Amodiaquine and artemether-lumefantrine select distinct alleles of the Plasmodium falciparum mdr1 gene in Tanzanian children treated for uncomplicated malaria
Amodiaquine and artemether-lumefantrine select distinct alleles of the Plasmodium falciparum mdr1 gene in Tanzanian children treated for uncomplicated malaria
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DOI：
10.1128/aac.00875-06
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发表时间：
2007-03-01
影响因子：
4.9
通讯作者：
Hallett, R. L.
中科院分区：
文献类型：
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作者：
Humphreys, G. S.;Merinopoulos, I.;Hallett, R. L.
以青蒿素为基础的联合疗法青蒿甲醚-鲁米芬(AL)和阿莫地喹(AQ)加青蒿琥酯已被许多非洲国家用于治疗恶性疟疾。对于这两种组合中的任何一种成分药物，都没有建立适合监测的寄生虫耐药性的分子标记。我们评估了300名坦桑尼亚儿童中存在的恶性疟原虫mdr1(Pfmdr1)等位基因，这些儿童表现为无并发症的恶性疟疾，这些儿童参加了抗疟疾治疗的临床试验。对182名AQ单一治疗失败儿童和54名AL治疗失败儿童的Pfmdr1基因分离株进行了Pfmdr1基因分析。Pfmdr1等位基因86Y、184Y和1246Y在AQ组治疗失败中比治疗前感染中更常见。而AIL治疗组则相反。携带86Y/184Y/1246Y Pfmdr1单倍型并接受AQ治疗的儿童，如果在治疗后随访期间寄生虫阳性，则明显比接受AIL治疗的儿童更有可能保留该单倍型(优势比，33.25；95%可信区间，4.171441；P，<；0.001)。结论：AL和AQ对恶性疟原虫Pfmdr1基因具有相反的宿主内选择作用。
The artemisinin-based combination therapies artemether-lumefantrine (AL) and amodiaquine (AQ) plus artesunate have been adopted for treatment of Plasmodium falciparum malaria in many African countries. Molecular markers of parasite resistance suitable for surveillance have not been established for any of the component drugs in either of these combinations. We assessed P.falciparum mdr1 (Pfmdr1) alleles present in 300 Tanzanian children presenting with uncomplicated falciparum malaria, who were enrolled in a clinical trial of antimalarial therapy. Pfmdr1 genotype analysis was also performed with isolates from 182 children who failed AQ monotherapy and 54 children who failed AL treatment. Pfmdr1 alleles 86Y, 184Y, and 1246Y were more common among treatment failures in the AQ group than among pretreatment infections. The converse was found in the AIL-treated group. Children presenting with the 86Y/184Y/1246Y Pfmdr1 haplotype and treated with AQ were significantly more likely to retain this haplotype if they were parasite positive during posttreatment follow-up than were children treated with AIL (odds ratio, 33.25; 95% confidence interval, 4.17 to 1441; P, < 0.001). We conclude that AL and AQ exert opposite within-host selective effects on the Pfmdr1 gene of P. falciparum.