Pascual Aurélie, Madamet Marilyn, Briolant Sébastien, Gaillard Tiphaine, Amalvict Rémy, Benoit Nicolas, Travers Dominique, Pradines Bruno
Malar J. 2015 Feb 5;14:49. doi: 10.1186/s12936-015-0586-6.
In 2002, the World Health Organization recommended that artemisinin-based combination therapy (ACT) be used to treat uncomplicated malaria. Dihydroartemisinin-piperaquine and artesunate-pyronaridine are two of these new combinations. The aim of the present work was to assess the distribution of the in vitro values of pyronaridine (PND) and piperaquine (PPQ) and to define a cut-off for reduced susceptibility for the two anti-malarial drugs.
The distribution and range of the 50% inhibitory concentration values (IC₅₀) of PND and PPQ were determined for 313 isolates obtained between 2008 and 2012 from patients hospitalized in France for imported malaria. The statistical Bayesian analysis was designed to answer the specific question of whether Plasmodium falciparum has different phenotypes of susceptibility to PND and PPQ.
The PND IC₅₀ values ranged from 0.6 to 84.6 nM, with a geometric mean of 21.1 ± 16.0 nM (standard deviation). These values were classified into three components. The PPQ IC₅₀ values ranged from 9.8 to 217.3 nM, and the geometric mean was 58.0 ± 34.5 nM. All 313 PPQ values were classified into four components. Isolates with IC₅₀ values greater than 60 nM or four-fold greater than 3D7 IC₅₀ are considered isolates that have reduced susceptibility to PND and those with IC₅₀ values greater than 135 nM or 2.3-fold greater than 3D7 IC₅₀ are considered isolates that have reduced susceptibility to PPQ.
The existence of at least three phenotypes for PND and four phenotypes for PPQ was demonstrated. Based on the cut-off values, 18 isolates (5.8%) and 13 isolates (4.2%) demonstrated reduced susceptibility to PND and PPQ, respectively.
2002年，世界卫生组织建议使用以青蒿素为基础的联合疗法（ACT）治疗非复杂性疟疾。双氢青蒿素哌喹和青蒿琥酯咯萘啶是其中两种新的联合用药。本研究的目的是评估咯萘啶（PND）和哌喹（PPQ）的体外值分布，并确定这两种抗疟药物敏感性降低的临界值。
测定了2008年至2012年间从法国因输入性疟疾住院的患者中分离出的313株疟原虫对PND和PPQ的50%抑制浓度值（IC₅₀）的分布和范围。统计贝叶斯分析旨在回答恶性疟原虫对PND和PPQ是否具有不同敏感性表型这一具体问题。
PND的IC₅₀值范围为0.6至84.6 nM，几何平均值为21.1±16.0 nM（标准差）。这些值分为三个组分。PPQ的IC₅₀值范围为9.8至217.3 nM，几何平均值为58.0±34.5 nM。所有313个PPQ值分为四个组分。IC₅₀值大于60 nM或比3D7的IC₅₀值大四倍的分离株被认为是对PND敏感性降低的分离株，而IC₅₀值大于135 nM或比3D7的IC₅₀值大2.3倍的分离株被认为是对PPQ敏感性降低的分离株。
证实了PND至少存在三种表型，PPQ存在四种表型。根据临界值，分别有18株（5.8%）和13株（4.2%）分离株对PND和PPQ的敏感性降低。
