title: Efficacy, safety, and selection of molecular markers of drug resistance by two ACTs in Mali.
abstract: 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.
authors.affiliation: 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
authors.forename: Abdoulaye A
authors.initials: AA
authors.lastname: Djimdé
authors.forename: Bakary
authors.initials: B
authors.lastname: Fofana
authors.forename: Issaka
authors.initials: I
authors.lastname: Sagara
authors.forename: Bakary
authors.initials: B
authors.lastname: Sidibe
authors.forename: Sekou
authors.initials: S
authors.lastname: Toure
authors.forename: Demba
authors.initials: D
authors.lastname: Dembele
authors.forename: Souleymane
authors.initials: S
authors.lastname: Dama
authors.forename: Dinkorma
authors.initials: D
authors.lastname: Ouologuem
authors.forename: Alassane
authors.initials: A
authors.lastname: Dicko
authors.forename: Ogobara K
authors.initials: OK
authors.lastname: Doumbo
mesh_terms: 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
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D015415:Biomarkers; D004338:Drug Combinations; D012717:Sesquiterpenes; D000655:Amodiaquine; C001205:fanasil, pyrimethamine drug combination; D000077332:Artesunate; D013413:Sulfadoxine; D011739:Pyrimethamine