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Evaluation of Host Serum Protein Biomarkers of Tuberculosis in sub-Saharan Africa.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Morris, Thomas C 
Hoggart, Clive J 
Chegou, Novel N 
Kidd, Martin 

Abstract

Accurate and affordable point-of-care diagnostics for tuberculosis (TB) are needed. Host serum protein signatures have been derived for use in primary care settings, however validation of these in secondary care settings is lacking. We evaluated serum protein biomarkers discovered in primary care cohorts from Africa reapplied to patients from secondary care. In this nested case-control study, concentrations of 22 proteins were quantified in sera from 292 patients from Malawi and South Africa who presented predominantly to secondary care. Recruitment was based upon intention of local clinicians to test for TB. The case definition for TB was culture positivity for Mycobacterium tuberculosis; and for other diseases (OD) a confirmed alternative diagnosis. Equal numbers of TB and OD patients were selected. Within each group, there were equal numbers with and without HIV and from each site. Patients were split into training and test sets for biosignature discovery. A nine-protein signature to distinguish TB from OD was discovered comprising fibrinogen, alpha-2-macroglobulin, CRP, MMP-9, transthyretin, complement factor H, IFN-gamma, IP-10, and TNF-alpha. This signature had an area under the receiver operating characteristic curve in the training set of 90% (95% CI 86-95%), and, after adjusting the cut-off for increased sensitivity, a sensitivity and specificity in the test set of 92% (95% CI 80-98%) and 71% (95% CI 56-84%), respectively. The best single biomarker was complement factor H [area under the receiver operating characteristic curve 70% (95% CI 64-76%)]. Biosignatures consisting of host serum proteins may function as point-of-care screening tests for TB in African hospitals. Complement factor H is identified as a new biomarker for such signatures.

Description

Keywords

Africa, HIV, biomarker, diagnosis, protein, serum, tuberculosis, Adult, Africa South of the Sahara, Biomarkers, Complement Factor H, Female, Fibrinogen, HIV Infections, HIV-1, Humans, Male, Middle Aged, Mycobacterium tuberculosis, Point-of-Care Testing, Tuberculosis, Pulmonary

Journal Title

Front Immunol

Conference Name

Journal ISSN

1664-3224
1664-3224

Volume Title

12

Publisher

Frontiers Media SA