Project Principal Investigator(s):
Alana Brennan
Project duration:
1 September 2019 – 31 December 2027
Funding source:
25IPA1450262 Innovate Project Award (PI: Brennan)
American Heart Association 07/2025-06/2027
Assess the Impact of Environmental Changes on Cardiometabolic Health in South Africa.
K01DK116929 (PI: Brennan)
NIH/NIDDK 09/2019–08/2024. NCE 12/31/2025.
Evidence of the burden of diabetes, gaps in the diabetes cascade-of-care and the impact of care and treatment on diabetes outcomes in people living with and without HIV in South Africa.
K01DK116929-05S (PI: Brennan)
NIH/NIDDK 09/2023–02/2025. NCE 12/31/2025.
Administrative Supplement Extension for Early Career Scientists Impacted by COVID-19. Evidence of the burden of diabetes, gaps in the diabetes cascade-of-care and the impact of care and treatment on diabetes outcomes in people living with and without HIV in South Africa.
K01DK116929-03S (PI: Brennan)
NIH/NIDDK 09/2021–08/2025. NCE 12/31/2025.
Administrative Supplement for Research Continuity and K Award Retention. Evidence of the burden of diabetes, gaps in the diabetes cascade-of-care and the impact of care and treatment on diabetes outcomes in people living with and without HIV in South Africa.
Meet the
Team
Alana Brennan
Boston University
Nigel Crowther
University of Witwatersrand
Koleka Mlisana
National Health Laboratory Service (NHLS)
Jaya George
University of the Witwatersrand / NHLS
Jacob Bor
Boston University
Matthew Fox
Boston University
William MacLeod
Boston University
Fredrick Raal
Boston University
Mhairi Maskew
University of the Witwatersrand
Dorina Onoya
University of the Witwatersrand
Naseem Cassim
University of Witwatersrand
Siyabonga Khoza
University of Witwatersrand
Nina Brooks
University of Michigan
Caradee Yael Wright
South African Medical Research Council (SAMRC)
Thandi Kapwata
South African Medical Research Council (SAMRC)
Project
Objectives
Through NIH funding, we developed the National Health Laboratory Service (NHLS) Multimorbidity Cohort, a national, laboratory-based dataset covering all public-sector laboratory records from 2004-2025, updated annually.
Using advanced probabilistic linkage methods, we connected millions of HIV, tuberculosis, and non-communicable disease (NCD) tests (including diabetes, kidney disease, lipid panels, and other routine labs) to create a unified longitudinal cohort of patients receiving care across South Africa. A large manual validation study confirmed that the linkage algorithm performs with very high accuracy, providing strong confidence in the cohort’s structure and reliability.
Today, this cohort is one of the most comprehensive national resources for understanding multimorbidity in South Africa. It supports population-level research on how chronic diseases emerge, are detected, and are managed within the public health system. Using this platform, we produced the first national analysis of the diabetes care cascade, revealing substantial gaps in diagnosis, treatment initiation, and long-term control. We also examined the type 1 diabetes cascade in youth, patterns of chronic kidney disease progression, and diagnostic challenges related to glycemic testing. The cohort has further enabled quasi-experimental analyses on the relationship between HIV treatment initiation and NCD outcomes, as well as multiple quantitative bias analyses to strengthen causal inference.
Building on this foundation, our new American Heart Association funded project will integrate health, climate, and air-quality data to evaluate how environmental exposures shape cardiometabolic health in South Africa. For the first time, we are linking the NHLS Multimorbidity Cohort with 20 years of environmental and atmospheric data, including the ERA5 Global Reanalysis Dataset, South Africa’s Air Quality Information System (SAAQIS), satellite-derived PM₂.₅ estimates, and Sentinel-5P TROPOMI pollution measures (NO₂, SO₂, O₃). This integration will enable large-scale analyses of how extreme heat and air pollution influence cardiometabolic biomarkers, incident disease, and hospitalisations, and how environmental exposures modify the impact of major national policies such as South Africa’s 2019 Carbon Tax and 2020 NCD Strategic Plan.
Together, these studies demonstrate the power of national laboratory–based surveillance and position the NHLS Multimorbidity Cohort as a first-in-Africa platform for climate–cardiometabolic research, generating evidence to inform climate-resilient health systems and policies.
Key Findings
And Impacts
Using the NHLS Multimorbidity Cohort (2004–2025), we conducted national studies describing diabetes and chronic kidney disease (CKD) care across South Africa’s public sector. These analyses provide the clearest picture to date of chronic disease detection, management, and progression.
Major Gaps in the Diabetes Care Cascade:
Across both Type 1 and Type 2 diabetes, we observed steep losses at every stage of the care cascade, from initial abnormal results to confirmation testing, treatment initiation, and long-term control.
For Type 1 diabetes (T1DM), most children flagged with hyperglycemia did not receive timely confirmation testing or regular follow-up. Fewer than 10% achieved glycemic control, highlighting critical system-level gaps in pediatric diabetes services.
CKD Is Often Detected Late and Progresses Quickly:
In our national CKD analysis, many adults first entered the system with already-reduced kidney function, suggesting that CKD is frequently identified only after substantial decline. Among those with CKD at baseline, ~40% progressed from Stage 3 to Stage 4 or 5, often within a 2–3-year window. Progression was significantly faster among individuals with diabetes or HIV.
Monitoring Rarely Meets National Guidelines:
Routine monitoring for diabetes and kidney disease falls far short of South Africa’s national clinical guidelines. Despite clear recommendations for regular HbA1c, lipid, and kidney function testing, most patients did not receive follow-up laboratories at the required intervals. These gaps were consistent across provinces, age groups, and facility types, indicating a system-wide challenge rather than site-level variation.
Resources
Publications
Brennan AT, Lauren E, Bor JT, George JA, Khoza S, Mlisana K, Kileel EM, Rosen S, Raal F, Hibberd P, Fox MP, Crowther NJ. Gaps in the Type 1 Diabetes Mellitus care cascade: a national perspective using South Africa’s National Health Laboratory Service (NHLS) database. medRxiv. 2025 Sep 26. doi:10.1101/2025.09.26.25336712. https://pubmed.ncbi.nlm.nih.gov/41040711/
Brennan AT, Lauren E, Bor J, George JA, Chetty K, Mlisana K, Dai A, Khoza S, Rosen S, Stokes AC, Raal F, Hibberd P, Alexanian SM, Fox MP#, Crowther NJ#. Gaps in the type 2 diabetes care cascade: a national perspective using South Africa’s National Health Laboratory Service (NHLS) database. BMC Health Serv Res. 2023 Dec 21;23(1):1452. doi: 10.1186/s12913-023-10318-9. PMID: 38129852. https://pubmed.ncbi.nlm.nih.gov/38129852/
Brennan AT*, Kileel E*^, Crowther NJ, Khoza S, Bor J, Rosen S, Raal F, Hibberd P, Chetty K, Mlisana K, Fox MP#, George JA#. Prevalence and progression of chronic kidney disease among adults undergoing creatinine testing in South African public healthcare facilities: a study leveraging data from South Africa’s National Health Laboratory Service (NHLS): BMJ Public Health. 2024 Jul 3;2:e000799. https://pubmed.ncbi.nlm.nih.gov/39698394/
Brennan AT*, Kileel EM*^, George JA, Fox MP, Khoza S, Rosen S, Raal F, Hibberd P, Mlisana K, Chetty K, Bor J#, Crowther NJ#. Assessing compliance with national guidelines in diabetes care: A study leveraging data from south Africa’s National Health Laboratory Service (NHLS). PLOS Glob Public Health. 2024 Sep 3;4(9):e0003014. doi: 10.1371/journal.pgph.0003014. PMID: 39226276. https://pubmed.ncbi.nlm.nih.gov/39226276/
Resources
Conference presentations
Kileel E^, Crowther NJ, Khoza S, Bor J, Rosen S, Raal F, Hibberd P, Chetty K, Mlisana K, Fox MP#, George JA#, Brennan AT#. Incidence of new onset renal insufficiency or chronic kidney disease among a national cohort of people living with HIV in South Africa. 13thIAS Conference on HIV Science, Kigali, Rwanda, July 13th-17th, 2025.
Kileel E^, Crowther NJ, Khoza S, Bor J, Rosen S, Raal F, Hibberd P, Chetty K, Mlisana K, Fox MP#, George JA#, Brennan AT#. Incidence of new onset renal insufficiency or chronic kidney disease among a national cohort of people living with HIV in South Africa. 27thInternational Workshop on HIV and Hepatitis Observational Databases, Toledo, Spain March 27st-29th, 2025.
Brennan AT*, Kileel E*^, Crowther NJ, Khoza S, Bor J, Rosen S, Raal F, Hibberd P, Chetty K, Mlisana K, Fox MP#, George JA#. Progression of Chronic Kidney Disease in South African Public Healthcare Facilities: A Comparative Analysis Based on HIV Status in Individuals Undergoing Creatinine Testing. Poster presentation. Abstract No. 83. 26thInternational Workshop on HIV and Hepatitis Observational Databases, Vilamoura, Portugal, March 21st-23rd, 2024.
Brennan AT*, Kileel EM*^, George JA, Fox MP, Khoza S, Rosen S, Raal F, Hibberd P, Mlisana K, Chetty K, Bor J#, Crowther NJ#. Diabetes Management and Monitoring by HIV Status in South Africa: An Analysis Using National Health Laboratory Service Data. Poster presentation. Abstract No. 87. 26th International Workshop on HIV and Hepatitis Observational Databases, Vilamoura, Portugal, March 21st-23rd, 2024.
Brennan AT*, Kileel E*^, Crowther NJ, Khoza S, Bor J, Rosen S, Raal F, Hibberd P, Chetty K, Mlisana K, Fox MP#, George JA#. Chronic kidney disease prevalence, progression, and associated risk factors among South African patients receiving creatinine tests in public sector health care facilities. Oral Presentation. 2024 World Congress of Epidemiology, Cape Town, South Africa, September 24-27th, 2024.
Brennan AT*, Kileel EM*^, George JA, Fox MP, Khoza S, Rosen S, Raal F, Hibberd P, Mlisana K, Chetty K, Bor J#, Crowther NJ#. Assessing Compliance with National Guidelines in Diabetes Care: A Study Leveraging Data from the National Health Laboratory Service (NHLS). Poster Presentation. 2024 World Congress of Epidemiology, Cape Town, South Africa, September 24-27th, 2024.
Kileel EM*, Brennan AT, Fox MP, Bor J, George J, Khoza S, Rosen S, Hibberd P, Raal F, Chetty K, Mlisana K, Crowther NJ. The impact of misclassification of HbA1c tests on the relationship between HIV and type 2 diabetes in South Africa: a quantitative bias analysis. PathReD Congress 2023. Abstract No. PRC23-660. Oral Presentation. August 31st-September 3rd, 2023.
Kileel EM*, Brennan AT, Fox MP, Bor J, Scott L, Jenkins HE, Horsburgh RC, Jacobson KR, Chetty K, Mlisana K, Stevens W. A quantitative bias analysis of tuberculosis diagnostic tests among a national sample of people living with and without HIV in South Africa. PathReD Congress 2023. Abstract No. PRC23-658. Poster Presentation. August 31st -September 3rd, 2023.
Lauren E*, Raal F, George JA, Khoza S, Bor J, Fox MP, Chetty K, Mlisana K, Rosen S, Hibberd P, Crowther NJ, Brennan AT. Quantifying overdiagnosis of diabetes by glycated hemoglobin compared to plasma glucose-based tests stratified by HIV status. PathReD Congress 2023. August 31-September 3, 2023. Abstract No. PRC23-1302. Oral Presentation.
Brennan AT, Lauren E*, Bor J, George JA, Chetty K, Mlisana K, Dai A, Khoza S, Rosen S, Stokes A, Raal F, Hibberd P, Alexanian SM, Fox MP, Crowther NJ. Gaps in the Type 1 Diabetes Care Cascade: A National Perspective Using South Africa’s National Health Laboratory Service (NHLs) Database. PathReD Congress 2023. August 31-September 3, 2023. Abstract No. PRC23-657. Oral Presentation.
Kileel EM*, Brennan AT, Fox MP, Bor J, George J, Khoza S, Rosen S, Hibberd P, Raal F, Chetty K, Mlisana K, Crowther NJ. The impact of misclassification of HbA1c tests on the relationship between HIV and type 2 diabetes in South Africa: a quantitative bias analysis. Society for Epidemiologic Research 2023. June 14-16, 2023. Portland, Oregon.
Kileel EM*, Brennan AT, Fox MP, Bor J, Scott L, Jenkins HE, Horsburgh RC, Jacobson KR, Chetty K, Mlisana K, Stevens W. A quantitative bias analysis of tuberculosis diagnostic tests among a national sample of people living with and without HIV in South Africa. Society for Epidemiologic Research 2023. June 14-16, 2023. Portland, Oregon.
Brennan AT, Lauren E*, Bor J, Crowther N, George J, Khoza S, Milsana K, Dai A, Rosen S, Stokes A, Fox MP. Gaps in the type 2 diabetes care-cascade and how HIV and/or TB disease impact movement through its stages: a national perspective using South Africa’s National Health Laboratory Service(NHLS) database. 24thInternational AIDS Conference 2022.
Brennan AT, Dai A, Crowther N, Bor J, Fox MP, Khoza S, Milsana K, Rosen S, Lauren E*, George J. Prevalence of chronic kidney disease stratified by HIV, TB, and diabetes status: a national perspective using South Africa’s National Health Laboratory Service (NHLS) database. 24thInternational AIDS Conference 2022.
Brennan AT, Dai A, Crowther N, Bor J, Fox MP, Khoza S, Milsana K, Rosen S, Lauren E*, George J. Predictors of incident renal insufficiency and chronic kidney disease in people living with HIV and diabetes using South Africa’s National Health Laboratory Service (NHLS) database. 24thInternational AIDS Conference 2022.
Bor J, Fox MP, Maskew M, Onoya D, Brennan AT, Haber NH, Bärnighausen T, Carmona S, Stevens W, Puren AJ, MacLeod WB. Impact of UTT on viral suppression in South Africa: A national cohort study. 27thConference on Retroviruses and Opportunistic Infections 2020.
Harlow A, Bor J, Brennan AT, Macleod B, Fox MP. The Effect of South Africa’s Viral Load Monitoring Policy on HIV Outcomes: A Regression Discontinuity Analysis. 23rd International Workshop on HIV Observational Databases 2019.
