TY - JOUR
T1 - Emergence of artemisinin-resistant Plasmodium falciparum with kelch13 C580Y mutations on the island of New Guinea
AU - Miotto, Olivo
AU - Sekihara, Makoto
AU - Tachibana, Shin Ichiro
AU - Yamauchi, Masato
AU - Pearson, Richard D.
AU - Amato, Roberto
AU - Gonçalves, Sonia
AU - Mehra, Somya
AU - Noviyanti, Rintis
AU - Marfurt, Jutta
AU - Auburn, Sarah
AU - Price, Ric N.
AU - Mueller, Ivo
AU - Ikeda, Mie
AU - Mori, Toshiyuki
AU - Hirai, Makoto
AU - Tavul, Livingstone
AU - Hetzel, Manuel W.
AU - Laman, Moses
AU - Barry, Alyssa E.
AU - Ringwald, Pascal
AU - Ohashi, Jun
AU - Hombhanje, Francis
AU - Kwiatkowski, Dominic P.
AU - Mita, Toshihiro
N1 - Publisher Copyright:
© 2020 Miotto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2020/12/15
Y1 - 2020/12/15
N2 - The rapid and aggressive spread of artemisinin-resistant Plasmodium falciparum carrying the C580Y mutation in the kelch13 gene is a growing threat to malaria elimination in Southeast Asia, but there is no evidence of their spread to other regions. We conducted cross-sectional surveys in 2016 and 2017 at two clinics in Wewak, Papua New Guinea (PNG) where we identified three infections caused by C580Y mutants among 239 genotyped clinical samples. One of these mutants exhibited the highest survival rate (6.8%) among all parasites surveyed in ring-stage survival assays (RSA) for artemisinin. Analyses of kelch13 flanking regions, and comparisons of deep sequencing data from 389 clinical samples from PNG, Indonesian Papua and Western Cambodia, suggested an independent origin of the Wewak C580Y mutation, showing that the mutants possess several distinctive genetic features. Identity by descent (IBD) showed that multiple portions of the mutants’ genomes share a common origin with parasites found in Indonesian Papua, comprising several mutations within genes previously associated with drug resistance, such as mdr1, ferredoxin, atg18 and pnp. These findings suggest that a P. falciparum lineage circulating on the island of New Guinea has gradually acquired a complex ensemble of variants, including kelch13 C580Y, which have affected the parasites’ drug sensitivity. This worrying development reinforces the need for increased surveillance of the evolving parasite populations on the island, to contain the spread of resistance.
AB - The rapid and aggressive spread of artemisinin-resistant Plasmodium falciparum carrying the C580Y mutation in the kelch13 gene is a growing threat to malaria elimination in Southeast Asia, but there is no evidence of their spread to other regions. We conducted cross-sectional surveys in 2016 and 2017 at two clinics in Wewak, Papua New Guinea (PNG) where we identified three infections caused by C580Y mutants among 239 genotyped clinical samples. One of these mutants exhibited the highest survival rate (6.8%) among all parasites surveyed in ring-stage survival assays (RSA) for artemisinin. Analyses of kelch13 flanking regions, and comparisons of deep sequencing data from 389 clinical samples from PNG, Indonesian Papua and Western Cambodia, suggested an independent origin of the Wewak C580Y mutation, showing that the mutants possess several distinctive genetic features. Identity by descent (IBD) showed that multiple portions of the mutants’ genomes share a common origin with parasites found in Indonesian Papua, comprising several mutations within genes previously associated with drug resistance, such as mdr1, ferredoxin, atg18 and pnp. These findings suggest that a P. falciparum lineage circulating on the island of New Guinea has gradually acquired a complex ensemble of variants, including kelch13 C580Y, which have affected the parasites’ drug sensitivity. This worrying development reinforces the need for increased surveillance of the evolving parasite populations on the island, to contain the spread of resistance.
UR - http://www.scopus.com/inward/record.url?scp=85098638332&partnerID=8YFLogxK
U2 - 10.1371/journal.ppat.1009133
DO - 10.1371/journal.ppat.1009133
M3 - Article
C2 - 33320907
AN - SCOPUS:85098638332
VL - 16
SP - 1
EP - 21
JO - PLoS Pathogens
JF - PLoS Pathogens
SN - 1553-7366
IS - 12
M1 - e1009133
ER -