Trypanosoma cruzi benznidazole susceptibility in vitro does not predict the therapeutic outcome of human Chagas disease
Mem. Inst. Oswaldo Cruz
; 105(7): 918-924, Nov. 2010. graf, tab
Article
en En
| LILACS
| ID: lil-566184
Biblioteca responsable:
BR1.1
ABSTRACT
Therapeutic failure of benznidazole (BZ) is widely documented in Chagas disease and has been primarily associated with variations in the drug susceptibility of Trypanosoma cruzi strains. In humans, therapeutic success has been assessed by the negativation of anti-T. cruzi antibodies, a process that may take up to 10 years. A protocol for early screening of the drug resistance of infective strains would be valuable for orienting physicians towards alternative therapies, with a combination of existing drugs or new anti-T. cruzi agents. We developed a procedure that couples the isolation of parasites by haemoculture with quantification of BZ susceptibility in the resultant epimastigote forms. BZ activity was standardized with reference strains, which showed IC50 to BZ between 7.6-32 µM. The assay was then applied to isolates from seven chronic patients prior to administration of BZ therapy. The IC50 of the strains varied from 15.6 ± 3-51.4 ± 1 µM. Comparison of BZ susceptibility of the pre-treatment isolates of patients considered cured by several criteria and of non-cured patients indicates that the assay does not predict therapeutic outcome. A two-fold increase in BZ resistance in the post-treatment isolates of two patients was verified. Based on the profile of nine microsatellite loci, sub-population selection in non-cured patients was ruled out.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
LILACS
Asunto principal:
Tripanocidas
/
Trypanosoma cruzi
/
Enfermedad de Chagas
/
Nitroimidazoles
Tipo de estudio:
Guideline
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Mem. Inst. Oswaldo Cruz
Asunto de la revista:
MEDICINA TROPICAL
/
PARASITOLOGIA
Año:
2010
Tipo del documento:
Article
Pais de publicación:
Brasil