Showing papers by "Ulrich Vogel published in 2018"

Predicting the Susceptibility of Meningococcal Serogroup B Isolates to Bactericidal Antibodies Elicited by Bivalent rLP2086, a Novel Prophylactic Vaccine.

Abstract: Bivalent rLP2086 (Trumenba), a vaccine for prevention of Neisseria meningitidis serogroup B (NmB) disease, was licensed for use in adolescents and young adults after it was demonstrated that it elicits antibodies that initiate complement-mediated killing of invasive NmB isolates in a serum bactericidal assay with human complement (hSBA). The vaccine consists of two factor H binding proteins (fHBPs) representing divergent subfamilies to ensure broad coverage. Although it is the surrogate of efficacy, an hSBA is not suitable for testing large numbers of strains in local laboratories. Previously, an association between the in vitro fHBP surface expression level and the susceptibility of NmB isolates to killing was observed. Therefore, a flow cytometric meningococcal antigen surface expression (MEASURE) assay was developed and validated by using an antibody that binds to all fHBP variants from both fHBP subfamilies and accurately quantitates the level of fHBP expressed on the cell surface of NmB isolates with mean fluorescence intensity as the readout. Two collections of invasive NmB isolates (n = 1,814, n = 109) were evaluated in the assay, with the smaller set also tested in hSBAs using individual and pooled human serum samples from young adults vaccinated with bivalent rLP2086. From these data, an analysis based on fHBP variant prevalence in the larger 1,814-isolate set showed that >91% of all meningococcal serogroup B isolates expressed sufficient levels of fHBP to be susceptible to bactericidal killing by vaccine-induced antibodies. IMPORTANCE Bivalent rLP2086 (Trumenba) vaccine, composed of two factor H binding proteins (fHBPs), was recently licensed for the prevention of N. meningitidis serogroup B (NmB) disease in individuals 10 to 25 years old in the United States. This study evaluated a large collection of NmB isolates from the United States and Europe by using a flow cytometric MEASURE assay to quantitate the surface expression of the vaccine antigen fHBP. We find that expression levels and the proportion of strains above the level associated with susceptibility in an hSBA are generally consistent across these geographic regions. Thus, the assay can be used to predict which NmB isolates are susceptible to killing in the hSBA and therefore is able to demonstrate an fHBP vaccine-induced bactericidal response. This work significantly advances our understanding of the potential for bivalent rLP2086 to provide broad coverage against diverse invasive-disease-causing NmB isolates.

Failure of first meningococcal vaccination in patients with atypical haemolytic uraemic syndrome treated with eculizumab.

Abstract: Background The C5 complement inhibitor eculizumab is a first-line treatment in atypical haemolytic uraemic syndrome (aHUS). Therapy with eculizumab is associated with a highly increased risk for meningococcal infection. Therefore, vaccination is highly recommended before beginning treatment. Efficacy of quadrivalent meningococcal vaccines (MenACWY) in patients treated with the C5 complement inhibitor eculizumab in aHUS has not yet been determined. Methods Patients with aHUS received one dose of a MenACWY conjugate vaccine before eculizumab treatment commenced. Bactericidal titres against meningococcal serogroups A, C, W and Y were determined using baby rabbit complement in 25 patients. Results Full immune response to meningococcal vaccination was detected in five patients (20%), while seven patients (28%) showed no immune response in any of the tested serogroups. The remaining 13 patients showed incomplete immune response with proof of protective antibody titres for one to three serogroups without perceptible preference for any serogroup. Bactericidal titres after re-vaccination were available for 17 patients. Nine patients with incomplete immune response after first vaccinations showed protective antibody titres for all serogroups after re-vaccination. Kidney function had improved in >50% of patients at the time of re-vaccination compared with the time of first vaccination and immunosuppressive therapy was only applied to re-vaccinated patients following kidney transplantation. Conclusions Immunogenicity of first quadrivalent meninongococcal vaccination is insufficient in patients with aHUS. Booster response is promising, but incomplete. Therefore, establishing antibiotic prophylaxes seems pivotal.

[Cause-of-death statistics and ICD, quo vadis?]

Abstract: Die Internationale statistische Klassifikation der Krankheiten und verwandter Gesundheitsprobleme (ICD) stellt den weltweit verbindlichen Standard zur Erstellung der Todesursachenstatistik dar. Fragestellungen: Welche Effekte haben bisherige Revisionen der ICD auf die Todesursachenstatistik und welche Chancen und Herausforderungen zeichnen sich beim moglichen Ubergang von der ICD-10 zur ICD-11 ab? Es wird die Ausschopfung der ICD-9 und ICD-10 durch die deutsche Todesursachenstatistik sowie die Dokumentationsqualitat berechnet. Verwendet werden die Ergebnisse der amtlichen Todesursachenstatistik und 67.000 Todesbescheinigungen, die mit dem Kodiersystem Iris/MUSE verarbeitet werden. Neben einer deutlichen Veranderung des Ausschopfungsgrades beim Ubergang von ICD-9 nach ICD-10 werden regionale Effekte sichtbar. Der Anteil schlecht beschriebener unikausaler Todesursachen liegt bei uber 10 %. Trotz umfangreicher Verbesserungen der ICD-Revisionen gibt es seit Jahren bekannte Defizite bei der Festlegung der Todesursachen, der Ausstellung der Todesbescheinigung und bei der Qualitat der Signierung. Um das Potenzial der ICD in Deutschland besser auszuschopfen, erscheinen folgende Masnahmen prioritar: 1. vollumfangliche Nutzung von Iris/MUSE, 2. Etablierung einer multikausalen Todesursachenstatistik, 3. Einfuhrung einer elektronischen Todesbescheinigung, 4 Verbesserung der arztlichen Todesursachenerfassung. Mit der in Kurze von der WHO bereitgestellten 11. Revision der ICD eroffnen sich zusatzliche Perspektiven fur die Weiterentwicklung der Todesursachenstatistik in Wissenschaft, Public Health und Politik. Ein abgestimmtes Vorgehen unter Einbeziehung von Prozessbeteiligten und Nutzergruppen ist erforderlich, um den damit verbundenen Herausforderungen gerecht zu werden.

Impact of different concentrations of an octenidine dihydrochloride mouthwash on salivary bacterial counts: a randomized, placebo-controlled cross-over trial.

Abstract: This bi-centric, placebo-controlled, randomized, evaluator-blinded, incomplete cross-over clinical phase II trial was initialized to identify the most appropriate concentration of octenidine dihydrochloride (OCT) in mouth rinses. Rinses of 0.10, 0.15, and 0.20% OCT were compared to a saline placebo rinse regarding the reduction of salivary bacterial counts (SBCs) in 90 gingivitis patients over 4 days. Changes in plaque (PI) and gingival index (GI), taste perception, and safety issues were evaluated. At baseline, the first OCT (0.10, 0.15, 0.20%) rinse resulted in a decrease of SBC (reduction by 3.63–5.44 log10 colony forming units [CFU]) compared to placebo (p < 0.001). Differences between OCT concentrations were not verified. After 4 days, the last OCT rinse again resulted in a significant SBC decrease (3.69–4.22 log10 CFU) compared to placebo (p < 0.001). Overall, SBC reduction between baseline and day 4 was significantly higher in OCT 0.15 and 0.20% groups compared to OCT 0.10% and placebo. Mean GI/PIs were significantly lower in OCT groups than in the placebo group (p < 0.001). Differences in GI/PI between OCT groups were not verified. Adverse effects increased with increasing OCT concentrations. Considering antibacterial efficacy, frequency of adverse events, and user acceptance, 0.10% OCT was identified as the preferred concentration to be used in future clinical trials. Due to its low toxicity and pronounced antibacterial properties, octenidine dihydrochloride (OCT) is a promising candidate for the use in antiseptic mouth rinses. OCT concentrations of 0.10% are recommended for future clinical trials evaluating the plaque-reducing properties of OCT mouth rinses. ( www.clinicaltrials.gov , NCT022138552)

[Field tests for the beta version of the ICD-11-MMS in Germany: background and methods]

Abstract: Seit 2007 arbeitet die Weltgesundheitsorganisation (WHO) an der 11. Revision zur Internationalen Klassifikation der Erkrankungen (ICD). Die ICD-11 unterscheidet sich in Umfang und Struktur deutlich von der ICD-10. Vor der Verabschiedung hatte die WHO daher Feldtests mit Kodierung von Diagnosen und Fallbeschreibungen vorgesehen. In der Arbeit sollen Hintergrund und Umsetzung der Feldtests in Deutschland beschrieben werden. Uber die Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) wurden interessierte Mitglieder zu Projektantragen aufgefordert. Die Koordination erfolgte durch die Technologie- und Methodenplattform fur die vernetzte medizinische Forschung e. V. (TMF) mit Unterstutzung des Deutschen Instituts fur Medizinische Dokumentation und Information (DIMDI). Zu untersuchen war eine Betaversion („draft for quality assurance“) der ICD-11 for Mortality and Morbidity Statistics (ICD-11-MMS), einer Fassung der ICD-11 zur Abbildung von Mortalitat und Morbiditat. Von Marz bis August 2017 konnten 11 Feldtests durchgefuhrt werden. Mit Ausnahme eines Tests uber die Diagnosenbezeichnungen aus dem Alphabetischen Verzeichnis zur ICD-10-GM fokussierten die Feldtests auf jeweils ein medizinisches Fachgebiet. Uber die 11 Feldtests wurden insgesamt 8 verschiedene Gutekriterien untersucht und 22 der 27 Kapitel der ICD-11-MMS zumindest anteilig einbezogen. Trotz engem Zeitrahmen liesen sich die Feldtests in Deutschland erfolgreich umsetzen. Weitestgehend wurde auf die Kodierwerkzeuge der WHO zuruckgegriffen. Ein Grosteil der Kapitel der ICD konnte anteilig abgedeckt werden. Erstmalig wurde demonstriert, dass Feldtests einen wertvollen Ansatz zu einer die Entwicklung begleitenden Evaluation der ICD darstellen. Die Feldtests sind allerdings noch in einen Methodenrahmen einzufugen, um alle relevanten Anforderungen bei einer Evaluation berucksichtigen zu konnen.

Wild-type isolates of Porphyromonas gingivalis derived from periodontitis patients display major variability in platelet activation.

Abstract: In vitro studies revealed that Porphyromonas gingivalis (Pg), a pathogen intimately associated with the onset and progression of periodontitis, is able to activate platelets, thus linking periodontal inflammation with the endangerment of vascular health. As wild-type Pg strains are characterized by major genetic heterogeneity, the commonness of platelet-activating Pg strains in periodontitis patients is unknown as of yet. Therefore, this study evaluated the platelet activation capacity of wild-type Pg isolates sampled from patients with aggressive periodontitis. Methods Extent and velocity of platelet aggregation were determined by light transmission aggregometry. Platelet surface expression of P-selectin was measured by flow cytometry, activation of p38 MAP kinase, and protein kinase C by Western blot using phospho-specific antibodies. Results Pg isolates displayed high variability regarding extent and velocity of platelet activation, as well as the involved activating pathways. Corresponding results were observed for platelet P-selectin expression, activation of p38 MAP kinase, or protein kinase C. Inhibitors of platelet immune receptor FcγRIIA and protease-activated receptors revealed several, diverging pathways of activation. Some isolates induced platelet aggregation even in the presence of potent therapeutical platelet inhibitors. Conclusions Chronic bacteremia involving specific, platelet-activating Pg strains may constitute a substantial hazard for the integrity of cardiovascular health.

Value of the eazyplex® CSF direct assay in rapid diagnosis of invasive meningococcal disease – Case report

Abstract: There is a need for easy-to-use molecular assays for diagnosis of invasive meningococcal disease. Here, we report the rapid identification of Neisseria meningitidis in a cerebrospinal fluid sample from a patient with purulent meningitis using a commercially available loop-mediated isothermal amplification assay, resulting in a prompt de-escalation of the initial empiric antibiotic therapy.