New guidance documents to support implementation of next generation sequencing to detect DR-TB

15 November 2023 | Paris -- To assist national TB programmes and other stakeholders in adopting and implementing next generation sequencing (NGS) for the detection of drug-resistant tuberculosis (DR-TB), the World Health Organization (WHO) is pleased to launch two new important guidance documents.

The first of these documents is the 2023 update of the “Catalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance”. The catalogue seeks to support TB laboratories around the world to interpret genome sequencing results and to guide the development of new molecular drug susceptibility tests, including next-generation sequencing.

This document represents an update of the previous catalogue published in 2021 and provides a standard reference for the interpretation of mutations conferring resistance to 13 anti-TB medicines. It summarises the analysis of over 52 000 isolates with matched data on whole genome sequencing and phenotypic drug susceptibility testing from 67 countries. The catalogue lists over 30 000 unique variants across 63 genes, their frequency and association with resistance and susceptibility.

The second document provides practical guidance on planning and implementing NGS technology for characterization of the Mycobacterium tuberculosis complex, entitled “The use of next-generation sequencing for the surveillance of drug-resistant tuberculosis: an implementation manual”. It complements WHO’s “Guidance for the surveillance of drug resistance in tuberculosis” (published in 2021). The intended audience includes staff of national TB programmes and ministries of health, implementing partners, laboratory managers and technical staff, clinicians, donors, and other stakeholders engaged in the surveillance of drug-resistant TB and TB laboratory strengthening.

“These two important publications will facilitate access to the rapid diagnosis of drug-resistant TB through innovative approaches using targeted NGS,” said Dr Tereza Kasaeva, Director of WHO’s Global TB Programme. “Ensuring that everyone in need can obtain a rapid and accurate diagnosis of drug resistant TB will save lives and reduce suffering”.

Targeted next generation sequencing (NGS) for the detection of drug-resistant TB is a new class of diagnostic technology. It provides an option for rapid and accurate genetic analysis and detection of mutations associated with resistance and susceptibility in a fraction of the time required for culture-based methods for detecting resistance. As announced in a Rapid Communication published by July 2023, WHO’s Global Tuberculosis Programme will release updated WHO consolidated guidelines for diagnosis of TB in 2023 which will incorporate recommendations on targeted NGS.

Source: World Health Organization