TY - JOUR
T1 - A rapid triage test for active pulmonary tuberculosis in adult patients with persistent cough
AU - Ahmad, Rushdy
AU - Xie, Liangxia
AU - Pyle, Margaret
AU - Suarez, Marta F.
AU - Broger, Tobias
AU - Steinberg, Dan
AU - Ame, Shaali M.
AU - Lucero, Marilla G.
AU - Szucs, Matthew J.
AU - MacMullan, Melanie
AU - Berven, Frode S.
AU - Dutta, Arup
AU - Sanvictores, Diozele M.
AU - Tallo, Veronica L.
AU - Bencher, Robert
AU - Eisinger, Dominic P.
AU - Dhingra, Usha
AU - Deb, Saikat
AU - Ali, Said M.
AU - Mehta, Saurabh
AU - Fawzi, Wafaie W.
AU - Riley, Ian D.
AU - Sazawal, Sunil
AU - Premji, Zul
AU - Black, Robert
AU - Murray, Christopher J.L.
AU - Rodriguez, Bill
AU - Carr, Steven A.
AU - Walt, David R.
AU - Gillette, Michael A.
N1 - Publisher Copyright:
© 2019 The Authors.
PY - 2019/10/23
Y1 - 2019/10/23
N2 - Improved tuberculosis (TB) prevention and control depend critically on the development of a simple, readily accessible rapid triage test to stratify TB risk. We hypothesized that a blood protein-based host response signature for active TB (ATB) could distinguish it from other TB-like disease (OTD) in adult patients with persistent cough, thereby providing a foundation for a point-of-care (POC) triage test for ATB. Three adult cohorts consisting of ATB suspects were recruited. A bead-based immunoassay and machine learning algorithms identified a panel of four host blood proteins, interleukin-6 (IL-6), IL-8, IL-18, and vascular endothelial growth factor (VEGF), that distinguished ATB from OTD. An ultrasensitive POC-amenable single-molecule array (Simoa) panel was configured, and the ATB diagnostic algorithm underwent blind validation in an independent, multinational cohort in which ATB was distinguished from OTD with receiver operator characteristic-area under the curve (ROC-AUC) of 0.80 [95% confidence interval (CI), 0.75 to 0.85], 80% sensitivity (95% CI, 73 to 85%), and 65% specificity (95% CI, 57 to 71%). When host antibodies against TB antigen Ag85B were added to the panel, performance improved to 86% sensitivity and 69% specificity. A blood-based host response panel consisting of four proteins and antibodies to one TB antigen can help to differentiate ATB from other causes of persistent cough in patients with and without HIV infection from Africa, Asia, and South America. Performance characteristics approach World Health Organization (WHO) target product profile accuracy requirements and may provide the foundation for an urgently needed blood-based POC TB triage test.
AB - Improved tuberculosis (TB) prevention and control depend critically on the development of a simple, readily accessible rapid triage test to stratify TB risk. We hypothesized that a blood protein-based host response signature for active TB (ATB) could distinguish it from other TB-like disease (OTD) in adult patients with persistent cough, thereby providing a foundation for a point-of-care (POC) triage test for ATB. Three adult cohorts consisting of ATB suspects were recruited. A bead-based immunoassay and machine learning algorithms identified a panel of four host blood proteins, interleukin-6 (IL-6), IL-8, IL-18, and vascular endothelial growth factor (VEGF), that distinguished ATB from OTD. An ultrasensitive POC-amenable single-molecule array (Simoa) panel was configured, and the ATB diagnostic algorithm underwent blind validation in an independent, multinational cohort in which ATB was distinguished from OTD with receiver operator characteristic-area under the curve (ROC-AUC) of 0.80 [95% confidence interval (CI), 0.75 to 0.85], 80% sensitivity (95% CI, 73 to 85%), and 65% specificity (95% CI, 57 to 71%). When host antibodies against TB antigen Ag85B were added to the panel, performance improved to 86% sensitivity and 69% specificity. A blood-based host response panel consisting of four proteins and antibodies to one TB antigen can help to differentiate ATB from other causes of persistent cough in patients with and without HIV infection from Africa, Asia, and South America. Performance characteristics approach World Health Organization (WHO) target product profile accuracy requirements and may provide the foundation for an urgently needed blood-based POC TB triage test.
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U2 - 10.1126/scitranslmed.aaw8287
DO - 10.1126/scitranslmed.aaw8287
M3 - Article
C2 - 31645455
AN - SCOPUS:85074087224
SN - 1946-6234
VL - 11
JO - Science translational medicine
JF - Science translational medicine
IS - 515
M1 - eaaw8287
ER -