| Autor: |
Muñoz-Calderón A; Laboratorio de Biología Molecular de la Enfermedad de Chagas, Instituto de Ingeniería Genética y Biología Molecular 'Dr. Héctor Torres', Buenos Aires CP1428ADN, Argentina., Ramírez JL; Centro de Biotecnología, Fundación Instituto de Estudios Avanzados, Caracas CP1080, Venezuela., Díaz-Bello Z; Instituto de Medicina Tropical 'Dr. Félix Pifano', Facultad de Medicina, Universidad Central de Venezuela, Caracas CP1050, Venezuela., Alarcón de Noya B; Instituto de Medicina Tropical 'Dr. Félix Pifano', Facultad de Medicina, Universidad Central de Venezuela, Caracas CP1050, Venezuela., Noya O; Instituto de Medicina Tropical 'Dr. Félix Pifano', Facultad de Medicina, Universidad Central de Venezuela, Caracas CP1050, Venezuela.; Centro de Estudios sobre Malaria, Instituto de Altos Estudios, Ministerio del Poder Popular para la Salud, Caracas CP1050, Venezuela., Schijman AG; Laboratorio de Biología Molecular de la Enfermedad de Chagas, Instituto de Ingeniería Genética y Biología Molecular 'Dr. Héctor Torres', Buenos Aires CP1428ADN, Argentina. |
| Abstrakt: |
The oral transmission of Chagas disease (oCD) in Venezuela announced its appearance in 2007. Different from other populations affected by oCD and despite close supervision during treatment with nitroheterocyclic drugs, the result was treatment failure. We studied genetic features of natural bloodstream parasite populations and populations after treatment of nine patients of this outbreak. In total, we studied six hemoculture isolates, eight Pre-Tx blood samples, and 17 samples collected at two or three Post-Tx time-points between 2007 and 2015. Parasitic loads were determined by quantitative polymerase chain reaction (qPCR), and discrete typing units (DTU), minicircle signatures, and Tcntr-1 gene sequences were searched from blood samples and hemocultures. Half-maximal inhibitory concentration (IC 50 ) values were measured from the hemocultures. All patients were infected by TcI. Significant decrease in parasitic loads was observed between Pre-Tx and Post-Tx samples, suggesting the evolution from acute to chronic phase of Chagas disease. 60% of intra-DTU-I variability was observed between Pre-Tx and Post-Tx minicircle signatures in the general population, and 43 single-nucleotide polymorphisms (SNPs) were detected in a total of 12 Tcntr-1 gene sequences, indicative of a polyclonal source of infection. SNPs in three post-Tx samples produced stop codons giving rise to putative truncated proteins or displaced open reading frames, which would render resistance genes. IC 50 values varied from 5.301 ± 1.973 to 104.731 ± 4.556 μM, demonstrating a wide range of susceptibility. The poor drug response in the Pre-Tx parasite populations may be associated with the presence of naturally resistant parasite clones. Therefore, any information that can be obtained on drug susceptibility from in vitro assays, in vivo assays, or molecular characterization of natural populations of Trypanosoma cruzi becomes essential when therapeutic guidelines are designed in a given geographical area. |
