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

## TL;DR

This review explores how drug resistance develops in Leishmania parasites, a cause of leishmaniasis, and emphasizes the need for new treatments and global cooperation.

## Contribution

The paper provides a comprehensive synthesis of drug resistance mechanisms in Leishmania and highlights the need for integrated therapeutic strategies.

## Key findings

- Drug resistance in Leishmania is linked to changes in parasite uptake, efflux, and intracellular sequestration.
- Environmental factors like arsenic exposure contribute to resistance in endemic regions.
- Molecular and genomic studies have identified potential resistance markers for further research.

## Abstract

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.

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.

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.