Favorable benefit-risk ratio with teriflunomide treatment in relapsing-remitting multiple sclerosis: Results of the 2-year, multicenter, prospective, noninterventional TAURUS MS study in Austria.

Objectives: A prospective, multicenter, open-label, noninterventional study assessed the efficacy, safety, tolerability, and patient satisfaction with teriflunomide therapy over a 24-month follow-up period under real-world conditions in Austria. Methods: An all-comer population aged ≥18 years was followed in clinic and office-based settings. The primary objective of the study was the annualized relapse rate after 12 and 24 months of teriflunomide treatment. Patient-reported outcomes included treatment satisfaction, health-related quality of life, and fatigue, and were assessed based on the Short Form Health-36, Fatigue Severity Scale, and Treatment Satisfaction Questionnaire for Medication (TSQM)-9 questionnaires. Results: Thirty-one patients were included in the analysis, 23 of whom were still on treatment after 24 months. At 12 months (n = 24), the annualized relapse rate was 0.3 (SD, 0.8), which indicated a significant decrease compared to the annualized relapse rate of 1.0 (SD, 0.9) observed during the 12-month reference period prior to treatment initiation (p = 0.009). Similarly, after 24 months of follow-up (n = 23), the annualized relapse rate of 0.2 (SD, 0.8) was significantly lower than that during the last 24 months reference period prior to treatment initiation of 0.7 (SD, 0.8) (p = 0.0003). The Expanded Disability Status Scale score remained stable over 12 and 24 months. This also applied to patient-reported fatigue of the Fatigue Severity Scale, with a mean change of 0.1 (SD, 1.0). Patient treatment satisfaction as assessed by the TSQM-9 increased for all three domains (i.e., effectiveness, convenience, global satisfaction). This was confirmed by the physician and multiple sclerosis nurse ratings of patient treatment satisfaction and ease of use. Adverse events occurred in 38.7%, with hair thinning and diarrhea as the most common. Conclusions: This noninterventional study showed a sustained favorable benefit-risk ratio for this disease-modifying treatment with teriflunomide over 24 months in patients with relapsing-remitting multiple sclerosis. Patient-reported outcomes and ratings performed by physicians and nurses showed overall trends to improvement for patient treatment satisfaction with teriflunomide treatment and its ease of administration.

Hepatitis E virus seroprevalence of domestic pigs in Germany determined by a novel in-house and two reference ELISAs.

Autochthonous hepatitis E virus (HEV) infections by zoonotic transmission of genotype 3 (GT3) have been reported increasingly from industrialized countries. In this paper the development and validation of an IgG ELISA for the detection of HEV-specific antibodies in domestic pigs is described. Comparison of the diagnostic value of Escherichia coli-expressed HEV-GT3 capsid protein (CP) derivatives revealed a carboxy-terminal derivative as most suitable. Validation of the in-house assay using a commercially available IgG ELISA revealed a high diagnostic specificity and sensitivity. The average HEV seroprevalence of domestic pigs from Germany and the federal state Baden-Wuerttemberg determined by the in-house test was 42.7% and 50.3%, respectively. The seroprevalence in different districts of Baden-Wuerttemberg ranged from 34.9% to 60%, but from 0% to 100% between different herds. These data were compared to those achieved by two commercially available ELISA kits and an in-house ratHEV-based ELISA. In conclusion, the CP-based in-house test proved sensitive and specific, indicating that the ORF3-encoded protein might be dispensable for diagnostics. The novel assay also allowed a parallel analysis by a homologous ratHEV-derived antigen. Thus, the novel IgG ELISA represents a useful tool for future standardized seroprevalence studies in domestic pigs from Germany and other regions of Europe.

[Epidemiological enquiries in two Q fever outbreaks in a community of Baden-Württemberg during 2008 and 2009]. / Epidemiologische Untersuchungen zu zwei Q-Fieber-Ausbrüchen in einer Gemeinde Baden-Württembergs in den Jahren 2008 und 2009.

In 2008 and 2009, two consecutive outbreaks of Q fever in humans were recorded in the district of Freudenstadt, northern Black Forrest, Baden-Württemberg, Germany. In 2008, a total of 41 persons from a single local community fell ill and were found infected with Coxiella burnetii. Although comprehensive diagnostic and epidemiological outbreak investigations were conducted and control measures taken which included vaccination of ruminants at risk in three parts of the affected community, re-occurrence of the disease in 2009 with further 29 confirmed human Q fever cases could not be prevented. While the origin of infection of the first outbreak was probably a flock of 550 sheep moved in the surrounding of the affected villages, the source of infection for the consecutive outbreak in 2009 could not be identified. It seems possible that meadows contaminated with infectious placenta or birth fluids represented the sources of infection.

Preclinical evaluation of an 18F-labelled beta1-adrenoceptor selective radioligand based on ICI 89,406.

PURPOSE: Radioligand binding studies indicate a down-regulation of myocardial beta(1)-adrenoceptors (beta(1)-AR) in cardiac disease which may or may not be associated with a decrease in beta(2)-ARs. We have chosen ICI 89,406, a beta(1)-selective AR antagonist, as the lead structure to develop new beta(1)-AR radioligands for PET and have synthesised a fluoro-ethoxy derivative (F-ICI). METHODS: (S)-N-[2-[3-(2-Cyano-phenoxy)-2-hydroxy-propylamino]-ethyl]-N'-[4-(2-[(18)F]fluoro-ethoxy)-phenyl]-urea ((S)-[(18)F]F-ICI) was synthesised. Myocardial uptake of radioactivity after intravenous injection of (S)-[(18)F]F-ICI into adult CD(1) mice or Wistar rats was assessed with positron emission tomography (PET) and postmortem dissection. Metabolism was assessed by high-performance liquid chromatography analysis of plasma and urine. RESULTS: The heart was visualised with PET after injection of (S)-[(18)F]F-ICI but neither unlabelled F-ICI nor propranolol (non-selective beta-AR antagonist) injected 15 min after (S)-[(18)F]F-ICI affected myocardial radioactivity. Ex vivo dissection demonstrated that predosing with propranolol or CGP 20712 (beta(1)-selective AR-antagonist) did not affect myocardial radioactivity. Radiometabolites rapidly appeared in plasma and both (S)-[(18)F]F-ICI and radiometabolites accumulated in urine. CONCLUSIONS: Myocardial uptake of (S)-[(18)F]F-ICI after intravenous injection was mainly at sites unrelated to beta(1)-ARs. (S)-[(18)F]F-ICI is not a suitable beta(1)-selective-AR radioligand for PET.

Relationship of immunosuppression to Epstein-Barr viral load and lymphoproliferative disease in pediatric heart transplant patients.

BACKGROUND: Post-transplant lymphoproliferative disease (PTLD) is a severe complication in transplant recipients. Detection of increased Epstein-Barr viral (EBV) load in the peripheral blood acts as a surrogate marker for increased risk of PTLD development. We prospectively monitored EBV load, immunosuppression and PTLD in pediatric heart transplant (HTx) patients to determine risk factors for an increased EBV load and risk of PTLD. METHODS: Forty-one pediatric heart transplant recipients were included and underwent prospective monitoring of their immunosuppression and ethylene-diamine tetraacetic acid (EDTA) blood sampling for EBV load (copies/microg DNA) measurement using quantitative real-time polymerase chain reaction (PCR; TaqMan) during January 2001 to December 2006. RESULTS: EBV load was measurable in 70% and was significantly increased (>2,000 copies/microg DNA) in 35% of the patients, with a median EBV load of 5,100 (range 0 to 50,665 copies/microg DNA). Increased EBV load was detected in patients receiving CsA-azathioprine or more than two doses of anti-thymocyte globulin (ATG) and in those <10 years of age, without any significant differences in CsA blood levels. Lowest or negative EBV load was measured in patients receiving CsA-mycophenolate mofetil (MMF) or CsA only. CsA blood levels were not predictable for increased EBV load or PTLD. Six patients developed a EBV-associated B-cell lymphoma (PTLD), among whom 4 (67%) were receiving CsA-azathioprine. CONCLUSIONS: Frequent EBV load monitoring identifies patients at high risk for PTLD development. Azathioprine and ATG are major risk factors for increased EBV load and PTLD and patients may benefit from a change of immunosuppression in addition to pre-emptive anti-viral or anti-tumor strategies.

Evaluation of the oral immunisation of wild boar against classical swine fever in Baden-Württemberg.

The oral immunisation of wild boar against classical swine fever (CSF) in Baden-Württemberg is described and evaluated. The bait vaccine based on the CSF virus (CSFV) strain "C" proved to be safe in wild boar of all age classes. The modified immunisation procedure consisting of three double vaccinations per year was very effective. CSFV was not detected beyond the second immunisation campaign. The average rate of seropositive wild boar diagnosed over all immunisation periods was 49.2%. The seroprevalence rate increased significantly during the first year of immunisation and reached its maximum after the third vaccination period with 72% antibody positive animals. The higher percentage of seropositive young boars in this field trial compared to the seroprevalence rates in this age class in other field trials in Germany may be attributed to the new vaccination scheme. Factors that may be responsible for the decreased herd immunity after the fourth or sixth immunisation period are discussed.