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Open Access Highly Accessed Research article

Host markers in Quantiferon supernatants differentiate active TB from latent TB infection: preliminary report

Novel N Chegou1*, Gillian F Black1, Martin Kidd2, Paul D van Helden1 and Gerhard Walzl1

Author Affiliations

1 Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Health Sciences, University of Stellenbosch, Cape Town, Western Cape Province, P.O. Box 19063, Tygerberg 7505, South Africa

2 Centre for Statistical Consultation, Department of Statistics and Actuarial Sciences, Faculty of Science, University of Stellenbosch, Cape Town, Western Cape Province, Private Bag X1, Matieland 7602, South Africa

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BMC Pulmonary Medicine 2009, 9:21  doi:10.1186/1471-2466-9-21

Published: 16 May 2009

Abstract

Background

Interferon gamma release assays, including the QuantiFERON® TB Gold In Tube (QFT) have been shown to be accurate in diagnosing Mycobacterium tuberculosis infection. These assays however, do not discriminate between latent TB infection (LTBI) and active TB disease.

Methods

We recruited twenty-three pulmonary TB patients and 34 household contacts from Cape Town, South Africa and performed the QFT test. To investigate the ability of new host markers to differentiate between LTBI and active TB, levels of 29 biomarkers in QFT supernatants were evaluated using a Luminex multiplex cytokine assay.

Results

Eight out of 29 biomarkers distinguished active TB from LTBI in a pilot study. Baseline levels of epidermal growth factor (EGF) soluble CD40 ligand (sCD40L), antigen stimulated levels of EGF, and the background corrected antigen stimulated levels of EGF and macrophage inflammatory protein (MIP)-1β were the most informative single markers for differentiation between TB disease and LTBI, with AUCs of 0.88, 0.84, 0.87, 0.90 and 0.79 respectively. The combination of EGF and MIP-1β predicted 96% of active TB cases and 92% of LTBIs. Combinations between EGF, sCD40L, VEGF, TGF-α and IL-1α also showed potential to differentiate between TB infection states. EGF, VEGF, TGF-α and sCD40L levels were higher in TB patients.

Conclusion

These preliminary data suggest that active TB may be accurately differentiated from LTBI utilizing adaptations of the commercial QFT test that includes measurement of EGF, sCD40L, MIP-1β, VEGF, TGF-α or IL-1α in supernatants from QFT assays. This approach holds promise for development as a rapid diagnostic test for active TB.