Institute Of Post Graduate Medical Education And Research
ilatimc@gmail.com
Project Overview
Implementation of the kala-azar/Visceral leishmaniasis (VL) program in South East Asia has translated into a steady decline in the incidence of VL, with new cases reduced by 95%, and South-East Asia accounting for less than 20% of the global disease burden. India is now focused on addressing the last mile challenges that include the lack of ‘point of care’ tools to monitor interruption of transmission of kala-azar. In this regard, the strongest contender for transmission, are cases of Post kala azar dermal leishmaniasis (PKDL), a chronic dermatological condition that usually follows apparent cure of 2-10% cases of VL. The strategy for elimination includes active surveillance and treating more than 95% of PKDL patients. A key challenge faced by clinicians is the monitoring of PKDL, HIV-VL and VL relapse cases, all of whom can sustain transmission. The existing dip stick test cannot distinguish between present and past infections. The PI as a JC Bose Fellow (2020-2025) has established a robust molecular assay and aiming to establish as a field applicable assay using the Recombinase Polymerase Assay (RPA) technology. The PI has established a quantitative PCR based assay for diagnosis of Leprosy, which has found high acceptance with dermatologists. These molecular tests have a high degree of acceptance and the PI’s team actively participates in active case surveillance from organizing medical camps, to confirming diagnosis of PKDL/Leprosy/VL-HIV/relapse of VL as also monitoring their parasite burden after completion of treatment. In the absence of an animal model, the pathogenesis of PKDL still remains poorly delineated, and the PI as a JC Bose Fellow (2020-2025) made substantial contributions to better understand the factors that contribute towards (i) parasite survival and (ii) etiopathogenesis of hypopigmentation, a feature unique to PKDL. The PI has over the last 20 years of her research developed a robust repository, and provided a sound overview of the immune landscape of PKDL cases. Medicinal plants provide unparalleled chemical diversity and bioactivity, and translated into the discovery of artemisinin, an endoperoxide effective in malaria. Exploiting the weak anti-oxidant defense mechanism of the Leishmania parasite makes them vulnerable to pro-oxidants /oxidative stress, which the PI aims to exploy using endoperoxides e.g. artemisinin. Objectives: The objectives of the proposed study are: 1. Validation of field applicable tools for monitoring transmitters of VL, i.e. cases of PKDL, VL relapse and HIV-VL 2. Development and validation of a molecular test for identification of Leprosy (especially pauci bacillary) and monitoring the treatment efficacy of Leprosy 3. Investigating the immunopathology of South Asian PKDL, with PKDL cases from India as the prototype. 4. Exploring the bioenergetics profile during Leishmania infection and the possible intervention by endoperoxides.