title: In vitro interaction of dihydroartemisin and lumefantrine in clinical field isolates from Bangladesh.
abstract: The combination of artemether and lumefantrine was introduced in 2005 as the official first line therapy for uncomplicated falciparum malaria in Bangladesh. Fresh P. falciparum samples from patients with acute uncomplicated falciparum malaria who presented to the field site at the Bandarban Sadar Hospital in Bangladesh were tested in checkerboard in vitro drug sensitivity assays to assess the interaction between dihydroartemisinin (DHA) and lumefantrine (LUM). Clearly synergistic interactions with an overall mean FIC(50) of 0.52 and individual mean FICs between 0.26 and 0.85 were found. Lowest FICs were 0.41, 0.18, 0.22, 0.15 and 0.11 at different combination ratios. The optimal combination ratio of the drug combination indicated by the lowest mean FIC average was found to be 1:150 DHA:LUM. Although activity correlations between DHA and lumefantrine were significant, indicating possible cross sensitivity patterns, our data confirm that artemether-lumefantrine is a highly synergistic drug combination.
authors.affiliation: Department of Specific Prophylaxis and Tropical Medicine, Center for Physiology and Pathophysiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Kamala
authors.initials: K
authors.lastname: Thriemer
authors.forename: Wasif Ali
authors.initials: WA
authors.lastname: Khan
authors.forename: Peter
authors.initials: P
authors.lastname: Starzengruber
authors.forename: Rashidul
authors.initials: R
authors.lastname: Haque
authors.forename: Matthias G
authors.initials: MG
authors.lastname: Vossen
authors.forename: Aung Swi Prue
authors.initials: AS
authors.lastname: Marma
authors.forename: Selim
authors.initials: S
authors.lastname: Akther
authors.forename: Mark
authors.initials: M
authors.lastname: Fukuda
authors.forename: Harald
authors.initials: H
authors.lastname: Noedl
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage*; D037621:Artemisinins / Q000008:administration & dosage*; D001459:Bangladesh; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000008:administration & dosage*; D005449:Fluorenes / Q000008:administration & dosage*; D006801:Humans; D007928:Lethal Dose 50; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000502:physiology*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004983:Ethanolamines; D005449:Fluorenes; C039060:artenimol; D000078102:Lumefantrine