Alelos mutantes asociados a la resistencia a cloroquina y sulfadoxina-pirimetamina en Plasmodium falciparum de las fronteras Ecuador-Perú y Ecuador-Colombia

Abstract

RESUMENSe evaluó la frecuencia de mutaciones en los genes pfCRT y DHFR/DHPS del Plasmodium falciparum asociados a la resistencia a cloroquina y sulfadoxina-pirimetamina en 83 cepas provenientes de los distritos Esmeralda y Machala ubicados en las fronteras entre Ecuador-Perú y Ecuador-Colombia durante el año 2002. Se empleó la reacción en cadena de polimerasa (PCR) convencional y sus variantes. El gen pfCRT presentó más de 90% de muestras mutantes en Esmeralda y Machala. Para el gen DHFR, el 90% de las cepas fueron muestras mutantes en Esmeralda, tres fueron mutaciones dobles y una triple; en Machala se encontró 25% de formas mutantes simples y 75% de formas mixtas (formas silvestres/mutantes). En conclusión, la resistencia a cloroquina se ha fijado en las cepas portadoras de la mutación K76T pfCRT, mientras que la impronta genética a la resistencia a pirimetamina está en evolución, principalmente en el distrito de Esmeralda.Palabras clave: Plasmodium falciparum; Resistencia bacteriana a fármacos; Cloroquina; Sulfadoxina; Pirimetamina (fuente: DeCS BIREME) MUTANT ALLELES ASSOCIATED TO CHLOROQUINE AND SULFADOXINE-PYRIMETHANIME RESISTANCE IN Plasmodium falciparum OF THE ECUADOR-PERU AND ECUADOR-COLOMBIA BORDERS ABSTRACTThe frequency of mutations in pfCRT and DHFR/DHPS genes of Plasmodium falciparum associated with resistance to chloroquine and sulfadoxine-pyrimethamine was evaluated in 83 strains from the districts of Esmeralda and Machala, located on the borders of Ecuador-Peru and Ecuador-Colombia in 2002. Polymerase chain reaction (PCR), conventional and its variants, was used. Mutations in the pfCRT gene were found in more than 90% of the samples from Esmeralda and Machala. For the DHFR gene, 90% of the strains were mutant samples from Esmeralda, 3 were double mutations and 1 was a triple mutation. In Machala, 25% were simple mutant forms and 75% mixed mutant forms (wild forms/mutant). In conclusion, resistance to chloroquine has been fixed in strains carrying K76T pfCRT mutation, whereas genetic imprinting for resistance to pyrimethamine is evolving, particularly in the district of Esmeralda.

Genotypes and phenotypes of resistance in Ecuadorian Plasmodium falciparum

“…The genotype with a simple mutation in position 108 (CNC N I) was only found in San Lorenzo county. These genotypes have previously been reported in Ecuador [25], Colombia [8] and Peru [10]. The C I C N I resistance genotype was found in San Lorenzo county and Orellana; Peru, Colombia and Brazil have also reported this genotype [8, 9].…”

“…The wild type genotype was previously found in samples from Esmeraldas in 2002 and 2013. No mutations in Pfdhps have ever been previously reported in Ecuador [25, 26].…”

“…In 2002, studies from Ecuador reported mutations in isolates collected in Esmeraldas. The parasites presented the CVMN T Pfcrt genotype and one, (position 108 N ) two (positions 108 N , 164 L ) or three (51 I , 108 N , 164 L ) mutations in Pfdhfr [25]. In 2013, parasite isolates showed wild type genotypes for Pfdhfr and Pfdhps , the CVMN T and CVM ET Pfcrt genotypes, and the mutations Y184 F and N1042 D in Pfmdr1 in an outbreak that occurred in Esmeraldas [26].…”

Clonal population expansion in an outbreak of Plasmodium falciparum on the northwest coast of Ecuador

“…However, three of these parasites differed from this outbreak samples in the chromosomal 10 locus 2490 and two differed in the chromosomal 6 locus TA109. While mostly CVMNK and CVMNT genotypes of pfcrt have been reported in Ecuador [ 33 ], Colombian parasites have been reported to be CVMET genotype [ 34 ]. Since there was no availability of parasite specimens from the index case(s), it was not possible to link the genetic data obtained with travel history information.…”

“…Ecuador changed its P. falciparum anti-malarial treatment policy in 2006, switching from chloroquine (CQ) to artesunate-sulfadoxine-pyrimethamine (AS-SP) and recently to artemether-lumefantrine (AL) [ 33 , 36 ]. It is important to note that even though the P. falciparum parasites from the outbreak have a CQ-resistant haplotype (CVMNT and CVMET), they carried wild type dhfr and dhps gentotypes associated with SP sensitivity.…”