National Institute of Public Health, Ministry of Health, Vientiane, Lao People's Democratic Republic.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel
Clin Infect Dis. 2017 Feb 15;64(4):451-458. doi: 10.1093/cid/ciw785.
The liver fluke Opisthorchis viverrini, highly prevalent in Southeast Asia, is an important public health burden, including a risk factor for developing an aggressive bile duct cancer, cholangiocarcinoma, in chronically infected patients. Praziquantel, administered at a single 40 mg/kg dose in preventive chemotherapy programs and 3 × 25 mg/kg for individual treatment, is the drug of choice, yet information on the nature of the dose-response relationship is lacking.
We performed a randomized, parallel, single-blind dose-ranging phase 2 trial in the Lao People’s Democratic Republic in O. viverrini–infected adults. Patients were randomly assigned to 30 mg/kg, 40 mg/kg, 50 mg/kg, or 3 × 25 mg/kg praziquantel or placebo. Adverse events were recorded at baseline, 3 hours, and 24 hours posttreatment. Cure rates (CRs) and egg reduction rates (ERRs) were estimated 3 weeks after drug administration using available case analysis. Dose-response curves were predicted using Emax models.
Two-hundred seventeen O. viverrini–infected patients were assigned to the 5 treatment arms. The majority (94.3%) of patients harbored light infections. The Emax model predicted a high efficacy among the observed dose range. We observed CRs ranging from 92.7% to 95.5% and ERRs >99.5% for all praziquantel treatment groups. Adverse events were mild but higher in the standard treatment group (3 × 25 mg/kg) than in the single-dose treatment arms.
Single-dose praziquantel appears to be as efficacious as the standard 3 × 25 mg/kg regimen for the treatment of O. viverrini infections, while presenting fewer adverse events. Further studies are necessary in moderate and heavy O. viverrini infections.
Randomized Controlled Trials (ISRCTN77186750).
肝吸虫（Opisthorchis viverrini）在东南亚高度流行，是一个重要的公共卫生负担，包括慢性感染患者发展为侵袭性胆管癌（胆管癌）的危险因素。在预防化疗计划中，单次给予 40mg/kg 的吡喹酮，或针对个体治疗给予 3×25mg/kg 的吡喹酮，是首选药物，但缺乏关于剂量-反应关系本质的信息。
我们在老挝人民民主共和国的肝吸虫感染者成年人中进行了一项随机、平行、单盲剂量范围的 2 期试验。患者被随机分配到 30mg/kg、40mg/kg、50mg/kg 或 3×25mg/kg 的吡喹酮或安慰剂组。在基线、治疗后 3 小时和 24 小时记录不良事件。在药物给药后 3 周使用可用病例分析估计治愈率（CR）和卵减少率（ERR）。使用 Emax 模型预测剂量反应曲线。
217 例肝吸虫感染者被分配到 5 个治疗组。大多数（94.3%）患者感染较轻。Emax 模型预测在观察到的剂量范围内具有较高的疗效。我们观察到所有吡喹酮治疗组的 CR 范围为 92.7%至 95.5%，ERR>99.5%。不良事件轻微，但在标准治疗组（3×25mg/kg）高于单剂量治疗组。
单次剂量的吡喹酮似乎与标准的 3×25mg/kg 方案一样有效治疗肝吸虫感染，同时不良反应较少。在中度和重度肝吸虫感染中还需要进一步的研究。
随机对照试验（ISRCTN77186750）。
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