Table of Content

10 April 2023, Volume 45 Issue 4

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Special Topic

Discussion on the nomenclature of recombinant Mycobacterium tuberculosis allergen skin test

Zhao Aihua, Du Weixin, Wang Guozhi, Xu Miao

Chinese Journal of Antituberculosis. 2023, 45(4):  333-335.  doi:10.19982/j.issn.1000-6621.20220486

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In view of the new tuberculosis infection test recommended by WHO in 2022, the MTB antigen-based skin tests (TBST) for the diagnosis of tuberculosis infection, the authors sorted out the name of new varieties of the same kind that have been listed and are under research, discussed the nomenclature of such products with reference to the principles related to nomenclature of biological products in China, expected to provide discussion and reference for experts from research and development, use and regulatory departments.

Interpretation of Standards

Interpretation of WHO consolidated guidelines on tuberculosis, Module 4: treatment-drug-resistant tuberculosis treatment, 2022 update

Fu Liang, Ren Tantan, Zhang Peize, Lu Shuihua

Chinese Journal of Antituberculosis. 2023, 45(4):  336-348.  doi:10.19982/j.issn.1000-6621.20220523

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World Health Organization (WHO) published the WHO consolidated guidelines on tuberculosis, Module 4: treatment-drug-resistant tuberculosis treatment, 2022 update on February 15, 2022. The author introduced the main points of the updated guidelines, including the recommendations on the treatment of drug-resistant tuberculosis (focusing on a new short-term plan), management, patient care, and treatment monitoring, and discussed the feasibility of the guidelines in clinical practice and future research directions in China.

Original Articles

Analysis of therapeutic effects and factors affecting treatment outcomes of Mycobacterium abscessus subspecies abscessus pulmonary disease for 6 months

Bao Shengjuan, Shao Lingling, Wang Jing, Han Xiqin, Huang Hairong, Duan Hongfei

Chinese Journal of Antituberculosis. 2023, 45(4):  349-354.  doi:10.19982/j.issn.1000-6621.20220522

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Objective: To assess the efficacy of different antibiotics combined on Mycobacterium abscessus subspecies abscessus pulmonary disease (M.abscessus-PD) and analyze the influencing factors of treatment outcomes for 6 months. Methods: Sixty-six patients in Beijing Chest Hospital, Capital Medical University diagnosed with M.abscessus-PD were enro1led prospectively from January 1st, 2016 to October 1st, 2022. Clinical information of the patients were collected, including gender, age, body mass index, clinical manifestations, history of past illness and anti-tuberculosis treatment, imaging examinations, laboratory examinations and medications. The factors influencing treatment outcomes of M.abscessus-PD for 6 months among different therapicregimens was compared. Results: After 6 months of treatment, 32 (48.5%) achieved sputum culture conversion and 34 (51.5%) didn’t among the 66 patients. The result shows that the 6-month sputum culture conversion rate of azithromycin users (57.4%, 27/47) was higher than clarithromycin users (26.3%, 5/19), with statistically significant (χ²=5.250,P=0.022). In 24 cases (36.4%, 24/66) treated with imipenem, 17 (70.8%, 17/24) achieved 6 months sputum culture conversion, which was higher than that of non-imipenem (35.7%, 15/42), with statistically significant difference (χ²=7.542, P=0.006). The efficacy of multidrug therapy regimen showed that macrolide combined with amikacin, imipenem, linezolid and clofazimine achieved 68.4% (13/19) culture conversion rate after 6 months. Multivariate analysis shows that patients treated with macrolide combined with imipenem were more likely to achieve sputum culture conversion within 6 months (OR (95%CI)=0.229 (0.077-0.676)). Conclusion: In the initial stage of treatment, at least 4 weeks of injection use (amikacin and imipenem), and the combination of macrolides with amikacin, clofazimine, and linezolid in the continued treatment, may have good curative effect on M.abscessus-PD.

Clinical analysis of 93 cases of pulmonary disease caused by nontuberculous mycobacteria

Han Xiqin, Wang Jing, Tan Qiuqing, Li Xiaohua, Zhang Liqun, Shao Lingling, Duan Hongfei

Chinese Journal of Antituberculosis. 2023, 45(4):  355-361.  doi:10.19982/j.issn.1000-6621.20220519

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Objective: To understand the characteristics of nontuberculous mycobacteria (NTM) pulmonary disease, and provide evidence for clinical diagnosis and treatment of NTM pulmonary disease. Methods: The clinical data of 93 patients with NTM pulmonary disease admitted to Beijing Chest Hospital affiliated to Capital Medical University between January 2018 and December 2019 were analyzed retrospectively. Treatment effectivenesses were compared for different treatment. Results: Among 93 patients with NTM pulmonary disease, there were 49 cases infected with Mycobacterium intracellular, 28 cases with Mycobacterium abscesses, 4 cases with Mycobacterium avium, 4 cases with Mycobacterium kansasii, 3 cases with Mycobacterium xenopi, 2 case co-infected with Mycobacterium abscesses and Mycobacterium intracellular, one case with Mycobacterium gordonii, Mycobacterium fortuitum or Mycobacterium stutzeri each. 61 patients (65.59%) had received antituberculosis treatment before the diagnosis of NTM pulmonary disease. 90 (96.77%) patients had complications, of which 52 (57.78%) patients had bronchiectasis, followed by 12 (13.33%) patients with chronic obstructive pulmonary disease (COPD). 83 cases (89.25%) received anti-NTM treatment, and 47 cases (56.63%) completed the course of treatment among whom the success rate of the treatment of pulmonary disease with Mycobacterium avium complex was 51.85% (14/27) while the treatment success rate of Mycobacterium abscesses pulmonary disease was 76.92% (10/13). 48 cases (57.83%) had adverse drug reactions of different degrees during the treatment, and 15 cases (18.07%) discontinued the treatment. 16 patients (19.28%) were lost to follow-up. Conclusion: Mycobacterium intracellular lung disease is the most common NTM pulmonary disease. Most patients were complicated with bronchiectasis, COPD and other basic lung diseases. The clinical characteristics of NTM pulmonary disease and pulmonary tuberculosis are similar, which are easily misdiagnosed as pulmonary tuberculosis. The cure rate of NTM pulmonary disease is low, and the rate of treatment interruption and loss to follow-up is high.

Application value of targeted next-generation sequencing for identification of non-tuberculous mycobacteria strains

Chen Hua, Chen Pinru, Li Yanyang, Deng Zhengxian, Xu Liuqing, Liang Feng, Hu Jinxing

Chinese Journal of Antituberculosis. 2023, 45(4):  362-366.  doi:10.19982/j.issn.1000-6621.20220530

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Objective: To explore the application value of targeted next-generation sequencing (tNGS) in the identification of non-tuberculous mycobacteria (NTM) strains. Methods: From July 2021 to September 2022, 428 samples of hospitalized patients in the NTM Diagnosis and Treatment Center of Guangzhou Chest Hospital were collected for study, including 312 sputum samples and 116 bronchial lavage fluid samples. These samples were identified by tNGS mycobacterium identification (“tNGS” for short) and microbial culture (BACTEC MGIT 960)+DNA microarray chip method (“culture method” for short), and the detection results of the two methods were analyzed. Results: (1) tNGS and culture method respectively isolated 102 and 56 samples of Mycobacterium tuberculosis respectively, and 150 and 182 NTM samples. (2) Detection rate of mycobacterium by tNGS was 58.88% (252/428), but there was no significant difference between tNGS and culture method (55.61% (238/428), χ²=0.936,P=0.333). (3) Taking culture method as the reference standard, the sensitivity, specificity, false negative rate, false positive rate, positive predictive value, negative predictive value and Kappa value of tNGS to detect mycobacterium were 80.65% (200/248), 92.22% (166/180), 22.43% (48/214), 6.54% (14/214), 93.46% (200/214), 77.57% (166/214) and 0.710, respectively. Conclusion: tNGS result is consistent with culture method, has good timeliness, sensitivity and specificity, which is conducive to formulating clinical treatment plan in the early stage.

Analysis of registration records of elderly pulmonary tuberculosis patients aged 65 and above in China,2015—2021

Teng Rencong, Li Tao, LI Yuhong, Yang Chenlu, Zhang Canyou, Zhao Yanlin, Zhang Hui

Chinese Journal of Antituberculosis. 2023, 45(4):  367-371.  doi:10.19982/j.issn.1000-6621.20220494

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Objective: To analyze the registration records of elderly pulmonary tuberculosis (PTB) patients aged 65 and above in China from 2015 to 2021, to provide basis for strengthening TB control among elderly population. Methods: The medical records of elderly PTB patients aged 65 and above from January 1, 2015 to December 31, 2021 were extracted from the Tuberculosis Management Information System (TBIMS), a subsystem of the Chinese Disease Control and Prevention Information System, which included data of gender, age, ethnic, population classification, current address, case finding methods, bacteriological test result, etc. The registration number of PTB patients from 2015 to 2021 was also obtained from the TBIMS. The number of elderly populations from 2015 to 2021 was derived from the 2021 National bulletin on the development of elderly population care issued by the National Bureau of Statistics. Descriptive analysis was made on the registration data and population characteristics of elderly PTB patients aged 65 and above. Results: From 2015 to 2021, a total of 1220494 elderly PTB patients aged 65 years and above were registered in China, and the registration rate dropped from 117.8/100000 (171033/145240000) in 2015 to 81.1/100000 (162565/200560000) in 2021, showing an overall statistically significant decline trend ( {\chi }_{\mathrm{T}\mathrm{r}\mathrm{e}\mathrm{n}\mathrm{d}}^2=21268.25, P<0.001). The proportion of elderly PTB patients among all PTB patients increased from 21.3% (171033/804164) in 2015 to 27.4% (162565/593743) in 2021 year by year, showing an overall statistically significant increasing trend ( {\chi }_{\mathrm{T}\mathrm{r}\mathrm{e}\mathrm{n}\mathrm{d}}^2=9195.04, P<0.001). The etiologically positive rate of elderly PTB patients increased from 33.0% (56426/171033) in 2015 to 64.1% (104182/162565) in 2021 year by year, showing an statistically significant increasing trend ( {\chi }_{\mathrm{T}\mathrm{r}\mathrm{e}\mathrm{n}\mathrm{d}}^2=67776.63, P<0.001). Among 1220494 elderly PTB patients, the male to female ratio was 2.37∶1 (858031/362463), the proportion of ethnic minorities was 15.7% (191525 patients), the proportion of farmers, herdsmen and fishermen was 76.8% (936988 patients), the proportions of patients from eastern, central and western regions were 28.0% (341971 patients), 36.7% (448430 patients) and 35.3% (430093 patients) respectively; the proportion of passive finding was 96.9% (1182243 patients). Conclusion: From 2015 to 2021, the registration rate of PTB patients aged 65 and above in China showed a decline trend, but its proportion among all patients had been increasing continuously. Therefore, the elderly are worth more attention, especially for men, ethnic minorities and people in the central and western regions; At the same time, scientifically and orderly developing PTB active case finding in elderly is worthy of further exploration.

Study on the feasibility of active tuberculosis screening strategy for the elderly based on public health service

Wu Tana, Li Yuhong, Liu Xiaoqiu

Chinese Journal of Antituberculosis. 2023, 45(4):  372-376.  doi:10.19982/j.issn.1000-6621.20220400

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Objective: To evaluate the feasibility of screening suspicious symptoms of pulmonary tuberculosis (PTB) and TB examination for the elderly relying on public health services. Methods: The retrospective survey method was used to collect the relevant information of the elderly aged 65 and above from July to December 2020 in three counties (cities) of Henan Province and three counties (cities) of Hubei Province at the implementation site of the project of “TB active screening among the elderly relying on primary medical and health institutions”, including basic information, physical examination or follow-up, symptom screening, referral and diagnosis of suspicious symptoms of PTB, and analysis of the effect of active screening strategy for PTB. Results: A total of 349842 people aged 65 and above in the above areas were included, of which 324598 were screened for suspicious symptoms of PTB, 321383 had valid screening records, and the actual screening rate was 91.87% (321383/349842). A total of 1466 cases of suspected symptoms of PTB were screened out, of which 1290 cases went to medical institutions for PTB examination. The examination rate of symptomatic PTB was 87.99% (1290/1466). Fifty-four active PTB patients were diagnosed, of which 53 had suspicious symptoms, and one had no symptoms related to PTB. The detection rate of PTB was 16.80/100000 (54/321383). In 2020, a total of 547 cases of PTB patients aged 65 years and above were found in 6 counties (cities), of which 54 cases were found through grass-roots active symptom screening. The implementation of active symptom screening strategy increased the number of elderly PTB patients by 10.95% (54/(547-54)). Conclusion: It is feasible and effective to carry out active PTB screening among the elderly by relying on primary medical and health institutions.

Epidemiological characteristics of MTB/HIV co-infection in Henan from 2016 to 2021

Zhang Pei, Zhao Ahui, Gao Min, Zhen Xinan, Yao Yuxia, Jiang Jianguo, Sun Jianwei, Sun Dingyong

Chinese Journal of Antituberculosis. 2023, 45(4):  377-382.  doi:10.19982/j.issn.1000-6621.20220366

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Objective: To analyze the epidemiological characteristics of Mycobacterium tuberculosis and HIV (MTB/HIV) co-infection in Henan, in order to provide a scientific basis for the prevention and control in the Henan and even in China. Methods: Data of co-infection in Henan from 2016 to 2021 were collected from the Annual Report of Prevention and Management of MTB/HIV co-infection in Henan Province, the statistical descriptive methods and chi-square test for linear trend were used to analyze the rate of bi-directional screening, registration, the distribution and change tendency of MTB/HIV co-infection from 2016 to 2021 in Henan. Results: Of the 591960000 permanent resident population in Henan, 290450 tuberculosis (TB) and 387785 HIV/AIDS patients were registered from 2016 to 2021. Among them, 1756 were MTB/HIV co-infection, the average annual registration rate was 0.30/100000 (1756/591960000), accounting for 0.60% (1756/290450) of TB and 0.45% (1756/387785) of HIV/AIDS patients. The detection rate of TB diagnosis from HIV/AIDS patients decreased from 0.46% (263/57116) in 2016 to 0.28% (199/69862) in 2021, and HIV antibody detected positive from TB patients decreased from 0.17% (47/27955) in 2016 to 0.10% (21/21914) in 2021, the registration rate of MTB/HIV co-infection decreased from 0.32/100000 (310/97780000) in 2016 to 0.22/100000 (220/98830000), showing a fluctuating downward trend ( {\chi }_{\mathrm{t}\mathrm{r}\mathrm{e}\mathrm{n}\mathrm{d}}^2=49.965, 44.786 and 38.841, respectively; all Ps<0.001). The proportion of MTB/HIV co-infected patients in male was significantly higher than that in female (78.72% (1365/1734) vs. 21.28% (369/1734)) from 2016 to 2021, but the difference in the proportion of male and female in the past five years was not significant ( {\chi }_{\mathrm{t}\mathrm{r}\mathrm{e}\mathrm{n}\mathrm{d}}^2=5.137, P=0.399). Meanwhile, the average annual registration rate of MTB/HIV co-infection in Zhengzhou and Zhoukou increased from 0.38/100000 (43/11190000) and 0.15/100000 (14/9220000) in 2016 to 0.46/100000 (58/127420000) and 0.26/100000 (23/88530000) in 2021, respectively, showing a fluctuating upward trend in each year ( {\chi }_{\mathrm{t}\mathrm{r}\mathrm{e}\mathrm{n}\mathrm{d}}^2=26.088, P<0.001; {\chi }_{\mathrm{t}\mathrm{r}\mathrm{e}\mathrm{n}\mathrm{d}}^2=15.536, P=0.008). Conclusion: The number of MTB/HIV co-infected patients in Henan showed a decreased trend year by year from 2016 to 2021, indicating that the MTB/HIV co-infection was effectively controlled, however, attention should be paid to the infection in male, as well as in the cities of Zhengzhou and Zhoukou.

Evaluation of implementation effect of pulmonary tuberculosis prevention and control strategy in southern Xinjiang based on synthetic control method

Mao Hongkai, Zhang Yan, Liang Zhichao, Xia Wenjun, Bao Liangliang, Mayisha·Daken , Wang Xiaomin, Cao Mingqin

Chinese Journal of Antituberculosis. 2023, 45(4):  383-390.  doi:10.19982/j.issn.1000-6621.20220509

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Objective: To evaluate the impact of the “Southern Xinjiang Model” policy on the epidemic situation of pulmonary tuberculosis (PTB) in Xinjiang Uygur Autonomous Region (referred to as “Xinjiang”) and the effect of prevention and control, to provide reference for promoting the implementation and optimization of PTB prevention and control measures in Xinjiang. Methods: Using the panel data of the reported incidence of PTB in 94 districts and counties of Xinjiang from 2011 to 2021 in the Infectious Disease Report Information Management System, the temporal trends of reported incidence of PTB in four regions of South Xinjiang (Hetian, Aksu, Kashgar, Kizilsu Kirgiz Autonomous Prefecture), other regions and the whole regions in Xinjiang were described, the correlation between them and the included influencing factors was analyzed. The “South Xinjiang Model” policy effect was evaluated using the synthetic control method, and the robustness of the results was verified with the aid of the placebo test. Results: The reported incidence rate of PTB in the four regions in southern Xinjiang from 2011 to 2021 was 316.19/100000 (337071/106601200), which was significantly higher than that in the other regions in Xinjiang (81.44/100000 (116950/143600500), χ²=186152.083, P<0.001). The results of correlation analysis showed that, from 2011 to 2021, the average reported incidence rate of PTB in 94 districts and counties in Xinjiang was 181.46/100000 (454023/250201700), which was correlated with the average proportion of agricultural population (0.436, 43.522/94) and per capita gross domestic product (GDP)(RMB 53578.10 yuan, 5036341/94)(Spearman rank correlation coefficient: 0.934 and -0.930, respectively; both Ps<0.001). Taking agricultural population proportion, GDP per capita, and number of medical beds per 1000 people, etc. as control variables, the synthetic control method was used for fitting analysis. The results showed that, from 2018 to 2021, the average annual reported incidence rate of PTB increased by 159.60/100000 (3667/2297600), 102.80/100000 (1678/1632300) and 185.22/100000 (4964/2680100), respectively, in Aksu, Hetian, and Kashgar with the policy effect of “South Xinjiang Model”. And the placebo test supported the results (all probabilities <0.05), which had a strong effect in the short term of policy intervention. Aksu and Hetian had the largest policy effect in 2019 (259.05/100000 and 165.47/100000), and Kashgar had the largest effect in 2018 (482.59/100000). Conclusion: The “South Xinjiang Model” for PTB prevention and control was conducive to discovery of PTB, and the short-term effect was particularly significant. It had a positive effect on reducing the overall transmission risk of PTB and the prevention and control of PTB epidemic in southern Xinjiang.

Effects of acetyltransferase fadA3 on acetylation of host protein and in vivo survival of Mycobacterium tuberculosis

Duan Yuheng, Zhang Lanyue, Dong Jing, Shi Yuting, Jia Hongyan, Li Zihui, Xing Aiying, Du Boping, Sun Qi, Pan Liping, Zhu Chuanzhi, Zhang Zongde

Chinese Journal of Antituberculosis. 2023, 45(4):  391-400.  doi:10.19982/j.issn.1000-6621.20220525

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Objective: To investigate the effects of acetyltransferase fadA3 in Mycobacterium tuberculosis (MTB) on acetylation modification of host protein, gene expression, and MTB survival in vivo. Methods: MTB standard strain (H37Rv) was selected from the Molecular Biology Laboratory of Institute of Tuberculosis and Thoracic Tumor/Beijing Chest Hospital, and the H37Rv-fadA3 knockout gene strain (ΔfadA3) was constructed by CRISPR-cas system-assisted non-homologous terminal conjugation (CRISPR-NHEJ). The absorbance (A value) and bacterial activity of H37Rv and ΔfadA3 were detected by microplate method in 7H9 liquid medium, and the growth curve and minimum inhibitory concentration (MIC) table were drawn. The changes in protein acetylation and gene expression of macrophages infected with H37Rv and ΔfadA3 was analyzed by Western blotting and transcriptome sequencing. The survival and pathological modifications of H37Rv and ΔfadA3 in lung tissue and macrophages of C57BL/6J mice was analyzed by colony count and hematoxylin-eosin staining. Results: The 1116 bp fragment of fadA3 was successfully knocked out to obtain the ΔfadA3 knockout strain. There was no significant difference in the A₆₀₀ values between H37Rv and ΔfadA3 on days 3, 6, 9, and 12 of cultivation (0.245±0.005 and 0.232±0.013, 0.403±0.122 and 0.385±0.009, 0.444±0.010 and 0.442±0.005, 0.675±0.027 and 0.662±0.026, respectively)(t values were 1.623, 2.351, 0.178, 0.848, respectively, all Ps>0.05). The MIC₉₀ of isoniazid, ethambutol, streptomycin, levofloxacin, PA-824, linezolid, clofazimine, rifampicin, bedaquiline, delamanid and other first and second-line antituberculosis drugs on ΔfadA3 was the same as that on H37Rv (0.006, 2.000, 0.313, 0.156, 0.250, 0.625, 1.250, 0.003, 0.125, 0.320 μg/ml, respectively). The grey value of acetylation modification in macrophages whole protein infected with H37Rv (243.100±7.125) was significantly different from that in the uninfected group (204.800±9.348) and ΔfadA3 infected group (154.500±14.890)(t=5.294, P=0.013; t=9.350, P=0.003). In ΔfadA3 infection group, 94 differential genes were up-regulated, and 7 were down-regulated compared to H37Rv infection. Moreover, there were significant differences in intracellular CFU count ((41.000±4.583)×10⁴ and (18.670±1.155)×10⁴, log₁₀ (5.531±0.203) and log₁₀ (4.541±0.276)) after H37Rv and ΔfadA3 infection in the macrophage model (72h) and mouse lung tissue (28d)(t=8.815, P=0.001; t=6.466, P<0.001). The pathological inflammatory infiltration of lung tissue in mice infected with ΔfadA3 was significantly weaker than in H37Rv-infected mice. Conclusion: The germicidal efficacy of anti-tuberculosis drugs on ΔfadA3 knockout strain was equivalent to H37Rv. The acetylation modification of host protein and gene expression could be significantly regulated by fadA3, which may act as an essential virulence factor for maintaining the survival of H37Rv in macrophages and mouse lung tissue, leading to the inflammatory infiltration of lung tissue. These finding provides the theoretical data for host-directed therapy targeting fadA3 and host protein acetylation.

Application value of Mycobacterium bovis lipopolysaccharide in the serological diagnosis of tuberculosis in animals

Wang Yuanzhi, Long Meizhen, Liu Yiduo, Zhou Xiangmei

Chinese Journal of Antituberculosis. 2023, 45(4):  401-405.  doi:10.19982/j.issn.1000-6621.20220496

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Objective: To evaluate the clinical application of Mycobacterium bovis (M.bovis) lipopolysaccharide in the serological diagnosis of tuberculosis in animals. Methods: Bioactive lipopolysaccharides were extracted from inactivated M.bovis, and tested using enzyme linked immunosorbent assay (ELISA) to detect negative bovine sera and positive bovine sera for tuberculosis, paratuberculosis, brucellosis, foot-and-mouth disease, chlamydiosis and neosporosis, to determine the specificity of lipopolysaccharides for the diagnosis of animal tuberculosis. Meanwhile, 245 bovine serum samples (177 were positive and 68 were negative for tuberculin skin test (TST)), 29 plum deer serum samples (10 were positive and 19 were negative for TST) and 14 roe deer serum samples (all positive for TST) were collected. The antibody levels were measured by ELISA, and the TST results were used as a reference to evaluate the clinical application of lipopolysaccharide in the serological diagnosis of tuberculosis in animals. Results: Except for the tuberculosis positive bovine sera, the results of the positive diseased bovine sera were not statistically different from those of the negative bovine sera (P>0.05) and were lower than the Cut off values. The overall compliance of the ELISA antibody assay based on lipopolysaccharide with the TST results was 88.54% (255/288), the overall sensitivity was 87.56% (176/201), and the overall specificity was 90.80% (79/87). Conclusion: M.bovis lipopolysaccharide can be used as one of the specific antigens for the serological diagnosis of animal tuberculosis, it helps to improve the specificity and detection rate of existing diagnostic methods, and has good application value.

Application value of multicolor melting curve analysis in detection of pre-extensive drug-resistant pulmonary tuberculosis

Zhu Yumei, Xia Zihan, Li Jinli, He Huishan, Wang Feng

Chinese Journal of Antituberculosis. 2023, 45(4):  406-411.  doi:10.19982/j.issn.1000-6621.20220418

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Objective: To evaluate the application value of multicolor melting curve analysis (MMCA) in detection of pre-extensive drug-resistant pulmonary tuberculosis (pre-XDR-PTB). Methods: A total of 129 sputum samples from 129 patients with positive culture and initially identified as multidrug-/rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB) were collected. All the patients were registered in the Shenzhen Center for Chronic Disease Control and district-level tuberculosis prevention and control institutions from January 2019 to December 2020. The samples were detected by drug susceptibility tests (DST) of three fluoroquinolones (ofloxacin (Ofx), levofloxacin (Lfx), and moxifloxacin (Mfx)) and MMCA. Sanger sequencing was performed as the third-party verification of the results. Using DST as the gold standard, the efficacy of MMCA in detecting fluoroquinolone resistance in patients with MDR/RR-PTB was analyzed. Results: Using DST as the gold standard, the sensitivity, specificity, and Kappa values of the MMCA method for detecting fluoroquinolone resistance in MDR/RR-PTB patients’ samples were 87.0% (40/46), 94.0% (78/83), and 0.813, respectively, for Ofx; 97.3% (36/37), 90.2% (83/92), and 0.822, respectively, for Lfx; 92.3% (24/26), 79.6% (82/103), and 0.565, respectively, for Mfx. If combining the DST results of three fluoroquinolones and defining fluoroquinolone resistance as resistance to any one of the three fluoroquinolones, the sensitivity, specificity, and Kappa value of the MMCA method for detecting fluoroquinolone resistance in MDR/RR-PTB patients’ samples were 85.1% (40/47), 93.9% (77/82), and 0.797, respectively. Sanger sequencing was performed on 52 suspected of drug resistance samples. Among these samples, 96.2% (50/52) had the same sequencing results as MMCA, and 3.8% (2/52) of the samples had mutations in the non-detection region of MMCA. Conclusion: The results of MMCA were consistent with those of DST, and thus MMCA could be used to detect pre-XDR-PTB.

Clinical characteristics and maternal and infant outcomes of 13 pregnant women with rifampicin resistant and multidrug resistant tuberculosis

Lai Min, Wu Guihui, Chen Hongde, Cheng Yao, Luo Haixia, He Kejing

Chinese Journal of Antituberculosis. 2023, 45(4):  412-419.  doi:10.19982/j.issn.1000-6621.20220506

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Objective: To investigate the clinical feature, treatment and outcome of rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) pregnant women. Methods: The clinical data of 13 pregnant women with drug-resistant tuberculosis (DR-TB) admitted to Public Health Clinical Center of Chengdu from January 2017 to April 2022 were retrospectively analyzed, and the clinical characteristics, treatment and outcome of the maternal and infant patients were descriptively analyzed. Results: A total of 13 pregnant women with RR/MDR-TB were enrolled in this study. Fever (53.8%, 7/13), cough (84.6%, 11/13) and expectoration (53.8%, 7/13) were the main clinical symptoms. Until November 2022, 11 patients survived (84.6%) and 2 patients died (15.4%), 9 patients (69.2%, 9/13) cured, 2 patients (15.4%, 2/13) were still in treatment (1 relapse after 1 year drug withdrawal). Severn patients (53.8%) had 9 adverse effects during the treatment, including liver dysfunction (30.8%, 4/13), myelosuppression (15.4%, 2/13), nausea and vomiting (7.7%, 1/13), blurred vision (7.7%, 1/13) and rash (7.7%, 1/13). Eight cases (61.5%, 8/13) had abortion or induced labor. Five cases (38.5%, 5/13) delivered, including 1 case of natural labor, 4 cases of cesarean section. Among the 5 newborns, 3 premature delivery, 2 low birth weight, all of whom with no birth defects or congenital tuberculosis. During the 5 to 66 months follow-up, all the infants survived, with one’s height and weight two standards lower than contemporary, 1 had language retardation, and the other 3 were normal. Conclusion: The pregnant women with RR/MDR-TB had no specific clinical manifestation. Most of them had favourable outcomes after effective anti-tuberculosis treatment. Most induced labor in early and middle pregnancy. There was no serious adverse outcomes in infants except partial growth restriction.

Review Articles

Progress in diagnosis and treatment of Mycobacterium avium-intracellular complex vertebral osteomyelitis

Zhou Weidong, Zhang Zhengdong, Lin Mei, Li Tongxia

Chinese Journal of Antituberculosis. 2023, 45(4):  420-425.  doi:10.19982/j.issn.1000-6621.20230020

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In recent years, more and more reports have been reported about the spinal infection of Mycobacterium avium-intracellular complex (MAC) group, and more cases of clinical misdiagnosis and mistreatment have been reported. The treatment effect of this disease is poor. This paper reviews the epidemiology and susceptibility factors of MAC vertebral osteomyelitis, the clinical manifestations, imaging examination and laboratory examination, and analyzes the causes of misdiagnosis and unsatisfactory therapeutic effect, so as to help clinicians understand more about MAC spinal infection, and promote the standardized diagnosis and treatment of MAC vertebral osteomyelitis.

Progress of innate immune mechanism activated by Mycobacterium tuberculosis DNA-mediated pattern recognition receptors

Wang Wenjing, Sun Hong, Sun Zhaogang

Chinese Journal of Antituberculosis. 2023, 45(4):  426-433.  doi:10.19982/j.issn.1000-6621.20220399

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Mycobacterium tuberculosis (MTB) is a major pathogen which cause tuberculosis. Innate immunity plays an important role in the host’s resistance to MTB invasion, and multiple pattern recognition receptors (PRR) in cells are involved in MTB. As the “initiator” of innate immunity, PRR activate innate immunity through signal transduction after recognizing MTB. There are many kinds of MTB components that can be recognized by PRR, including DNA, lipopolysaccharide, protein, etc. This paper focuses on the MTB DNA, from its source, the types of PRR which can recognize MTB DNA, and the mechanism by which PRR uses MTB DNA as a pathogenic-associated molecular pattern to mediate related molecular signaling pathways to activate innate immunity. The process of MTB DNA activating innate immunity via PRR was reviewed in three aspects, and the research progress of the innate immune mechanism activated by PRR such as Toll-like receptor 9, cyclic GMP-AMP synthase and absent in melanoma 2-like receptors was emphatically discussed. At last, the application prospects of MTB DNA were discussed, to expand the development of MTB DNA-related vaccines and the diagnosis of tuberculosis.

Short Articles

The diagnostic value of simultaneous amplification and testing for Mycobacterium tuberculosis technique on alveolar lavage fluid for diagnosing pulmonary tuberculosis

Zou Yuanwu, Li Jing, Wang Biao, Wang Zhuo, Qu Shaoyi, Yuan Zhimin, Wu Qianhong

Chinese Journal of Antituberculosis. 2023, 45(4):  434-436.  doi:10.19982/j.issn.1000-6621.20230006

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Alveolar lavage fluid specimens from inpatients with clinical diagnosis of suspected tuberculosis in Shaanxi Provincial Hospital of Tuberculosis Prevention and Treatment from October 2021 to July 2022 were collected, and acid-fast bacilli smear, mycobacterium culture (MGIT 960) and strain identification, GeneXpert MTB/RIF and simultaneous amplification and testing for Mycobacterium tuberculosis (SAT-TB) test were performed. The results were analyzed and evaluated. Taking culture result (MGIT 960) as the standard, the sensitivity of SAT-TB in the diagnosis of tuberculosis was 80.61% (399/495), and the specificity was 87.74% (1259/1435), the positive predictive value was 69.39% (399/575), the negative predictive value was 92.92% (1259/1355), and the Youden index was 0.68. SAT-TB technique has high sensitivity and specificity, is of certain value for rapid diagnosis of active tuberculosis in clinic practice.