Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China.
College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China.
Vet Parasitol. 2024 Oct;331:110279. doi: 10.1016/j.vetpar.2024.110279. Epub 2024 Aug 2.
Cryptosporidium is among the top causes of life-threatening diarrheal infection in public health and livestock sectors. Despite its high prevalence and economic importance, currently, there is no vaccine. Control of this protozoan is difficult due to the excretion of many resistant oocysts in the feces of the infected host, which contaminate the environment. Paromomycin shows inconsistent results and isn't considered a reliable therapy for cryptosporidiosis. Nitazoxanide (NTZ), the only FDA-approved drug against this parasite, is less productive in impoverished children and PLWHA (people living with HIV/AIDS). The absence of mitochondria and apicoplast, its unique location inside enterocytes separated by parasitophorous vacuole, and, most importantly, challenges in its genetic manipulations are some hurdles to the drug-discovery process. A library of compounds has been tested against Cryptosporidium during in vitro and in vivo trials. However, there has still not been sufficient success in finding the drug of choice against this parasite. Recent genome editing technologies based on CRISPR/Cas-9 have explored the functions of the vital genes by producing transgenic parasites that help to screen a collection of compounds to find target-specific drugs, provided the sufficient availability of in vitro culturing platforms, efficient transfection methods, and analytic techniques. The use of herbal remedies against Cryptosporidium is also an emerging area of interest with sufficient clinical success due to enhanced concern regarding anthelmintic resistance. Here, we highlighted present treatment options with their associated limitations, the use of genetic tools and natural products against it to find safe, effective, and inexpensive drugs to control the ever-increasing global burden of this disease.
隐孢子虫是公共卫生和畜牧业领域导致危及生命的腹泻感染的主要原因之一。尽管它的发病率很高，具有重要的经济意义，但目前还没有疫苗。由于感染宿主粪便中排出许多具有抗性的卵囊，这些卵囊污染了环境，因此难以控制这种原生动物。巴龙霉素的效果不一致，不被认为是隐孢子虫病的可靠治疗方法。硝唑尼特（NTZ）是唯一获得 FDA 批准的针对这种寄生虫的药物，但在贫困儿童和 PLWHA（艾滋病毒/艾滋病感染者）中的效果较差。它缺乏线粒体和质体，其在被吞噬小泡分隔的肠细胞内的独特位置，以及最重要的是，在其遗传操作方面的挑战，是药物发现过程中的一些障碍。已经在体外和体内试验中对化合物库进行了针对隐孢子虫的测试。然而，在找到针对这种寄生虫的首选药物方面，仍然没有取得足够的成功。基于 CRISPR/Cas-9 的最近基因组编辑技术通过产生转基因寄生虫来探索重要基因的功能，有助于筛选一组化合物以寻找针对特定目标的药物，前提是有足够的体外培养平台、有效的转染方法和分析技术。利用草药治疗隐孢子虫也是一个新兴的研究领域，由于对抗寄生虫药物耐药性的关注增加，取得了足够的临床成功。在这里，我们重点介绍了目前的治疗选择及其相关的局限性，以及利用遗传工具和天然产物来对抗它，以找到安全、有效和廉价的药物来控制这种疾病在全球不断增加的负担。
