Faculty of Tropical Medicine, Department of Clinical Pharmacology, Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, 10400, Thailand.
Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso.
Nat Commun. 2019 Jan 29;10(1):480. doi: 10.1038/s41467-019-08297-9.
Young children are the population most severely affected by Plasmodium falciparum malaria. Seasonal malaria chemoprevention (SMC) with amodiaquine and sulfadoxine-pyrimethamine provides substantial benefit to this vulnerable population, but resistance to the drugs will develop. Here, we evaluate the use of dihydroartemisinin-piperaquine as an alternative regimen in 179 children (aged 2.33-58.1 months). Allometrically scaled body weight on pharmacokinetic parameters of piperaquine result in lower drug exposures in small children after a standard mg per kg dosage. A covariate-free sigmoidal E-model describes the interval to malaria re-infections satisfactorily. Population-based simulations suggest that small children would benefit from a higher dosage according to the WHO 2015 guideline. Increasing the dihydroartemisinin-piperaquine dosage and extending the dose schedule to four monthly doses result in a predicted relative reduction in malaria incidence of up to 58% during the high transmission season. The higher and extended dosing schedule to cover the high transmission period for SMC could improve the preventive efficacy substantially.
儿童是受恶性疟原虫疟疾影响最严重的人群。季节性疟疾化学预防（SMC）使用阿莫地喹和磺胺多辛-乙胺嘧啶为这一脆弱人群提供了巨大的益处，但这些药物会产生耐药性。在这里，我们评估了二氢青蒿素-哌喹在 179 名儿童（年龄 2.33-58.1 个月）中的替代方案的使用。根据药物动力学参数的比例缩放体重，在标准毫克/千克剂量后，哌喹在幼儿体内的药物暴露水平较低。无协变量的 Sigmoidal E 模型令人满意地描述了疟疾再感染的间隔。基于人群的模拟表明，根据世卫组织 2015 年的指导方针，幼儿将从更高的剂量中受益。增加二氢青蒿素-哌喹的剂量并将剂量方案延长至四个月剂量，在高传播季节期间，疟疾发病率的预测相对降低高达 58%。在 SMC 的高传播期间，更高和更长的剂量方案可以大大提高预防效果。
