This pragmatic cross-sectional study describes the yield of active tuberculosis (TB) disease and the prevalence of TB infection among household contacts (HHC) of pulmonary TB patients in Cambodia. The investigation compared contacts of bacteriologically confirmed and bacteriologically unconfirmed TB index cases and assessed the potential implications for contact investigation strategies and delivery of TB preventive treatment (TPT).
The study was conducted in five operational districts from February 2023 to April 2024. Household contacts of persons with pulmonary TB in the preceding two years were screened for active TB disease. For estimating the prevalence of TB infection, two purposively selected sites (one urban and one rural) recruited eligible contacts aged 5 years or older who were HIV negative. Blood samples were collected for Interferon Gamma Release Assay (IGRA) testing using QuantiFERON-TB Gold Plus.
Analysis used modified Poisson regression with robust variance estimation to identify factors independently associated with IGRA positivity. The study report provides overall counts, proportions, and 95% confidence intervals for key outcomes reported in the screening population.
A total of 864 household contacts were screened. Among these, 26 contacts were diagnosed with active TB disease.
Notably, a large proportion of the TB cases identified were asymptomatic at the time of screening:
For TB infection assessment, there were 453 valid IGRA results. Of these, 21.2% (95% CI 17.5–25.2) were IGRA positive, indicating a substantial burden of latent or recent TB infection in the screened contacts.
The analysis identified several factors independently associated with a positive IGRA result. IGRA positivity was associated with:
These associations indicate demographic and exposure-related variation in TB infection risk among household contacts within the study settings.
Findings from this operational assessment have direct implications for programmatic strategies:
Limiting contact investigation to index patients with bacteriologically confirmed TB may lead to missed active TB cases, since contacts of bacteriologically unconfirmed index cases in this study had a comparable or higher observed disease yield.
Relying solely on symptom screening risks failing to identify a meaningful proportion of active TB among contacts because many of the detected cases were asymptomatic, particularly among contacts of bacteriologically unconfirmed index cases.
Without testing for infection (for example with IGRA), offering TPT broadly to household contacts may result in many people receiving preventive therapy despite not being infected, while conversely some contacts with asymptomatic active disease could inappropriately receive preventive treatment rather than being diagnosed and managed as active TB.
These results support reconsideration of current contact investigation algorithms and suggest that programs should weigh the trade-offs of symptom-only screening and of restricting investigation to bacteriologically confirmed index cases. Incorporating infection testing or broader diagnostic approaches may help differentiate who should receive TPT versus active TB treatment.
The report provides summary results from a pragmatic cross-sectional evaluation in selected programmatic districts and two purposively chosen IGRA testing sites (one urban, one rural). Detailed operational characteristics, longer-term follow-up, and broader geographic representativeness were not described in the abstract.
In these selected Cambodian programmatic settings, the study found that contacts of both bacteriologically confirmed and unconfirmed pulmonary TB patients had measurable rates of active TB disease and that more than one in five tested contacts were IGRA positive. The presence of a substantial proportion of asymptomatic active TB among contacts and the pattern of IGRA associations with age, urban residence, and exposure to bacteriologically confirmed index cases indicate that current strategies that limit contact investigation or rely on symptom screening alone may miss cases or misallocate preventive treatment.
Clinicians and TB program managers should consider these findings when designing or updating contact investigation approaches and TPT eligibility criteria. The study underscores the potential value of infection testing and broader diagnostic assessment in household contact workflows to better target preventive and curative TB services.