Selection of parasites with diminished drug susceptibility by amodiaquine-containing antimalarial regimens in Uganda.
Selection of parasites with diminished drug susceptibility by amodiaquine-containing antimalarial regimens in Uganda.
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DOI：
10.1086/647988
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发表时间：
2009-12-01
期刊：
影响因子：
--
通讯作者：
Rosenthal PJ
中科院分区：
文献类型：
--
作者：
Nawaz F;Nsobya SL;Kiggundu M;Joloba M;Rosenthal PJ
在推荐的抗疟方案中，阿莫地喹（AQ）与青蒿琥酯（AS）或磺胺嘧啶-乙胺嘧啶（SP）配对。目前尚不清楚联合化疗是否容易选择AQ耐药。我们收集了61个恶性疟原虫样本，从乌干达儿童队列随机治疗AQ/SP，AS/AQ，或蒿甲醚-苯芴醇（AL）的无并发症疟疾。采用基于组氨酸富集蛋白-2的ELISA法测定了MDAQ的体外敏感性，并评估了潜在的耐药介导多态性pfmdr-1。12周内曾接受AQ/SP或AS/AQ治疗的受试者的寄生虫对MDAQ的敏感性较低（n=18;平均IC 50 62.9 nM;范围12.7-158.3 nM）（n=43;平均IC 50 37.5 nM;范围6.3-184.7 nM; p=0.0085）或仅不含AQ的治疗组中的那些（n=20;平均IC 50 28.8 nM;范围6.3-121.8 nM; p=0.0042）。具有多态性的菌株的比例预期介导减少响应AQ（pfmdr-1 86 Y和1246 Y）后，先前的AQ治疗增加，但差异不显着。先前选择的治疗对MDAQ的反应减弱，表明含AQ的方案在非洲可能会迅速失去疗效。MDAQ反应减弱的机制不能完全由pfmdr-1中的已知突变来解释。
Amodiaquine (AQ) is paired with artesunate (AS) or sulfadoxine-pyrimethamine (SP) in recommended antimalarial regimens. It is unclear how readily AQ resistance will be selected with combination chemotherapy. We collected 61 Plasmodium falciparum samples from a cohort of Ugandan children randomized to treatment with AQ/SP, AS/AQ, or artemether-lumefantrine (AL) for uncomplicated malaria. In vitro sensitivity to monodesethylamodiaquine (MDAQ) was measured with a histidine rich protein-2-based ELISA, and potential resistance-mediating polymorphisms pfmdr-1were evaluated. Parasites from subjects previously treated with AQ/SP or AS/AQ within 12 weeks were less sensitive to MDAQ (n=18; mean IC50 62.9 nM; range 12.7–158.3 nM) than parasites from those not treated within 12 weeks (n=43; mean IC50 37.5 nM; range 6.3–184.7 nM; p=0.0085) or only those in the treatment arm that did not contain AQ (n=20; mean IC50 28.8 nM; range 6.3–121.8 nM; p=0.0042). The proportion of strains with polymorphisms expected to mediate diminished response to AQ (pfmdr-1 86Y and 1246Y) increased after prior AQ therapy, although differences were not significant. Prior therapy selected for diminished response to MDAQ, suggesting that AQ-containing regimens may rapidly lose efficacy in Africa. The mechanism of diminished MDAQ response is not fully explained by known mutations in pfmdr-1.
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影响因子：
6.4
作者：
Nsobya, Samuel L.;Kiggundu, Moses;Rosenthal, Philip J.
通讯作者：
Rosenthal, Philip J.
影响因子：
1.5
作者：
Duraisingh, MT;Jones, P;Warhurst, DC
通讯作者：
Warhurst, DC
影响因子：
4.9
作者：
Kaddouri, Halima;Nakache, Serge;Le Bras, Jacques
通讯作者：
Le Bras, Jacques
DOI：
10.4269/ajtmh.2006.75.381
发表时间：
2006-09-01
影响因子：
3.3
作者：
Menard, Didier;Yapou, Ferdinand;Talarmin, Antoine
通讯作者：
Talarmin, Antoine
影响因子：
168.9
作者：
Mutabingwa, TK;Anthony, D;Whitty, CJM
通讯作者：
Whitty, CJM