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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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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. |
format | Online Article Text |
id | pubmed-7771869 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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