A sudden, potentially life-threatening swelling condition called angioedema is poorly understood and managed across Sub-Saharan Africa, where common blood pressure drugs may trigger it at higher rates in Black populations. This matters because angiotensin-converting enzyme inhibitors (ACEIs) are cheap and widely used for Africa's hypertension epidemic, but the most dangerous side effect—ACEI-induced angioedema—may be more common in people of African ancestry. Meanwhile, hereditary angioedema goes massively undiagnosed, and the role of food additives in triggering attacks through gut barrier damage has never been studied in this region. If successful, the project will produce a simple, low-cost urine test—similar to a pregnancy test—to identify patients at risk of ACEI-induced swelling before they take the drug. It will also train healthcare workers via telemedicine, run community awareness campaigns, and test whether a low-additive diet reduces recurrent attacks in a randomised trial of 200 patients. The research could save lives, reduce hospital visits, and multiply the impact of scarce allergy specialists across the continent.
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This study focuses on understanding, preventing, and managing angioedema in Sub-Saharan Africa(SSA). It specifically addresses angiotensin-converting enzymes inhibitors (ACEI)-induced angioedema(ACEI-AE), hereditary angioedema, and the impact of food-additives and gut-barrier disruption on recurrent angioedemas. In SSA, the awareness and management of angioedema, a potentially life-threatening condition characterised by sudden swelling, are limited. ACEI-AE, the most dangerous ACEI adverse reaction, may be increased in African populations, limiting the use of these affordable agents for Africa's epidemic of hypertension. Hereditary angioedemas, requiring specific treatments, are massively under-diagnosed in SSA. The impact of food additives on gut barrier disruption and angioedema remains unexplored in the African context with high co-morbid gastrointestinal infections. This project aims to address these priority gaps. The project has three aims to: i) validate a urine protein biomarker signature to identify those at risk of ACEI-AE and develop a simple, low-cost test format; ii) improve the management of angioedema and hereditary angioedema (HAE) diagnosis in underserved SSA; and iii) investigate the role of gut-barrier damage and increased permeability in recurrent angioedema, focusing on the contribution of food-additives and the therapeutic efficacy of a low-food-additive diet. Methods Aim 1 will bio-bank urine samples from diverse populations of ACEI-AE cases(N=50/country) matched to drug-tolerant and confounding disease controls(N>100/country). We will develop a prototype lateral flow assay using validated urine proteins with a SA biotech partner. Aim 2 will use workshops with diverse stakeholder engagements to formulate a comprehensive strategy of healthcare worker trainings, scaled telemedicine allergy-specialist support, and community-level awareness campaigns. Aim 3 will use a UCT-based prospective cohort of recurrent angioedema cases(N=200) to dissect the roles of food additives, chronic gastrointestinal infections and auto-allergy on gut permeability and disease burden. A nested randomised-controlled trial(RCT) will assess the efficacy of a locally-feasible low-food-additive diet on patient-reported angioedema activity scores(AAS, AECT). All project activities involve patients, communities, and allergy organisations in Africa, with integral inputs to the development of educational materials and advocacy campaigns. Timelines and impact The initial two years will focus on: i) biobanking and validation of urine proteins for ACEI-AE, ii) selection of the optimal detection system for lateral flow assay, iii) set-up of the recurrent angioedema study, iv) landscaping of food-additives and diets, and v) patient engagements to develop a comprehensive strategy for aim 2. Year 3-5 will shift to actual development of the prototype lateral flow assay, implementation of trainings and awareness campaigns; and the low-food-additive diet RCT. This research is expected to significantly enhance the understanding and management of angioedema in SSA, with implications for global health practices, particularly in the context of ACEI usage and dietary management of angioedema. Anticipated impacts include a novel diagnostic tool for ACEI-AE, improved management practices for angioedema in SSA multiplying the impact of limited allergy specialists, and new insights into the role of diet in angioedema aetiology and treatment. Findings will be disseminated through academic publications, conferences, media, and community events. Success could include the saving of individual SSA lives, reduced angioedema morbidity and health system spending.
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