Farid Tahsin, Tumas Keyla C, Stone Heather A, Duggal Mili
Office of Medical Policy, Center for Drug Evaluation and Research (CDER), United States Food and Drug Administration, Silver Spring, MD, USA.
Division of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Rockville, MD, USA.
Curr Fungal Infect Rep. 2025 Dec;19(1). doi: 10.1007/s12281-025-00504-z. Epub 2025 May 29.
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.
足菌肿、着色芽生菌病和孢子丝菌病是世界卫生组织认定的仅有的四种被忽视热带病（NTDs）中的三种真菌感染。它们是美洲、非洲和亚洲亚热带和热带地区发病的重要原因。针对这些疾病获批的治疗方法非常少。临床医生通常采用药物重新利用，即使用现有药物的非标签用法来治疗。本文是对过去五年（2019 - 2024年）发表的关于真菌性被忽视热带病治疗的文献的系统综述。它将概述每种真菌性被忽视热带病、其当前的治疗情况以及治疗相关的挑战。
伊曲康唑仍然是治疗这些真菌性被忽视热带病最广泛使用的抗真菌药物。新型抗真菌药物如伏沙康唑在降低不良事件和服药负担的同时，疗效与现有药物相当。其他有前景的治疗策略包括将免疫调节剂（如咪喹莫特）、类固醇（如泼尼松龙）或非甾体抗炎药与传统抗真菌药物联合使用。
经常被重新利用的药物包括伊曲康唑、泊沙康唑、伏立康唑、两性霉素B、特比萘芬、碘化钾和5 - 氟胞嘧啶。这些药物大多有显著的副作用、治愈率不理想以及成本高昂，限制了它们的使用。系统收集这种药物重新利用的数据，并使用CURE ID等平台进行汇总分析，有可能产生药物疗效信号。然后可以在临床试验中对这些有前景的候选药物进行全面研究以获得药物批准。
