Diagnostic performance of a seven-marker serum protein biosignature for the diagnosis of active TB disease in African primary healthcare clinic attendees with signs and symptoms suggestive of TB

Chegou, N. N. et al. (2016) Diagnostic performance of a seven-marker serum protein biosignature for the diagnosis of active TB disease in African primary healthcare clinic attendees with signs and symptoms suggestive of TB. Thorax, 71(9), pp. 785-794. (doi: 10.1136/thoraxjnl-2015-207999) (PMID:27146200)

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Abstract

Background: User-friendly, rapid, inexpensive yet accurate TB diagnostic tools are urgently needed at points of care in resource-limited settings. We investigated host biomarkers detected in serum samples obtained from adults with signs and symptoms suggestive of TB at primary healthcare clinics in five African countries (Malawi, Namibia, South Africa, The Gambia and Uganda), for the diagnosis of TB disease. Methods: We prospectively enrolled individuals presenting with symptoms warranting investigation for pulmonary TB, prior to assessment for TB disease. We evaluated 22 host protein biomarkers in stored serum samples using a multiplex cytokine platform. Using a pre-established diagnostic algorithm comprising of laboratory, clinical and radiological findings, participants were classified as either definite TB, probable TB, questionable TB status or non-pulmonary TB. Results: Of the 716 participants enrolled, 185 were definite and 29 were probable TB cases, 6 had questionable TB disease status, whereas 487 had no evidence of TB. A seven-marker biosignature of C reactive protein, transthyretin, IFN-γ, complement factor H, apolipoprotein-A1, inducible protein 10 and serum amyloid A identified on a training sample set (n=491), diagnosed TB disease in the test set (n=210) with sensitivity of 93.8% (95% CI 84.0% to 98.0%), specificity of 73.3% (95% CI 65.2% to 80.1%), and positive and negative predictive values of 60.6% (95% CI 50.3% to 70.1%) and 96.4% (95% CI 90.5% to 98.8%), respectively, regardless of HIV infection status or study site. Conclusions: We have identified a seven-marker host serum protein biosignature for the diagnosis of TB disease irrespective of HIV infection status or ethnicity in Africa. These results hold promise for the development of a field-friendly point-of-care screening test for pulmonary TB.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Crampin, Professor Mia
Authors: Chegou, N. N., Sutherland, J. S., Malherbe, S., Crampin, A. C., Corstjens, P. L.A.M., Geluk, A., Mayanja-Kizza, H., Loxton, A. G., van der Spuy, G., Stanley, K., Kotzé, L. A., van der Vyver, M., Rosenkrands, I., Kidd, M., van Helden, P. D., Dockrell, H. M., Ottenhoff, T. H.M., Kaufmann, S. H.E., and Walzl, G.
College/School:College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health
Journal Name:Thorax
Publisher:BMJ Publishing Group
ISSN:0040-6376
ISSN (Online):1468-3296
Published Online:04 May 2016
Copyright Holders:Copyright © 2016 BMJ Publishing Group Ltd & British Thoracic Society
First Published:First published in Thorax 71(9):785-794
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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