Fourth-Generation QuantiFERON-TB Gold Plus: What Is the Evidence?

Area of Science:

• Immunology
• Infectious Diseases
• Diagnostics

Background:

• QuantiFERON-TB Gold Plus (QFT-Plus) is a new interferon gamma release assay (IGRA) approved by the U.S. FDA, replacing QuantiFERON-TB Gold In-Tube (QFT-GIT).
• QFT-Plus elicits responses from both CD4 and CD8 T cells, aiming for improved detection of latent tuberculosis infection (LTBI).

Purpose of the Study:

• To compare the performance of QFT-Plus against QFT-GIT in various populations, including active tuberculosis (TB) patients, high-risk groups, and low-risk individuals.
• To evaluate the potential advantages of QFT-Plus in detecting LTBI, particularly in recently exposed individuals, immunocompromised hosts, and children.

Main Methods:

• A minireview summarizing recent publications that directly compared QFT-Plus and QFT-GIT.
• Analysis of study data focusing on sensitivity in active TB patients and LTBI surrogates, agreement in high-risk groups, and specificity in low-risk populations.

Main Results:

• Studies do not currently support superior performance of QFT-Plus over QFT-GIT in active TB and LTBI patients; sensitivity differences were not significant (-4.0% to 2.0%).
• High-risk groups showed strong agreement between QFT-Plus and QFT-GIT (89.9%-96.0%, kappa 0.80-0.91).
• QFT-Plus demonstrated slightly lower specificity than QFT-GIT in low-risk populations (-7.4% to 0%).

Conclusions:

• Current evidence does not confirm QFT-Plus's superior performance in detecting active TB or LTBI compared to QFT-GIT.
• Further research is necessary to assess QFT-Plus sensitivity in immunocompromised individuals and children.
• Additional studies are needed to validate modified interpretations for identifying false positives in low-risk healthcare workers.