Effectiveness and Implementation of a Clinical Risk Score for Early Diagnosis of Tuberculosis in Uganda: A Pragmatic, Clustered Randomization Clinical Trial

<b>Rationale:</b> Undertreatment of tuberculosis (TB) is common in resource-limited settings where same-day microbiological diagnosis is unavailable. <b>Objectives:</b> We evaluated if a simple clinical risk score for predicting active TB could facilitate treatment initiation among individuals at high risk for TB. <b>Methods:</b> We conducted a pragmatic, implementation-effectiveness study in periurban primary health clinics in Uganda. Four intervention clinics were paired with standard-of-care comparison clinics. Providers in intervention clinics were trained to use the score and set a threshold score for considering same-day treatment initiation; treatment decisions were at the providers' discretion. Our primary effectiveness outcome was the change in the proportion of individuals with confirmed TB who started on treatment within 7 days of presentation, comparing preintervention and postintervention periods. <b>Results:</b> Among intervention clinics, 594 (83%) of 720 people diagnosed with TB started treatment within 7 days during the preintervention period versus 264 (84%) of 316 after implementation (pre-post difference, 1%; 95% confidence interval [95% CI], -6%, 8%). In comparison clinics, 7-day treatment initiation changed from 312 (86%) of 363 preintervention to 153 (73%) of 211 postintervention (pre-post difference, -13%; 95% CI, -22, -5%). A difference-in-differences estimate was 14% (95% CI, 10%, 19%). In intervention clinics, 1,206 (66%) of 1,826 people presenting with TB symptoms were administered the risk score. Two hundred twenty-nine (19%) had a score above the treatment threshold, and 105 (46%) initiated treatment on the same day. <b>Conclusions:</b> An easy-to-use clinical risk score did not increase 7-day empiric treatment initiation in intervention clinics. However, it improved rapid treatment initiation relative to clinics using the prevailing standard of care. The score was also highly acceptable to clinical providers. Clinical trial registered with www.clinicaltrials.gov (NCT05122624).