Background: Preventive therapy for tuberculosis reduces the risk of disease in people who have been infected but who are not sick. High-tuberculosis-burden countries expanding preventive therapy use must decide how tuberculosis infection testing should be used for risk-stratification among household contacts of tuberculosis patients.
Methods: We modelled the risk of tuberculosis disease and risk of severe adverse events, comparing two preventive therapy strategies: preventive therapy for all household contacts, or preventive therapy for only household contacts with a positive tuberculin skin test (TST) result. We used data from clinical trials and literature on tuberculosis natural history to model outcomes assuming different preventive therapy regimens, ages, and TST positivity prevalences.
Findings: Assuming 25% prevalence of TST positivity among 1000 household contacts aged 0-17 years, a treat-all approach with isoniazid-rifapentine compared to a treat-TST-only approach led to 13 fewer incident tuberculosis cases (interquartile range [IQR]: -5, -18) and 4 additional severe adverse events (IQR: 2,6). Similar results were seen for other regimens. For adults, a treat-all approach led to fewer incident tuberculosis cases, and additional adverse events increased with age; a rifampicin-only regimen was associated with the fewest additional severe
adverse events.
Interpretation: Based on available data, giving preventive therapy to all contacts would likely reduce the incidence of tuberculosis contacts in high-burden settings. Adverse events can be minimized by using non-isoniazid regimens and, in adults older than 18 years, focusing treatment on individuals with a positive infection test.