Biomarkers of Protective Immunity against TB in the context of HIV/AIDS in Africa
This study follows a prospective cohort design, whereby enrolled index cases with active TB, and all enrolled close contacts of index cases will be followed over a respective 2 year period. Progressors to active TB will be compared with non-progressors in nested case-control studies. Progression to active TB will be the study endpoint.
Development of natural protective immunity will be evaluated during the follow-up of TB index cases (maximum of 300 at Stellenbosch University), and household contacts (maximum of 2000 at Stellenbosch University) with recent M. tuberculosis infection. We will recruit similar prospective cohorts at each of 4 separate African sites. To assess the impact of progressive HIV-1 infection on immunity against M. tuberculosis, including the effect of antiretroviral treatment, we will recruit two prospective cohorts of 300 HIV-1 seropositive individuals (and similar numbers at each of 5 separate African sites) and prospectively follow them up for 2 years to monitor acquisition or progression of M. tuberculosis infection.
Longitudinal analysis will be performed of antigen-specific T cell responses and expression of host biomarkers (including various cytokines) in order to define true correlates of natural protective immunity and surrogate markers of TB disease. TB index cases will undergo blood sampling at recruitment and month 18, whereas participants without active TB will also be bled at month 6.
The Evaluation of Mycobacterium tuberculosis (Mtb) Specific Host Cytokine Signatures in Whole Blood Culture Supernatants as Diagnostic Biomarkers for Active TB Infection
400 Consecutive HIV infected TB suspects will be recruited and followed up for 6 months at primary health care clinics at 5 of the African Consortium Institutions. The aim of the study is to evaluate the performance of the combination levels of cytokine and growth factors in WBA s
upernatants, measured by lateral flow up converting phosphor test strips to enable the accurate diagnosis of active tuberculosis in a rapid-friendly assay. Such a test would be a significant improvement over current tests as it would not require advanced laboratory capacity, as it would provide a result within 24 hours and as it may enable diagnosis of active disease in patients with paucibacillary or extra pulmonary disease.
Mycobacterium tuberculosis Biomarkers for Diagnosis and Cure
This study uses the PET/CT technology to determine possible Biomarkers for the diagnosis and cure of TB patients who had undergone treatment. PET will be correlated with extent markers of disease, TB culture (MGIT) time to positivity and other markers. TB infection and disease resistance is also confirmed by the GeneXpert technology.
Discovery of Biomarkers for Response to TB Treatment
This study performed in collaboration with BECTON DICKINSON AND COMPANY, is aimed at identifying markers of treatment response in patients with newly diagnosed active tuberculosis who go on to start therapy. Blood is drawn and analysed by flow cytometry using the BD FACSCAP technology to identify the regulation of 212 surface markers expressed on peripheral blood cells. This data will be compared to control participants who have no TB or have other lung diseases in order to identify disease specific biomarkers.