Publication: Emergence of artemisinin-resistant Plasmodium falciparum with kelch13 C580Y mutations on the island of New Guinea
Issued Date
2020-12-15
Resource Type
ISSN
15537374
15537366
15537366
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2-s2.0-85098638332
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Mahidol University
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SCOPUS
Bibliographic Citation
PLoS Pathogens. Vol.16, No.12 (2020)
Suggested Citation
Olivo Miotto, Makoto Sekihara, Shin Ichiro Tachibana, Masato Yamauchi, Richard D. Pearson, Roberto Amato, Sonia Gonçalves, Somya Mehra, Rintis Noviyanti, Jutta Marfurt, Sarah Auburn, Ric N. Price, Ivo Mueller, Mie Ikeda, Toshiyuki Mori, Makoto Hirai, Livingstone Tavul, Manuel W. Hetzel, Moses Laman, Alyssa E. Barry, Pascal Ringwald, Jun Ohashi, Francis Hombhanje, Dominic P. Kwiatkowski, Toshihiro Mita Emergence of artemisinin-resistant Plasmodium falciparum with kelch13 C580Y mutations on the island of New Guinea. PLoS Pathogens. Vol.16, No.12 (2020). doi:10.1371/journal.ppat.1009133 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/60869
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Title
Emergence of artemisinin-resistant Plasmodium falciparum with kelch13 C580Y mutations on the island of New Guinea
Author(s)
Olivo Miotto
Makoto Sekihara
Shin Ichiro Tachibana
Masato Yamauchi
Richard D. Pearson
Roberto Amato
Sonia Gonçalves
Somya Mehra
Rintis Noviyanti
Jutta Marfurt
Sarah Auburn
Ric N. Price
Ivo Mueller
Mie Ikeda
Toshiyuki Mori
Makoto Hirai
Livingstone Tavul
Manuel W. Hetzel
Moses Laman
Alyssa E. Barry
Pascal Ringwald
Jun Ohashi
Francis Hombhanje
Dominic P. Kwiatkowski
Toshihiro Mita
Makoto Sekihara
Shin Ichiro Tachibana
Masato Yamauchi
Richard D. Pearson
Roberto Amato
Sonia Gonçalves
Somya Mehra
Rintis Noviyanti
Jutta Marfurt
Sarah Auburn
Ric N. Price
Ivo Mueller
Mie Ikeda
Toshiyuki Mori
Makoto Hirai
Livingstone Tavul
Manuel W. Hetzel
Moses Laman
Alyssa E. Barry
Pascal Ringwald
Jun Ohashi
Francis Hombhanje
Dominic P. Kwiatkowski
Toshihiro Mita
Other Contributor(s)
Papua New Guinea Institute of Medical Research
Eijkman Institute for Molecular Biology
Walter and Eliza Hall Institute of Medical Research
Organisation Mondiale de la Santé
University of Melbourne
Menzies School of Health Research
The University of Tokyo
Universitat Basel
Swiss Tropical and Public Health Institute (Swiss TPH)
Deakin University
Mahidol University
Juntendo University School of Medicine
Nuffield Department of Medicine
Wellcome Sanger Institute
Burnet Institute
Divine Word University
Eijkman Institute for Molecular Biology
Walter and Eliza Hall Institute of Medical Research
Organisation Mondiale de la Santé
University of Melbourne
Menzies School of Health Research
The University of Tokyo
Universitat Basel
Swiss Tropical and Public Health Institute (Swiss TPH)
Deakin University
Mahidol University
Juntendo University School of Medicine
Nuffield Department of Medicine
Wellcome Sanger Institute
Burnet Institute
Divine Word University
Abstract
© 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. 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.