Risk of progression to pulmonary tuberculosis among household contacts with chest radiographic abnormalities in South Africa.

Background: High-risk subgroups among household contacts of persons with tuberculosis (TB) might benefit from additional interventions. However, the significance of an abnormal baseline chest radiograph (CXR) suggestive of TB, despite negative sputum microbiology, is uncertain. Methods: Adults (≥18 years) with recent household TB exposure were enrolled at three South African sites (April 2021-September 2022). All participants underwent symptom screening, CXR, and sputum Xpert Ultra and MGIT culture. Pulmonary TB diagnosis was microbiologically-confirmed. Participants were followed for symptomatic incident TB through 12 months. Multivariable logistic regression identified factors associated with abnormal CXR suggestive of TB. Poisson regression estimated incidence rate ratios (IRR). Results: Baseline CXR were abnormal in 157/795 (19.7%) participants; associated with older age (adjusted odds ratio, aOR=1.04, 95%CI 1.02-1.05); prior TB (aOR=6.39, 95%CI 4.18-9.78); and current smoking (aOR=1.61, 95%CI 1.00-2.62). Symptomatic incident TB developed in 8/795 (1.0%) participants, including 7/8 (87.5%) who were asymptomatic and 4/8 (50.0%) with abnormal CXR at baseline. TB incidence was four-fold higher in those with abnormal versus normal CXR (IRR=4.02, 95%CI 1.01-15.97), with a risk difference of 1,969 (95%CI -657-4,595) per 100,000 person-years, but after median 12.1 (IQR 11.1-13.1) months follow-up, 153/157 (97.5%) had not progressed to incident TB. Conclusions: Adult contacts with CXR abnormalities, but without prevalent TB, had a four-fold higher risk of TB within one year, compared to those with normal CXR. This additional risk warrants targeted preventive treatment and extended surveillance, but since most remained TB-free, therapeutic TB treatment is not justified.