PREVALENCE OF PLASMODIUM FALCIPARUM KELCH13 POLYMORPHISMS IN MALAYSIA (2008 - 2017)

Artemisinin combination therapies (ACTs) are recommended by the World Health Organization for treatment of uncomplicated malaria caused by Plasmodium falciparum. However, artemisinin resistance in the Greater Mekong Subregion was detected in 2008 and has since spread to the other parts of the region. Mutations in the propeller domain of P. falciparum kelch-13 protein (pfk13) serve as molecular markers for partial artemisinin resistance (delayed parasite clearance). Prevalence of pfk13 propellar domain mutations/substitutions in 125 archived diagnostic blood samples in Malaysia from 2008 to 2017 were determined by nested-PCR and direct sequencing. Pfk13, C580Y and P553L mutations, previously confirmed and validated as markers for artemisinin resistance, were found in two samples; N537I and A675V mutations, classified as candidates/ associated with delayed parasite clearance, in three samples; and eight novel substitutions, with seven sequences containing two amino acid changes. These findings constitute baseline data and further investigations are needed to correlate amino acid changes present in pfk13 propellar domain with delayed parasite clearance, in vitro and ex vivo parasite artemisinin sensitivity.