A Leishmania infantum genetic marker associated with miltefosine treatment failure for visceral leishmaniasis.

ABSTRACT:

Background

Miltefosine has been used successfully to treat visceral leishmaniasis (VL) in India, but it was unsuccessful for VL in a clinical trial in Brazil.

Methods

To identify molecular markers that predict VL treatment failure whole genome sequencing of 26 L. infantum isolates, from cured and relapsed patients allowed a GWAS analysis of SNPs, gene and chromosome copy number variations.

Findings

A strong association was identified (p = 0·0005) between the presence of a genetically stable L. infantumMiltefosine Sensitivity Locus (MSL), and a positive response to miltefosine treatment. The risk of treatment failure increased 9·4-fold (95% CI 2·11-53·54) when an isolate did not have the MSL. The complete absence of the MSL predicted miltefosine failure with 0·92 (95%

SUBMITTER: Carnielli JBT 

PROVIDER: S-EPMC6197651 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature