Timing and predictors of disease incidence among named contacts of reported tuberculosis patients in a low incidence setting

Contact investigations are crucial for tuberculosis (TB) control, yet the temporal dynamics of disease progression among exposed contacts remain poorly understood. We conducted a retrospective cohort study of 44,106 contacts linked to 6,243 index TB cases diagnosed between 2009 and 2023. During the 15-year follow-up, 454 contacts developed TB disease, with 43.4% being incident cases. Using time-to-event analysis with left truncation to account for varying follow-up times, and mixed effect Cox models to account for index case and county-level variability, we estimated the median time to TB incidence at 11 (IQR 4-48) months after initiating contact investigation. The risk of TB disease varied markedly by age and immune status. Children aged 0-15 showed over nine times higher risk compared to adults aged 25-44 (aHR = 9.59; 95% CI: 3.17-29.02; p < 0.001). Contacts co-infected with HIV demonstrated a three-fold increased risk of TB (aHR = 2.35; 95% CI: 1.08-5.10; p = 0.031) relative to those without HIV. A history of a previous TB diagnosis conferred a protective effect on the risk of TB incident (aHR = 0.40; 95% CI: 0.20-0.80; p = 0.009). Additionally, individuals who had incomplete therapy for latent TB infection (LTBI) also experienced a protective effect (aHR = 0.32; 95% CI: 0.15-0.71; p = 0.005). These findings highlight a critical window for intervention with follow-up needed for at least 1-4 years after initial contact investigations. The results also emphasize the need for targeted, risk-stratified surveillance and LTBI treatment for children and individuals with HIV who are contacts of confirmed TB cases.