Henry Maud, Briolant Sébastien, Zettor Agnès, Pelleau Stéphane, Baragatti Meili, Baret Eric, Mosnier Joel, Amalvict Rémy, Fusai Thierry, Rogier Christophe, Pradines Bruno
Unité de Recherche en Biologie et Epidémiologie Parasitaires, Institut de Médecine Tropicale du Service de Santé des Armées, UMR 6236, Allée du Médecin Colonel Jamot, Parc le Pharo, BP 60109, 13262 Marseille Cedex 07, Marseille, France.
Antimicrob Agents Chemother. 2009 May;53(5):1926-30. doi: 10.1128/AAC.01243-08. Epub 2009 Mar 9.
Polymorphisms in the Plasmodium falciparum crt (Pfcrt), Pfmdr1, and Pfmrp genes were not significantly associated with quinine (QN) 50% inhibitory concentrations (IC(50)s) in 23 strains of Plasmodium falciparum. An increased number of DNNND repeats in Pfnhe-1 microsatellite ms4760 was associated with an increased IC(50) of QN (P = 0.0007). Strains with only one DNNND repeat were more susceptible to QN (mean IC(50) of 154 nM). Strains with two DNNND repeats had intermediate susceptibility to QN (mean IC(50) of 548 nM). Strains with three DNNND repeats had reduced susceptibility to QN (mean IC(50) of 764 nM). Increased numbers of NHNDNHNNDDD repeats were associated with a decreased IC(50) of QN (P = 0.0020). Strains with profile 7 for Pfnhe-1 ms4760 (ms4760-7) were significantly associated with reduced QN susceptibility (mean IC(50) of 764 nM). The determination of DNNND and NHNDNHNNDDD repeats in Pfnhe-1 ms4760 could be a good marker of QN resistance and provide an attractive surveillance method to monitor temporal trends in P. falciparum susceptibility to QN. The validity of the markers should be further supported by analyzing more isolates.
恶性疟原虫的crt（Pfcrt）、Pfmdr1和Pfmrp基因多态性与23株恶性疟原虫的奎宁（QN）50%抑制浓度（IC50）无显著相关性。Pfnhe-1微卫星ms4760中DNNND重复序列数量增加与QN的IC50升高相关（P = 0.0007）。仅含一个DNNND重复序列的菌株对QN更敏感（平均IC50为154 nM）。含两个DNNND重复序列的菌株对QN的敏感性中等（平均IC50为548 nM）。含三个DNNND重复序列的菌株对QN的敏感性降低（平均IC50为764 nM）。NHNDNHNNDDD重复序列数量增加与QN的IC50降低相关（P = 0.0020）。Pfnhe-1 ms4760的7型（ms4760 - 7）与QN敏感性降低显著相关（平均IC50为764 nM）。测定Pfnhe-1 ms4760中的DNNND和NHNDNHNNDDD重复序列可能是QN耐药性的良好标志物，并为监测恶性疟原虫对QN的易感性的时间趋势提供一种有吸引力的监测方法。应通过分析更多分离株进一步支持这些标志物的有效性。
