Identification of immune mechanisms and genes associated with the high rate of relapse in patient with visceral leishmaniasis and HIV co-infections (360G-Wellcome-204797_Z_16_Z)

Visceral leishmaniasis (VL), a neglected tropical disease caused by Leishmania parasites, has emerged as an opportunistic infection in HIV patients. In Ethiopia, over a third of VL patients are co-infected with HIV. In contrast to VL patients, VL/HIV co-infected patients have a high rate of VL relapse after successful treatment. The mechanisms accounting for this increased relapse rate are poorly characterised. In the present study, I propose to identify immunological mechanisms and actively expressed genes that can be associated with frequent relapse in VL/HIV patients. To do this, I will recruit VL and VL/HIV patients from the Leishmaniasis Research and Treatment Center at the University of Gondar Hospital. Blood samples will be collected at time of diagnosis, at the end of anti-leishmanial treatment, and up to 12 months following cessation of treatment, in patients who relapse and those who don’t. I will measure neutrophil, monocyte and T-cell effector functions; furthermore, genome-wide transcript analysis from VL and VL/HIV patients will be used to identify transcripts of immune response pathways and functions that are differentially expressed in patients who relapse. The results of my work will contribute to a better understanding of the immunological mechanisms accounting for VL relapse in HIV/VL patients.