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Assessment of drug resistance related genes as candidate markers for treatment outcome prediction of cutaneous leishmaniasis in Brazil.

Authors :
Torres DC
Ribeiro-Alves M
Romero GA
Dávila AM
Cupolillo E
Source :
Acta tropica [Acta Trop] 2013 May; Vol. 126 (2), pp. 132-41. Date of Electronic Publication: 2013 Feb 12.
Publication Year :
2013

Abstract

The great public health problem posed by leishmaniasis has substantially worsened in recent years by the emergence of clinical failure. In Brazil, the poor prognosis observed for patients infected by Leishmania braziliensis (Lb) or L. guyanensis (Lg) may be related to parasite drug resistance. In the present study, 19 Lb and 29 Lg isolates were obtained from infected patients with different treatment outcomes. Translated amino acid sequence polymorphisms from four described antimony resistance related genes (AQP1, hsp70, MRPA and TRYR) were tested as candidate markers for antimonial treatment failure prediction. Possibly due to the low intraspecific variability observed in Lg samples, none of the prediction models had good prognosis values. Most strikingly, one mutation (T579A) found in hsp70 of Lb samples could predict 75% of the antimonial treatment failure clinical cases. Moreover, a multiple logistic regression model showed that the change from adenine to guanine at position 1735 of the hsp70 gene, which is responsible for the T579A mutation, significantly increased the chance of Lb clinical isolates to be associated with treatment failure (OR=7.29; CI 95%=[1.17, 45.25]; p=0.0331). The use of molecular markers to predict treatment outcome presents practical and economic advantages as it allows the development of rapid assays to monitor the emergence of drug resistant parasites that can be clinically applied to aid the prognosis of cutaneous leishmaniasis in Brazil.<br /> (Copyright © 2013 Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1873-6254
Volume :
126
Issue :
2
Database :
MEDLINE
Journal :
Acta tropica
Publication Type :
Academic Journal
Accession number :
23416123
Full Text :
https://doi.org/10.1016/j.actatropica.2013.02.002