Head-to-head evaluation of host blood biomarkers for point-of-care TB triage: diagnostic accuracy study.

Global tuberculosis (TB) incidence is slowly decreasing, partly because undiagnosed TB continues to fuel transmission. Point-of-care TB triage tests (TTTs) performed near a patient or at the site of patient care may help bridge this gap, but head-to-head comparisons of different host blood biomarkers within the same cohort are limited. In ambulatory adults in Uganda aged ≥15 years with any cough, fever, weight loss, or night sweats, we evaluated the diagnostic accuracy of C-reactive protein (CRP), monocyte-to-lymphocyte ratio (MLR), interferon-gamma-induced protein 10 (IP-10), and hemoglobin (anemia) head-to-head using a reference standard comprised of culture and/or Xpert MTB/RIF Ultra. Cut-offs of CRP and anemia were from World Health Organization (WHO) recommendations, MLR from the literature, and IP-10 from Youden's index. We included 623 participants (193 people living with HIV [PLWHIV]), of whom 111 (18%) were reference standard-positive. Sensitivity and specificity (95% CI) were 91% (84%-96%) and 78% (74%-81%) for CRP (≥10 mg/L); 72% (63%-78%) and 80% (77%-84%) for MLR (≥0.378); 86% (79%-92%) and 73% (69%-77%) for IP-10 (≥28.75); 69% (60%-78%) and 76% (72%-80%) for anemia (<12 g/dL [female], <13 g/dL [male]), respectively. At 90% sensitivity, specificity was 76% (58%-83%) for CRP; 62% (47%-74%) for MLR; 64% (47%-75%) for IP-10, and 28% (17%-51%) for anemia. There was no significant difference for any of the four TTTs in diagnostic odds ratio between participants with and without a history of previous TB, between smokers and non-smokers, and between males and females. However, MLR performed significantly (