Tuberculosis disease and infection among household contacts of bacteriologically confirmed vs unconfirmed tuberculosis in Cambodia: considerations for optimising contact investigation and preventive treatment

Background This study aimed to describe the yield of tuberculosis (TB) disease among household contacts (HHC) of individuals with bacteriologically confirmed and unconfirmed pulmonary TB, to estimate the prevalence of TB infection using Interferon Gamma Release Assay (IGRA), and to identify factors associated with IGRA positivity.Methods We conducted a pragmatic, cross-sectional study in five operational districts between February 2023 and April 2024. HHC of persons with pulmonary TB in the preceding two years were screened for TB. Among eligible contacts (aged ≥5 years and HIV negative) at two purposively selected sites (one urban and one rural), blood samples were collected for IGRA using QuantiFERON®-TB Gold Plus. Modified Poisson regression with robust variance estimation was used to identify factors independently associated with IGRA positivity.Results Among 864 HHC, 26 were diagnosed with TB disease: 2.7 per 100 (95% CI 1.4–4.6) among contacts of bacteriologically confirmed TB and 3.4 per 100 (95% CI 1.9–5.6) among contacts of bacteriologically unconfirmed TB. More than half were asymptomatic (37.5% bacteriologically confirmed, 66.7% bacteriologically unconfirmed). Of 453 valid IGRA results, 21.2% (95% CI 17.5–25.2) were positive. IGRA positivity was associated with older age, urban residence, and being contacts of bacteriologically confirmed TB.Conclusion In these selected programmatic settings, limiting contact investigation to bacteriologically confirmed TB and relying on symptom screening may result in missed cases. Without infection testing, most HHC offered TPT may not require it, while others with asymptomatic TB disease may inappropriately receive preventive treatment.