Increased in the Prevalence of Plasmodium Falciparum With Kelch13 C580Y Mutations and the Decline in pfcrt and pfmdr1 Mutant Alleles in Papua New Guinea

Abstract BackgroundThe C580Y mutation in Plasmodium falciparum kelch13 (pfk13) is the most commonly observed variant in artemisinin-resistant isolates in the Greater Mekong Subregion (GMS). Until 2017, it had not been identified outside GMS, except for Guyana. In 2017, we identified three parasites carrying the C580Y mutation in Papua New Guinea (PNG). As the C580Y allele rapidly spread in the GMS, there is concern that this mutant is now spreading in PNG. MethodsIn 2020, we conducted a cross-sectional survey at two clinics in Wewak, PNG. Symptomatic patients infected with P. falciparum were treated with artemether plus lumefantrine following a national treatment policy. Blood samples were obtained before treatment, and polymorphisms in pfk13, pfcrt, and pfmdr1 were determined. Parasite positivity was examined on day 3. ResultsA total of 94 patients were included in this analysis. The prevalence of C580Y was significantly increased (2.2% in 2017, 5.7% in 2018, and 6.4% in 2020; p = 4.2×10-3). A significant upward trend of wild-type prevalence was found for pfcrt (1.9% in 2016 to 46.7% in 2020; p = 8.9×10-16) and pfmdr1 (59.5% in 2016 to 91.4% in 2020; p = 2.3×10-6). Among 26 patients, including three with C580Y infections successfully followed on day 3, none showed positive parasitemia. ConclusionsUnder the conditions of significant increases in pfcrt K76 and pfmdr1 N86 alleles in PNG, the increase in pfk13 C580Y mutants may be a warning indicator of the emergence of parasites resistant to the currently used first-line treatment regimen of artemether plus lumefantrine. Therefore, nationwide surveillance of molecular markers for drug resistance and assessment of its therapeutic effect, are important.