Role of QuantiFERON-TB Gold, Interferon Gamma Inducible Protein-10 and Tuberculin Skin Test in Active Tuberculosis Diagnosis

Abstract

BackgroundThe measurement of Interferon gamma or Interferon gamma inducible protein (IP)-10 in antigen stimulated blood samples is suggested as an alternative method for latent tuberculosis (TB) diagnosis. Nonetheless, their role in active TB diagnosis, particularly in TB endemic settings is yet to be defined. In this study, the sensitivities and specificities of Interferon gamma release assay (IGRA), IP-10 assay and tuberculin skin test (TST) in detecting active TB cases were assessed in human immunodeficiency virus (HIV) sero-negative TB patients and healthy controls respectively.Methods/Principal FindingsA total of 177 adult TB patients and 100 healthy controls were included for this study. QuantiFERON-TB Gold In-tube (QFT-IT) method was used to analyze the sensitivity and specificity of IGRA. QFT-IT, IP-10 and TST yielded the diagnostic sensitivities of 90.6% (95%CI: 86.3%–94.9%), 92.5% (95%CI: 88.6%–96.4%) and 68.9% (95%CI: 60.6%–77.2%) and specificities of 55% (95% CI: 35.2%–54.8%), 48% (95% CI: 38.2%–57.8%) and 75.5% (95% CI: 66.8%–84.2%), respectively. The extent of pulmonary involvement or presence of diabetes mellitus did not appear to influence the sensitivities of any of these tests. The combination of any of the two tests among QFT-IT, IP-10 and TST showed >98% sensitivity among smear negative cases and particularly the combination of IP-10, TST and smear microscopy showed 100% sensitivity, however, the specificity was decreased to 44.8%.Conclusions/SignificanceQFT-IT and IP-10 were highly sensitive in detecting active TB cases. The combination with TST improved the sensitivity of QFT-IT and IP-10 significantly. Although the higher sensitivity of combination of QFT-IT/IP-10 and TST may be useful in active TB diagnosis, they are limited by their poor specificity due to the high prevalence of latent TB in our settings.

Potential of interferon- -inducible protein 10 in improving tuberculosis diagnosis in HIV-infected patients

“…Combining the tests significantly increased sensitivity to 96% in HIV-negative and 88% in HIV-positive patients (table 1). We and others have found a similar improvement in sensitivity among patients from low-endemic setting without a compromise in specificity [8,9]. Thus, combining tests appears to be a feasible way to improve performance of the antigen-specific assays.…”

HIV and Tuberculosis: a Deadly Human Syndemic

“…For the T-SPOT.TB assay, the sensitivity was between 79 and 95% and the specificity was between 64% and 100% for active TB in HIV-infected patients (74). The sensitivity of the QFT-GIT test for culture-confirmed pulmonary TB in HIV-infected patients ranged from 65% to 91% in previously reported studies, and the likelihood of indeterminate results increased with lower CD4 counts (1,9,74,158,177,242,254). Aabye et al found that 22% of HIV-infected patients with culture-confirmed pulmonary TB had indeterminate results with the QFT-GIT test, and patients with CD4 counts below 300 cells/l were nearly 3 times as likely to have indeterminate results as patients with CD4 counts above 300 cells/l (1).…”

Immunodiagnosis of Tuberculosis: a Dynamic View of Biomarker Discovery

“…The diagnostic potential of IP-10 (125) also has been evaluated, with mixed results (54,149,167). Since secretion of IP-10 is less affected than that of IFN-␥ by immunosuppression (55) and is age independent (85), IP-10 has been proposed as an adjunct marker of LTBI diagnosis in pediatric and HIV-coinfected populations (85,124).…”