Genetic Markers of Piperaquine Resistance in P. falciparum

First, the exomes of culture-adapted artemisinin-resistant Cambodian P falciparum lines defined as piperaquine-susceptible or piperaquine-resistant based on their PSA survival rates⁷ (link) were compared for single-nucleotide polymorphisms (SNPs) and copy number variations (CNVs). This process identified an increased copy number of the plasmepsin 2–plasmepsin 3 gene cluster as a putative genetic signature associated with in-vitro piperaquine resistance. Increased plasmepsin 2 gene copy number was then assessed as a candidate resistance marker in isolates with documented ex-vivo PSA survival rates and in blood samples collected during the years 2009–15 from Cambodian patients treated with dihydroartemisinin–piperaquine and followed up for 42 days. Finally, we investigated the geographical and temporal distribution of multicopy plasmepsin 2 parasites in the country from 2002 to 2015 and its correlation with dihydroartemisinin–piperaquine treatment failures.