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Title: Rapid dissemination of Plasmodium falciparum drug resistance despite strictly controlled antimalarial use
Authors: Nitchakarn Noranate
Rémy Durand
Adama Tall
Laurence Marrama
André Spiegel
Cheikh Sokhna
Bruno Pradines
Sandrine Cojean
Micheline Guillotte
Emmanuel Bischoff
Marie Théreèse Ekala
Christiane Bouchier
Thierry Fandeur
Frédéric Ariey
Jintana Patarapotikul
Jacques Le Bras
Jean François Trape
Christophe Rogier
Odile Mercereau-Puijalon
CNRS Centre National de la Recherche Scientifique
Hopital Avicenne
Institut Pasteur de Dakar
Institut de Recherche pour le Developpement Dakar
IMTSSA Institut de Medecine Tropicale du Service de Sante des Armees
Universite Paris Descartes
Institut Pasteur du Cambodge
Mahidol University
Keywords: Agricultural and Biological Sciences;Biochemistry, Genetics and Molecular Biology
Issue Date: 3-Jan-2007
Citation: PLoS ONE. Vol.2, No.1 (2007)
Abstract: Background. 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.
ISSN: 19326203
Appears in Collections:Scopus 2006-2010

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