Predictors for false-negative QuantiFERON-TB Gold assay results in patients with extrapulmonary tuberculosis

Abstract

BackgroundsExtrapulmonary tuberculosis (EPTB) is a heterogeneous disease, and diagnosis is sometimes difficult. We investigated the diagnostic performance of the QuantiFERON-TB Gold assay (QFT-GIT) according to sites of EPTB and predictors for false-negative QFT-GIT results.MethodsA total of 2176 patients were registered with active TB from January 2012 to December 2016 in Seoul St. Mary’s Hospital, a 1200-bed tertiary teaching hospital in Seoul, Korea. We retrospectively reviewed the medical records of 163 EPTB patients who underwent QFT-GIT.ResultsFalse negative QFT-GIT results were found in 28.8% (95% CI 0.22–0.36) of patients with EPTB. In the proven TB group, negative QFT-GIT results were found in 28.6% (95% CI 0.04–0.71) of pleural, 8.3% 0.002–0.38of lymph node, 8.3% (95% CI 0.002–0.38) of skeletal and 5.8% (95% CI 0.001–0.28) of gastrointestinal TB cases. Among probable TB cases, QFT-GIT negative results were identified in 46.2% (95% CI 0.19–0.75) of skeletal, 33.3% (95% CI 10–0.65) of pericardial, 30.8% (95% CI 0.09–0.61) of pleural and 17.2% (95% CI 0.10–0.56) of gastrointestinal TB cases. In the possible TB cases, central nervous system TB (n = 21) was most frequent, and 66.7% (95% CI 0.43–0.85) of those showed QFT-GIT negative results. By multivariate analysis, possible TB was independently associated with false-negative QFT-GIT results (OR 4.92, 95% CI 1.51–16.06, p = 0.008).ConclusionsPrudent interpretation of QFT-GIT results might be needed according to anatomic site of involvement and diagnostic criteria in patients with high suspicion of EPTB.

Factors associated with false negative interferon-γ release assay results in patients with tuberculosis: A systematic review with meta-analysis

“…Extrapulmonary TB. Five studies evaluated the influence of extrapulmonary TB on false negative results of IGRA 15,19,21,24,26 . QFT-GIT and T-SPOT were used for the evaluation of TB in one 19 and four 15,21,24,26 studies, respectively.…”

Tuberculous pleural effusion

“…IFN‐γ release assays (IGRA) such as the QuantiFERON‐TB Gold (QIAGEN, Hilden, Germany) and T‐SPOT.TB (Oxford Immunotec, Oxford, UK) use Mtb‐derived antigen to stimulate the release of IFN‐γ from T lymphocytes in a specimen, which is then quantified. IGRA have so far demonstrated poor sensitivity and specificity in pleural fluid, possibly attributable to the T lymphocytes' already being in a maximally stimulated state within the pleural space …”

“…IGRA have so far demonstrated poor sensitivity and specificity in pleural fluid, possibly attributable to the T lymphocytes' already being in a maximally stimulated state within the pleural space. [66][67][68] Other pleural fluid biomarkers Lysozyme, a neutrophil cytoplasmic granule enzyme, is found in concentrations >15 mg/dL in 80% of tuberculous effusions. It is however a non-specific test.…”

Perianal ulceration as primary presentation in a patient with disseminated multi‐drug resistant tuberculosis

“…The workup of this patient was elaborate, as a previous histopathological examination did not show signs of TB, and Ziehl-Neelsen staining of the biopsy and the interferon-gamma release assay were negative. False negative QuantiFERON results are reported in up to 29 % of extrapulmonary TB cases and should therefore be interpreted carefully [13].…”