PT - JOURNAL ARTICLE AU - D.I. Ling AU - M. Pai AU - V. Davids AU - L. Brunet AU - L. Lenders AU - R. Meldau AU - G. Calligaro AU - B. Allwood AU - R. van Zyl-Smit AU - J. Peter AU - E. Bateman AU - R. Dawson AU - K. Dheda TI - Are interferon-γ release assays useful for diagnosing active tuberculosis in a high-burden setting? AID - 10.1183/09031936.00181610 DP - 2011 Sep 01 TA - European Respiratory Journal PG - 649--656 VI - 38 IP - 3 4099 - http://erj.ersjournals.com/content/38/3/649.short 4100 - http://erj.ersjournals.com/content/38/3/649.full SO - Eur Respir J2011 Sep 01; 38 AB - Although interferon-γ release assays (IGRAs) are intended for diagnosing latent tuberculosis (TB), we hypothesised that in a high-burden setting: 1) the magnitude of the response when using IGRAs can distinguish active TB from other diagnoses; 2) IGRAs may aid in the diagnosis of smear-negative TB; and 3) IGRAs could be useful as rule-out tests for active TB. We evaluated the accuracy of two IGRAs (QuantiFERON®-TB Gold In-tube (QFT-GIT) and T-SPOT®.TB) in 395 patients (27% HIV-infected) with suspected TB in Cape Town, South Africa. IGRA sensitivity and specificity (95% CI) were 76% (68–83%) and 42% (36–49%) for QFT-GIT and 84% (77–90%) and 47% (40–53%) for T-SPOT®.TB, respectively. Although interferon-γ responses were significantly higher in the TB versus non-TB groups (p<0.0001), varying the cut-offs did not improve discriminatory ability. In culture-negative patients, depending on whether those with clinically diagnosed TB were included or excluded from the analysis, the negative predictive value (NPV) of QFT-GIT, T-SPOT®.TB and chest radiograph in smear-negative patients varied between 85 and 89, 87 and 92, and 98% (for chest radiograph), respectively. Overall accuracy was independent of HIV status and CD4 count. In a high-burden setting, IGRAs alone do not have value as rule-in or -out tests for active TB. In smear-negative patients, chest radiography had better NPV even in HIV-infected patients.