resistance genes. Among the 11 MTB strains that were sensitive in Roche's proportion method but resistant in BMD method, 5 strains (45.45%) had mutations in relevant resistance genes. Conclusion BMD method is an accurate and rapid MDR-MTB susceptibility testing method, but further improvement and optimization are still needed. Drug resistance is closely related to mutations in relevant resistance genes.

8 Rifampicin resistance and its influencing factors in re-treated pulmonary tuberculosis patients in Chongqing City from 2018 to 2022

Rong-rong LEI , Jian CHEN , Lin SHI , Ya YU

2024, 23(7):847-851. DOI: 10.12138/j.issn.1671-9638.20244933

[Abstract](61) [HTML](626) [PDF 874.33 K](585)

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Objective To analyze the status and influencing factors of rifampicin resistance in re-treated pulmonary tuberculosis (PTB) patients registered in Chongqing City, and provide basis for the prevention and control of drug-resistant tuberculosis in this city. Methods Descriptive epidemiological method was adopted to analyze the status of rifampicin resistance in re-treated PTB patients registered in districts and counties of Chongqing City from 2018 to 2022. Chi-square test and binary logistic regression were used to analyze the influencing factors for the status of ri-fampicin resistance in re-treated PTB patients. Results The detection rate of rifampicin resistance in re-treated PTB patients in districts and counties of Chongqing City from 2018 to 2022 was 14.45% (558/3 862), presenting an overall downward trend (χ²_trend=22.739, P < 0.001). Univariate analysis showed that among re-treated PTB patients, the detection rate of rifampicin resistance was the highest among migrant population, residents in urban areas, workers, and migrant workers (all P < 0.05); rifampicin resistance decreased with the increase of age (P _trend < 0.001). Multivariate logistic regression analysis showed that the risk of rifampicin resistance gradually decreased with the increase of age; OR value decreased from 2.778 in the < 25 year old group to 1.654 in the ≥45 year old group (all P < 0.001). The risk factors for rifampicin resistance in re-treated PTB patients were migrant population, residents in urban areas, workers, and migrant workers, with statistically significant differences (all P < 0.05). Conclusion Although the detection rate of rifampicin resistance in re-treated PTB patients in Chongqing has been decreasing year by year, the situation is still severe, and special attention should be paid to the migrant population, young population, population in the main urban areas, and migrant workers.

Hai-nan WEN , Shou-jun XIE , Jun CHEN

2021(4):370-373. DOI: 10.12138/j.issn.1671-9638.20217376

[Abstract](88) [HTML](304) [PDF 997.28 K](256)

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10 Clinical significance of serum PTX3, IL-10, and HBP detection in the diagnosis of pulmonary tuberculosis

Wei HAN , Yan-jing PAN , Xiu-fang LI , Jian HUANG , Pan-pan GAO , Jun-wei CUI

2022(6):579-583. DOI: 10.12138/j.issn.1671-9638.20222103

[Abstract](63) [HTML](209) [PDF 945.15 K](168)

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Objective To analyze the clinical significance of serum pentraxin (PTX3), interleukin (IL-10), and heparin-binding protein (HBP) in the diagnosis of pulmonary tuberculosis (PTB). Methods 122 patients with PTB treated in a hospital from December 2018 to June 2021 were selected as the tuberculosis group, they were subdivided into cavity group and non-cavity group according to whether there was a pulmonary cavity; 113 patients who underwent physical examination in this hospital during the same period were selected as control group, and 109 patients with latent infection were selected as latent group. The expression levels of PTX3, IL-10, and HBP in different populations and with or without pulmonary cavity were compared; the expression levels of PTX3, IL-10, and HBP were compared between patients with and without cavity absorption after treatment; the expression levels of PTX3, IL-10, and HBP in patients with PTB after 1, 2 and 3 months treatment were compared, the value of PTX3, IL-10, and HBP in the diagnosis of PTB were analyzed. Results The expression levels of PTX3, IL-10, and HBP in tuberculosis group were all higher than those in latent infection group and control group, differences were all significant (all P < 0.05). The expression levels of PTX3, IL-10, and HBP in cavity group were all higher than those in non-cavity group, differences were all significant (all P < 0.001). After treatment, the expression levels of PTX3, IL-10, and HBP in the cavity absorption group were all lower than those in cavity non-absorption group (all P < 0.001). Levels of PTX3, IL-10, and HBP decreased gradually after treatment, levels of PTX3, IL-10, and HBP in patients with PTB at 3 months were all lower than those at 1 and 2 months after treatment (all P < 0.05). The area under the curve (AUC) of PTX3, IL-10, and HBP for the diagnosis of PTB were 0.756, 0.745 and 0.752 respectively, PTX3 was slightly higher than IL-10, and HBP, but there was no significant difference among the three (P > 0.05). Conclusion PTX3, IL-10, and HBP are highly expressed in patients with PTB, which is expected to become a reference indicator for the evaluation of disease condition of patients with PTB, and provide new ideas for clinical diagnosis and treatment.

11 Relationship between capreomycin resistance and related gene mutations in Mycobacterium tuberculosis in Guizhou from 2017 to 2020

Qiu-yang LI , Qiang-lin ZENG , Xiao-jv CHEN , Ling CHEN

2023(1):7-13. DOI: 10.12138/j.issn.1671-9638.20233193

[Abstract](82) [HTML](234) [PDF 915.50 K](189)

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Objective To detect the mutations of capreomycin (CM) resistance related genes of Mycobacterium tuberculosis (M.tb), explore the relationship between genotype and phenotype, and provide guidance for the clinical use of CM. Methods Sputum specimens of tuberculosis patients with positive acid-fast staining in a hospital from 2017 to 2020 were collected, from which M. tb strains were clinically isolated. Drug resistance phenotypes of the strains were identified through drug susceptibility testing (DST). DNA was extracted and underwent whole-genome sequencing (WGS) to detect mutations of CM-resistance-related genes tlyA, rrs, rpsL, eis, Rv0194 and Rv1258C. Relationship between CM and rifampicin (RIF) phenotypic resistance was explored. Results 123 M.tb strains were isolated, out of which 23 nonsynonymous mutation sites in 6 CM resistance-related genes were detected via WGS. DST showed that 52 strains were resistant to RIF and 4 strains were resistant to both CM and RIF. Nonsynonymous mutation sites (A1401G in rrs, A128G in rpsL, C3293T and T221C in Rv0194) were detected in CM-resis-tant strains. Correlation between CM and RIF resistance was statistically significant (P < 0.05). Conclusion CM resistance of M. tb may be related to the mutations of rrs gene A1401G, rpsL gene A128G and Rv0194 gene C3293T, and there may be cross resistance between CM and RIF, which can be used as a reference in formulating anti-tuberculosis treatment plan.

12 Seasonal characteristics, cycles, as well as long- and short-term predictions of pulmonary tuberculosis in China

Chao LIU , Liu-ming DU , Xin-rong NIE , Shao-jie FANG , Hai-liang NIE

2023(7):751-757. DOI: 10.12138/j.issn.1671-9638.20234107

[Abstract](123) [HTML](307) [PDF 1.13 M](252)

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Objective To analyze the seasonal characteristics and cycle of pulmonary tuberculosis (PTB) in China, make long- and short-term predictions, and provide basis for the formulation of prevention and control measures. Methods The seasonal characteristics of PTB occurrence in China were analyzed by the CensusX-13 seasonal adjustment method. The cycle of PTB occurrence was analyzed by Hodrick-Prescott (HP) filtering method. Long-term prediction was conducted by the linear regression model based on the decomposed long-term trend, and the short-term prediction was made by Holt-Winter seasonal exponential smoothing model. Results The occurrence of PTB in China from 2010 to 2021 exhibited clear seasonal characteristics, with a concentration of reported cases in the se- cond quarter of each year. The peak period for reported cases was from March to July annually. There were approximately 6 cycles, with an average length of 21 months.Overall, there was a declining long-term trend. The short- and long-term prediction results were good. Conclusion Taking into consideration the seasonal characteristics and cycle of PTB, combined with the pathological features of PTB, effective preventive and control measures should be taken before the peak period of the disease.

13 Epidemiological characteristics of pulmonary tuberculosis epidemic in schools in Daxing District, Beijing, 2016-2021

Hong-yan CUI , Wen-jun HOU , Fei-fei TIAN , Shi-yu ZHANG , Peng-cheng ZHANG , Yao-wen ZHANG , Yan-qing GAO

2023(7):782-787. DOI: 10.12138/j.issn.1671-9638.20234011

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Objective To analyze the epidemiological characteristics of pulmonary tuberculosis (PTB) in schools in Daxing District, Beijing, from 2016 to 2021, and provide scientific evidence for PTB prevention and control in schools within this district. Methods The school-related PTB cases in Daxing District of Beijing were co-llected through the "China Disease Prevention and Control Information System-Surveillance Report Management" and the monthly report table of PTB epidemic surveillance in schools of Daxing District of Beijing from 2016 to 2021. The epidemiological characteristics were analyzed. Results A total of 446 school-related cases were reported, mostly were student cases (n=386, 86.55%). The number of reported cases decreased from 192 in 2016 to 37 in 2021, and both the number of reported cases and the proportion of student cases showed a declining trend. The male to female ratio was 2.72 ∶1, and the incidence peak was mainly distributed in April-May or September-October. The cases in low age schools (kindergartens, primary schools) were mainly teaching staff, accounting for 87.50% and 54.55%, respectively. The cases were mainly distributed in vocational schools and universities, accounting for 78.48%. The proportion of patients with negative pathogenic results was ralatively high (63.90%), but the number of patients with positive pathogenic results increased significantly after 2018. A total of three PTB clustered epidemics and one public health emergency event were reported, with 181 cases involved. Conclusion PTB epidemic in schools in Da-xing District decreased steadily from 2016 to 2021. Teaching staff were the main cases in kindergartens and primary schools, while students in vocational schools and universities were the major population for PTB prevention and control in schools. It is necessary to improve the ability of active monitoring, detect the epidemic as early as possible, so as to effectively prevent the spread of tuberculosis epidemic in schools.

14 Research progress in transmission dynamics models of tuberculosis

Jun-jie MAO , Xun ZHUANG

2023(7):864-868. DOI: 10.12138/j.issn.1671-9638.20233381

[Abstract](79) [HTML](236) [PDF 874.33 K](223)

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Tuberculosis (TB) imposes a significant disease burden globally, emphasizing the importance of TB prevention and control. In recent years, COVID-19 pandemic has severely disrupted the progress of global TB prevention and control programs, raising concerns about TB prevention and control. Transmission dynamics models have played a crucial role in TB research by providing insights into the patterns and dynamics of TB transmission from both macro and micro perspectives, and evaluating the effectiveness of various intervention measures. This review introduces five TB transmission dynamics models: the compartmental model, the metapopulation model, the agent-based model, the network model, and the phylodynamics model, providing reference and support for the prevention, control and further research of TB.

15 Epidemic characteristics and changing trend of pulmonary tuberculosis in children in Guangzhou City from 2006 to 2020

Zhi-qiang DONG , Wei LIU , Wen-sui HU , Jian-rong HOU , Li-li SUN , Xue-ji WU , Yuan LIU

2021(9):801-806. DOI: 10.12138/j.issn.1671-9638.20218422

[Abstract](126) [HTML](194) [PDF 1.04 M](258)

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Objective To analyze the epidemic characteristics and changing trend of pulmonary tuberculosis(PTB) in children in Guangzhou City, and provide reference for formulating scientific prevention and control measures. Methods Data of reported PTB occurrence among children aged 0-14 years in Guangzhou City from 2006 to 2020 were collected, spatial, temporal and population distribution were analyzed, the Joinpoint regression model was used to analyze the trend of disease incidence. Results A total of 1 397 PTB children aged 0-14 years were reported, accounting for 0.66% of the reported cases of PTB in the whole population. The reported incidence dropped from 7.31/100 000 in 2006 to 2.90/100 000 in 2020, and presented overall declining trend, with an average annual decline of 3.90% (AAPC=-3.90, 95%CI: -5.64﹣-2.13), the average annual decline rate of boys (AAPC=-4.74, 95%CI: -6.77﹣-2.66, P < 0.01) was faster than that of girls (AAPC=-2.86, 95%CI: -4.78﹣-0.91, P < 0.01); reported incidence of PTB in children in urban areas averagely decreased by 4.14% (AAPC=-4.14, 95%CI: -5.99﹣-2.24, P < 0.01) annually, there was no significant change in incidence in children in rural areas (β=-0.02, t=1.00, P=0.34), but the overall reported incidence was slightly lower than that of urban children; incidence of PTB in children aged 0-2 and 10-14 was relatively higher, except for the 10-14 year old group without significant change in the reported incidence of PTB, children in other age groups showed a downward trend. Conclusion Reported incidence of PTB in children aged 0-14 years in Guangzhou City generally showed a downward trend, decline trend for children in rural area and aged 10-14 years is not obvious, it is necessary to focus on strengthening the prevention and control of PTB for these children.

16 Bioinformatics analysis and prokaryotic expression of the protein Rv3529c of Mycobacterium tuberculosis

Rui-feng CHEN , Xuan WANG , Feng-xi MA , Xiang-fang LI , Shou-peng DING , Li-xian WU

2023(6):621-628. DOI: 10.12138/j.issn.1671-9638.20233642

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Objective To predict the structure and function of the protein encoded by Mycobacterium tuberculosis gene Rv3529c through bioinformatics software and perform prokaryotic expression of the protein. Methods The secondary and tertiary structure, physicochemical properties, hydrophobicity, signal peptide, transmembrane domain, subcellular localization and immune epitopes of Rv3529c-encoded protein were analyzed and predicted through bioinformatics prediction software such as The UniproKB database, PredictProtein service, AlphaFold system, SWISS-MODEL service, ProtParam protein analysis tool, ProtScale, DeepTMHMM service, SignalP-5.0 service, ProtCompB method, IEDB database and STRING database. Expression plasmid vector pET-32a-Rv3529c was constructed and performed prokaryotic expression by molecular cloning technique. Amino acid sequences were compared by the Blast tool of UniprotKB database, and evolutionary tree was constructed by MEGA 11 software for phylogenetic analysis. Interactions among proteins were analyzed with STRING database. Results Gene Rv3529c was 1 155bp in length and encoded 384 amino acids. Gene Rv3529c encoded a protein with a molecular weight of 43.35 kDa and an isoelectric point of 6.04, and its secondary structure was mainly α-helixi, which was a stable hydrophilic protein without transmembrane domain and signal peptide. It was predicted that its subcellular location was in cytoplasm or cell membrane, with multiple antigen-antibody epitopes, and interacted with various proteins. The protein Rv3529c with high concentration and purity was obtained after cloning, expression, identification and purification. Conclusion The protein Rv3529c of Mycobacterium tuberculosis is successfully cloned, expressed and purified, and its structure and function is tentatively predicted.

17 Drug resistance of Mycobacterium tuberculosis in five monitoring sites of Henan Province, 2013-2018

Shao-hua WANG , Rui-qin CHEN , Wen-jing CHANG , Ru-yue SHU , Xiao-guang MA , Dan-wei ZHENG , Yan-kun ZHU , Jie SHI , Guo-qing SUN , Ding-yong SUN , Yi-bin HAO

2023(6):629-636. DOI: 10.12138/j.issn.1671-9638.20233646

[Abstract](96) [HTML](196) [PDF 889.84 K](237)

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Objective To understand the drug resistance of Mycobacterium tuberculosis (M. tuberculosis) in five drug resistance monitoring sites in Henan Province, and provide reference for formulating the control strategies of tuberculosis epidemic. Methods The strains and clinical information of 1 716 tuberculosis patients were collected from five drug resistance monitoring sites in Henan Province in 2013-2018. M. tuberculosis was tested for the sensitivity to nine anti-tuberculosis drugs by proportional method, changes in their drug resistance was analyzed. Results The total drug resistance rate and multidrug resistance (MDR) rate of tuberculosis patients were 24.07% (413/1 716) and 3.73% (64/1 716) respectively. Drug resistance rates of the first-line anti-tuberculosis drugs from high to low were as follows: streptomycin (SM) 13.34% (n=229), isoniazid (INH) 10.08% (n=173), rifampicin (RIF) 5.19% (n=89), and ethambutol (EMB) 4.49% (n=77). Drug resistance rates of the second-line anti-tuberculosis drugs from high to low were as follows: ofloxacin (OFX) 3.15% (n=54), kanamycin (KAM) 2.51% (n=43), capreomycin (CPM) 2.51% (n=43), p-aminosalicylic acid (PAS) 1.98% (n=34), and prothionamide (PTO) 1.46% (n=25). Drug resistance profile showed that 413 strains were distributed among 68 different drug resistance types, mono-drug resistance rate of SM, poly-drug resistance of INH+SM, as well as MDR rates of INH+RIF and INH+RIF+SM were higher. The drug resistance rates and MDR rates of initial treated patients were 20.13% (216/1 073) and 2.80% (30/1 073), respectively. Drug resistance rates and MDR rates of retreated patients were 30.64% (197/643) and 5.29% (34/643), respectively. Drug resistance rates and MDR rates of retreated patients were both higher than those of initial treated patients (both P < 0.05). Patients aged 41 to 60 years had the highest drug resistance rate of 29.25%, and patients aged 2 to 20 years had the lowest drug resistance rate of 13.56%. There was statistically significant difference in drug resistance rates among different age groups (P < 0.05). Drug resistance trend analysis showed that only the MDR rate increased year by year in 2013-2018 (P < 0.05). Conclusion Drug resistance of Mycobacterium tuberculosis in five drug resistance monitoring sites in Henan Province is still serious, drug resistance profile showed that the types of drug resistance were diverse and complicated, drug resistance rates of patients aged 41-60 years and retreated patients are high, and MDR rate showed a rising trend. Therefore, it is necessary to standardize treatment, carry out screening on drug resistance, reduce the occurrence of drug-resistant patients, strengthen the treatment and management of MDR patients to prevent transmission.

18 Three cases of chronic obstructive pulmonary disease and inhaled glucocorticoid-related pulmonary tuberculosis

Ruo-yan XIONG , Yan CHEN , Zhi-qi ZHAO , Huan-huan LU , Hui-hui ZENG

2022(10):1026-1030. DOI: 10.12138/j.issn.1671-9638.20222559

[Abstract](76) [HTML](210) [PDF 914.16 K](164)

Abstract:
Inhaled glucocorticoids (ICS) is widely used in the treatment of patients with chronic obstructive pulmonary disease (COPD), but long-term use of ICS is prone to various infections due to local immunosuppression. Three patients with COPD and pulmonary tuberculosis were admitted in department of respiratory and critical care medicine of a hospital in 2015, 2019 and 2021 respectively. According to medical history and relevant examination, pulmonary tuberculosis might be related to ICS. This article intends to analyze the diagnosis and treatment process of 3 cases of ICS-related pulmonary tuberculosis in this hospital, combined with existing research to discuss the diagnosis and treatment strategy of patients with COPD and ICS-related pulmonary tuberculosis.

19 Comparison of recombinant Mycobacterium tuberculosis fusion protein skin test and tuberculin skin test for screening latent tuberculosis infection in school students

Qian SU , Qing-ya WANG , Ting ZHANG , Ying LIU

2023(5):547-551. DOI: 10.12138/j.issn.1671-9638.20233724

[Abstract](99) [HTML](460) [PDF 981.60 K](238)

Abstract:
Objective To compare the effectiveness and cost-effectiveness of the recombinant Mycobacterium tuberculosis fusion protein skin test (EC) and the tuberculin skin test (TST) for detecting latent tuberculosis infection (LTBI), and to explore a more suitable screening method for LTBI in school students. Methods 283 high school freshmen enrolled in September 2021 in Chongqing City were divided into EC group (n=138) and TST group (n=145) by cluster random sampling. Each student was intracutaneously injected with 0.1 mL of either EC or TST into the left forearm, and skin reactions were observed 72 hours after injection. Before skin test, venous blood of all 283 students was collected for in vitro interferon-γ release assay (IGRA). Taking the IGRA test result as the standard, the sensitivity, specificity, misdiagnosis rate, and consistency between EC/TST and IGRA were calculated respectively. Cost-effectiveness of the three methods were compared. Results The sensitivity, specificity, misdiagnosis rate, and consistency rate of EC were 54.55%, 93.70%, 45.45%, and 90.58% respectively, while those of TST were 61.11%, 81.10%, 38.89%, and 78.62% respectively. The detection cost for detecting one tuberculosis infection case using TST, EC, and IGRA were 124.29 Yuan, 492.86 Yuan and 4 879.31 Yuan, respectively. Conclusion The consistency between EC and IGRA is good, and the specificity, consistency and cost-effectiveness of EC are higher than TST. EC is also easy to perform, making it a potential new screening method for LTBI among school students.

20 Survey on health care workers' awareness of tuberculosis in medical institutions in Gansu Province

Jin-ping FAN , Feng-jing HU , Hao-jun ZHANG , Yu-juan FENG , Lei WANG , Jun-ling WANG , Xia LIN

2023(5):563-568. DOI: 10.12138/j.issn.1671-9638.20233625

[Abstract](99) [HTML](289) [PDF 917.66 K](214)

Abstract:
Objective To understand the cognition on tuberculosis (TB) and its influencing factors among health care workers (HCWs) in medical institutions (MIs) in Gansu Province, and to provide a basis for improving HCWs' awareness on tuberculosis prevention and control. Methods Questionnaire about HCWs' cognition status on TB in MIs in Gansu Province was designed. HCWs' cognition status on TB in MIs in Gansu Province was surveyed through "Questionnaire Star", and influencing factors for HCWs' cognition on TB was analyzed statistically. Results A total of 60 636 valid questionnaires were collected. Among the surveyed HCWs, women accounted for 78.89%. 39.64% HCWs were aged 30-39 years. Nursing staff accounted for 53.05%. 57 440 (94.73%) HCWs got qualified score on cognition on TB (total score ≥14 points), 3 196 was unqualified (total score ≤13 points), accounting for 5.27%. Univariate analysis results showed that there were statistically significant differences in HCWs' cognitive qualification rate on TB in terms of hospital level and type, whether there were infectious disease department, gender, age, nationality, educational background, professionaity, professional title, years of work experience, and the number of times participating in occupational protection training (all P < 0.05). Conclusion There are multiple factors that influence HCWs' cognition on TB in Gansu Province. HCWs' cognition on TB can be improved by increasing the frequency of TB prevention and control knowledge training, improving HCWs' academic qualification, and strengthening the learning of relevant professional knowledge.

21 Mutation characterization of isoniazid resistance genes of Mycobacterium tuberculosis in Guangxi region

Yi-xiang QIN , Ru-shu LAN , Hui-fang QIN , Jing YE , Xiao-ling QIN , Li GAN , Gang LIU , Ruo-lan XU , Dan LUO

2023(3):280-286. DOI: 10.12138/j.issn.1671-9638.20233443

[Abstract](69) [HTML](226) [PDF 927.81 K](230)

Abstract:
Objective To analyze the mutation characteristics of isoniazid (INH) resistance gene of Mycobacterium tuberculosis (MTB)in Guangxi region, and provide basis for molecular diagnosis of drug-resistant tuberculosis. Methods 122 INH-resistant strains and 530 susceptible strains were obtained from the MTB strain library collected from 30 tuberculosis drug resistance monitoring points in Guangxi region, and underwent whole genome sequencing. Results Among 652 strains of MTB complex group, 127 (19.48%) had INH resistance gene mutations, including katG (15.64%, n=102), fabG1 (1.69%, n=11), ahpC (1.07%, n=7), kasA (0.61%, n=4) and inhA (0.46%, n=3) gene mutations. The coincidence rate of INH resistance phenotype and gene mutation was 90.03%, and the coincidence rate of INH resistance detected by proportional method and gene mutation detected by gene sequencing was not high (Kappa=0.677). There are 19 types of mutations, with single locus mutation accounting for 96.85% and combined mutation accounting for 3.15%. The locus with the highest mutation rate was katG315 (71.65%). The proportion of base change in the form of AGC-ACC was the highest (12.13%). The proportion of mutations in katG, ahpC and kasA genes in INH-resistant strains was higher than that in susceptible strains (all P < 0.05). There was no significant difference in the proportion of mutations in inhA and fabG1 genes between INH-resistant strains and susceptible strains (all P>0.05). Beijing strains and non-Beijing strains had the highest mutation rates of katG315, which were 18.75% (81/432) and 4.55% (10/220) respectively. Difference in distribution of mutation loci of katG gene in two genotypes of strains was statistically significant(χ²=16.253, P=0.039). Conclusion The mutation of INH resistance gene in Guangxi region is mainly at katG315 locus, and the INH resistance phenotype and gene mutation are not consistent. Mutations in katG, ahpC and kasA genes are associated with INH phenotypic resistance. Beijing genotype is associated with the mutation of katG gene.

22 Advances in the application of whole genome sequencing technique in molecular epidemiology of tuberculosis

Xi LING , Lu WANG , Ze-wen ZHANG , Li-rong LIU , Jiang-hong DAI , Fan-ka LI

2022(4):399-403. DOI: 10.12138/j.issn.1671-9638.20221354

[Abstract](93) [HTML](352) [PDF 756.05 K](222)

Abstract:
Tuberculosis has brought serious disease burden to the world, prevention and control of tuberculosis is of great significance. Molecular epidemiology of tuberculosis integrates the technique of Mycobacterium tuberculosis typing and epidemiological data, and plays an extremely important role in the study of the spread and epidemic characteristics of tuberculosis. Whole genome sequencing (WGS) can construct complete DNA sequences of the genome of an organism, which has the advantages of high resolution, high throughput and accurate results, it is very attractive and has great development potential in the study of molecular epidemiology of tuberculosis. This paper compares WGS technique with the traditional Mycobacterium tuberculosis typing technique, points advantages of WGS, introduces technical route and progress of WGS, reviews its application achievements in epidemic tracing, drug resistance research and mixed infection diagnosis, so as to provide reference and support for prevention, control and research of tuberculosis.

23 Identification and VNTR typing of Beijing genotype strains of Mycobacterium tuberculosis in Yichang area

Dan LI , Xiao-hong HU , Xin-juan XU , De-bing DU , Wen-yan WU , De-cheng WANG , Qian ZHUANG , Zhi-jie CHEN , Zhu JIN

2022(3):232-238. DOI: 10.12138/j.issn.1671-9638.20221895

[Abstract](72) [HTML](213) [PDF 1.08 M](190)

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Objective To study the polymorphism and epidemic characteristics of the Beijing genotype strains of Mycobacterium tuberculosis (Mtb) in Yichang area, reveal the molecular epidemiological characteristics of tuberculosis in this area, and provide scientific evidence for the prevention and treatment of tuberculosis. Methods 298 strains of Mtb with complete case information from January 2018 to December 2019 were selected for the identification of human Mtb, Beijing genotype strains were identified by multiplex polymerase chain reaction (DTM-PCR) which amplifying RD105 deletion fragment; polymorphism of Beijing genotype strains was analyzed by optimized 9-locus variable-number tandem repeat technique. Results Among 298 strains of Mtb, 260 strains were human Mtb, DTM-PCR identification found that 140 strains (53.85%) were Beijing genotype and 120 strains (46.15%) were non-Beijing genotype. Drug resistance rate of Beijing genotype strains was higher than that of non-Beijing genotype strains (32.14% vs 10.83%, P < 0.05). The resolution of VNTR-9 locus to Beijing genotype strains was 0.998 5 and the clustering rate was 12.15%. Conclusion Beijing genotype strains showed a high prevalence trend in Yichang area, drug resistance rate of Beijing genotype strains is higher. VNTR-9 genotyping method used to identify Beijing genotype strains of Mtb in this area can accurately reflect the molecular epidemiological characteristics of Mtb in Yichang.

24 Screening of tuberculosis among freshmen in 156 schools in Baoding City

Yong-qiang ZHANG , Huan-huan YANG , Ya-ya WANG , Jing-ru TIAN , Yang LI , Xiu-zheng WANG

2024, 23(1):95-99. DOI: 10.12138/j.issn.1671-9638.20244477

[Abstract](49) [HTML](242) [PDF 858.87 K](167)

Abstract:
Objective To investigate the screening and prevalence of tuberculosis among freshmen in different schools in Baoding City, and provide reference for tuberculosis control in schools. Methods Screening data of tuberculosis and tuberculin test (PPD) of freshmen from 156 schools in different regions of Baoding City from September 2021 to March 2022 were collected. PPD screening results of students from different regions and different school stages were analyzed and compared. Results A total of 68 177 freshmen from 156 schools were investigated for suspected symptoms and close contact history of pulmonary tuberculosis. PPD screening was conducted on 63 939 students. 13 821 students were PPD positive, with a positive rate of 21.62%. 3 083 students were strongly positive, with a strong positive rate of 4.82%. 15 cases of tuberculosis were found, and the reported incidence was 23.46/100 000. PPD positive rate and strong positive rate as well as incidence of tuberculosis in students in different school stages presented statistically significant differences (all P < 0.01). Positive rate and strong positive rate in students in different school stages showed upward trends (all P < 0.01). PPD positive rate and strong positive rate of students from schools in plain and mountainous areas presented statistically significant differences ([22.28% vs 17.89%]; [4.85% vs 3.62%], both P < 0.01). PPD positive rate and strong positive rate between students from boarding junior school and non-boarding junior school were significantly different, respectively ([23.94% vs 21.60%]; [5.07% vs 3.56%], both P < 0.01). Conclusion It is necessary to strengthen tuberculosis screening and health education for freshmen, especially those from boarding schools in plain areas, screening latent Mycobacterium tuberculosis infection as early as possible, take corresponding measures to prevent and control the spread of tuberculosis, and reduce the risk of tuberculosis.

25 Interim efficacy of bedaquiline-containing regimen in treatment of MDR/XDR-TB: a prospective cohort study

Yi PEI , Jian-cai CHEN , Wen-jun FENG , Xiao-yun YANG , Yun-hui HUANG , Fang HE , Yu-meng HU , Li-ping LEI , Li SHI

2021(12):1102-1108. DOI: 10.12138/j.issn.1671-9638.20211484

[Abstract](70) [HTML](274) [PDF 942.03 K](205)

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Objective To evaluate the efficacy and safety of bedaquiline (BDQ-containing) regimen for the treatment of multidrug-resistant tuberculosis (MDR-TB)/extensively drug-resistant tuberculosis (XDR-TB), and provide clinical data for the use of BDQ in drug-resistant TB patients in China. Methods Clinical data of tuberculosis patients receiving BDQ-containing regimen in a hospital from March 2018 to September 2019 were collected, efficacy and adverse reactions during treatment were analyzed. Results Sixty-nine patients were enrolled, 10 (14.5%) of whom had XDR-TB, 63 cases (91.3%) completed 24 weeks of BDQ-containing treatment, two patients died of cardiac arrest and respiratory failure during treatment, three were transferred, one was lost to follow-up, 39 patients (56.5%) reported 108 times of adverse events, most adverse events were classified as grade 1 or grade 2 (75 times, 69.4%), and the most common grade 3 and above adverse events were QT interval prolongation. 29 cases (46.0%) were positive in sputum culture at baseline, the negative conversion rates of sputum culture at week 8, 12 and 24 were 93.1% (27 cases), 100.0% (29 cases) and 93.1% (27 cases) respectively, sputum culture of 2 patients returned to positive at week 24; the median time of negative conversion of sputum culture was 24 days (interquartile interval: 14-61 days). Among 52 patients with pulmonary cavity, 48 (92.3%) completed 24 weeks of BDQ-containing treatment, the cavity closure rates at week 12 and 24 were 37.5% and 64.6% respectively. Conclusion Compared with the traditional treatment regimen, BDQ-containing treatment regimen for 24 weeks can improve the negative conversion rate of sputum culture and cavity closure rate in patients with MDR/XDR-TB, but attention should be paid to the monitoring and management of QT interval.

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