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Evaluation of the therapeutic efficacy of praziquantel against schistosomes in seven countries with ongoing large-scale deworming programs
International Journal for Parasitology: Drugs and Drug Resistance ( IF 4.1 ) Pub Date : 2020-10-17 , DOI: 10.1016/j.ijpddr.2020.10.003
B Levecke 1 , J Vlaminck 1 , L Andriamaro 2 , S Ame 3 , V Belizario 4 , A Degarege 5 , D Engels 6 , B Erko 7 , A D Garba 6 , G M Kaatano 8 , Z Mekonnen 9 , A Montresor 6 , P Olliaro 10 , O S Pieri 11 , M Sacko 12 , S O Sam-Wobo 13 , L A Tchuem Tchuenté 14 , J P Webster 15 , J Vercruysse 1
Affiliation  

The World Health Organization (WHO) recommends periodic assessment of the therapeutic efficacy of praziquantel (PZQ) to detect reduced efficacy that may arise from drug resistance in schistosomes. In this multi-country study (2014), we assessed the therapeutic efficacy of a single oral dose of PZQ (40 mg/kg) against Schistosoma mansoni (Brazil, Cameroon, Ethiopia, Mali, Madagascar and Tanzania), S. haematobium (Cameroon, Ethiopia, Mali, Tanzania and Zanzibar) and S. japonicum (the Philippines) infections in school-aged children, across a total of 12 different trials. Each trial was performed according to the standardized methodology for evaluating PZQ efficacy as described by the WHO. Overall, therapeutic efficacy, measured as the reduction in arithmetic mean of schistosome egg counts following drug administration (egg reduction rate; ERR), was high for all three schistosome species (S. mansoni: 93.4% (95%CI: 88.8–96.8); S. haematobium: 97.7% (95%CI: 96.5–98.7) and S. japonicum: 90.0% (95%CI: 68.4–99.3). At the trial level, therapeutic efficacy was satisfactory (point estimate ERR ≥90%) for all three Schistosoma species with the exception of S. mansoni in Cameroon where the ERR was 88.5% (95%CI: 79.0–95.1). Furthermore, we observed that in some trials individual drug response could vary significantly (wide 95%CI) and that few non-responsive individuals could significantly impact ERR point estimates. In conclusion, these results do not suggest any established reduced efficacy of the standard PZQ treatment to any of the three schistosome species within these countries. Nevertheless, the substantial degree of variation in individual responses to treatment in some countries underpins the need for future monitoring. The reported ERR values serve as reference values to compare with outcomes of future PZQ efficacy studies to ensure early detection of reduced efficacies that could occur as drug pressure continues increase. Finally, this study highlights that 95%CI should be considered in WHO guidelines to classify the therapeutic efficacy of PZQ.



中文翻译:

在七个正在进行大规模驱虫计划的国家评估吡喹酮对血吸虫的治疗效果

世界卫生组织 (WHO) 建议定期评估吡喹酮 (PZQ) 的治疗效果,以检测血吸虫耐药性可能导致的疗效降低。在这项多国研究(2014 年)中,我们评估了单次口服 PZQ(40 毫克/千克)对曼氏血吸虫(巴西、喀麦隆、埃塞俄比亚、马里、马达加斯加和坦桑尼亚)、血吸虫(喀麦隆)的治疗效果、埃塞俄比亚、马里、坦桑尼亚和桑给巴尔)和S. japonicum(菲律宾)学龄儿童感染,共 12 项不同试验。每项试验均根据 WHO 描述的用于评估 PZQ 疗效的标准化方法进行。总体而言,以给药后血吸虫卵数算术平均值的减少(卵减少率;ERR)来衡量的治疗功效对于所有三种血吸虫物种都很高(曼氏血吸虫:93.4%(95%CI:88.8-96.8) ; S. haematobium : 97.7% (95%CI: 96.5–98.7) and S. japonicum : 90.0% (95%CI: 68.4–99.3). 在试验水平,治疗效果令人满意(点估计 ERR ≥ 90%)除曼氏血吸虫外的所有三种血吸虫在喀麦隆,ERR 为 88.5%(95%CI:79.0–95.1)。此外,我们观察到,在某些试验中,个体药物反应可能存在显着差异(95% CI),并且很少有无反应个体会显着影响 ERR 点估计值。总之,这些结果并未表明标准 PZQ 治疗对这些国家内三种血吸虫物种中的任何一种的既定疗效降低。然而,在一些国家,个体对治疗的反应差异很大,因此有必要对未来进行监测。报告的 ERR 值可作为参考值,与未来 PZQ 疗效研究的结果进行比较,以确保及早发现随着药物压力持续增加而可能发生的疗效下降。最后,

更新日期:2020-10-30
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