Are interferon-γ release assays useful for diagnosing active tuberculosis in a high-burden setting?

Area of Science:

• Immunology
• Infectious Diseases
• Diagnostics

Background:

• Interferon-γ release assays (IGRAs) are primarily used for latent tuberculosis (TB) diagnosis.
• The utility of IGRAs in distinguishing active TB in high-burden settings remains under investigation.
• Previous studies have not conclusively determined the role of IGRAs in diagnosing smear-negative TB or as rule-out tests.

Purpose of the Study:

• To evaluate the accuracy of two IGRAs (QuantiFERON®-TB Gold In-tube and T-SPOT®.TB) in diagnosing active TB in a high-burden setting.
• To assess if IGRA response magnitude can differentiate active TB from other conditions.
• To determine the effectiveness of IGRAs as rule-out tests for active TB, particularly in smear-negative cases.

Main Methods:

• A study involving 395 patients with suspected TB in Cape Town, South Africa.
• Evaluation of QuantiFERON®-TB Gold In-tube (QFT-GIT) and T-SPOT®.TB performance.
• Analysis of IGRA accuracy, sensitivity, specificity, and negative predictive value (NPV), considering HIV status and CD4 count.

Main Results:

• QFT-GIT sensitivity was 76% and specificity 42%; T-SPOT®.TB sensitivity was 84% and specificity 47%.
• Higher interferon-γ responses were observed in TB patients, but cut-off variations did not improve discrimination.
• In smear-negative patients, chest radiography had a superior NPV (98%) compared to QFT-GIT (85-89%) and T-SPOT®.TB (87-92%).

Conclusions:

• IGRAs alone are insufficient as rule-in or rule-out tests for active TB in high-burden settings.
• Chest radiography is a more reliable diagnostic tool for smear-negative TB, including in HIV-infected individuals.
• The diagnostic accuracy of IGRAs was not significantly influenced by HIV status or CD4 count.