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

NoorAzian Md Yusuf1*, Afiqah Saleh Huddin1, Jose Miguel Rubio2, Mohd Ridzuan Mohd Abd Razak3, Nurul Shuhada Mohd Ali1, Renuka Devi1, MacCallyster Anak Isa1, Adela Ida Jiram1, Nurhamimah Zainal Abidin1, Nurhainis Ogu Salim1, Nur Fariha Amir1, Mohd Hafizi Abd Hamid4, Jenarun Jelip4 and Shamilah Hisam1

Abstract

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.