Project: IMmune-mediated Adverse drug Reactions In African TB HIV endemic settings

Acronym	IMARI-Africa (Reference Number: TMA2017SF-1981)
Duration	01/03/2019 - 29/02/2024
Project Topic	The proposed Senior Fellow, Associate Professor Jonathan Peter, is Head of Division of Allergology & Clinical Immunology at the University of Cape Town (UCT). He is the first registered adult allergist in South Africa. He is now seeking to become a senior African researcher by: 1. Acquiring advanced and formal training in project management and leadership. 2. Mentoring junior African researchers to investigate precision phenotyping of immune-mediated adverse drug reactions (IM-ADRs) using advanced immunology and “omic” technologies to understand mechanisms and identify novel biomarkers. 3. Developing an AfriSCAR network as a research platform to grow capacity and conduct well-powered clinical trials of candidate biomarkers to eliminate IM-ADRs These broad objectives will be achieved in 3 ways: i. Mentoring and training African students directly involved in this project; ii. Conducting extensive networking activities across five sub-Saharan African (SSA) countries; iii. Acquiring hands-on expertise in advanced immunology and the relevant bioinformatics analytical pipelines, needed to decipher IM-ADRs, through traineeships to Vanderbilt University Medical Centre (VUMC); iv. Attending specific seminars, both at UCT and VUMC, in advanced genomics, immunology, project and financial management. The proposed mentorship, development and capacity-building activities will be focused on treatment-limiting severe cutaneous adverse drug reactions (SCAR) – a life-threatening IM-ADR. IM-ADRs are over-represented in Africa, both in relation to the unique drugs being used, and the populations of HIV-TB co-infected individuals being affected; occurring at an estimated 100-fold higher prevalence in HIV infected individuals. This proposed project will continue our current prospective case-controlled study on the epidemiology of SCAR in South Africa; where we already have exciting data on Nevirapine and 1 st line anti-TB SCAR. Through the proposed collaborations, we will develop the AfriSCAR network to conduct similar SCAR epidemiology studies in four additional SSA countries. This will allow introduction of our safe drug rechallenge protocols and advanced immunophenotyping approaches to identify culprit drugs – a challenge, given the polypharmacy of HIV/TB coinfected patients with SCAR. Complementary laboratory studies will focus on identifying candidate biomarkers for each drug-reaction combination in our prospective cohorts. Techniques will include: genomics focused on HLA and other pharmacogenomic risk alleles, single cell deep sequencing to identify dominant T-cell receptors at both site-of-disease and in peripheral blood. These activities will offer critical insights into our understanding SCAR in African populations; provide opportunities for further biomarkers discovery, and establish an African network for conducting future well-powered clinical trials to prevent or treat these devastating reactions.
Network	EDCTP2
Call	Senior Fellowships 2017

Project partner

Number	Name	Role	Country
1	University of Cape Town Lung Institute (Pty) Ltd	Coordinator	South Africa