Development and appliation of cellular and molecular tools for monitoring miltefosine resistance in Leishmania donovani isolates from Nepal

Miltefosine (MIL) is being used as first line drug in the kala-azar elimination programme (KAEP) of the Indian sub-continent, but it is feared that parasite MIL resistance will emerge rapidly. Monitoring parasite resistance against MIL is therefore of crucial importance to guide VL drug policy. This requires simple and validated tools that are currently not available. The proposed PhD project aims to contribute to fill this gap. Two laboratory assays will be developed and evaluated with reference strains: (i) a cellular assay to test in vitro MIL-susceptibility of L. donovani and (ii) a molecular test to detect genetic markers associated with MIL resistance. Both assays will be simplified, standardized and transferred to BPKIHS (Dharan, Nepal). These tests will be applied on well-documented clinical isolates and samples which are currently collected from a cohort of Nepalese kala-azar patients treated with MIL at BPKHIS. The predictive value for MIL treatment outcome of both assays will be determined and their potential usefulness for epidemiological study of MIL resistance/MIL efficacy will be assessed accordingly. A report on the epidemiological dynamics of MIL resistance in Nepal will be produced. This project is embedded in an international and multidisciplinary initiative studying drug resistance and treatment response in Visceral Leishmaniasis in the Indian sub-continent (Kaladrug-R).

Trefwoorden:B780-tropische-geneeskunde