Abstract
This study aimed to determine in vitro sensitivities of artemisinin derivatives and their partner drugs in artemisinin derivative based combination therapy (ACT) and genetic characterization of resistant genes in 95 Plasmodium falciparum isolates collected from Thai-Myanmar and Thai-Cambodia borders. Almost all isolates were sensitive to artesunate และ dihydroartemisinin. Approximately seventy seven percent of the samples had a mutation on an artemisinin-resistant gene, Kelch13 propeller which C580Y mutation was predominant. All parasites isolated from Thai-Cambodia border contained 184F allele with 1 copy number of pfmdr1 gene. In contrast, the parasites collected from Thai-Myanmar border had the pfmdr1 184F allele at 47.2% and contained a few copy number of the pfmdr1 gene with the average of 2.5 copies. Most isolates were resistant to mefloquine which might lead to treatment failure of artesunate-mefloquine in Thailand. Consequently, The Ministry of Public Health has changed the first-line treatment for falciparum malaria to dihyroartemisinin-piperaquine. The present study shows that the parasites containing the pfmdr1 86Y allele exhibited reduced piperaquine sensitivity. Prior to nationwide implication of dihydroartemisinin-piperaquine usage in Thailand, efficacy testing should be conducted. In addition, regular monitoring should be properly performed especially in Thai-Malaysia border where most parasites contained the pfmdr1 86Y allele. Artesunate-pyronaridine is a new effective ACT. The parasites’ pyronaridine IC50 in this study were 3-220 times lower than the IC50 of a recrudescent parasite previously reported in Thailand. In addition, there was no significant difference of pyronaridine IC50 among the parasites with different haplotypes. Thus, artesunate-pyronaridine may be a suitable ACT of choice in the area containing parasites with varied resistant haplotypes especially the pfmdr1 haplotypes. In vitro sensitivities and genotypic characterization of the resistant genes of P. falciparum should be continuously monitored in order to detect the emergence of antimalarial resistance. Rationale drug use can be guided using this information.
