Abstract
Blood-based interferon-gamma (IFN-γ) release assays (IGRAs) have been proven to be useful in the diagnosis of Mycobacterium tuberculosis (Mtb) infection. However, IGRAs have not been recommended for clinical practice in most low-income settings due to cost-intensive limitations and shortage of clinical data available. The established T-SPOT. TB assay containing Mtb-specific antigens ESAT-6 and CFP10 are widely used for immunodiagonsis of Mtb infection, but the high cost is one of the restricting factors against its clinical application in the developing countries. More recently, a cost-saving IGRA assay, TS-SPOT, was approved in China. This new assay contains an additional antigen Rv3615c. Rv3615c contains broadly recognized CD4+ and CD8+ epitopes, and T-cell responses to Rv3615c are as specific for Mtb infection as the responses to ESAT-6 and CFP10 in both Mtb-infected humans and M. bovis-infected cattle. Therefore, we assessed the likely effect of inclusion of Rv3615c as stimulus besides ESAT-6 and CFP10 in an IGRA assay and evaluated the performance of TS-SPOT for diagnosis of Mtb infection and active TB compared with T-SPOT.TB. We tested 155 active TB patients, 90 non-TB lung disease patients, and 55 healthy individuals. The results presented an improved positive rate for diagnosis of active TB and Mtb infection, that could be attributable to inclusion of Rv3615c in the mixture of stimulatory antigens. The diagnostic efficiency of TS-SPOT assay for active TB was as follows: sensitivity 80.00%, specificity 83.45%, positive predictive value (PPV) 83.78%, negative predictive value (NPV) 83.45%, positive likelihood ratio (LR+) 4.83, and negative likelihood ratio (LR−) 0.24. The results were similar to those of T-SPOT.TB, with an excellent agreement (κ = 0.91, 95% CI: 0.85–0.95) being observed between these two assays. The sensitivities of the TS-SPOT assay varied for patients with different forms of active TB, with the highest sensitivity for patients with culture-positive pulmonary TB (92.16%) and the lowest for those with tuberculosis meningitis (50.00%). Taken together, the current evidence indicates that this new TS-SPOT assay is a useful adjunct to the current tests for rapid diagnosis of active TB and Mtb infection in low-income and high-incidence settings due to its characteristics of cost-effectiveness and high-quality.
Highlights
Tuberculosis (TB), the disease caused by Mycobacterium tuberculosis (Mtb), still remains a major global public health concern
Of the 155 clinically diagnosed active TB (ATB) patients (76.13% pulmonary tuberculosis (PTB) and 23.87% extra-pulmonary tuberculosis (EPTB)), 124 and 119 cases were detected positively by using the TS-SPOT and T-SPOT.TB, respectively, which resulted in the diagnostic sensitivity of 80.00% (124/155) and 76.77% (119/155), respectively
interferon-gamma (IFN-γ) release assays (IGRAs) are in vitro immunologic diagnostic tests to identify Mtb infection
Summary
Tuberculosis (TB), the disease caused by Mycobacterium tuberculosis (Mtb), still remains a major global public health concern. According to the updated WHO global TB report, approximately one-third of the world’s populations are infected asymptomatically with Mtb, and about 5–10% of these people develop active TB. In 2015, there were an estimated 10.4 million new TB cases and 1.4 million TB deaths worldwide, and an additional 0.4 million deaths resulting from TB disease among people co-infected with HIV (WHO, 2016). The results of the fifth Chinese national TB epidemiological survey in 2010 showed that the TB prevalence was 469/100,000 among population over 15 years old, and 4.99 million active TB cases were estimated across the country (The Office of the Fifth National TB Epidemiological Survey, 2012). Diagnosis and treatment decisions may be difficult in cases with clinical suspicion of TB and negative AFB sputum smears. Being rapid and easy to apply, tuberculin skin test (TST) has been used as an immunodiagnostic tool to support the physician’s decision process for decades, but it suffers from poor specificity due to the cross-reaction of non-tuberculosis mycobacteria (NTM) or Bacillus Calmette-Guerin (BCG) vaccination (Richeldi, 2006), especially in developing countries with high TB prevalence
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