Diagnostic Assays for TB Disease and Drug Resistance Detection-Advances and Latest WHO Recommendations

Accurate and timely diagnosis of active tuberculosis (TB) and its drug-resistant forms are essential for effective patient care and global TB disease control. This paper summarizes the latest advances in TB disease diagnostics. We describe mechanisms of drug resistance in Mycobacterium tuberculosis, including both well-characterized and emerging pathways. Approaches for the initial detection of active TB disease are discussed, highlighting the key role of nucleic acid amplification tests of varying complexity across pulmonary and extrapulmonary specimens. Follow-on drug resistance testing using rapid molecular assays and next-generation sequencing (NGS) enables the early identification of resistance to first- and second-line drugs. Traditional culture-based and phenotypic drug susceptibility testing remain crucial for comprehensive profiling, particularly for drugs with limited molecular markers. These topics are discussed in the context of World Health Organization (WHO) recommendations. We also outline future directions, emphasizing the integration of molecular and phenotypic methods, expansion of NGS applications, and standardization of diagnostic algorithms. This synthesis provides a concise overview of contemporary diagnostic tools to guide therapy and policy decisions in TB disease management.