3. Global review of antimalarial drug efficacy and drug resistanceFigure 10. Treatment failure rates with artemether搇umefantrine in the Greater Mekong subregion (2001�009)40 maximum median minimumTreatment failure (%)3020100 Thailand Lao People's Democratic Republic Myanmar CambodiaThe box plots depict the following summary statistics for the efficacy studies conducted for each country and drug with a follow-up of 28 days: the minimum value (bottom whisker), the 25th percentile, the median value, the 75th percentile and the maximum value (upper whisker). Countries are sorted by median values, in ascending order. Only data for countries where three or more studies were conducted have been presented. The box plots do not illustrate variations in sample size, protocol year or study location. The red line indicates the threshold of 10% of treatment failure at which countries should initiate a change of the antimalarial medicine recommended in their national malaria treatment policy.The efficacy of artemether搇umefantrine combination is strongly influenced by the wide variation in the pharmacokinetics of lumefantrine among individuals. As its absorption is enhanced by concomitant intake of fatty foods (Ezzet, Mull & Karbwang, 1998), treatment failures with this combination might be due to insufficient absorption of lumefantrine. The main determinant of the efficacy of the combination is the area under the curve of the plasma concentration of lumefantrine, or its surrogate, the plasma concentration of lumefantrine on day 7 (White, van Vugt & Ezzet, 1999; Price et al., 2006). Artemether搇umefantrine remains highly effective in most parts of the world, with the exception of Cambodia. Although no time trends have been observed in any of subregions, continuous monitoring is necessary. Artemether搇umefantrine was reported to select for the wild-type Pfmdr1 Asn86 allele in recurrent infections, which could be a marker of reduced susceptibility to lumefantrine. In order to ensure early detection of lumefantrine resistance, therapeutic efficacy studies should be complemented with measurement of the blood concentration of lumefantrine on day 7 and with studies of Pfmdr1 polymorphisms.40
