1. Studies on antimalarial drug susceptibility in Colombia, in relation to Pfmdr1 and Pfcrt.
- Author
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Restrepo-Pineda E, Arango E, Maestre A, Do Rosário VE, and Cravo P
- Subjects
- Amodiaquine analogs & derivatives, Amodiaquine pharmacology, Animals, Chloroquine pharmacology, Colombia epidemiology, Humans, Malaria, Falciparum epidemiology, Malaria, Falciparum parasitology, Mefloquine pharmacology, Parasitic Sensitivity Tests, Plasmodium falciparum genetics, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Antimalarials pharmacology, Drug Resistance genetics, Membrane Transport Proteins genetics, Multidrug Resistance-Associated Proteins genetics, Plasmodium falciparum drug effects, Polymorphism, Single Nucleotide, Protozoan Proteins genetics
- Abstract
In Colombia, Plasmodium resistance to antimalarials such as chloroquine and antifolates is a serious problem. As a result, the national Colombian health authorities are monitoring the efficacy of alternative drugs and schemes. The study of genetic polymorphisms related with drug resistance is required in the region. In vitro responses to chloroquine, quinine, mefloquine, amodiaquine, desethylamodiaquine, artesunate and dihydroartesunate were carried out by HRP ELISA. SNP analysis in Pfcrt and Pfmdr1 genes was performed by PCR-RFLP in 77 samples from the North West region of Colombia. In vitro resistance to chloroquine was high (74%), followed by mefloquine (30%) and desethylamodiaquine (30%). A positive correlation between the IC(50) of paired drugs was also detected. The allele Pfmdr1 N86 (wild) was present in 100% of the samples and 1246Y (mutant) in 92%. However, their presence did not correlate with in vitro drug resistance. Presence of the mutations K76T and N75E in Pfcrt was confirmed in all samples. Analysis of 4 codons (72, 74, 75 and 76) in pfcrt confirmed the presence of the haplotypes CMET in 91% and SMET in 9% of the samples.
- Published
- 2008
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