title: pfcrt Polymorphism and the spread of chloroquine resistance in Plasmodium falciparum populations across the Amazon Basin.
abstract: The widespread occurrence of drug-resistant malaria parasites in South America presents a formidable obstacle to disease control in this region. To characterize parasite populations and the chloroquine-resistance profile of Plasmodium falciparum in the Amazon Basin, we analyzed a DNA segment of the pfcrt gene, spanning codons 72-76, and genotyped 15 microsatellite (MS) markers in 98 isolates from 6 areas of Brazil, Peru, and Colombia where malaria is endemic. The K76T mutation, which is critical for chloroquine resistance, was found in all isolates. Five pfcrt haplotypes (S[tct]MNT, S[agt]MNT, CMNT, CMET, and CIET) were observed, including 1 previously found in Asian/African isolates. MS genotyping showed relatively homogeneous genetic backgrounds among the isolates, with an average of 3.8 alleles per marker. Isolates with identical 15-loci MS haplotypes were found in different locations, suggesting relatively free gene flow across the Amazon Basin. Allopatric isolates carrying SMNT and CMNT haplotypes have similar genetic backgrounds, although parasites carrying the CIET haplotype have some exclusive MS alleles, suggesting that parasites with CIET alleles were likely to have been introduced into Brazil from Asia or Africa. This study provides the first evidence of the Asian pfcrt allele in Brazil and a detailed analysis of P. falciparum populations, with respect to pfcrt haplotypes, in the Amazon Basin.
authors.affiliation: Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), Ilha do Fundao, Rio de Janeiro, Gerencia de Malaria, Fundacao de Medicina Tropical do Amazonas, Manaus, Brazil.
authors.forename: Pedro Paulo
authors.initials: PP
authors.lastname: Vieira
authors.forename: Marcelo Urbano
authors.initials: MU
authors.lastname: Ferreira
authors.forename: Maria das Gracas
authors.initials: Md
authors.lastname: Alecrim
authors.forename: Wilson D
authors.initials: WD
authors.lastname: Alecrim
authors.forename: Luiz Hidelbrando P
authors.initials: LH
authors.lastname: da Silva
authors.forename: Moises M
authors.initials: MM
authors.lastname: Sihuincha
authors.forename: Deirdre A
authors.initials: DA
authors.lastname: Joy
authors.forename: Jianbing
authors.initials: J
authors.lastname: Mu
authors.forename: Xin-Zhuan
authors.initials: XZ
authors.lastname: Su
authors.forename: Mariano G
authors.initials: MG
authors.lastname: Zalis
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D001938:Brazil / Q000453:epidemiology; D002738:Chloroquine / Q000494:pharmacology*; D016054:DNA, Protozoan / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification; D004351:Drug Resistance / Q000235:genetics*; D019353:Endemic Diseases; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000469:parasitology*; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D018895:Microsatellite Repeats; D017720:Molecular Epidemiology; D020125:Mutation, Missense; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA; D013020:South America
chemical_list: D000962:Antimalarials; D016054:DNA, Protozoan; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine