Stettler M, Siles-Lucas M, Sarciron E, Lawton P, Gottstein B, Hemphill A
Institute of Parasitology, University of Bern, Bern, Switzerland.
Antimicrob Agents Chemother. 2001 Aug;45(8):2256-62. doi: 10.1128/AAC.45.8.2256-2262.2001.
Alveolar echinococcosis (AE) is caused by the metacestode stage of the fox tapeworm Echinococcus multilocularis. The disease affects the human liver and occasionally other organs and is fatal if treatment is unsuccessful. The present chemotherapy of AE is based on the administration of benzimidazole carbamate derivatives, such as mebendazole and albendazole. Albendazole treatment has been found to be ineffective in some cases, parasitostatic rather than parasiticidal, and the recurrence rate is rather high. Therefore, chemotherapy usually involves the lifelong uptake of massive doses of albendazole and new treatment options are urgently needed. In order to avoid costly and time-consuming animal experimentation, a first step in searching for novel parasiticidal compounds could be the in vitro drug screening of novel compounds by employing metacestode cultivation. However, presently used techniques (e.g., transmission electron microscopy) for determination of parasite viability involve costly equipment and time-consuming preparation of rather large amounts of parasite material. We therefore searched for a parasite marker which can be easily traced and the presence or absence of which is indicative of parasite viability. In this study we show that the increase of E. multilocularis alkaline phosphatase activity in culture supernatants during in vitro drug treatment with albendazole derivatives correlates with the progressive degeneration and destruction of the metacestode tissue. The inexpensive and rapid assay presented here will serve as an ideal tool for performing first-round in vitro tests on the efficacy of a large number of antiparasitic compounds.
泡型包虫病（AE）由狐绦虫多房棘球绦虫的中绦期幼虫引起。该病影响人体肝脏，偶尔也会累及其他器官，若治疗失败则会致命。目前AE的化疗基于苯并咪唑氨基甲酸酯衍生物的给药，如甲苯咪唑和阿苯达唑。已发现阿苯达唑治疗在某些情况下无效，具有抑制寄生虫生长而非杀灭寄生虫的作用，且复发率相当高。因此，化疗通常需要终身大量服用阿苯达唑，迫切需要新的治疗选择。为了避免昂贵且耗时的动物实验，寻找新型杀寄生虫化合物的第一步可以是通过使用中绦期幼虫培养对新型化合物进行体外药物筛选。然而，目前用于确定寄生虫活力的技术（如透射电子显微镜）需要昂贵的设备，且制备相当大量的寄生虫材料耗时。因此，我们寻找一种易于追踪的寄生虫标志物，其存在与否可指示寄生虫的活力。在本研究中，我们表明在用阿苯达唑衍生物进行体外药物治疗期间，培养上清液中多房棘球绦虫碱性磷酸酶活性的增加与中绦期幼虫组织的渐进性退化和破坏相关。本文介绍的这种廉价且快速的检测方法将成为对大量抗寄生虫化合物的疗效进行首轮体外测试的理想工具。
