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青蒿素-磷酸萘喹对埃及血吸虫成虫的疗效:剂量效应关系及体表变化

Efficacy of artemisinin-naphthoquine phosphate against Schistosoma haematobium adult flukes: dose-effect relationship and tegumental alterations.

作者信息

El-Beshbishi S N, El Bardicy S, Tadros M, Ayoub M, Taman A

机构信息

Department of Medical Parasitology,Faculty of Medicine,Mansoura University,Mansoura 35516-Egypt.

Department of Medical Malacology,Theodor Bilharz Research Institute,Warrak El Hadar,Imbaba,Giza,Egypt.

出版信息

J Helminthol. 2019 Jul;93(4):513-518. doi: 10.1017/S0022149X18000421. Epub 2018 May 21.

DOI:10.1017/S0022149X18000421
PMID:29779499
Abstract

Schistosoma haematobium and Schistosoma mansoni infections have broadly overlapping geographical distributions. Praziquantel is the only treatment for human schistosomiasis, so drug tolerance and/or resistance are major concerns. Artemisinin-naphthoquine phosphate (CO-ArNp), an artemisinin-based combination therapy endorsed by the World Health Organization as a gold standard therapy for malaria, has also been identified as a promising treatment for S. mansoni. In this in vitro study, we tested the effect of 1-40 μg/ml CO-ArNp on S. haematobium worms, and inspected tegumental changes by using scanning electron microscopy (SEM), aiming to determine if this combination therapy has a broad-spectrum antischistosomal activity. Incubation of S. haematobium adults with 20 or 30 μg/ml CO-ArNp caused 100% mortality of worms within 72 or 48 h, respectively. SEM examination showed extensive tegumental alterations such as oedema, constriction, shortening and loss of spines, fissuring, sloughing and perforation, resulting in exposure of the underlying basal lamina, mainly in treated male schistosomes. Besides the well-established potent efficacy, bioavailability, tolerability and safety of the antimalarial artemisinin-naphthoquine phosphate combined therapy, these results may also suggest its possible utilization as a new broad-spectrum antischistosomal agent.

摘要

埃及血吸虫和曼氏血吸虫感染的地理分布大致重叠。吡喹酮是治疗人类血吸虫病的唯一药物,因此药物耐受性和/或耐药性是主要关注点。青蒿素-磷酸萘喹(CO-ArNp)是一种基于青蒿素的联合疗法,被世界卫生组织认可为治疗疟疾的金标准疗法,也已被确定为治疗曼氏血吸虫的一种有前景的药物。在这项体外研究中,我们测试了1-40μg/ml的CO-ArNp对埃及血吸虫虫体的作用,并通过扫描电子显微镜(SEM)检查体表变化,旨在确定这种联合疗法是否具有广谱抗血吸虫活性。用20或30μg/ml的CO-ArNp孵育埃及血吸虫成虫,分别在72小时或48小时内导致100%的虫体死亡。SEM检查显示体表有广泛的改变,如水肿、收缩、缩短和棘突缺失、裂开、脱落和穿孔,导致底层基膜暴露,主要发生在经治疗的雄血吸虫中。除了抗疟青蒿素-磷酸萘喹联合疗法已确立的强效疗效、生物利用度、耐受性和安全性外,这些结果还可能表明其有可能作为一种新型广谱抗血吸虫药物加以利用。

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引用本文的文献

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