TY - JOUR T1 - 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 JF - Thorax JO - Thorax SP - 785 LP - 794 DO - 10.1136/thoraxjnl-2015-207999 VL - 71 IS - 9 AU - Novel N Chegou AU - Jayne S Sutherland AU - Stephanus Malherbe AU - Amelia C Crampin AU - Paul L A M Corstjens AU - Annemieke Geluk AU - Harriet Mayanja-Kizza AU - Andre G Loxton AU - Gian van der Spuy AU - Kim Stanley AU - Leigh A Kotzé AU - Marieta van der Vyver AU - Ida Rosenkrands AU - Martin Kidd AU - Paul D van Helden AU - Hazel M Dockrell AU - Tom H M Ottenhoff AU - Stefan H E Kaufmann AU - Gerhard Walzl Y1 - 2016/09/01 UR - http://thorax.bmj.com/content/71/9/785.abstract N2 - 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. ER -