In vitro interaction of dihydroartemisin and lumefantrine in clinical field isolates from Bangladesh

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 FIC50 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.