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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Plasmodium falciparum drug resistance phenotype as assessed by patient antimalarial drug levels and its association with pfmdr1 polymorphisms
Journal of Infectious Diseases, Volume 207, No. 5, Year 2013
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Description
Background. Multidrug-resistant Plasmodium falciparum is a major threat to global malaria control. Parasites develop resistance by gradually acquiring genetic polymorphisms that decrease drug susceptibility. The aim of this study was to investigate the extent to which parasites with different genetic characteristics are able to withstand individual drug blood concentrations. Methods. We analyzed 2 clinical trials that assessed the efficacy and effectiveness of artemether-lumefantrine. As a proof of concept, we used measured day 7 lumefantrine concentrations to estimate the concentrations at which reinfections multiplied. P. falciparum multidrug resistance gene 1 (pfmdr1) genotypes of these parasites were then correlated to drug susceptibility.Results. Reinfecting parasites with the pfmdr1 N86/184F/D1246 haplotype were able to withstand lumefantrine blood concentrations 15-fold higher than those with the 86Y/Y184/1246Y haplotype.Conclusions. By estimating drug concentrations, we were able to quantify the contribution of pfmdr1 single-nucleotide polymorphisms to reduced lumefantrine susceptibility. The method can be applied to all long-half-life antimalarial drugs, enables early detection of P. falciparum with reduced drug susceptibility in vivo, and represents a novel way for unveiling molecular markers of antimalarial drug resistance. © 2012 The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3563306/bin/supp_207_5_842__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC3563306/bin/supp_jis747_jis747supp.docx
Authors & Co-Authors
Malmberg, M.
Sweden, Stockholm
Karolinska Institutet
Ferreira, Pedro Eduardo
Sweden, Stockholm
Karolinska Institutet
Portugal, Faro
Universidade do Algarve
Japan, Nagasaki
Nagasaki University
Tarning, Joel
Thailand, Nakhon Pathom
Mahidol University
United Kingdom, Oxford
Nuffield Department of Medicine
Ursing, Johan
Sweden, Stockholm
Karolinska Institutet
Ngasala, Billy E.
Sweden, Stockholm
Karolinska Institutet
Tanzania, Dar es Salaam
Muhimbili University of Health and Allied Sciences
Bjǒrkman, Anders B.
Sweden, Stockholm
Karolinska Institutet
Mårtensson, Andreas A.
Sweden, Stockholm
Karolinska Institutet
Sweden, Stockholm
Division of Global Health
Gil, Jose Pedro
Sweden, Stockholm
Karolinska Institutet
Portugal, Faro
Universidade do Algarve
United States, Binghamton
Binghamton University State University of new York
Statistics
Citations: 8
Authors: 8
Affiliations: 8
Identifiers
Doi:
10.1093/infdis/jis747
ISSN:
00221899
Research Areas
Genetics And Genomics
Health System And Policy
Infectious Diseases