Zhao Jingnan, Qian Chengyu, Jiang Youqiao, He Wangrui, Wu Wenhua
Tuberculosis Control Department, Jiangxi Provincial Center for Disease Control and Prevention, Nanchang, 330029, People's Republic of China.
Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, 101149, People's Republic of China.
Infect Drug Resist. 2024 Jun 1;17:2213-2223. doi: 10.2147/IDR.S460267. eCollection 2024.
In this study, we aimed to determine the transmission pattern of multidrug-resistant tuberculosis (MDR-TB) isolates circulating in Jiangxi Province with whole-genome sequencing (WGS). In addition, we also sought to describe mutational resistome of MDR-TB isolates.
A total of 115 MDR-TB isolates determined by the phenotypic proportion method of drug susceptibility testing between January 2018 and December 2022 from provincial drug surveillance (DRS) in Jiangxi were included in our analysis. The demographic data and treatment history were extracted from the National TB Registry System. WGS was used to analyze the genotypic characteristics of drug resistance and transmissions.
About 62.6% of MDR-TB strains were isolated from cases that received previous anti-tuberculosis treatment. According to the WGS results, 96.5% were genotypic MDR-TB, and more than half of MDR-TB isolates tested were also resistant to streptomycin (59.1%), ethambutol (56.5%), and fluroquinolones (53.0%), while resistance to cycloserine and linezolid was lowest, only in two (1.7%) and one (0.9%) isolate, respectively. Ser450Leu in , Ser315Thr in , Met306Val in , Lys43Arg in , Ala90Val in were predominant mutant types among the rifampin-, isoniazid-, ethambutol-, streptomycin-, fluoroquinolones-resistant isolates, respectively. Lineage 2 (East Asian genotype) occurred at the highest frequency with 97 cases (84.3%), followed by lineage 4 (Euro-American genotype) with 18 cases (15.7%). Additionally, 5 clusters consisting of 10 isolates were identified in the present study, demonstrating a clustering rate of 8.7%.
MDR/Rifampicin-Resistant (RR)-TB epidemic in this region is driven by lineage 2 clade that also show higher resistance to other anti-tuberculosis drugs. Lower cluster rates compared with a relatively higher proportion of new MDR-TB cases indicate that a considerable number of MDR-TB cases remain undiagnosed.
在本研究中，我们旨在通过全基因组测序（WGS）确定江西省流行的耐多药结核病（MDR-TB）分离株的传播模式。此外，我们还试图描述MDR-TB分离株的突变耐药组。
我们纳入了2018年1月至2022年12月间通过江西省省级药物监测（DRS）的药物敏感性试验表型比例法确定的115株MDR-TB分离株进行分析。人口统计学数据和治疗史从国家结核病登记系统中提取。WGS用于分析耐药性和传播的基因型特征。
约62.6%的MDR-TB菌株分离自接受过抗结核治疗的病例。根据WGS结果，96.5%为基因型MDR-TB，超过一半的MDR-TB分离株还对链霉素（59.1%）、乙胺丁醇（56.5%）和氟喹诺酮类（53.0%）耐药，而对环丝氨酸和利奈唑胺的耐药率最低，分别仅在2株（1.7%）和1株（0.9%）分离株中出现。在耐利福平、耐异烟肼、耐乙胺丁醇、耐链霉素、耐氟喹诺酮类的分离株中，rpoB基因的Ser450Leu、katG基因的Ser315Thr、embB基因的Met306Val、rrs基因的Lys43Arg、gyrA基因的Ala90Val分别是主要的突变类型。2系（东亚基因型）出现频率最高，有97例（84.3%），其次是4系（欧美基因型），有18例（15.7%）。此外，本研究中鉴定出由10株分离株组成的5个聚类，聚类率为8.7%。
该地区耐多药/耐利福平（RR）-TB的流行是由2系分支驱动的，该分支对其他抗结核药物也表现出较高的耐药性。与相对较高比例的新发MDR-TB病例相比，聚类率较低表明相当数量的MDR-TB病例仍未被诊断出来。
