Advances in molecular techniques for detecting Mycobacterium leprae: A narrative review of progress, challenges, and future directions

Leprosy remains a neglected infectious disease where delayed diagnosis leads to disability and ongoing transmission, particularly in paucibacillary and pure neural forms. This narrative review summarizes molecular diagnostic approaches for Mycobacterium leprae, including polymerase chain reaction (PCR), isothermal nucleic acid amplification tests, clustered regularly interspaced short palindromic repeats (CRISPR)-Cas-based diagnostic systems, next-generation sequencing (NGS), microarrays, and biosensors. PCR remains the most established method, now expanded to multiplex, quantitative, and droplet digital formats for improved detection and antimicrobial resistance surveillance. Isothermal methods such as loop-mediated isothermal amplification (LAMP), recombinase polymerase amplification (RPA), and multiple cross displacement amplification (MCDA) offer rapid, field-deployable options but require further validation. Emerging platforms, including CRISPR-Cas diagnostics, targeted sequencing, and biosensors, show promise but remain limited by cost and infrastructure needs. Overall, molecular approaches have substantially expanded the diagnostic and surveillance capacity for leprosy, particularly in paucibacillary, pure neural, and clinically ambiguous presentations where conventional methods lack sensitivity. Future advances should integrate optimized biomarkers, improved sample processing, and simplified platforms to further enable early diagnosis, treatment monitoring, and antimicrobial resistance surveillance, thereby supporting global leprosy control and elimination.