Elsevier

Acta Tropica

Volume 126, Issue 2, May 2013, Pages 132-141
Acta Tropica

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

https://doi.org/10.1016/j.actatropica.2013.02.002Get rights and content
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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.

Graphical abstract

L. braziliensis hsp70 and MRPA translated amino acid sequences presented the best antimonial treatment outcome prediction models with up to 75% and 69% accuracy, respectively.

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Highlights

► Assessment of therapeutic outcome prediction for American cutaneous leishmaniasis. ► AQP1, MRPA, TRYR and hsp70 DNA sequencing allows L. (Viannia) species typing. ► L. braziliensis has higher intraspecific genetic variability than L. guyanensis. ► A to G change at position 1735 of hsp70 gene increased treatment failure chances. ► hsp70 of L. braziliensis showed the best treatment failure prediction model.

Keywords

Cutaneous leishmaniasis
Treatment failure
Molecular markers
Leishmania braziliensis
Leishmania guyanensis

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