Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/42831
Title: Artemisinin resistance without pfkelch13 mutations in Plasmodium falciparum isolates from Cambodia
Authors: Angana Mukherjee
Selina Bopp
Pamela Magistrado
Wesley Wong
Rachel Daniels
Allison Demas
Stephen Schaffner
Chanaki Amaratunga
Pharath Lim
Mehul Dhorda
Olivo Miotto
Charles Woodrow
Elizabeth A. Ashley
Arjen M. Dondorp
Nicholas J. White
Dyann Wirth
Rick Fairhurst
Sarah K. Volkman
Harvard School of Public Health
Broad Institute
National Institute of Allergy and Infectious Diseases
Worldwide Antimalarial Resistance Network
Nuffield Department of Clinical Medicine
Mahidol University
Wellcome Trust Centre for Human Genetics
Wellcome Trust Sanger Institute
Academic Medical Centre, University of Amsterdam
Simmons College
Keywords: Immunology and Microbiology
Issue Date: 12-May-2017
Citation: Malaria Journal. Vol.16, No.1 (2017)
Abstract: © 2017 The Author(s). Background: Artemisinin resistance is associated with delayed parasite clearance half-life in vivo and correlates with ring-stage survival under dihydroartemisinin in vitro. Both phenotypes are associated with mutations in the PF3D7_1343700 pfkelch13 gene. Recent spread of artemisinin resistance and emerging piperaquine resistance in Southeast Asia show that artemisinin combination therapy, such as dihydroartemisinin-piperaquine, are losing clinical effectiveness, prompting investigation of drug resistance mechanisms and development of strategies to surmount emerging anti-malarial resistance. Methods: Sixty-eight parasites isolates with in vivo clearance data were obtained from two Tracking Resistance to Artemisinin Collaboration study sites in Cambodia, culture-adapted, and genotyped for pfkelch13 and other mutations including pfmdr1 copy number; and the RSA0-3h survival rates and response to antimalarial drugs in vitro were measured for 36 of these isolates. Results: Among these 36 parasites one isolate demonstrated increased ring-stage survival for a PfKelch13 mutation (D584V, RSA0-3h = 8%), previously associated with slow clearance but not yet tested in vitro. Several parasites exhibited increased ring-stage survival, yet lack pfkelch13 mutations, and one isolate showed evidence for piperaquine resistance. Conclusions: This study of 68 culture-adapted Plasmodium falciparum clinical isolates from Cambodia with known clearance values, associated the D584V PfKelch13 mutation with increased ring-stage survival and identified parasites that lack pfkelch13 mutations yet exhibit increased ring-stage survival. These data suggest mutations other than those found in pfkelch13 may be involved in conferring artemisinin resistance in P. falciparum. Piperaquine resistance was also detected among the same Cambodian samples, consistent with reports of emerging piperaquine resistance in the field. These culture-adapted parasites permit further investigation of mechanisms of both artemisinin and piperaquine resistance and development of strategies to prevent or overcome anti-malarial resistance.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85018866604&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/42831
ISSN: 14752875
Appears in Collections:Scopus 2016-2017

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