Musset Lise, Bouchaud Olivier, Matheron Sophie, Massias Laurent, Le Bras Jacques
Laboratoire de biologie animale et parasitaire, EA209, Université Paris Descartes, 4 av de l'observatoire, 75006 Paris, France.
Microbes Infect. 2006 Sep;8(11):2599-604. doi: 10.1016/j.micinf.2006.07.011. Epub 2006 Aug 10.
Plasmodium falciparum resistance to atovaquone-proguanil has so far been associated with Y268S or Y268N mutations in cytochrome b, although these changes were identified in only seven of the 11 treatment failures. Here, we describe 10 new cases of atovaquone-proguanil treatment failures among which the parasite resistance was confirmed in six cases, either by identifying correct plasma drug concentrations or by observing in vitro atovaquone resistance. Resistance was consistently associated with codon 268 mutations (Y268S or a previously unidentified mutation, Y268C). Notably, mutations were not detected before the treatment but only after the drug exposure.
到目前为止，恶性疟原虫对阿托伐醌-氯胍的耐药性与细胞色素b中的Y268S或Y268N突变有关，尽管在11例治疗失败病例中只有7例发现了这些变化。在此，我们描述了10例新的阿托伐醌-氯胍治疗失败病例，其中6例通过确定正确的血浆药物浓度或观察体外阿托伐醌耐药性证实了寄生虫耐药性。耐药性始终与密码子268突变（Y268S或先前未鉴定的突变Y268C）相关。值得注意的是，在治疗前未检测到突变，仅在药物暴露后才检测到。
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