Abstract
BACKGROUND AND PURPOSE: Leishmaniasis, a neglected tropical disease caused by the protozoan parasite Leishmania, remains a significant public health concern in endemic regions. The disease manifests in various forms, including cutaneous, mucocutaneous, and visceral leishmaniasis, each associated with specific Leishmania species and influenced by host immune responses. Over the past few decades, treatment for leishmaniasis has relied on a limited range of drugs, including pentavalent antimonials, amphotericin B formulations, miltefosine, and paromomycin. However, widespread drug resistance, particularly in visceral leishmaniasis, has severely compromised treatment efficacy, leading to rising cases of treatment failure. This review aims to provide a comprehensive understanding of the mechanisms underlying drug resistance in leishmaniasis and to highlight the factors that contribute to its development. EXPERIMENTAL APPROACH: The study synthesizes existing literature on resistance mechanisms among anti-leishmanial drugs, focusing on changes in parasite uptake and efflux, intracellular sequestration, and modulation of stress responses. It also examines the impact of environmental factors, such as arsenic exposure in endemic regions, and reviews recent molecular and genomic studies that have identified resistance-associated markers. CONCLUSION: The review underscores the urgent need for innovative therapeutic strategies and highlights the importance of an integrated approach to combat drug resistance through enhanced surveillance, molecular insights, and global collaboration.