The use of next-generation sequencing for the surveillance of drug-resistant tuberculosis: an implementation manual

This implementation manual provides practical guidance for integrating next-generation sequencing (NGS) into surveillance systems for drug-resistant tuberculosis (DR-TB). Developed to complement existing WHO guidance on tuberculosis surveillance and sequencing technologies, the document outlines strategic, technical and operational considerations for implementing NGS-based drug susceptibility testing within national DR-TB surveillance programmes. It addresses the public health importance of strengthening surveillance for rifampicin-resistant and multidrug-resistant tuberculosis and explains the potential role of targeted and whole genome sequencing in improving detection of resistance-associated mutations, monitoring transmission dynamics and supporting comprehensive surveillance activities.

The manual describes key steps required for implementation, including country planning, readiness assessment, regulatory processes, laboratory infrastructure, equipment selection, biosafety, quality assurance, data management, recording and reporting, workforce training, and monitoring and evaluation. It also discusses the advantages and limitations of targeted next-generation sequencing and whole genome sequencing, particularly in low- and middle-income settings. Annexes provide operational tools, checklists, reporting templates and examples intended to support countries in establishing standardized, sustainable and quality-assured NGS capacity for DR-TB surveillance.