在马里两种青蒿素联合疗法的疗效、安全性及耐药性分子标志物的选择
Efficacy, safety, and selection of molecular markers of drug resistance by two ACTs in Mali.
作者信息
Djimdé Abdoulaye A, Fofana Bakary, Sagara Issaka, Sidibe Bakary, Toure Sekou, Dembele Demba, Dama Souleymane, Ouologuem Dinkorma, Dicko Alassane, Doumbo Ogobara K
机构信息
Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Odonto-Stomatology, University of Bamako, Bamako, Mali.
出版信息
Am J Trop Med Hyg. 2008 Mar;78(3):455-61.
We conducted a randomized single-blinded trial comparing the efficacy and safety of artesunate (AS) + amodiaquine (AQ, 3 days) versus AS (3 days) + sulfadoxine-pyrimethamine (SP, single dose) versus AS monotherapy (5 days) in Southern Mali. Uncomplicated malaria cases were followed for 28 days. Molecular markers of drug resistance were determined. After identification of recrudescences by genotyping, both artemisinin-based combination therapies (ACTs) reached nearly 100% efficacy at Day 14 and Day 28 versus 98.3% and 96.5% for AS, respectively (P > 0.05). AS + SP significantly selected DHFR and DHPS mutations associated with sulfadoxine and pyrimethamine resistance (P < 0.001), and AS + AQ equally selected PfCRT and PfMDR1 point mutations associated with chloroquine and AQ resistance (P < 0.001). No significant adverse event attributable to any of the study drugs was found. The ACTs were efficacious and safe, but the selection of markers for resistance to the partner drugs raises concerns over their lifespan in areas of intense malaria transmission.
我们在马里南部开展了一项随机单盲试验，比较青蒿琥酯（AS）+阿莫地喹（AQ，3天疗程）与AS（3天疗程）+磺胺多辛-乙胺嘧啶（SP，单剂量）及AS单药治疗（5天疗程）的疗效和安全性。对非复杂性疟疾病例进行了28天的随访，并测定了耐药分子标志物。通过基因分型鉴定复发情况后，两种基于青蒿素的联合疗法（ACTs）在第14天和第28天的疗效均接近100%，而AS单药治疗的相应疗效分别为98.3%和96.5%（P>0.05）。AS+SP显著筛选出与磺胺多辛和乙胺嘧啶耐药相关的二氢叶酸还原酶（DHFR）和二氢蝶酸合成酶（DHPS）突变（P<0.001），AS+AQ同样筛选出与氯喹和AQ耐药相关的疟原虫氯喹抗性转运蛋白（PfCRT）和多药耐药蛋白1（PfMDR1）点突变（P<0.001）。未发现任何研究药物所致的显著不良事件。ACTs有效且安全，但对联合用药耐药标志物的筛选引发了对其在疟疾传播活跃地区使用寿命的担忧。
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