Tuberculosis Gold In-Tube Test Research Articles

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

To the Editors: In patients latently infected with Mycobacterium tuberculosis , immunosuppression significantly augments the risk of progression to active tuberculosis (TB) and TB is still one of the most frequent opportunistic infections worldwide. Prevention of TB in HIV-positive patients using the tuberculin skin testing (TST) followed by targeted preventive treatment is an effective strategy, but has thus far shown limited clinical success, in part due to the lack of a reliable test for latent TB infection (LTBI) 1. Interferon (IFN)-γ release assays (IGRAs) have shown great potential in the improvement of LTBI diagnosis, but the tests perform suboptimally in immunocompromised populations. We and others have previously shown that HIV-positive patients have high rates of indeterminate QuantiFERON®-TB Gold In-Tube test (QFT-IT) results and that this, at least in part, is due to low CD4 T-cell count 2–4. We and others have also shown that IFN-γ-inducible protein 10 (IP-10/CXCL-10) is an alternative biomarker may improve immunodiagnosis of M. tuberculosis infection. IP-10 is induced specifically and in large quantities upon in vitro stimulation of whole blood with M. tuberculosis -specific antigens. We have developed an IP-10 based test 5 and shown that the IP-10 test performs comparably to the QFT-IT in adult patients with intact immune function 6. We compared the sensitivity of an IP-10 based test with the QFT-IT for diagnosing M. tuberculosis infection in HIV-negative and HIV-positive patients with culture-confirmed active pulmonary tuberculosis (PTB). 300 patients newly diagnosed with PTB were recruited prospectively through the National Tuberculosis and Leprosy Programme (Mwanza, Tanzania). Blood was drawn for IGRA and HIV testing, and CD4 cell counts. Sputum was collected for microscopy and M. tuberculosis culture. Patients >15 yrs of age with a positive sputum culture result were enrolled. All HIV-positive patients were newly diagnosed in the study …

Kinetics of the QuantiFERON®-TB Gold In-Tube test during treatment of patients with sputum smear-positive tuberculosis in relation to initial TST result and severity of disease

The QuantiFERON-TB Gold In-Tube test (QFN) measures interferon-gamma production in response to Mycobacterium tuberculosis antigens. Our aim was to assess the kinetics of the QFN and initial tuberculin skin test (TST) result in relation to severity of disease in a tuberculosis (TB) endemic area. Smear-positive TB patients (n = 71) were recruited at Gondar University Hospital, Ethiopia. The TST, QFN, CD4+ cell count and clinical symptoms (TB score) were assessed and followed up during treatment. From baseline to 7 months after treatment, there was a significant decrease in QFN reactivity (93.8% to 62.5% in HIV-negative/TB; 70.3% to 33.3% in HIV-positive/TB patients) down to a level comparable to a control group of blood donors (51.2%). The agreement between TST and QFN was poor in TB patients compared to healthy controls. A negative TST correlated to more advanced TB in contrast to a negative QFN test. We conclude that the QFN reactivity is significantly reduced at the end of treatment against active TB to the background level of healthy blood donors, and that the agreement between TST and QFN is poor including correlation to the severity of disease.

Evaluating the potential of IP-10 and MCP-2 as biomarkers for the diagnosis of tuberculosis

The aim of the present study was to evaluate the potential of diagnostic tests based on interferon-gamma inducible protein (IP)-10 and monocyte chemotactic protein (MCP)-2, and compare the performance with the QuantiFERON TB Gold In-Tube (QFT-IT; Cellestis, Carnagie, Australia) test. IP-10 and MCP-2 were determined in supernatants from whole blood stimulated with Mycobacterium tuberculosis-specific antigens. Samples were obtained from 80 patients with culture- and/or PCR-proven tuberculosis (TB), and 124 unexposed healthy controls: 86 high school students and 38 high school staff. IP-10 and MCP-2 test cut-offs were established based on receiver operating characteristic curve analysis. TB patients produced significantly higher levels (median) of IP-10 (2158 pg x mL(-1)) and MCP-2 (379 pg x mL(-1)) compared with interferon (IFN)-gamma (215 pg x mL(-1)). The QFT-IT, IP-10 and MCP-2 tests detected 81, 83 and 71% of the TB patients; 0, 3 and 0% of the high school students and 0, 16 and 3% of the staff, respectively. Agreement between tests was high (>89%). By combining IP-10 and IFN-gamma tests, the detection rate increased among TB patients to 90% without a significant increase in positive responders among the students. In conclusion, interferon-gamma inducible protein-10 and monocyte chemotactic protein-2 responses to Mycobacterium tuberculosis-specific antigens could be used to diagnose infection. Combining interferon-gamma inducible protein-10 and interferon-gamma may be a simple approach to increase the detection rate of the Mycobacterium tuberculosis-specific in vitro tests.