The impact of Rotavirus mass vaccination on hospitalization rates, nosocomial Rotavirus gastroenteritis and secondary blood stream infections

Background The aim of the study was to evaluate the effects of universal mass vaccination (UMV) against rotavirus (RV) on the hospitalization rates, nosocomial RV infections and RV-gastroenteritis (GE)-associated secondary blood stream infections (BSI). Methods The retrospective evaluation (2002–2009) by chart analysis included all clinically diagnosed and microbiologically confirmed RV-GE cases in a large tertiary care hospital in Austria. The pre-vaccination period (2002–2005) was compared with the recommended and early funded (2006–2007) and the funded (2008–2009) vaccination periods. Primary outcomes were RV-GE-associated hospitalizations, secondary outcomes nosocomial RV disease, secondary BSI and direct hospitalization costs for children and their accompanying persons. Results In 1,532 children with RV-GE, a significant reduction by 73.9% of hospitalized RV-GE cases per year could be observed between the pre-vaccination and the funded vaccination period, which was most pronounced in the age groups 0–11 months (by 87.8%), 6–10 years (by 84.2%) and 11–18 years (88.9%). In the funded vaccination period, a reduction by 71.9% of nosocomial RV-GE cases per year was found compared to the pre-vaccination period. Fatalities due to nosocomial RV-GE were only observed in the pre-vaccination period (3 cases). Direct costs of hospitalized, community-acquired RV-GE cases per year were reduced by 72.7% in the funded vaccination period. The reduction of direct costs for patients (by 86.9%) and accompanying persons (86.2%) was most pronounced in the age group 0–11 months. Conclusions UMV may have contributed to the significant decrease of RV-GE-associated hospitalizations, to a reduction in nosocomial RV infections and RV-associated morbidity due to secondary BSI and reduced direct hospitalization costs. The reduction in nosocomial cases is an important aspect considering severe disease courses in hospitalized patients with co-morbidities and death due to nosocomial RV-GE

Thymectomy as a model for premature immunosenescence

Das Altern des Immunsystems, auch Immunoseneszenz genannt, beginnt mit der Involution des Thymus. Die T Zell Immunoseneszenz ist charakterisiert durch eine Abnahme der naïven T Zellen, eine kompensatorische Autoproliferation peripherer Gedächtnis T Zellen, eine oligoklonale Expansion der T Zell Rezeptor Diversität und eine oligoklonale Expansion von virusspezifischen T Zellen. Des weiteren kommt es zu einer Abnahme der Antikörperantwort auf Impfungen oder Neo-Antigene. Ein Ziel unserer Studie war es, herauszufinden, ob eine Thymektomie im frühen Kindesalter als Modell für eine prämature Immunoseneszenz dienen kann. In thymektomierten Patienten und Kontrollen wurden periphere T Zell Subpopulationen (naïve T Zellen, Gedächtnis T Zellen, intestinale T Zellen, IL-7 Rezeptor (CD127+) tragende T Zellen) durchflusszytometrisch bestimmt und verglichen. Der Einfluss von IL-7 Konzentrationen und chronischen CMV Infektionen auf spezifische T Zell Subpopulationen und die T Zell Rezeptor Diversistät wurde bestimmt. Ein weiterer Teil unserer Studie befasste sich mit dem Einfluss von Thymektomie im Kindesalter auf die T Zell vermittelte Immunantwort auf Impfungen (Früh-Sommer-Meningo-Enzephalitis Impfung und Masern-Mumps-Röteln Impfung).Unsere Studie zeigte eine sinkende Anzahl von naïven T Zellen (v.a. CD8+) in thymektomierten Patienten. Thymektomierte Patienten zeigten höhere prozentuelle Anteile an CD8+CD103+ T Zellen, sowie geringfügig höhere IL-7 Konzentrationen als Kontrollen. CMV seropositive thymektomierte Patienten zeigten eine verstärkte monoklonale T Zell Rezeptor Diversität. Thymektomierte Kinder zeigten eine verzögerte Immunantwort auf Impfungen. Unsere Studie zeigte somit Veränderungen im T Zell Immunsystem, vergleichbar mit den Veränderungen eines gealterten Immunsystems.Aging of the immune system (immunosenescence) starts soon after birth with thymus involution. T cell immunosenescence is characterized by a decreased number of naïve T cells, a compensatory autoproliferation of peripheral memory T cells, an oligoclonal expansion of T cell receptor (TCR) distribution, and an oligoclonal expansion of perpetuated CD8+ T cells due to chronic CMV infection. Consequently a low antibody response to vaccinations and neo-antigens is described. Former studies assumed that thymectomy in early childhood leads to a premature immunosenescence, mimicking changes of the aged immune system. Our study was aimed to prove, if thymectomy in early childhood may serve as a model for premature immunosenescence. Therefore changes in the peripheral T cell subpopulations (naïve and memory T cells, intestinal derived naïve T cells, IL-7 receptor (CD127)-expressing T cells) and TCR distribution were analyzed. The influence of IL-7 values and chronic CMV infection on specific T cell subpopulations was measured. A clinical study was conducted to determine the influence of thymectomy on T cell immunity (response to tick-borne-encephalitis-virus vaccination and mumps-measles-rubella-vaccination). Our study detected lower numbers of naïve T cells , especially in the CD8+ T cell pool. We detected higher rates of CD8+CD103+ T cells in thymectomized patients and a peripheral autoproliferation of pre-existing memory T cells. IL-7 values in thymectomized patients are slightly higher. CMV seropositivity predicts a more monoclonal TCR distribution in thymectomized patients. Thymectomized children showed a delayed immune response to neo-antigens but a normal immune response to revaccination with a live-attenuated vaccine. It remains to be evaluated, if vaccine-specific IgG antibody concentrations of thymectomized children vanish earlier than in controls, and if immunization schedules should be adapted.eingereicht von Manuela ZlamyAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersEnth. u.a. 2 Veröff. d. Verf. aus den Jahren 2009 - 2010 . - Zsfassung in dt. SpracheInnsbruck, Med. Univ., Diss., 2014OeBB(VLID)14582

Increased replication of CD4+ naive T cells and changes in T cell homeostasis in a case of acute exacerbation of juvenile idiopathic arthritis: a case comparison study

Introduction Juvenile idiopathic arthritis is a heterogeneous T cell-mediated autoimmune disease with symptoms of premature aging of the immune system (immunosenescence). The present work is an investigation of immunosenescence parameters, such as quantity of naive and CD28- T cells, T cell receptor excision circles, relative telomere length and alterations of peripheral T cell replication, and was performed via comparison of a case of acute exacerbation of juvenile idiopathic arthritis against six patients with juvenile idiopathic arthritis with disease remission and six age-matched healthy donors over a follow-up course of 12 months. Case presentation Phenotypical T cell characterization and intracellular interferon γ, tumor necrosis factor α, and interleukin 2 production were studied in peripheral blood mononuclear cells from seven patients with juvenile idiopathic arthritis and six healthy control donors, with findings determined by flow cytometry. T cell receptor excision circles and relative telomere length quantification were performed on deoxyribonucleic acid isolated from naive (CD4+CD28+CD45RA+) T cells and investigated via reverse transcription polymerase chain reaction. Ki67 expression was studied by immunohistochemistry on naive T cells. The non-parametric Mann-Whitney U test and Wilcoxon test for two independent groups of variables were used to compare healthy donors with patients with juvenile idiopathic arthritis. During follow-up, patients with juvenile idiopathic arthritis showed lower total counts of naive and CD28-expressing T cells compared to healthy donors. Acute exacerbation led to low naive and CD28+ T cell populations and elevated proportions of Ki67-expressing CD4+ naive T cells. In conditions of exacerbation, T cell receptor excision circle numbers were in the lower range in patients with juvenile idiopathic arthritis and increased after follow-up. Healthy donors showed significantly higher relative telomere lengths compared to patients with juvenile idiopathic arthritis. Conclusions This investigation illustrates that the changes in T cell homeostasis in patients with juvenile idiopathic arthritis may be the result of several mechanisms, such as diminished thymus function and peripheral exertions to maintain the peripheral T cell pool. The results also demonstrate that hallmarks of immunosenescence such as decreased naive T cell levels and lower T cell receptor excision circle numbers can only be interpreted together with replication markers such as relative telomere length or Ki67 expression

Thymectomy in early childhood: significant alterations of the CD4+CD45RA+CD62L+ T cell compartment in later life (Figures)

Figure

The value of axillary skin electron microscopic analysis in the diagnosis of lysosomal storage disorders

Both lysosomal storage diseases and mitochondrial diseases are a group of genetic-inherited metabolic disorders. In an era, where "old fashioned methods" are apparently being replaced by evolving molecular techniques (i.e. exome and whole genome sequencing), the "old fashioned methods" might help to characterise and thus narrow down the potential differential diagnosis. Therefore, we retrospectively evaluated the relevance of electron microscopy of axillary skin for the diagnosis of lysosomal storage or mitochondrial diseases (=inherited metabolic disorders of energy metabolism). Methods and patients: We included 74 patients with developmental delay with regression or neurodegeneration who underwent an axillary skin biopsy for both fibroblast culture and electron microscopy. Because of insufficient skin biopsy quality, for 8 patients no electron microscopy result was obtained. The electron microscopy biopsies revealed abnormalities in 37/66 (56.1%) patients. 29/66 electron microscopy biopsies showed normal results. A definite diagnosis was established in 21/66 (31.8%) patients with a pathological results of axillary skin electron microscopy analysis. In total, in 25/66 (37.8%) of the patients who underwent an axillary skin electron microscopy analysis, a definite diagnosis was finally established. Taking an axillary skin biopsy during anaesthesia or with use of local intradermal lidocaine application is an inexpensive alternative and useful to establish a diagnosis in patients suspected to have a lysosomal storage disease (or inherited metabolic disorder of energy metabolism)

Efforts of the human immune system to maintain the peripheral CD8+ T cell compartment after childhood thymectomy

Background Homeostatic mechanisms to maintain the T cell compartment diversity indicate an ongoing process of thymic activity and peripheral T cell renewal during human life. These processes are expected to be accelerated after childhood thymectomy and by the influence of cytomegalovirus (CMV) inducing a prematurely aged immune system. The study aimed to investigate proportional changes and replicative history of CD8+ T cells, of recent thymic emigrants (RTEs) and CD103+ T cells (mostly gut-experienced) and the role of Interleukin-(IL)-7 and IL-7 receptor (CD127)-expressing T cells in thymectomized patients compared to young and old healthy controls. Results Decreased proportions of naive and CD31 + CD8+ T cells were demonstrated after thymectomy, with higher proliferative activity of CD127-expressing T cells and significantly shorter relative telomere lengths (RTLs) and lower T cell receptor excision circles (TRECs). Increased circulating CD103+ T cells and a skewed T cell receptor (TCR) repertoire were found after thymectomy similar to elderly persons. Naive T cells were influenced by age at thymectomy and further decreased by CMV. Conclusions After childhood thymectomy, the immune system demonstrated constant efforts of the peripheral CD8+ T cell compartment to maintain homeostasis. Supposedly it tries to fill the void of RTEs by peripheral T cell proliferation, by at least partly IL-7-mediated mechanisms and by proportional increase of circulating CD103+ T cells, reminiscent of immune aging in elderly. Although other findings were less significant compared to healthy elderly, early thymectomy demonstrated immunological alterations of CD8+ T cells which mimic features of premature immunosenescence in humans