PDF(Pubmed)
Abstract：
BACKGROUND: Reliance on praziquantel for the treatment and control of schistosomiasis is likely to facilitate the emergence of drug resistance. Combination therapy targeting adult and juvenile schistosome worms is urgently needed to improve praziquantel efficacy and delay the potential development of drug resistance. We assessed the efficacy and safety of single-dose praziquantel combined with single-dose artesunate plus sulfalene-pyrimethamine in the treatment of Kenyan children with schistosomiasis.
METHODS: This was an open-label, randomised clinical trial involving 426 school-aged children (7-15 years old) diagnosed with Schistosoma mansoni (by Kato-Katz) or S. haematobium (by urine filtration). They were randomly assigned (1:1:1) to receive a single dose of praziquantel (40 mg/kg), a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate) or combination therapy using a single dose of praziquantel (40 mg/kg) combined with a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate). The primary outcome was cure and egg reduction rates at 6 weeks post-treatment in the available case population. Adverse events were assessed within 3 h after treatment.
RESULTS: Of the 426 children enrolled, 135 received praziquantel, 150 received artesunate plus sulfalene-pyrimethamine, and 141 received combination therapy. Outcome data were available for 348 (81.7%) children. For S. mansoni-infected children (n = 335), the cure rates were 75.6%, 60.7%, and 77.8%, and the egg reduction rates were 80.1%, 85.0%, and 88.4% for praziquantel, artesunate plus sulfalene-pyrimethamine, and combination therapy, respectively. For S. haematobium-infected children (n = 145), the corresponding cure rates were 81.4%, 71.1%, and 82.2%, and the egg reduction rates were 95.6%, 97.1%, and 97.7%, respectively. Seventy-one (16.7%) children reported mild-intensity adverse events. The drugs were well tolerated and no serious adverse events were reported.
CONCLUSIONS: A single oral dose of praziquantel combined with artesunate plus sulfalene-pyrimethamine cured a high proportion of children with S. haematobium but did not significantly improve the treatment efficacy for either urinary or intestinal schistosomiasis. Sequential administration of praziquantel and artesunate plus sulfalene-pyrimethamine may enhance the efficacy and safety outcomes.
METHODS: This was an open-label, randomised clinical trial involving 426 school-aged children (7-15 years old) diagnosed with Schistosoma mansoni (by Kato-Katz) or S. haematobium (by urine filtration). They were randomly assigned (1:1:1) to receive a single dose of praziquantel (40 mg/kg), a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate) or combination therapy using a single dose of praziquantel (40 mg/kg) combined with a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate). The primary outcome was cure and egg reduction rates at 6 weeks post-treatment in the available case population. Adverse events were assessed within 3 h after treatment.
RESULTS: Of the 426 children enrolled, 135 received praziquantel, 150 received artesunate plus sulfalene-pyrimethamine, and 141 received combination therapy. Outcome data were available for 348 (81.7%) children. For S. mansoni-infected children (n = 335), the cure rates were 75.6%, 60.7%, and 77.8%, and the egg reduction rates were 80.1%, 85.0%, and 88.4% for praziquantel, artesunate plus sulfalene-pyrimethamine, and combination therapy, respectively. For S. haematobium-infected children (n = 145), the corresponding cure rates were 81.4%, 71.1%, and 82.2%, and the egg reduction rates were 95.6%, 97.1%, and 97.7%, respectively. Seventy-one (16.7%) children reported mild-intensity adverse events. The drugs were well tolerated and no serious adverse events were reported.
CONCLUSIONS: A single oral dose of praziquantel combined with artesunate plus sulfalene-pyrimethamine cured a high proportion of children with S. haematobium but did not significantly improve the treatment efficacy for either urinary or intestinal schistosomiasis. Sequential administration of praziquantel and artesunate plus sulfalene-pyrimethamine may enhance the efficacy and safety outcomes.
摘要：
背景：依赖吡喹酮治疗和控制血吸虫病可能会促进耐药性的出现。迫切需要针对成年和幼年血吸虫的联合治疗，以提高吡喹酮的疗效并延迟潜在的耐药性发展。我们评估了单剂量吡喹酮联合单剂量青蒿琥酯加次硫烯-乙胺嘧啶治疗肯尼亚血吸虫病儿童的疗效和安全性。
方法：这是一个开放标签，纳入426名学龄儿童（7-15岁）的随机临床试验被诊断为曼氏血吸虫（Kato-Katz）或血吸虫链球菌（通过尿液过滤）。他们被随机分配（1：1：1）接受单剂量吡喹酮（40mg/kg），单剂量青蒿琥酯加次硫烯-乙胺嘧啶（12mg/kg青蒿琥酯）或使用单剂量吡喹酮（40mg/kg）联合单剂量青蒿琥酯加次硫烯-乙胺嘧啶（12mg/kg青蒿琥酯）的联合治疗。主要结果是在可用病例人群中治疗后6周时的治愈和减卵率。治疗后3小时内评估不良事件。
结果：在注册的426名儿童中，135收到吡喹酮,150名接受青蒿琥酯加亚硫烯-乙胺嘧啶，141人接受联合治疗。结果数据为348（81.7%）儿童。对于S.mansoni感染的儿童（n=335），治愈率为75.6%,60.7%,77.8%,减蛋率为80.1%,85.0%,吡喹酮占88.4%，青蒿琥酯加次硫烯-乙胺嘧啶，和联合治疗，分别。对于S.Hematomium感染的儿童（n=145），相应的治愈率为81.4%，71.1%,和82.2%，产蛋率为95.6%,97.1%,和97.7%，分别。71名（16.7%）儿童报告轻度不良事件。药物耐受性良好，未报告严重不良事件。
结论：单次口服吡喹酮联合青蒿琥酯加次硫烯-乙胺嘧啶可治愈高比例的儿童血吸虫病，但对泌尿或肠道血吸虫病的治疗效果均无显著改善。吡喹酮和青蒿琥酯加次硫烯-乙胺嘧啶的顺序给药可提高疗效和安全性。
方法：这是一个开放标签，纳入426名学龄儿童（7-15岁）的随机临床试验被诊断为曼氏血吸虫（Kato-Katz）或血吸虫链球菌（通过尿液过滤）。他们被随机分配（1：1：1）接受单剂量吡喹酮（40mg/kg），单剂量青蒿琥酯加次硫烯-乙胺嘧啶（12mg/kg青蒿琥酯）或使用单剂量吡喹酮（40mg/kg）联合单剂量青蒿琥酯加次硫烯-乙胺嘧啶（12mg/kg青蒿琥酯）的联合治疗。主要结果是在可用病例人群中治疗后6周时的治愈和减卵率。治疗后3小时内评估不良事件。
结果：在注册的426名儿童中，135收到吡喹酮,150名接受青蒿琥酯加亚硫烯-乙胺嘧啶，141人接受联合治疗。结果数据为348（81.7%）儿童。对于S.mansoni感染的儿童（n=335），治愈率为75.6%,60.7%,77.8%,减蛋率为80.1%,85.0%,吡喹酮占88.4%，青蒿琥酯加次硫烯-乙胺嘧啶，和联合治疗，分别。对于S.Hematomium感染的儿童（n=145），相应的治愈率为81.4%，71.1%,和82.2%，产蛋率为95.6%,97.1%,和97.7%，分别。71名（16.7%）儿童报告轻度不良事件。药物耐受性良好，未报告严重不良事件。
结论：单次口服吡喹酮联合青蒿琥酯加次硫烯-乙胺嘧啶可治愈高比例的儿童血吸虫病，但对泌尿或肠道血吸虫病的治疗效果均无显著改善。吡喹酮和青蒿琥酯加次硫烯-乙胺嘧啶的顺序给药可提高疗效和安全性。
