Partner study description

ARC3, an international collaboration led by the World Health Organization, supported clinical trials of artesunate monotherapy in Cambodia, Thailand and Bangladesh. ARC3 aimed to confirm clinical resistance to artemisinin in South-East Asia, define in vitro drug resistance phenotypes, and identify molecular markers of resistance. One aspect of this work was developing methods to identify candidate markers of drug resistance using outputs from Illumina sequencing, laying the groundwork for large-scale studies to use whole genome sequencing and other high-throughput technologies to rapidly identify genetic loci associated with artemisinin resistance. This collaboration included investigating signatures of selection and genome-wide association studies of sensitive and resistant parasite isolates collected in the ARC3 trials, and resulted in improved handling and sequencing methods for field samples. Candidate markers discovered using this approach will be assessed for their ability to predict clinical drug resistance, and if validated, used to develop surveillance tools to guide containment efforts.