Latent tuberculosis diagnosis in children by using the QuantiFERON-TB Gold In-Tube test.

BACKGROUND: The QuantiFERON-TB Gold test was the first blood test to be approved for the diagnosis of latent tuberculosis infection. Although it has been shown to be sensitive and specific in adults, limited data on its performance in children are available. METHODS: This was a prospective study of children receiving health care in New York, New York. Each child was assessed for risk factors for Mycobacterium tuberculosis infection, underwent tuberculin skin testing, and had a QuantiFERON-TB Gold In-Tube test performed. The concordance between tuberculin skin test and QuantiFERON-TB Gold In-Tube test results was calculated, and the results were analyzed according to the likelihood of exposure to M tuberculosis. RESULTS: Data for 207 children with valid tuberculin skin test and QuantiFERON-TB Gold In-Tube test results were analyzed. There was excellent correlation between negative tuberculin skin test results and negative QuantiFERON-TB Gold In-Tube test results; however, only 23% of children with positive tuberculin skin test results had positive QuantiFERON-TB Gold In-Tube test results. Positive QuantiFERON-TB Gold In-Tube test results were associated with increased likelihood of M tuberculosis exposure, and interferon gamma levels were higher in children with known recent exposure to M tuberculosis, compared with children with older exposure histories. Younger children produced lower interferon gamma levels in response to the mitogen (phytohemagglutinin) control used in the QuantiFERON-TB Gold In-Tube test, but indeterminant results were low for children of all ages. Performance characteristics were similar across all age groups. CONCLUSION: The QuantiFERON-TB Gold In-Tube test is a specific test for M tuberculosis exposure in children, with performance characteristics similar to those for adults residing in regions with low levels of endemic disease. Concerns about test sensitivity, especially for children <2 years of age, will require additional prospective long-term evaluation.

Interleukin-29 functions cooperatively with interferon to induce antiviral gene expression and inhibit hepatitis C virus replication.

The interferon (IFN)-related cytokine interleukin (IL)-29 (also known as IFN-lambda1) inhibits virus replication by inducing a cellular antiviral response similar to that activated by IFN-alpha/beta. However, because it binds to a unique receptor, this cytokine may function cooperatively with IFN-alpha/beta or IFN-gamma during natural infections to inhibit virus replication, and might also be useful therapeutically in combination with other cytokines to treat chronic viral infections such as hepatitis C (HCV). We therefore investigated the ability of IL-29 and IFN-alpha or IFN-gamma to cooperatively inhibit virus replication and induce antiviral gene expression. Compared with the individual cytokines alone, the combination of IL-29 with IFN-alpha or IFN-gamma was more effective at blocking vesicular stomatitis virus and HCV replication, and this cooperative antiviral activity correlated with the magnitude of induced antiviral gene expression. Although the combined effects of IL-29 and IFN-alpha were primarily additive, the IL-29/IFN-gamma combination synergistically induced multiple genes and had the greatest antiviral activity. Two different mechanisms contributed to the enhanced gene expression induced by the cytokine combinations: increased activation of ISRE promoter elements and simultaneous activation of both ISRE and GAS elements within the same promoter. These findings provide new insight into the coregulation of a critical innate immune response by functionally distinct cytokine families.