Evaluating latent tuberculosis infection diagnostics using latent class analysis

Abstract

Background: Lack of a gold standard for latent TB infection has precluded direct measurement of test characteristics of the tuberculin skin test and interferon-γ release assays (QuantiFERON Gold In-Tube and T-SPOT.TB).

Objective: We estimated test sensitivity/specificity and latent TB infection prevalence in a prospective, US-based cohort of 10 740 participants at high risk for latent infection.

Methods: Bayesian latent class analysis was used to estimate test sensitivity/specificity and latent TB infection prevalence among subgroups based on age, foreign birth outside the USA and HIV infection.

Results: Latent TB infection prevalence varied from 4.0% among foreign-born, HIV-seronegative persons aged <5 years to 34.0% among foreign-born, HIV-seronegative persons aged ≥5 years. Test sensitivity ranged from 45.8% for the T-SPOT.TB among foreign-born, HIV-seropositive persons aged ≥5 years to 80.7% for the tuberculin skin test among foreign-born, HIV-seronegative persons aged ≥5 years. The skin test was less specific than either interferon-γ release assay, particularly among foreign-born populations (eg, the skin test had 70.0% specificity among foreign-born, HIV-seronegative persons aged ≥5 years vs 98.5% and 99.3% specificity for the QuantiFERON and T-SPOT.TB, respectively). The tuberculin skin test's positive predictive value ranged from 10.0% among foreign-born children aged <5 years to 69.2% among foreign-born, HIV-seropositive persons aged ≥5 years; the positive predictive values of the QuantiFERON (41.4%) and T-SPOT.TB (77.5%) were also low among US-born, HIV-seropositive persons aged ≥5 years.

Conclusions: These data reinforce guidelines preferring interferon-γ release assays for foreign-born populations and recommending against screening populations at low risk for latent TB infection.

Trial registration number: NCT01622140.

Keywords: clinical epidemiology; tuberculosis.

Figure 1

Flow chart of enrolled participants. QFT, QuantiFERON Gold In-Tube; TSPOT, T-SPOT.TB; TST, tuberculin skin test.

Figure 2

Latent TB infection prevalence and test characteristics (sensitivity and specificity) for foreign-born, HIV-seronegative participants aged ≥5 years. On the x-axis, the label ‘CI’ stands for the model that assumes conditional independence of the tests; ‘R’ stands for the model that includes a random effect (to model conditional dependence between the tests); and ‘Prior’ indicates the scientific literature-based prior distribution (for test sensitivity only). The horizontal lines in the centre of the rectangles are the Bayesian posterior means, and the top and bottom lines in each box are the boundaries of the first and third quartiles, respectively. The tips of the vertical lines span the 95% credible interval for each parameter. For purposes of this analysis, TSPOT was evaluated by using the international criteria for a positive test (≥6 spots is positive; ≤5 spots is negative). CI, conditional independence model; Prev, latent TB prevalence; Prior, scientific literature-based prior distribution (for test sensitivity only); R, random effect model; sensQFT, sensitivity of QuantiFERON Gold In-Tube; sensTSPOT, sensitivity of T-SPOT.TB; sensTST, sensitivity of the tuberculin skin test; specQFT, specificity of QuantiFERON Gold In-Tube; specTSPOT, specificity of T-SPOT.TB; specTST, specificity of the tuberculin skin test.