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dc.contributor.authorNitchakarn Noranateen_US
dc.contributor.authorRémy Duranden_US
dc.contributor.authorAdama Tallen_US
dc.contributor.authorLaurence Marramaen_US
dc.contributor.authorAndré Spiegelen_US
dc.contributor.authorCheikh Sokhnaen_US
dc.contributor.authorBruno Pradinesen_US
dc.contributor.authorSandrine Cojeanen_US
dc.contributor.authorMicheline Guillotteen_US
dc.contributor.authorEmmanuel Bischoffen_US
dc.contributor.authorMarie Théreèse Ekalaen_US
dc.contributor.authorChristiane Bouchieren_US
dc.contributor.authorThierry Fandeuren_US
dc.contributor.authorFrédéric Arieyen_US
dc.contributor.authorJintana Patarapotikulen_US
dc.contributor.authorJacques Le Brasen_US
dc.contributor.authorJean François Trapeen_US
dc.contributor.authorChristophe Rogieren_US
dc.contributor.authorOdile Mercereau-Puijalonen_US
dc.contributor.otherCNRS Centre National de la Recherche Scientifiqueen_US
dc.contributor.otherHopital Avicenneen_US
dc.contributor.otherInstitut Pasteur de Dakaren_US
dc.contributor.otherInstitut de Recherche pour le Developpement Dakaren_US
dc.contributor.otherIMTSSA Institut de Medecine Tropicale du Service de Sante des Armeesen_US
dc.contributor.otherUniversite Paris Descartesen_US
dc.contributor.otherInstitut Pasteur du Cambodgeen_US
dc.contributor.otherMahidol Universityen_US
dc.identifier.citationPLoS ONE. Vol.2, No.1 (2007)en_US
dc.description.abstractBackground. Inadequate treatment practices with antimalarials are considered major contributors to Plasmodium falciparum resistance to chloroquine, pyrimethamine and sulfadoxine. The longitudinal survey conducted in Dielmo, a rural Senegalese community, offers a unique frame to explore the impact of strictly controlled and quantified antimalarial use for diagnosed malaria on drug resistance. Methodology/Principal Findings. We conducted on a yearly basis a retrospective survey over a ten-year period that included two successive treatment policies, namely quinine during 1990-1994, and chloroquine (CQ) and sulfadoxine/pyrimethamine (SP) as first and second line treatments, respectively, during 1995-1999. Molecular beacon-based genotyping, gene sequencing and microsatellite analysis showed a low prevalence of Pfcrt and Pfdhfr-ts resistance alleles of Southeast Asian origin by the end of 1994 and their effective dissemination within one year of CQ and SP implementation. The Pfcrt resistant allele rose from 9% to 46% prevalence during the first year of CQ reintroduction, i.e., after a mean of 1.66 CQ treatment courses/person/year. The Pfdhfr-ts triple mutant rose from 0% to 20% by end 1996, after a mean of 0.35 SP treatment courses/person in a 16-month period. Both resistance alleles were observed at a younger age than all other alleles. Their spreading was associated with enhanced in vitro resistance and rapidly translated in an increased incidence of clinical malaria episodes during the early post-treatment period. Conclusion/Significance. In such a highly endemic setting, selection of drug-resistant parasites took a single year after drug implementation, resulting in a rapid progression of the incidence of clinical malaria during the early post-treatment period. Controlled antimalarial use at the community level did not prevent dissemination of resistance haplotypes. This data pleads against reintroduction of CQ in places where resistant allele frequency has dropped to a very low level after CQ use has been discontinued, unless drastic measures are put in place to prevent selection and spreading of mutants during the post-treatment period. © 2007 Noranate et al.en_US
dc.rightsMahidol Universityen_US
dc.subjectAgricultural and Biological Sciencesen_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.titleRapid dissemination of Plasmodium falciparum drug resistance despite strictly controlled antimalarial useen_US
Appears in Collections:Scopus 2006-2010

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