title: Haplotypes associated with resistance to sulfadoxine-pyrimethamine in Plasmodium falciparum in two malaria endemic locations in Colombia.
abstract: Colombia has four main malaria transmission zones. In vivo efficacy studies carried out in these areas showed big differences in the response of Plasmodium falciparum to treatment with sulphadoxine-pyrimethamine. In addition, there is still insufficient information about the genetics of P. falciparum populations. The objective of this study was to determine the haplotypes in dhfr and dhps genes of P. falciparum circulating in two distinct endemic zones. Samples from patients with non-complicated P. falciparum malaria were collected: 135 from Tumaco and 206 from Tierralta. Alleles 108 and 51 of the dhfr gene, and 437 and 540 of the dhps gene were analyzed by PCR/enzymatic restriction, while alleles 59 and 164 (dhfr), and 581(dhps) by PCR/dot blot/hybridization. Five different haplotypes were found, of which the triple mutant 51I/C59/108N/I164/437G/K540/A581 was the most frequent (54.6%). In Tumaco, the parasites with wild haplotype predominated, while mutant parasites predominated in Tierralta. Another interesting finding is the presence of the C59R mutation in the dhfr gene in two samples, a mutation rarely found in South America. These data provide information about parasite population genetics and highlight the importance of starting a long term molecular surveillance program.
authors.affiliation: Grupo de Bioquímica y Biología Celular, Instituto Nacional de Salud, Bogotá, Colombia.
authors.forename: Diana Carolina
authors.initials: DC
authors.lastname: Hernández
authors.forename: Angela Patricia
authors.initials: AP
authors.lastname: Guerra
authors.forename: Zulma Milena
authors.initials: ZM
authors.lastname: Cucunubá
authors.forename: Ruben Santiago
authors.initials: RS
authors.lastname: Nicholls
authors.forename: Sandra Milena
authors.initials: SM
authors.lastname: Barrera
mesh_terms: D000328:Adult; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D003105:Colombia; D004094:Dihydropteroate Synthase / Q000235:genetics; D004338:Drug Combinations; D004351:Drug Resistance; D019353:Endemic Diseases; D005260:Female; D017125:Genes, Protozoan; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology; D008297:Male; D009154:Mutation / Q000235:genetics; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D011739:Pyrimethamine / Q000494:pharmacology* / Q000627:therapeutic use; D013413:Sulfadoxine / Q000494:pharmacology* / Q000627:therapeutic use; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine
keywords: Colombia; Haplotypes; Mutations; Plasmodium falciparum; dhfr; dhps