Table of Content

10 June 2021, Volume 43 Issue 6

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Standard·Guide·Consensus

Guideline for clinical management of adverse reactions of bacillus Calmette-Guérin

Chinese Journal of Antituberculosis. 2021, 43(6):  532-538.  doi:10.3969/j.issn.1000-6621.2021.06.002

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Bacillus Calmette-Guérin (BCG) is a live attenuated vaccine against tuberculosis, and is one of the most widely used and safest vaccines in the world. The prevalence and mortality of miliary tuberculosis and tuberculous meningitis in children have significantly decreased since being vaccinated with BCG from 1978 in China. BCG is applicated in the prevention of tuberculosis, in addition, it is also commonly used in perfusion therapy for bladder carcinoma in situ. BCG instillation helps to reduce and delay the recurrence and progression of non-muscle invasive bladder carcinoma, it is considered as the best intravesical instillation drug at present. However, due to the production process, the virulence of the vaccine, the methods of usage of the vaccine, individual differences and other factors, the adverse reactions after BCG vaccination and perfusion often occur. The clinical treatment of BCG adverse reactions has not been standardized by now. Therefore, the Tuberculosis Branch of Chinese Medical Association, the School and Children Tuberculosis Branch of Chinese Antituberculosis Association organized some experts to formulated the “Guideline for Clinical Treatment of BCG Adverse Reactions” after discussions. The guideline includes the types of BCG, the methods of usage, and clinical characteristics, diagnostic criteria, treatment and prevention of the adverse reactions of BCG vaccine, in order to standardize with the treatment for the adverse reactions of BCG.

Interpretation of Standards

Interpretation of the new definition of extensive drug-resistant tuberculosis defined by World Health Organization

LI Ren-zhong, RUAN Yun-zhou, LI Yu-hong

Chinese Journal of Antituberculosis. 2021, 43(6):  539-541.  doi:10.3969/j.issn.1000-6621.2021.06.003

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The definition of extensive drug-resistant tuberculosis (XDR-TB) first proposed by World Health Organization (WHO) in 2006 has played an important role in guiding the prevention and control of drug-resistant tuberculosis. With the development of new diagnostic technologies and new drugs, WHO updated the original definition of XDR-TB in January 2021. In this paper, the background, history, reasons and general principles of the new definition of XDR-TB were interpreted, and the impact and significance of the new definition for the tuberculosis control in the future were summarized, in order to provide reference for tuberculosis control workers in China.

Interpretation of the Chinese Guidelines for Prevention and Control of Tuberculosis in Schools

CHEN Hui, ZHANG Hui, CHENG Jun

Chinese Journal of Antituberculosis. 2021, 43(6):  542-545.  doi:10.3969/j.issn.1000-6621.2021.06.004

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In order to guide the prevention and control of tuberculosis in schools and reduce the spread of tuberculosis in schools, the National Health Commission and the Ministry of Education organized experts to formulate and published “Chinese Guidelines for Prevention and Control of Tuberculosis in Schools”. Based on the practical experience and relevant technical strategies development in recent years, the prevention and control measures are further standardized and detailed in this guidelines, and the necessary forms and cards are attached, which is instructive and operational. The author describes the formulation background, main contents and characteristics of guidelines, to improve the relevant personnel’s ability of tuberculosis prevention and control in schools

Thematic Discussion

Discussion on the comorbidities and management of tuberculosis in China

CHEN Qiu-qi, DENG Guo-fang

Chinese Journal of Antituberculosis. 2021, 43(6):  546-549.  doi:10.3969/j.issn.1000-6621.2021.06.005

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With the increase of coexisting diseases in tuberculosis patients, comorbidities of tuberculosis have attracted more attention. Researches on comorbidities are no lack in China, but the concept of comorbidity is rarely used in the field of tuberculosis, the management of comorbidity between tuberculosis and other diseases needs more improvement. The expression and use of comorbidity, and the role and significance of tuberculosis and comorbidities management were summarized to further explore the related problems.

Original Articles

Analysis on the characteristics of tuberculosis patients detected through active case finding in the elderly

CHEN Hui, SUN Yan-bo, SHEN Xin, ZHU Li-mei, WANG Xiao-meng, SUN Ding-yong, ZHOU Lin, LIN Ding-wen, CHEN Chuang, ZHANG Can-you, ZHANG Hui, WANG Li-xia, ZHAN Si-yan, CHENG Jun

Chinese Journal of Antituberculosis. 2021, 43(6):  550-556.  doi:10.3969/j.issn.1000-6621.2021.06.006

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Objective To explore the characteristics of patients and detection rate by active screening of pulmonary tuberculosis in the elderly population in the pilot sites. Methods During 2013—2019, the basic information and tuberculosis (TB) screening were carried out four times among permanent residents over 65 years old in 12 towns or communities in 8 counties (Xinzhuang Town, Minhang District, Shanghai; Daoshu Town, Danyang County, Jiangsu Province; Qinghu Town, Jiangshan City, Quzhou City, Zhejiang Province; Donghuan Street, Panyu District, Guangzhou City, Guangdong Province; Zhangshi Town, Weishi County, Kaifeng City, He’nan Province; Anjia Town and Changbao Town, Wuchang County, Harbin City, Heilongjiang Province; Houba Town, Erlangmiao Town and Chonghua town, Jiangyou City, Mianyang City, Sichuan Province; Jiucheng Town, Haicheng Town, Pingguo County, Baise City, Guangxi Zhuang Autonomous Region), the prevalence of TB among elderly was obtained and the characteristics of patients and the trend of detection rate were compared. Results From 2018 to 2019, among the 36843 individuals, 23566 completed chest X-ray examination with the screening rate of 63.96%, and 82 patients were diagnosed. The PTB detection rate in the elderly was significantly higher in men (519.53/100000, 56/10779) than in women (203.44/100000, 26/12780) (χ²=16.843, P<0.01). The detection rate increased with age, from 275.70/100000 (65-74 years old group, 45/16322) to 542.01/100000 (85-113 years old group, 6/1107)(χ²_trend=7.385, P=0.007). The detection rate was higher in western regions (Guangxi and Sichuan, 657.50/100000 (66/10038)) compared to the counties located in middle and eastern regions of China. The detection rate of close contacts and previous TB patients was significantly higher (9547.74/100000 (19/199) and 1108.03/100000(4/361)) compared to that of non-close contacts and new cases, respectively. From 2013 to 2019, there were four times screenings conducted in the same pilot site, the bacteriology positive rate of sputum smear in elderly TB patients (31.43% (55/175), 21.15% (33/156), 35.29% (36/102), 12.20% (10/82)) decreased with the year (χ²_trend=7.290, P=0.007). The TB detection rate in the elderly was 650.49/100000 (175/26903), 618.07/100000 (156/25240), 474.79/100000 (102/21483) and 347.96/100000 (82/23566) respectively, which decreased year by year (χ²_trend=25.659, P<0.01). Conclusion After frequent active case finding in the same area, the TB detection rate in the elderly decreased significantly. It reflects high risk factors, frequency and screening method should be considered when an active screening policy is developed.

A study on the effect of artificial intelligence automatic film reading technology in active tuberculosis screening of HIV/AIDS population

WANG Qian, HE Jin-ge, LI Yu-hong, CHEN Ming-ting, ZHOU Lin

Chinese Journal of Antituberculosis. 2021, 43(6):  557-561.  doi:10.3969/j.issn.1000-6621.2021.06.007

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Objective To evaluate the effect of artificial intelligence (AI) automatic film reading technology in tuberculosis screening of HIV/AIDS patients, and to provide scientific basis and reference for the formulation and improvement of active tuberculosis detection strategies in high risk population. Methods A retrospective study was conducted in 633 HIV/AIDS patients who were actively screened for tuberculosis using digital X-ray photography (digital radiography, DR) in 2019. Of them, 47 (7.4%) were pathogen-positive tuberculosis patients. Data of chest X-ray (“chest film”) of the patients were read using the AI automatic film reading technology from 3 different enterprises, and 3 senior experts were also invited to read the film. The results were analyzed, and the diagnostic effectiveness of manual reading and AI automatic reading technology was compared by reference to the etiological diagnosis of pulmonary tuberculosis. Results Of the 633 subjects, 198 (31.3%, 198/633) were diagnosed as suspected active tuberculosis by manual reading. The numbers of suspected cases detected by the three reviewers were 139 (22.0%, 139/633), 100 (15.8%, 100/633), and 90 (14.2%, 90/633), respectively. Of the 47 patients complicated with pathogen-positive tuberculosis, 19 (40.4%, 19/47), 29 (61.7%, 29/47) and 21(44.7%, 21/47) were diagnosed by the 3 experts, respectively, and a total of 14 cases (29.8%, 14/47) were misdiagnosed. By AI automatic film reading technology, 434 cases (68.6%) were diagnosed as suspected active tuberculosis. Using the technologies of 3 enterprises, the numbers of suspected cases detected by were 260 (41.1%, 260/633), 299 (47.2%, 299/633) and 247 (39.0%, 247/633), respectively. Of the 47 patients complicated with pathogen-positive tuberculosis, 32 (68.1%, 32/47), 30 (63.8%, 30/47), and 33 (70.2%, 33/47) were diagnosed, respectively. A total of 5 cases (10.6%) were misdiagnosed. Based on pathogen-positive diagnosis, the sensitivity of HIV/AIDS complicated with pathogen-positive tuberculosis was 70.2% (33/47), the specificity was 71.8% (421/586), and the consistency rate was 71.7% (454/633) by manual film-reading method; while by AI automatic film reading technology, the sensitivity was 89.4% (42/47), specificity was 33.1% (194/586), and the consistency rate was 37.3% (236/633). Conclusion AI automatic film reading technology is more sensitive than manual reading methods in diagnosis of pathogen-positive tuberculosis in HIV/AIDS population, and is suitable for active screening of tuberculosis.

Analysis of the epidemiological characteristics and therapeutic prognosis of new smear-positive pulmonary tuberculosis in Urumqi from 2014 to 2019

ZHANG Wei-sheng, LI De-yang, CHEN Yang-gui, MA Li, YANG Jian-dong, CAO Ming-qin

Chinese Journal of Antituberculosis. 2021, 43(6):  562-568.  doi:10.3969/j.issn.1000-6621.2021.06.008

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Objective To explore the epidemiological characteristics of new smear-positive pulmonary tuberculosis (PTB) in Urumqi from 2014 to 2019, and to analyze the influencing factors of the therapeutic prognosis. Methods The information of newly diagnosed smear-positive tuberculosis patients registered in Urumqi from 2014 to 2019 was collected through the TB Information Management System of the Chinese Disease Prevention and Control Information System, including population information, diagnostic information and information of first-diagnosed medical institutions. The annual resident population data and administrative division information of Urumqi from 2014 to 2019 were from the statistical bulletin of national economic and social development of Urumqi. The epidemiological characteristics of new smear-positive tuberculosis were described, and the influencing factors of therapeutic prognosis were analyzed. Results A total of 3029 new smear-positive tuberculosis patients were registered in Urumqi from 2014 to 2019, with an average annual registration rate of 14.31/100000. The annual registered incidence ranged from 12.76/100000 (449 cases) to 16.81/100000 (597 cases). Among the newly diagnosed smear-positive PTB patients, the majority were males (60.71% (1839/3029)) and aged ≤45 years (48.90% (1481/3029)). The incidence was high in spring and summer (26.81% (812/3029) and 26.78% (811/3029), respectively). The incidence was high in the central urban area (76.96% (2331/3029)). Multivariate logistic regression showed that: of the new smear-positive tuberculosis patients, female (OR=0.100, 95%CI=0.071-0.152), 46-65 years old (OR=0.453, 95%CI=0.302-0.683) and patients with smear-negative in sputum examination at the end of 2 months after treatment (OR=0.192, 95%CI=0.134-0.292) were more likely to be successfully treated; while treatment failure was more likely to occurred in patients without sputum examination at the end of 2 months after treatment (OR=24.442, 95%CI=10.751-55.533). Conclusion From 2014 to 2019, the registration rate of new smear-positive PTB in Urumqi City first decreased and then increased. The key prevention and control of male and middle-aged people should be strengthened in the spring and summer seasons in densely populated central urban areas. Sputum smear examination should be carried out carefully at the end of two months after treatment.

Establishment of ARIMA model and its application on the prediction of pulmonary tuberculosis incidence in Guangzhou

LEI Yu, HE Li-qian, ZHANG Guang-chuan, LAI Keng, XIE Wei, DU Yu-hua

Chinese Journal of Antituberculosis. 2021, 43(6):  569-575.  doi:10.3969/j.issn.1000-6621.2021.06.009

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ObjectiveTo establish an Auto-regressive Integrated Moving Average (ARIMA) model of tuberculosis (TB) in Guangzhou and use it to make prediction on the number of notified pulmonary tuberculosis (PTB) cases in Guangzhou, so as to provide a reference for the prevention and control of TB in Guangzhou. MethodsThe monthly notification incidence data of TB in Guangzhou from January 2010 to December 2019 was collected through the “Chinese Disease Prevention and Control Information System”. ARIMA model was established by conducting time series analysis to predict the notification incidence of PTB in Guangzhou in 2021. In addition, the stability of model parameters and the accuracy of prediction model were tested by re-fitting the model with data from 2010 to 2018. ResultsA total of 115887 PTB cases were notified in Guangzhou from 2010 to 2019, which showed a downward trend year by year together with a significant seasonality. The number of cases reached a peak from March to May every year, and the trough always occurred in February. The best fitting model was ARIMA(1,1,1)×(0,1,1)₁₂ (P_{residual test}=0.693, AIC=1215.300), and the mean absolute percentage error (MAPE) between the actual value and the predicted value fitted by the model for January to December 2020 was 7.29%. According to the data from 2010 to 2018, the optimal model was still ARIMA(1,1,1)×(0,1,1)₁₂ (P_{residual test}=0.847, AIC=1089.260) and MAPE between the actual value and the predicted value fitted by model for January to December in 2019 was 4.91%. The predicted number of PTB cases in Guangzhou in 2021 was 8270, and the average number of monthly cases was 689. The incidence level was slightly higher than that in 2020. Conclusion The ARIMA (1,1,1)×(0,1,1)₁₂ model made a good prediction on the number of notified PTB cases in Guangzhou, and could be used for short-term forecasting and dynamic analysis of TB in Guangzhou.

Study of the mechanism of the new antidrug-resistant tuberculosis drug pyrifazimine mediated by quinone oxidoreductase

ZHANG Lei, LI Yuan-yuan, CHEN Xi, LIU Hai-ting, XU Jian, WANG Ning, DING Yang-ming, LU Yu

Chinese Journal of Antituberculosis. 2021, 43(6):  576-583.  doi:10.3969/j.issn.1000-6621.2021.06.010

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Objective To study the mechanism of pyrifazimine (TBI-166) accumulating reactive oxygen species (ROS) to kill Mycobacterium tuberculosis(MTB) through quinone oxidoReductase (QOR). Methods MtbQOR protein was expressed and purified. The decrease of NADPH (ΔA) at A_{340 nm} in blank control group and TBI-166 (0.03、0.3、3μg/ml) groups were detected by microplate reader; NADPH/NADP⁺ ratio of H37Rv after exposure to TBI-166 of different concentrations were detected by coenzyme Ⅱ NADP (H) detection kit; ROS fluorescence value of H37Rv strains and clinical collected strains were tested by bacterial ROS detection kit. Results The ΔA of control group (0.316±0.032) was lower than that of 0.03, 0.3, 3μg/ml TBI-166 groups (0.506±0.107, 0.531±0.054, 0.801±0.079) (t=-3.799,P<0.05;t=-7.634,P<0.01;t=-12.683,P<0.01). Within 48 hours, the NADPH/NADP⁺ratio of TBI-166 groups (0.847±0.229) was lower than that of the control group (1.728±0.384). ROS fluorescence value of H37Rv strains in TBI-166 groups (23072±2584) was higher than that of the control group (8282±448) (F=33.334, P<0.01). ROS fluorescence value of the strain number 12897 in TBI-166 groups (18369±3118) was higher than that of the control group (12268±2735) (F=5.026, P<0.05). ROS fluorescence value of the strain number 15171 in 3μg/ml TBI-166 group (17572±249) was higher than that of the control group (11109±343)(F=122.601, P<0.01). There was no significant difference detected in ROS fluorescence value between TBI-166 groups and blank control group in the strains numbered 11492 and 11195 (F=161.440, P>0.05; F=44.788, P>0.05). Conclusion TBI-166 could enhance redox reaction mediated by MtbQOR, decrease the ratio of NADPH/NADP⁺ and accumulate intra-bacterial ROS to kill MTB.

Diagnostic value of GeneXpert MTB/RIF Ultra for pulmonary tuberculosis in children using gastric juice

FANG Min, SHI Yan, DUAN Li, SHI Xiao-mei, QUAN Shu-ting, WANG Ya-cui, PENG Xiao-shan, JIA Ji-hang, QI Hui, JIAO Wei-wei, ZHU Yu, SUN Lin

Chinese Journal of Antituberculosis. 2021, 43(6):  584-589.  doi:10.3969/j.issn.1000-6621.2021.06.011

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Objective To evaluate the performance of GeneXpert MTB/RIF Ultra (Xpert Ultra) for pulmonary tuberculosis (PTB) diagnosis in children using gastric juice. Methods In this retrospective study, a total of 173 eligible children were enrolled, who admitted to Pediatric Department of the 1st People’s Hospital of Liangshan Yizu Autonomous Prefecture between July 2019 and July 2020. Using composite reference standard (CRS) as reference, 114 of them were diagnosed with PTB (case group), and 59 were non-TB patients with other respiratory infectious diseases (control group). Gastric juice and sputum samples were collected and subjected to culture and Xpert Ultra. The performance of Xpert Ultra was evaluated in gastric juice and sputum samples using CRS as gold standard. Results Using CRS as reference, the diagnostic sensitivity, specificity, accordance rate and Kappa value of Xpert Ultra for PTB diagnosis in children using gastric juice samples was 53.5% (61/114), 98.3% (58/59), 68.8% (119/173) and 0.43, respectively. The sensitivity of Xpert Ultra using gastric juice samples in pre-school (0-6 years) children was significantly higher than that in school-aged (6-14 years) children (66.7% (26/39) vs. 46.7% (35/75),χ²=4.126, P=0.042). The sensitivity of MTB culture was only 20.2% (23/114). Among 65 children who underwent Xpert Ultra of both gastric juice and sputum samples, the sensitivity of Xpert Ultra in gastric juice samples was higher than that in sputum samples (52.2% (24/46) vs. 43.5% (20/46)). However, the difference was not significant (χ²=0.697, P=0.404). Among 150 culture-negative children, 40 were positive using Xpert Ultra, in which trace result accounted for 37.5% (15/40). The percentage of trace result was only 14.3% (3/21) among culture-positive children. Five children were found to be rifampicin resistant among 61 Xpert Ultra-positive patients. Conclusion The performance of Xpert Ultra for PTB diagnosis in children using gastric juice samples is good, making it useful for early diagnosis of pediatric TB. The gastric juice samples are valuable alternative types for those who can’t expectorate or preschool children who can’t provide qualified sputum samples.

Identification and analysis of 261 strains of non-tuberculous mycobacteria in Fujian Province

LIN Jian, ZHAO Yong, DAI Zhi-song, WEI Shu-zhen, LIN Shu-fang

Chinese Journal of Antituberculosis. 2021, 43(6):  590-595.  doi:10.3969/j.issn.1000-6621.2021.06.012

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Objective To identify non-tuberculous mycobacteria (NTM) strains and analyze their distributions in Fujian Province, so as to provide scientific evidence for clinical diagnosis, treatment and epidemiological research of NTM disease in Fujian Province. Methods A total of 3355 strains of mycobacterium were collected from nine drug-resistant tuberculosis surveillance sites and nine tuberculosis laboratories of municipal level Center for Disease Control and Prevention in Fujian Province from June 2016 to December 2019. A total of 261 NTM strains were identified by PNB growth test, and then tested with the GenoType Mycobacterium CM kit. DNA sequencing or MeltPro Myco kit were used for further identification of strains that could not be identified by the above method. Results Among 261 strains, 213 (81.61%) were NTM and the separation rate of NTM was 6.35% (213/3355). Among them, the top three species of all NTM were M.intracellulare (65.73%,140/213), M.abscessus (17.37%,37/213) and M.kansasii (4.22%,9/213). In this study, six rare species of mycobacteria were found-M.arupense, M.peregrinum, M.phocaicum, M.sinense, M.vanbaalenii and M.dioxanotrophicus. In addition, 9 mixed infection strains were identified, including 8 mixed infections of MTBC and M.intracellulare, and 1 mixed infection of MTBC and M.avium. Conclusion Three identification methods of NTM species were combined to reveal that the three most prevalent NTM species in Fujian were M.intracellulare, M.abscessus and M.kansasii, and 6 rare NTM and 9 mixed infection strains have been found.

Analysis on gene mutation characteristics of drug resistant Mycobacterium tuberculosis and its correlation with genotypes in Guangxi

LUO Dan, QIN Hui-fang, YE Jing, ZHAO Jin-ming, QIN Yi-xiang, LAN Ru-shu

Chinese Journal of Antituberculosis. 2021, 43(6):  596-601.  doi:10.3969/j.issn.1000-6621.2021.06.013

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Objective To investigate the characteristics of Mycobacterium tuberculosis(MTB) gene mutation which are related with drug resistance to five first-line anti-tuberculosis drugs and their correlations with genotypes. Methods Whole-genome sequencing were performed on 721 MTB strains collected from drug resistance surveillance in Guangxi Zhuang Autonomous Region in 2017. Analyze the characteristics of drug resistance-related gene mutations and their correlation with genotypes. Results The total drug resistance-related gene mutation rate was 30.93% (223/721). The top 5 genes of mutation were katG (16.09%,116/721), rpoB (12.21%,88/721), embB (8.46%,61/721), rpsL (6.10%,44/721) and rrs (4.72%,34/721). The top 5 mutation loci were katG315 (12.34%,89/721), rpsL43 (5.27%,38/721), rpoB450 (4.85%,35/721), embB306 (4.02%,29/721) and rpoB445 (2.91%,21/721). RpsL, rpsL43 and rpoB445 mutation rate were higher in Beijing genotype strains than in non-Beijing genotype strains (10.51% (43/409) vs. 0.32% (1/312),χ²=32.090,P=0.000; 9.05% (37/409) vs. 0.32% (1/312),χ²=26.992,P=0.000; 4.40% (18/409) vs. 0.96% (3/312), χ²=7.404,P=0.007). Conclusion KatG,rpoB,embB,rpsL,rrs were the main drug resistance-related gene mutations in Guangxi MTB strains. The mutations in rpsL, rpsL43 and rpoB445 were correlated with Beijing genotype.

Correlation between neutrophil-to-lymphocyte ratio and the secondary pulmonary infection in type 2 diabetes mellitus complicated with pulmonary tuberculosis

TAN Shou-yong, YUAN Yuan, KUANG Hao-bin, GONG Fang, WANG Min

Chinese Journal of Antituberculosis. 2021, 43(6):  602-605.  doi:10.3969/j.issn.1000-6621.2021.06.014

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Objective To investigate the changes of neutrophil-to-lymphocyte ratio (NLR) in peripheral blood of secondary pulmonary infection patients with type 2 diabetes mellitus (T2DM) complicated with pulmonary tuberculosis (PTB). Methods A retrospective study was conducted in 951 T2DM patients complicated with PTB, who were hospitalized for the first time in the Tuberculosis Department of Guangzhou Chest Hospital from January 2013 to January 2018. They were newly treated and the TB detection is positive, the clinical data including age, gender, clinical symptoms, diabetes history, glycosylated hemoglobin A1c (HbA1c), peripheral blood white blood cell (WBC) count, neutrophil count, lymphocyte count and anti-infective treatment effect were analyzed. All the patients were divided into infection group and non-infection group according to whether they had secondary pulmonary infection when admission; according to whether the peripheral blood lymphocyte count was ≥0.8×10⁹/L when admission, they were divided into normal group and low lymphocyte count group. The correlation between NLR and secondary lung infections in the study subjects was analyzed. Results Of the patients, 524 suffered secondary lung infection (55.10%); the lesion mainly involved 5-6 lung fields in the infected group (60.5%, 317/524), which was significantly higher than that in the non-infected group (41.0%, 175/427) (χ²=42.587, P=0.000). The NLR level of the infected group (M(Q₁,Q₃)) was 6.79 (5.10, 9.70), which was significantly higher than that of the non-infected group (3.01 (2.27, 3.55)) (U=16 545.00, P=0.000). The NLR levels (M(Q₁,Q₃)) of patients with low peripheral blood lymphocyte counts in the infected and non-infected groups were 12.09 (8.67, 16.05) and 4.26 (3.71, 6.39), respectively, both significantly higher than those of patients whose peripheral blood lymphocytes counts were normal (5.90 (4.71, 7.55), U=5964.00, P=0.000 and 2.97 (2.25, 3.80), U=1695.50, P=0.000, respectively). The neutrophil count (M(Q₁,Q₃)) of patients with low peripheral blood lymphocyte counts were 6.42 (5.01, 9.07)×10⁹/L and 3.13 (1.88, 3.51)×10⁹/L, in the two groups, which were significantly lower than those of patients with normal peripheral blood lymphocyte count (7.90 (6.72, 9.27)×10⁹/L, U=18697.00, P=0.000 and 4.57 (3.70, 5.40)×10⁹/L, U=1257.00, P=0.000, respectively). Conclusion The level of NLR in the secondary pulmonary infection in T2DM patients complicated with PTB was significantly increased, and patients with low peripheral blood lymphocyte counts were prone to secondary lung infection.

Analysis of the effects of patient-centered comprehensive supportive care service for MDR/RR-TB patients

ZHAO A-li, YUAN Rong, LUO Hui, HE Xiao-mou, DANG Li-yun

Chinese Journal of Antituberculosis. 2021, 43(6):  606-611.  doi:10.3969/j.issn.1000-6621.2021.06.015

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Objective To analyze the implementation effectiveness of patient-centered comprehensive supportive care service for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) patients. Methods The MDR/RR-TB patients diagnosed in Xi ’an Chest Hospital were selected as the subjects. Among them, all newly diagnosed MDR/RR-TB patients from June to December 2019 (182 cases), who received the patient-care services, were enrolled as the intervention group for analysis. Meanwhile, all newly diagnosed MDR/RR-TB patients from June to December 2018 (159 cases) were enrolled as the control group. Patients in the control group were given regular compliance assessment, health education and psychological support during hospitalization and follow-up by telephone after discharge. On the basis of routine measures, patients in the intervention group were provided with individualized care services, including one-on-one consultation and community referral during hospitalization, and subsequent visit reminders, follow-up consultation, group activities and peer support, etc., after discharge. The differences of the treatment rate, the rate of loss to follow-up (LTFU) at the 12th month, and the rate of subsequent visits were compared between the two groups. Results The treatment rate and the 12-month follow-up rate of patients in the intervention group were 92.9% (169/182) and 92.6% (1308/1413) respectively, which were significantly higher than those in the control group (84.9% (135/159) and 78.3% (930/1188) respectively), and the differences were statistically significant (χ²=5.547, P=0.019; χ²=109.689, P<0.01). The LTFU rate at the 12th month of the control group was 7.0% (11/157), which was significantly lower than the control group (32.3%, 43/133). The difference was statistically significant (χ²=30.474, P<0.01). Ten cases (10/11) of the intervention group and 27 cases (62.8%, 27/43) of the control group were LTFU in the first 6 months. Conclusion Patient-centered supportive care services could help to improve the treatment rate and treatment adherence of the MDR/RR-TB patients, and reduce the rate of LTFU at the 12th month.

Analysis of clinical characteristics in patients with primary non-specific spinal infection and spinal tuberculosis

YAO Li-ming, DONG Zhao-liang, WANG Lian-bo, JIA Chen-guang, LI Zhuo, LIU Feng-sheng

Chinese Journal of Antituberculosis. 2021, 43(6):  612-618.  doi:10.3969/j.issn.1000-6621.2021.06.016

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Objective To analyze the clinical characteristics of the patients with primary non-specific spinal infection and spinal tuberculosis (TB). Methods A retrospective analysis was conducted in 197 patients with spinal infectious diseases who were admitted in the Department of Orthopedics of Hebei Provincial Chest Hospital from January 2014 to December 2015. According to the type of pathogenic bacteria, those enrolled patients were divided into two groups: one was the primary non-specific spinal infection group(non-specific infection group, 21 cases (10.7%))and the other was spinal TB group (TB group, 176 cases (89.3%)). The clinical materials, laboratory examination results and imaging manifestations of the patients in the two groups were compared, and the results of pathogeny detection and treatment outcome of the patients in the non-specific infection group were summarized. Results The age (62.0 (49.5, 66.5) years), mean peak value of body temperature in fever ((38.8±0.9) ℃), white blood cells (WBC) count (8.4 (6.9, 9.4)×10 ⁹/L), erythrocyte sedimentation rate (ESR) (76.0 (61.5, 103.5) mm/1 h) and C-reactive protein (CRP) (68.0 (56.9, 79.0) mg/L) of the patients in the non-specific infection group were significantly higher than those of the patients in the TB group respectively (38.5 (24.0, 54.5) years, (37.8±0.6) ℃, 6.5 (5.2, 7.4)×10 ⁹/L, 40.0 (30.0,50.0) mm/1 h, 24.0 (18.0, 28.0) mg/L), and those differences were statistically significant (U=914.000,P=0.000;t=4.320,P=0.000;U=1005.000,P=0.001;U=307.500,P=0.000;U=100.000,P=0.000). However, the onset time (1.5 (1.0, 2.0) months) of the patients in the non-specific infection group was significantly shorter than that of the patients in the TB group (6.0 (4.0, 7.8) months; U=120.000, P=0.000). The incidences of bone bridge formation showed in X-ray plain (38.1% (8/21)), sequestrum (38.1% (8/21)) and paraspinal abscess (19.0% (4/21)) showed in CT imaging of the patients in the non-specific infection group were statistically significantly different compared with those of the patients in the TB group (9.7% (17/176), 72.2% (127/176), 52.3% (92/176), χ ²=11.246, 10.094, 8.290 and P=0.000, 0.001, 0.004). In the non-specific infection group, the postoperative focus was uncured in 4 cases. Eventually they were cured by adjusting antibiotics treatment and performing debridement combined with continuous catheter irrigation and drainage. There was no recurrence during the follow-up. Conclusion Compared with the patients with spinal TB, the patients with non-specific infection were older, had higher peak value of body temperature, WBC count, ESR and CRP, but their onset time was shorter and they were more likely to have bone bridge and sequestrum which showed in imaging manifestations. By the treatment of drug and surgery, the patients could be completely cured without recurrence.

Review Articles

Research progress of bedaquiline for the treatment of multidrug-resistant tuberculosis

LIAO Wei-ming, FU Liang, DENG Guo-fang, YUAN Xiao-liang

Chinese Journal of Antituberculosis. 2021, 43(6):  619-624.  doi:10.3969/j.issn.1000-6621.2021.06.017

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The emergence and spread of multidrug-resistant tuberculosis (MDR-TB) has become a major obstacle to the World Health Organization’s End TB Strategy by 2035. Some studies have shown that the treatment success rate of MDR-TB with second-line anti-TB drugs was lower, and it was even worse in the patients with extensive drug-resistant tuberculosis (XDR-TB). Therefore, there is an urgent need to develop new anti-tuberculosis drugs. Bedaquiline is the first drug approved for the treatment of MDR-TB in the past 50 years. It can significantly increase the cure rate of MDR-TB and shorten the treatment duration. In order to improve the clinical doctors’ understanding of bedaquiline on MDR-TB treatment, we wrote this paper by reviewing the status of bedaquiline in the treatment of MDR/XDR-TB, the clinical research progress and several relevant issues.

Research progress of tuberculosis vaccine and vaccination strategy

WANG Yuan-zhi, LIANG Zheng-min, QU Meng-jin, ZHOU Xiang-mei

Chinese Journal of Antituberculosis. 2021, 43(6):  625-630.  doi:10.3969/j.issn.1000-6621.2021.06.018

Abstract ( 481 )   HTML ( 33 )   PDF (755KB) ( 273 )   Save

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BCG vaccine is now the only approved and the most widely used tuberculosis vaccine worldwide. It can effectively prevent the tuberculous meningitis in infant and the disseminated tuberculosis, however, for teenagers and adults, as well as those who have been infected with MTB, the protection effect is poor. Therefore, the main research direction of tuberculosis prevention and control includes to develop new effective vaccines, to increase the immune intensity of vaccine and extend protection time of vaccines. The authors reviewed various tuberculosis vaccine types, inoculation routes and immunization strategies, and summarized the information of improving vaccine efficacy, in order to provide reference for the parallel improvement of pre-clinical and clinical trial protocols.

Short Articles

A case of T-cell large granular lymphocyte leukemia complicated with Mycobacterium avium meningitis together with literature review

HONG Piao-ru, JIANG Hui-fang, TAO Die-hong, SU Chuan-yong, GUO Shu-ping, WU Hai-ying, JIANG Yu-xia, YE Ying-yan

Chinese Journal of Antituberculosis. 2021, 43(6):  631-635.  doi:10.3969/j.issn.1000-6621.2021.06.019

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Non-tuberculous mycobacteria (NTM) central nervous system infection is rare in China. The author reported a case of Mycobacterium avium meningitis. The patient was a 44 years old female, admitted to hospital with “diagnosed as T-cell large granular lymphocyte leukemia for more than 3 years, having fever for 1 day”. After admission, cerebrospinal fluid was tested, and Mycobacterium avium was found with cerebrospinal fluid next generation sequencing, then patient was cured with effective treatment for Mycobacterium avium meningitis. By reviewing relevant literature, the author discusses about the treatment of NTM central nervous system infection, reminds clinicians to be alert to the occurrence and severity of NTM disease, to identify the causes as soon as possible and to take necessary intervention measures.

Investigation of drug resistance status and risk factors of multidrug-resistance in 249 aged pulmonary tuberculosis patients

XI Ying, TANG Jun, QIAO Rui-jun, SUN Feng, YU Yan-hong

Chinese Journal of Antituberculosis. 2021, 43(6):  636-641.  doi:10.3969/j.issn.1000-6621.2021.06.020

Abstract ( 394 )   HTML ( 16 )   PDF (738KB) ( 221 )   Save

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Results of drug sensitivity test and clinical data of 249 aged pulmonary tuberculosis patients with positive sputum culture hospitalized in Shenyang Tenth People’s Hospital from January 1, 2020 to December 31, 2020 were collected. Strains from all the patients were identified as Mycobacterium tuberculosis. A single factor and multiple factors unconditioned logistic regression analysis were used to analyze the risk factors of drug resistance. The total drug resistance rate (TDRR), initial treatment DRR and retreatment DRR were 32.53% (81/249), 24.24% (40/165) and 48.81% (41/84), respectively. The retreatment DRR was significantly higher than initial treatment DRR (χ²=15.307, P=0.000). The total multi-drug resistance rate, initial treatment and retreatment multi-drug resistance rate were 12.85% (32/249), 7.27% (12/165) and 23.81% (20/84), respectively. The multi-drug resistance rate of retreatment was significantly higher than that of initial treatment (χ²=13.591, P=0.000). No extensive drug resistance was found. According to multiple factors logistic regression analysis, retreatment (OR=4.201, 95%CI=1.467-12.033) and tuberculous cavity (OR=2.406, 95%CI=1.019-5.681) were independent risk factors of multidrug-resistance in elderly pulmonary tuberculosis patients. The drug resistance rate of elderly pulmonary tuberculosis was high, the drug resistance screening should be actively carried out.