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Background and Aims Immunocompromised patients are at risk of chronic hepatitis E which can be acquired by blood transfusions. Currently, screening of blood donors (BDs) for HEV RNA with a limit of detection (LOD) of 2000 IU/ml is required in Germany. However, this may result in up to 440,000 IU HEV RNA in blood products depending on their plasma volume. We studied the residual risk for transfusion-transmitted (tt) HEV infection when an LOD of 2000 IU/ml is applied. Methods Highly sensitive individual donor testing for HEV RNA on the Grifols Procleix Panther system (LOD 7.89 IU/ml) was performed. HEV loads were quantified by real time PCR. Results 31 of 16,236 donors (0.19 %) were HEV RNA positive. Three BDs had virus loads between 710 and 2000 IU/ml, a significant risk for tt hepatitis E in case of any type of blood product. Eight BDs had virus loads of >32 to 710 IU/ml, a risk for tt hepatitis E by platelet or plasma transfusions due to their higher plasma volume compared to red blood cell concentrates. Eight of these eleven potentially infectious BDs were seronegative for HEV indicating a recent infection. Only 8 of 31 donors had virus loads >2000 IU/ml and would also have been detected by the required screening procedure and 12 had very low HEV loads (<32 IU/ml). Conclusions Screening of BDs with an LOD of 2000 IU/ml reduced the risk for tt HEV infection by about 73% for red blood cell concentrates whereas merely a 42% risk reduction was achieved for platelet and fresh frozen plasma transfusions. Single donor screening (LOD < 32 IU/ml) should reach an almost 100% risk reduction. Lay summary The risk of transfusion-transmitted hepatitis E in solid organ and hematopoietic stem cell recipients may not be sufficiently controlled by (mini-)pool HEV RNA screening of blood donors.
Anne K. Cordes; Lilia Goudeva; Marc Lütgehetmann; Jürgen J. Wenzel; Patrick Behrendt; Heiner Wedemeyer; Albert Heim. Risk of transfusion-transmitted hepatitis E virus infection from pool-tested platelets and plasma. Journal of Hepatology 2021, 1 .
AMA StyleAnne K. Cordes, Lilia Goudeva, Marc Lütgehetmann, Jürgen J. Wenzel, Patrick Behrendt, Heiner Wedemeyer, Albert Heim. Risk of transfusion-transmitted hepatitis E virus infection from pool-tested platelets and plasma. Journal of Hepatology. 2021; ():1.
Chicago/Turabian StyleAnne K. Cordes; Lilia Goudeva; Marc Lütgehetmann; Jürgen J. Wenzel; Patrick Behrendt; Heiner Wedemeyer; Albert Heim. 2021. "Risk of transfusion-transmitted hepatitis E virus infection from pool-tested platelets and plasma." Journal of Hepatology , no. : 1.
Hepatocellular carcinoma (HCC) still remains a difficult to cure malignancy. In recent years, the focus has shifted to lipid metabolism for the treatment of HCC. Very little is known about hepatitis B virus (HBV) and C virus (HCV)-related hepatic lipid disturbances in non-malignant and cancer tissues. The present study showed that triacylglycerol and cholesterol concentrations were similar in tumor adjacent HBV and HCV liver, and were not induced in the HCC tissues. Higher levels of free cholesterol, polyunsaturated phospholipids and diacylglycerol species were noted in non-tumorous HBV compared to HCV liver. Moreover, polyunsaturated phospholipids and diacylglycerols, and ceramides declined in tumors of HBV infected patients. All of these lipids remained unchanged in HCV-related HCC. In HCV tumors, polyunsaturated phosphatidylinositol levels were even induced. There were no associations of these lipid classes in non-tumor tissues with hepatic inflammation and fibrosis scores. Moreover, these lipids did not correlate with tumor grade or T-stage in HCC tissues. Lipid reprogramming of the three analysed HBV/HCV related tumors mostly resembled HBV-HCC. Indeed, lipid composition of non-tumorous HCV tissue, HCV tumors, HBV tumors and HBV/HCV tumors was highly similar. The tumor suppressor protein p53 regulates lipid metabolism. The p53 and p53S392 protein levels were induced in the tumors of HBV, HCV and double infected patients, and this was significant in HBV infection. Negative correlation of tumor p53 protein with free cholesterol indicates a role of p53 in cholesterol metabolism. In summary, the current study suggests that therapeutic strategies to target lipid metabolism in chronic viral hepatitis and associated cancers have to consider disease etiology.
Elisabeth Haberl; Thomas Weiss; Georg Peschel; Kilian Weigand; Nikolai Köhler; Josch Pauling; Jürgen Wenzel; Marcus Höring; Sabrina Krautbauer; Gerhard Liebisch; Christa Buechler. Liver Lipids of Patients with Hepatitis B and C and Associated Hepatocellular Carcinoma. International Journal of Molecular Sciences 2021, 22, 5297 .
AMA StyleElisabeth Haberl, Thomas Weiss, Georg Peschel, Kilian Weigand, Nikolai Köhler, Josch Pauling, Jürgen Wenzel, Marcus Höring, Sabrina Krautbauer, Gerhard Liebisch, Christa Buechler. Liver Lipids of Patients with Hepatitis B and C and Associated Hepatocellular Carcinoma. International Journal of Molecular Sciences. 2021; 22 (10):5297.
Chicago/Turabian StyleElisabeth Haberl; Thomas Weiss; Georg Peschel; Kilian Weigand; Nikolai Köhler; Josch Pauling; Jürgen Wenzel; Marcus Höring; Sabrina Krautbauer; Gerhard Liebisch; Christa Buechler. 2021. "Liver Lipids of Patients with Hepatitis B and C and Associated Hepatocellular Carcinoma." International Journal of Molecular Sciences 22, no. 10: 5297.
The hepatitis E virus (HEV) is one of the main causes of acute hepatitis and the de facto global burden is underestimated. HEV‐related clinical complications are often undetected and are not considered in the differential diagnosis. Convincing findings from studies suggest that HEV is clinically relevant not only in developing countries but also in industrialized countries. Eight HEV genotypes (HEV‐1 to HEV‐8) with different human and animal hosts and other HEV‐related viruses are in circulation. Transmission routes vary by genotype and location, with large waterborne outbreaks in developing countries and zoonotic food‐borne infections in developed countries. An acute infection can be aggravated in pregnant women, organ transplant recipients, patients with pre‐existing liver disease, and immunosuppressed patients. HEV during pregnancy affects the fetus and newborn with an increased risk of vertical transmission, preterm and stillbirth, neonatal jaundice and miscarriage. Hepatitis E is associated with extrahepatic manifestations that include neurological disorders such as neuralgic amyotrophy (NA), Guillain‐Barre syndrome (GBS) and encephalitis, renal injury and hematological disorders. The risk of transfusion‐transmitted HEV is increasingly recognized in Western countries where the risk may be due to a zoonosis. RNA testing of blood components is essential to determine the risk of transfusion‐transmitted HEV. There are currently no approved drugs or vaccines for HEV infections. This review focuses on updating the latest developments in zoonoses, screening and diagnostics, drugs in use and under development, and vaccines.
Thirumalaisamy P. Velavan; Srinivas Reddy Pallerla; Reimar Johne; Daniel Todt; Eike Steinmann; Mathias Schemmerer; Jürgen J. Wenzel; Jörg Hofmann; James Wai Kuo Shih; Heiner Wedemeyer; Claus‐Thomas Bock. Hepatitis E: An update on One Health and clinical medicine. Liver International 2021, 41, 1462 -1473.
AMA StyleThirumalaisamy P. Velavan, Srinivas Reddy Pallerla, Reimar Johne, Daniel Todt, Eike Steinmann, Mathias Schemmerer, Jürgen J. Wenzel, Jörg Hofmann, James Wai Kuo Shih, Heiner Wedemeyer, Claus‐Thomas Bock. Hepatitis E: An update on One Health and clinical medicine. Liver International. 2021; 41 (7):1462-1473.
Chicago/Turabian StyleThirumalaisamy P. Velavan; Srinivas Reddy Pallerla; Reimar Johne; Daniel Todt; Eike Steinmann; Mathias Schemmerer; Jürgen J. Wenzel; Jörg Hofmann; James Wai Kuo Shih; Heiner Wedemeyer; Claus‐Thomas Bock. 2021. "Hepatitis E: An update on One Health and clinical medicine." Liver International 41, no. 7: 1462-1473.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) RNA is detected by reverse-transcription quantitative real-time PCR (RT-qPCR) from respiratory specimens. This study compares throat washings (TW), nasopharyngeal swabs (NS) and oropharyngeal swabs (OS). A total of 102 samples from 34 adult patients with confirmed SARS-CoV-2 infection were analysed by RT-qPCR with absolute quantification. The median concentrations and diagnostic sensitivities were
Florian Hitzenbichler; Stilla Bauernfeind; Bernd Salzberger; Barbara Schmidt; Jürgen Wenzel. Comparison of Throat Washings, Nasopharyngeal Swabs and Oropharyngeal Swabs for Detection of SARS-CoV-2. Viruses 2021, 13, 653 .
AMA StyleFlorian Hitzenbichler, Stilla Bauernfeind, Bernd Salzberger, Barbara Schmidt, Jürgen Wenzel. Comparison of Throat Washings, Nasopharyngeal Swabs and Oropharyngeal Swabs for Detection of SARS-CoV-2. Viruses. 2021; 13 (4):653.
Chicago/Turabian StyleFlorian Hitzenbichler; Stilla Bauernfeind; Bernd Salzberger; Barbara Schmidt; Jürgen Wenzel. 2021. "Comparison of Throat Washings, Nasopharyngeal Swabs and Oropharyngeal Swabs for Detection of SARS-CoV-2." Viruses 13, no. 4: 653.
Serological testing is crucial in detection of previous infection and in monitoring convalescent and vaccine-induced immunity. During the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) pandemic, numerous assay platforms have been developed and marketed for clinical use. Several studies recently compared clinical performance of a limited number of serological tests, but broad comparative evaluation is currently missing. Within this study, a panel of 161 sera from SARS-CoV-2 infected, seasonal CoV-infected and SARS-CoV-2 naïve subjects was enrolled to evaluate 16 ELISA/ECLIA-based and 16 LFA-based tests. Specificities of all ELISA/ECLIA-based assays were acceptable and generally in agreement with the providers’ specifications, but sensitivities were lower as specified. Results of the LFAs were less accurate as compared to the ELISAs, albeit with some exceptions. We found a sporadic unequal immune response for different antigens and thus recommend the use of a nucleocapsid protein (N)- and spike protein (S)-based test combination when maximal sensitivity is necessary. Finally, the quality of the immune response in terms of neutralization should be tested using S-based IgG tests.
Maren Werner; Philip Pervan; Vivian Glück; Florian Zeman; Michael Koller; Ralph Burkhardt; Thomas Glück; Jürgen Wenzel; Barbara Schmidt; André Gessner; David Peterhoff. Evaluation of a Broad Panel of SARS-CoV-2 Serological Tests for Diagnostic Use. Journal of Clinical Medicine 2021, 10, 1580 .
AMA StyleMaren Werner, Philip Pervan, Vivian Glück, Florian Zeman, Michael Koller, Ralph Burkhardt, Thomas Glück, Jürgen Wenzel, Barbara Schmidt, André Gessner, David Peterhoff. Evaluation of a Broad Panel of SARS-CoV-2 Serological Tests for Diagnostic Use. Journal of Clinical Medicine. 2021; 10 (8):1580.
Chicago/Turabian StyleMaren Werner; Philip Pervan; Vivian Glück; Florian Zeman; Michael Koller; Ralph Burkhardt; Thomas Glück; Jürgen Wenzel; Barbara Schmidt; André Gessner; David Peterhoff. 2021. "Evaluation of a Broad Panel of SARS-CoV-2 Serological Tests for Diagnostic Use." Journal of Clinical Medicine 10, no. 8: 1580.
Treatment of advanced melanoma with combined PD-1/CTLA-4 blockade commonly causes serious immune-mediated complications. Here, we identify a subset of patients predisposed to immune checkpoint blockade-related hepatitis who are distinguished by chronic expansion of effector memory CD4+ T cells (TEM cells). Pre-therapy CD4+ TEM cell expansion occurs primarily during autumn or winter in patients with metastatic disease and high cytomegalovirus (CMV)-specific serum antibody titres. These clinical features implicate metastasis-dependent, compartmentalised CMV reactivation as the cause of CD4+ TEM expansion. Pre-therapy CD4+ TEM expansion predicts hepatitis in CMV-seropositive patients, opening possibilities for avoidance or prevention. 3 of 4 patients with pre-treatment CD4+ TEM expansion who received αPD-1 monotherapy instead of αPD-1/αCTLA-4 therapy remained hepatitis-free. 4 of 4 patients with baseline CD4+ TEM expansion given prophylactic valganciclovir and αPD-1/αCTLA-4 therapy remained hepatitis-free. Our findings exemplify how pathogen exposure can shape clinical reactions after cancer therapy and how this insight leads to therapeutic innovations.
James A. Hutchinson; Katharina Kronenberg; Paloma Riquelme; Jürgen J. Wenzel; Gunther Glehr; Hannah-Lou Schilling; Florian Zeman; Katja Evert; Martin Schmiedel; Marion Mickler; Konstantin Drexler; Florian Bitterer; Laura Cordero; Lukas Beyer; Christian Bach; Josef Koestler; Ralph Burkhardt; Hans J. Schlitt; Dirk Hellwig; Jens M. Werner; Rainer Spang; Barbara Schmidt; Edward K. Geissler; Sebastian Haferkamp. Virus-specific memory T cell responses unmasked by immune checkpoint blockade cause hepatitis. Nature Communications 2021, 12, 1 -15.
AMA StyleJames A. Hutchinson, Katharina Kronenberg, Paloma Riquelme, Jürgen J. Wenzel, Gunther Glehr, Hannah-Lou Schilling, Florian Zeman, Katja Evert, Martin Schmiedel, Marion Mickler, Konstantin Drexler, Florian Bitterer, Laura Cordero, Lukas Beyer, Christian Bach, Josef Koestler, Ralph Burkhardt, Hans J. Schlitt, Dirk Hellwig, Jens M. Werner, Rainer Spang, Barbara Schmidt, Edward K. Geissler, Sebastian Haferkamp. Virus-specific memory T cell responses unmasked by immune checkpoint blockade cause hepatitis. Nature Communications. 2021; 12 (1):1-15.
Chicago/Turabian StyleJames A. Hutchinson; Katharina Kronenberg; Paloma Riquelme; Jürgen J. Wenzel; Gunther Glehr; Hannah-Lou Schilling; Florian Zeman; Katja Evert; Martin Schmiedel; Marion Mickler; Konstantin Drexler; Florian Bitterer; Laura Cordero; Lukas Beyer; Christian Bach; Josef Koestler; Ralph Burkhardt; Hans J. Schlitt; Dirk Hellwig; Jens M. Werner; Rainer Spang; Barbara Schmidt; Edward K. Geissler; Sebastian Haferkamp. 2021. "Virus-specific memory T cell responses unmasked by immune checkpoint blockade cause hepatitis." Nature Communications 12, no. 1: 1-15.
Early diagnosis of invasive pulmonary aspergillosis (IPA) is crucial to prevent lethal disease in immunocompromized hosts. So far, lipopolysaccharide binding protein (LBP) and bactericidal/permeability-increasing protein (BPI) levels have not been evaluated as biomarkers for IPA. IL-8, previously introduced as a biomarker for IPA, was also included in this study. Bronchoalveolar lavage fluid (BALF) of IPA patients and control patients with non-infectious lung disease was collected according to clinical indications. Measurements in BALF displayed significantly higher levels of LBP (p < 0.0001), BPI (p = 0.0002) and IL-8 (p < 0.0001) in IPA compared to control patients. Receiver operating characteristic curve analysis revealed higher AUC for LBP (0.98, 95% CI 0.95–1.00) than BPI (0.84, 95% CI 0.70–0.97; p = 0.0301). Although not significantly different, AUC of IL-8 (0.93, 95% CI 0.85–1.00) also tended to be higher than AUC for BPI (p = 0.0624). When the subgroup of non-hematological patients was analyzed, test performance of LBP (AUC 0.99, 95% CI 0.97–1.00), BPI (AUC 0.97, 95% CI 0.91–1.00) and IL-8 (AUC 0.96, 95% CI: 0.90–1.00) converged. In conclusion, LBP and—to a lesser extend—BPI displayed high AUCs that were comparable to those of IL-8 for diagnosis of IPA in BALF. Further investigations are worthwhile, especially in non-hematological patients in whom sensitive biomarkers for IPA are lacking.
Sigrid Bülow; Robert Heyd; Martina Toelge; Katharina U. Ederer; Annette Schweda; Stefan H. Blaas; Okka W. Hamer; Andreas Hiergeist; Jürgen J. Wenzel; André Gessner. Lipopolysaccharide Binding Protein and Bactericidal/Permeability-Increasing Protein as Biomarkers for Invasive Pulmonary Aspergillosis. Journal of Fungi 2020, 6, 304 .
AMA StyleSigrid Bülow, Robert Heyd, Martina Toelge, Katharina U. Ederer, Annette Schweda, Stefan H. Blaas, Okka W. Hamer, Andreas Hiergeist, Jürgen J. Wenzel, André Gessner. Lipopolysaccharide Binding Protein and Bactericidal/Permeability-Increasing Protein as Biomarkers for Invasive Pulmonary Aspergillosis. Journal of Fungi. 2020; 6 (4):304.
Chicago/Turabian StyleSigrid Bülow; Robert Heyd; Martina Toelge; Katharina U. Ederer; Annette Schweda; Stefan H. Blaas; Okka W. Hamer; Andreas Hiergeist; Jürgen J. Wenzel; André Gessner. 2020. "Lipopolysaccharide Binding Protein and Bactericidal/Permeability-Increasing Protein as Biomarkers for Invasive Pulmonary Aspergillosis." Journal of Fungi 6, no. 4: 304.
Objectives To describe characteristics of a large hepatitis A virus (HAV) outbreak among men who have sex with men (MSM) in Berlin and to assess the impact of implemented measures. Methods We analysed cases of laboratory-confirmed, symptomatic HAV-infections notified in Berlin, Germany between 08/2016 and 02/2018 using routine and enhanced surveillance data including genotyping results. Several studies involving different groups of participants were conducted to further investigate the outbreak, including surveys on knowledge and practices of HAV vaccination among physicians and vaccination coverage and determinants of vaccination status among MSM. Implemented measures were categorised by target group in a Gantt chart. To assess their impact, we analysed health insurance data on HAV vaccination uptake comparing Berlin and other federal states. Results In the outbreak period, n = 222 cases were reported (of which n = 91 were sequence-confirmed), with a peak in case numbers in 01/2017. Physicians were aware of existing vaccination recommendations, but vaccination coverage among n = 756 MSM was low with 32.7%/17.3% being completely/incompletely vaccinated before 2017. HAV vaccination before 2017 was associated with being born in Germany (OR 2.36) and HIV positive (OR 1.80). HAV monovalent vaccination uptake increased by 164% from 2016-2017 among males in Berlin compared to 7% in other federal states. Conclusions We successfully implemented multiple measures targeting the MSM community, physicians and public health to increase HAV vaccination uptake. To prevent future HAV outbreaks we recommend monitoring vaccination coverage among MSM, promoting awareness of existing recommendations among physicians, and ensuring access for foreign born and young MSM.
Ruth Zimmermann; Mirko Faber; Sandra Dudareva; Patrick Ingiliz; Heiko Jessen; Judith Koch; Ulrich Marcus; Kai Michaelis; Thorsten Rieck; Claudia Ruscher; Birte Schilling; Jakob Schumacher; Dagmar Sissolak; Janine Thoulass; Jürgen J. Wenzel; Dirk Werber; Daniel Sagebiel. Hepatitis A outbreak among MSM in Berlin due to low vaccination coverage: Epidemiology, management, and successful interventions. International Journal of Infectious Diseases 2020, 103, 146 -153.
AMA StyleRuth Zimmermann, Mirko Faber, Sandra Dudareva, Patrick Ingiliz, Heiko Jessen, Judith Koch, Ulrich Marcus, Kai Michaelis, Thorsten Rieck, Claudia Ruscher, Birte Schilling, Jakob Schumacher, Dagmar Sissolak, Janine Thoulass, Jürgen J. Wenzel, Dirk Werber, Daniel Sagebiel. Hepatitis A outbreak among MSM in Berlin due to low vaccination coverage: Epidemiology, management, and successful interventions. International Journal of Infectious Diseases. 2020; 103 ():146-153.
Chicago/Turabian StyleRuth Zimmermann; Mirko Faber; Sandra Dudareva; Patrick Ingiliz; Heiko Jessen; Judith Koch; Ulrich Marcus; Kai Michaelis; Thorsten Rieck; Claudia Ruscher; Birte Schilling; Jakob Schumacher; Dagmar Sissolak; Janine Thoulass; Jürgen J. Wenzel; Dirk Werber; Daniel Sagebiel. 2020. "Hepatitis A outbreak among MSM in Berlin due to low vaccination coverage: Epidemiology, management, and successful interventions." International Journal of Infectious Diseases 103, no. : 146-153.
Infection with hepatitis E virus (HEV) represents the most common source of viral hepatitis globally. Although infecting over 20 million people annually in endemic regions, with major outbreaks described since the 1950s, hepatitis E remains an underestimated disease. This review gives a current view of the global circulation and epidemiology of this emerging virus. The history of HEV, from the first reported enteric non-A non-B hepatitis outbreaks, to the discovery of the viral agent and the molecular characterization of the different human pathogenic genotypes, is discussed. Furthermore, the current state of research regarding the virology of HEV is critically assessed, and the challenges towards prevention and diagnosis, as well as clinical risks of the disease described. Together, these points aim to underline the significant impact of hepatitis E on global health and the need for further in-depth research to better understand the pathophysiology and its role in the complex disease manifestations of HEV infection.
Srinivas Reddy Pallerla; Dominik Harms; Reimar Johne; Daniel Todt; Eike Steinmann; Mathias Schemmerer; Jürgen J. Wenzel; Jörg Hofmann; James Wai Kuo Shih; Heiner Wedemeyer; C.-Thomas Bock; Thirumalaisamy P. Velavan. Hepatitis E Virus Infection: Circulation, Molecular Epidemiology, and Impact on Global Health. Pathogens 2020, 9, 856 .
AMA StyleSrinivas Reddy Pallerla, Dominik Harms, Reimar Johne, Daniel Todt, Eike Steinmann, Mathias Schemmerer, Jürgen J. Wenzel, Jörg Hofmann, James Wai Kuo Shih, Heiner Wedemeyer, C.-Thomas Bock, Thirumalaisamy P. Velavan. Hepatitis E Virus Infection: Circulation, Molecular Epidemiology, and Impact on Global Health. Pathogens. 2020; 9 (10):856.
Chicago/Turabian StyleSrinivas Reddy Pallerla; Dominik Harms; Reimar Johne; Daniel Todt; Eike Steinmann; Mathias Schemmerer; Jürgen J. Wenzel; Jörg Hofmann; James Wai Kuo Shih; Heiner Wedemeyer; C.-Thomas Bock; Thirumalaisamy P. Velavan. 2020. "Hepatitis E Virus Infection: Circulation, Molecular Epidemiology, and Impact on Global Health." Pathogens 9, no. 10: 856.
Following outbreaks linked to frozen strawberries in Sweden and Austria in 2018, 65 cases linked to the same hepatitis A virus strain were detected in Germany between October 2018 and January 2020, presenting in two waves. Two case–control studies and a comparison of cases’ consumption frequencies with purchase data from a large consumer panel provided strong evidence for frozen strawberry cake as the main vehicle of transmission. Of 46 cases interviewed, 27 reported consuming frozen strawberry cake and 25 of these identified cake(s) from brand A spontaneously or in product picture-assisted recall. Trace back investigations revealed that the Polish producer involved in the previous outbreaks in Sweden and Austria had received frozen strawberries from Egypt via a wholesaler that also delivered frozen strawberries to manufacturer of brand A. Phylogenetic analyses linked the outbreak strain to similar strains formerly isolated from sewage, stool and strawberries in Egypt. Complete trace back and timely recall of products with strong evidence of contamination is important to control an outbreak and prevent later resurgence, particularly for food items with a long shelf life. Continued molecular surveillance of hepatitis A is needed to identify outbreaks and monitor the success of food safety interventions.
Claudia Ruscher; Mirko Faber; Dirk Werber; Klaus Stark; Julia Bitzegeio; Kai Michaelis; Daniel Sagebiel; Jürgen Wenzel; Julia Enkelmann. Resurgence of an international hepatitis A outbreak linked to imported frozen strawberries, Germany, 2018 to 2020. Eurosurveillance 2020, 25, 1900670 .
AMA StyleClaudia Ruscher, Mirko Faber, Dirk Werber, Klaus Stark, Julia Bitzegeio, Kai Michaelis, Daniel Sagebiel, Jürgen Wenzel, Julia Enkelmann. Resurgence of an international hepatitis A outbreak linked to imported frozen strawberries, Germany, 2018 to 2020. Eurosurveillance. 2020; 25 (37):1900670.
Chicago/Turabian StyleClaudia Ruscher; Mirko Faber; Dirk Werber; Klaus Stark; Julia Bitzegeio; Kai Michaelis; Daniel Sagebiel; Jürgen Wenzel; Julia Enkelmann. 2020. "Resurgence of an international hepatitis A outbreak linked to imported frozen strawberries, Germany, 2018 to 2020." Eurosurveillance 25, no. 37: 1900670.
Objective The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic challenges national health systems and the global economy. Monitoring of infection rates and seroprevalence can guide public health measures to combat the pandemic. This depends on reliable tests on active and former infections. Here, we set out to develop and validate a specific and sensitive enzyme linked immunosorbent assay (ELISA) for detection of anti-SARS-CoV-2 antibody levels. Methods In our ELISA, we used SARS-CoV-2 receptor-binding domain (RBD) and a stabilized version of the spike (S) ectodomain as antigens. We assessed sera from patients infected with seasonal coronaviruses, SARS-CoV-2 and controls. We determined and monitored IgM-, IgA- and IgG-antibody responses towards these antigens. In addition, for a panel of 22 sera, virus neutralization and ELISA parameters were measured and correlated. Results The RBD-based ELISA detected SARS-CoV-2-directed antibodies, did not cross-react with seasonal coronavirus antibodies and correlated with virus neutralization (R 2 = 0.89). Seroconversion started at 5 days after symptom onset and led to robust antibody levels at 10 days after symptom onset. We demonstrate high specificity (99.3%; N = 1000) and sensitivity (92% for IgA, 96% for IgG and 98% for IgM; > 10 days after PCR-proven infection; N = 53) in serum. Conclusions With the described RBD-based ELISA protocol, we provide a reliable test for seroepidemiological surveys. Due to high specificity and strong correlation with virus neutralization, the RBD ELISA holds great potential to become a preferred tool to assess thresholds of protective immunity after infection and vaccination.
David Peterhoff; Vivian Glück; Matthias Vogel; Philipp Schuster; Anja Schütz; Philip Neubert; Veruschka Albert; Stefanie Frisch; Mara Kiessling; Philip Pervan; Maren Werner; Nicole Ritter; Leon Babl; Maria Deichner; Frank Hanses; Matthias Lubnow; Thomas Müller; Dirk Lunz; Florian Hitzenbichler; Franz Audebert; Viola Hähnel; Robert Offner; Martina Müller; Stephan Schmid; Ralph Burkhardt; Thomas Glück; Michael Koller; Hans Helmut Niller; Bernhard Graf; Bernd Salzberger; Jürgen Wenzel; Jonathan Jantsch; André Gessner; Barbara Schmidt; Ralf Wagner. A highly specific and sensitive serological assay detects SARS-CoV-2 antibody levels in COVID-19 patients that correlate with neutralization. Infection 2020, 49, 75 -82.
AMA StyleDavid Peterhoff, Vivian Glück, Matthias Vogel, Philipp Schuster, Anja Schütz, Philip Neubert, Veruschka Albert, Stefanie Frisch, Mara Kiessling, Philip Pervan, Maren Werner, Nicole Ritter, Leon Babl, Maria Deichner, Frank Hanses, Matthias Lubnow, Thomas Müller, Dirk Lunz, Florian Hitzenbichler, Franz Audebert, Viola Hähnel, Robert Offner, Martina Müller, Stephan Schmid, Ralph Burkhardt, Thomas Glück, Michael Koller, Hans Helmut Niller, Bernhard Graf, Bernd Salzberger, Jürgen Wenzel, Jonathan Jantsch, André Gessner, Barbara Schmidt, Ralf Wagner. A highly specific and sensitive serological assay detects SARS-CoV-2 antibody levels in COVID-19 patients that correlate with neutralization. Infection. 2020; 49 (1):75-82.
Chicago/Turabian StyleDavid Peterhoff; Vivian Glück; Matthias Vogel; Philipp Schuster; Anja Schütz; Philip Neubert; Veruschka Albert; Stefanie Frisch; Mara Kiessling; Philip Pervan; Maren Werner; Nicole Ritter; Leon Babl; Maria Deichner; Frank Hanses; Matthias Lubnow; Thomas Müller; Dirk Lunz; Florian Hitzenbichler; Franz Audebert; Viola Hähnel; Robert Offner; Martina Müller; Stephan Schmid; Ralph Burkhardt; Thomas Glück; Michael Koller; Hans Helmut Niller; Bernhard Graf; Bernd Salzberger; Jürgen Wenzel; Jonathan Jantsch; André Gessner; Barbara Schmidt; Ralf Wagner. 2020. "A highly specific and sensitive serological assay detects SARS-CoV-2 antibody levels in COVID-19 patients that correlate with neutralization." Infection 49, no. 1: 75-82.
Constantin A. Hintschich; Jürgen J. Wenzel; Thomas Hummel; Mohammed K. Hankir; Thomas Kühnel; Veronika Vielsmeier; Christopher Bohr. Psychophysical tests reveal impaired olfaction but preserved gustation in COVID‐19 patients. International Forum of Allergy & Rhinology 2020, 10, 1105 -1107.
AMA StyleConstantin A. Hintschich, Jürgen J. Wenzel, Thomas Hummel, Mohammed K. Hankir, Thomas Kühnel, Veronika Vielsmeier, Christopher Bohr. Psychophysical tests reveal impaired olfaction but preserved gustation in COVID‐19 patients. International Forum of Allergy & Rhinology. 2020; 10 (9):1105-1107.
Chicago/Turabian StyleConstantin A. Hintschich; Jürgen J. Wenzel; Thomas Hummel; Mohammed K. Hankir; Thomas Kühnel; Veronika Vielsmeier; Christopher Bohr. 2020. "Psychophysical tests reveal impaired olfaction but preserved gustation in COVID‐19 patients." International Forum of Allergy & Rhinology 10, no. 9: 1105-1107.
Infection with the hepatitis E virus (HEV) is one of the main causes of acute hepatitis worldwide. Given that, the histopathology of hepatitis E is relatively poorly characterized, and it is unclear what exactly determines its remarkable variability. The aim of our study was a systematic analysis of hepatitis E histology, especially with regard to the clinical setting. Fifty-two liver samples (48 biopsies, 1 liver explant, 3 autopsy livers) from 41 patients with molecularly proven hepatitis E (28 HEV genotype (gt) 3, three gt 1, one gt 4 and 9 undetermined gt) were systematically evaluated for 33 histopathologic features. Following one approach, the biopsies were assigned to one of five generic histologic patterns. In another approach, they were subjected to hierarchical clustering. We found that 23/41 (56%) patients were immunocompromised, whereas 18 (44%) had no known immunosuppression. Five patients (12%) had pre-existing liver disease (LD). The histopathologic spectrum ranged from almost normal to acute, chronic, and steato-hepatitis to subtotal necrosis, and was thus distributed across all five generic patterns. Hierarchical clustering, however, identified three histopathologic clusters (C1–C3), which segregated along the immune status and pre-existing LD: C1 comprised mostly patients with pre-existing LD; histology mainly reflected the respective LD without pointing to the additional hepatitis E. C2 comprised mostly immunocompetent patients; histology mainly displayed florid hepatitis. C3 comprised mostly immunocompromised patients; histology mainly displayed smoldering hepatitis. Accordingly, C1–C3 differed markedly with respect to their clinical and histopathologic differential diagnoses. Hierarchical clustering suggests three groups with distinct histopathologies, indicating biologically different manifestations of hepatitis E. The association of histopathologic changes with the patient’s immune status and pre-existing LD plausibly explains the diversity of hepatitis E histopathology, and suggests that these factors are the crucial underlying determinants. We expect our results to improve patient management by guiding the clinico-pathologic diagnosis of hepatitis E.
Daniela Lenggenhager; Samuel Pawel; Hanna Honcharova-Biletska; Katja Evert; Jürgen J. Wenzel; Matteo Montani; Eva Furrer; Montserrat Fraga; Darius Moradpour; Christine Sempoux; Achim Weber. The histologic presentation of hepatitis E reflects patients’ immune status and pre-existing liver condition. Modern Pathology 2020, 34, 233 -248.
AMA StyleDaniela Lenggenhager, Samuel Pawel, Hanna Honcharova-Biletska, Katja Evert, Jürgen J. Wenzel, Matteo Montani, Eva Furrer, Montserrat Fraga, Darius Moradpour, Christine Sempoux, Achim Weber. The histologic presentation of hepatitis E reflects patients’ immune status and pre-existing liver condition. Modern Pathology. 2020; 34 (1):233-248.
Chicago/Turabian StyleDaniela Lenggenhager; Samuel Pawel; Hanna Honcharova-Biletska; Katja Evert; Jürgen J. Wenzel; Matteo Montani; Eva Furrer; Montserrat Fraga; Darius Moradpour; Christine Sempoux; Achim Weber. 2020. "The histologic presentation of hepatitis E reflects patients’ immune status and pre-existing liver condition." Modern Pathology 34, no. 1: 233-248.
A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China in late 2019 and subsequently caused a pandemic. Surveillance is important to better appreciate this evolving pandemic and to longitudinally monitor the effectiveness of public health measures. We aimed to provide a rapid, easy to establish and costeffective laboratory-based surveillance tool for SARS-CoV-2. Study design: We used minipools of RNA prepared from nucleic acid extractions of routine respiratory samples. We technically validated the assay and distributed the protocol within an informal network of five German university laboratories. We tested a total of 70 minipools resembling 700 samples shortly before the upsurge of cases in Germany from 17.02.2020 to 10.03.2020. One minipool reacted positive and after resolution one individual sample tested SARS-CoV-2 positive. This sample was from a hospitalized patient not suspected of having contracted SARS-CoV-2. Our approach of a laboratory-based surveillance for SARSCoV-2 using minipools proved its concept is easily adaptable and resource-saving. It might assist not only public health laboratories in SARS-CoV-2 surveillance.
Anna M. Eis-Hübinger; Mario Hönemann; Jürgen J. Wenzel; Annemarie Berger; Marek Widera; Barbara Schmidt; Souhaib Aldabbagh; Benjamin Marx; Hendrik Streeck; Sandra Ciesek; Uwe G. Liebert; Daniela Huzly; Hartmut Hengel; Marcus Panning. Ad hoc laboratory-based surveillance of SARS-CoV-2 by real-time RT-PCR using minipools of RNA prepared from routine respiratory samples. Journal of Clinical Virology 2020, 127, 104381 -104381.
AMA StyleAnna M. Eis-Hübinger, Mario Hönemann, Jürgen J. Wenzel, Annemarie Berger, Marek Widera, Barbara Schmidt, Souhaib Aldabbagh, Benjamin Marx, Hendrik Streeck, Sandra Ciesek, Uwe G. Liebert, Daniela Huzly, Hartmut Hengel, Marcus Panning. Ad hoc laboratory-based surveillance of SARS-CoV-2 by real-time RT-PCR using minipools of RNA prepared from routine respiratory samples. Journal of Clinical Virology. 2020; 127 ():104381-104381.
Chicago/Turabian StyleAnna M. Eis-Hübinger; Mario Hönemann; Jürgen J. Wenzel; Annemarie Berger; Marek Widera; Barbara Schmidt; Souhaib Aldabbagh; Benjamin Marx; Hendrik Streeck; Sandra Ciesek; Uwe G. Liebert; Daniela Huzly; Hartmut Hengel; Marcus Panning. 2020. "Ad hoc laboratory-based surveillance of SARS-CoV-2 by real-time RT-PCR using minipools of RNA prepared from routine respiratory samples." Journal of Clinical Virology 127, no. : 104381-104381.
We report a laboratory-based surveillance for SARS-CoV-2 using minipools of respiratory samples submitted for routine diagnostics. We tested a total of 70 minipools resembling 700 samples shortly before the upsurge of cases in Germany. We identified one SARS-CoV-2 positive patient. Our approach proved its concept, is easily adaptable and resource-saving.
Anna M. Eis-Hübinger; Mario Hoenemann; Juergen J. Wenzel; Annemarie Berger; Marek Widera; Barbara Schmidt; Souhaib Aldabbagh; Benjamin Marx; Hendrik Streeck; Sandra Ciesek; Uwe. G. Liebert; Daniela Huzly; Hartmut Hengel; Marcus Panning. Ad hoc laboratory-based surveillance of SARS-CoV-2 by real-time RT-PCR using minipools of RNA prepared from routine respiratory samples. 2020, 1 .
AMA StyleAnna M. Eis-Hübinger, Mario Hoenemann, Juergen J. Wenzel, Annemarie Berger, Marek Widera, Barbara Schmidt, Souhaib Aldabbagh, Benjamin Marx, Hendrik Streeck, Sandra Ciesek, Uwe. G. Liebert, Daniela Huzly, Hartmut Hengel, Marcus Panning. Ad hoc laboratory-based surveillance of SARS-CoV-2 by real-time RT-PCR using minipools of RNA prepared from routine respiratory samples. . 2020; ():1.
Chicago/Turabian StyleAnna M. Eis-Hübinger; Mario Hoenemann; Juergen J. Wenzel; Annemarie Berger; Marek Widera; Barbara Schmidt; Souhaib Aldabbagh; Benjamin Marx; Hendrik Streeck; Sandra Ciesek; Uwe. G. Liebert; Daniela Huzly; Hartmut Hengel; Marcus Panning. 2020. "Ad hoc laboratory-based surveillance of SARS-CoV-2 by real-time RT-PCR using minipools of RNA prepared from routine respiratory samples." , no. : 1.
Summary Background In 2018–19, Borna disease virus 1 (BoDV-1), the causative agent of Borna disease in horses, sheep, and other domestic mammals, was reported in five human patients with severe to fatal encephalitis in Germany. However, information on case frequencies, clinical courses, and detailed epidemiological analyses are still lacking. We report the occurrence of BoDV-1-associated encephalitis in cases submitted to the Institute of Clinical Microbiology and Hygiene, Regensburg University Hospital, Regensburg, Germany, and provide a detailed description of newly identified cases of BoDV-1-induced encephalitis. Methods All brain tissues from 56 encephalitis cases from Bavaria, Germany, of putative viral origin (1999–2019), which had been submitted for virological testing upon request of the attending clinician and stored for stepwise diagnostic procedure, were systematically screened for BoDV-1 RNA. Two additional BoDV-1-positive cases were contributed by other diagnostic centres. Positive results were confirmed by deep sequencing, antigen detection, and determination of BoDV-1-reactive antibodies in serum and cerebrospinal fluid. Clinical and epidemiological data from infected patients were collected and analysed. Findings BoDV-1 RNA and bornavirus-reactive antibodies were detected in eight newly analysed encephalitis cases and the first human BoDV-1 isolate was obtained from an unequivocally confirmed human BoDV-1 infection from the endemic area. Six of the eight BoDV-1-positive patients had no record of immunosuppression before the onset of fatal disease, whereas two were immunocompromised after solid organ transplantation. Typical initial symptoms were headache, fever, and confusion, followed by various neurological signs, deep coma, and severe brainstem involvement. Seven of nine patients with fatal encephalitis of unclear cause were BoDV-1 positive within one diagnostic centre. BoDV-1 sequence information and epidemiological analyses indicated independent spillover transmissions most likely from the local wild animal reservoir. Interpretation BoDV-1 infection has to be considered as a potentially lethal zoonosis in endemic regions with reported spillover infections in horses and sheep. BoDV-1 infection can result in fatal encephalitis in immunocompromised and apparently healthy people. Consequently, all severe encephalitis cases of unclear cause should be tested for bornaviruses especially in endemic regions. Funding German Federal Ministry of Education and Research.
Hans Helmut Niller; Klemens Angstwurm; Dennis Rubbenstroth; Kore Schlottau; Arnt Ebinger; Sebastian Giese; Silke Wunderlich; Bernhard Banas; Leonie F Forth; Donata Hoffmann; Dirk Höper; Martin Schwemmle; Dennis Tappe; Jonas Schmidt-Chanasit; Daniel Nobach; Christiane Herden; Christoph Brochhausen; Natalia Velez-Char; Andreas Mamilos; Kirsten Utpatel; Matthias Evert; Saida Zoubaa; Markus J Riemenschneider; Viktoria Ruf; Jochen Herms; Georg Rieder; Mario Errath; Kaspar Matiasek; Jürgen Schlegel; Friederike Liesche-Starnecker; Bernhard Neumann; Kornelius Fuchs; Ralf A Linker; Bernd Salzberger; Tobias Freilinger; Lisa Gartner; Jürgen Wenzel; Udo Reischl; Wolfgang Jilg; André Gessner; Jonathan Jantsch; Martin Beer; Barbara Schmidt. Zoonotic spillover infections with Borna disease virus 1 leading to fatal human encephalitis, 1999–2019: an epidemiological investigation. The Lancet Infectious Diseases 2020, 20, 467 -477.
AMA StyleHans Helmut Niller, Klemens Angstwurm, Dennis Rubbenstroth, Kore Schlottau, Arnt Ebinger, Sebastian Giese, Silke Wunderlich, Bernhard Banas, Leonie F Forth, Donata Hoffmann, Dirk Höper, Martin Schwemmle, Dennis Tappe, Jonas Schmidt-Chanasit, Daniel Nobach, Christiane Herden, Christoph Brochhausen, Natalia Velez-Char, Andreas Mamilos, Kirsten Utpatel, Matthias Evert, Saida Zoubaa, Markus J Riemenschneider, Viktoria Ruf, Jochen Herms, Georg Rieder, Mario Errath, Kaspar Matiasek, Jürgen Schlegel, Friederike Liesche-Starnecker, Bernhard Neumann, Kornelius Fuchs, Ralf A Linker, Bernd Salzberger, Tobias Freilinger, Lisa Gartner, Jürgen Wenzel, Udo Reischl, Wolfgang Jilg, André Gessner, Jonathan Jantsch, Martin Beer, Barbara Schmidt. Zoonotic spillover infections with Borna disease virus 1 leading to fatal human encephalitis, 1999–2019: an epidemiological investigation. The Lancet Infectious Diseases. 2020; 20 (4):467-477.
Chicago/Turabian StyleHans Helmut Niller; Klemens Angstwurm; Dennis Rubbenstroth; Kore Schlottau; Arnt Ebinger; Sebastian Giese; Silke Wunderlich; Bernhard Banas; Leonie F Forth; Donata Hoffmann; Dirk Höper; Martin Schwemmle; Dennis Tappe; Jonas Schmidt-Chanasit; Daniel Nobach; Christiane Herden; Christoph Brochhausen; Natalia Velez-Char; Andreas Mamilos; Kirsten Utpatel; Matthias Evert; Saida Zoubaa; Markus J Riemenschneider; Viktoria Ruf; Jochen Herms; Georg Rieder; Mario Errath; Kaspar Matiasek; Jürgen Schlegel; Friederike Liesche-Starnecker; Bernhard Neumann; Kornelius Fuchs; Ralf A Linker; Bernd Salzberger; Tobias Freilinger; Lisa Gartner; Jürgen Wenzel; Udo Reischl; Wolfgang Jilg; André Gessner; Jonathan Jantsch; Martin Beer; Barbara Schmidt. 2020. "Zoonotic spillover infections with Borna disease virus 1 leading to fatal human encephalitis, 1999–2019: an epidemiological investigation." The Lancet Infectious Diseases 20, no. 4: 467-477.
Introduction Sequence-based typing of hepatitis A virus (HAV) is important for outbreak detection, investigation and surveillance. In 2013, sequencing was central to resolving a large European Union (EU)-wide outbreak related to frozen berries. However, as the sequenced HAV genome regions were only partly comparable between countries, results were not always conclusive. Aim The objective was to gather information on HAV surveillance and sequencing in EU/European Economic Area (EEA) countries to find ways to harmonise their procedures, for improvement of cross-border outbreak responses. Methods In 2014, the European Centre for Disease Prevention and Control (ECDC) conducted a survey on HAV surveillance practices in EU/EEA countries. The survey enquired whether a referral system for confirming primary diagnostics of hepatitis A existed as well as a central collection/storage of hepatitis A cases’ samples for typing. Questions on HAV sequencing procedures were also asked. Based on the results, an expert consultation proposed harmonised procedures for cross-border outbreak response, in particular regarding sequencing. In 2016, a follow-up survey assessed uptake of suggested methods. Results Of 31 EU/EEA countries, 23 (2014) and 27 (2016) participated. Numbers of countries with central collection and storage of HAV positive samples and of those performing sequencing increased from 12 to 15 and 12 to 14 respectively in 2016, with all countries typing an overlapping fragment of 218 nt. However, variation existed in the sequenced genomic regions and their lengths. Conclusions While HAV sequences in EU/EEA countries are comparable for surveillance, collaboration in sharing and comparing these can be further strengthened.
Theresa Enkirch; Ettore Severi; Harry Vennema; Lelia Thornton; Jonathan Dean; Maria-Louise Borg; Anna Rita Ciccaglione; Roberto Bruni; Iva Christova; Siew Lin Ngui; Koye Balogun; Vratislav Němeček; Mia Kontio; Mária Takács; Andrea Hettmann; Rita Korotinska; Arthur Löve; Ana Avellon; Milagros Muñoz-Chimeno; Rita De Sousa; Denisa Janta; Jevgenia Epštein; Sofieke Klamer; Vanessa Suin; Stephan W Aberle; Heidemarie Holzmann; Kassiani Mellou; Josefine Lundberg Ederth; Lena Sundqvist; Anne-Marie Roque-Afonso; Sanja Kurečić Filipović; Mario Poljak; Line Vold; Kathrine Stene-Johansen; Sofie Midgley; Thea Kølsen Fischer; Mirko Faber; Jürgen Wenzel; Johanna Takkinen; Katrin Leitmeyer. Improving preparedness to respond to cross-border hepatitis A outbreaks in the European Union/European Economic Area: towards comparable sequencing of hepatitis A virus. Eurosurveillance 2019, 24, 1 .
AMA StyleTheresa Enkirch, Ettore Severi, Harry Vennema, Lelia Thornton, Jonathan Dean, Maria-Louise Borg, Anna Rita Ciccaglione, Roberto Bruni, Iva Christova, Siew Lin Ngui, Koye Balogun, Vratislav Němeček, Mia Kontio, Mária Takács, Andrea Hettmann, Rita Korotinska, Arthur Löve, Ana Avellon, Milagros Muñoz-Chimeno, Rita De Sousa, Denisa Janta, Jevgenia Epštein, Sofieke Klamer, Vanessa Suin, Stephan W Aberle, Heidemarie Holzmann, Kassiani Mellou, Josefine Lundberg Ederth, Lena Sundqvist, Anne-Marie Roque-Afonso, Sanja Kurečić Filipović, Mario Poljak, Line Vold, Kathrine Stene-Johansen, Sofie Midgley, Thea Kølsen Fischer, Mirko Faber, Jürgen Wenzel, Johanna Takkinen, Katrin Leitmeyer. Improving preparedness to respond to cross-border hepatitis A outbreaks in the European Union/European Economic Area: towards comparable sequencing of hepatitis A virus. Eurosurveillance. 2019; 24 (28):1.
Chicago/Turabian StyleTheresa Enkirch; Ettore Severi; Harry Vennema; Lelia Thornton; Jonathan Dean; Maria-Louise Borg; Anna Rita Ciccaglione; Roberto Bruni; Iva Christova; Siew Lin Ngui; Koye Balogun; Vratislav Němeček; Mia Kontio; Mária Takács; Andrea Hettmann; Rita Korotinska; Arthur Löve; Ana Avellon; Milagros Muñoz-Chimeno; Rita De Sousa; Denisa Janta; Jevgenia Epštein; Sofieke Klamer; Vanessa Suin; Stephan W Aberle; Heidemarie Holzmann; Kassiani Mellou; Josefine Lundberg Ederth; Lena Sundqvist; Anne-Marie Roque-Afonso; Sanja Kurečić Filipović; Mario Poljak; Line Vold; Kathrine Stene-Johansen; Sofie Midgley; Thea Kølsen Fischer; Mirko Faber; Jürgen Wenzel; Johanna Takkinen; Katrin Leitmeyer. 2019. "Improving preparedness to respond to cross-border hepatitis A outbreaks in the European Union/European Economic Area: towards comparable sequencing of hepatitis A virus." Eurosurveillance 24, no. 28: 1.
The hepatitis E virus (HEV) is transmitted via the faecal-oral route in developing countries (genotypes 1 and 2) or through contaminated food and blood products worldwide (genotypes 3 and 4). In Europe, HEV subtypes 3c, 3e and 3f are predominant. HEV is the leading cause of acute hepatitis globally and immunocompromised patients are particularly at risk. Because of a lack of cell culture systems efficiently propagating wild-type viruses, research on HEV is mostly based on cell culture-adapted isolates carrying uncommon insertions in the hypervariable region (HVR). While optimizing the cell culture system using the cell culture-adapted HEV strain 47832c, we isolated three wild-type strains derived from clinical specimens representing the predominant spectrum of HEV in Europe. The novel isolates 14-16753 (3c), 14-22707 (3e) and 15-22016 (3f-like) replicate to high viral loads of 108, 109 and 106.5 HEV RNA copies/mL at 14 days post-inoculation, respectively. In addition, they could be kept as persistently infected cell cultures with constant high viral loads (~109 copies/mL) for more than a year. In contrast to the latest isolates 47832c, LBPR-0379 and Kernow-C1, the new isolates do not carry genome insertions in the HVR. Optimization of HEV cell culture identified amphotericin B, distinct salts and fetal calf serum (FCS) as important medium supplements. Overconfluent cell layers increased infectivity and virus production. PLC/PRF/5, HuH-7-Lunet BLR, A549 and HepG2/C3A supported replication with different efficiencies. The novel strains and optimized cell culture system may be useful for studies on the HEV life cycle, inactivation, specific drug and vaccine development.
Mathias Schemmerer; Reimar Johne; Monika Erl; Wolfgang Jilg; Jürgen J. Wenzel; Erl; Jilg. Isolation of Subtype 3c, 3e and 3f-Like Hepatitis E Virus Strains Stably Replicating to High Viral Loads in an Optimized Cell Culture System. Viruses 2019, 11, 483 .
AMA StyleMathias Schemmerer, Reimar Johne, Monika Erl, Wolfgang Jilg, Jürgen J. Wenzel, Erl, Jilg. Isolation of Subtype 3c, 3e and 3f-Like Hepatitis E Virus Strains Stably Replicating to High Viral Loads in an Optimized Cell Culture System. Viruses. 2019; 11 (6):483.
Chicago/Turabian StyleMathias Schemmerer; Reimar Johne; Monika Erl; Wolfgang Jilg; Jürgen J. Wenzel; Erl; Jilg. 2019. "Isolation of Subtype 3c, 3e and 3f-Like Hepatitis E Virus Strains Stably Replicating to High Viral Loads in an Optimized Cell Culture System." Viruses 11, no. 6: 483.
Hepatitis E virus (HEV) genotype 3 infection frequently progresses to chronic disease with persisting HEV viremia in immunocompromised patients. Here, we evaluated the prevalence of HEV infection in renal allograft recipients and investigated the efficacy and tolerability of ribavirin monotherapy. A total of 947 recipients on average 8.7 years posttransplant were screened for anti-HEV IgG, IgM and HEV-RNA. Sixteen HEV-viremic renal allograft recipients were treated with ribavirin for 12 weeks. HEV-RNA concentration, laboratory and clinical parameters were assessed at baseline, during therapy and 12 weeks after treatment cessation. HEV-genotyping was performed in all HEV-viremic patients. Past HEV infection was detected serologically in 18% of the renal allograft recipients. Ongoing HEV replication was found in 16 recipients (all genotype 3). Unanimously, distinct HEV-sequences were revealed in all HEV-viremic patients. At start of ribavirin treatment, median HEV-RNA viral load was 4.3x106 (8000-5.0x106 ) IU/mL. 94% of HEV-infected allograft recipients showed a sustained virological response 12 weeks after treatment cessation. Ribavirin treatment was associated with rapid decrease in liver enzymes and rare occurrence of anemia. Prevalence of active HEV infection is important in renal transplant patients without signs of nosocomial infection. Ribavirin treatment was safe and effective. This article is protected by copyright. All rights reserved.
Justa Friebus‐Kardash; Ute Eisenberger; Jessica Ackermann; Andreas Kribben; Oliver Witzke; Jürgen Wenzel; Hana Rohn; Melanie Fiedler. Prevalence of active hepatitis E virus infection and efficacy of ribavirin treatment in renal allograft recipients. Transplant Infectious Disease 2019, 21, e13088 .
AMA StyleJusta Friebus‐Kardash, Ute Eisenberger, Jessica Ackermann, Andreas Kribben, Oliver Witzke, Jürgen Wenzel, Hana Rohn, Melanie Fiedler. Prevalence of active hepatitis E virus infection and efficacy of ribavirin treatment in renal allograft recipients. Transplant Infectious Disease. 2019; 21 (3):e13088.
Chicago/Turabian StyleJusta Friebus‐Kardash; Ute Eisenberger; Jessica Ackermann; Andreas Kribben; Oliver Witzke; Jürgen Wenzel; Hana Rohn; Melanie Fiedler. 2019. "Prevalence of active hepatitis E virus infection and efficacy of ribavirin treatment in renal allograft recipients." Transplant Infectious Disease 21, no. 3: e13088.
Hepatitis A (HAV) is a viral infection causing a range of symptoms, sudden onset of fever, malaise, diarrhea, and jaundice. It is mostly transmitted fecal-oral through contaminated food, with immediate household and sexual contacts having a higher risk of infection. Since 2016 an increased number of HAV infections, mostly affecting men who have sex with men (MSM) have been noticed worldwide, with three main genotypes circulating. We report here on the first spillover outbreak of the MSM-associated HAV genotype RIVM-HAV16-090 in the German general population in November 2017-February 2018. In total, twelve cases could be attributed to the outbreak with the index case and a coworker in a butchers shop being the most probable source of the outbreak. The identical HAV genotype was detected in two environmental samples in the premises of the butchers shop and in nine cases. Outbreak control measures included detailed contact tracing and stool examinations, several environmental investigations, thorough cleaning, and disinfection of the premises of the butchers shop. Post-exposure vaccination was recommended to all unprotected contacts during the investigation. Furthermore, although hand-washing facilities were in accordance with the required law, additional installment of soap and disinfectant dispensers and contactless faucets has been recommended.
Durdica Marosevic; Anne Belting; Katharina Schönberger; Anja Carl; Jürgen J. Wenzel; Roland Brey. Hepatitis A Outbreak in the General Population due to a MSM-Associated HAV Genotype Linked to a Food Handler, November 2017–February 2018, Germany. Food and Environmental Virology 2019, 11, 149 -156.
AMA StyleDurdica Marosevic, Anne Belting, Katharina Schönberger, Anja Carl, Jürgen J. Wenzel, Roland Brey. Hepatitis A Outbreak in the General Population due to a MSM-Associated HAV Genotype Linked to a Food Handler, November 2017–February 2018, Germany. Food and Environmental Virology. 2019; 11 (2):149-156.
Chicago/Turabian StyleDurdica Marosevic; Anne Belting; Katharina Schönberger; Anja Carl; Jürgen J. Wenzel; Roland Brey. 2019. "Hepatitis A Outbreak in the General Population due to a MSM-Associated HAV Genotype Linked to a Food Handler, November 2017–February 2018, Germany." Food and Environmental Virology 11, no. 2: 149-156.