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Relationship between the Pfcrt T76 and the Pfmdr-1 Y86 mutations in Plasmodium falciparum and in vitro/in vivo chloroquine resistance in Burkina Faso, West Africa

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dc.contributor.author Tinto, H. en_US
dc.contributor.author Ouédraogo, J. B. en_US
dc.contributor.author Erhart, A. en_US
dc.contributor.author Van Overmeir, C. en_US
dc.contributor.author Dujardin, J. C. en_US
dc.contributor.author Van Marck, E. en_US
dc.contributor.author Guiguemdé, T. R. en_US
dc.contributor.author D'Alessandro, U. en_US
dc.date.accessioned 2007-12-06T14:34:16Z
dc.date.available 2007-12-06T14:34:16Z
dc.date.issued 2003 en_US
dc.identifier.issn 1567-1348 en_US
dc.identifier.other ITG-P3A en_US
dc.identifier.other ITG-P4B en_US
dc.identifier.other ITG-P5A en_US
dc.identifier.other ITG-PLA en_US
dc.identifier.other PARAS en_US
dc.identifier.other U-MALAR en_US
dc.identifier.other U-PROTO en_US
dc.identifier.other JIF en_US
dc.identifier.other ABSTRACT en_US
dc.identifier.uri http://hdl.handle.net/10390/299
dc.description.abstract The relationship between Pfcrt T76 and Pfmdr-1 Y86 mutations in Plasmodium falciparum was explored in samples from patients with uncomplicated malaria and tested in vitro and in vivo with chloroquine (CQ) in Burkina Faso. The two mutations were strongly related. The Pfcrt T76 mutation was found in 82% of the samples having the Pfmdr-1 Y86 mutation too (odds ratio (OR)=4.8 [95% CI: 1.7-13.3]; P=0.002). However, only half (16/34) of samples with Pfcrt T76 mutation had also the Pfmdr-1 Y86 mutation. The latter was apparently associated with in vitro resistance (OR=4.8 [95% CI: 1.4-16.5]; P=0.01) but such association disappeared (P=0.77) after adjusting for the presence of the Pfcrt T76 mutation. This suggests that the occurrence of the Pfmdr-1 Y86 mutation is dependent on that of Pfcrt T76 mutation and could explain previous reports linking the Pfmdr-1 Y86 mutation with CQ resistance (CQR). The isolates carrying both the Pfcrt K76 and Pfmdr-1 N86 alleles (wild/wild (WW)) and the single mutant Pfmdr-1 Y86 (WM) had the lowest IC50 geometric mean (GMIC50) values, while those carrying both Pfcrt T76/Pfmdr-1 Y86 alleles (mutant/mutant (MM)), and the single mutant Pfcrt T76 (MW) had the highest. Among pre-treatment samples there was a strong linkage disequilibrium with an excess of MM and WW and a deficit of single mutants (MW and WM), suggesting that parasite fitness is higher for the former and lower for the latter. en_US
dc.language English en_US
dc.subject Protozoal diseases en_US
dc.subject Malaria en_US
dc.subject Plasmodium falciparum en_US
dc.subject Mutations en_US
dc.subject Pfcrt en_US
dc.subject Pfmdr-1 en_US
dc.subject Drug resistance en_US
dc.subject Chloroquine en_US
dc.title Relationship between the Pfcrt T76 and the Pfmdr-1 Y86 mutations in Plasmodium falciparum and in vitro/in vivo chloroquine resistance in Burkina Faso, West Africa en_US
dc.type Article en_US
dc.citation.jtitle Infection, Genetics and Evolution en_US
dc.citation.volume 3 en_US
dc.citation.pages 287-292 en_US
dc.identifier.pmid http://www.ncbi.nlm.nih.gov/pubmed/14636690
dc.citation.jabbreviation Infect Genet Evol en_US


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