TB diagnosis is still hampered by inadequate tests. Diagnostic aspects of active pleural TB, pulmonary TB and TB meningitis were investigated in the high TB prevalence area of Cape Town. We investigated diagnostic host markers and found pleural fluid IFN-γ levels to be highly sensitive with good specificity for TB pleuritis. A three-marker cytokine signature was identified in cerebro spinal fluid that performed better than any other diagnostic modality on its own to diagnose TB meningitis in children. Our pulmonary TB diagnostic program evaluated multiple mycobacterial proteins as stimulants for the production of multiple host inflammatory markers but test performance did not warrant the long lag time to obtaining a result. However, serum cytokine signatures were found with promising diagnostic potential and we are currently working on point of care, lateral flow-based tests to measure such signatures as part of screening tests for active TB. I served as primary or co-investigator on these studies.
Biomarkers for natural or vaccine-induced protective immunity against the progression to active TB could play an important role in the evaluation of new TB vaccines and might guide preventative measures after exposure to M. tuberculosis. My group has participated in the recruitment and two-year follow-up of large household contact cohorts (>1.400 in Cape Town, which form part of the >4.000 contacts recruited across Africa by the GC6-74 consortium). Biomarkers for incident TB are being investigated through complimentary ‘omics’ technologies, including next generation RNA sequencing, metabolomics and proteomics. Early data indicated promising predictive biosignatures.