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Background Medical students come into contact with infectious diseases early on their career. Immunity against vaccine-preventable diseases is therefore vital for both medical students and the patients with whom they come into contact. Methods The purpose of this study was to compare the medical history and serological status of selected vaccine-preventable diseases of medical students in Germany. Results The overall correlation between medical history statements and serological findings among the 150 students studied was 86.7 %, 66.7 %, 78 % and 93.3 % for measles, mumps, rubella and varicella, conditional on sufficient immunity being achieved after one vaccination. Conclusions Although 81.2 % of the students medical history data correlated with serological findings, significant gaps in immunity were found. Our findings indicate that medical history alone is not a reliable screening tool for immunity against the vaccine-preventable diseases studied.
Trotz der Spenderauswahl, des serologischen Screenings der Blutspenden auf antiHIV-1, anti-HIV-2, anti-HCV und HBsAg, Inaktivierungs- und Eliminierungsverfahren bleibt ein Restrisiko für hämatogen übertragbare Viren bei Plasmapools und den daraus hergestellten Präparaten. Als zusätzliche Screeningmethode zur Erhöhung der Virussicherheit wird inzwischen die Testung der Einzelspende bzw. von Minipools auf HCV-RNA verlangt. In der vorliegenden Arbeit wurden 142 HBsAg, anti-HCV- und anti-HIV-11-2 negative Plasmapools, sowie Plasmapräparate (Immunglobulinpräparat und F IX Präparat), welche zum Teil aus für HGV-RNA PCR-positiven Ausgangspools hergestellt worden waren, mittels PCR auf das Vorhandensein von HGV-Nukleinsäure untersucht. Alle untersuchten Pools bzw. Plasmapräparate stammten von Spenden zwischen 1994 und 1996, also vor der Einführung der genannten Pflichttestung auf HCV-RNA. HGV-RNA wurde in 117 der 142 Plasmapools (82,4%) amplifiziert. Allerdings war HGV-RNA nur in einer (6,3%) von 16 IgG-Chargen aus für HGV-Nukleinsäure positiven Kryoüberständen nachweisbar. In 2 (6,5%) von 31 unselektierten Immunglobulinpräparaten war eine HGV- Kontamination vorhanden. Eine routinemäßige Anwendung der PCR ist zur Zeit aus technischen sowie Kosten-Nutzen-Überlegungen für HGV nicht zu empfehlen, solange die klinische Relevanz nicht gesichert ist. Die Ergebnisse unterstreichen die Wichtigkeit der im Herstellungsprozeß integrierten Viruseliminierungsverfahren, denn bei der vorliegenden Studie konnte nur in einem geringen Anteil der Endproduktchargen HGV-Nukleinsäure nachgewiesen werden.
Es wurde die Seroprävalenz von Erregern mit und ohne Tropismus zu Gefäßendothelzellen, wie Chlamydia (C.) pneumoniae, C. trachomatis, C. psittaci, verschiedene Herpesviren (Cytomegalie-Virus (CMV), Epstein-Barr-Virus (EBV), Herpes simplex Typ l und 2-Virus, Varizella Zoster-Virus (VZV)) sowie Masern- und Mumpsviren, bei Patienten mit koronarer Herzerkrankung (KHK) (n=167) und zwei Kontrollkollektiven ohne Herzerkrankung (n=400, n=108) ermittelt. Die IgG-Antikörperprävalenzen betrugen im KHK-Kollektiv für C. pneumoniae 79,6% bzw. in den Kontrollkollektiven 72,5% und 66,7%, für C. trachomatis 4,8% bzw. 6,8% und 2,8%, für C. psittaci 3% bzw. 3,5% und 6,5%, für CMV 72,9% bzw. 74,3% und 79,2%, für EBV 95,1% bzw. 93.1% und 94%, für Herpes simplex 1/2 91,8% bzw. 87,4% und 91,3%, für Masern 99,2% bzw. 100% und für Mumps 93,4% bzw. 86,5% und 84,8%. Die Prävalenzen der VZV-IgA waren 60,3% bzw. 57,3% und 54%. Bei dieser Untersuchung zeigten sich somit keine signifikanten Unterschiede in den Antikörperprävalenzen zwischen den einzelnen Kollektiven. Wurden kranke, stationäre Patienten aus dem Kontrollkollektiv ausgeschlossen, so fand sich in diesem zweiten Kontrollkollektiv mittels Chi2-Test eine signifikant niedrigere Prävalenz (66,7%) der C. pneumoniae-IgG-Antikörper im Vergleich zu Patienten mit KHK (79,6%), (p=0,02). Die Untersuchung der geschlechtsspezifischen Prävalenzen zeigte für Männer (82,6% bzw. 78,5% und 73,2%) eine höhere Durchseuchung als für Frauen (55,6% bzw. 63% und 59,6%). Beim Vergleich gleichgeschlechtlicher Gruppen fanden sich keine signifikanten Unterschiede. Eine Assoziation von C. pneumoniae oder CMV mit der atherosklerotischen, koronaren Herzerkrankung konnte somit durch unsere* Untersuchung nicht bestätigt werden. Die Wahl der Kontroll-Gruppen kann möglicherweise die Ergebnisse der Metaanalyse früherer Assoziationsstudien beeinflußt haben.
Omeprazole was shown to improve the anti-cancer effects of the nucleoside analogue 5-fluorouracil. Here, we combined omeprazole with the antiviral nucleoside analogues ribavirin and acyclovir. Omeprazole did not affect the antiviral effects of ribavirin in non-toxic concentrations up to 80 μg/mL but increased the acyclovir-mediated effects on herpes simplex virus 1 and 2 (HSV-1 and -2) replication in a dose-dependent manner. Omeprazole alone reduced HSV-1 and -2 titers [but not HSV-induced formation of cytopathogenic effects (CPE)] at concentrations ≥40 μg/mL. However, it exerted substantially stronger effects on acyclovir activity and also increased acyclovir activity at lower concentrations that did not directly interfere with HSV replication. Omeprazole 80 μg/mL caused a 10.8-fold (Vero cells) and 47.7-fold (HaCaT cells) decrease of the acyclovir concentrations that reduced HSV-1-induced CPE formation by 50% (IC50). In HSV-2-infected cells, omeprazole 80 μg/mL reduced the acyclovir IC50 by 7.3- (Vero cells) and 12.9-fold (HaCaT cells). In HaCaT cells, omeprazole 80 μg/mL reduced the HSV-1 titer in the presence of acyclovir 1 μg/mL by 1.6 × 105-fold and the HSV-2 titer in the presence of acyclovir 2 μg/mL by 9.2 × 103-fold. The proton pump inhibitors pantoprazole, rabeprazole, lansoprazole, and dexlansoprazole increased the antiviral effects of acyclovir in a similar fashion as omeprazole, indicating this to be a drug class effect. In conclusion, proton pump inhibitors increase the anti-HSV activity of acyclovir and are candidates for antiviral therapies in combination with acyclovir, in particular for topical preparations for the treatment of immunocompromised individuals who are more likely to suffer from severe complications.
The demand to develop convergent technology platforms, such as bio-functionalized medical devices, is rapidly increasing. However, the loss of biological function of the effector molecules during sterilization represents a significant and general problem. Therefore, we have developed and characterized a nano-coating (NC) formulation capable of maintaining the functionality of proteins on biological-device combination products. As a proof of concept, the NC preserved the structural and functional integrity of an otherwise highly fragile antibody immobilized on polyurethane during deleterious sterilizing irradiation (≥ 25 kGy). The NC procedure enables straight-forward terminal sterilization of bio-functionalized materials while preserving optimal conditioning of the bioactive surface.
Multicentre comparison of quantitative PCR-based assays to detect SARS-CoV-2, Germany, March 2020
(2020)
Containment strategies and clinical management of coronavirus disease (COVID-19) patients during the current pandemic depend on reliable diagnostic PCR assays for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we compare 11 different RT-PCR test systems used in seven diagnostic laboratories in Germany in March 2020. While most assays performed well, we identified detection problems in a commonly used assay that may have resulted in false-negative test results during the first weeks of the pandemic.
Herpes genitalis is caused mainly by herpes simplex virus type 2 (HSV-2) and to a lesser extent but with increasing frequency, by herpes simplex virus type 1 (HSV-1). Today, the diagnosis of genital herpes is based "on laboratory methods. Serology is useful to distinguish primary infection from latent infection and for seroepidemiological investigations. Newer type-specific antibody tests based on single recombinant or purified viral antigens have a higher sensitivity and specificity for detecting anti HSV-2 antibodies. The tests also allow the discrimination between HSV-1 or -2 specific antibodies. Since serology is not able to recognize reactivation, isolation in cell culture remains the standard. If cell culture is not available or optimal transport is not possible and rapid results are needed, direct antigen detection, or in selected cases, the highly sensitive and specific PCR should be used.
Influenza A (H1N1) 2009 : impact on Frankfurt in due consideration of health care and public health
(2010)
Background: In April 2009 a novel influenza A H1N1/2009 virus was identified in Mexico and in the United States which quickly spread around the world. Most of the countries established infection surveillance systems in order to track the number of (laboratory-confirmed) H1N1 cases, hospitalizations and deaths. Methods: The impact of the emergence of the novel pandemic (H1N1) 2009 virus on Frankfurt was statistically evaluated by the Health Protection Authority, City of Frankfurt am Main. Vaccination rates of the health care workers (HCWs) of the University Hospital Frankfurt were measured by the Occupational Health Service. Results: Although the virulence of pandemic (H1N1) 2009 seems to be comparable with seasonal influenza, a major patient load and wave of hospital admissions occurred in the summer of 2009. Even though the 2009 vaccination rate of the University Hospital Frankfurt (seasonal influenza [40.5%], swine flu [36.3%]) is better than the average annual uptake of influenza vaccine in the German health care system (approximately 22% for seasonal and 15% for swine flu), vaccination levels remain insufficient. However, physicians were significantly (p < 0.001) more likely to have been vaccinated against swine flu and seasonal influenza than nurses. Conclusions: The outbreak of the pandemic (H1N1) 2009 in April 2009 provided a major challenge to health services around the world. Nosocomial transmission of H1N1/2009 has been documented. Present experience should be used to improve pandemic preparedness plans and vaccination programs ought to target as many HCWs as possible.
Background In October 2007, the working group CEN/TC 216 of the European Committee for standardisation suggested that the Sabin oral poliovirus vaccine type 1 strain (LSc-2ab) presently used for virucidal tests should be replaced by another attenuated vaccine poliovirus type 1 strain, CHAT. Both strains were historically used as oral vaccines, but the Sabin type 1 strain was acknowledged to be more attenuated. In Germany, vaccination against poliomyelitis was introduced in 1962 using the oral polio vaccine (OPV) containing Sabin strain LSc-2ab. The vaccination schedule was changed from OPV to an inactivated polio vaccine (IPV) containing wild polio virus type 1 strain Mahoney in 1998. In the present study, we assessed potential differences in neutralising antibody titres to Sabin and CHAT in persons with a history of either OPV, IPV, or OPV with IPV booster. Methods Neutralisation poliovirus antibodies against CHAT and Sabin 1 were measured in sera of 41 adults vaccinated with OPV. Additionally, sera from 28 children less than 10 years of age and immunised with IPV only were analysed. The neutralisation assay against poliovirus was performed according to WHO guidelines. Results The neutralisation activity against CHAT in adults with a complete OPV vaccination series was significantly lower than against Sabin poliovirus type 1 strains (Wilcoxon signed-rank test P < 0.025). In eight sera, the antibody titres measured against CHAT were less than 8, although the titre against Sabin 1 varied between 8 and 64. Following IPV booster, anti-CHAT antibodies increased rapidly in sera of CHAT-negative adults with OPV history. Sera from children with IPV history neutralised CHAT and Sabin 1 strains equally. Conclusion The lack of neutralising antibodies against the CHAT strain in persons vaccinated with OPV might be associated with an increased risk of reinfection with the CHAT polio virus type 1, and this implies a putative risk of transmission of the virus to polio-free communities. We strongly suggest that laboratory workers who were immunised with OPV receive a booster vaccination with IPV before handling CHAT in the laboratory.
Reliable, easy-to-handle phenotypic screening platforms are needed for the identification of anti-SARS-CoV-2 compounds. Here, we present caspase 3/7 activity as a readout for monitoring the replication of SARS-CoV-2 isolates from different variants, including a remdesivir-resistant strain, and of other coronaviruses in numerous cell culture models, independently of cytopathogenic effect formation. Compared to other models, the Caco-2 subline Caco-2-F03 displayed superior performance. It possesses a stable SARS-CoV-2 susceptibility phenotype and does not produce false-positive hits due to drug-induced phospholipidosis. A proof-of-concept screen of 1,796 kinase inhibitors identified known and novel antiviral drug candidates including inhibitors of phosphoglycerate dehydrogenase (PHGDH), CDC like kinase 1 (CLK-1), and colony stimulating factor 1 receptor (CSF1R). The activity of the PHGDH inhibitor NCT-503 was further increased in combination with the hexokinase II (HK2) inhibitor 2-deoxy-D-glucose, which is in clinical development for COVID-19. In conclusion, caspase 3/7 activity detection in SARS-CoV-2-infected Caco-2-F03 cells provides a simple phenotypic high-throughput screening platform for SARS-CoV-2 drug candidates that reduces false-positive hits.