Efficacy, safety, and selection of molecular markers of drug resistance by two ACTs in Mali.
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.
Djimdé
Abdoulaye A
AA
Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Odonto-Stomatology, University of Bamako, Bamako, Mali. adjimde@mrtcbko.org
Fofana
Bakary
B
Sagara
Issaka
I
Sidibe
Bakary
B
Toure
Sekou
S
Dembele
Demba
D
Dama
Souleymane
S
Ouologuem
Dinkorma
D
Dicko
Alassane
A
Doumbo
Ogobara K
OK
D000655:Amodiaquine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077332:Artesunate; D015415:Biomarkers / Q000032:analysis; D004338:Drug Combinations; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology; D008302:Mali / Q000453:epidemiology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics; D011739:Pyrimethamine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D014839:Vomiting / Q000139:chemically induced
D000962:Antimalarials; D037621:Artemisinins; D015415:Biomarkers; D004338:Drug Combinations; D012717:Sesquiterpenes; D000655:Amodiaquine; C001205:fanasil, pyrimethamine drug combination; D000077332:Artesunate; D013413:Sulfadoxine; D011739:Pyrimethamine