National Public Health Laboratory, National Centre for Infectious Diseases, Singapore, Singapore.
National Tuberculosis Programme, National Centre for Infectious Diseases, Singapore, Singapore.
Microb Genom. 2023 Nov;9(11). doi: 10.1099/mgen.0.001139.
The National Tuberculosis Programme (NTBP) monitors the occurrence and spread of tuberculosis (TB) and multidrug-resistant TB (MDR-TB) in Singapore. Since 2020, whole-genome sequencing (WGS) of isolates has been performed at the National Public Health Laboratory (NPHL) for genomic surveillance, replacing spoligotyping and mycobacterial interspersed repetitive unit-variable number tandem repeats analysis (MIRU-VNTR). Four thousand three hundred and seven samples were sequenced from 2014 to January 2023, initially as research projects and later developed into a comprehensive public health surveillance programme. Currently, all newly diagnosed culture-positive cases of TB in Singapore are prospectively sent for WGS, which is used to perform lineage classification, predict drug resistance profiles and infer genetic relationships between TB isolates. This paper describes NPHL's operational and technical experiences with implementing the WGS service in an urban TB-endemic setting, focusing on cluster detection and genomic drug susceptibility testing (DST). Cluster detection: WGS has been used to guide contact tracing by detecting clusters and discovering unknown transmission networks. Examples have been clusters in a daycare centre, housing apartment blocks and a horse-racing betting centre. Genomic DST: genomic DST prediction (gDST) identifies mutations in core genes known to be associated with TB drug resistance catalogued in the TBProfiler drug resistance mutation database. Mutations are reported with confidence scores according to a standardized approach referencing NPHL's internal gDST confidence database, which is adapted from the World Health Organization (WHO) TB drug mutation catalogue. Phenotypic-genomic concordance was observed for the first-line drugs ranging from 2959/2998 (98.7 %) (ethambutol) to 2983/2996 (99.6 %) (rifampicin). Aspects of internal database management, reporting standards and caveats in results interpretation are discussed.
新加坡国家结核病规划 (NTBP) 监测结核病 (TB) 和耐多药结核病 (MDR-TB) 的发生和传播。自 2020 年以来，国家公共卫生实验室 (NPHL) 对分离株进行了全基因组测序 (WGS)，用于基因组监测，取代了 spoligotyping 和分枝杆菌插入重复单元-可变数量串联重复分析 (MIRU-VNTR)。从 2014 年到 2023 年 1 月，对 4307 个样本进行了测序，最初是作为研究项目进行的，后来发展成为一项全面的公共卫生监测计划。目前，新加坡所有新诊断的培养阳性结核病病例都前瞻性地进行 WGS，用于进行谱系分类、预测耐药谱并推断结核分离株之间的遗传关系。本文描述了 NPHL 在城市结核病流行环境中实施 WGS 服务的操作和技术经验，重点介绍了集群检测和基因组药敏试验 (DST)。集群检测：WGS 已用于通过检测集群和发现未知传播网络来指导接触者追踪。例如，在日托中心、住房公寓楼和赛马投注中心发现了集群。基因组 DST：基因组 DST 预测 (gDST) 识别了 TBProfiler 耐药突变数据库中列出的与结核病药物耐药性相关的核心基因中的突变。突变根据一种标准化方法报告，该方法参考了 NPHL 内部 gDST 置信度数据库，该数据库改编自世界卫生组织 (WHO) 的结核病药物突变目录。观察到一线药物的表型-基因组一致性范围为 2959/2998(98.7%) (乙胺丁醇)至 2983/2996(99.6%) (利福平)。讨论了内部数据库管理、报告标准和结果解释中的注意事项。
