Impact of targeted testing for latent tuberculosis infection using commercially available diagnostics

Abstract

Background: The interferon-γ release assays (IGRAs) are increasingly being used as an alternative to the tuberculin skin test (TST). Although IGRAs may have better specificity and certain logistic advantages to the TST, their use may contribute to overtesting of low-prevalence populations if testing is not targeted. The objective of this study was to evaluate the accuracy of a risk factor questionnaire in predicting a positive test result for latent tuberculosis infection using the 3 commercially available diagnostics.

Methods: A cross-sectional comparison study was performed among recruits undergoing Army basic training at Fort Jackson, South Carolina, from April through June 2009. The tests performed included: (1) a risk factor questionnaire; (2) the QuantiFERON Gold In-Tube test (Cellestis Limited, Carnegie, Victoria, Australia); (3) the T-SPOT.TB test (Oxford Immunotec Limited, Abingdon, United Kingdom); and (4) the TST (Sanofi Pasteur Ltd., Toronto, Ontario, Canada). Prediction models used logistic regression to identify factors associated with positive test results. RFQ prediction models were developed independently for each test.

Results: Use of a 4-variable model resulted in 79% sensitivity, 92% specificity, and a c statistic of 0.871 in predicting a positive TST result. Targeted testing using these risk factors would reduce testing by >90%. Models predicting IGRA outcomes had similar specificities as the skin test but had lower sensitivities and c statistics.

Conclusions: As with the TST, testing with IGRAs will result in false-positive results if the IGRAs are used in low-prevalence populations. Regardless of the test used, targeted testing is critical in reducing unnecessary testing and treatment.

Clinical trial registration: NCT00804713.

Figures

Figure 1.

Flow chart of study comparing the tuberculin skin test with 2 interferon-γ release assays in 2009 at Fort Jackson, South Carolina.

Figure 2.

Receiver operator characteristics curve for predictors of latent tuberculosis infection (LTBI), as measured by the tuberculin skin test (TST), QuantiFERON® Gold In-Tube (QFT), and T-SPOT®.TB (T-Spot) among US Army Recruits. Predictors included in the logistic regression model: close contact with a tuberculosis (TB) case, casual contact with a TB case, TB prevalence in country of birth, history of living with parent born outside the US, prior positive skin test result, prior TB treatment, history of living in a congregate setting, and health care work. AUC, area under the curve.