title: A cross-sectional survey of Plasmodium falciparum pfcrt mutant haplotypes in the Democratic Republic of Congo.
abstract: In the Democratic Republic of the Congo (DRC), artesunate-amodiaquine is first-line therapy for falciparum malaria; little is known about the prevalence of molecular markers of parasite drug resistance. Across the DRC, we genotyped 166 parasites in Plasmodium falciparum chloroquine resistance transporter (pfcrt) using polymerase chain reaction (PCR) and sequencing. Of these parasites, 73 (44%) parasites were pure wild-type CVMNK, 55 (31%) parasites were chloroquine-resistant CVIET: , 35 (21.1%) parasites were mixed CVMNK and CVIET: , and 3 parasites were other genotypes. Ninety-two infections (55.4%) harbored the pfcrt K76T: substitution that is highly correlated with chloroquine failure. The amodiaquine-resistant S: VMNT: haplotype was absent. Geographically, pfcrt haplotypes were not clearly clustered. Chloroquine accounted for 19.4% of antimalarial use, and amodiaquine accounted for 15.3% of antimalarial use; there were no associations between drug use and mutant haplotype prevalence. In the DRC, our molecular survey indicates that resistance to chloroquine is substantial but that resistance to amodiaquine is absent. These contrasting findings highlight the need for molecular surveillance of drug resistance to inform malaria control policies.
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina; Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina; Department of Geography, University of North Carolina, Chapel Hill, North Carolina; Carolina Population Center, University of North Carolina, Chapel Hill, North Carolina; Ecole de Sante Publique, Faculte de Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo.
authors.forename: Alejandro L
authors.initials: AL
authors.lastname: Antonia
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina; Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina; Department of Geography, University of North Carolina, Chapel Hill, North Carolina; Carolina Population Center, University of North Carolina, Chapel Hill, North Carolina; Ecole de Sante Publique, Faculte de Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo stevemyertaylor@gmail.com.
authors.forename: Steve M
authors.initials: SM
authors.lastname: Taylor
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina; Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina; Department of Geography, University of North Carolina, Chapel Hill, North Carolina; Carolina Population Center, University of North Carolina, Chapel Hill, North Carolina; Ecole de Sante Publique, Faculte de Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo.
authors.forename: Mark
authors.initials: M
authors.lastname: Janko
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina; Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina; Department of Geography, University of North Carolina, Chapel Hill, North Carolina; Carolina Population Center, University of North Carolina, Chapel Hill, North Carolina; Ecole de Sante Publique, Faculte de Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo.
authors.forename: Michael
authors.initials: M
authors.lastname: Emch
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina; Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina; Department of Geography, University of North Carolina, Chapel Hill, North Carolina; Carolina Population Center, University of North Carolina, Chapel Hill, North Carolina; Ecole de Sante Publique, Faculte de Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo.
authors.forename: Antoinette K
authors.initials: AK
authors.lastname: Tshefu
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina; Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina; Department of Geography, University of North Carolina, Chapel Hill, North Carolina; Carolina Population Center, University of North Carolina, Chapel Hill, North Carolina; Ecole de Sante Publique, Faculte de Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Meshnick
mesh_terms: D000655:Amodiaquine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D037621:Artemisinins / Q000494:pharmacology* / Q000627:therapeutic use; D002738:Chloroquine / Q000494:pharmacology* / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D015023:Democratic Republic of the Congo / Q000453:epidemiology; D004338:Drug Combinations; D004351:Drug Resistance; D005838:Genotype; D006239:Haplotypes; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000453:epidemiology*; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015995:Prevalence; D015800:Protozoan Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D016054:DNA, Protozoan; D004338:Drug Combinations; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; C515299:amodiaquine, artesunate drug combination; D000655:Amodiaquine; D002738:Chloroquine
references.citation: J Infect Dis. 2006 Jun 15;193(12):1738-41
references.pmid: 16703518
references.citation: Emerg Infect Dis. 2007 Jun;13(6):872-7
references.pmid: 17553226
references.citation: Malar J. 2009 May 04;8:89
references.pmid: 19413906
references.citation: J Clin Pharm Ther. 2007 Apr;32(2):123-32
references.pmid: 17381662
references.citation: Malar J. 2010 Dec 23;9:374
references.pmid: 21182787
references.citation: PLoS One. 2011 Jan 31;6(1):e16420
references.pmid: 21305011
references.citation: Malar J. 2012 May 25;11:174
references.pmid: 22631564
references.citation: Infect Genet Evol. 2006 Jul;6(4):262-8
references.pmid: 16154388
references.citation: PLoS One. 2012;7(8):e42284
references.pmid: 22912697
references.citation: Malar J. 2011 May 09;10:116
references.pmid: 21554692
references.citation: Malar J. 2010 Jun 18;9:174
references.pmid: 20565881
references.citation: Malar J. 2012 Apr 01;11:105
references.pmid: 22463364
references.citation: Antimicrob Agents Chemother. 2010 Sep;54(9):3714-6
references.pmid: 20547800
references.citation: Science. 2011 Aug 5;333(6043):724-9
references.pmid: 21817045
references.citation: Trop Med Int Health. 2003 Oct;8(10):868-75
references.pmid: 14516297
references.citation: J Infect Dis. 2011 Jan 15;203(2):228-36
references.pmid: 21288823
references.citation: J Infect Dis. 2010 Sep 1;202(5):801-8
references.pmid: 20662717
references.citation: Am J Trop Med Hyg. 2009 Apr;80(4):555-8
references.pmid: 19346374
references.citation: J Infect Dis. 2011 Jan 1;203(1):109-16
references.pmid: 21148503
references.citation: Science. 2002 Oct 4;298(5591):210-3
references.pmid: 12364805
references.citation: PLoS One. 2011;6(8):e23430
references.pmid: 21858115
references.citation: N Engl J Med. 2006 Nov 9;355(19):1959-66
references.pmid: 17093247