Childhood tuberculosis in Vienna between 2010 and 2016.

BACKGROUND: Tuberculosis (TB) has become a rare disease in developed countries. Austria is a low incidence country for TB with an incidence rate of 7.2/100,000 in 2016. The incidence of TB has shown a constant decline in Austria from 2008 (9.8/100,000) to 2015 (6.7/100,000) but recently stagnated in 2016 (7.2/100,000). In recent years migration to Austria from countries with high TB incidence rates has increased. Therefore, this study aimed to describe the recent epidemiology of childhood TB in Vienna. METHODS: Data of pediatric patients with active TB infections, who were hospitalized for further investigations or isolation precautions between 2010 and 2016 at the Wilhelminenspital, Austria's reference center for childhood tuberculosis, were retrospectively analyzed. Demographic and clinical data (symptoms, microbiology, radiology, immunology) were collected, compared and evaluated. RESULTS: A total of 127 patients with active tuberculosis were included in the study. The number of admissions varied between n = 7 in 2010 and n = 26 in 2016. There were two age peaks of infected children (0-5 years: n = 41 and 15-18 years: n = 45). In 35% of the cases one parent had active TB and was suspected to be the index case. In 36% the source of infection remained unknown. Compared to young children (<5 years), adolescents (15-18 years) showed proportionally more TB-related symptoms, such as cough (41% vs. 24%), fever (15% vs. 14%) and weight loss (22% vs. 0%). At the time of admission 51% of the young children and 33% of the adolescents were free of symptoms. Intrathoracic disease was found in 80.8%, extrathoracic disease in 19.2% and 11% of the cases were tuberculous lymphadenitis. Of the patients with intrathoracic TB 54% (n = 64) had a positive microbiological result (auramine staining, bacteriological culture, PCR). In young children hilar lymphadenopathy was the most frequent radiological finding (50%), whereas in adolescents lung infiltrates were most common (36%). The sensitivity of interferon-gamma release assays (IGRA) was 0.94 compared to 0.88 of the tuberculin skin test (TST). Both test methods showed moderate concordance (ϕ-coefficient = 0.48). CONCLUSION: A high number of asymptomatic children and adolescents with active TB were observed, which underlines the importance of efficient screening measures. Thorough history taking in all patients with TB is essential to maximize the effect of contact tracing. Overall, infection rates remained consistently low during the observation period.

A Th17- and Th2-skewed cytokine profile in cystic fibrosis lungs represents a potential risk factor for Pseudomonas aeruginosa infection.

RATIONALE: Cystic fibrosis (CF) is characterized by progressive pulmonary inflammation that is infection-triggered. Pseudomonas aeruginosa represents a risk factor for deterioration of lung function and reduced life expectancy. OBJECTIVES: To assess T-cell cytokine/chemokine production in clinically stable children with CF and evaluate the association between T-cell subtypes and susceptibility for infection with P. aeruginosa. METHODS: T-cell cytokine/chemokine profiles were measured in bronchoalveolar lavage fluid (BALF) from children with CF (n = 57; 6.1 ± 5.9 yr) and non-CF control subjects (n = 18; 5.9 ± 4.3 yr). Memory responses to Aspergillus fumigatus and P. aeruginosa were monitored. High-resolution computed tomography-based Helbich score was assessed. In a prospective observational trial the association between BALF cytokine/chemokine profiles and subsequent infection with P. aeruginosa was studied. MEASUREMENTS AND MAIN RESULTS: Th1- (INF-γ), Th2- (IL-5, IL-13), Th17- (IL-17A), and Th17-related cytokines (IL-1ß, IL-6) were significantly up-regulated in airways of patients with CF. IL-17A, IL-13, and IL-5 were significantly higher in BALF of symptomatic as compared with clinically asymptomatic patients with CF. IL-17A and IL-5 correlated with the percentage of neutrophils in BALF (r = 0.41, P < 0.05 and r = 0.46, P < 0.05, respectively). Th17- (IL-17A, IL-6, IL-1ß, IL-8) and Th2-associated cytokines and chemokines (IL-5, IL-13, TARC/CCL17), but not IFN-γ levels, significantly correlated with high-resolution computed tomography changes (Helbich score; P < 0.05). P. aeruginosa- and A. fumigatus-specific T cells from patients with CF displayed significantly higher IL-5 and IL-17A mRNA expression. IL-17A and TARC/CCL17 were significantly augmented in patients that developed P. aeruginosa infection within 24 months. CONCLUSIONS: We propose a role for Th17 and Th2 T cells in chronic inflammation in lungs of patients with CF. High concentrations of these cytokines/chemokines in CF airways precede infection with P. aeruginosa.

Lung transplantation in children and young adults: a 20-year single-centre experience.

Lung transplantation in adults is an accepted therapeutic option, whereas there is ongoing debate on its positive impact on survival in children. We report our experience of the first 20 yrs of paediatric lung transplantation at a single centre in Austria. Patient survival, organ survival and freedom from bronchiolitis obliterans were estimated by Kaplan-Meier curves. Pre- and post-transplant parameters were assessed and their influence on patient and organ survival evaluated by univariate tests and stepwise multivariate analyses. A total of 55 transplantations were performed in 43 patients. 1- and 5-yr patient survival rates were 72.1% and 60.6%, respectively, and 52.6% of patients were found to be free from bronchiolitis obliterans syndrome at 5 yrs post-transplant. Analysing different eras of transplantation suggests an improvement over the years with a 5-yr survival rate of 70.6% in the second decade. A positive effect of pre-transplant diabetes mellitus and immunosuppression was found with the newer drug tacrolimus, and a negative effect of pre-transplant in-hospital admission was reported. A high rate of successful re-transplantation prolonged total patient survival.