EDCTP Alumni Network

Title

Novel Biomarkers predictive of susceptibility and treatment response in patients with MDR-TB

Objectives

To compare compartment-specific IFN- antigen-specific responses in TB versus non-TB patients. To procure and bank biological material (alveolar lavage fluid and cells) from HIV negative close contacts (of sputum smear positive patients) that have laboratory evidence of LTBI (TST+, IGRA+ i.e.converters) versus those that do not (TST-, IGRA- i.e. nonconverters). To compare expression and function of innate markers of protective immunity (pathogen recognition molecules/ receptors, cytokines, humoral factors and cell phenotypes) in converters and nonconverters.

Host Organisation

Institution	Country
University of Cape Town Lung Institute (Pty) Ltd	South Africa

Study Design

Immunological studies

Results & Outcomes

Rapid diagnosis of TB meningitis by smear microscopy and PCR is problematic and the diagnostic delay can often translate into increased morbidity and mortality due to the poor sensitivity of these assays. The TB-specific quantitative T cell ELISPOT assay, when using CSF mononuclear cells and in conjunction with other rapid confirmatory tests (Gram stain and cryptococcal latex-agglutination) is an accurate and rapid rule-in test for TBM in a TB and HIV endemic setting. The RD-1, but not the purified-protein-derivative, cerebrospinal fluid-lymphocyte IFN-γ ELISPOT response is a useful rapid immunodiagnostic test for TBM. Further studies are continuing from the work described above.

Publications

Patel VB, Singh R, Connolly C, ,Coovadia Y, Peer A, Parag P, Kasprowicz V, Zumla A, Ndung’u T, Dheda K. Cerebrospinal T cell responses aid the diagnosis of tuberculous meningitis in a HIV and TB endemic population. Am J Respir Crit Care Med. 2010 Aug 15;182(4):569-77. doi: 10.1164/rccm.200912- 1931OC. Epub 2010 May 4.

Patel VB, Bhigjee AI, Paruk HF, Singh R, Meldau R, Connolly C, Ndung’u T, Dheda K. Utility of a novel lipoarabinomannan assay for the diagnosis of tuberculous meningitis in a resource-poor high-HIV prevalence setting. Cerebrospinal Fluid Research. 2009 November,2;6:13. PMID: 19878608

Cashmore TJ , Peter GJ, van Zyl-Smit RN, Semple PL, Maredza A, Meldau R, Zumla A, Nurse B, Dheda K. Feasibility and diagnostic utility of antigen-specific interferon-gamma responses for rapid immunodiagnosis of tuberculosis using induced sputum. PLoS One. 2010 Apr 28;5(4):e10389. PMID: 20442850