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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Rapid dissemination of Plasmodium falciparum drug resistance despite strictly controlled antimalarial use
PLoS ONE, Volume 2, No. 1, Article e139, Year 2007
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Description
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.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC1764034/bin/pone.0000139.s001.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC1764034/bin/pone.0000139.s002.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC1764034/bin/pone.0000139.s003.pdf
Authors & Co-Authors
Noranate, Nitchakarn
France, Paris
Cnrs Centre National de la Recherche Scientifique
Thailand, Nakhon Pathom
Mahidol University
Durand, Rémy
France, Bobigny
Hopital Avicenne
Tall, Adama
Senegal, Dakar
Institut Pasteur de Dakar
Marrama, Laurence
Senegal, Dakar
Institut Pasteur de Dakar
Spiegel, André
Senegal, Dakar
Institut Pasteur de Dakar
Sokhna, Cheikh Sadibou
Senegal, Dakar
Institut de Recherche Pour le Développement Dakar
Pradines, Bruno
France, Marseille
Imtssa Institut de Médecine Tropicale du Service de Santé Des Armées
Cojean, Sandrine
France, Paris
Université Paris Cité
Guillotte, Micheline
France, Paris
Cnrs Centre National de la Recherche Scientifique
Bischoff, Emmanuel
France, Paris
Cnrs Centre National de la Recherche Scientifique
Ekala, Marie Thérèse
France, Paris
Cnrs Centre National de la Recherche Scientifique
Bouchier, Christiane
France, Paris
Institut Pasteur, Paris
Fandeur, Thierry
Cambodia, Phnom Penh
Institut Pasteur du Cambodge
Ariey, Frédéric
Cambodia, Phnom Penh
Institut Pasteur du Cambodge
Patarapotikul, Jintana
Thailand, Nakhon Pathom
Mahidol University
Le Bras, Jacques L.
France, Paris
Université Paris Cité
Trape, Jean François
Senegal, Dakar
Institut de Recherche Pour le Développement Dakar
Rogier, Christophe
Senegal, Dakar
Institut Pasteur de Dakar
France, Marseille
Imtssa Institut de Médecine Tropicale du Service de Santé Des Armées
Mercereau-Puijalon, Odile
France, Paris
Cnrs Centre National de la Recherche Scientifique
Statistics
Citations: 67
Authors: 19
Affiliations: 9
Identifiers
Doi:
10.1371/journal.pone.0000139
e-ISSN:
19326203
Research Areas
Genetics And Genomics
Infectious Diseases
Study Design
Cross Sectional Study
Cohort Study
Study Approach
Quantitative