Challenges with QuantiFERON-TB Gold assay for large-scale, routine screening of U.S. healthcare workers

Abstract

Rationale: North American occupational health programs that switched from the tuberculin skin test (TST) to IFN-γ release assays for latent tuberculosis screening are reporting challenges with interpretation of serial testing results in healthcare workers (HCWs). However, limited data exist on the reproducibility of serial IFN-γ release assay results in low-risk HCWs.

Objectives: To evaluate the short-term reproducibility of QuantiFERON-TB Gold In-Tube (QFT) in a large cohort of HCWs and to define a QFT cutoff yielding a conversion rate equivalent to historical TST rates.

Methods: We retrospectively evaluated the QFT results from HCWs with two or more QFT tests performed between June 2008 and July 2010 at an academic institution. Outcome measures were proportions of reproducibility, quantitative results, and conversion rates with alternate QFT cutoffs.

Measurements and main results: A total of 9,153 HCWs with two or more QFT tests were included in the analysis. Of 8,227 individuals with a negative result, 4.4% (n = 361) converted their QFT result over 2 years. A total of 261 (72.3%) of the HCWs with conversions underwent repeat short-term testing after the first positive result with 64.8% reverting (n = 169). An IFN-γ cutoff of 5.3 IU/ml or higher (manufacturer's cutoff is ≥0.35 IU/ml) yielded a conversion rate of 0.4%, equal to our institution's historical TST conversion rate.

Conclusions: The manufacturer's definition of QFT conversion results in an inflated conversion rate that is incompatible with our low-risk setting. A significantly higher QFT cutoff value is needed to match the historical TST conversion rate. Nonreproducible conversions in most converters suggested false-positive results.

Figure 1.

QFT serial test results for all HCWs in the cohort. Conversions (Neg→Pos) = HCWs with a qualitative change from a negative to a positive QFT at any point in the individual’s testing sequence; HCWs = healthcare workers; Indeterminates = HCWs with at least one indeterminate result; Persistent negatives (Neg→Neg) = HCWs with greater than or equal to two negative QFT results; Persistent positives (Pos→Pos) = HCWs with greater than or equal to two positive QFT results; QFT = QuantiFERON; Reversions (Pos→Neg) = HCWs with a qualitative change from a positive to a negative QFT at any point in the individual’s testing sequence.

Figure 2.

QFT serial test results for healthcare workers (HCWs) who converted and underwent short-term repeat testing. Neg = negative QFT test result; Pos = positive QFT test result; QFT = QuantiFERON.

Figure 3.

QFT conversion rate (CR) versus QFT cutoff. The historical tuberculin skin test conversion rate at our institution is 0.4%. The dashed reference line at 0.35 IU/ml is the QFT cutoff. Using this cutoff, the CR is 4.4%. CR = proportion of healthcare workers who converted from a negative to a positive QFT result; n = number of healthcare workers converting at varying conversion rates; QFT = QuantiFERON.

Figure 4.

Percentage of persistently positive healthcare workers classified as positive on initial testing versus QFT cutoff. The dashed reference line at 0.35 IU/ml is the QFT cutoff. n = number of healthcare workers; QFT = QuantiFERON.