New tools for monitoring drug resistance and treatment response in visceral leishmaniasis in the Indian subcontinent

General

We aim to develop, evaluate and disseminate new tools for evaluation of drug resistance in L. donovani as well as innovative methodologies for monitoring Kala-Azar treatment effectiveness in routine conditions.

Specific

Develop an innovative approach for monitoring the effectiveness of Kala-Azar drug treatments in routine conditions (WP2: 48 months).Develop new tools for the assessment of natural resistance to MIL and SSG in L. donovani parasites. We will document the genomic background and molecular/biological mechanisms leading to natural resistance to MIL and SSG, establish the basis for simplified monitoring assays and evaluate their performance on clinical samples (WPs 5-7 and 9: 48 months).Recruit and follow-up cohorts of patients treated with MIL in India and Nepal, provide complete clinical documentation and obtain pre-treatment samples as well as samples from treatment failure for validation of the above mentioned assays (WPs 3-4: 36 months).Explore, in experimental conditions, pathways leading to parasite resistance to Paromomycin, a drug which is currently in phase IV (WP8: 48 months).Build models to understand the dynamics of the past spread of parasite SSG resistance as a model for resistance to MIL or future drugs (WPs 10 and 12: 24 and 36 months).Study the impact of drug resistance on the parasite fitness (WP11: 48 months).To get research results into policy at regional level and disseminate the generated knowledge and the validated tools in other regions in the world endemic for leishmaniasis (WPs 13-14: 48 months).