Commercial Interferon Gamma Release Assays Compared to the Tuberculin Skin Test for Diagnosis of Latent Mycobacterium tuberculosis Infection in Childhood Contacts in the Gambia

Background: We compared the performance of tuberculin skin test (TST), Quantiferon-TB Gold in-tube (QFT-GIT), and T-SPOT. TB in diagnosing latent tuberculosis (LTBI) among childhood TB contacts in a TB endemic setting with high BCG coverage. We evaluated the performance of interferon gamma release assays (IGRAs) and TST when combined in an algorithm. Methods: Childhood contacts of newly diagnosed TB patients were tested with TST, QFT-GIT, and T-SPOT. The level of exposure in contacts was categorized according to whether they slept in the same room, same house, or a different house as the index case. For the evaluation of combined test performance, prior estimates for prevalence of latent TB were used in Bayesian models that assumed conditional dependence between tests. Results: A total of 285 children were recruited. Overall, 26.5%, 33.0%, and 33.5% were positive for TST, T-SPOT, or QFT-GIT, respectively. All 3 tests responded to the gradient of sleeping proximity to the index case. Neither TST nor IGRA results were confounded by BCG vaccination. There was moderate agreement (kappa = 0.40-0.68) between all 3 tests. Combination of either IGRA with TST increased sensitivity (by 9.3%-9.6%) especially in contacts in the highest exposure category but was associated with loss of specificity (9.9%-11.3%). Conclusion: IGRAs and TST are similar in their diagnostic performance for LTBI. An approximate 10% sensitivity benefit for using the TST and an IGRA in combination is associated with a slightly greater specificity loss. Testing strategies combining an IGRA and TST with an or statement may be useful only in situations where there is a high pretest probability of latent infection.