Insights into drug resistance in Leishmania: Mechanisms, therapeutics, and clinical case studies: Review paper

Gajala Deethamvali  Ghousepeer; Mansi  Rani; Aman  Kumar; Shubhankar Kumar  Singh; Anjali  Priyadarshini; Elcio  Leal; Shailja  Singh; V. Samuel  Raj; Subhajit  Basu; Ramendra Pati  Pandey

doi:10.5599/admet.2992

Authors

Gajala Deethamvali Ghousepeer School of Health Science and Technology, UPES, Dehradun, India https://orcid.org/0000-0002-4210-636X
Mansi Rani Indian Council of Medical Research-Rajendra Memorial Research Institute of Medical Science, Patna, India https://orcid.org/0009-0009-1027-691X
Aman Kumar Indian Council of Medical Research-Rajendra Memorial Research Institute of Medical Science, Patna, India https://orcid.org/0009-0008-2328-1040
Shubhankar Kumar Singh Indian Council of Medical Research-Rajendra Memorial Research Institute of Medical Science, Patna, India https://orcid.org/0000-0003-0292-6483
Anjali Priyadarshini Centre for Drug Design Discovery and Development (C4D), SRM University, Delhi-NCR, India https://orcid.org/0000-0003-4191-8152
Elcio Leal Laboratório de Diversidade Viral, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belem, 66075-000, Brazil https://orcid.org/0000-0003-3463-0492
Shailja Singh Special Center for Molecular Medicine, Jawaharlal Nehru University, Delhi, India https://orcid.org/0000-0001-5286-6605
V. Samuel Raj Centre for Drug Design Discovery and Development (C4D), SRM University, Delhi-NCR, India https://orcid.org/0000-0003-4669-504X
Subhajit Basu School of Health Science and Technology, UPES, Dehradun, India https://orcid.org/0000-0003-2888-9721
Ramendra Pati Pandey Centre for Drug Design Discovery and Development (C4D), SRM University, Delhi-NCR, India and School of Biosciences and Bioengineering, D Y Patil International University, Pune, India https://orcid.org/0000-0002-5196-6468

DOI:

https://doi.org/10.5599/admet.2992

Keywords:

Leishmaniasis, neglected tropical disease, immune responses, treatment

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.

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