Variable gene expression and parasite load predict treatment outcome in cutaneous leishmaniasis

Area of Science:

• Immunology
• Genomics
• Infectious Diseases

Background:

• Leishmania braziliensis causes chronic cutaneous leishmaniasis lesions.
• Treatment failure is common with current antiparasite drugs.
• Gene expression variability in lesions may impact disease outcomes.

Purpose of the Study:

• Investigate if highly variable gene expression in lesions correlates with treatment outcomes.
• Identify specific genes and pathways linked to treatment failure.
• Develop a predictive marker for treatment response.

Main Methods:

• Transcriptomic profiling of lesion biopsies from patients before treatment.
• Correlation analysis between gene expression, parasite load, and treatment outcome.
• Validation of a predictive gene marker in independent patient cohorts.

Main Results:

• Identified highly variably expressed genes correlating with treatment outcomes.
• Found cytolytic pathway gene expression linked to parasite load and treatment failure.
• Developed a three-gene host-pathogen marker predicting treatment outcome with high accuracy.

Conclusions:

• Variable gene expression, particularly in the cytolytic pathway, predicts treatment failure in cutaneous leishmaniasis.
• A simple gene marker can identify patients likely to fail treatment before therapy begins.
• Findings support point-of-care diagnostics and precision medicine for improved leishmaniasis management.