Adaptive evolution of malaria parasites in French Guiana: Reversal of chloroquine resistance by acquisition of a mutation in pfcrt

In regions with high malaria endemicity, the withdrawal of chloroquine (CQ) as first-line treatment ofPlasmodium falciparuminfections has typically led to the restoration of CQ susceptibility through the reexpansion of the wild-type (WT) allele K76 of the chloroquine resistance transporter gene (pfc...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2015-09, Vol.112 (37), p.11672-11677
Hauptverfasser: Pelleau, Stéphane, Moss, Eli L., Dhingra, Satish K., Volney, Béatrice, Casteras, Jessica, Gabryszewski, Stanislaw J., Volkman, Sarah K., Wirth, Dyann F., Legrand, Eric, Fidock, David A., Neafsey, Daniel E., Musset, Lise
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Sprache:eng
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Zusammenfassung:In regions with high malaria endemicity, the withdrawal of chloroquine (CQ) as first-line treatment ofPlasmodium falciparuminfections has typically led to the restoration of CQ susceptibility through the reexpansion of the wild-type (WT) allele K76 of the chloroquine resistance transporter gene (pfcrt) at the expense of less fit mutant alleles carrying the CQ resistance (CQR) marker K76T. In low-transmission settings, such as South America, drug resistance mutations can attain 100% prevalence, thereby precluding the return of WT parasites after the complete removal of drug pressure. In French Guiana, despite the fixation of the K76T allele, the prevalence of CQR isolates progressively dropped from >90% to
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1507142112