Use of T cell-based diagnosis of tuberculosis infection to optimize interpretation of tuberculin skin testing for child tuberculosis contacts.

BACKGROUND: Treatment of recent tuberculosis infection in children aged <2 years is essential, because of high risk of progression to disease, but diagnosis is hindered by the inaccuracy of the tuberculin skin test (TST). More-accurate T cell-based tests of infection could enhance diagnosis by optimizing interpretation of the TST results. METHODS: A total of 979 child tuberculosis contacts in Istanbul underwent the TST and enzyme-linked immunospot assay. Using enzyme-linked immunospot test results as a reference standard, we assessed the effect of age and bacille Calmette-Guérin (BCG) vaccination on the sensitivity and specificity of the TST, and we computed the optimal TST cutoff points, using receiver operating characteristic curves. RESULTS: With a TST cutoff point of >or=10 mm, the sensitivity of the TST was 66% for children aged <2 years, which was lower than that for older children (P= .006). Specificity was 75% for BCG-vaccinated children, compared with 92% for unvaccinated children (P= .001). Optimal cutoff points improved TST specificity for children with 1 BCG scar, with little loss of sensitivity. Despite the use of optimal cutoff points, TST sensitivity remained <70% for children aged <2 years, specificity remained <87% for BCG-vaccinated children aged >or=2 years, and overall accuracy was low for children with >1 BCG scar. CONCLUSIONS: Negative results of the TST cannot exclude tuberculosis infection for child tuberculosis contacts aged <2 years, which supports the use of preventive therapy regardless of the TST results for this age group. In children aged >or=2 years, the accuracy of the TST can be improved by adjustment of cutoff points for BCG-vaccinated children but remains poor for children with >1 BCG scar. This methodology can define optimal TST cutoff points for diagnosis of tuberculosis infection tailored to target populations.

Optimal timing and temperature for hyperthermic preconditioning in an animal model of fecal peritonitis.

The impact of immune parameters in the mechanism of hyperthermia is yet to be explained. In this study, the optimal timing and temperature of thermal treatment for reversing the abnormal immunologic parameters obtained in a rat model of peritonitis were planned to be determined. Male Sprague-Dawley rats were grouped as sham, control peritonitis, and thermally treated rats at the time of peritonitis or 4 h prior to induction of peritonitis both at 40 and 42 degrees C. Peritonitis was induced by the cecal ligation and perforation model. Eight hours after the induction of peritonitis, rats were sacrified and samples were taken for measurements of CD4+, CD8+, CD(11b), B cells, NK cells, and tumor necrosis factor alpha (TNFalpha) and thiobarbituric acid-reactive substances (TBARS) levels. CD4+ expression and B cell amount were decreased whereas TNFalpha levels, CD8+ and CD(11b) expression, and NK cell amount were found to be increased in the control peritonitis group when compared to the sham group. Peritonitis induction also increased TBARS levels in liver tissue. Hyperthermic preconditioning at either 40 or 42 degrees C applied 4 h prior to peritonitis induction returned all parameters to their normal levels, which is similar to the results of the sham laparotomy group. The results of TNFalpha values in preconditioned rats were varied according to the temperature that was applied. The levels were increased at 40 degrees C, whereas they showed a decline at 42 degrees C. Hyperthermic preconditioning prevented the oxidative damage in liver as well as TNFalpha elevation, particularly at 42 degrees C. Results from this study suggest that hyperthermic preconditioning 4 h prior to the onset of septic events may improve the adverse outcome in sepsis.