The Current Landscape of Repurposed Drugs for Fungal Neglected Tropical Diseases

Eumycetoma, chromoblastomycosis, and sporotrichosis are three of only four fungal infections recognized as Neglected Tropical Diseases (NTDs) by the World Health Organization. They are a significant source of morbidity in subtropical and tropical regions of the Americas, Africa, and Asia. There are very few treatments approved for these diseases. Clinicians often use drug repurposing, off-label use of existing drugs, for their treatment. This article is a systematic review of the published literature on the treatment of fungal NTDs from the last five years (2019-2024). It will provide an overview for each fungal NTD, their current treatment landscape, and the challenges associated with their treatment.

Itraconazole remains the most widely used antifungal for the treatment of these fungal NTDs. Newer antifungals such as fosravuconazole have matched the efficacy of currently available drugs while reducing adverse events and pill burden. Other promising treatment strategies involve the use of immunomodulators (e.g., imiquimod), steroids (e.g., prednisolone), or non-steroidal anti-inflammatory agents in combination with traditional antifungal agents.

Frequently repurposed drugs include itraconazole, posaconazole, voriconazole, amphotericin B, terbinafine, potassium iodide, and 5-flucytosine. Most of these drugs have significant side effects, unsatisfactory cure rates, and significant cost that restricts their use. Systematic collection of this drug repurposing data and analyzing it in aggregate using platforms such as CURE ID has the potential to generate efficacy signals for drugs. These promising candidates can then be studied comprehensively in clinical trials for drug approval.