Neville Andrew J, Zach Sydney J, Wang Xiaofang, Larson Joshua J, Judge Abigail K, Davis Lisa A, Vennerstrom Jonathan L, Davis Paul H
Department of Biology, University of Nebraska at Omaha, Omaha, Nebraska, USA.
College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Antimicrob Agents Chemother. 2015 Dec;59(12):7161-9. doi: 10.1128/AAC.02009-15. Epub 2015 Sep 21.
Toxoplasma gondii is an apicomplexan parasite of humans and other mammals, including livestock and companion animals. While chemotherapeutic regimens, including pyrimethamine and sulfadiazine regimens, ameliorate acute or recrudescent disease such as toxoplasmic encephalitis or ocular toxoplasmosis, these drugs are often toxic to the host. Moreover, no approved options are available to treat infected women who are pregnant. Lastly, no drug regimen has shown the ability to eradicate the chronic stage of infection, which is characterized by chemoresistant intracellular cysts that persist for the life of the host. In an effort to promote additional chemotherapeutic options, we now evaluate clinically available drugs that have shown efficacy in disease models but which lack clinical case reports. Ideally, less-toxic treatments for the acute disease can be identified and developed, with an additional goal of cyst clearance from human and animal hosts.
刚地弓形虫是一种寄生于人类和包括家畜及伴侣动物在内的其他哺乳动物的顶复门寄生虫。虽然包括乙胺嘧啶和磺胺嘧啶方案在内的化疗方案可改善急性或复发疾病,如弓形虫性脑炎或眼弓形虫病,但这些药物通常对宿主有毒性。此外,目前尚无获批的治疗方案可用于治疗感染的孕妇。最后,尚无任何药物方案能够根除感染的慢性阶段,该阶段的特征是存在对化疗耐药的细胞内囊肿,会在宿主的生命周期内持续存在。为了推动更多化疗方案的出现,我们现在评估在疾病模型中已显示出疗效但缺乏临床病例报告的临床可用药物。理想情况下,可确定并开发出毒性较小的急性疾病治疗方法,另外一个目标是清除人类和动物宿主中的囊肿。