Naing Cho, Racloz Vanessa, Whittaker Maxine Anne, Aung Kyan, Reid Simon Andrew, Mak Joon Wah, Tanner Marcel
School of Population Health, University of Queensland, Herston, Australia ; International Medical University, Kuala Lumpur, Malaysia.
PLoS One. 2013 Dec 3;8(12):e78819. doi: 10.1371/journal.pone.0078819. eCollection 2013.
This study aimed to synthesize available evidence on the efficacy of dihydroartemisinin-piperaquine (DHP) in treating uncomplicated Plasmodium vivax malaria in people living in endemic countries.
This is a meta-analysis of randomized controlled trials (RCT). We searched relevant studies in electronic databases up to May 2013. RCTs comparing efficacy of (DHP) with other artemisinin-based combination therapy (ACT), non-ACT or placebo were selected. The primary endpoint was efficacy expressed as PCR-corrected parasitological failure. Efficacy was pooled by hazard ratio (HR) and 95% CI, if studies reported time-to-event outcomes by the Kaplan-Meier method or data available for calculation of HR Nine RCTs with 14 datasets were included in the quantitative analysis. Overall, most of the studies were of high quality. Only a few studies compared with the same antimalarial drugs and reported the outcomes of the same follow-up duration, which created some difficulties in pooling of outcome data. We found the superiority of DHP over chloroquine (CQ) (at day > 42-63, HR:2.33, 95% CI:1.86-2.93, I (2): 0%) or artemether-lumefentrine (AL) (at day 42, HR:2.07, 95% CI:1.38-3.09, I (2): 39%). On the basis of GRADE criteria, further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
DISCUSSION/CONCLUSION: Findings document that DHP is more efficacious than CQ and AL in treating uncomplicated P. vivax malaria. The better safety profile of DHP and the once-daily dosage improves adherence, and its fixed co-formulation ensures that both drugs (dihydroartemisinin and piperaquine) are taken together. However, DHP is not active against the hypnozoite stage of P. vivax. DHP has the potential to become an alternative antimalarial drug for the treatment uncomplicated P. vivax malaria. This should be substantiated by future RCTs with other ACTs. Additional work is required to establish how best to combine this treatment with appropriate antirelapse therapy (primaquine or other drugs under development).
本研究旨在综合现有证据，探讨双氢青蒿素哌喹（DHP）治疗疟疾流行国家无并发症间日疟原虫疟疾患者的疗效。
这是一项对随机对照试验（RCT）的荟萃分析。我们检索了截至2013年5月的电子数据库中的相关研究。选择了比较双氢青蒿素哌喹（DHP）与其他青蒿素类联合疗法（ACT）、非ACT或安慰剂疗效的随机对照试验。主要终点是经PCR校正的寄生虫学失败表示的疗效。如果研究通过Kaplan-Meier方法报告事件发生时间结局或提供可用于计算风险比（HR）的数据，则通过风险比（HR）和95%置信区间（CI）汇总疗效。定量分析纳入了9项随机对照试验的14个数据集。总体而言，大多数研究质量较高。只有少数研究与相同的抗疟药物进行比较，并报告相同随访期的结局，这给结局数据的汇总带来了一些困难。我们发现双氢青蒿素哌喹（DHP）优于氯喹（CQ）（在第42 - 63天之后，HR：2.33，95%CI：1.86 - 2.93，I²：0%）或蒿甲醚 - 本芴醇（AL）（在第42天，HR：2.07，95%CI：1.38 - 3.09，I²：39%）。根据GRADE标准，进一步的研究可能会对我们对效应估计的信心产生重要影响，并可能改变估计值。
讨论/结论：研究结果表明，双氢青蒿素哌喹（DHP）在治疗无并发症间日疟原虫疟疾方面比氯喹（CQ）和蒿甲醚 - 本芴醇（AL）更有效。双氢青蒿素哌喹（DHP）更好的安全性和每日一次的剂量提高了依从性，其固定复方制剂确保两种药物（双氢青蒿素和哌喹）一起服用。然而，双氢青蒿素哌喹（DHP）对间日疟原虫的休眠子阶段无活性。双氢青蒿素哌喹（DHP）有可能成为治疗无并发症间日疟原虫疟疾的替代抗疟药物。这一点应由未来与其他青蒿素类联合疗法（ACT）进行的随机对照试验来证实。还需要开展更多工作，以确定如何最好地将这种治疗方法与适当的抗复发疗法（伯氨喹或其他正在研发的药物）相结合。
