Utility of a three-gene transcriptomic signature in the diagnosis of tuberculosis in a low-endemic hospital setting

Background Host transcriptomic blood signatures have demonstrated diagnostic potential for tuberculosis (TB), requiring further validation across different geographical settings. Discriminating TB from other diseases with similar clinical manifestations is crucial for the development of an accurate immunodiagnostic tool. In this exploratory cohort study, we evaluated the performance of potential blood-based transcriptomic signatures in distinguishing TB disease from non-TB lower respiratory tract infections in hospitalised patients in a TB low-endemic country. Method Quantitative real-time polymerase chain reaction qPCR) was used to evaluate 26 previously published genes in blood from 31 patients (14 TB and 17 lower respiratory tract infection cases) admitted to Oslo University Hospital in Norway. The diagnostic accuracies of differentially expressed genes were determined by receiver operating characteristic curves. Results A significant difference (p < .01) in the age distribution was observed between patients with TB (mean age, 40 ± 15 years) and lower respiratory tract infection (mean age 59 ± 12 years) . Following adjustment for age, ETV7, GBP1, GBP5, P2RY14 and BLK were significantly differentially expressed between patients with TB and those with LRI. A general discriminant analysis generated a three-gene signature (BAFT2, ETV7 and CD1C), which diagnosed TB with an area under the receiver operating characteristic curve (AUC) of 0.86 (95% CI, 0.69 − 1.00), sensitivity of 69.23% (95% CI, 38.57%−90.91%) and specificity of 94.12% (95% CI, 71.31%−99.85%). Conclusion The three-genes signature may have potential to improve diagnosis of TB in a hospitalised low-burden setting. However, the influence of confounding variables or covariates such as age requires further evaluation in larger studies

Current use and acceptability of novel diagnostic tests for active tuberculosis: a worldwide survey

ABSTRACT Objective: To determine the current use and potential acceptance (by tuberculosis experts worldwide) of novel rapid tests for the diagnosis of tuberculosis that are in line with World Health Organization target product profiles. Methods: A multilingual survey was disseminated online between July and November of 2016. Results: A total of 723 individuals from 114 countries responded to the survey. Smear microscopy was the most commonly used rapid tuberculosis test (available to 90.9% of the respondents), followed by molecular assays (available to 70.7%). Only a small proportion of the respondents in middle- and low-income countries had access to interferon-gamma-release assays. Serological and lateral flow immunoassays were used by more than a quarter (25.4%) of the respondents. Among the respondents who had access to molecular tests, 46.7% were using the Xpert assay overall, that proportion being higher in lower middle-income countries (55.6%) and low-income countries (76.6%). The data also suggest that there was some alignment of pricing for molecular assays. Respondents stated they would accept novel rapid tuberculosis tests if available, including molecular assays (acceptable to 86.0%) or biomarker-based serological assays (acceptable to 81.7%). Simple biomarker-based assays were more commonly deemed acceptable in middle- and low-income countries. Conclusions: Second-generation molecular assays have become more widely available in high- and low-resource settings. However, the development of novel rapid tuberculosis tests continues to be considered important by tuberculosis experts. Our data also underscore the need for additional training and education of end users

Cytokine profile in the sputum of subjects with post-tuberculosis airflow obstruction and in those with tobacco related chronic obstructive pulmonary disease

CITATION: Guiedem, E., et al. 2020. Cytokine profile in the sputum of subjects with post-tuberculosis airflow obstruction and in those with tobacco related chronic obstructive pulmonary disease. BMC Immunology, 21:52, doi:10.1186/s12865-020-00381-w.The original publication is available at https://bmcimmunol.biomedcentral.comBackground: Previous studies have shown that tuberculosis (TB) is a risk factor for chronic airflow limitation. Chronic obstructive pulmonary disease (COPD) is recognized as the result of chronic inflammation, usually related to noxious particles. Post-TB airflow obstruction and tobacco-related COPD have the same functional pathway characterized by persistent airflow limitation. We sought to compare the profile of 29 cytokines in the sputum of subjects with post-TB airflow obstruction and those with COPD related to tobacco. Results: The forced expiratory volume in the first second (FEV1) and forced expiratory volume/forced vital capacity (FEV/FVC) ratio were lower in the COPD patients with the history of smoking compared to the post-TB airflow obstruction subgroup. The stages of the disease were more advanced in COPD / tobacco patients. Among the cytokines, IL-1α, IL-1β, MIP-1β, sCD40L and VEGF levels were higher in COPD patients, compared to the controls with p values of 0.003, 0.0001, 0.03, 0.0001 and 0.02 respectively. When the two COPD subgroups were compared, IL-1α, IL-6, TNF-α and IL-8 levels were higher in the COPD patients with the history of tobacco compared to the COPD patients with the history of TB with p-values of 0.031, 0.05, 0.021 and 0.016, respectively. Conclusion: COPD related to tobacco is more severe than post-TB airflow obstruction. The pathogenesis of post-TB airflow obstruction appears to involve the cytokines IL-1RA, IL-1α, IL-1β, IL-17, GRO and sCD40L, while COPD related to tobacco involves more cytokines.https://bmcimmunol.biomedcentral.com/articles/10.1186/s12865-020-00381-wPublisher's versio