title: Polymorphisms in cg2 and pfcrt genes and resistance to chloroquine and other antimalarials in vitro in Plasmodium falciparum isolates from Colombia.
abstract: Polymorphisms in Plasmodium falciparum cg2 and pfcrt genes and their association with chloroquine resistance in vitro in Colombian parasites were evaluated in this study. Association of chloroquine resistance with resistance to other antimalarial drugs in vitro was also examined. Polymerase chain reactions (PCR) for kappa and omega cg2 regions and nested PCR and digestion with ApoI enzyme for K-76T pfcrt point mutation defined corresponding polymorphisms in 83 samples collected between 1995 and 1999. The isotopic microtest was used to evaluate sensitivity in vitro in a subgroup of 18 isolates. The predominant cg2 pattern observed was 13K/14omega repeats (46/83 [55.4%]) and all samples presented the K-76T mutant allele. Seventy-eight percent of samples were resistant to chloroquine in vitro, 35.3% to amodiaquine, 16.7% to mefloquine, and 5.6% to quinine. Significant correlations (P < 0.05) were observed between the IC50s of chloroquine and arteether, and among IC50s of arteether, mefloquine, and quinine. These results suggest the development of multiple and cross-resistance of Colombian P. falciparum isolates to second- and third-line antimalarials and new alternative drugs.
authors.affiliation: Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM), Avenida IN # 3-03, Cali, Colombia. cideim@cideim.org.co
authors.forename: Iveth J
authors.initials: IJ
authors.lastname: González
authors.forename: Rubén E
authors.initials: RE
authors.lastname: Varela
authors.forename: Claribel
authors.initials: C
authors.lastname: Murillo
authors.forename: Beatriz E
authors.initials: BE
authors.lastname: Ferro
authors.forename: Jenny
authors.initials: J
authors.lastname: Salas
authors.forename: Luis E
authors.initials: LE
authors.lastname: Giraldo
authors.forename: Mariano G
authors.initials: MG
authors.lastname: Zalis
authors.forename: Nancy G
authors.initials: NG
authors.lastname: Saravia
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology*; D016054:DNA, Protozoan / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000235:genetics; D017125:Genes, Protozoan; D005819:Genetic Markers; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008826:Microbial Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics*
chemical_list: D000962:Antimalarials; C109422:CG2 protein, Plasmodium falciparum; D016054:DNA, Protozoan; D005819:Genetic Markers; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine