Zwang Julien, Olliaro Piero L
Independent researcher, Bangkok, Thailand.
UNICEF/UNDP/WB/WHO Special Programme for Research & Training in Tropical Diseases (TDR), Geneva, Switzerland; Centre for Tropical Medicine, University of Oxford, Oxford, United Kingdom.
PLoS Negl Trop Dis. 2014 Nov 20;8(11):e3286. doi: 10.1371/journal.pntd.0003286. eCollection 2014.
Extensive use of praziquantel for treatment and control of schistosomiasis requires a comprehensive understanding of efficacy and safety of various doses for different Schistosoma species.
METHODOLOGY/PRINCIPAL FINDINGS: A systematic review and meta-analysis of comparative and non-comparative trials of praziquantel at any dose for any Schistosoma species assessed within two months post-treatment. Of 273 studies identified, 55 were eligible (19,499 subjects treated with praziquantel, control treatment or placebo). Most studied were in school-aged children (64%), S. mansoni (58%), and the 40 mg/kg dose (56%); 68% of subjects were in Africa. Efficacy was assessed as cure rate (CR, n=17,017) and egg reduction rate (ERR, n=13,007); safety as adverse events (AE) incidence. The WHO-recommended dose of praziquantel 40 mg/kg achieved CRs of 94.7% (95%CI 92.2-98.0) for S. japonicum, 77.1% (68.4-85.1) for S. haematobium, 76.7% (95%CI 71.9-81.2) for S. mansoni, and 63.5% (95%CI 48.2-77.0) for mixed S. haematobium/S. mansoni infections. Using a random-effect meta-analysis regression model, a dose-effect for CR was found up to 40 mg/kg for S. mansoni and 30 mg/kg for S. haematobium. The mean ERR was 95% for S. japonicum, 94.1% for S. haematobium, and 86.3% for S. mansoni. No significant relationship between dose and ERR was detected. Tolerability was assessed in 40 studies (12,435 subjects). On average, 56.9% (95%CI 47.4-67.9) of the subjects receiving praziquantel 40 mg/kg experienced an AE. The incidence of AEs ranged from 2.3% for urticaria to 31.1% for abdominal pain.
CONCLUSIONS/SIGNIFICANCE: The large number of subjects allows generalizable conclusions despite the inherent limitations of aggregated-data meta-analyses. The choice of praziquantel dose of 40 mg/kg is justified as a reasonable compromise for all species and ages, although in a proportion of sites efficacy may be lower than expected and age effects could not be fully explored.
广泛使用吡喹酮治疗和控制血吸虫病需要全面了解不同剂量对不同血吸虫种类的疗效和安全性。
方法/主要发现：对治疗后两个月内评估的任何剂量吡喹酮针对任何血吸虫种类的比较性和非比较性试验进行系统评价和荟萃分析。在检索到的273项研究中，55项符合要求（19499名接受吡喹酮、对照治疗或安慰剂的受试者）。大多数研究对象为学龄儿童（64%）、曼氏血吸虫（58%）和40mg/kg剂量组（56%）；68%的受试者来自非洲。疗效评估指标为治愈率（CR，n = 17017）和虫卵减少率（ERR，n = 13007）；安全性评估指标为不良事件（AE）发生率。世界卫生组织推荐的吡喹酮剂量40mg/kg对日本血吸虫的治愈率为94.7%（95%CI 92.2 - 98.0），对埃及血吸虫为77.1%（68.4 - 85.1），对曼氏血吸虫为76.7%（95%CI 71.9 - 81.2），对埃及血吸虫/曼氏血吸虫混合感染为63.5%（95%CI 48.2 - 77.0）。使用随机效应荟萃分析回归模型，发现曼氏血吸虫CR在40mg/kg剂量范围内存在剂量效应，埃及血吸虫在30mg/kg剂量范围内存在剂量效应。日本血吸虫的平均ERR为95%，埃及血吸虫为94.1%，曼氏血吸虫为86.3%。未检测到剂量与ERR之间存在显著关系。在40项研究（12435名受试者）中评估了耐受性。平均而言，接受40mg/kg吡喹酮的受试者中有56.9%（95%CI 47.4 - 67.9）经历了不良事件。不良事件的发生率从荨麻疹的2.3%到腹痛的31.1%不等。
结论/意义：尽管汇总数据荟萃分析存在固有局限性，但大量受试者使得能够得出可推广的结论。选择40mg/kg的吡喹酮剂量对于所有种类和年龄来说是合理的折衷方案，尽管在部分地点疗效可能低于预期，且年龄效应未能充分探究。
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