Khan Shahbaz M, Witola William H
Department of Pathobiology, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Urbana, IL, United States.
Front Cell Infect Microbiol. 2023 Jan 24;13:1115522. doi: 10.3389/fcimb.2023.1115522. eCollection 2023.
The intracellular protozoan parasite of the genus is among the leading causes of waterborne diarrheal disease outbreaks throughout the world. The parasite is transmitted by ingestion of infective oocysts that are highly stable in the environment and resistant to almost all conventional disinfection methods and water treatments. Control of the parasite infection is exceedingly difficult due to the excretion of large numbers of oocysts in the feces of infected individuals that contaminate the environment and serve as a source of infection for susceptible hosts including humans and animals. Drug development against the parasite is challenging owing to its limited genetic tractability, absence of conventional drug targets, unique intracellular location within the host, and the paucity of robust cell culture platforms for continuous parasite propagation. Despite the high prevalence of the parasite, the only US Food and Drug Administration (FDA)-approved treatment of infections is nitazoxanide, which has shown moderate efficacy in immunocompetent patients. More importantly, no effective therapeutic drugs are available for treating severe, potentially life-threatening cryptosporidiosis in immunodeficient patients, young children, and neonatal livestock. Thus, safe, inexpensive, and efficacious drugs are urgently required to reduce the ever-increasing global cryptosporidiosis burden especially in low-resource countries. Several compounds have been tested for both and efficacy against the disease. However, to date, only a few experimental compounds have been subjected to clinical trials in natural hosts, and among those none have proven efficacious. This review provides an overview of the past and present anti- pharmacotherapy in humans and agricultural animals. Herein, we also highlight the progress made in the field over the last few years and discuss the different strategies employed for discovery and development of effective prospective treatments for cryptosporidiosis.
属的细胞内原生动物寄生虫是全球水源性腹泻病暴发的主要原因之一。该寄生虫通过摄入感染性卵囊传播，这些卵囊在环境中高度稳定，几乎能抵抗所有传统消毒方法和水处理。由于受感染个体粪便中大量卵囊的排泄污染了环境，并成为包括人类和动物在内的易感宿主的感染源，控制该寄生虫感染极其困难。针对该寄生虫的药物开发具有挑战性，原因在于其遗传可操作性有限、缺乏传统药物靶点、在宿主体内独特的细胞内定位，以及缺乏用于寄生虫持续繁殖的强大细胞培养平台。尽管该寄生虫感染率很高，但美国食品药品监督管理局（FDA）批准的唯一治疗隐孢子虫感染的药物是硝唑尼特，它在免疫功能正常的患者中显示出中等疗效。更重要的是，对于免疫缺陷患者、幼儿和新生家畜中严重的、可能危及生命的隐孢子虫病，没有有效的治疗药物。因此，迫切需要安全、廉价且有效的药物来减轻全球日益增加的隐孢子虫病负担，尤其是在资源匮乏的国家。已经对几种化合物进行了针对该疾病的体外和体内疗效测试。然而，迄今为止，只有少数实验性化合物在天然宿主中进行了临床试验，其中没有一种被证明有效。本综述概述了过去和现在人类及家畜的抗隐孢子虫药物治疗。在此，我们还强调了该领域在过去几年取得的进展，并讨论了用于发现和开发隐孢子虫病有效前瞻性治疗方法的不同策略。
