Accuracy and safety of C-TST for tuberculosis infection: A clinical trial in Brazil

BACKGROUND: Tuberculosis infection (TBI) diagnosis in BCG-vaccinated, high-burden settings remains challenging. RESEARCH QUESTION: We aimed to assess the sensitivity, specificity, and safety of the C-tuberculin skin test (C-TST), compared with PPD RT-23, for tuberculosis infection in BCG-vaccinated adults. STUDY DESIGN AND METHODS: Randomised, double-blind clinical trial in Brazil. Adults with pulmonary tuberculosis (PTB) and asymptomatic controls without known TB exposure or prior TB/TPT underwent C-TST, PPD RT-23, and QuantiFERON-TB Gold Plus (QFT-Plus). Skin tests were read by two strategies: (a) induration only or (b) induration or erythema, at a ≥5-mm cut-off. Sensitivity was assessed in PTB; specificity for C-TST and PPD RT-23 was estimated against QFT-Plus. Adverse events were monitored. RESULTS: Among 446 participants (141 PTB; 305 controls), at the 5-mm cut-off, C-TST showed lower sensitivity but higher specificity than PPD RT-23. With strategy (a) and (b), C-TST sensitivity was 0.67 and 0.68, specificity was 0.92 and 0.9, compared to 0.74 sensitivity and 0.78 specificity for PPD RT-23. Adverse events were more frequent in PTB: 12.1% (C-TST) and 6.4% (PPD RT-23); none were serious. CONCLUSION: In BCG‑vaccinated adults, C-TST showed a trade-off of higher specificity and lower sensitivity than PPD RT-23 at the 5-mm cut-off; and a favourable safety profile. Adding erythema to readings did not improve accuracy, suggesting that C-TST may be a useful alternative for programmatic TBI screening in high-burden settings. TRIAL REGISTRATION: Trial registry number RBR-7tn2ysw (https://ensaiosclinicos.gov.br/ registered on 25 January 2021).