Charles Darwin University

CDU eSpace
Institutional Repository

 
CDU Staff and Student only
 

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

Venkatesan, Meera, Gadalla, Nahla B., Stepniewska, Kasia, Dahal, Prabin, Nsanzabana, Christian, Moriera, Clarissa, Price, Ric N., Martensson, Andreas, Rosenthal, Philip J., Dorsey, Grant, Sutherland, Colin J., Guerin, Philippe, Davis, Timothy M.E., Menard, Didier, Adam, Ishag, Ademowo, George, Arze, Cesar, Baliraine, Frederick and Berens-Riha, Nicole (2014). 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,91(4):833-843.

Document type: Journal Article
Citation counts: Altmetric Score Altmetric Score is 18
Google Scholar Search Google Scholar
Attached Files (Some files may be inaccessible until you login with your CDU eSpace credentials)
Name Description MIMEType Size Downloads
Download this reading Price_49195.pdf Published version application/pdf 433.38KB 78
Reading the attached file works best in Firefox, Chrome and IE 9 or later.

IRMA ID 75039815xPUB528
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 Venkatesan, Meera
Gadalla, Nahla B.
Stepniewska, Kasia
Dahal, Prabin
Nsanzabana, Christian
Moriera, Clarissa
Price, Ric N.
Martensson, Andreas
Rosenthal, Philip J.
Dorsey, Grant
Sutherland, Colin J.
Guerin, Philippe
Davis, Timothy M.E.
Menard, Didier
Adam, Ishag
Ademowo, George
Arze, Cesar
Baliraine, Frederick
Berens-Riha, Nicole
Journal Name American Journal of Tropical Medicine and Hygiene
Publication Date 2014
Volume Number 91
Issue Number 4
ISSN 0002-9637   (check CDU catalogue open catalogue search in new window)
Scopus ID 2-s2.0-84906937961
Start Page 833
End Page 843
Total Pages 11
Place of Publication United States of America
Publisher American Society of Tropical Medicine and Hygiene
HERDC Category C1 - Journal Article (DIISR)
Abstract 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 resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (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.
DOI http://dx.doi.org/10.4269/ajtmh.14-0031   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)
Additional Notes This is an Open Access article distributed under the terms of the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Description for Link Link to CC Attribution 4.0 License
URL https://creativecommons.org/licenses/by/4.0/au


© copyright

Every reasonable effort has been made to ensure that permission has been obtained for items included in CDU eSpace. If you believe that your rights have been infringed by this repository, please contact digitisation@cdu.edu.au.

 
Versions
Version Filter Type
Access Statistics: 101 Abstract Views, 78 File Downloads  -  Detailed Statistics
Created: Wed, 19 Aug 2015, 12:16:48 CST