Systematic Review: T-Cell–Based Assays for the Diagnosis of Latent Tuberculosis Infection: An Update

5 August 2008 | Volume 149 Issue 3

Background: Interferon-–release assays (IGRAs) are alternatives to the tuberculin skin test (TST). A recent meta-analysis showed that IGRAs have high specificity, even among populations that have received bacille Calmette–Guérin (BCG) vaccination. Sensitivity was suboptimal for TST and IGRAs.

Purpose: To incorporate new evidence into an updated meta-analysis on the sensitivity and specificity of IGRAs.

Data Sources: PubMed was searched through 31 March 2008, and citations of all original articles, guidelines, and reviews for studies published in English were reviewed.

Study Selection: Studies that evaluated QuantiFERON-TB Gold, QuantiFERON-TB Gold In-Tube (both from Cellestis, Victoria, Australia), and T-SPOT.TB (Oxford Immunotec, Oxford, United Kingdom) or its precommercial ELISpot version, when data on the commercial version were lacking. For assessing sensitivity, the study sample had to have microbiologically confirmed active tuberculosis. For assessing specificity, the sample had to comprise healthy, low-risk individuals without known exposure to tuberculosis. Studies with fewer than 10 participants and those that included only immunocompromised participants were excluded.

Data Extraction: One reviewer abstracted data on participant characteristics, test characteristics, and test performance from 38 studies; these data were double-checked by a second reviewer. The original investigators were contacted for additional information when necessary.

Data Synthesis: A fixed-effects meta-analysis with correction for overdispersion was done to pool data within prespecified subgroups. The pooled sensitivity was 78% (95% CI, 73% to 82%) for QuantiFERON-TB Gold, 70% (CI, 63% to 78%) for QuantiFERON-TB Gold In-Tube, and 90% (CI, 86% to 93%) for T-SPOT.TB. The pooled specificity for both QuantiFERON tests was 99% among non–BCG-vaccinated participants (CI, 98% to 100%) and 96% (CI, 94% to 98%) among BCG-vaccinated participants. The pooled specificity of T-SPOT.TB (including its precommercial ELISpot version) was 93% (CI, 86% to 100%). Tuberculin skin test results were heterogeneous, but specificity in non–BCG-vaccinated participants was consistently high (97% [CI, 95% to 99%]).

Limitation: Most studies were small and had limitations, including no gold standard for diagnosing latent tuberculosis and variable TST methods and cutoff values. Data on the specificity of the commercial T-SPOT.TB assay were limited.

Conclusion: The IGRAs, especially QuantiFERON-TB Gold and QuantiFERON-TB Gold In-Tube, have excellent specificity that is unaffected by BCG vaccination. Tuberculin skin test specificity is high in non–BCG-vaccinated populations but low and variable in BCG-vaccinated populations. Sensitivity of IGRAs and TST is not consistent across tests and populations, but T-SPOT.TB appears to be more sensitive than both QuantiFERON tests and TST.

Editors' Notes Context Tuberculin skin tests (TSTs) and new interferon-–release assays (IGRAs) are alternative tests for detecting latent tuberculosis. Contribution This updated meta-analysis of 38 studies found that sensitivity of IGRAs and TST was not consistent across tests and populations, but TSPOT.TB seemed to be more sensitive than QuantiFERON tests and TST. Both the TST and IGRAs had high specificity (>95%) for tuberculosis in populations not vaccinated with bacille Calmette–Guérin (BCG). The specificity of IGRAs was also high in populations vaccinated with BCG, whereas TST specificity was low and highly variable. Caution The studies had many limitations, including small sample sizes and no gold standard for diagnosing latent tuberculosis. Implication The specificity of IGRAs for detecting latent tuberculosis is good and seems unaffected by BCG vaccination status. —The Editors

 

Author and Article Information

From McGill University and Montreal Chest Institute, Montreal, Quebec, Canada.

Grant Support: By the Canadian Institutes of Health Research (grant MOP-81362). Dr. Pai is a recipient of a New Investigator Career Award from the Canadian Institutes of Health Research. Dr. Menzies is a recipient of a career award from the Fonds de la recherche en santé du Québec.

Potential Financial Conflicts of Interest: Other: Dr. Pai serves as an external consultant for the Foundation for Innovative New Diagnostics, Geneva, a nonprofit agency that collaborates with several industry partners, including Cellestis, Carnegie, Australia, for the development of new diagnostics for neglected infectious diseases. No industry partner was involved in the preparation of this manuscript.

Corresponding Author: Madhukar Pai, MD, PhD, Department of Epidemiology, Biostatistics & Occupational Health, McGill University, 1020 Pine Avenue West, Montreal, Quebec, H3A 1A2 Canada; e-mail: madhukar.pai{at}mcgill.ca.

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