Publication:
Polymorphisms in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes: Parasite risk factors that affect treatment outcomes for P. falciparum malaria after artemether-lumefantrine and artesunate-amodiaquine

Issued Date

2014-01-01

Resource Type

Article

ISSN

00029637

DOI

10.4269/ajtmh.14-0031

Other identifier(s)

2-s2.0-84906937961

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

American Journal of Tropical Medicine and Hygiene. Vol.91, No.4 (2014), 833-843

Suggested Citation

Meera Venkatesan, Nahla B. Gadalla, Kasia Stepniewska, Prabin Dahal, Christian Nsanzabana, Clarissa Moriera, Ric N. Price, Andreas Ma˚rtensson, Philip J. Rosenthal, Grant Dorsey, Colin J. Sutherland, Philippe Guérin, Timothy M.E. Davis, Didier Ménard, Ishag Adam, George Ademowo, Cesar Arze, Frederick N. Baliraine, Nicole Berens-Riha, Anders Björkman, Steffen Borrmann, Francesco Checchi, Meghna Desai, Mehul Dhorda, Abdoulaye A. Djimdé, Badria B. El-Sayed, Teferi Eshetu, Frederick Eyase, Catherine Falade, Jean Franc¸ois Faucher, Gabrielle Fröberg, Anastasia Grivoyannis, Sally Hamour, Sandrine Houzé, Jacob Johnson, Erasmus Kamugisha, Simon Kariuki, Jean René Kiechel, Fred Kironde, Poul Erik Kofoed, Jacques LeBras, Maja Malmberg, Leah Mwai, Billy Ngasala, Francois Nosten, Samuel L. Nsobya, Alexis Nzila, Mary Oguike, Sabina Dahlström Otienoburu, Bernhards Ogutu, Jean Bosco Ouédraogo, Patrice Piola, Lars Rombo, Birgit Schramm, A. Fabrice Somé, Julie Thwing, Johan Ursing, Rina P.M. Wong, Ahmed Zeynudin, Issaka Zongo, Christopher V. Plowe, Carol Hopkins Sibley Polymorphisms in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes: Parasite risk factors that affect treatment outcomes for P. falciparum malaria after artemether-lumefantrine and artesunate-amodiaquine. American Journal of Tropical Medicine and Hygiene. Vol.91, No.4 (2014), 833-843. doi:10.4269/ajtmh.14-0031 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/34113

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Title

Polymorphisms in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes: Parasite risk factors that affect treatment outcomes for P. falciparum malaria after artemether-lumefantrine and artesunate-amodiaquine

Author(s)

Meera Venkatesan
 Nahla B. Gadalla
 Kasia Stepniewska
 Prabin Dahal
 Christian Nsanzabana
 Clarissa Moriera
 Ric N. Price
 Andreas Ma˚rtensson
 Philip J. Rosenthal
 Grant Dorsey
 Colin J. Sutherland
 Philippe Guérin
 Timothy M.E. Davis
 Didier Ménard
 Ishag Adam
 George Ademowo
 Cesar Arze
 Frederick N. Baliraine
 Nicole Berens-Riha
 Anders Björkman
 Steffen Borrmann
 Francesco Checchi
 Meghna Desai
 Mehul Dhorda
 Abdoulaye A. Djimdé
 Badria B. El-Sayed
 Teferi Eshetu
 Frederick Eyase
 Catherine Falade
 Jean Franc¸ois Faucher
 Gabrielle Fröberg
 Anastasia Grivoyannis
 Sally Hamour
 Sandrine Houzé
 Jacob Johnson
 Erasmus Kamugisha
 Simon Kariuki
 Jean René Kiechel
 Fred Kironde
 Poul Erik Kofoed
 Jacques LeBras
 Maja Malmberg
 Leah Mwai
 Billy Ngasala
 Francois Nosten
 Samuel L. Nsobya
 Alexis Nzila
 Mary Oguike
 Sabina Dahlström Otienoburu
 Bernhards Ogutu
 Jean Bosco Ouédraogo
 Patrice Piola
 Lars Rombo
 Birgit Schramm
 A. Fabrice Somé
 Julie Thwing
 Johan Ursing
 Rina P.M. Wong
 Ahmed Zeynudin
 Issaka Zongo
 Christopher V. Plowe
 Carol Hopkins Sibley

Other Contributor(s)

University of Maryland School of Medicine
 National Institute of Allergy and Infectious Diseases
 Tropical Medicine Research Institute Sudan
 Nuffield Department of Clinical Medicine
 Menzies School of Health Research
 Karolinska Institutet
 University of California, San Francisco
 London School of Hygiene & Tropical Medicine
 University of Western Australia Faculty of Medicine and Dentistry
 Institut Pasteur du Cambodge
 University of Khartoum Faculty of Medicine
 University of Ibadan
 LeTourneau University
 Ludwig-Maximilians-Universitat Munchen
 Sveriges lantbruksuniversitet
 Wellcome Trust Research Laboratories Nairobi
 Magdeburg School of Medicine
 Save the Children Fund
 Centers for Disease Control and Prevention
 Epicentre
 University of Sciences
 Jimma University
 Kenya Medical Research Institute
 Besançon University Medical Center
 IRD Institut de Recherche pour le Developpement
 University of Washington, Seattle
 UCL
 Hopital Bichat-Claude-Bernard AP-HP
 Universite Paris Descartes
 Catholic University of Health and Allied Sciences-Bugando
 Drugs for Neglected Diseases Initiative
 Makerere University
 St. Augustine International University
 Projecto de Saúde de Bandim
 Kolding Sygehus
 The University of British Columbia
 Muhimbili University of Health and Allied Sciences
 Mahidol University
 King Fahd University of Petroleum and Minerals
 Bernard Hospital
 Centre MURAZ
 Institut Pasteur de Madagascar

Abstract

Copyright © 2014 by The American Society of Tropical Medicine and Hygiene. Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemetherlumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29-9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36-17.97, P < 0.001) were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine.

Keyword(s)

Immunology and Microbiology
 Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/34113

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