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. Issue 9 (4th May 2016)

• Record Type: Journal Article
• Authors: Chegou, Novel N; Sutherland, Jayne S; Malherbe, Stephanus; Crampin, Amelia C; Corstjens, Paul L A M; Geluk, Annemieke; Mayanja-Kizza, Harriet; Loxton, Andre G; van der Spuy, Gian; Stanley, Kim; Kotzé, Leigh A; van der Vyver, Marieta; Rosenkrands, Ida; Kidd, Martin; van Helden, Paul D; Dockrell, Hazel M; Ottenhoff, Tom H M; Kaufmann, Stefan H E; Walzl, Gerhard
• Other Names: author non-byline.; Kriel Magdalena author non-byline.; Malherbe Stephanus author non-byline.; Kriel Belinda author non-byline.; Awoniyi Dolapo O author non-byline.; Maasdorp Elizna author non-byline.; Owolabi Olumuyiwa author non-byline.; Sillah Abdou author non-byline.; Mendy Joseph author non-byline.; Gindeh Awa author non-byline.; Donkor Simon author non-byline.; Togun Toyin author non-byline.; Ota Martin author non-byline.; Simukonda Felanji author non-byline.; Amberbir Alemayehu author non-byline.; Chilongo Femia author non-byline.; Houben Rein author non-byline.; Kassa Desta author non-byline.; Gebrezgeabher Atsbeha author non-byline.; Mesfin Getnet author non-byline.; Belay Yohannes author non-byline.; Gebremichael Gebremedhin author non-byline.; Alemayehu Yodit author non-byline.; Amutenya Faustina N author non-byline.; Nelongo Josefina N author non-byline.; Monye Lidia author non-byline.; Sheehama Jacob A author non-byline.; Iipinge Scholastica author non-byline.; Namuganga Ann Ritah author non-byline.; Muzanye Grace author non-byline.; Nsereko Mary author non-byline.; Peters Pierre author non-byline.; Howe Rawleigh author non-byline.; Mihret Adane author non-byline.; Bekele Yonas author non-byline.; Tessema Bamlak author non-byline.; Yamuah Lawrence author non-byline.; Ottenhoff Tom HM author non-byline.; Franken Kees LMC author non-byline.; Corstjens Paul LAM author non-byline.; Fat Elisa M Tjon Kon author non-byline.; de Dood Claudia J author non-byline.; van der Ploeg-van Schip Jolien J author non-byline.; Aagaard Claus author non-byline.; Kaufmann Stefan HE author non-byline.; Esterhuyse Maria M. author non-byline.; Cliff Jacqueline M author non-byline.;
• Is Part Of: Thorax. Volume 71:Issue 9(2016)
• Page Start: 785
• Page End: 794
• Publication Date: 2016-05-04
• Subjects: Tuberculosis; Chest -- Diseases -- Periodicals; Thorax; Chest -- Diseases; Periodicals; Periodicals; 617.54
• DOI: 10.1136/thoraxjnl-2015-207999
• Languages: English
• ISSNs: 0040-6376

Abstract

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.