Hayley Warsinske,
Postdoctoral Scholar,
ITI, Stanford

Abstract:
The World Health Organization (WHO) has identified the need for a non-sputum based triage test for active tuberculosis disease that can be used to identify those who need further testing and ultimately treatment. We investigated whether our previously described 3-gene TB score could identify individuals with active tuberculosis (ATB) prior to seeking care (“active case detection”). We further investigated how the 3-gene TB score correlated with the timing of disease onset, disease severity, and response to treatment. This study consisted of a prospective nested case-control trial, Brazil Active Screening Study (BASS; 2016), and re-analysis of data from two prospective cohort studies, the Adolescent Cohort Study (ACS; 2005-2007) and the Catalysis Treatment Response Cohort (CTRC; 2010-2013). The 3-gene TB score diagnosed ATB patients with high accuracy. In the ACS, the 3-gene TB score predicted progression from LTBI to ATB 6 months prior to positive sputum test.  In the CTRC, the 3-gene TB score correlated with glycolytic activity ratio of PET-CT at baseline and at end of treatment. In the CTRC, the 3-gene TB score at baseline predicted the likelihood of prolonged sputum positivity following treatment initiation and treatment response at 6 months Collectively, across all cohorts, the 3-gene TB score identified ATB patients with 90% sensitivity and 70% specificity, and had 99% negative predictive value (NPV) at 5% prevalence. The 3-gene TB score closely approaches the WHO target product profile benchmarks for non-sputum-based triage test at high NPV. These performance characteristics make it a potential test for ruling out ATB and for monitoring disease status.