1,721,147 research outputs found
The role of IGRA in the diagnosis of tuberculosis infection, differentiating from active tuberculosis, and decision making for initiating treatment or preventive therapy of tuberculosis infection
Full text linkObjectives: The World Health Organization estimated that a quarter of the global population is infected by Mycobacterium tuberculosis (Mtb). A better control of tuberculosis (TB) is based on the ability to detect Mtb infection, identifying the progressors to TB disease, undergoing to preventive therapy and implementing strategies to register the infections and treatment completion. Design: we reviewed the literature regarding the tests available for TB infection diagnosis, the preventive therapies options and the cascade of care for controlling TB at a public health level. Results: current tests for TB infection diagnosis as IFN-γ release assays or tuberculin skin tests are based on the detection of an immune response to Mtb in the absence of clinical disease. The main limit is their low accuracy to detect progressors to disease. New preventive treatments are available with short duration that are associated with better adherence. Options to register TB infections are presented. Conclusions: Tests to diagnose TB infection are available but they lack accuracy to identify the progressors from infection to TB disease. Shorter preventive TB therapy are available but need to be implemented worldwide. A TB infection registry is crucial for improving the cascade of care leading to a better TB control
The role of IGRA in the diagnosis of tuberculosis infection, differentiating from active tuberculosis, and decision making for initiating treatment or preventive therapy of tuberculosis infection
No full textObjectives: The World Health Organization estimated that a quarter of the global population is infected by Mycobacterium tuberculosis (Mtb). A better control of tuberculosis (TB) is based on the ability to detect Mtb infection, identifying the progressors to TB disease, undergoing to preventive therapy and implementing strategies to register the infections and treatment completion. Design: we reviewed the literature regarding the tests available for TB infection diagnosis, the preventive therapies options and the cascade of care for controlling TB at a public health level. Results: current tests for TB infection diagnosis as IFN-γ release assays or tuberculin skin tests are based on the detection of an immune response to Mtb in the absence of clinical disease. The main limit is their low accuracy to detect progressors to disease. New preventive treatments are available with short duration that are associated with better adherence. Options to register TB infections are presented. Conclusions: Tests to diagnose TB infection are available but they lack accuracy to identify the progressors from infection to TB disease. Shorter preventive TB therapy are available but need to be implemented worldwide. A TB infection registry is crucial for improving the cascade of care leading to a better TB control
C1q and HBHA-specific IL-13 levels as surrogate plasma biomarkers for monitoring tuberculosis treatment efficacy: a cross-sectional cohort study in Paraguay
Full text linkIntroduction New diagnostic tools are needed to rapidly assess the efficacy of pulmonary tuberculosis (PTB) treatment. The aim of this study was to evaluate several immune biomarkers in an observational and cross-sectional cohort study conducted in Paraguay. Methods Thirty-two patients with clinically and microbiologically confirmed PTB were evaluated before starting treatment (T0), after 2 months of treatment (T1) and at the end of treatment (T2). At each timepoint plasma levels of IFN-y, 17 pro- and anti-inflammatory cytokines/chemokines and complement factors C1q, C3 and C4 were assessed in unstimulated and Mtb-specific stimulated whole blood samples using QuantiFERON-TB gold plus and recombinant Mycobacterium smegmatis heparin binding hemagglutinin (rmsHBHA) as stimulation antigen. Complete blood counts and liver enzyme assays were also evaluated and correlated with biomarker levels in plasma. Results In unstimulated plasma, C1q (P<0.001), C4 (P<0.001), hemoglobin (P<0.001), lymphocyte proportion (P<0.001) and absolute white blood cell count (P=0.01) were significantly higher in PTB patients at baseline than in cured patients. C1q and C4 levels were found to be related to Mycobacterium tuberculosis load in sputum. Finally, a combinatorial analysis identified a plasma host signature comprising the detection of C1q and IL-13 levels in response to rmsHBHA as a tool differentiating PTB patients from cured TB profiles, with an AUC of 0.92 (sensitivity 94% and specificity 79%). Conclusion This observational study provides new insights on host immune responses throughout anti-TB treatment and emphasizes the role of host C1q and HBHA-specific IL-13 response as surrogate plasma biomarkers for monitoring TB treatment efficacy
The ubiquitin ligase TRIM32 promotes the autophagic response to Mycobacterium tuberculosis infection in macrophages
Full text linkMycobacterium tuberculosis (Mtb) is known to evade host immune responses and persist in macrophages for long periods. A mechanism that the host uses to combat Mtb is xenophagy, a selective form of autophagy that targets intracellular pathogens for degradation. Ubiquitination of Mtb or Mtb-containing compartments is a key event to recruit the autophagy machinery and mediate the bacterial delivery to the lysosome. This event relies on the coordinated and complementary activity of different ubiquitin ligases, including PARKIN, SMURF1, and TRIM16. Because each of these factors is responsible for the ubiquitination of a subset of the Mtb population, it is likely that additional ubiquitin ligases are employed by macrophages to trigger a full xenophagic response during Mtb infection. In this study, we investigated the role TRIM proteins whose expression is modulated in response to Mtb or BCG infection of primary macrophages. These TRIMs were ectopically expressed in THP1 macrophage cell line to assess their impact on Mtb replication. This screening identified TRIM32 as a novel player involved in the intracellular response to Mtb infection, which promotes autophagy-mediated Mtb degradation. The role of TRIM32 in xenophagy was further confirmed by silencing TRIM32 expression in THP1 cells, which causes increased intracellular growth of Mtb associated to impaired Mtb ubiquitination, reduced recruitment of the autophagy proteins NDP52/CALCOCO2 and BECLIN 1/BECN1 to Mtb and autophagosome formation. Overall, these findings suggest that TRIM32 plays an important role in the host response to Mtb infection through the induction of autophagy, representing a promising target for host-directed tuberculosis therapies
Commemorating World Tuberculosis Day 2022: recent ERJ articles of critical relevance to ending TB and saving lives
No full textCardiovascular outcomes and tumour necrosis factor antagonists in chronic inflammatory rheumatic disease. a focus on rheumatoid arthritis
No full textMany chronic rheumatic diseases have an inflammatory etiology, leading to accelerated atherosclerosis and increased occurrence of vascular diseases. In rheumatoid arthritis (RA), a reduction in cardiovascular (CV) events has been reported under treatments reducing systemic inflammation. Areas covered: Given the central role of tumour necrosis factor alpha (TNFα) in chronic inflammatory conditions and in atherosclerosis, it has been suggested that TNFα-antagonists may reduce CV risk and mortality. Although there are no randomized controlled or head-to-head trials investigating the effect of specific anti-TNF-agents on CV outcomes, observational cohort studies, national registry data, and meta-analyses in RA have reported improved CV outcomes with anti-TNF therapy. Expert opinion: It is unclear whether this is due to reduced systemic inflammation or a specific anti-TNF effect at the atherosclerotic plaque level. Observed CV benefits appear to correlate with anti-TNF response. Conversely, although inconsistently, anti-TNF agents have also been linked with increased incidence/worsening of heart failure. Additional CV adverse events with anti-TNFs include vasculitis and venous thromboembolic events. We provide an overview of the likely effects of anti-TNF therapy on CV risk and adverse events, and evaluated differences in CV outcomes among different anti-TNF-agents
Detection of Mycobacterium tuberculosis DNA in CD34+ peripheral blood mononuclear cells of adults with tuberculosis infection and disease
Full text linkObjectives: To investigate whether Mycobacterium tuberculosis (Mtb) DNA is detected in peripheral blood mononuclear cells (PBMC) of subjects with tuberculosis (TB) or TB infection (TBI) living in a low-burden country. Methods: We prospectively enrolled 57 patients with TB, 41 subjects with TBI, and 39 controls in Rome, Italy. PBMC were isolated, cluster of differentiation (CD)34+ and CD34- cells were immunomagnetic separated, DNA was extracted, and digital polymerase chain reaction for IS6110 and rpoB sequences was used to detect Mtb DNA in PBMC subsets and unfractionated PBMC. Results: We detected Mtb DNA at a low copy number in CD34+ cells in 4o f 30 (13%) patients with TB, 2 of 24 (8%) subjects with TBI, and 1 of 24 (4%) controls. Mtb DNA was detected in unfractionated PBMC in 3 of 51 (6%) patients with TB, 2 of 38 (5%) subjects with TBI, and 2 of 36 (6%) controls. In CD34- cells, only 1 of 31 (3%) subjects with TBI tested positive for Mtb DNA. Conclusions: Mtb DNA was detected at low frequencies and levels in the PBMC of subjects with TBI and donors with TB living in a low-burden country. In particular, Mtb DNA was detected more frequently in CD34+ cells, supporting the hypothesis that these cells may represent a Mtb niche. This finding informs biological understanding of Mtb pathogenesis and may support the development of a microbial blood biomarker for Mtb infection
Clinical Utility of Induced Sputum and Bronchoalveolar Lavage Cultures in Diagnosing Nontuberculous Mycobacterial Pulmonary Disease
No full textDiagnosing non-tuberculous mycobacterial pulmonary disease (NTM-PD) in patients unable to produce sputum spontaneously requires invasive procedures to obtain valid respiratory specimens. In this retrospective study, we evaluated the results of microbiological tests performed on respiratory samples of 132 patients affected by NTM-PD. In the diagnostic workout, 98 patients performed both induced sputum (IS) and bronchoalveolar lavage (BAL) and were enrolled in our study. A total of 93 out of 98 BAL samples (95%) were culture-positive for mycobacteria, whereas only 67/153 (44%) induced sputum cultures were positive for NTM (p < 0.001). Molecular identification of NTM with real-time polymerase chain reaction (PCR) was positive in 48/64 BAL (75%) and in 47/139 (34%) IS samples (p < 0.001). Patients affected by nodular-bronchiectatic form were 65/98 (66%): BAL culture was positive in 95% of cases (62/65 BAL), while only 30/99 IS cultures were positive (30%; p < 0.001). PCR was positive in 76% of BAL samples examined (26/34) and in 26% of the IS samples (24 out of 91) (p < 0.001). Among 33 patients with a fibro-cavitary radiological pattern, 65% of IS (35/54) were culture-positive for NTM, whereas 94% of cases (31/33) had a positive culture for NTM from BAL (p = 0.002). PCR was positive in 73% of BAL samples tested (22/30) and 48% of IS samples tested (23/48) (p = 0.031). Our results confirm BAL mycobacterial culture as the gold standard for the diagnosis of pulmonary mycobacteriosis. FBS with BAL should be performed in every patient with a strong suspicion of NTM-PD, if other respiratory samples are repeatedly negative. Sputum induction is a useful technique to obtain valid respiratory samples when patients are unable to produce spontaneous sputum, especially in the outpatient setting. However, during the diagnostic workup of NTM-PD, we should not forget that PCR and mycobacterial culture of induced sputum have a lower yield than when performed on BAL, especially in the nodular-bronchiectatic form of the disease
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