Brega Sara, de Monbrison Frédérique, Severini Carlo, Udomsangpetch Rachanee, Sutanto Inge, Ruckert Paul, Peyron François, Picot Stéphane
Service de Parasitologie, Faculté de Médecine, 8 avenue Rockefeller, 69373 Lyon cedex 08, France.
Antimicrob Agents Chemother. 2004 Jul;48(7):2581-7. doi: 10.1128/AAC.48.7.2581-2587.2004.
Mutations in the dhfr gene of Plasmodium vivax (pvdhfr) are associated with resistance to the antifolate antimalarial drugs. Polymorphisms in the pvdhfr gene were assessed by hybridization probe technology on the LightCycler instrument with 134 P. vivax-infected blood samples from Turkey (n = 24), Azerbaijan (n = 39), Thailand (n = 16), Indonesia (n = 53), and travelers (n = 19). Double mutations (S58R and S117N) or quadruple mutations (F57L/I, S58R, T61M, and S117N) in the pvdhfr genes were found in all Thai samples (100%). pvdhfr mutant-type alleles were significantly more common in samples from travelers (42%) than in those from patients from Indonesia (5%). Surprisingly, the pvdhfr single-mutation allele (S117N) was identified at a high frequency in parasites from Turkey and Azerbaijan (71 and 36%, respectively), where sulfadoxine-pyrimethamine is not recommended for the treatment of P. vivax malaria by the World Health Organization and the Malaria National Programs.
间日疟原虫二氢叶酸还原酶（pvdhfr）基因的突变与对抗叶酸类抗疟药物的耐药性相关。采用杂交探针技术，在罗氏LightCycler仪器上对来自土耳其（n = 24）、阿塞拜疆（n = 39）、泰国（n = 16）、印度尼西亚（n = 53）的134份间日疟原虫感染血样以及旅行者（n = 19）的血样进行了pvdhfr基因多态性评估。在所有泰国血样（100%）中均发现了pvdhfr基因的双突变（S58R和S117N）或四突变（F57L/I、S58R、T61M和S117N）。pvdhfr突变型等位基因在旅行者血样（42%）中比在印度尼西亚患者血样（5%）中更为常见。令人惊讶的是，在土耳其和阿塞拜疆的疟原虫中，pvdhfr单突变等位基因（S117N）的检出频率很高（分别为71%和36%），而世界卫生组织和各国疟疾防治项目均不建议在这两个国家使用磺胺多辛-乙胺嘧啶治疗间日疟。
