• Media type: E-Article
  • Title: Increase in the proportion of Plasmodium falciparum with kelch13 C580Y mutation and decline in pfcrt and pfmdr1 mutant alleles in Papua New Guinea
  • Contributor: Yoshida, Naoko; Yamauchi, Masato; Morikawa, Ryosuke; Hombhanje, Francis; Mita, Toshihiro
  • imprint: Springer Science and Business Media LLC, 2021
  • Published in: Malaria Journal
  • Language: English
  • DOI: 10.1186/s12936-021-03933-6
  • ISSN: 1475-2875
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>The C580Y mutation in the <jats:italic>Plasmodium falciparum kelch13</jats:italic> gene is the most commonly observed variant in artemisinin-resistant isolates in the Greater Mekong Subregion (GMS). Until 2017, it had not been identified outside the GMS, except for Guyana/Amazonia. In 2017, three parasites carrying the C580Y mutation were identified 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.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>In 2020, a cross-sectional survey was conducted at two clinics in Wewak, PNG. Symptomatic patients infected with <jats:italic>P. falciparum</jats:italic> were treated with artemether plus lumefantrine following a national treatment policy. Blood samples were obtained before treatment, and polymorphisms in <jats:italic>kelch13</jats:italic>, <jats:italic>pfcrt</jats:italic>, and <jats:italic>pfmdr1</jats:italic> were determined. Parasite positivity was examined on day 3. The results were compared with those of previous studies conducted in 2002, 2003, and 2016–2018.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>A total of 94 patients were included in this analysis. The proportion of C580Y was significantly increased (2.2% in 2017, 5.7% in 2018, and 6.4% in 2020; p = 4.2 × 10<jats:sup>–3</jats:sup>). A significant upward trend was observed in the wild-type proportion for <jats:italic>pfcrt</jats:italic> (1.9% in 2016 to 46.7% in 2020; p = 8.9 × 10<jats:sup>–16</jats:sup>) and <jats:italic>pfmdr1</jats:italic> (59.5% in 2016 to 91.4% in 2020; p = 2.3 × 10<jats:sup>–6</jats:sup>). Among 27 patients successfully followed on day 3, including three with C580Y infections, none showed positive parasitaemia.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Under the conditions of significant increases in <jats:italic>pfcrt</jats:italic> K76 and <jats:italic>pfmdr1</jats:italic> N86 alleles in PNG, the increase in <jats:italic>kelch13</jats:italic> 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 effects are important.</jats:p> </jats:sec>
  • Access State: Open Access