Investigating the link between post-tuberculosis lung disease (PTLD) and circulatory biomarkers in a South African cohort
type: CreativeWork
description: Tuberculosis (TB) is a leading cause of death from a single infectious agent, despite being preventable and curable. While global health efforts have significantly improved diagnostic and therapeutic strategies, emerging evidence demonstrates that many patients experience long-term pulmonary complications after completing TB treatment. These complications are collectively termed post-tuberculosis lung disease (PTLD). PTLD is a complex and heterogeneous disease which contributes to increased mortality in this patient population. Its pathogenesis, however, remains poorly understood. This dissertation investigates whether endothelial dysfunction and immunopathological mechanisms associate with PTLD, by examining systemic biomarkers in patients with active TB and those with a history of TB. The central hypothesis is that endothelial dysfunction and a chronic pro-inflammatory state persist beyond microbiological cure, contributing to PTLD development. Three interrelated sub-studies were conducted to explore this hypothesis. The first sub-study measured endothelial and oxidative stress biomarkers, including ADMA, VCAM-1, VEGF, angiopoietin-1, TBARS, NT-pro-BNP, and cardiac troponin-I, in patients stratified by the number of previous TB episodes and the time since the last treatment. VEGF and angiopoietin-1 were significantly elevated (up to 6500-fold above normal), with positive correlations to TB episode count. ADMA levels were 70-fold higher, though weakly negatively correlated with TB history. TBARS concentrations were low, and NT-pro-BNP and cardiac troponin-I were undetectable. The second sub-study assessed inflammatory markers IL-6, IL-8, TNF-α, CRP, and IL-1Ra in two cohorts: individuals with prior TB (>1-year post-treatment) and patients undergoing treatment for drug-sensitive TB. IL-6, TNF-α, and CRP were markedly elevated in both groups, indicating a sustained inflammatory response. IL-8 and IL-1Ra showed variable expression between cohorts, suggesting different…
abstract: Tuberculosis (TB) is a leading cause of death from a single infectious agent, despite being preventable and curable. While global health efforts have significantly improved diagnostic and therapeutic strategies, emerging evidence demonstrates that many patients experience long-term pulmonary complications after completing TB treatment. These complications are collectively termed post-tuberculosis lung disease (PTLD). PTLD is a complex and heterogeneous disease which contributes to increased mortality in this patient population. Its pathogenesis, however, remains poorly understood. This dissertation investigates whether endothelial dysfunction and immunopathological mechanisms associate with PTLD, by examining systemic biomarkers in patients with active TB and those with a history of TB. The central hypothesis is that endothelial dysfunction and a chronic pro-inflammatory state persist beyond microbiological cure, contributing to PTLD development. Three interrelated sub-studies were conducted to explore this hypothesis. The first sub-study measured endothelial and oxidative stress biomarkers, including ADMA, VCAM-1, VEGF, angiopoietin-1, TBARS, NT-pro-BNP, and cardiac troponin-I, in patients stratified by the number of previous TB episodes and the time since the last treatment. VEGF and angiopoietin-1 were significantly elevated (up to 6500-fold above normal), with positive correlations to TB episode count. ADMA levels were 70-fold higher, though weakly negatively correlated with TB history. TBARS concentrations were low, and NT-pro-BNP and cardiac troponin-I were undetectable. The second sub-study assessed inflammatory markers IL-6, IL-8, TNF-α, CRP, and IL-1Ra in two cohorts: individuals with prior TB (>1-year post-treatment) and patients undergoing treatment for drug-sensitive TB. IL-6, TNF-α, and CRP were markedly elevated in both groups, indicating a sustained inflammatory response. IL-8 and IL-1Ra showed variable expression between cohorts, suggesting different…
author: Jumaar, Chrisstoffel
language: en
date published: 2026-03
date modified: 2026-07-24T04:40:09Z
provider: Stellenbosch University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Stellenbosch : Stellenbosch University