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Associate Professor
Jonathan Peter

South Africa

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Profile EDCTP Fellowship 1

Project Title

IMmune-mediated Adverse drug Reactions In African TB HIV endemic settings (IMARI-Africa)

Project Objectives

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.

Results & Outcomes

The IMARI-Africa project built and expanded the AfriSCAR network, an unprecedented collaborative platform spanning several several sites in South African and other African countries. Sites in South Africa (University of Cape Town, Walter Sisulu University, University of the Free State) and other African partners (University of Zambia) successfully enrolled participants and contributed clinical data and biospecimens. Through these efforts, the IMARI Registry and Biorepository now includes over 290 validated and precision phenotyped SCAR cases and 611 matched controls. This resource is the largest of its kind globally, and it is uniquely enriched for patients with darker skin tones and co-infections with HIV and TB—factors often underrepresented in previous studies. A key scientific achievement of the project was the comprehensive genetic and immunological profiling of participants. Over 97% of cases and controls underwent high-resolution HLA typing, with a similarly high proportion undergoing ERAP and KIR genotyping. These datasets have already begun to yield important associations between genetic markers and drug-specific SCAR phenotypes, especially in relation to anti-TB drugs and cotrimoxazole. Importantly, data from Zambia and South Africa were integrated into multi-country analyses, helping validate findings across diverse African and global populations. The project produced over fifteen peer-reviewed publications. Among the most impactful outputs were studies describing the utility of sequential additive drug challenge (SADC) in safely reintroducing essential TB drugs in DRESS patients, and a multiomic single-cell study published in Nature Communications that defined tissue-specific immune responses in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis. These publications not only advanced scientific understanding but also informed clinical practice. Dissemination efforts included presentations at local, regional, and international scientific meetings, as

Host Organisation

Department Institution Country
Division of Allergology and Clinical Immunology The University of Cape Town Lung Institute (Pty) Ltd ZA

EDCTP Project

TMA2017SF-1981

EDCTP Program

EDCTP2

EDCTP Project Call

Senior Fellowship (SF)

Study Design

Observational

Project Summary

The IMARI-Africa grant (IMmune-mediated Adverse drug Reactions In African TB HIV endemic settings) is focused on the study of severe, treatment-limiting adverse drug reactions relevant to African populations. The major aims of the project include to research the epidemiology, and immune mechanisms of these reactions to describe important population-specific features to improve patient management and identify biomarkers that may be used to prevent and predict reactions. Toward this aim the AFRISCAR network has been established – a collaborative network of researchers in Sub-Saharan Africa (SSA) collectively focused on improving the diagnosis and treatment of Immune-Mediated Adverse Drug Reactions (IM-ADRs) in HIV/TB endemic settings of SSA. During the 6th and final year of IMARI, emphasis was placed on finalising validations of provisional SCAR cases and genotyping of samples such that at the end of the grant this globally valuable resource was precision phenotypes for all further downstream clinical and laboratory studies. Our final cumulative targets exceeded expectations including 290 validated SCAR and 611 controls (all sites). In addition, we confirmed alternative diagnosis for an additional 122 cases in the repository, and these will form an important comparative control group for the study of SCAR. Drug causality scoring is ongoing. HLA typing by VUMC has occurred for 99.8% of the registry cases and 98.1% of controls thus far, ERAP typing for 99.8% of the registry cases and 91.4% of controls and KIR typing for 90% of the registry cases and 66.3% of controls. Preliminary findings suggest HLA risk alleles for both Rifampicin DRESS and Pyrazinamide SJS/TEN, and we have submitted for publication our cotrimoxazole HLA association. Period 6 also saw a successful hosting of an AfriSCAR workshop in Tunisia, with emphasis on learning and sharing around the specific issues pertaining to IM-ADRs across Africa. Our research has not only contributed valuable insights to the scientific community, but has also led to the development of multiple MSc, MMED, and PhD students, fostering the next generation of researchers in this critical field. Several collaborative publications have emerged, strengthening outputs of the AfriSCAR network and expanding the global reach of the research. Moving forward, the integration of multiomic data, immune profiling, and genetic analysis will continue to advance the understanding of SCAR and allow for a personalised approach to management with the potential to significantly impact both global health and the clinical management of hypersensitivity reactions.