a Department of Internal Medicine , University of Texas Medical Branch , Galveston , Texas , USA.
b Infectious Diseases Division, Department of Internal Medicine , University of Texas Medical Branch , Galveston , Texas , USA.
Expert Rev Anti Infect Ther. 2018 Aug;16(8):655-661. doi: 10.1080/14787210.2018.1500457. Epub 2018 Jul 17.
Cryptosporidium is a protozoan pathogen that can cause diarrheal disease in healthy and immunosuppressed individuals, worldwide. Recent studies have highlighted the impact of cryptosporidiosis on children in resource-limited countries. Nitazoxanide is the only Food and Drug Administration approved treatment, but it is not consistently effective therapy for cryptosporidiosis in the most vulnerable populations. Areas covered: This review focused on recent published studies evaluating novel drugs and new compounds for the treatment of cryptosporidiosis. Expert commentary: Combinations of approved drugs have demonstrated some activity. Broad screens have demonstrated activity against Cryptosporidium for a number of available drugs, including statins and clofazimine, and the latter has advanced into clinical trials. Cryptosporidium calcium-dependent protein kinase 1 (CDPK1) has been identified as an attractive target for treatment, and bumped kinase inhibitors have been developed which inhibit CDPK1 and are active against Cryptosporidium growth both in vitro and in vivo. Inhibition of Plasmodium lipid kinase PI(4)K8 of Cryptosporidium by KDU731 greatly reduced oocyst shedding and improved diarrhea in calves with limited effects on the human PI(4)K. Another novel potent inhibitor MMV665917 was efficacious in mouse models with cidal activity against Cryptosporidium. Additional compounds have proved active in vitro. So far, only clofazimine has entered human trials.
隐孢子虫是一种原生动物病原体，可在全球范围内导致健康和免疫抑制个体的腹泻病。最近的研究强调了隐孢子虫病对资源有限国家儿童的影响。硝唑尼特是唯一获得美国食品和药物管理局批准的治疗药物，但对于最脆弱人群的隐孢子虫病并非始终有效。
这篇综述重点介绍了最近发表的评估新型药物和新化合物治疗隐孢子虫病的研究。
联合使用已批准的药物已显示出一些活性。广泛的筛选已证明许多现有药物对隐孢子虫具有活性，包括他汀类药物和氯法齐明，后者已进入临床试验。隐孢子虫钙依赖性蛋白激酶 1（CDPK1）已被确定为有吸引力的治疗靶点，已经开发出了 bumped 激酶抑制剂，可抑制 CDPK1，并在体外和体内对隐孢子虫的生长均具有活性。KDU731 抑制隐孢子虫的疟原虫脂质激酶 PI(4)K8 可大大减少卵囊脱落并改善腹泻，对人类 PI(4)K 的影响有限。另一种新型有效的强效抑制剂 MMV665917 在小鼠模型中具有杀菌活性，对隐孢子虫有效。其他化合物已被证明在体外具有活性。到目前为止，只有氯法齐明已进入人体试验。
