Randomized, controlled dose-optimization studies of dihydroartemisinin-piperaquine for the treatment of uncomplicated multidrug-resistant falciparum malaria in Thailand
Randomized, controlled dose-optimization studies of dihydroartemisinin-piperaquine for the treatment of uncomplicated multidrug-resistant falciparum malaria in Thailand
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DOI：
10.1086/425015
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发表时间：
2004-11-15
影响因子：
6.4
通讯作者：
White, NJ
中科院分区：
文献类型：
--
作者：
Ashley, EA;Krudsood, S;White, NJ
背景双氢青蒿素-哌喹（DP）是一种新的、相对廉价的含青蒿素的固定复方抗疟药。成人疗程含6.4 mg/kg双氢青蒿素（DHA），比大多数含青蒿素复方制剂的水平低40%以上。这就提出了一种可能性，即目前的复方制剂在治疗多药耐药恶性疟中的疗效可能不是最佳的。在泰国进行的2项大型随机对照研究中，将DP的推荐剂量与额外的青蒿素衍生物（12 mg/kg; DP+）和甲氟喹加青蒿琥酯（MAS 3）方案进行了比较。共纳入731例患者：201例在医院研究中，530例在社区研究中。在基于医院的研究中，第28天治愈率为100%（95%置信区间[CI]，93.9%-100%）（MAS 3和DP+组）和98.3%（95% CI，91%-99.7%）（DP组），在第21天出现单次复发。在社区研究中，DP组、DP+组和MAS 3组第63天的聚合酶链反应基因分型校正治愈率分别为96.1%（95% CI，92.6%-99.7%）、98.3%（95% CI，96.1%-100%）和94.9%（95% CI，91.2%-98.6%）（P = 0.2）。不良事件很少，DP组有轻度腹痛。当前剂量的DP（6.4 mg/kg DHA和51.2 mg/kg磷酸哌喹）在48小时内给药，对于治疗多药耐药恶性疟疾是高效、安全和耐受性良好的，并且其疗效不会因添加更多DHA而改善。
Background. Dihydroartemisinin-piperaquine (DP) is a new and relatively inexpensive artemisinin-containing fixed-combination antimalarial treatment. An adult treatment course contained 6.4 mg/kg dihydroartemisinin (DHA), which is >40% lower than the level in most artemisinin-containing combinations. This raised the possibility that the efficacy of the current coformulation may not be optimal in the treatment of multidrug-resistant falciparum malaria.Methods. In 2 large randomized, controlled studies in Thailand, the recommended dose of DP was compared with a regimen with additional artemisinin derivative ( 12 mg/kg; DP+) and with mefloquine plus artesunate (MAS3).Results. A total of 731 patients were included: 201 in a hospital-based study and 530 in a community study. Day-28 cure rates in the hospital-based study were 100% (95% confidence interval [CI], 93.9%-100%) in the MAS3 and DP+ groups and 98.3% (95% CI, 91%-99.7%) in the DP group, with a single recrudescence on day 21. In the community study, polymerase chain reaction genotyping-adjusted cure rates on day 63 were 96.1% ( 95% CI, 92.6%-99.7%) in the DP group, 98.3% ( 95% CI, 96.1%-100%) in the DP+ group, and 94.9% (95% CI, 91.2%-98.6%) in the MAS3 group (P = .2). Adverse events were few, with an excess of mild abdominal pain in the DP group.Conclusions. The current dosage of DP ( 6.4 mg/kg DHA and 51.2 mg/kg piperaquine phosphate) given over the course of 48 h is highly effective, safe, and well tolerated for the treatment of multidrug-resistant falciparum malaria, and its efficacy is not improved by the addition of more DHA.