Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.
University of Basel, Basel, Switzerland.
Clin Infect Dis. 2019 Aug 16;69(5):845-852. doi: 10.1093/cid/ciy999.
The global strategy to control soil-transmitted helminthiasis is mainly focused on preventive chemotherapy with albendazole and mebendazole. We assessed the efficacy and safety of ascending tribendimidine doses against hookworm infections in African school-aged children, key information for the development of tribendimidine.
We performed a single blind, randomized, controlled trial in Côte d'Ivoire between June and August 2017. Eligible participants were randomly assigned to placebo, 100, 200, or 400 mg tribendimidine. Cure rates (CRs, primary outcome) and egg reduction rates (ERRs) were determined 14-21 days after treatment. Clinical symptoms were assessed before treatment and adverse events monitored 3 and 24 hours posttreatment.
CRs calculated for 130 children dose-dependently increased. The observed CRs were 20.6% (7/34), 21.2% (7/33), 38.7% (12/31), and 53.1% (17/32) for placebo, 100, 200, and 400 mg of tribendimidine, respectively. The Emax model predicted a placebo corrected net effect of 34.3 percentage points (95% confidence interval [CI], 13.3-54.4) for the 400-mg tribendimidine dose. The ERRs (geometric mean) were 30.6% (95% CI, -24.7 to 64.1), 65.4% (95% CI, 24.5-85.9), 82.1% (95% CI, 58.4-92.5) and 92.2% (95% CI, 81.0-97.1) for placebo, 100, 200, and 400 mg tribendimidine, respectively. The Emax model predicted an ERR of 95% at 500 mg. Only mild adverse events and no abnormal biochemical parameters were observed.
A 400-mg dose of tribendimidine yielded the highest efficacy and was well tolerated. Because children were mostly lightly infected, further investigations with tribendimidine against moderate/heavy hookworm infection are needed.
The trial is registered at www.isrctn.com number ISRCTN81391471.
全球控制土壤传播性蠕虫病的策略主要侧重于使用阿苯达唑和甲苯达唑进行预防性化疗。我们评估了递增剂量曲苯达唑治疗非洲学龄儿童钩虫感染的疗效和安全性，这是曲苯达唑开发的关键信息。
我们于 2017 年 6 月至 8 月在科特迪瓦进行了一项单盲、随机、对照试验。合格的参与者被随机分配到安慰剂、100、200 或 400 毫克曲苯达唑组。治疗后 14-21 天确定治愈率（主要结局）和虫卵减少率（ERR）。在治疗前评估临床症状，并在治疗后 3 小时和 24 小时监测不良事件。
根据剂量计算，儿童的治愈率呈剂量依赖性增加。观察到的治愈率分别为安慰剂组 20.6%（7/34）、21.2%（7/33）、38.7%（12/31）和 53.1%（17/32），100、200 和 400 毫克曲苯达唑组分别为 21.2%（7/33）、38.7%（12/31）和 53.1%（17/32）。Emax 模型预测 400 毫克曲苯达唑的安慰剂校正净效应为 34.3 个百分点（95%置信区间，13.3-54.4）。几何均数 ERR 分别为 30.6%（95%置信区间，-24.7 至 64.1）、65.4%（95%置信区间，24.5-85.9）、82.1%（95%置信区间，58.4-92.5）和 92.2%（95%置信区间，81.0-97.1），安慰剂、100、200 和 400 毫克曲苯达唑组分别为 30.6%（95%置信区间，-24.7 至 64.1）、65.4%（95%置信区间，24.5-85.9）、82.1%（95%置信区间，58.4-92.5）和 92.2%（95%置信区间，81.0-97.1）。Emax 模型预测 ERR 在 500 毫克时为 95%。仅观察到轻度不良事件和无异常生化参数。
400 毫克剂量的曲苯达唑疗效最高，且耐受性良好。由于儿童大多感染较轻，因此需要进一步研究曲苯达唑对中度/重度钩虫感染的疗效。
该试验在 www.isrctn.com 注册，编号为 ISRCTN81391471。
