10 research outputs found
PPD-induced monocyte mitochondrial damage is associated with a protective effect to develop tuberculosis in BCG vaccinated individuals: A cohort study.
INTRODUCTION:The mechanisms of mononuclear phagocyte death have been associated with the permissiveness and resistance to mycobacterial replication, but it remains unknown whether or not they help predict the risk of developing TB. OBJECTIVE:To describe the factors associated with the induction of monocyte mitochondrial and membrane damage in response to PPD as well as determine if this type of damage might predict the susceptibility of developing active tuberculosis in a cohort of household contacts (HHCs) from Medellin, Colombia from 2005 to 2008. METHODS:The prospective cohort study contains 2060 HHCs patients with pulmonary tuberculosis who were meticulously followed for two years. A survey of the socio-demographic, clinical, epidemiological factors and blood samples were collected. Mononuclear cell cultures were stimulated with or without PPD and the type of monocyte death was determined by the flow of cytometry, an indicator was also used for its analysis. Logistic regression was adjusted by the Generalized Estimations Equations and the survival was estimated with the Kaplan-Meier and Cox regression. Confidence intervals were used for estimating the association. RESULTS:1,859 out of 2,060 blood samples of the HHCs patients analyzed showed monocyte death. In response to PPD, 83.4% underwent mitochondrial damage while 50.9% had membrane damage. The membrane damage in response to PPD was higher in children under 4 years (OR: 1.57; (95% CI: 1.1 to 2.4) and the HHCs who slept regularly in the same household has an index case of (OR: 1.54; 95% CI: 1.0 to 2.3). After adjustment by age, comorbidities, nutritional status, proximity to index case and overcrowding, the risk of developing active TB among BCG vaccinated HHCs individuals with induction of mitochondrial damage was HR = 0.19 (95% CI: 0.1 to 0.5). CONCLUSIONS:The induction of monocytes mitochondrial damage by PPD stimulation correlates with protection of TB disease development in BCG-vaccinated HHCs. This represents a potential tool to predict susceptibility of developing active disease in this population
ROC curves showing the predictive capacity of the level of mitochondrial damage to predict active TB development in household contacts of smear-positive patients with or without BCG vaccination.
<p>The gray area shows the confidence interval of AUC (Area Under Curve),Se (Sensitivity), Sp (Specificity).</p
Effect of PPD stimulation on mitochondrial and cell membrane damage in mononuclear phagocytes from household contacts of smear-positive patients in Colombia.
<p>The level of mitochondrial damage was calculated as the difference between the percentage of PPD stimulated cells minus the percentage of non-stimulated cells for mitochondrial damage and cell membrane damage.</p
Incidence of tuberculosis according to the level of mitochondrial damage in household contacts of smear-positive patients with or without BCG vaccination.
<p>The level of mitochondrial damage was categorized by quartiles. The trend in decreasing incidence of active TB was assessed with chi square test for trend (chi square test for trend = 8.66, p = 0.003).</p
TB incidence and non-adjusted Hazard Ratio (HR) that influences development of TB according to various factors related to households of smear-positive patients in Colombia.
<p>TB incidence and non-adjusted Hazard Ratio (HR) that influences development of TB according to various factors related to households of smear-positive patients in Colombia.</p
Distribution of the percentage of monocytes with mitochondrial damage and membrane damage in peripheral blood mononuclear cells (PBMC) cultures from household contacts stimulated and non-stimulated with PPD.
<p>The inset shows the Median (Me) of the percentage of monocytes with mitochondrial (Panels A and C) and cell membrane damage (Panels B and D).Stimulated and non-stimulated cultures were compared using the Wilcoxon test.</p
Risk factors associated with the induction of monocytes’ mitochondrial and membrane damage in response to PPD, in mononuclear phagocytes obtained from household contacts of smear-positive TB patients in Colombia.
<p>Risk factors associated with the induction of monocytes’ mitochondrial and membrane damage in response to PPD, in mononuclear phagocytes obtained from household contacts of smear-positive TB patients in Colombia.</p
Risk factors associated with TB incidence according to the presence of BCG scar in household contacts of smear-positive TB patients in Colombia.
<p>Risk factors associated with TB incidence according to the presence of BCG scar in household contacts of smear-positive TB patients in Colombia.</p
Effect of the induction of mitochondrial monocyte damage and BCG vaccination on the probability of developing tuberculosis in household contacts (HHC) of smear-positive TB patients.
<p>The dotted line shows the probability of the HHC that did not have mitochondrial damage (MD -); the black line shows the probability of HHC that did have mitochondrial damage (MD+). Household contacts of smear-positive patients were followed up for two years to detect development of active TB disease. Probabilities were calculated by Kaplan-Meier and compared by Log-Rank test. HR: Hazard Ratio.</p