Unité de Recherche en Biologie et Epidémiologie Parasitaires, Institut de Recherche Biomédicale des Armées-Antenne de Marseille, Allée du Médecin-colonel Jamot, Parc le Pharo, BP 60109, 13262 Marseille Cedex 7, France.
Antimicrob Agents Chemother. 2010 Sep;54(9):3537-44. doi: 10.1128/AAC.00183-10. Epub 2010 Jun 14.
We have analyzed the profiles of 23 of Plasmodium falciparum strains for their in vitro chemosusceptibilities to piperaquine (PPQ), dihydroartemisinin (DHA), chloroquine, monodesethylamodiaquine, quinine, mefloquine, lumefantrine, atovaquone, pyrimethamine, and doxycycline (DOX) in association with polymorphisms in genes involved in quinoline resistance (Plasmodium falciparum crt [pfcrt], pfmdr1, pfmrp, and pfnhe). The 50% inhibitory concentrations (IC(50)s) for PPQ ranged from 29 to 98 nM (geometric mean = 57.8 nM, 95% confidence interval [CI] = 51 to 65) and from 0.4 to 5.8 nM for DHA (geometric mean = 1.8 nM, 95% CI = 1.4 to 2.3). We found a significant positive correlation between the responses to PPQ and DHA (r(2) = 0.17; P = 0.0495) and between the responses to PPQ and DOX (r(2) = 0.41; P = 0.001). We did not find a significant association between the PPQ IC(50) (0.0525 < P < 0.9247) or the DHA IC(50) (0.0138 < P < 0.9018) and polymorphisms in the pfcrt, pfmdr1, pfmrp, and pfnhe-1 genes. There was an absence of cross-resistance with quinolines, and the IC(50)s for PPQ and DHA were found to be unrelated to mutations in the pfcrt, pfmdr1, pfmrp, and pfnhe-1 transport protein genes, which are involved in quinoline antimalarial drug resistance. These results confirm the interest in and the efficacy of the combination of PPQ and DHA for areas in which parasites are resistant to chloroquine or other quinolines.
我们分析了 23 株恶性疟原虫株对哌喹（PPQ）、双氢青蒿素（DHA）、氯喹、去乙基阿莫地喹、奎宁、甲氟喹、青蒿琥酯、阿托伐醌、氨苯砜和强力霉素（DOX）的体外化学敏感性，并与涉及奎宁耐药的基因（恶性疟原虫 CRT [pfcrt]、pfmdr1、pfmrp 和 pfnhe）中的多态性相关联。PPQ 的 50%抑制浓度（IC（50））范围为 29 至 98 nM（几何平均值 = 57.8 nM，95%置信区间 [CI] = 51 至 65），DHA 的 IC（50）范围为 0.4 至 5.8 nM（几何平均值 = 1.8 nM，95%CI = 1.4 至 2.3）。我们发现 PPQ 和 DHA 的反应之间存在显著的正相关（r（2）= 0.17；P = 0.0495），以及 PPQ 和 DOX 的反应之间存在显著的正相关（r（2）= 0.41；P = 0.001）。我们没有发现 PPQ IC（50）（0.0525 < P < 0.9247）或 DHA IC（50）（0.0138 < P < 0.9018）与 pfcrt、pfmdr1、pfmrp 和 pfnhe-1 基因多态性之间存在显著关联。与喹啉类药物没有交叉耐药性，PPQ 和 DHA 的 IC（50）与 pfcrt、pfmdr1、pfmrp 和 pfnhe-1 转运蛋白基因的突变无关，这些基因与喹啉类抗疟药物耐药有关。这些结果证实了 PPQ 和 DHA 联合使用的有效性和前景，适用于对氯喹或其他喹啉类药物有耐药性的寄生虫的地区。
