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

Miotto, O, Sekihara, M, Tachibana, SI, Yamauchi, M, Pearson, RD, Amato, R, Gonçalves, S, Mehra, S, Noviyanti, R, Marfurt, J, Auburn, S, Price, RN, Mueller, I, Ikeda, M, Mori, T, Hirai, M, Tavul, L, Hetzel, MW, Laman, M, Barry, A, Ringwald, P, Ohashi, J, Hombhanje, F, Kwiatkowski, DP and Mita, T 2020, Emergence of artemisinin-resistant Plasmodium falciparum with kelch13 C580Y mutations on the island of New Guinea, PLoS Pathogens, vol. 16, no. 12, pp. 1-21, doi: 10.1371/journal.ppat.1009133.

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Title Emergence of artemisinin-resistant Plasmodium falciparum with kelch13 C580Y mutations on the island of New Guinea
Author(s) Miotto, O
Sekihara, M
Tachibana, SI
Yamauchi, M
Pearson, RD
Amato, R
Gonçalves, S
Mehra, S
Noviyanti, R
Marfurt, J
Auburn, S
Price, RN
Mueller, I
Ikeda, M
Mori, T
Hirai, M
Tavul, L
Hetzel, MW
Laman, M
Barry, AORCID iD for Barry, A orcid.org/0000-0002-1189-2310
Ringwald, P
Ohashi, J
Hombhanje, F
Kwiatkowski, DP
Mita, T
Journal name PLoS Pathogens
Volume number 16
Issue number 12
Start page 1
End page 21
Total pages 21
Publisher PLOS
Place of publication San Francisco, CA
Publication date 2020-12-15
ISSN 1553-7366
1553-7374
Keyword(s) Papua New Guinea
Artemisinin
Haplotypes
Genomics
Single nucleotide polymorphisms
Parasitic diseases
Islands
Mutation
Science & Technology
Life Sciences & Biomedicine
Microbiology
Parasitology
Virology
DIHYDROARTEMISININ-PIPERAQUINE
P. FALCIPARUM
IN-VITRO
MALARIA
CAMBODIA
SENSITIVITY
DIVERSITY
GENOME
SPREAD
PAPUA
Summary 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.
Language eng
DOI 10.1371/journal.ppat.1009133
Indigenous content off
Field of Research 0605 Microbiology
1107 Immunology
1108 Medical Microbiology
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2020, Miotto et al.
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30146878

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.