A rapid triage test for active pulmonary tuberculosis in adult patients with persistent cough

Rushdy Ahmad, Liangxia Xie, Margaret Pyle, Marta F. Suarez, Tobias Broger, Dan Steinberg, Shaali M. Ame, Marilla G. Lucero, Matthew J. Szucs, Melanie MacMullan, Frode S. Berven, Arup Dutta, Diozele M. Sanvictores, Veronica L. Tallo, Robert Bencher, Dominic P. Eisinger, Usha Dhingra, Saikat Deb, Said M. Ali, Saurabh MehtaWafaie W. Fawzi, Ian D. Riley, Sunil Sazawal, Zul Premji, Robert Black, Christopher J.L. Murray, Bill Rodriguez, Steven A. Carr, David R. Walt, Michael A. Gillette

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbereaaw8287
JournalScience translational medicine
Volume11
Issue number515
DOIs
StatePublished - Oct 23 2019

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ahmad, R., Xie, L., Pyle, M., Suarez, M. F., Broger, T., Steinberg, D., Ame, S. M., Lucero, M. G., Szucs, M. J., MacMullan, M., Berven, F. S., Dutta, A., Sanvictores, D. M., Tallo, V. L., Bencher, R., Eisinger, D. P., Dhingra, U., Deb, S., Ali, S. M., ... Gillette, M. A. (2019). A rapid triage test for active pulmonary tuberculosis in adult patients with persistent cough. Science translational medicine, 11(515), [eaaw8287]. https://doi.org/10.1126/scitranslmed.aaw8287