Zongo Issaka, Somé Fabrice A, Somda Serge A M, Parikh Sunil, Rouamba Noel, Rosenthal Philip J, Tarning Joel, Lindegardh Niklas, Nosten François, Ouédraogo Jean Bosco
Direction Régionale de l'Ouest, Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso.
Non Transmissible disease department, Centre Muraz Bobo-Dioulasso, Bobo-Dioulasso, Burkina Faso.
PLoS One. 2014 Aug 18;9(8):e103200. doi: 10.1371/journal.pone.0103200. eCollection 2014.
One promising new Artemisinin-based combination therapies (ACTs) is dihydroartemisinin-piperaquine (DHA-PQ). However, the pharmacokinetics of piperaquine and the relationship between drug levels and clinical efficacy are incompletely characterized, particularly in children.
We performed a single-arm open-label trial in Bobo-Dioulasso, Burkina Faso. A total of 379 participants aged 6 months or more with uncomplicated falciparum malaria were enrolled. Each participant received daily dose of DHA-PQ for three days and followed for 42 days. Parasitological efficacy was analyzed, considering rates of recrudescence and overall recurrence. PK was an exploratory endpoint and a priori, no sample size had been determined. Day 7 capillary and venous plasma concentrations of piperaquine were measured in children aged 2-10 years.
Of the 379 participants, 365 (96.3%) completed 42 days of follow-up. The median daily dose of PQ was 18.5 mg/kg [6.5-24]. Treatment with DHA-PQ was well tolerated with fever and parasitemia resolution within 48 hours in nearly all children. Recurrent malaria within 42 days of follow-up occurred in 31.3% (10/34) of children less than 2 years old, 16.0% (16/106) of those aged 2-5 years, 9.4% (15/160) of those aged 5-10 years, and none (0/68) of those over 10 years old. After genotyping, 3 of 41 recurrent episodes were recrudescence. An exploratory analysis shows that children with successful treatment outcomes had significantly higher median plasma concentrations of PQ compared to those with recurrent malaria within 42 days after therapy, considering either capillary samples (68 ng/ml [50-85] compared to 48 ng/ml [36-55], p<0.001) or venous samples (42 ng/ml [29-59] compared to 25 ng/ml [19-44], p<0.001).
DHA-PQ was effective for uncomplicated P. falciparum malaria treatment and offers an alternative to other ACTs. Recurrent malaria was mainly due to new infections after treatment and was correlated with low day 7 PQ concentration in the youngest patients.
Controlled-Trials.com ISRCTN59761234.
一种有前景的新型青蒿素联合疗法（ACTs）是双氢青蒿素-哌喹（DHA-PQ）。然而，哌喹的药代动力学以及药物水平与临床疗效之间的关系尚未完全明确，尤其是在儿童中。
我们在布基纳法索的博博迪乌拉索进行了一项单臂开放标签试验。共纳入379名6个月及以上的无并发症恶性疟原虫疟疾患者。每位参与者连续三天每日服用DHA-PQ，并随访42天。分析了寄生虫学疗效，考虑复发率和总体复发情况。药代动力学是一个探索性终点，且事先未确定样本量。测量了2至10岁儿童第7天的毛细血管和静脉血浆中哌喹的浓度。
379名参与者中，365名（96.3%）完成了42天的随访。PQ的每日中位剂量为18.5mg/kg[6.5-24]。DHA-PQ治疗耐受性良好，几乎所有儿童在48小时内发热和寄生虫血症均得到缓解。随访42天内，2岁以下儿童复发性疟疾发生率为31.3%（10/34），2至5岁儿童为16.0%（16/106），5至10岁儿童为9.4%（15/160），10岁以上儿童无一例（0/68）复发。基因分型后，41次复发中有3次为再燃。一项探索性分析表明，与治疗后42天内复发性疟疾的儿童相比，治疗成功的儿童血浆中PQ的中位浓度显著更高，无论是毛细血管样本（68ng/ml[50-85]对比48ng/ml[36-55]，p<0.001）还是静脉样本（42ng/ml[29-59]对比25ng/ml[19-44]，p<0.001）。
DHA-PQ对无并发症恶性疟原虫疟疾治疗有效，为其他ACTs提供了一种替代方案。复发性疟疾主要是由于治疗后新感染所致，且与最年幼患者第7天PQ浓度低相关。
Controlled-Trials.com ISRCTN59761234。
