Abstract
The accurate diagnosis of latent tuberculosis infection reduces the risk of progression to severe disseminated disease. However, in young children, a major limitation of the standard tuberculin skin test is that false-negative results cannot be detected. The new interferon-gamma release assays QuantiFERON-TB Gold (Cellestis Carnegie Victoria, Australia), QuantiFERON-TB In-Tube (Cellestis), and T-SPOT.TB (Oxford Immunotec, Abingdon, United Kingdom) show promise of greater accuracy, but they may also be affected by impaired cellular immunity, resulting in indeterminate results (ie, insufficient response in positive-control wells). To evaluate the impact of age on the performance of interferon-gamma release assays when used in a routine hospital setting among children tested for suspected active or latent TB infection. We retrospectively studied 496 children 0 to 19 years of age who had been tested with the tuberculin skin test and at least 1 interferon-gamma release assay: 181 with QuantiFERON-TB Gold and 315 with QuantiFERON-TB In-Tube. In 154 of the children, paired interferon-gamma release assay testing was available: 87 with QuantiFERON-TB Gold/T-SPOT.TB and 67 with QuantiFERON-TB In-Tube/T-SPOT.TB. Compared with T-SPOT.TB, the rates of indeterminate results were significantly higher for both QuantiFERON-TB Gold and QuantiFERON-TB In-Tube. QuantiFERON-TB Gold and QuantiFERON-TB In-Tube also gave indeterminate results more frequently in children <4 years of age than in those >/=4 years of age. Indeterminate results were associated with younger age for both QuantiFERON-TB Gold and QuantiFERON-TB In-Tube but not for T-SPOT.TB. Considering age as a binary variable (<4 and >/=4 years of age), a significantly higher concentration of phytohaemagglutinin-produced interferon-gamma was observed in older children with both QuantiFERON-TB Gold and QuantiFERON-TB In-Tube. Different blood tests for the diagnosis of latent tuberculosis infection in children seem to perform differently, because both QuantiFERON-TB tests were more likely than T-SPOT.TB to give indeterminate results in children <4 years of age.
Highlights
The accurate diagnosis of latent tuberculosis infection reduces the risk of progression to severe disseminated disease
Compared with T-SPOT.TB, the rates of indeterminate results were significantly higher for both QuantiFERON-TB Gold and QuantiFERON-TB In-Tube
Indeterminate results were associated with younger age for both QuantiFERON-TB Gold and QuantiFERON-TB In-Tube but not for T-SPOT.TB
Summary
The accurate diagnosis of latent tuberculosis infection reduces the risk of progression to severe disseminated disease. In young children, a major limitation of the standard tuberculin skin test is that false-negative results cannot be detected. The new interferon-␥ release assays QuantiFERON-TB Gold (Cellestis Carnegie Victoria, Australia), QuantiFERON-TB In-Tube (Cellestis), and T-SPOT.TB www.pediatrics.org/cgi/doi/10.1542/ peds.2008-1722 doi:10.1542/peds.2008-1722. (Oxford Immunotec, Abingdon, United Kingdom) show promise of greater accuracy, but they may be affected by impaired cellular immunity, resulting in indeterminate results (ie, insufficient response in positive-control wells)
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