Rason Marie-Ange, Andrianantenaina Herilalaina B, Ariey Frédéric, Raveloson Andrianirina, Domarle Olivier, Randrianarivelojosia Milijaona
Unité de Recherche sur le Paludisme, Antananarivo, Institut Pasteur de Madagascar, Madagascar.
Am J Trop Med Hyg. 2007 Jun;76(6):1079-83.
We assessed the status of point mutations associated with chloroquine resistance in pfcrt codon 76 and in pfmdr1 codon 86 among Plasmodium falciparum isolates from symptomatic patients in 3 sites in Madagascar. The in vitro susceptibility of P. falciparum isolates to quinoline-containing drugs was also determined. All isolates (N = 117) successfully typed were pfcrt wild-type, except one from Tsiroanomandidy (1 of 27). However, 67.5% (95% CI: 58.2-75.9%) of these isolates contained mutant pfmdr1 86Y. The pfmdr1 N86Y mutation is associated with higher mefloquine susceptibility, but it did not affect the sensitivity of parasites to chloroquine or quinine. Our findings demonstrate that pfmdr1 mutant P. falciparum are prevalent in Madagascar and confirm the low prevalence of pfcrt mutant P. falciparum after 60 years of chloroquine use. They provide additional field-based evidence for increased mefloquine susceptibility in pfmdr1 mutant P. falciparum and are suggestive of the intrahost selection of pfmdr1 mutant parasites.
我们评估了马达加斯加3个地点有症状患者的恶性疟原虫分离株中,与氯喹抗性相关的pfcrt第76密码子和pfmdr1第86密码子的点突变情况。还测定了恶性疟原虫分离株对含喹啉药物的体外敏感性。除了来自齐罗阿农曼迪的1株(27株中的1株)外,所有成功分型的分离株(N = 117)均为pfcrt野生型。然而,这些分离株中有67.5%(95%置信区间:58.2 - 75.9%)含有突变型pfmdr1 86Y。pfmdr1 N86Y突变与较高的甲氟喹敏感性相关,但不影响寄生虫对氯喹或奎宁的敏感性。我们的研究结果表明,pfmdr1突变型恶性疟原虫在马达加斯加很普遍,并证实了使用氯喹60年后,pfcrt突变型恶性疟原虫的低流行率。它们为pfmdr1突变型恶性疟原虫中甲氟喹敏感性增加提供了更多基于现场的证据,并提示了pfmdr1突变型寄生虫在宿主体内的选择。