The emergence and spread of kelch 13 mutations associated with artemisinin resistance in Plasmodium falciparum parasites in twelve Thai provinces from 2007 - 2016 [PublishAheadOfPrint]

Artemisinin-based combination therapy (ACT) is the most effective and widely used treatment for uncomplicated Plasmodium falciparum (Pf) malaria and is a cornerstone for malaria control and prevention globally. Resistance to artemisinin derivatives has been confirmed in the Greater Mekong Subregion (GMS), which manifest as slow parasite clearance in patients and reduced ring-stage susceptibility to artemisinins in survival assays. The Pf kelch 13 gene mutations associated with artemisinin resistant parasites are now wide-spread in the GMS. We genotyped 277 samples collected during an observational study from 2012-2016 from eight provinces in Thailand to identify Pf kelch 13 mutations. The results were combined with previously reported genotyping results from Thailand to construct a map illustrating the evolution of Pf kelch 13 mutations from 2007 – 2016 in the country. Different mutant alleles were found in strains with different geographical origins. The artemisinin resistant Y493H and R539T mutations were detected mainly in eastern Thailand (bordering Cambodia), while P574L was only found in western Thailand and R561H in northwestern Thailand. The C580Y mutation was found across the entire country and was nearing fixation along the Thai-Cambodia border. Overall the prevalence of artemisinin resistant mutations increased over the last ten years across Thailand, especially along the Thai-Cambodia border. Molecular surveillance and therapeutic efficacy monitoring should be intensified in the region to further assess the extent and spread of artemisinin resistance.

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