Mycobacterial diseases, including tuberculosis, leprosy, and a growing number of nontuberculous mycobacterial (NTM) infections, pose persistent challenges for molecular epidemiology and diagnostics. These pathogens are notoriously difficult to detect and monitor due to their slow growth, genetic diversity, and ability to cause chronic or subclinical diseases. For many species, diagnosis relies on limited tools that lack sensitivity or field applicability, and drug resistance detection remains technically demanding and inconsistent across regions. Paradoxically, despite their slow replication rates, drug resistance in mycobacteria can emerge and spread rapidly, often outpacing surveillance efforts and complicating treatment strategies. Among these, leprosy stands out as particularly challenging because of the uncultivable Mycobacterium leprae and M. lepromatosis and is characterized by a long incubation period, subtle early manifestations, and limited diagnostic accessibility, especially in low-resource settings (1). These biological and logistical hurdles continue to hinder the timely diagnosis, surveillance, and mapping of transmission dynamics. With 182,815 new cases in 2023, a 5% increase over 2022 (2), leprosy remains a significant but neglected public health concern in countries on every continent. This Research Topic brings together recent advances that confront these barriers, with a primary focus on molecular tools and epidemiological strategies designed to improve leprosy control. .....

https://doi.org/10.3389/fitd.2025.1622530