Table of Content

10 August 2024, Volume 46 Issue 8

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Special Topic

Diagnosis and treatment of nontuberculous mycobacteria diseases in the past 60 years

Duan Hongfei

Chinese Journal of Antituberculosis. 2024, 46(8):  863-868.  doi:10.19982/j.issn.1000-6621.20240114

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Nontuberculous mycobacteria (NTM) diseases have been recognized for over six decades, with progressively advancing levels of diagnosis and treatment. During the 1990s, a pivotal randomized controlled multicenter study demonstrated the efficacy of macrolide-based regimens against Mycobacterium avium complex infections. Concurrently, the advent of molecular biology techniques for bacterial identification supplanted traditional biochemical methods, greatly enhancing the capacity of medical institutions to diagnose and treat NTM infections. Recent years have witnessed critical developments, including the rapid identification of Mycobacterium species in clinical specimens, the recognition of reinfection as a primary cause of treatment failures in NTM disease, and the proven effectiveness of amikacin liposomes in treating Mycobacterium avium complex pulmonary disease. Drawing on experiences from tuberculosis management, future strategies for NTM should focus on developing rapid diagnostic tests for core drug sensitivities to facilitate the formulation of concise and effective treatment regimens.

Interpretation of Standards

Interpretation of WHO consolidated guidelines on tuberculosis. Module 6: tuberculosis and comorbidities-HIV

Li Zhili, Liu Yuhong

Chinese Journal of Antituberculosis. 2024, 46(8):  869-873.  doi:10.19982/j.issn.1000-6621.20240225

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In April 2024, the World Health Organization (WHO) published the WHO consolidated guidelines on tuberculosis: Module 6: tuberculosis and comorbidities-HIV contained specific recommendations on screening, diagnosis, treatment, care, and prevention of HIV-associated tuberculosis. These recommendations aim to reduce the disease burden, morbidity, and mortality among patients with both tuberculosis and HIV. The author interprets the key content of this guideline for reference.

Interpretation of World Health Organization’s Co-administration of Treatment for Drug-resistant Tuberculosis and Hepatitis C: 2024 Update

Yang Liangzi, Zhang Peize, Lu Shuihua

Chinese Journal of Antituberculosis. 2024, 46(8):  874-876.  doi:10.19982/j.issn.1000-6621.20240191

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On April 9, 2024, the World Health Organization published the updated guidelines for the Co-administration of Treatments for Drug-resistant Tuberculosis and Hepatitis C, as part of a rapid communication effort. This paper elucidates key aspects of the guideline, detailing the epidemiological background, pivotal evidence underpinning the updates, and significant findings. A comprehensive summary and forthcoming steps for the guideline’s advancement are presented. Additionally, the authors evaluate the practical applicability of these guidelines in Chinese clinical settings and propose areas for future research, aiming to enhance the management of these coexisting conditions.

Interpretation of clinical standards for drug-susceptible tuberculosis in children and adolescents

Li Qinjing, Jiao Weiwei, Wang Zeming, Shen Adong

Chinese Journal of Antituberculosis. 2024, 46(8):  877-885.  doi:10.19982/j.issn.1000-6621.20240202

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To standardize and guide the diagnosis, treatment, and management of drug-sensitive tuberculosis (DS-TB) in children and adolescents, the International Journal of Tuberculosis and Lung Diseases published the Clinical Standards for Drug-Sensitive Tuberculosis in Children and Adolescents on February 27, 2023. These standards were developed by 52 global experts in pediatric tuberculosis diagnosis and treatment, basic research, public health, microbiology, epidemiology, and social sciences through a Delphi-method consensus. They recommended eight standards for optimal diagnosis, treatment, and management of DS-TB in children and adolescents. This article interprets these standards with the aim of promoting standardized management of DS-TB among healthcare professionals involved in tuberculosis diagnosis and treatment, ultimately contributing to the goal of ending tuberculosis.

Original Articles

Analysis of clinical results of blood concentration detection of antituberculosis drugs by liquid chromatography-tandem mass spectrometry

Shi Lulu, Jing Hui, Liang Min, Li Xuezheng

Chinese Journal of Antituberculosis. 2024, 46(8):  886-891.  doi:10.19982/j.issn.1000-6621.20240115

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Objective: To assess the plasma concentrations of first-line antituberculosis drugs in patients diagnosed with pulmonary tuberculosis using liquid chromatography-tandem mass spectrometry. Methods: This retrospective study enrolled patients treated for pulmonary tuberculosis at the Shandong Public Health Clinical Center from January to December 2023. Patients included in the analysis underwent first-line antituberculosis drug plasma concentration measurements. The cohort comprised 144 patients administered ethambutol (EMB; 0.75 g orally once daily), 209 patients given isoniazid (INH; 0.3 g orally once daily), 78 patients prescribed pyrazinamide (PZA; 0.75 g orally twice daily), and 181 patients on rifampicin (RFP; 0.6 g orally once daily). Demographic data, including age and gender, as well as the results of blood drug concentration measurements for first-line antituberculosis drugs, were collected. The study analyzed plasma concentrations of EMB, INH, PZA, and RFP two hours post-administration, assessing their correlations with gender and age. Results: Two hours following administration, a significant proportion of patients exhibited plasma drug concentrations below the established reference ranges: 62.5% (90/144) for EMB, 54.1% (113/209) for INH, 34.6% (27/78) for PZA, and 22.7% (41/181) for RFP. Subgroup analyses revealed gender-related differences in plasma drug concentrations below the therapeutic threshold: 67.4% (64/95) of male patients for EMB (<2 mg/L), 53.1% (68/128) for INH (<3 mg/L), 38.9% (21/54) for PZA (<20 mg/L), and 25.9% (30/116) for RFP (<8 mg/L); compared to 53.1% (26/49), 55.6% (45/81), 25.0% (6/24), and 16.9% (11/65) of female patients for the same drugs, respectively. However, these differences were not statistically significant (χ² values were 2.823, 0.118, 1.416, and 1.900 with P values of 0.093, 0.731, 0.234, and 0.168, respectively). Additionally, no correlation was observed between the age distribution of the study subjects and the prevalence of subtherapeutic drug concentrations. Conclusion: It is frequently observed that patients with pulmonary tuberculosis exhibit subtherapeutic plasma concentrations of first-line antituberculosis drugs just two hours post-administration. Notably, the prevalence of low plasma concentrations is higher for EMB and isoniazid INH compared to PZA and RFP.

Reliability analysis of rifampicin-resistance detected by different diagnostics as a predictor for multidrug-resistant tuberculosis

Xue Yi, Liang Qian, Qi Haoran, Liang Ruixia, Huang Hairong

Chinese Journal of Antituberculosis. 2024, 46(8):  892-896.  doi:10.19982/j.issn.1000-6621.20240131

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Objective: To evaluate the reliability of rifampicin-resistance (RR) detected by different diagnostics as a predictor for multidrug-resistant tuberculosis (MDR-TB). Methods: A retrospective study was performed by searching the Hospital Information System of Henan Chest Hospital. A total of 130 TB patients who had performed MassARRAY assay for drug resistance detection from July 2021 to November 2022 were enrolled. Of these patients, their GeneXpert MTB/RIF assay (Xpert) and phenotypic drug susceptibility testing (pDST) results were collected for comparative analysis. Results: Among the 130 enrolled patients, 37 (28.46%) were reported as RR by MassARRAY, 38 (37.25%) of 102 patients with Xpert-positive result were categorized as RR patients, 22 (45.83%) of the 48 patients who underwent pDST after a positive culture were categorized as RR. Among patients with RR detected in MassARRAY, the proportion of MDR diagnosed by MassARRAY and pDST was 83.78% (31/37) and 90.48% (19/21), respectively. Among RR patients detected by Xpert, the proportion of MDR diagnosed by MassARRAY and pDST was 73.68% (28/38) and 76.00% (19/25), respectively. In patients with RR detected by pDST, the proportion of MDR diagnosed by MassARRAY and pDST was 90.91% (20/22) and 95.23% (20/21), respectively. Among RR patients diagnosed both by MassARRAY and Xpert, 88.89% (24/27) and 88.89% (16/18) were diagnosed as MDR by MassARRAY or pDST, respectively. Among RR patients detected by any method of MassARRAY or Xpert, 72.92% (35/48) and 75.00% (21/28) were reported as MDR by MassARRAY or pDST, respectively. Conclusion: The RR diagnosed by different diagnostics is a reliable indicator of MDR-TB, but the predictive reliability is related to the accuracy of RR diagnosis.

Analysis of screening effect of recombinant Mycobacterium tuberculosis fusion protein in screening Mycobacterium tuberculosis infection in close contacts of pulmonary tuberculosis patients

Xu Chunhua, Zhu Shiyu, Hu Yi, Yi Kehua, Song Canlei, Wang Zichun, Wu Yong, Wang Qing, Yang Qianru, Shen Xin

Chinese Journal of Antituberculosis. 2024, 46(8):  897-902.  doi:10.19982/j.issn.1000-6621.20240137

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Objective: To evaluate the accuracy and feasibility of recombinant Mycobacterium tuberculosis fusion protein (EC) skin test in tuberculosis screening among close contacts of pulmonary tuberculosis patients and to provide technical recommendations for improving tuberculosis control,and to understand the status of latent infection of Mycobacterium tuberculosis (LTBI) in close contacts. Methods: A total of 140 close contacts of tuberculosis patients from Fengxian and Jinshan Districts in Shanghai City were selected as the study subjects. Both IGRA and EC skin tests were administered. Kappa test was used to assess the consistency between the results of those two methods, and chi-square test was employed to compare the differences between these two detection methods. A P-value of <0.05 was considered statistically significant. Results: A total of 140 subjects were included in the study, consisting of 55 males and 85 females. The positive rate of IGRA was 15.00% (21/140), while the positive rate of EC skin test was 14.29% (20/140). There was no statistically significant difference between them (χ²=0.029, P=0.866), with a Kappa value of 0.857 (P=0.001), indicating a high degree of consistency. When IGRA was used as the reference standard for tuberculosis infection, EC skin test demonstrated a sensitivity of 85.71% (18/21), a specificity of 98.32% (117/119), a positive predictive value of 90.00% (18/20), and a negative predictive value of 97.50% (117/120). The positive rate of EC in males (32.73%, 18/55) was significantly higher than that in females (2.35%, 2/85), and the difference was statistically significant (χ²=17.983,P<0.001). Conclusion: EC skin test demonstrates high specificity and can be utilized for Mycobacterium tuberculosis infection screening among close contacts of tuberculosis patients. However, due to limitations regarding age range and contraindications for use, implementing a combined screening method of EC and IGRA is advisable.

Construction and evaluation of a model for predicting malnutrition in patients with pulmonary tuberculosis and diabetes mellitus

Liu Ling, Zeng Yi, Wang Jin, Liu Xiaoling, Liu Yan, Lin Feishen, Guo Jing

Chinese Journal of Antituberculosis. 2024, 46(8):  903-909.  doi:10.19982/j.issn.1000-6621.20240140

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Objective: To explore the influencing factors of malnutrition in patients with pulmonary tuberculosis complicated with diabetes mellitus, construct and verify a nomogram prediction model. Methods: The clinical data of 401 patients with tuberculosis combined with diabetes admitted to the Tuberculosis Department of Nanjing Second Hospital from October 2021 to September 2023 were collected with convenience sampling. The patients were divided into modeling group (n=281) and validation group (n=120) according to a ratio of 7∶3. Logistic regression analysis was performed to construct a nomogram prediction model. Area under curve (AUC) and Hosmer-Lemeshow goodness of fit test were used to evaluate the prediction efficiency and calibration degree of the model. Results: Age (OR=3.796, 95%CI: 1.159-12.627), duration of disease >1 month (OR=5.711, 95%CI: 1.879-17.274), glycosylated hemoglobin (OR=5.951, 95%CI: 1.517-23.269), Charlson comorbidity index (OR=8.079, 95%CI: 2.345-27.681) and FRAIL (fatigue, resistance, ambulation, illness and loss) score ≥3 (OR=9.145, 95%CI: 2.404-34.172) were independent risk factors for malnutrition. The above variables were used to construct a nomogram prediction model. Hosmer-Lemeshow test of the model showed that P=0.625, AUC=0.897, the Youden index was 0.584 and the optimal critical value was 0.615. The sensitivity of the verification group was 67.5%, the specificity was 93.8%, and the prediction accuracy was 85.0%. Conclusion: The nomogram model constructed in this study has certain predictive value and clinical applicability, could provide reference for early identification of malnutrition and thereafter taking targeted nutrition intervention measures in clinical work.

Clinical analysis of low dose thalidomide in the adjuvant treatment of 20 cases of adult tuberculous meningitis complicated with paradoxical reactions

Zhao Xueyao, Han Lijun, Feng Guodong, Qin Guixiang, Sun Li

Chinese Journal of Antituberculosis. 2024, 46(8):  910-917.  doi:10.19982/j.issn.1000-6621.20240069

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Objective: To analyze the clinical effectiveness and safety of low dose thalidomide in the adjuvant treatment of tuberculous meningitis (TBM) complicated with paradoxical reactions in adults. Methods: A total of 20 patients who met the diagnostic criteria of TBM complicated with paradoxical reactions admitted to Changchun Infectious Disease Hospital from January 1, 2020 to December 30, 2022 were selected for retrospective study. Oral thalidomide (25 mg, 4 times/day) was administered without adjusting the dosage of original hormone and anti-tuberculosis therapy regimen. Clinical symptoms, cerebrospinal fluid (CSF) parameters, imaging findings and adverse drug reactions were analyzed. Results: Among the 20 patients, 14 (70.0%) had new tuberculoma, 11 (55.0%) had deterioration of original tuberculoma, 10 (50.0%) had increased cisternal effusion, and 5 (25.0%) had new cerebral infarction. After treatment with thalidomide, the lesions of 14 patients with new tuberculoma and 11 patients with deterioration of original tuberculoma improved significantly, tuberculous nodules ≤3 mm could be completely absorbed, and tuberculous nodules >3 mm could be completely absorbed or the lesions shrank. In 10 patients with increased cisternal exudation, the lesions subsided significantly. In 5 patients with cerebral infarction, no progressive stroke occurred, and the edema around the infarction significantly subsided to a softening lesion. Of the 17 patients with abnormal CSF, 8 had their CSF white blood cell counts recovered to normal, and 9 had CSF parameters improved and stabilized. The median treatment time of thalidomide was 16 (12,16) weeks. All patients stopped thalidomide after intracranial lesions got improved significantly or CSF parameters improved and stabilized. During treatment, 2 patients developed peripheral neuritis which improved after receiving nutritional neurotherapy, and no other adverse events attributable to thalidomide were reported. Conclusion: Low dose thalidomide adjuvant treatment on tuberculous meningitis paradoxical reaction can effectively improve intracranial lesions and CSF parameters of patients, with good safety.

Application of individualized 3D printed artificial vertebral body replacement in reconstruction of complex tuberculosis-affected spine

Liu Siyuan, Cun Xinhua, Wu Lei, Bai Ping, Zhou Yi, Rao Tao, Chen Lin, Dou Jichen, Zhao Heng, Wang Yizhou

Chinese Journal of Antituberculosis. 2024, 46(8):  918-925.  doi:10.19982/j.issn.1000-6621.20240092

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Objective: To investigate the clinical effectiveness of individualized 3D printed artificial vertebrae in vertebral reconstruction of tuberculosis-affected spine. Methods: From May 2021 to May 2023, 208 patients with spinal tuberculosis were treated in Department of Orthopedics of the Third People’s Hospital of Kunming City, among whom 15 were treated with debridement surgery and individualized 3D printed artificial vertebral reconstruction. The patients included 5 males and 10 females, aged from 31 to 72 years old (45.1±13.2) years. Lesions located at thoracic vertebra for 2 cases, at thoracolumbar spine for 2 cases, at lumbar spine for 1 case and at lumbosacral spine for 10 cases. Lesions affected 2 vertebrae in 6 cases, and more than 3 vertebrae in 9 cases. Postoperative stability of artificial vertebral body, bone ingrowth of adjacent vertebral body, preoperative and postoperative neurological changes, visual analogue scale (VAS) scores, deformity correction, and recurrence of tuberculosis were observed and analyzed. Results: All 15 patients successfully completed the operation without serious vascular and neurological complications. Among them, there were 8 cases taking anterior surgery approach, 2 cases taking posterior approach and 5 cases taking combined posterior and anterior approach. The average operative time was (292.2±119.0) min, and the average intraoperative blood loss was (553.3±333.5) ml. Compared with the preoperative VAS score (5.7±0.9), average VAS scores at 7 d postoperative and at last follow up (2.9±0.5 and 1.8±0.5) declined significantly (t=9.599, P<0.001; t=13.752, P<0.001). At 1 month after surgery, one case with preoperative Frankel grade A gradually recovered to grade D, 2 cases with preoperative Frankel grade B recovered to grade D, and 1 case with Frankel grade B recovered to grade C. In 2 patients underwent kyphosis correction during surgery, no loosening and displacement of the artificial vertebrae and no failure of internal fixation were observed during the follow-up. All 15 patients had no tuberculosis recurrence during follow-up. Conclusion: The short-term effectiveness of individualized 3D printed artificial vertebral body in the reconstruction of tuberculosis-affected spine is relatively good, while the fusion of artificial vertebral bodies needs to be further observed and studied.

Analysis of the clinical characteristics and influencing factors of pulmonary tuberculosis patients with diabetes mellitus in Shantou City from 2016 to 2022

Cai Qinghe, Fu Hui, Chen Ruiming, Fan Youming, Yang Qingwei

Chinese Journal of Antituberculosis. 2024, 46(8):  926-934.  doi:10.19982/j.issn.1000-6621.20240093

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Objective: To analyze the clinical characters and influencing factors for pulmonary tuberculosis (PTB) patients with diabetes mellitus (DM), so as to provide basis for improving the case detection and treatment effect of comorbid patients. Methods: The clinical data of tuberculosis patients registered and treated in designated tuberculosis hospitals in Shantou from 2016 to 2022 were obtained through the “Shantou Tuberculosis Surveillance and Report Management System”, a subsystem of the “China Disease Control and Prevention Information System”. The data included the number of registered patients, sociodemographic characteristics (including age, gender, ethnicity, place of residence, occupation and floating population, etc.), clinical characteristics (including the type of tuberculosis, previous treatment history and diabetes mellitus) and anti-tuberculosis treatment information (including the pathway of patient visit and anti-tuberculosis treatment outcomes). The disease characteristics of patients with or without diabetes mellitus were analyzed. Logistic regression model was used to analyze the relevant factors affecting whether pulmonary tuberculosis was combined with diabetes. Results: From 2016 to 2022, a total of 21085 pulmonary tuberculosis patients were registered in Shantou City, and 20968 eligible patients were included as the study subjects. The proportion of tuberculosis patients with diabetes was 8.08% (1694/20968), and increased from 1.97% (67/3406) in 2016 to 15.78% (346/2192) in 2022 with annual increasing trend ( {\chi }_{\mathrm{t}\mathrm{r}\mathrm{e}\mathrm{n}\mathrm{d}}^2=438.749, P<0.001). The proportion of PTB-DM who visited the clinic within one month (39.27% (665/20968)) was significantly lower than that of the tuberculosis patients without diabetes (46.99% (9056/20968)), with a statistically significant difference (χ²=42.536, P<0.001). The results of multivariate analysis showed that compared with local reseidents, people aged <30 years, farmer/fisherman/worker, patients with symptoms, negative etiology, cured, negative sputum result at the end of two month of treatment, patient who visited clinic within one month, floating population, patients aged 30-59 years or 60-95 years old, management cadres/medical personnel, housekeeping, retired persons, business service personnel, patients detected by tracking, health examination, positive etiology, people lost to follow-up, positive sputum result at the end of 2 months of treatment, patients who visited within 1-3 months, 3-6 months and 6-12 months were more likely to have diabetes (OR (95%CI)=1.294 (1.156-1.449), 17.026 (10.783-26.882), 20.966 (13.240-33.199), 2.521 (1.401-4.536), 1.943 (1.709-2.210), 3.630 (2.755-4.783), 2.945 (1.953-4.442), 1.598 (1.354-1.887), 1.820 (1.190-2.783), 2.554 (2.151-3.031), 2.114 (1.572-2.843), 2.717 (2.085-3.540), 1.229 (1.094-1.381), 1.312 (1.101-1.563), 1.244 (1.001-1.544)). Conclusion: The average prevalence of PTB-DM patients in Shantou is significantly lower than the previous reported average level, but its annual increasing rate has exceeded the reported average level, which should be paid attention to. In addition, the early detection and treatment monitoring of diabetes among the floating population, the elderly patients, the light physical labor, patients by tracing, the patients with positive sputum test at initial diagnosis and the end of 2 months of treatment, and patients failed to visit clinic within one month should be strengthened, and timely intervention should be provided.

Study on the effect of thiol acetyltransferase mshD on the growth and stress response of Mycobacterium tuberculosis

Zhang Lanyue, Wang Yingchao, Liu Weiyi, Shang Xuetian, Jia Hongyan, Zhu Chuanzhi, Zhang Zongde, Pan Liping

Chinese Journal of Antituberculosis. 2024, 46(8):  935-941.  doi:10.19982/j.issn.1000-6621.20240184

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Objective: To investigate the influence of thiol acetyltransferase MshD on the growth dynamics, stress resilience, and reactive oxygen species (ROS) modulation in Mycobacterium tuberculosis (MTB) under in vitro conditions. Methods: Employing CRISPR-NHEJ gene editing, this study established an mshD gene knockout strain (ΔmshD) and a complemented strain (ΔmshD::mshD). We monitored the growth trajectories of the H37Rv wild-type strain (WT), the ΔmshD strain, and the ΔmshD::mshD strain in both liquid and solid media. Additionally, we assessed the impact of exogenously added L-cysteine and catalase on the growth of these strains. The sensitivity of the strains to various stressors, including H₂O₂, dithiothreitol (DTT), and sodium dodecyl sulfate(SDS), and their recovery post-stress intervention with exogenous catalase were evaluated. Furthermore, flow cytometry was utilized to measure the ROS levels in the strains both prior to and following SDS exposure. Results: The ΔmshD strain exhibited significantly slower growth on solid media compared to the WT and ΔmshD::mshD strains. However, the introduction of exogenous catalase reinstated their growth patterns to near-normal levels. In survival assays, the ΔmshD strain showed markedly reduced resilience against DTT (WT: (6.96±2.02) %, ΔmshD: (0.02±0.00) %, ΔmshD::mshD: (6.64±0.77) %; F=29.700, P<0.001), H₂O₂ (WT: (0.23±0.06) %, ΔmshD: (0.01±0.00) %, ΔmshD::mshD: (0.26±0.06) %; F=25.520, P=0.001), and SDS (WT: (0.12±0.03) %, ΔmshD: (0.01±0.00) %, ΔmshD::mshD: (0.18±0.04) %; F=19.540, P=0.002), with all differences reaching statistical significance. Catalase supplementation notably restored the survival rate of the ΔmshD strain. Additionally, ROS levels in the ΔmshD strain were elevated compared to WT (WT: 95.100±2.553, ΔmshD: 106.000±4.000, ΔmshD::mshD: 94.667±3.055; F=11.650, P=0.009) and further increased following SDS exposure (WT: 436.000±8.000, ΔmshD: 533.667±4.726, ΔmshD::mshD: 441.333±2.517; F=292.900, P<0.001), underlining significant oxidative stress responses. Conclusion: Deletion of the mshD gene impairs growth in solid culture mediums and diminishes MTB’s ability to withstand various stressors. The ΔmshD strain exhibited elevated endogenous ROS levels. Importantly, the exogenous application of catalase was able to partially rectify the growth and survival deficits observed in the ΔmshD strain.

Consistency between phenotypic resistance to fluoroquinolones and genetic mutations in rifampicin resistant Mycobacterium tuberculosis strains

Yu Lan, Chen Shuangshuang, Wang Nenhan, Tian Lili, Zhao Yanfeng, Fan Ruifang, Liu Haican, Li Chuanyou, Dai Xiaowei

Chinese Journal of Antituberculosis. 2024, 46(8):  942-950.  doi:10.19982/j.issn.1000-6621.20240133

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Objective: To elucidate the mutation profiles of fluoroquinolones (FQs) resistance genes in Mycobacterium tuberculosis (MTB) and to analyze the correlation between specific genetic mutations and the minimum inhibitory concentrations (MICs) of FQs. Methods: Positive strains isolated and cultured from rifampicin-resistant tuberculosis (RR-TB) patients, who were admitted to tuberculosis prevention and control institutions and designated hospitals in Beijing between 2016 and 2021, were selected for drug sensitivity testing using the microplate method. The MICs of levofloxacin (Lfx) and moxifloxacin (Mfx) for these RR-MTB strains were determined and summarized. Concurrently, first-generation sequencing was performed. The relationship between the mutation characteristics of the gyrA and gyrB genes, which were associated with FQs resistance, and the MICs of FQs was analyzed. Phenotypic drug sensitivity testing (pDST) results were used as a reference standard to evaluate the performance of genotypic drug sensitivity testing (gDST) in detecting FQs resistance. Additionally, the reasons for discrepancies between phenotypic and genotypic resistance in RR-MTB strains were investigated. Results: Among the 303 RR-MTB strains analyzed, the pDST resistance rate to FQs was 27.7% (84/303), and the detection rate of gyrA gene mutations was 25.1% (76/303). No gyrB gene mutations were detected. Using pDST results as the reference standard, the sensitivity and specificity of gDST for detecting FQ resistance in RR-MTB were 84.5% (71/84; 95%CI: 74.6%-91.2%) and 97.7% (214/219; 95%CI: 94.5%-99.1%), respectively. There were 25 strains with inconsistent results between the two methods, resulting in an inconsistency rate of 8.3% (25/303). The MIC of FQs-resistant strains was predominantly 2 μg/ml, with the most common mutation site located at codon 94 (53.9%, 41/76). The gyrA gene mutations at codons 88 and 94 were completely consistent with pDST resistance, while the consistency rates of pDST resistance at codons 90 and 91 were 95.8% (23/24) and 3/5, respectively. The mutation at position 88 was linked to resistance to Lfx in pDST and high-level resistance to Mfx. The mutation at codon 90, predominantly an alanine-to-valine substitution (92.3%, 24/26), resulted in MICs at the critical concentrations for Lfx (1 μg/ml) and Mfx (0.25 μg/ml). The aspartic acid mutation at codon 94 was associated with high-level resistance to Lfx and Mfx when mutated to asparagine (1/1). Additionally, this aspartic acid mutation, when altered to tyrosine, was linked to resistance to Lfx (1/1) and high-level resistance to Mfx (1/1). Conclusion: The primary mechanism of FQs resistance in RR-MTB in Beijing is attributed to mutations in the gyrA gene. Different gyrA mutations are indicative of varying levels of FQs resistance. The concordance between pDST and gDST for detecting FQs resistance in RR-MTB is high. Consequently, gDST can be implemented early to identify FQs resistance in RR-TB patients, facilitating the clinical development of effective treatment plans.

Analysis of tuberculosis incidence and influencing factors in type 2 diabetic patients in community

Jiang Bijia, Chen Cheng, Zhou Jinyi, Zhu Limei, Su Jian, Lu Wei

Chinese Journal of Antituberculosis. 2024, 46(8):  951-957.  doi:10.19982/j.issn.1000-6621.20240051

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Objective: To investigate the incidence and determinants of tuberculosis among community-dwelling patients with type 2 diabetes, aiming to establish a theoretical foundation for developing integrated prevention and treatment strategies for this comorbidity. Methods: This retrospective cohort study involved 20053 community-dwelling type 2 diabetes patients aged 35 and above, registered in the basic public health service management systems of Changshu City, Qingjiangpu District, and Huai’an District of Jiangsu Province from December 2013 to December 2019. Using the Tuberculosis Management Information System, we matched the data of newly diagnosed tuberculosis patients during the same period to identify affected individuals within the study cohort. A nested case-control study was established, matching non-tuberculosis patients to tuberculosis patients using a 1∶4 propensity score. Multivariate logistic regression was employed to analyze factors influencing the incidence of tuberculosis among type 2 diabetes patients in the community. Results: Among the 20053 diabetic patients studied, there were 123 new cases of tuberculosis, including 4 extrapulmonary cases. The cumulative incidence rate was 613.37 per 100000 (123/20053), with an average annual incidence of 102.23 per 100000 (20.5/20053). The cumulative incidence was significantly higher in males at 1119.31 per 100000 (88/7862) compared to females at 287.10 per 100000 (35/12191), with a statistically significant difference (χ²=54.301, P<0.001). Additionally, rural residents exhibited a higher cumulative incidence rate of 718.93 per 100000 (83/11545) compared to urban residents at 470.15 per 100000, also statistically significant (χ²=4.973, P=0.026). Multivariate logistic regression analysis identified an increased body mass index as a protective factor against tuberculosis among diabetic patients, with an odds ratio (OR) of 0.422 (95%CI: 0.288-0.617). In contrast, elevated levels of glycosylated hemoglobin (OR=2.019, 95%CI: 1.195-3.410) and urea (OR=1.727, 95%CI: 1.121-2.661) emerged as significant risk factors for tuberculosis. Furthermore, analysis from 2013 to 2019 revealed a negative correlation between the mean years to TB onset and increased fasting blood glucose (r=-0.130) in the TB cohort. Conclusion: This study demonstrates that the cumulative incidence of tuberculosis among community-dwelling type 2 diabetes patients is substantially higher than the general population during the same period. It underscores the necessity of targeting interventions towards diabetic patients with suboptimal glycemic control and related complications to mitigate their elevated risk of tuberculosis.

Strategy-analysis of drug-resistant tuberculosis screening based on all suspected tuberculosis patients of Liuzhou City, Guangxi, 2019—2020

Liang Yuexin, Liu Aimei, Zeng Huipin, Huang Lihua, Lyu Liuying, Zeng Xinyan, Li Liyuan, Huang Junli

Chinese Journal of Antituberculosis. 2024, 46(8):  958-966.  doi:10.19982/j.issn.1000-6621.20240121

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Objective: To understand the situation of drug-resistant tuberculosis (DR-TB) screening in all suspected TB patients in Liuzhou, Guangxi, and to provide a scientific basis for further optimization of screening strategies. Methods: A prospective study was conducted by selecting 6050 suspected tuberculosis patients from 5 urban districts (Chengzhong, Yufeng, Liunan, Liubei, Liujiang) and 5 counties (Liucheng, Luzhai, Rongshui, Rong’an, Sanjiang) in Liuzhou, from January 1st, 2019 to December 31st, 2020, in the Tuberculosis Report of Infectious Disease Surveillance System of the National Center for Disease Control and Prevention,using molecular biology techniques and phenotypic antimicrobial susceptibility test to screen for drug resistance in 2943 strains identified as Mycobacterium tuberculosis complex (MTBC), including 2514 strains in new patients and 429 strains in patients from drug-resistant high-risk groups, and the epidemiological characteristics of DR-TB and the clinical effectiveness of the two detection techniques were analyzed. Results: Of the 6050 suspected tuberculosis patients, the etiologically positive rate was 52.23% (3160/6050), the drug resistance screening rate of the etiologically positive patients was 93.13% (2943/3160), and a total of 132 strains of DR-TB were detected from 2943 strains of MTBC, with a drug-resistance detection rate of 4.49% (132/2943), among which, rifampicin-resistant tuberculosis (RR-TB) was 2.04% (60/2943), multidrug-resistant tuberculosis (MDR-TB) was 2.38% (70/2943), and extensively drug-resistant tuberculosis (XDR-TB) was 0.07% (2/2943); drug-resistant detection rate in high-risk groups (12.59% (54/429)) was significantly higher than that of new patients (3.10% (78/2514), χ²=76.954, P<0.001). Among high-risk groups, drug resistance detection rate was highest in relapsed patients (32.65% (32/98)), significantly higher than that in relapsed treatment failure patients (2.63% (2/76), χ²=44.106, P<0.001). Epidemiological characteristics of DR-TB patients showed that drug-resistance rates of patients aged 65 years or older, retired, from high-risk groups, patients with a history of smoking, alcohol consumption or diabetes mellitus (5.92% (58/979), 8.22% (12/146), 12.59% (54/429), 43.81% (46/105), 38.13% (53/139), 66.67% (12/18)) were significant higher than patients aged 18-64 years, being farmers, new patients, without history of smoking, alcohol consumption and diabetes mellitus (3.98% (72/1810), 4.10% (91/2221), 3.10% (78/2514), 3.03% (86/2838), 2.82% (79/2804), and 4.10% (120/2925), χ² values were 9.471, 10.061, 76.954, 393.038, 385.474, and 163.457, P values were 0.009, 0.039, <0.001, <0.001, <0.001, and <0.001, respectively). Conclusion: The drug-resistant detection rates in etiologically positive tuberculosis patients and high-risk groups in Liuzhou, Guangxi, were both lower than those were required by the World Health Organization. Patients being old and weak, retired, having bad behavioral habits or history of diabetes mellitus were all high-risk factors for developing DR-TB. It is recommended to enhance health education among etiologically positive patients and drug-resistant screening among drug-resistant high-risk groups. Simultaneously using both molecular biology techniques and phenotypic antimicrobial susceptibility test for drug resistance screening could significantly improve screening accuracy and diagnosis timeliness.

Review Articles

Research progress on comprehensive treatment beyond antibiotic therapy for nontuberculous mycobacterium pulmonary disease

Tan Shouyong

Chinese Journal of Antituberculosis. 2024, 46(8):  967-970.  doi:10.19982/j.issn.1000-6621.20240019

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In recent years, the incidence and prevalence of pulmonary disease caused by non-tuberculous mycobacteria (NTM) infection have been increasing rapidly. However, non-tuberculous mycobacterial pulmonary disease (NTM-PD) has the characteristics of low cure rate, high case fatality rate and high recurrence rate. Therefore, some scholars have proposed that clinicians should first manage the host factors and handle the controllable characteristics of NTM-PD, followed by optimizing anti-NTM treatment. This paper provides a review of the current status of comprehensive treatment beyond antibiotic therapy for NTM-PD, and propose that the important measures to improve the cure rate and reduce the recurrence rate of the disease are as follows: strengthening the comprehensive treatment beyond antibiotic therapy during treating NTM-PD, reducing or avoiding exposure to the NTM environment, enhancing the body’s immunity and improving the pulmonary internal environment caused by structural lung disease.

Research progress on osteoclasts activated by receptor activator of nuclear factor-κB ligand signaling pathway for the treatment of bone tuberculosis

Tian Hongjing, Zhang Yanjun, Deng Qiang, Li Junjie, Yang Jun, Liu Xinfeng, Du Jianqiang

Chinese Journal of Antituberculosis. 2024, 46(8):  971-975.  doi:10.19982/j.issn.1000-6621.20240103

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Bone tuberculosis represents a grave orthopedic infectious disease that poses significant threats to human health. The hallmark of the disease is the absorption and subsequent destruction of bone tissue, primarily mediated by osteoclasts. These multinucleated cells, originating from hematopoietic stem cells, are primarily regulated by the receptor activator of nuclear factor-κB ligand (RANKL) and its receptor, RANK. Mycobacterium tuberculosis triggers osteoclasts to produce transcription factors via the RANKL signaling pathway, thus intensifying the degradation of bone. This review delineates the architecture of the RANKL signaling pathway, explores recent advances in osteoclast research, and discusses their prospective applications in the clinical management of bone tuberculosis, offering novel insights for future investigations.

Advances in the application of metagenomic sequencing for tuberculosis prevention and control

Wang Yiting, Meng Xiangli, Fu Yin, Cao Xiaolong, Zheng Huiwen, He Wencong, Song Zexuan, Zhao Yanlin

Chinese Journal of Antituberculosis. 2024, 46(8):  976-981.  doi:10.19982/j.issn.1000-6621.20240111

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Effective diagnosis is crucial for controlling tuberculosis outbreaks, yet conventional diagnostic approaches lack sensitivity and are notably time-consuming, failing to satisfy the demands for high-efficiency clinical diagnostics. With the advent of advanced sequencing technologies and bioinformatics, metagenomic sequencing has increasingly been recognized for its utility in the diagnosis of a broad spectrum of infectious diseases. This study explores the application of metagenomic sequencing in the management and diagnosis of tuberculosis, emphasizing its transformative potential for future enhancements in the prevention of tuberculosis.