Leishmaniases: Strategies in treatment development

Leishmaniases are vector-borne parasitic diseases that pose a threat to over 1 billion people worldwide. The parasites target cells of the reticulohistiocytic system, such as macrophages, where they replicate. The disease manifests in various forms, ranging from localized cutaneous leishmaniasis to life-threatening visceral forms, which are fatal in 95% of cases without treatment. Current treatments rely on the invasive administration of toxic and expensive drugs that are increasingly encountering resistance. Therefore, finding alternative treatments for this disease is imperative. This literature review focuses on recent advancements in alternative treatments and aims to present the various strategies designed to address current limitations, including cost, toxicity, off-target effects, administration routes, and the emergence of drug resistance. Starting with an overview of the existing approved treatments and their specific limitations, we categorize treatment development strategies into five key sections: (i) combination therapies using existing approved treatments to enhance efficacy and reduce resistance; (ii) nanoparticle formulations, which enable targeted delivery to infected organs and improved therapeutic efficiency; (iii) drug repositioning, a strategy that has already contributed to the approval of over half of current therapeutic compounds; (iv) immunomodulation, used in conjunction with standard chemotherapies to enhance treatment efficacy and lower relapse rates; and (v) ethnobotanicals, which have demonstrated promising in vitro results by combining low toxicity, immunomodulatory properties, and potent anti-parasitic effects. In summary, this review outlines current strategies in treatment development, emphasizing their advantages over conventional therapies while acknowledging their limitations.