The recent emergence of artemisinin resistance in the Greater Mekong Subregion poses a major threat to the global effort to control malaria. Tracking the spread and evolution of artemisinin-resistant parasites is critical in aiding efforts to contain the spread of resistance. A total of 417 patient samples from the year 2007, collected during malaria surveillance studies across ten provinces in Thailand, were genotyped for the candidate Plasmodium falciparum molecular marker of artemisinin resistance K13. Parasite genotypes were examined for K13 propeller mutations associated with artemisinin resistance, signatures of positive selection, and for evidence of whether artemisinin-resistant alleles arose independently across Thailand. A total of seven K13 mutant alleles were found (N458Y, R539T, E556D, P574L, R575K, C580Y, S621F). Notably, the R575K and S621F mutations have previously not been reported in Thailand. The most prevalent artemisinin resistance-associated K13 mutation, C580Y, carried two distinct haplotype profiles that were separated based on geography, along the Thai-Cambodia and Thai-Myanmar borders. It appears these two haplotypes may have independent evolutionary origins. In summary, parasites with K13 propeller mutations associated with artemisinin resistance were widely present along the Thai-Cambodia and Thai-Myanmar borders prior to the implementation of the artemisinin resistance containment project in the region.

RealAmp was comparable to PCR in detecting malaria parasites and shows promise as a tool to detect submicroscopic infections in malaria control and elimination programs worldwide.

Both oral and intramuscular artemether were well-tolerated. In most cases, artemether and dihydroartemisinin were detected in plasma after 30 min and declined to levels below the limit of detection within 18-24 h. Compared with intramuscular administration, oral administration of artemether resulted in a relatively rapid but incomplete absorption [Cmax: 474 vs 540 ng.ml-1; tmax: 2.0 vs 3.9 h; AUC: 2.17 vs 5.20 micrograms.h.ml-1]. Geographic means of lag-time and absorption half-life (t1/2a) of oral vs intramuscular artemether were 0.28 and 1.1 h vs 0.30 and 2 h, respectively, t1/2z was significantly shortened after the oral dose [2.8 vs 6.9 h]. Mean oral bioavailability relative to intramuscular administration was 43.2%. The ratio of the AUCs of artemether to dihydroartemisinin was significantly lower after the oral than after the intramuscular dose (geometric mean: 0.29 vs 0.60). artemisinin, which is commercially available in China, Vietnam, Thailand and some African countries. The drug is administered as solution in oil for intramuscular injection or as oral tablets. The clinical efficacy of artemether is dependent on the formulation, dosing scheme, duration of treatment, and the severity of the disease [1, 2]. Oral artemether is effective but with short-term treatment, the relapse rate is high. While the efficacy of intramuscular artemether against multidrug-resistant P. falciparum in either uncomplicated or severe cases has been confirmed, its pharmacokinetic documentation is limited. Formulations with high bioavailability and low costs are essential. With high-performance liquid chromatography and electrochemical detection, more sensitive and reliable assay of artemisinin and derivatives in biological fluids has been achieved [3-4]. In the present study, we have assessed the pharmacokinetics and bioavailability of oral and intramuscular artemether, in healthy Thai males.

The emergence and spread of drug-resistant Plasmodium falciparum have been a major impediment for the control of malaria worldwide. Earlier studies have shown that similar to chloroquine (CQ) resistance, high levels of pyrimethamine resistance in P. falciparum originated independently 4 to 5 times globally, including one origin at the Thailand-Cambodia border. In this study we describe the origins and spread of sulfadoxineresistance-conferring dihydropteroate synthase (dhps) alleles in Thailand. The dhps mutations and flanking microsatellite loci were genotyped for P. falciparum isolates collected from 11 Thai provinces along the Burma, Cambodia, and Malaysia borders. Results indicated that resistant dhps alleles were fixed in Thailand, predominantly being the SGEGA, AGEAA, and SGNGA triple mutants and the AGKAA double mutant (mutated codons are underlined). These alleles had different geographical distributions. The SGEGA alleles were found mostly at the Burma border, while the SGNGA alleles occurred mainly at the Cambodia border and nearby provinces. Microsatellite data suggested that there were two major genetic lineages of the triple mutants in Thailand, one common for SGEGA/SGNGA alleles and another one independent for AGEAA. Importantly, the newly reported SGNGA alleles possibly originated at the Thailand-Cambodia border. All parasites in the Yala province (Malaysia border) had AGKAA alleles with almost identical flanking microsatellites haplotypes. They were also identical at putatively neutral loci on chromosomes 2 and 3, suggesting a clonal nature of the parasite population in Yala. In summary, this study suggests multiple and independent origins of resistant dhps alleles in Thailand.