title: Are interferon-γ release assays useful for diagnosing active tuberculosis in a high-burden setting?
abstract: 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.
authors.affiliation: Dept of Medicine, Groote Schuur Hospital, Observatory, Cape Town, South Africa.
authors.forename: D I
authors.initials: DI
authors.lastname: Ling
authors.forename: M
authors.initials: M
authors.lastname: Pai
authors.forename: V
authors.initials: V
authors.lastname: Davids
authors.forename: L
authors.initials: L
authors.lastname: Brunet
authors.forename: L
authors.initials: L
authors.lastname: Lenders
authors.forename: R
authors.initials: R
authors.lastname: Meldau
authors.forename: G
authors.initials: G
authors.lastname: Calligaro
authors.forename: B
authors.initials: B
authors.lastname: Allwood
authors.forename: R
authors.initials: R
authors.lastname: van Zyl-Smit
authors.forename: J
authors.initials: J
authors.lastname: Peter
authors.forename: E
authors.initials: E
authors.lastname: Bateman
authors.forename: R
authors.initials: R
authors.lastname: Dawson
authors.forename: K
authors.initials: K
authors.lastname: Dheda
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D059425:Interferon-gamma Release Tests / Q000379:methods / Q000592:standards*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000378:metabolism; D011237:Predictive Value of Tests; D011320:Primary Health Care / Q000379:methods; D013902:Radiography, Thoracic / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013019:South Africa; D014374:Tuberculin Test / Q000379:methods; D014376:Tuberculosis / Q000175:diagnosis* / Q000378:metabolism
chemical_list: D007371:Interferon-gamma