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Emergence of artemisinin-resistant Plasmodium falciparum with kelch13 C580Y mutations on the island of New Guinea

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 201...

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Autores principales: Miotto, Olivo, Sekihara, Makoto, Tachibana, Shin-Ichiro, Yamauchi, Masato, Pearson, Richard D., Amato, Roberto, Gonçalves, Sonia, Mehra, Somya, Noviyanti, Rintis, Marfurt, Jutta, Auburn, Sarah, Price, Ric N., Mueller, Ivo, Ikeda, Mie, Mori, Toshiyuki, Hirai, Makoto, Tavul, Livingstone, Hetzel, Manuel W., Laman, Moses, Barry, Alyssa E., Ringwald, Pascal, Ohashi, Jun, Hombhanje, Francis, Kwiatkowski, Dominic P., Mita, Toshihiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771869/
https://www.ncbi.nlm.nih.gov/pubmed/33320907
http://dx.doi.org/10.1371/journal.ppat.1009133
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author Miotto, Olivo
Sekihara, Makoto
Tachibana, Shin-Ichiro
Yamauchi, Masato
Pearson, Richard D.
Amato, Roberto
Gonçalves, Sonia
Mehra, Somya
Noviyanti, Rintis
Marfurt, Jutta
Auburn, Sarah
Price, Ric N.
Mueller, Ivo
Ikeda, Mie
Mori, Toshiyuki
Hirai, Makoto
Tavul, Livingstone
Hetzel, Manuel W.
Laman, Moses
Barry, Alyssa E.
Ringwald, Pascal
Ohashi, Jun
Hombhanje, Francis
Kwiatkowski, Dominic P.
Mita, Toshihiro
author_facet Miotto, Olivo
Sekihara, Makoto
Tachibana, Shin-Ichiro
Yamauchi, Masato
Pearson, Richard D.
Amato, Roberto
Gonçalves, Sonia
Mehra, Somya
Noviyanti, Rintis
Marfurt, Jutta
Auburn, Sarah
Price, Ric N.
Mueller, Ivo
Ikeda, Mie
Mori, Toshiyuki
Hirai, Makoto
Tavul, Livingstone
Hetzel, Manuel W.
Laman, Moses
Barry, Alyssa E.
Ringwald, Pascal
Ohashi, Jun
Hombhanje, Francis
Kwiatkowski, Dominic P.
Mita, Toshihiro
author_sort Miotto, Olivo
collection PubMed
description 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.
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spelling pubmed-77718692021-01-08 Emergence of artemisinin-resistant Plasmodium falciparum with kelch13 C580Y mutations on the island of New Guinea Miotto, Olivo Sekihara, Makoto Tachibana, Shin-Ichiro Yamauchi, Masato Pearson, Richard D. Amato, Roberto Gonçalves, Sonia Mehra, Somya Noviyanti, Rintis Marfurt, Jutta Auburn, Sarah Price, Ric N. Mueller, Ivo Ikeda, Mie Mori, Toshiyuki Hirai, Makoto Tavul, Livingstone Hetzel, Manuel W. Laman, Moses Barry, Alyssa E. Ringwald, Pascal Ohashi, Jun Hombhanje, Francis Kwiatkowski, Dominic P. Mita, Toshihiro PLoS Pathog Research Article 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. Public Library of Science 2020-12-15 /pmc/articles/PMC7771869/ /pubmed/33320907 http://dx.doi.org/10.1371/journal.ppat.1009133 Text en © 2020 Miotto et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Miotto, Olivo
Sekihara, Makoto
Tachibana, Shin-Ichiro
Yamauchi, Masato
Pearson, Richard D.
Amato, Roberto
Gonçalves, Sonia
Mehra, Somya
Noviyanti, Rintis
Marfurt, Jutta
Auburn, Sarah
Price, Ric N.
Mueller, Ivo
Ikeda, Mie
Mori, Toshiyuki
Hirai, Makoto
Tavul, Livingstone
Hetzel, Manuel W.
Laman, Moses
Barry, Alyssa E.
Ringwald, Pascal
Ohashi, Jun
Hombhanje, Francis
Kwiatkowski, Dominic P.
Mita, Toshihiro
Emergence of artemisinin-resistant Plasmodium falciparum with kelch13 C580Y mutations on the island of New Guinea
title Emergence of artemisinin-resistant Plasmodium falciparum with kelch13 C580Y mutations on the island of New Guinea
title_full Emergence of artemisinin-resistant Plasmodium falciparum with kelch13 C580Y mutations on the island of New Guinea
title_fullStr Emergence of artemisinin-resistant Plasmodium falciparum with kelch13 C580Y mutations on the island of New Guinea
title_full_unstemmed Emergence of artemisinin-resistant Plasmodium falciparum with kelch13 C580Y mutations on the island of New Guinea
title_short Emergence of artemisinin-resistant Plasmodium falciparum with kelch13 C580Y mutations on the island of New Guinea
title_sort emergence of artemisinin-resistant plasmodium falciparum with kelch13 c580y mutations on the island of new guinea
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771869/
https://www.ncbi.nlm.nih.gov/pubmed/33320907
http://dx.doi.org/10.1371/journal.ppat.1009133
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