Obonyo Charles O, Were Vincent O, Wamae Peter, Muok Erick M O
Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya.
Antimicrob Agents Chemother. 2025 Feb 13;69(2):e0073924. doi: 10.1128/aac.00739-24. Epub 2024 Dec 19.
Praziquantel alone is insufficient for the control of schistosomiasis due to poor efficacy against juvenile worms and increasing concerns about the risk of drug resistance. We compared the efficacy and safety of praziquantel combined with four different artemisinin-based combinations to praziquantel alone in treating infection in Kenyan children. In this randomized, open-label, five-arm, head-to-head, non-inferiority trial, children (aged 9-15 years) with infection according to duplicate Kato Katz thick smears from a stool sample in the Mwea irrigation scheme of central Kenya, were enrolled. Participants were randomly assigned (1:1:1:1:1) via a computer-generated block randomization procedure to receive a single oral dose of praziquantel (PZQ) (40 mg/kg/day) alone or in combination with a 3-day course (4 mg/kg of artesunate) of artesunate plus sulfalene-pyrimethamine (As + SP), artesunate plus amodiaquine (As + AQ), artesunate plus mefloquine (As + MQ) or dihydroartemisinin-piperaquine (DHAP). Laboratory technicians were masked to treatment allocation, but participants, clinicians, and study nurses were not. The primary outcomes were the cure rate and frequency of adverse events, which were assessed 6 weeks after treatment in the available case population using a per-protocol analysis. The non-inferiority margin was set at -10% for the risk difference in cure rates between combination therapy and PZQ alone. Between 12 September 2018 and 11 January 2019, 540 participants were assigned to receive PZQ alone ( = 108), PZQ plus As + SP ( = 108), PZQ plus As + AQ ( = 108), PZQ plus As + MQ ( = 108), or PZQ plus DHAP ( = 108). Primary outcome data were available for 523 (96.9%) participants. The cure rate was 82.5% (85/103) in PZQ alone, 81.7% (85/104) in PZQ plus As + SP, 76.2% (80/105) in PZQ plus As + AQ, 88.7% (94/106) in PZQ plus As + MQ, and 85.7% (90/105) in PZQ plus DHAP arm. Non-inferiority was declared for PZQ plus As + MQ (difference 6.2 [95% confidence interval: -3.3 to 15.6]) and PZQ plus DHAP (3.2 [-6.7 to 13.1]) but not for PZQ plus As + SP (-0.8 [-11.2 to 9.6]) or PZQ plus As + AQ (-6.3 [-17.3 to 4.6]). Adverse events were reported by 26% (138/540) of participants, including abdominal pain, headache, and vomiting. There were no serious adverse events. Alternatives to praziquantel should include praziquantel plus artesunate-mefloquine or praziquantel plus dihydroartemisinin-piperaquine. However, further multicentre trials are needed in different epidemiological settings and population groups to confirm these findings.CLINICAL TRIALSThis study is registered with the Pan-African Clinical Trials Registry under PACTR202001919442161.
由于对幼虫的疗效不佳以及对耐药风险的担忧日益增加，仅使用吡喹酮不足以控制血吸虫病。我们比较了吡喹酮联合四种不同的青蒿素类复方药物与单独使用吡喹酮治疗肯尼亚儿童感染的疗效和安全性。在这项随机、开放标签、五臂、头对头、非劣效性试验中，纳入了肯尼亚中部姆韦亚灌溉区根据粪便样本的重复加藤厚涂片确诊感染的儿童（9至15岁）。参与者通过计算机生成的区组随机化程序被随机分配（1:1:1:1:1），接受单剂量口服吡喹酮（PZQ）（40mg/kg/天），或与青蒿琥酯加磺胺多辛-乙胺嘧啶（As + SP）、青蒿琥酯加阿莫地喹（As + AQ）、青蒿琥酯加甲氟喹（As + MQ）或双氢青蒿素哌喹（DHAP）的3天疗程（4mg/kg青蒿琥酯）联合使用。实验室技术人员对治疗分配情况不知情，但参与者、临床医生和研究护士知情。主要结局是治愈率和不良事件发生率，在治疗后6周对可用病例人群采用符合方案分析进行评估。联合治疗与单独使用PZQ的治愈率风险差异的非劣效界值设定为-10%。在2018年9月12日至2019年1月11日期间，540名参与者被分配接受单独的PZQ（n = 108）、PZQ加As + SP（n = 108）、PZQ加As + AQ（n = 108）、PZQ加As + MQ（n = 108）或PZQ加DHAP（n = 108）。523名（96.9%）参与者有主要结局数据。单独使用PZQ的治愈率为82.5%（85/103），PZQ加As + SP为81.7%（85/104），PZQ加As + AQ为76.2%（80/105），PZQ加As + MQ为88.7%（94/106），PZQ加DHAP组为85.7%（90/105）。宣布PZQ加As + MQ（差异6.2 [95%置信区间：-3.3至15.6]）和PZQ加DHAP（3.2 [-6.7至13.1]）非劣效，但PZQ加As + SP（-0.8 [-11.2至9.6]）或PZQ加As + AQ（-6.3 [-17.3至4.6]）并非如此。26%（138/540）的参与者报告了不良事件，包括腹痛、头痛和呕吐。没有严重不良事件。吡喹酮的替代方案应包括吡喹酮加青蒿琥酯-甲氟喹或吡喹酮加双氢青蒿素哌喹。然而，需要在不同的流行病学环境和人群组中进行进一步的多中心试验以证实这些发现。临床试验本研究已在泛非临床试验注册中心注册，注册号为PACTR202001919442161。
