Absence of in vivo selection for K13 mutations after artemether-lumefantrine treatment in Uganda.
Absence of in vivo selection for K13 mutations after artemether-lumefantrine treatment in Uganda.
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在乌干达，没有体内选择K13突变的体内选择。
DOI：
10.1186/s12936-016-1663-1
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发表时间：
2017-01-09
期刊：
影响因子：
3
通讯作者：
Tsuboi T
中科院分区：
文献类型：
--
作者：
Balikagala B;Mita T;Ikeda M;Sakurai M;Yatsushiro S;Takahashi N;Tachibana SI;Auma M;Ntege EH;Ito D;Takashima E;Palacpac NM;Egwang TG;Onen JO;Kataoka M;Kimura E;Horii T;Tsuboi T
个体药物治疗可能会选择人体内的耐药寄生虫，这一过程称为体内选择。恶性疟原虫氯喹耐药转运蛋白（pfcrt）和多药耐药基因1（pfmdr 1）的一些单核苷酸多态性已被报道后蒿甲醚-苯芴醇治疗选择。然而，关于恶性疟原虫Kelch螺旋桨结构域的体内选择的数据很少（pfkelch 13）多态性，导致亚洲的青蒿素耐药性，以及六种可能的青蒿素耐药性背景突变;铁氧还蛋白中的D193 Y，多重抗性蛋白2中的T484 I，顶质体核糖体蛋白S10中的V127 M，pfcrt中的I356 T，V1157 L蛋白磷酸酶和C1484 F磷酸肌醇结合蛋白。2014年在北方乌干达进行了为期28天的蒿甲醚-苯芴醇疗效研究。在给药前和给药后第3、7、28天对上述基因型进行比较分析。在61例成功随访的患者中，蒿甲醚-本芴醇治疗方案非常有效，PCR校正的疗效为95.2%。在治疗前获得的146株分离株中，在pfkelch 13中98.6%的分离株中观察到野生型等位基因，在除pfcrt中I356 T外的6个假定背景基因中的所有分离株中观察到野生型等位基因，其中2.4%的分离株为混合感染。体内选择研究显示，在随访期间检测到的所有分离株都携带pfkelch 13和6个背景基因中的野生型等位基因。pfkelch 13和6个背景基因的突变可能不会在乌干达蒿甲醚-本芴醇治疗后的体内选择中发挥重要作用。不同的机制可能与治疗后寄生虫的存在有关。本文的在线版本（doi：10.1186/s12936-016-1663-1）包含补充材料，可供授权用户使用。
Individual drug treatment may select resistant parasites in the human body, a process termed in vivo selection. Some single nucleotide polymorphisms in Plasmodium falciparum chloroquine-resistance transporter (pfcrt) and multidrug resistance gene 1 (pfmdr1) genes have been reportedly selected after artemether–lumefantrine treatment. However, there is a paucity of data regarding in vivo selection of P. falciparum Kelch propeller domain (pfkelch13) polymorphisms, responsible for artemisinin-resistance in Asia, and six putative background mutations for artemisinin resistance; D193Y in ferredoxin, T484I in multiple resistance protein 2, V127M in apicoplast ribosomal protein S10, I356T in pfcrt, V1157L in protein phosphatase and C1484F in phosphoinositide-binding protein. Artemether–lumefantrine efficacy study with a follow-up period of 28 days was conducted in northern Uganda in 2014. The above-mentioned genotypes were comparatively analysed before drug administration and on days; 3, 7, and 28 days after treatment. In 61 individuals with successful follow-up, artemether–lumefantrine treatment regimen was very effective with PCR adjusted efficacy of 95.2%. Among 146 isolates obtained before treatment, wild-type alleles were observed in 98.6% of isolates in pfkelch13 and in all isolates in the six putative background genes except I356T in pfcrt, which had 2.4% of isolates as mixed infections. In vivo selection study revealed that all isolates detected in the follow-up period harboured wild type alleles in pfkelch13 and the six background genes. Mutations in pfkelch13 and the six background genes may not play an important role in the in vivo selection after artemether–lumefantrine treatment in Uganda. Different mechanisms might rather be associated with the existence of parasites after treatment. The online version of this article (doi:10.1186/s12936-016-1663-1) contains supplementary material, which is available to authorized users.