Ding Feng, Liu Wanfei, Wu Chi, Zhang Wensi, Chen Shuyan, Lai Wenjie, Qu Jiayao, Lin Qiang, Lu Shuihua, Qu Jiuxin
National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, China.
Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.
Front Cell Infect Microbiol. 2025 Jan 21;14:1488547. doi: 10.3389/fcimb.2024.1488547. eCollection 2024.
Tuberculosis (TB) remains a serious global public health problem. The (MTB) is responsible for approximately 10 million new TB cases globally each year. This study aimed to investigate transmission pattern and drug resistance of MTB in Shenzhen, China.
A retrospective study on 286 samples from 184 TB patients collected between 2015 and 2018 in Shenzhen Third People's Hospital was conducted using whole-genome sequencing. Drug susceptibility testing (DST) was performed using both phenotypic DST (pDST) and molecular DST (mDST). Sample diversity was evaluated by SNPs and transmission clusters were identified based on SNP differences of 12 or fewer in genetic clusters.
Except four samples identified as non-tuberculous mycobacteria, 282 MTB samples (181 patients) underwent mDST, with 244 samples (162 patients) undergoing pDST. The overall multidrug-resistant rate in patients was 22.31% in pDST (12.00% for new patients and 40.82% for retreatment patients) and 34.48% in mDST (20.41% for new patients and 58.21% for retreatment patients). Totally 92 transmission clusters were identified, encompassing 70.21% samples (57.46% patients), with 5 clusters containing samples (15, 5.32%) from different patients (9, 4.97%), indicating recent transmission. The drug-resistant mutations in 36 of 45 transmission clusters (80.00%) were identical in all samples, suggesting the transmission of drug resistance. Patients with multiple samples were categorized into simultaneous sampling (SS) and continuous sampling (CS) groups, revealing significant differences in treatment types, treatment outcomes, residential addresses, and drug resistance types. mDST showed greater accuracy than pDST in SS and CS groups. A novel method based on heterozygous SNPs and two-sample Kolmogorov-Smirnov test were developed and identified 12 (4.26%) samples as mixed infection samples. Six of 12 patients had mixed and pure samples together, and major strains of mixed samples were closer to corresponding pure strains than minor strains.
This retrospective study, conducted at the only municipal hospital specializing in infectious diseases in Shenzhen, provides the opportunity to understand drug resistance of TB patients, which mainly are refractory patients. The study revealed transmission patterns of MTB, analyzed mixed infections, and tracked changes in MTB strains during short/long-term treatment.
结核病仍然是一个严重的全球公共卫生问题。结核分枝杆菌（MTB）每年在全球导致约1000万例新的结核病病例。本研究旨在调查中国深圳MTB的传播模式和耐药性。
对2015年至2018年期间在深圳市第三人民医院收集的184例结核病患者的286份样本进行回顾性研究，采用全基因组测序。使用表型药敏试验（pDST）和分子药敏试验（mDST）进行药敏试验。通过单核苷酸多态性（SNP）评估样本多样性，并根据基因簇中12个或更少的SNP差异识别传播簇。
除4份样本被鉴定为非结核分枝杆菌外，282份MTB样本（181例患者）进行了mDST，244份样本（162例患者）进行了pDST。患者的总体多重耐药率在pDST中为22.31%（新患者为12.00%，复治患者为40.82%），在mDST中为34.48%（新患者为20.41%，复治患者为58.21%）。共识别出92个传播簇，涵盖70.21%的样本（57.46%的患者），其中5个簇包含来自不同患者的样本（15份，5.32%）（9例，4.97%），表明近期有传播。45个传播簇中的36个（80.00%）的耐药突变在所有样本中相同，表明耐药性的传播。将有多份样本的患者分为同时采样（SS）组和连续采样（CS）组，结果显示在治疗类型、治疗结果、居住地址和耐药类型方面存在显著差异。在SS组和CS组中，mDST显示出比pDST更高的准确性。开发了一种基于杂合SNP和双样本柯尔莫哥洛夫-斯米尔诺夫检验的新方法，识别出12份（4.26%）样本为混合感染样本。12例患者中有6例同时有混合样本和纯样本，混合样本的主要菌株比次要菌株更接近相应的纯菌株。
这项在深圳唯一一家专门治疗传染病的市级医院进行的回顾性研究，提供了了解结核病患者耐药性的机会，这些患者主要是难治性患者。该研究揭示了MTB的传播模式，分析了混合感染情况，并跟踪了短期/长期治疗期间MTB菌株的变化。
