Diagnostic potential of combining plasma biomarkers of tissue damage and inflammation in pediatric TB.

INTRODUCTION: Immune-based diagnostic tests for tuberculosis (TB) have suboptimal sensitivity in children and cannot differentiate between latent infection (LTBI) and active disease. This study evaluated the diagnostic potential of a broad range of biomarkers of tissue damage and inflammation in unstimulated plasma in children. METHODS: We analyzed 17 biomarkers in 15 non-M. tuberculosis (MTB)-infected controls and 33 children with TB infection (LTBI, n = 8; probable TB, n = 19; confirmed TB, n = 6). Biomarker concentrations were measured using a Luminex magnetic bead-based platform and multiplex sandwich immunoassays. Concentrations, correlations and diagnostic accuracy assessments were conducted among patient groups. RESULTS: Confirmed TB cases had significantly higher concentrations of IFN-γ and IL-2 and higher IFN-γ/MCP-1 and IL-2/MCP-1 ratios compared to LTBI and non-MTB-infected children. Among children with confirmed TB, there was a strong correlation between IFN-γ and IL-10 (r = 0.95; p < 0.001) and a significant correlation between IL-2 and IL-1ra (r = 0.92), IL-21 (r = 0.91), MCP-3 (r = 0.84), and MMP-1 (r = 0.85). The IFN-γ/MCP-1 ratio was the most accurate biomarker combination for differentiating between MTB-infected and non-MTB-infected children (AUC, 0.82; sensitivity, 87.9%; specificity, 66.6%; p < 0.001) and between active TB and non-MTB-infected children (AUC 0.82; sensitivity 88.0%; specificity 60.0%; p < 0.001). None of the biomarkers investigated were able to discriminate between LTBI and active TB. CONCLUSION: Our data suggest that combining the analyses of multiple biomarkers in plasma has the potential to enhance diagnosis of TB in children and, thus, warrants additional investigation. In particular, the diagnostic potential of IFN-γ/MCP-1 ratios should be further explored in larger pediatric cohorts.

Immunomodulation with AM3 and antioxidants creates an adequate framework for skin repair and decreases the monocyte proinflammatory stage in smoker women.

Smoking has been considering a crucial factor in promoting skin and systemic aging that is associated with the development of a low-level, systemic, chronic inflammation known as "inflammaging" in which monocytes play a pivotal role. Our aim was to investigate the effects of AM3 plus antioxidants vs placebo in the activation status, function of monocytes and cutaneous aging parameters in healthy smoker middle-aged women. A total of 32 women were 1:1 randomly assigned to AM3 plus antioxidants or placebo for three months. Peripheral mononuclear blood cells and cutaneous biopsy were obtained and flow cytometry and immunohistological studies, respectively, were performed before and after the treatment. AM3 plus antioxidants treatment compared with placebo significantly reduced the monocyte production of the proinflammatory interleukin 1 (IL-1), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) cytokines as well as increased the regulatory IL-10 in middle-aged smoker women. Furthermore, AM3 and antioxidants did not modify ROS production by monocytes and granulocytes but increased their phagocytic activity. The active combination also stimulated a significative increase in reticular dermis depth as well as an increase in the expression of CD117 and CD31. Thus, AM3 and antioxidants treatment reduces the systemic proinflammatory monocyte disturbance of heathy smoker middle-aged women and encourage skin repair mechanisms.

Prevalence and Clinical Characteristics of Children With Nonsevere Tuberculosis in Spain.

BACKGROUND: To assess the prevalence and characteristics of nonsevere TB among children in Spain. It has been recently demonstrated that these children can be treated with a 4-month regimen instead of the classical 6-month treatment regimen, with the same effectivity and outcomes, decreasing toxicity and improving adherence. METHODS: We conducted a retrospective cohort study in a cohort of children ≤16 years of age with TB. Nonsevere TB cases included smear-negative children with respiratory TB confined to 1 lobe, with no significant airway obstruction, no complex pleural effusion, no cavities and no signs of miliary disease, or with peripheral lymph-node disease. The remaining children were considered to have severe TB. We estimated the prevalence of nonsevere TB and compared the clinical characteristics and outcomes between children with nonsevere and severe TB. RESULTS: A total of 780 patients were included [46.9% males, median age 5.5 years (IQR: 2.6-11.1)], 477 (61.1%) of whom had nonsevere TB. Nonsevere TB was less frequent in children <1 year (33% vs 67%; P < 0.001), and >14 years of age (35% vs 65%; P = 0.002), mostly diagnosed in contact tracing studies (60.4% vs 29.2%; P < 0.001) and more frequently asymptomatic (38.3% vs 17.7%; P < 0.001). TB confirmation in nonsevere disease was less frequent by culture (27.0% vs 57.1%; P < 0.001) and by molecular tests (18.2% vs 48.8%; P < 0.001). Sequelae were less frequent in children with nonsevere disease (1.7 vs 5.4%; P < 0.001). No child with nonsevere disease died. CONCLUSIONS: Two-thirds of children had nonsevere TB, mostly with benign clinical presentation and negative microbiologic results. In low-burden countries, most children with TB might benefit from short-course regimens.