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Abstract

Leishmaniasis, which is an infectious tropical disease that is caused by Leishmania protozoa, continues to be a leading global public health problem. This disease is prevalent in about 89 countries, with over one billion individuals being at risk of infection. Current treatments have many limitations, and the efficacy of currently available leishmanial drugs has been undermined by the development of resistant strains of Leishmania. This review highlights the prevailing patterns regarding drug resistance in Leishmania and looks forward to future ways to deal with this problem. The genomic plasticity seen in Leishmania, which includes aneuploidy, gene amplification, chromosome rearrangement, and epigenetics, allows for the quick development of adaptations to drug exposure. We will look at resistance strategies related to the major antileishmanial drugs used, including decreased drug uptake through aquaglyceroporin expression in antimonial resistance, changes in drug targets and efflux in amphotericin B resistance, and multi-factorial mechanisms of miltefosine resistance. There is growing research that suggests the significance of translational reprogramming and epistasis in the development of resistance phenotypes. Moreover, the clinical significance of drug resistance in endemic areas, specifically India and Latin America, has been described in this review in the context of increased rates of treatment failure. Ultimately, some of the strategies that can be utilized in the future include genomic surveillance, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR-based functional genomics), optimized combinations and new antileishmanial drugs that can fight the resistant parasite.

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