Randomized, Double-Blind, Placebo-Controlled Trial of Monthly versus Bimonthly Dihydroartemisinin-Piperaquine Chemoprevention in Adults at High Risk of Malaria
Randomized, Double-Blind, Placebo-Controlled Trial of Monthly versus Bimonthly Dihydroartemisinin-Piperaquine Chemoprevention in Adults at High Risk of Malaria
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DOI：
10.1128/aac.05877-11
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发表时间：
2012-03-01
影响因子：
4.9
通讯作者：
Nosten, Francois
中科院分区：
文献类型：
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作者：
Lwin, Khin Maung;Phyo, Aung Pyae;Nosten, Francois
间歇性预防治疗（IPT）越来越多地用于降低儿童和孕妇的疟疾发病率和死亡率。IPT的疗效取决于所使用的抗疟药物的药代动力学和药效学特性。在泰国西北边境，职业使其处于疟疾高风险的健康成年男性志愿者被随机分配接受每月（DPm）或每2个月（DPalt） 3天的双氢青蒿素-哌喹治疗剂量，或在9个月期间接受含脂肪或不含脂肪的相同安慰剂（6.4g/剂量）。所有志愿者每周都接受监测。招募了1000名成年人。双氢青蒿素-哌喹耐受性良好。114例疟疾（恶性疟原虫49例，间日疟原虫63例，卵形疟原虫2例）。36周时，DPm组对所有疟疾的保护效力为98%(95%可信区间[CI]， 96%至99%)，DPalt组为86% (95% CI， 81%至90%)（与安慰剂组相比，两者的P< 0.0001）。因此，安慰剂组在研究期间的红细胞比容也较低（P< 0.0001）。哌喹槽血药浓度是疗效的主要决定因素；谷浓度高于31 ng/ml的参与者未发生疟疾。血浆哌喹浓度和疗效均不受脂肪联合给药的影响。DPm使用安全，在间日疟原虫和耐多药恶性疟原虫流行地区的成年男性中预防疟疾有效。
Intermittent preventive treatment (IPT) is increasingly used to reduce malaria morbidity and mortality in children and pregnant women. The efficacy of IPT depends on the pharmacokinetic and pharmacodynamic properties of the antimalarial drugs used. Healthy adult male volunteers whose occupation put them at high risk of malaria on the Northwest border of Thailand were randomized to receive a 3-day-treatment dose of dihydroartemisinin-piperaquine monthly (DPm) or every 2 months (DPalt) or an identical placebo with or without fat (6.4g/dose) over a 9-month period. All volunteers were monitored weekly. One thousand adults were recruited. Dihydroartemisinin-piperaquine was well tolerated. There were 114 episodes of malaria (49 Plasmodium falciparum, 63 P. vivax, and 2 P. ovale). The protective efficacy against all malaria at 36 weeks was 98% (95% confidence interval [CI], 96% to 99%) in the DPm group and 86% (95% CI, 81% to 90%) in the DPalt group (for both, P< 0.0001 compared to the placebo group). As a result, the placebo group also had lower hematocrits during the study (P< 0.0001). Trough plasma piperaquine concentrations were the main determinant of efficacy; no malaria occurred in participants with a trough concentration above 31 ng/ml. Neither plasma piperaquine concentration nor efficacy was influenced by the coadministration of fat. DPm is safe to use and is effective in the prevention of malaria in adult males living in an area where P. vivax and multidrug-resistant P. falciparum malaria are endemic.