Sensibilidad al benzonidazol de cepas de Trypanosoma cruzi sugiere la circulación de cepas naturalmente resistentes en Colombia

Abstract

Introducción. La enfermedad de Chagas, causada por Trypanosoma cruzi, es uno de los problemas más graves de salud pública en el continente americano. El benzonidazol es uno de los dos medicamentos utilizados para tratar la enfermedad de Chagas. Sin embargo, la variación de la sensibilidad del parásito a este medicamento es una de las principales causas del fracaso del tratamiento. Objetivo. Evaluar la sensibilidad in vitro al benzonidazol de cepas colombianas de T. cruzi de diferentes orígenes y procedencia geográfica. Materiales y métodos. Treinta y tres cepas colombianas de T. cruzi aisladas de humanos, vectores y mamíferos, se analizaron in vitro mediante el micrométodo enzimático de MTT para determinar la concentración inhibitoria 50 (CI 50 ) al benzonidazol. Se estudió la correlación entre la sensibilidad in vitro al medicamento y diferentes parámetros biológicos y eco-epidemiológicos. Resultados. El análisis de sensibilidad al medicamento indicó que el 36 % de las cepas eran sensibles, el 48 %, parcialmente resistentes y, el 16 %, resistentes al benzonidazol. Los análisis de correlación entre las CI 50 con algunos parámetros biológicos y eco-epidemiológicos, mostraron diferencias en cuanto a la sensibilidad según el origen biológico y el área geográfica de procedencia de la cepa. Conclusiones. Existe una gran variabilidad en cuanto a la sensibilidad al benzonidazol de las cepas circulantes de T. cruzi en Colombia, lo cual sugiere la presencia de cepas naturalmente resistentes en el país. Palabras clave:Trypanosoma cruzi, enfermedad de Chagas/terapia, inmunidad innata, Colombia. Trypanosoma cruzi strains resistant to benznidazole occurring in ColombiaIntroduction. Chagas disease caused by Trypanosoma cruzi is one of the most serious public health problems in the Americas. Benznidazole is one of two drugs used to treat Chagas' disease. However, the variation in susceptibility of the parasite to this drug is one of the main causes of treatment failure. Objective. The in vitro susceptibility to benznidazole was assessed in Colombian strains of T. cruzi from several sources and geographical regions. Materials and methods. Thirty-three Colombian T. cruzi strains were isolated from humans, vectors and mammals. These were analyzed in vitro by the MTT enzymatic micromethod to determine the IC 50 to benznidazole. Additionally, the in vitro susceptibility was correlated with several biological and ecoepidemiological parameters. Results. Thirty-six percent of the strains were considered to be sensitive, 48% partially resistant, and 16% were resistant. Correlations between the IC 50 and several biological and eco-epidemiological parameters indicated that differences in susceptibility depended on the biological source and geographical origin of the strain. Conclusions. A high degree of variability exists in the susceptibility to benznidazole of T. cruzi strains in Colombia. The distribution data indicate the presence and circulation of naturally resistant strains.

Untangling the transmission dynamics of primary and secondary vectors of Trypanosoma cruzi in Colombia: parasite infection, feeding sources and discrete typing units

“…5a). All these findings could be a signal of an intrusive process from sylvatic ecotopes to domestic ones facilitated by adaptation, occurring in parallel in Colombia, Venezuela and Brazil [42–45], even accompanied by morphological changes in insects [54, 55]. This pattern of ecotope intrusion explains the incrimination of P. geniculatus in oral outbreaks in Colombia [28, 56]; it is mandatory that surveillance strategies are deployed not only to avoid incrimination but also a possible domiciliation process.…”

Transcriptome and Functional Genomics Reveal the Participation of Adenine Phosphoribosyltransferase in Trypanosoma cruzi Resistance to Benznidazole

“…T. cruzi parasites from the DA strain (MHOM/COL/DA) (TcI) were used in this study. DA was isolated from a human who had never received treatment with Bz; the strain was classified as resistant according to Mejía‐Jaramillo et al [], with an IC 50 to Bz of 32.7 μM. The DA strain was cloned using the single cell cycling mode of a MOFLO XDP cell sorter (Beckman Coulter, Ontario, CA) with 97% performance.…”

Aldo‐keto reductase and alcohol dehydrogenase contribute to benznidazole natural resistance in Trypanosoma cruzi

“…In this work, we used two clones isolated from a T . cruzi strain that was previously classified as Bz‐resistant (Mejía‐Jaramillo et al ., ). Interestingly, these two clones showed different EC 50 to Bz but similar genetic backgrounds and slight differences in some biological features.…”