Efficacy and Safety of Artemether in the Treatment of Chronic Fascioliasis in Egypt: Exploratory Phase-2 Trials

BackgroundFascioliasis is an emerging zoonotic disease of considerable veterinary and public health importance. Triclabendazole is the only available drug for treatment. Laboratory studies have documented promising fasciocidal properties of the artemisinins (e.g., artemether). MethodologyWe carried out two exploratory phase-2 trials to assess the efficacy and safety of oral artemether administered at (i) 6×80 mg over 3 consecutive days, and (ii) 3×200 mg within 24 h in 36 Fasciola-infected individuals in Egypt. Efficacy was determined by cure rate (CR) and egg reduction rate (ERR) based on multiple Kato-Katz thick smears before and after drug administration. Patients who remained Fasciola-positive following artemether dosing were treated with single 10 mg/kg oral triclabendazole. In case of treatment failure, triclabendazole was re-administered at 20 mg/kg in two divided doses. Principal FindingsCRs achieved with 6×80 mg and 3×200 mg artemether were 35% and 6%, respectively. The corresponding ERRs were 63% and nil, respectively. Artemether was well tolerated. A high efficacy was observed with triclabendazole administered at 10 mg/kg (16 patients; CR: 67%, ERR: 94%) and 20 mg/kg (4 patients; CR: 75%, ERR: 96%). Conclusions/SignificanceArtemether, administered at malaria treatment regimens, shows no or only little effect against fascioliasis, and hence does not represent an alternative to triclabendazole. The role of artemether and other artemisinin derivatives as partner drug in combination chemotherapy remains to be elucidated.

【背景】片形吸虫病（Fascioliasis）是一种新发人兽共患病，在兽医与公共卫生领域具有相当重要的意义。三氯苯达唑（Triclabendazole）是目前唯一可用的治疗药物。实验室研究已证实青蒿素类（artemisinins，如青蒿素甲醚（artemether））具备良好的杀片形吸虫活性。
【方法学】我们开展了两项探索性II期临床试验，评估口服青蒿素甲醚的疗效与安全性，给药方案分别为：（i）连续3天每日给药80mg，共6次；（ii）24小时内分3次给药，每次200mg。受试对象为埃及的36名片形吸虫感染者。疗效通过治愈率（CR, Cure Rate）与虫卵减少率（ERR, Egg Reduction Rate）进行判定，判定依据为给药前后多次Kato-Katz厚涂片检测结果。对于青蒿素甲醚治疗后仍呈片形吸虫阳性的患者，给予单次口服10mg/kg剂量的三氯苯达唑治疗；若治疗失败，则将三氯苯达唑剂量调整为20mg/kg，分两次给药。
【主要结果】6次80mg方案与3次200mg方案的青蒿素甲醚治疗治愈率分别为35%和6%，对应的虫卵减少率分别为63%和0%。青蒿素甲醚的耐受性良好。10mg/kg剂量三氯苯达唑组（16名患者）的治愈率为67%，虫卵减少率为94%；20mg/kg剂量组（4名患者）的治愈率为75%，虫卵减少率为96%，均展现出较高的治疗效果。
【结论与意义】采用疟疾治疗方案的青蒿素甲醚，对片形吸虫病仅表现出微弱甚至无治疗效果，因此无法作为三氯苯达唑的替代治疗药物。青蒿素甲醚及其他青蒿素类衍生物作为联合化疗辅助药物的作用，仍有待进一步阐明。