Combining tuberculin skin test with follow-on interferon gamma release assay markedly improves screening of household contacts

Introduction In Hong Kong, tuberculin skin test (TST) with a 15 mm cut-off was used at 0 and 3 months for contact screening, but half of future tuberculosis cases might be missed. Follow-on interferon-gamma release assay (IGRA) was added for those with tuberculin reaction of 5-14 mm in a pilot programme. Methods This was a prospective cohort study. All household contacts of smear-positive tuberculosis aged 12-64 registered in Hong Kong Tuberculosis and Chest Service from 1 July 2018 to 30 June 2022 were prospectively tracked through medical records and the territory-wide tuberculosis notification registry for active tuberculosis till 31 December 2022. Results Among untreated contacts with tuberculin reaction of 5-14 mm in either the initial test or second test at 3 months, the tuberculosis rate among those with a follow-on reactive IGRA was significantly higher than those with a non-reactive IGRA (12.44 vs 0.75 per 1000 person-years, relative risk: 16.52, p=0.003). After adjustment for the efficacy of preventive treatment among all treated cases, the estimated proportions of tuberculosis cases captured by the pilot programme criterion of TST≥15 mm/TST 5-14 mm and IGRA reactive/TST conversion were similar to those captured by TST cut-offs of 5 mm or 10 mm, despite consistently lower positive rates. With an overall test-positive rate of 54.5%, the pilot programme captured 95.8% of estimated future tuberculosis cases at a relative risk between test-positive and test-negative cases of 19. Conclusion Combining TST with follow-on IGRA for those with tuberculin reaction of 5-14 mm markedly improves screening of household contacts in an intermediate burden setting.