Humoral and cellular immune response to tick-borne-encephalitis (TBE) vaccination depends on booster doses in patients with Juvenile Idiopathic Arthritis (JIA).

Juvenile Idiopathic Arthritis (JIA) patients living in areas with high prevalence of tick-borne-encephalitis-virus-(TBEV)-infection are recommended for administration of inactivated TBE-vaccination. However, there are serious concerns regarding protective vaccine-induced immune responses against TBEV in immunocompromised patients. The present study aimed to analyze the humoral and cellular immune response to TBE-vaccination in previously TBE-vaccinated JIA patients compared to healthy controls (HC) including investigation of IgG-anti-TBEV avidity, neutralization capacity, cellular reactivity by IFNgamma-ELISPOT and cytokine secretion assays. Similar IgG-anti-TBEV antibody concentrations, neutralization titers and cellular reactivity were found between JIA and HC. The number and the early timing of booster vaccinations after primary vaccination had the most prominent effect on neutralizing antibodies in JIA and on IgG-anti-TBEV concentrations in both JIA and HC. Administration of booster vaccinations made it more likely for JIA patients to have IgG-anti-TBEV concentrations ≥165 VIEU/ml and avidities >60%. TNF-alpha inhibitors had a positive and MTX administration a negative effect on humoral immune responses. In conclusion, irrespective of having JIA or not, vaccinated children showed similar humoral and cellular immunity against TBEV several years after primary TBE-vaccination. However, in JIA, booster vaccinations mounted a significantly higher humoral immune response than in JIA without boosters. Our results highlight the need for timely administration of boosters particularly in JIA. Although immunosuppressive treatment at vaccinations in diagnosed JIA had a negative effect mainly on TBEV-specific cellular immunity, most JIA patients mounted a favorable humoral immune response which was maintained over time. Thus, successful TBE-vaccination seems highly feasible in JIA patients with immunosuppressive regimens.

Differences of IgG antibody avidity after an acellular pertussis (aP) booster in adolescents after a whole cell (wcP) or aP primary vaccination.

Compared to whole cell pertussis (wcP) vaccines, acellular pertussis vaccines (aP) have a better safety profile with lower reactogenicity, although their short and long-term efficacy was found to be slightly lower. Up to now, no established serological parameter to predict long-term protection exists. IgG-anti-pertussis avidity possibly determines the effect of different pertussis vaccines and boosting intervals on long-term immunity. Thus, the avidity of a tetanus-diphtheria-aP booster at 10-14 years was tested in three groups of adolescents who had been previously immunized with either five doses of aP (5aP) at 2, 4, 6, 15-18 months and 5-6 years of age, four doses of aP (4aP) or four doses of wcP (4wcP) at 2, 4, 6 and 15-18 months of age. Relative avidity index (RAI) of IgG-anti-pertussis toxin (PT) and IgG-anti-filamentous-hemagglutinin (FHA) was assessed by an adapted ELISA. RAI of IgG-anti-PT and of IgG-anti-FHA correlated positively with antibody concentrations in the pre-vaccination and in the post-vaccination analysis and significantly increased after adolescent booster with aP in all groups. Pre- and post-vaccination, the proportion of participants with IgG-anti-PT RAI>40% (moderate to high avidity) was significantly lower in the 4wcP group (52.9% and 88.9%) compared to the 5aP group (89.5% and 100.0%). In conclusion, TdaP in adolescence induces an increase of antibody avidity and, thus, is able to enhance the binding-quality of antibodies against pertussis. The study suggests including antibody avidity into serological studies on the humoral response to provide information about the long-term efficacy of the vaccine.

Assessment of IgG avidity against pertussis toxin and filamentous hemagglutinin via an adapted enzyme-linked immunosorbent assay (ELISA) using ammonium thiocyanate.

Antibody avidity, defined as the strength of binding between antibody and antigen, represents a functional measure of affinity maturation of antibodies. Determination of the antibody avidity is usually performed separating high and low avidity antibodies by dissociating agents, but measurement of the antibody avidity in humans is rather complicated, due to the heterogeneity of the antibodies produced in response to complex antigens, e.g. after vaccinations. The purpose of the present study was to evaluate the experimental determinants of the assessment of avidities of IgG antibodies directed against pertussis toxin (IgG-anti-PT) and filamentous hemagglutinin (IgG-anti-FHA) produced after pertussis vaccination using an adapted ELISA and ammonium thiocyanate (NH(4)SCN) as dissociating agent. Our experiments revealed that the results of avidity testing depend very much on experimental conditions and may over- or underestimate the relative avidity of IgG-anti-PT and IgG-anti-FHA antibodies. Whereas in our findings avidity seems to be independent from the initial antibody concentration in a wide range of measures, RAI depends on NH(4)SCN concentration, time of incubation and temperature of the reaction. The presented method allows an accurate measurement of the IgG antibody avidity against both Bordetella pertussis antigens PT and FHA, using NH(4)SCN as chaotropic agent in concentrations lower than 3.0M for 20 min time of incubation at 37 °C. Different experimental conditions in testing pertussis-specific IgG antibody avidity should be considered in interpretation and comparability of data of different studies.

[Infections with pneumococci, menigococci, H. influenzae and diphtheria in Germany: the RKI Reference Network for Invasive Bacterial Infections (IBI) at the 5th Würzburg Workshop on Epidemiology, Prevention and Therapy for Invasive Meningococcal Diseases 2010 (meeting report)]. / Infektionen mit Pneumokokken, Meningokokken, H. influenzae und Diphtherie in Deutschland: das RKI Referenznetzwerk für Invasive Bakterielle Infektionen (IBI) beim 5. Würzburger Workshop zur Epidemiologie, Prävention und Therapie von invasiven Meningokokkenerkrankung 2010 (Tagungsbericht).

The surveillance and prevention of invasive bacterial infections requires flexible strategic coordination of all involved health-care professionals. For this purpose, the German National Reference Centres for Meningococci, Streptococci and the Consultant Laboratories for Haemophilus influenzae and diphtheria have formed the Reference Network for Invasive bacterial infections (IBI). The 5th Würzburg Workshop on Meningococcal Diseases 2010 provided the network with a forum for the interdisciplinary exchange between scientists, public health professionals, medical microbiologists and clinicians. The topics covered the analysis of surveillance data for meningococcal disease in the last decade, as well as methods to control for antibody response following vaccination, including a serum bactericidal antibody (SBA) assay, and the development of new vaccines that also include the most common serogroup B. The presentation on diphtheria showed that this rare disease in Germany has become a diagnostic challenge, and that apart from the classical pathogen also toxigenic C. ulcerans strains must be considered. Due to the successful vaccination against Hib, H. influenzae disease has changed from a classical childhood disease to an infection of elderly people mainly caused by unencapsulated strains. Following the introduction of vaccines, changes in the serotype distribution and antibiotic resistance profiles have become apparent for S. pneumoniae infections. The epidemiological data were complemented by clinical aspects concerning the vaccination of immunocompromised children.

Use of linezolid in neonatal and pediatric inpatient facilities--results of a retrospective multicenter survey.

The purpose of this investigation was to describe the use of linezolid in pediatric inpatient facilities. A retrospective multicenter survey including data from nine participating tertiary care pediatric inpatient facilities in Germany and Austria was undertaken. Data on 126 off-label linezolid treatment courses administered to 108 patients were documented. The survey comprises linezolid treatment in a broad spectrum of clinical indications to children of all age groups; the median age was 6.8 years (interquartile range 0.6-15.5 years; range 0.1-21.2 years; ten patients were older than 18 years of age but were treated in pediatric inpatient units). Of the 126 treatment courses, 27 (21%) were administered to preterm infants, 64 (51%) to pediatric oncology patients, and 5% to patients soon after liver transplantation. In 25%, the infection was related to a medical device. Linezolid iv treatment was started after intensive pre-treatment (up to 11 other antibiotics for a median duration of 14 days) and changed to enteral administration in only 4% of all iv courses. In 39 (53%) of 74 courses administered to children older than 1 week and younger than 12 years of age, the dose was not adjusted to age-related pharmacokinetic parameters. In only 17 courses (13%) was a pediatric infectious disease consultant involved in the clinical decision algorithm. Linezolid seemed to have contributed to a favorable outcome in 70% of all treatment courses in this survey. Although retrospective, this survey generates interesting data on the off-label use of linezolid and highlights several important clinical aspects in which the use of this rescue antibiotic in children might be improved.

Lyme neuroborreliosis: aetiology and diagnosis of facial palsy in children from Tyrol.

BACKGROUND: Lyme neuroborreliosis (LNB) is the second most common manifestation of Borrelia burgdorferi sensu lato (s. l.) infection in Europe. LNB is difficult to differentiate from other aetiologies of aseptic meningitis. Diagnostic criteria for LNB in children are not established. Therfore, based on the epidemiology of LNB in children from Tyrol, the aim of our study was to point out the necessity of a clear definition of pediatric LNB to avoid underdiagnosis and overtreatment. PATIENTS AND METHODS: All medical charts of patients presented with acute peripheral facial palsy from January 2002 to December 2005 were reviewed. The patients were rediagnosed according to the criteria of the German Society of Neurology (DGN). RESULTS: We identified 66 patients with peripheral facial palsy. 30 children were handled as B. burgdorferi s. l. infection. 5 patients were overtreated with antibiotic therapy. After reevaluation according to the DGN criteria 7 cases were reclassified as possible, 16 cases as probable and 7 cases as confirmed LNB. CONCLUSIONS: Utilization of the established DGN criteria for pediatric LNB might help to elucidate the propability of LNB. Prospective studies are required to establish a classification system. A diagnostic tool, based on laboratory and clinical data, should avoid overtreatment of pediatric LNB.

Successful treatment of severe juvenile microscopic polyangiitis with rituximab.

Microscopic polyangiitis (MPA) previously called hypersensitivity angiitis is a systemic necrotizing vasculitis affecting predominantly small vessels. MPA involves multiple organ systems including the lung, the kidneys, the joints, and the skin. MPA mostly affects adults in their fourth and fifth decade of life. MPA and Wegener;s granulomatosis are grouped together as ANCA-associated vasculitis. MPA is associated with high titre of myeloperoxidase antineutrophil cytoplasmic antibodies (MPO)-ANCA. We present a 14-year-old female patient presented with MPA. She was treated with steroids and cyclophosphamide. After the complication of severe lung involvement, rituximab was administered as immune-modulating treatment. The MPA came to remission. This is the first report of a pediatric patient with MPA treated with rituximab. Rituximab might be a potential therapeutic option for relapsing ANCA associated vasculitis in childhood.

CTX-M-1-related extended-spectrum beta-lactamases producing Escherichia coli: so far a sporadic event in Western Austria.

BACKGROUND: The present study was aimed to searching for CTX-M-type extended-spectrum beta-lactamases in community- and hospital-acquired Escherichia coli (E. coli) collected in western Austria and to investigate their clonal relatedness and their ability to spread. PATIENTS AND METHODS: All patients with E. coli positive cultures collected from a catchment population of 186,000 between January and July 2006 were enrolled into the study. CTX-M-producing E. coli were identified by antibiotic susceptibility testing and blaCTX-M multiplex PCR. Clonal relatedness was analyzed by pulsed-field gel electrophoresis (PFGE). RESULTS: In 2,042 E. coli isolates, 20 isolates (16 from urine, 4 from blood cultures) demonstrated CTX-M-1-related genes and no CTX-M-2- or CTX-M-9-related enzymes or CTX-M-15-producing strains were identified. We did not find clonal relatedness among CTX-M-1 producers isolated from the same referring center. E. coli were investigated for plasmid transfer ability of CTX-M-1-encoding genes. Plasmid digest patterns were not consistent with episomal spread of resistance loci. Transfection of CTX-M-encoding plasmids failed. CONCLUSION: Our data suggest that the emergence of CTX-M-1-producing E. coli in western Austria may be attributed to multiple independent events.

EpCAM is predominantly expressed in high grade and advanced stage urothelial carcinoma of the bladder.

BACKGROUND: EpCAM is an adhesion molecule of the basolateral membranes in a variety of epithelial cells. Over-expression has been detected in many epithelial tumours and has been associated with high stage, high grade and a worse survival in some tumour types. AIMS: To assess the prognostic value of EpCAM in urothelial carcinoma of the bladder. METHODS: EpCAM expression was analysed by immunohistochemistry using a monoclonal antibody (clone VU-1D9) on a tissue microarray comprising 99 urothelial carcinomas of the bladder diagnosed between 1994 and 1997. RESULTS: A significant relationship between high grade, advanced stage, and EpCAM expression was found, and expression of EpCAM was associated with a worse overall survival when compared to EpCAM negative tumours (p = 0.033). Multivariate analysis showed that EpCAM expression was not an independent prognostic factor for overall survival in urothelial carcinoma of the bladder. CONCLUSION: EpCAM expression is associated with advanced stage, high grade and poor overall survival in urothelial carcinoma of the bladder, but lacks an independent prognostic significance. The strong association with high grade tumours suggests a possible role during tumour progression and makes EpCAM a potential target for antibody mediated therapy.

Demand for evaluation of vaccination antibody titers in children considered for renal transplantation.

Vaccinations are recommended for achieving protection against vaccine-preventable infections in solid-organ transplant recipients. In order to evaluate the protection at the time of renal transplantation, the antibody titers against measles, mumps, rubella, varicella, hepatitis B, diphtheria, and tetanus were determined in 35 children one month prior to transplantation. Only 26% of patients on dialysis listed for transplantation showed protective antibodies against all tested pathogens. Particularly, low protection was found for hepatitis B. Children younger than four yr showed significantly lower protective antibody titers compared with older children for almost all vaccines. Children who completed vaccination in the last six months to six yr prior to renal transplantation showed higher rates of protective antibody titers against all pathogens compared with children who had vaccination more than six yr before transplantation. Preventive strategies in children with chronic renal failure include repeated measurements of serum antibodies and appropriate revaccination if titers decline. Our results underline the demand for continuous surveillance of specific antibody titers against vaccine-preventable diseases in the risk group of renal transplant recipients.

Bilateral renal vein thrombosis in a twin newborn without known risk factors.

Neonatal renal vein thrombosis (RVT) is associated with neonatal stress, catheters and genetic prothrombotic risk factors. In an unusual case of bilateral RVT a twin newborn showed initial good adaptation at birth (weight 2,720 g). The placenta was monochorionic, diamnionic. The infant (gestational week 37) exhibited a severe macrohematuria within 24 hours after birth. Sonography of the kidneys showed a dense cortical parenchyma, loss of cortico-medullary differentiation and negative diastolic flow in both renal arteries and veins, while no thrombus in the main renal veins could be detected. No prothrombotic blood parameters and positive infection serology were detected. Because of acute renal failure peritoneal dialysis was necessary for 6 weeks. The patient was treated by heparinization for 5 days. Interestingly, it was kidney biopsy which confirmed the diagnosis of RVT in addition to the clinical presentation, whereas sonography was unspecific. Histology exhibited the picture of an ischemic contracted kidney with numerous siderophages. At present (age 19 months), the patient suffers from chronic renal failure (calculated glomerular filtration rate according to Schwartz 12 ml/min/1.73 m2). In conclusion, our case teaches that, despite the lack of a clinically obvious shock event, absence of known risk factors and indirect ultrasound findings, renal vein thrombosis should be considered in a macrohematuric newborn with renal failure. For clinical suspicion of RVT correct therapy was initiated, however, the diagnosis remained unclear until a renal biopsy was performed.