Leprosy in the Brazilian Amazon: Four Decades of Progress, Scientific Advances and Future Challenges.

Leprosy remains a major public health challenge in the state of Amazonas, Brazil, despite a remarkable 95.7% reduction in detection rates between 1981 and 2024. In 2024, 326 cases were reported, 80.4% of which were new diagnoses, predominantly multibacillary forms, with 9.3% presenting grade 2 disability on diagnosis. The continued occurrence of cases among children under 15 years of age (3.4%) indicates active transmission, particularly in geographically isolated municipalities. The Fundação Hospitalar Alfredo da Matta (FUHAM) serves as the main regional reference center, coordinating surveillance, diagnosis, rehabilitation and research activities. The decentralization of primary care and the integration of telehealth strategies have strengthened diagnostic capacity and improved the management of leprosy reactions. Historically, Amazonas has played a pivotal role in advancing scientific knowledge on leprosy, from early reports of dapsone resistance to participation in key clinical trials such as U-MDT/CT-BR, and studies on leprosy/HIV coinfection, immunopathogenesis and host genetic susceptibility (NOD2, IFNG, PKLR). More recently, genomic surveillance in the region has identified both classical and novel antimicrobial resistance mutations, consolidating Amazonas as a sentinel site for molecular monitoring. Persistent challenges include limited professional training, delayed diagnosis and ongoing social stigma. Research priorities for the next decade include strengthening active case detection, validating simplified diagnostic algorithms, expanding antimicrobial resistance monitoring, exploring genetic determinants of susceptibility and adopting One Health approaches to understand environmental and zoonotic transmission. These integrated strategies are crucial to sustain progress toward the elimination of leprosy as a public health problem in the Amazonian context.