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Knuf M.,Johannes Gutenberg University Mainz | Pankow-Culot H.,Pediatric Office | Grunert D.,Praxis Inc. | Rapp M.,Pediatric Practice | And 7 more authors.
Pediatric Infectious Disease Journal | Year: 2012

Background: Induction of immunologic memory was assessed following primary vaccination with 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). Methods: Infants were randomized (1:1) to receive 3 doses of PHiD-CV or 7vCRM (7-valent CRM197-conjugated pneumococcal conjugate vaccine [PCV]) at 2, 3, and 4 months of age followed by 23-valent pneumococcal polysaccharide vaccine (23vPS) booster dose at 11 to 14 months of age. Pneumococcal geometric mean antibody concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers were measured. Results: Postprimary immune responses were consistent with those in previous PHiD-CV and 7vCRM studies. Following 23vPS boosting, vaccine serotype-specific antibody GMCs increased 6.5-to 33.3-fold and 4.8-to 32.2-fold versus prebooster in the PHiD-CV and 7vCRM groups, respectively. Postbooster OPA titers increased 2.8-to 38.8-fold and 2.6-to 58.9-fold, respectively. Postbooster antibody GMCs exceeded postprimary levels but, for some serotypes, postbooster OPA geometric mean titers were lower than postprimary in both groups. An additional dose of the same PCV received for priming was administered to 52 children aged 46 to 50 months, resulting in higher responses versus postprimary vaccination for all serotypes, but not always higher than post-23vPS booster. Conclusions: Induction of immunologic memory following PHiD-CV priming was confirmed. Additional PCV boosting in 4-year-olds did not provide strong evidence of hyporesponsiveness induced by previous 23vPS boosting. However, our results did not rule out depletion of the memory B cell pool following 23vPS vaccination, resulting in subsequent attenuated immune responses, and therefore support the use of PCV rather than 23vPS for booster vaccination in the second year of life. © 2012 Lippincott Williams & Wilkins.

Behre U.,Pediatric Practice | Bleckmann G.,Kinder und Jugendarzt | Crasta P.D.,Glaxosmithkline | Leyssen M.,Glaxosmithkline | And 3 more authors.
Human Vaccines and Immunotherapeutics | Year: 2012

This paper presents data from two studies that evaluated 5-y and 10-y persistence of antibodies against hepatitis B (HBV) surface antigen (anti-HBs) and immune response to an HBV vaccine challenge in children and adolescents who had received three doses of a HBV vaccine in infancy as part of routine clinical practice [NCT00519649/NCT00984139]. Anti-HBs antibody concentrations ≥10 mIU/ml persisted in 83.3% (95% confidence interval [CI]: 78.5-87.5) and 78.3% (95% CI: 73.1-83.0) of subjects aged 7-8 y and 12-13 y, respectively 5-10 y after infant vaccination. One month postchallenge dose, 98.2% (95% CI: 95.9-99.4) and 93.7% (95% CI: 90.2-96.2) of subjects in the two age groups, respectively had anti-HBs antibody concentrations ≥100 mIU/ml. Overall, 99.6% (95% CI: 98-100) and 97.2% (95% CI: 94.5-98.8) of subjects aged 7-8 y and 12-13 y mounted an anamnestic response to the HBV challenge dose, which was well-tolerated. Healthy children aged 7-8 y and adolescents aged 12-13 y received three doses of a monovalent pediatric HBV vaccine (10 μg of HBsAg) before 18 mo of age. Serum samples collected before and one month post-HBV vaccine challenge dose were tested for anti-HBs antibody concentrations. Safety assessments were made for the HBV vaccine challenge dose. A three-dose childhood HBV immunization regimen induced persistence of antibodies against HBV infection for 10 y, up to adolescence. This vaccination regimen also conferred long-term immune memory against HBV as evidenced by the strong anamnestic response to the HBV vaccine challenge, despite waning anti-HBs antibody levels. © 2012 Landes Bioscience.

Anderson C.L.,Charite - Medical University of Berlin | Anderson C.L.,Robert Koch Institute | Remschmidt C.,Robert Koch Institute | Drobnitzky F.-P.,Pediatric Practice | And 4 more authors.
Human Vaccines and Immunotherapeutics | Year: 2016

In Germany, vaccination of infants against hepatitis B is recommended since 1995. However, data on long-term immunity is sparse and the necessity of a booster dose remains uncertain. Aims of this study were to assess the long-term persistence of antibodies to the hepatitis B surface antigen (anti-HBs) after immunization during infancy and the effect of a subsequent hepatitis B booster vaccination during adolescence on anti-HBs levels. Patients from a private pediatric practice who had received a full vaccination course of hepatitis B as infants and who were quantitatively tested for anti-HBs during adolescence (pre-booster levels) were included. In those participants who received a hepatitis B booster, post-booster anti-HBs levels were measured. Univariate analyses were conducted to determine factors associated with pre- and post-booster anti-HBs levels, respectively. 106 participants (53% male) were included in the study. At an average of 13.7 y after primary vaccination, 14% of participants had an anti-HBs level of ≥100 IU/l, while 46% were at 10–99 IU/l and 40% had anti-HBs levels of <10 IU/l. In total, 34 received a booster vaccination. Of those, 97% (33/34) had post-booster anti-HBs levels ≥ 100 IU/l, which were independent from pre-booster levels. No other patient characteristics were associated with pre-booster or post-booster anti-HBs≥ 100 IU/l. Although almost half of study participants showed low anti-HBs levels at follow-up, robust responses to booster vaccination suggest that adolescents who received the full vaccination course during infancy are still protected against hepatitis B infection. © 2016, Taylor & Francis.

Bohn B.,University of Ulm | Rosenbauer J.,Heinrich Heine University Dusseldorf | Icks A.,Heinrich Heine University Dusseldorf | Vogel C.,Childrens Hospital Chemnitz | And 8 more authors.
Experimental and Clinical Endocrinology and Diabetes | Year: 2016

Background: Data on regional differences in the quality of medical care in Germany are scarce. This study aimed to compare outcome quality and medical treatment of pediatric patients with type 1 diabetes between the federal states of Germany. Methods: 24 928 patients (< 18 years of age) with type 1 diabetes and German residence were selected from the Diabetes-Patienten-Verlaufsdokumentation database. Indicators of outcome quality were HbA1C, overweight prevalence, and rate of severe hypoglycemia. To reflect medical treatment, use of insulin pumps and use of rapid-acting or long-acting insulin analogues were analyzed. Logistic regression models were created for binary variables with federal state as independent predictor. Linear regression was applied for HbA1C and Poisson regression for rate of severe hypoglycemia. Confounders: Sex, age, diabetes duration, migratory background. Results: Disparity was observed for indicators of outcome quality between the 16 federal states of Germany (all p<0.05). After adjustment, HbA1C varied between 55.8 mmol/mol and 67.3 mmol/mol, overweight prevalence between 10.0 and 15.3%, severe hypoglycemia ranged from 0.06 events/PY to 0.21 events/PY. Overall, the best outcome quality appeared to be present in Saxony. Medical treatment also differed. The percentage of pediatrics on insulin pumps varied between 26.3 and 51.8%. The use of rapid-acting analogues ranged from 56.6 to 96.2% and the use of long-acting analogues varied between 41.9 and 96.9% (all p<0.0001). Conclusions: Medical treatment and outcome quality in pediatrics with type 1 diabetes differed within Germany. Disparities in individual socioeconomic status, regional deprivation, or differences in medical reimbursement decisions might have contributed to the patterns observed. © 2016 J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

Bulow L.,Johannes Gutenberg University Mainz | Lissewski C.,University Hospital | Bressel R.,Pediatric Practice | Rauch A.,University of Zurich | And 3 more authors.
American Journal of Medical Genetics, Part A | Year: 2015

Fetal hydrops, fetal pleural effusions, hydrothorax, and chylothorax, may be associated with various genetic disorders, in particular with the Noonan, cardio-facio-cutaneous and Costello syndromes. These syndromes, collectively called RASopathies, are caused by mutations in the RAS/MAPK pathway, which is known to play a major role in lymphangiogenesis. Recently, germline mutations in the Casitas B-cell lymphoma (CBL) gene were reported in 25 patients and of these, 20 had juvenile myelomonocytic leukemia (JMML). The disorder was named "CBL syndrome" or "Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia" (NSLL). To date, prenatal abnormalities have not been reported and it is still debated whether the CBL syndrome falls into the category of a RASopathy, or represents a different entity. Here we report on three unrelated patients with CBL mutations manifesting with hydrops fetalis, fetal pleural effusions and/or congenital hydro-/chylothorax. Our findings further connect the CBL syndrome with the RASopathies. © 2014 Wiley Periodicals, Inc.

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