Intrahost selection of Plasmodium falciparum pfmdr1 alleles after antimalarial treatment on the northwestern border of Thailand
Intrahost selection of Plasmodium falciparum pfmdr1 alleles after antimalarial treatment on the northwestern border of Thailand
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DOI：
10.1086/509809
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发表时间：
2007-01-01
影响因子：
6.4
通讯作者：
Price, Ric N.
中科院分区：
文献类型：
--
作者：
Uhlemann, Anne-Catrin;McGready, Rose;Price, Ric N.
背景资料。Pfmdr1拷贝数的增加与结构上无关的抗疟疾药物的敏感性降低有关。我们评估了不同抗疟疾药物的使用如何改变治疗失败患者体内寄生虫的pfmdr1基因多态性。在泰国西北部边境进行的研究中，比较了抗疟疾药物治疗前后pfmdr1的扩增和单核苷酸多态。在反复感染的患者中，20%(26/132)观察到pfmdr1拷贝数在宿主内的变化。在甲氟喹治疗后复发的感染中，pfmdr1拷贝数增加的比例为68%(95%可信区间[CI]，46%~85%)，下降的比例为2%(95%可信区间[CI]，0.4%~11%)，相应比例在蒿甲醚-鲁米芬净治疗后分别为25%(2/8)和11%(2/19)，在奎宁治疗后分别为50%(1/2)和40%(4/10)；单独应用青蒿素后，分离率分别为0%(0/10)和19%(3/16)。基于pfmdr1拷贝数的宿主内选择经常发生在个体患者的寄生虫群体中。扩增会产生多重耐药性，但可能会给寄生虫带来巨大的适应成本。
Background. Increased pfmdr1 copy number is associated with reduced susceptibility to structurally unrelated antimalarial drugs. We assessed how administration of different antimalarial drugs altered pfmdr1 polymorphism in parasites from patients who experienced treatment failure.Methods. In studies conducted on the northwestern border of Thailand, amplifications and single-nucleotide polymorphisms in pfmdr1 were compared before and after antimalarial drug treatment.Results. Intrahost changes in pfmdr1 copy number were observed in 20% (26/132) of patients with recurrent infections. Among infections that recrudesced after mefloquine-containing regimens, increases in pfmdr1 copy number occurred in 68% (95% confidence interval [CI], 46%-85%), and decreases occurred in 2% (95% CI, 0.4%-11%) of isolates; corresponding proportions after artemether-lumefantrine were 25% (2/8) and 11% (2/19); after quinine, 50% (1/2) and 40% (4/10); and after artemisinins alone, 0% (0/10) and 19% (3/16) of isolates (overall P < .001).Conclusions. Intrahost selection based on pfmdr1 copy number occurs frequently in parasite populations within individual patients. Amplification confers multidrug resistance but probably imposes a significant fitness cost to the parasites.