Improving T-Cell Assays for the Diagnosis of Latent TB Infection: Potential of a Diagnostic Test Based on IP-10

Background: There is a need for simple tools such as the M. tuberculosis specific IFN-gamma release assays (IGRA) to improve diagnosis of M. tuberculosis-infection in children. The aim of the study was to evaluate the performance of an IP-10 and IL-2 based tests for the diagnosis of M. tuberculosis-infection in recently exposed children from Nigeria. Methodology and Principal Findings: Samples were obtained from 59 children at high risk of infection with M. tuberculosis (contacts of adults with smear and culture-positive tuberculosis) and 61 at low risk (contacts of smear-negative/culture-positive tuberculosis or community controls). IP-10 and IL-2 was measured in plasma after stimulation of whole-blood with M. tuberculosis specific antigens and mitogen. Previously developed criteria for positive IP-10 and IL-2 tests were used and the diagnostic performances of the IP-10 and IL-2 tests were compared with the Quantiferon In-Tube (QFT-IT) and the Tuberculin Skin Tests (TST). In response to M. tuberculosis specific antigens, the high-risk children expressed significantly higher levels of IP-10 (1358 pg/ml[IQR 278-2535 pg/ml]) and IL-2 (164 pg/ml[11-590 pg/ml]) than low risk groups 149 pg/ml( 25-497 pg/ml), and 0 pg/ml(0-3 pg/ml), respectively. There was excellent agreement (>89%, k>0.80) between IP-10, IL-2 tests and QFT-IT, better than with TST (>74%, k>0.49). The IP-10 and IL-2 responses were strongly associated with M. tuberculosis exposure and with grade of infectiousness of the index cases (p<0.0001). IP-10, IL-2, and TST but not QFT-IT was associated with age of the child in the low risk groups (p<0.02). Conclusions/Significance: IP-10 is expressed in high levels and results of the IP-10 test were comparable to the QFT-IT. IL-2 was released in low amounts in response to the antigens and not in response to the mitogen therefore IL-2 seems a less useful marker. We have demonstrated that IP-10 and possibly IL-2 could be alternative or adjunct markers to IFN-gamma in the diagnosis infection with M. tuberculosis.