Ebiloma Godwin U, Alhejeli Amani, de Koning Harry P
School of Science, Engineering & Environment, University of Salford, Manchester M5 4NT, UK.
Biology Department, Darb University College, Jazan 45142, Saudi Arabia.
Pharmaceuticals (Basel). 2025 Sep 19;18(9):1415. doi: 10.3390/ph18091415.
Kinetoplastids are protozoa that possess a unique organelle called a kinetoplast. These include the parasites , and related , and spp. These parasites cause a variety of neglected tropical diseases in humans and livestock, with devastating consequences. In the absence of any vaccine, pharmaceutical interventions are the mainstay of control, but these have historically been underfunded, fragmented, and inadequately aligned with the complex zoonotic and ecological realities of the parasites' transmission dynamics. In this review, the landscape of current and emerging drugs for treating leishmaniasis, Chagas disease, and African trypanosomiasis is critically evaluated across both veterinary and human contexts. It examines the challenges of legacy compounds, the pharmacological shortcomings in multi-host, multi-tropic and multi-stage disease systems, and the gaps in veterinary therapeutics, specifically for African animal trypanosomiasis and canine leishmaniasis but also the animal reservoir of . Emphasis is placed on pharmacokinetic divergence between species, the accompanying risks with the use of off-label human drugs in animals, and the ecological effects of environmental drug exposure. We propose a far-reaching One Health framework for pharmaceutical research and development, promoting dual-indication co-development, ecological pharmacology, regulatory harmonisation, and integrated delivery systems. In this context, we argue that the drug development pipeline must be rationalised as a transdisciplinary and ecologically embedded process, able to interrupt parasite transmission to human, animal, and vector interfaces. Our findings reveal that we can bridge age-old therapeutic gaps, advance towards sustainable control, and eventually eliminate the neglected diseases caused by kinetoplastid protozoan parasites by aligning pharmaceutical innovation with One Health principles. This article aims to promote future research and development of innovative drugs that are sustainable under the One Health framework.
动质体是一种原生动物，拥有一种名为动质体的独特细胞器。这些包括寄生虫、锥虫属和相关的属，以及种。这些寄生虫在人类和牲畜中引发了多种被忽视的热带疾病，后果极为严重。由于没有任何疫苗，药物干预是控制疾病的主要手段，但这些干预措施在历史上一直资金不足、零散且与寄生虫传播动态的复杂人畜共患病和生态现实不太契合。在本综述中，对当前和新兴的用于治疗利什曼病、恰加斯病和非洲锥虫病的药物在兽医和人类背景下进行了严格评估。它审视了传统化合物面临的挑战、多宿主、多宿主范围和多阶段疾病系统中的药理学缺陷，以及兽医治疗方面的差距，特别是针对非洲动物锥虫病和犬利什曼病，但也涉及的动物宿主。重点关注物种间的药代动力学差异、在动物中使用未标注适应症的人类药物所带来的风险，以及环境药物暴露的生态影响。我们提出了一个影响深远的“同一健康”药物研发框架，促进双适应症共同研发、生态药理学、监管协调和综合给药系统。在此背景下，我们认为药物研发流程必须作为一个跨学科且融入生态的过程进行合理化，能够阻断寄生虫向人类、动物和媒介界面的传播。我们的研究结果表明，通过使药物创新与“同一健康”原则保持一致，我们可以弥合由来已久的治疗差距，朝着可持续控制迈进，并最终消除由动质体原生动物寄生虫引起的被忽视疾病。本文旨在推动在“同一健康”框架下可持续的创新药物的未来研发。
Zotero 插件