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The Journal of the Royal Institute of Thailand Volume II - 2010 Combination Anti-malarial Therapy and WHO Recommendations 102 compared to northwestern Thailand (Dondorp et al, 2009). In the last decade P. vivax in Indonesia also developed resistance to chloroquine (the cheap and widely available antimalarial drug). High-level chloroquine resistance has been well documented on the northern part of the island of New Guinea and in Sumatra, and there have been sporadic reports from other geographic locations. The use of antimalarial combinations will delay the onset and slow the rate of spread of resistance–especially when drug resistance mutant alleles are rare. The concept that resistance could be delayed or prevented by combining drugs with different targets was developed first in the treatment of tuberculosis. It has since been adopted widely for the treatment of cancer and HIV infection. Thus combinations will considerably delay the emergence of drug resistance. They also inhibit the spread and further increase of established low-grade resistance. In the last two decade, there have been several clinical studies on various antimalarial drugs in combination for the treatment of chloroquine resistant falciparum malaria. The choice of combined drugs for uncomplicated falciparum malaria is usually an antimalarial-antibiotic or two antimalarials with short and long half lives. For adult patients, artemisinin-based combination therapy (ACT) and quinine-tetracycline are effective worldwide with > 90% cure rates (Figure 2). Artemisinin-based combination therapy (ACT) The artemisinin drugs have considerable advantages over other compounds for use in antimalarial combinations (Pukrittayakamee & White, 2002, WHO, 2010). They are very active and well tolerated, and they reduce parasite numbers more than the other antimalarials by approximately 10,000 fold per asexual cycle. Although there are some minor differences in oral absorption and bioavailability between the different artemisinin derivatives, there is no evidence that these differences are clinically significant in currently available formulations. It is the properties of the partner medicine that determine the efficacy and choice of combination. Resistance to the artemisinins’ partner medicines compromises the efficacy of the ACT (Figure 3). The available ACTs already recommended for the treatment of uncomplicated falciparum malaria are artesunate plus mefloquine, artemether plus lumefantrine, artesunate plus amodiaquine and artesunate plus sulfadoxine-pyrimethamine. Other additions to the list of ACTs options for the treatment of uncomplicated falciparum malaria are dihydroartemsinin-piperaquine (Artekin) and pyuronaridine-artesunate (Pyramax).