Efficacy, safety, and selection of molecular markers of drug resistance by two ACTs in Mali

被引：65

作者：

Djimde, Abdoulaye A. ^{[1
]}

Fofana, Bakary ^{[1
]}

Sagara, Issaka ^{[1
]}

Sidibe, Bakary ^{[1
]}

Toure, Sekou ^{[1
]}

Dembele, Demba ^{[1
]}

Dama, Souleymane ^{[1
]}

Ouologuem, Dinkorma ^{[1
]}

Dicko, Alassane ^{[1
]}

Doumbo, Ogobara K. ^{[1
]}

机构：

[1] Univ Bamako, Fac Med Pharm & Odonto Stomatol, Dept Epidemiol Parasit Dis, Malaria Res & Training Ctr, Bamako, Mali

来源：

AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE | 2008年 / 78卷 / 03期

关键词：

D O I：

10.4269/ajtmh.2008.78.455

中图分类号：

R1 [预防医学、卫生学];

学科分类号：

1004 ; 120402 ;

摘要：

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.

引用

页码：455 / 461

页数：7

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