The Effect of Dosing Regimens on the Antimalarial Efficacy of Dihydroartemisinin-Piperaquine: A Pooled Analysis of Individual Patient Data
The Effect of Dosing Regimens on the Antimalarial Efficacy of Dihydroartemisinin-Piperaquine: A Pooled Analysis of Individual Patient Data
复制标题
DOI：
10.1371/journal.pmed.1001564
复制
发表时间：
2013-12-01
期刊：
影响因子：
15.8
通讯作者：
Zongo, Issaka
中科院分区：
文献类型：
--
作者：
Achan, Jane;Adam, Ishag;Zongo, Issaka
背景资料：在许多疟疾流行的国家，越来越多地推荐使用双氢青蒿素-哌喹（DP）进行抗疟治疗;然而，人们对它在幼儿中的潜在剂量不足表示担忧。我们调查了不同的给药方案对DP的临床efficacy.Methods和Findings的影响：进行了系统的文献检索，以确定1960年和2013年2月之间发表的所有研究，在这些研究中，患者被招募和DP治疗。主要研究者被邀请与全球抗疟药耐药网络（WWARN）分享个体患者数据。使用标准化方法汇总数据。使用考克斯回归模型确定寄生虫复发的单变量和多变量风险因素，并在研究中心进行共享脆弱性。24项已发表和2项未发表的研究（n = 7，072例患者）纳入分析。通过寄生虫基因分型校正再感染后，Kaplan-Meier生存率估计值在第42天和第63天分别为97.7%（95%CI 97.3%-98.1%）和97.2%（95%CI 96.7%-97.7%）。总体而言，28.6%（979/3，429）的1 - 5岁儿童接受的哌喹总剂量低于48 mg/kg（WHO推荐的下限）;与其他年龄组相比，该风险高2.3-2.9倍，并与第63天疗效降低相关（94.4% [95%CI 92.6%-96.2%]，p
Background: Dihydroartemisinin-piperaquine (DP) is increasingly recommended for antimalarial treatment in many endemic countries; however, concerns have been raised over its potential under dosing in young children. We investigated the influence of different dosing schedules on DP's clinical efficacy.Methods and Findings: A systematic search of the literature was conducted to identify all studies published between 1960 and February 2013, in which patients were enrolled and treated with DP. Principal investigators were approached and invited to share individual patient data with the WorldWide Antimalarial Resistance Network (WWARN). Data were pooled using a standardised methodology. Univariable and multivariable risk factors for parasite recrudescence were identified using a Cox's regression model with shared frailty across the study sites. Twenty-four published and two unpublished studies (n = 7,072 patients) were included in the analysis. After correcting for reinfection by parasite genotyping, Kaplan-Meier survival estimates were 97.7% (95% CI 97.3%-98.1%) at day 42 and 97.2% (95% CI 96.7%-97.7%) at day 63. Overall 28.6% (979/3,429) of children aged 1 to 5 years received a total dose of piperaquine below 48 mg/kg (the lower limit recommended by WHO); this risk was 2.3-2.9-fold greater compared to that in the other age groups and was associated with reduced efficacy at day 63 (94.4% [95% CI 92.6%-96.2%], p