Evaluation of the GenoScreen Deeplex Myc-TB workflow for drug-resistant tuberculosis testing in South Africa.

Tuberculosis (TB) remains a leading cause of death globally, particularly in low- and middle-income countries, where healthcare systems are under-resourced and the burden of drug-resistant disease is highest. We assessed the feasibility of future integration of the GenoScreen Deeplex Myc-TB assay - a targeted next-generation sequencing (tNGS) assay for Mycobacterium tuberculosis detection and drug-resistance profiling within a national reference laboratory in South Africa. Rather than reporting routine implementation with patient testing in parallel to standard care, this study evaluated pre-implementation readiness through workflow optimisation, infrastructure preparation, staff training, and troubleshooting across the sequencing pathway. The main challenges identified were DNA extraction from complex specimens, targeted PCR quality control, manual library preparation, sequencing consistency, proprietary analysis software, and procurement and cost constraints. Overall, these findings show that the Deeplex Myc-TB assay has potential to complement routine diagnostic testing in high-burden settings, but that sustained adoption will require appropriate extraction methods, additional local quality control measures, reliable procurement pathways, recognised reporting, and longer-term investment in laboratory and data systems.