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Recently, the number of artificial intelligence powered computer-aided detection (CAD) products that detect tuberculosis (TB)-related abnormalities from chest X-rays (CXR) available on the market has increased. Although CXR is a relatively effective and inexpensive method for TB screening and triaging, a shortage of skilled radiologists in many high TB-burden countries limits its use. CAD technology offers a solution to this problem. Before adopting a CAD product, TB programmes need to consider not only the diagnostic accuracy but also implementation-relevant features including operational characteristics, deployment mechanism, input and machine compatibility, output format, options for integration into the legacy system, costs, data sharing and privacy aspects, and certification. A landscaping analysis was conducted to collect this information among CAD developers known to have or soon to have a TB product. The responses were reviewed and finalized with the developers, and are published on an open-access website: www.ai4hlth.org. CAD products are constantly being improved and the site will continuously be updated to account for updates and new products. This unique online resource aims to inform the TB community about available CAD tools, their features and set-up procedures, to enable TB programmes to identify the most suitable product to incorporate in interventions., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Interferon-γ release assays cannot differentiate latent from active tuberculosis (TB), nor identify the recently infected with increased risk of active disease. The objective of this study was to identify biomarkers of recent infection following exposure to tuberculosis, to increase the positive predictive value for incipient TB. Contacts to patients with pulmonary TB were tested repeatedly with interferon-γ release assays and flow-cytometry. Proliferative CD4 + T cell responses to purified protein derivative (PPD) and 11 M. tuberculosis antigens were analysed. The individual probability of recent and remote infection was estimated using clinical data in a novel mathematical model and compared with CD4 + responses in a prediction model. The most specific prediction of recent infection was high CD4 + proliferative responses to CFP-10 and PPD and a low CD4 + response to ESAT-6. CD4 + proliferative responses to Rec85a, Rec85b and Rv1284 were also observed in recent infection, but did not reach significance in the prediction model. CONCLUSIONS: High CD4 + proliferative responses to CFP-10 and PPD and a low response to ESAT-6 may be used as biomarkers to improve positive predictive values for recent LTBI and thus, increased risk of incipient TB. Rec85a, Rec85b and Rv1284 are also of interest to study further in this context., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Interferon-γ (IFN-γ) inducible protein 10kD (IP-10) and IFN-γ release assays (IGRAs) are immunodiagnostic tests aiming to identify the presence of specific cellular immune responses, interpreted as markers for latent infection with Mycobacterium tuberculosis. Incubation at higher temperatures could affect IFN-γ and IP-10 responsiveness in order to improve the performance of IP-10 release assays and IGRAs., Aim: The aim of this study was to assess the robustness of whole blood based IP-10 release assay and IGRAs and the effect of hyper-thermic incubation (39 °C) on the diagnostic accuracy of IP-10 release assay and IGRAs., Results: We included 65 patients with confirmed pulmonary tuberculosis and 160 healthy controls from 6 European centres collaborating in the TBnet. In patients, IP-10 responses increased 1.07 (IQR 0.90-1.36) fold and IFN-γ responses decreased 0.88 (IQR 0.57-1.02) fold, with 39 °C compared to 37 °C incubation temperature. At 37 °C IGRA sensitivity was 85% and IP-10 sensitivity was 82%, whereas specificity was 97% for both tests (p > 0.8). These minor changes observed as a result of hyper-thermic incubation were not sufficient to impact IGRA and IP-10 release assay test performance., Conclusion: The performance of IGRA and IP-10 release assays is robust despite variations in the incubation temperature between 37 °C and 39 °C., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: The role of B cells in human host response to Mycobacterium tuberculosis (Mtb) infection is still controversial, but recent evidence suggest that B cell follicle like structures within the lung may influence host responses through regulation of the local cytokine environment. A candidate for such regulation could be the chemokine CXCL10. CXCL10 is mainly produced by human monocytes, but a few reports have also found CXCL10 production by human B cells. The objective of this study was to investigate CXCL10 production by human B cells in response to in vitro stimulation with Mtb antigens., Methodology/principal Findings: We analyzed human blood samples from 30 volunteer donors using multiparameter flow cytometry, and identified a subgroup of B cells producing CXCL10 in response to in vitro stimulation with antigens. T cells did not produce CXCL10, but CXCL10 production by B cells appeared to be mediated via IFN-γ and dependent on contact with antigen-specific T cells recognizing the antigen., Conclusion: Human B cells are able to produce CXCL10 in an IFN-γ and T cell contact-dependent manner. The present findings suggest a possible mechanism through which B cells in part may influence granuloma formation in human tuberculosis (TB) and participate in infection control., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

IP-10 has potential as a diagnostic marker for infection with Mycobacterium tuberculosis, with comparable accuracy to QuantiFERON-TB Gold In-Tube test (QFT-IT). The aims were to assess the sensitivity and specificity of IP-10, and to evaluate the impact of co-morbidity on IP-10 and QFT-IT. 168 cases with active TB, 101 healthy controls and 175 non-TB patients were included. IP-10 and IFN-γ were measured in plasma of QFT-IT stimulated whole blood and analyzed using previously determined algorithms. A subgroup of 48 patients and 70 healthy controls was tested in parallel with T-SPOT.TB IP-10 and QFT-IT had comparable accuracy. Sensitivity was 81% and 84% with a specificity of 97% and 100%, respectively. Combining IP-10 and QFT-IT improved sensitivity to 87% (p < 0.0005), with a specificity of 97%. T-SPOT.TB was more sensitive than QFT-IT, but not IP-10. Among non-TB patients IP-10 had a higher rate of positive responders (35% vs 27%, p < 0.02) and for both tests a positive response was associated with relevant risk factors. IFN-γ but not IP-10 responses to mitogen stimulation were reduced in patients with TB and non-TB infection. This study confirms and validates previous findings and adds substance to IP-10 as a novel diagnostic marker for infection with M. tuberculosis. IP-10 appeared less influenced by infections other than TB; further studies are needed to test the clinical impact of these findings., (Copyright © 2011 Elsevier Ltd. All rights reserved.)