title: Rapid selection of Plasmodium falciparum chloroquine resistance transporter gene and multidrug resistance gene-1 haplotypes associated with past chloroquine and present artemether-lumefantrine use in Inhambane District, southern Mozambique.
abstract: Chloroquine (CQ) use in Mozambique was stopped in 2002 and artemether-lumefantrine (AL) was implemented in 2008. In light of no use of CQ and extensive use of AL, we determined the frequency of molecular markers of Plasmodium falciparum drug resistance/tolerance to CQ and AL in persons living in Linga-Linga, an isolated peninsula and in Furvela village, which is located 8 km inland. The P. falciparum chloroquine resistance transporter gene CVMNK wild type increased in frequency from 43.9% in 2009 to 66.4% in 2010 (P ≤ 0.001), and combined P. falciparum multidrug resistance gene 1 N86-184F-D1246 haplotype increased significantly between years (P = 0.039). The combination of P. falciparum chloroquine resistance transporter gene CVMNK and P. falciparum multidrug resistance gene NFD increased from 24.3% (2009) to 45.3% in (2010, P = 0.017). The rapid changes observed may largely be caused by decreased use of CQ and large-scale use of AL. In the absence of a clear AL-resistance marker and the (almost) continent-wide use of AL in sub-Saharan Africa, and when considering CQ reintroduction, continued monitoring of these markers is needed.
authors: Section for Functional Genomics, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark. thomas.thomsen@bio.ku.dk
authors: Thomas T
authors: TT
authors: Thomsen
authors: Laura B
authors: LB
authors: Madsen
authors: Helle H
authors: HH
authors: Hansson
authors: Elsa V E
authors: EV
authors: Tomás
authors: Derek
authors: D
authors: Charlwood
authors: Ib C
authors: IC
authors: Bygbjerg
authors: Michael
authors: M
authors: Alifrangis
mesh_terms: D000962:Antimalarials / Q000494:pharmacology; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage / Q000627:therapeutic use*; D002738:Chloroquine / Q000494:pharmacology / Q000627:therapeutic use*; D016054:DNA, Protozoan / Q000235:genetics; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics*; D004983:Ethanolamines / Q000008:administration & dosage / Q000627:therapeutic use*; D005449:Fluorenes / Q000008:administration & dosage / Q000627:therapeutic use*; D006239:Haplotypes; D006801:Humans; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000469:parasitology; D026901:Membrane Transport Proteins; D009073:Mozambique / Q000453:epidemiology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D015800:Protozoan Proteins; D012641:Selection, Genetic; D013997:Time Factors
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D002738:Chloroquine; D016054:DNA, Protozoan; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; C513498:Mdr1 protein, Plasmodium falciparum; C416369:PfCRT protein, Plasmodium falciparum
references: J Infect Dis. 2009 Mar 1;199(5):750-7
references: 19210165
references: Lancet. 2012 May 26;379(9830):1960-6
references: 22484134
references: Mol Cell. 2000 Oct;6(4):861-71
references: 11090624
references: Malar J. 2008 Jul 01;7:115
references: 18590577
references: Am J Trop Med Hyg. 2012 Oct;87(4):640-645
references: 22927495
references: PLoS One. 2011;6(10):e25992
references: 22022487
references: Trop Med Int Health. 2004 Feb;9(2):200-8
references: 15040556
references: N Engl J Med. 2009 Jul 30;361(5):455-67
references: 19641202
references: Clin Infect Dis. 2010 Dec 1;51(11):e82-9
references: 21028985
references: N Engl J Med. 2006 Nov 9;355(19):1959-66
references: 17093247
references: Acta Trop. 2012 Jan;121(1):50-4
references: 21996622
references: Science. 2004 Aug 20;305(5687):1124
references: 15326348
references: Mol Microbiol. 2000 May;36(4):955-61
references: 10844681
references: Am J Trop Med Hyg. 2009 Apr;80(4):523-7
references: 19346369
references: N Engl J Med. 2008 Dec 11;359(24):2619-20
references: 19064625
references: Am J Trop Med Hyg. 2005 Feb;72(2):155-62
references: 15741552
references: Malar J. 2003 Sep 19;2:31
references: 14599295
references: Med Vet Entomol. 2011 Sep;25(3):240-6
references: 21073491
references: Infect Genet Evol. 2011 Mar;11(2):512-7
references: 21251998
references: J Infect Dis. 2011 Oct 1;204(7):1120-4
references: 21881128
references: N Engl J Med. 2001 Jan 25;344(4):257-63
references: 11172152
references: J Infect Dis. 2003 Jun 15;187(12):1870-5
references: 12792863
references: Malar J. 2003 Feb 17;2:2
references: 12636875
references: Acta Trop. 2012 Feb;121(2):148-51
references: 22118982
references: Lancet. 1985 Oct 19;2(8460):897-8
references: 2864613
references: J Infect Dis. 2001 May 1;183(9):1413-6
references: 11294676
references: Acta Trop. 2012 Sep;123(3):202-7
references: 22641431
references: Malar J. 2009 May 18;8:106
references: 19450282
references: J Vector Ecol. 2011 Dec;36(2):382-94
references: 22129410
references: Malar J. 2006 Apr 26;5:34
references: 16638153
references: Antimicrob Agents Chemother. 2007 Mar;51(3):991-7
references: 17194834
references: Nature. 2002 Jul 18;418(6895):320-3
references: 12124623
references: Lancet. 2003 Apr 5;361(9364):1174-81
references: 12686039
references: Am J Trop Med Hyg. 2011 Dec;85(6):979-83
references: 22144430
references: Malar J. 2011 May 09;10:116
references: 21554692
references: Acta Trop. 2005 Jun;94(3):251-9
references: 15845348