WHO operational handbook on tuberculosis: module 3: diagnosis: web annex D: TB interferon gamma release assays and targeted next generation sequencing solutions: systematic review and technical advisory group reports

This web annex to the WHO operational handbook on tuberculosis, Module 3: diagnosis, summarizes the evidence reviewed by the WHO Technical Advisory Group on Tuberculosis Diagnostics and Laboratory Strengthening regarding new and updated diagnostic technologies for tuberculosis infection and drug-resistant tuberculosis. The document presents the methods, findings and policy considerations from Pathway B evaluations of interferon-gamma release assays (IGRAs) for detection of TB infection and targeted next generation sequencing (tNGS) solutions for detection of resistance to anti-tuberculosis medicines. It describes systematic reviews, meta-analyses and multicountry diagnostic accuracy assessments comparing index technologies with WHO-recommended reference tests.

The report reviews the performance characteristics, implementation considerations and evidence requirements for within-class assessment of six IGRA products and two tNGS solutions. It summarizes findings on sensitivity, specificity, inter-test agreement, indeterminate rates and failure rates, and outlines criteria used to determine comparability with WHO-recommended technologies. The publication also discusses future approaches for evaluating emerging diagnostic tools, including strengthened evidence requirements for IGRA assessments and considerations for updating performance benchmarks for tNGS solutions as knowledge of molecular mechanisms of drug resistance evolves.