A biomarker is a characteristic that can be objectively measured for a person to indicate some biological process, whether normal, pathogenic or a response to treatment for example.  Potential TB biomarkers should differentiate between latent and active TB, change with effective therapy and predict treatment outcomes in varied populations, as well as predict vaccine efficacy.  We are involved in several long-term follow-up studies at all the intersections of the TB spectrum.  

Biomarkers of Protective Immunity

Household contacts of patients with active TB are a useful group to study for discovering factors that predispose to becoming TB infected after exposure and also to develop disease after having been infected.  Only 10% of the TB infected become diseased. Antigen-specific T cell responses and expression of various cytokines (amongst others) from a large cohort of household contacts of active TB cases have been followed up for two years. These are being studied to find biomarkers that distinguish those who become ill from those who seem to have a natural protective immunity.  

Diagnostic markers for latent TB infection

One serious limitation of current diagnostics for latent TB infection (sub-clinical TB) is the inability of tests to differentiate between recent and remote infection.  This is important as the risk for progression is highest in the first year after infection.  Tests also do not differentiate between the presence of live bacteria and immune memory in the absence live bacteria.  We are investigating responses other than Interferon Gamma production to address these limitations.

Diagnostic markers for active TB disease

Even though TB diagnostics have seen significant developments over the last decade, many challenges remain.  We contribute to improvements in this field by striving to develop a rapid point-of-care test for TB, utilizing lateral flow technology recognizing cytokine signatures in whole blood.

Markers for Treatment Response, Cure, Failure and Relapse

Currently early TB treatment response is mainly evaluated by Week 8 sputum conversion and the clinical state of the patient.  This is not always adequate.  We have recent evidence on end of treatment PET/CT scans that most patients who are clinically and microbiologically cured according to the National TB program, are not free of pulmonary inflammation.  Biomarkers of treatment response and risk of treatment failure or TB recurrence/relapse are needed to distinguish patients who are truly cured at end of treatment from those who failed treatment or are at risk of relapse. PET/CT is one such biomarker that we are investigating in a few projects and it shows potential to be used in specific research settings to act as biomarker of treatment response and failure/ recurrence.  Other potential candidates are cell surface markers and cytokines. ?

We have just completed a Bill and Melinda Gates Foundation and EDCTP-co-funded clinical trial on a PET/CT driven treatment shortening strategy. The treatment shortening in patients with less extensive pulmonary disease was not non-inferior to standard 6-month treatment, but we are currently performing a large whole blood RNA sequencing study to look for mRNA signatures for a high risk for poor treatment outcomes. 

Immune-endocrine interactions during TB infection and disease

The Interplay between the Endocrine and the Immune System during TB Infection

There is increasing evidence that the immune system and the endocrine system influence each other. Cytokines produced during an immune response feedback to the hypothalamus and alter the secretion of hormones such as those involved in the hypothalamic-pituitary-adrenal and the hypothalamus-pituitary-gonadal axes. In turn, steroid hormones as well as metabolic hormones, can bind to their respective receptors on immune cells and affect the secretion of cytokines and chemokines. We are studying how TB influences the hormonal balance, and are trying to identify the underlying molecular mechanisms of the interplay between the immune and endocrine systems.

The Endocrine dysregulation during type 2 diabetes and risk for TB

An emerging challenge for TB control is the steadily rising number of individuals with Type 2 Diabetes (T2D), particularly in developing countries where TB is endemic. T2D increases the risk of TB by three fold and there are now more people affected by TB-T2D co-morbidity than TB-HIV co-infection. A better understanding of the link between TB and T2D is essential to identify individuals at increased risk for TB progression. 

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TB Vaccine Trials

The group is actively involved in TB vaccine research. The main focus of our participation revolves around the exploratory immunological laboratory analysis of the TB vaccines. We need to understand the complexity of the immune responses induced by the different vaccines. Here we evaluate the phenotype and multi-functionality of cells induced by vaccination. We have been involved in several trials ranging from booster vaccines to potential BCG replacements. The latest of the trials is in collaboration with Vakzine Projekt Management GmbH, a German vaccine company and the Serum Institute of India. We are the lead immunological facility for a trial with several partners. We are also working in close collaboration with the South African Vaccine Initiative (SATVI) and with FAMCRU in an attempt to harmonize and standardize assays used for vaccine analysis.?

Bioinformatics

The Stellenbosch 中国体育彩票 Immunology Research Group has established the South African TB Biomarker Bioinformatics Initiative and has recruited a senior bioinformatician to lead the group. The focus is on training post-graduate students in bioinformatics and setting up data automation and pipelines to enable high-throughput analysis of omics data sets. This greatly increased our capacity to harness the large amounts of immunological and genetic information that TB studies are generating and serve the TB  biomarker community in an institutionally independent manner.  We are part of international and local research collaborations that aim to promote biomarker bioinformatics as a means to find answers to many of the key questions in tuberculosis immunology.