Epidemiologie der Virushepatitiden A bis E in Deutschland

Mit Virushepatitis A bis E werden verschiedene infektiöse Entzündungen des Leberparenchyms bezeichnet, die durch die Hepatitisviren A bis E (HAV, HBV, HCV, HDV und HEV) ausgelöst werden. Zwar ähneln sich die Krankheitsbilder, die Erreger gehören jedoch zu verschiedenen Virusfamilien und unterscheiden sich bezüglich der Pathogenese, der Übertragungswege, des klinischen Verlaufs und der Präventions- und Therapiemöglichkeiten. In Deutschland besteht eine namentliche Meldepflicht nach Infektionsschutzgesetz (IfSG) für den direkten oder indirekten Nachweis und für Verdacht, Erkrankung und Tod. Die Daten werden an das Robert Koch-Institut übermittelt. In diesem Beitrag wird die Epidemiologie der Hepatitiden A bis E anhand publizierter Studien und Meldedaten beschrieben und es werden aktuelle Herausforderungen und Präventionsansätze aufgezeigt. Letztere bestehen insbesondere in der verbesserten Umsetzung bereits bestehender Impfempfehlungen (Hepatitis A und B), dem verbesserten Zugang zu Prävention, Testung und Versorgung, einschließlich Therapie mit antiviralen Medikamenten (Hepatitis B, C und D), und der Erkennung und Verhinderung lebensmittelbedingter Infektionen und Ausbrüche und Verbesserungen auf dem Gebiet der Lebensmittelsicherheit (Hepatitis A und E).Viral hepatitis A to E describes various infectious inflammations of the liver parenchyma that are caused by the hepatitis viruses A to E (HAV, HBV, HCV, HDV, and HEV). Although the clinical pictures are similar, the pathogens belong to different virus families and differ in terms of pathogenesis, transmission routes, clinical course, prevention, and therapy options. In Germany, there is mandatory reporting according to the Infection Protection Act (IfSG) for direct or indirect laboratory evidence and for suspicion, illness, and death of viral hepatitis. The data are transmitted to the Robert Koch Institute. In this article, on the basis of published studies and notification data, we describe the epidemiology of hepatitis A to E as well as current challenges and prevention approaches. In particular, the latter contains the improvement of existing vaccination recommendations (hepatitis A and B); improvement of access to prevention, testing, and care including therapy with antiviral drugs (hepatitis B, C, and D) and the detection and prevention of foodborne infections and outbreaks; and improvements in the field of food safety (hepatitis A and E).Peer Reviewe

NCAM: a surface marker for human small cell lung cancer cells

Immunocytochemical and immunochemical techniques were used to study the expression of the neural cell adhesion molecule (NCAM) by human lung cancer cell lines. Intense surface staining for NCAM was found at light and electron microscopic levels on small cell lung cancer cells. The NCAM polypeptide of Mr 140000 (NCAM 140) was detected by immunoblotting in all of 7 small cell lung cancer cell lines examined and in one out of two of the closely related large cell cancer cell lines: it was not detected in cell lines obtained from one patient with a mesothelioma, in two cases of adenocarcinoma, nor in two cases of squamous cell cancer. In contrast, neuron-specific enolase was found by immunoblotting in all the lung cancer cell lines tested and synaptophysin in all but the adenocarcinoma cell lines. These antigens were localized intracellularly. The specific expression of NCAM 140 by human small and large cell lung carcinomas suggests its potential as a diagnostic marker

Atmospheric phase correction using CARMA-PACS: high angular resolution observations of the FU Orionis star PP 13S*

We present 0".15 resolution observations of the 227 GHz continuum emission from the circumstellar disk around the FU Orionis star PP 13S*. The data were obtained with the Combined Array for Research in Millimeter-wave Astronomy (CARMA) Paired Antenna Calibration System (C-PACS), which measures and corrects the atmospheric delay fluctuations on the longest baselines of the array in order to improve the sensitivity and angular resolution of the observations. A description of the C-PACS technique and the data reduction procedures are presented. C-PACS was applied to CARMA observations of PP 13S*, which led to a factor of 1.6 increase in the observed peak flux of the source, a 36% reduction in the noise of the image, and a 52% decrease in the measured size of the source major axis. The calibrated complex visibilities were fitted with a theoretical disk model to constrain the disk surface density. The total disk mass from the best-fit model corresponds to 0.06 M_⊙, which is larger than the median mass of a disk around a classical T Tauri star. The disk is optically thick at a wavelength of 1.3 mm for orbital radii less than 48 AU. At larger radii, the inferred surface density of the PP 13S* disk is an order of magnitude lower than that needed to develop a gravitational instability

Cluster scaling relations from cosmological hydrodynamic simulations in dark energy dominated universe

Clusters are potentially powerful tools for cosmology provided their observed properties such as the Sunyaev-Zel'dovich (SZ) or X-ray signals can be translated into physical quantities like mass and temperature. Scaling relations are the appropriate mean to perform this translation. It is therefore, important to understand their evolution and their modifications with respect to the physics and to the underlying cosmology. In this spirit, we investigate the effect of dark energy on the X-ray and SZ scaling relations. The study is based on the first hydro-simulations of cluster formation for diferent models of dark energy. We present results for four dark energy models which differ from each other by their equations of state parameter, $w$. Namely, we use a cosmological constant model $w=-1$ (as a reference), a perfect fluid with constant equation of state parameter $w=-0.8$ and one with $w = -1.2$ and a scalar field model (or quintessence) with varying $w$. We generate N-body/hydrodynamic simulations that include radiative cooling with the public version of the Hydra code, modified to consider an arbitrary dark energy component. We produce cluster catalogues for the four models and derive the associated X-ray and SZ scaling relations. We find that dark energy has little effect on scaling laws making it safe to use the $\Lambda$CDM scalings for conversion of observed quantities into temperature and masses.Comment: 9 pages, 7 figures, submitted to A&

Detection of Q129H Immune Escape Mutation in Apparently Healthy Hepatitis B Virus Carriers in Southwestern Nigeria

As the global effort to eradicate hepatitis B continues, immune escape mutations (IEMs) and drug resistance mutations (DRMs) affecting its diagnosis, treatment, and prevention are compromising this goal. However, knowledge about the prevalence and circulation of these mutations in Nigeria is scarce. Serum samples (n = 199) from apparently healthy prospective blood donors, pregnant women, and individuals presenting with fever in southwestern Nigeria were analyzed for the presence of IEMs and DRMs by means of nested PCR in the HBV S (HBs) and HBV polymerase (Pol) genes, followed by phylogenetic and mutational analyses. In total, 25.1% (n = 50/199) of samples were positive for HBV, as measured by PCR. In 41 samples (20.6%), both fragments could be amplified, whereas the HBs gene and the Pol gene fragment alone were detected in 0.5% (n = 1/199) and 4% (n = 8/199) of samples, respectively. Sequences were successfully obtained for all 42 HBs gene fragments but for only 31/49 Pol gene fragments (totaling 73 sequences from 44 individuals). All sequences were identified as HBV genotype E. IEMs were present in 18.2% (n = 8/44) of the sequences of HBV-positive individuals with available sequences. IEM Q129H was detected in eight out of the 44 (18.2%) HBV isolates sequenced in this study; however, no DRMs were observed. This study confirms the circulation of HBV IEMs and reports the presence of Q129H IEM for the first time in Nigeria. Intensified research on the dynamics of IEM is necessary in order to enhance the elimination of HBV.Peer Reviewe

Chromatin mapping and single-cell immune profiling define the temporal dynamics of ibrutinib response in CLL

The Bruton tyrosine kinase (BTK) inhibitor ibrutinib provides effective treatment for patients with chronic lymphocytic leukemia (CLL), despite extensive heterogeneity in this disease. To define the underlining regulatory dynamics, we analyze high-resolution time courses of ibrutinib treatment in patients with CLL, combining immune-phenotyping, single-cell transcriptome profiling, and chromatin mapping. We identify a consistent regulatory program starting with a sharp decrease of NF-kappa B binding in CLL cells, which is followed by reduced activity of lineage-defining transcription factors, erosion of CLL cell identity, and acquisition of a quiescence-like gene signature. We observe patient-to-patient variation in the speed of execution of this program, which we exploit to predict patient-specific dynamics in the response to ibrutinib based on the pre-treatment patient samples. In aggregate, our study describes time-dependent cellular, molecular, and regulatory effects for therapeutic inhibition of B cell receptor signaling in CLL, and it establishes a broadly applicable method for epigenome/transcriptome-based treatment monitoring

Advanced sequencing approaches detected insertions of viral and human origin in the viral genome of chronic hepatitis E virus patients

The awareness of hepatitis E virus (HEV) increased significantly in the last decade due to its unexpectedly high prevalence in high-income countries. There, infections with HEV-genotype 3 (HEV-3) are predominant which can progress to chronicity in immunocompromised individuals. Persistent infection and antiviral therapy can select HEV-3 variants; however, the spectrum and occurrence of HEV-3 variants is underreported. To gain in-depth insights into the viral population and to perform detailed characterization of viral genomes, we used a new approach combining long-range PCR with next-generation and third-generation sequencing which allowed near full-length sequencing of HEV-3 genomes. Furthermore, we developed a targeted ultra-deep sequencing approach to assess the dynamics of clinically relevant mutations in the RdRp-region and to detect insertions in the HVR-domain in the HEV genomes. Using this new approach, we not only identified several insertions of human (AHNAK, RPL18) and viral origin (RdRp-derived) in the HVR-region isolated from an exemplary sample but detected a variant containing two different insertions simultaneously (AHNAK- and RdRp-derived). This finding is the first HEV-variant recognized as such showing various insertions in the HVR-domain. Thus, this molecular approach will add incrementally to our current knowledge of the HEV-genome organization and pathogenesis in chronic hepatitis E.Peer Reviewe

Hepatitis E virus infection in high-risk populations in Osun State, Nigeria

Hepatitis E virus (HEV) infection is an emerging infection that is of major public health concern, especially in some vulnerable groups like immunosuppressed individuals, pregnant women and HBV-coinfected individuals. HEV is transmitted faecal/oral or zoonotically depending on the HEV-genotype. This study aimed at investigating HEV infections among different at-risk populations in Osun State, Southwestern Nigeria. A total of 720 serum samples were collected from animal handlers, pregnant women, people living with HIV/AIDS, and Hepatitis B virus (HBV) infected individuals. Commercially available Enzyme-Linked Immunosorbent Assays (ELISA) were used for the detection of anti-HEV total and IgM antibodies. Polymerase chain reaction (PCR) was carried out in the HEV seropositive samples and all the samples from individuals infected with HBV. Descriptive analysis and chi-square test of association were performed. The anti-HEV total antibody seroprevalence in HIV-positive individuals, animal handlers and pregnant women was 11.4% (n = 47/411), 7.9% (n = 7/89), and 6.3% (n = 10/160), respectively. Markers of acute HEV infection (anti-HEV IgM) were detected in 2.2% of HIV-positive individuals (n = 9/411) and 1.8% of animal handlers (n = 2/89), respectively, and in 0.6% of pregnant women (n = 1/160). However, all samples were HEV RNA negative. This study analysed the presence of markers of HEV infection among different at-risk populations without clinical symptoms of HEV infection. Our results showed that HEV is an underestimated threat to public health in Nigeria and underlines the need of an HEV surveillance system to understand the distribution and transmission of HEV infection in animals and/to humans.Peer Reviewe

Influence of entrance-channel magicity and isospin on quasi-fission

The role of spherical quantum shells in the competition between fusion and quasi-fission is studied for reactions forming heavy elements. Measurements of fission fragment mass distributions for different reactions leading to similar compound nuclei have been made near the fusion barrier. In general, more quasi-fission is observed for reactions with non-magic nuclei. However, the $^{40}$Ca+$^{208}$Pb reaction is an exception, showing strong evidence for quasi-fission, though both nuclei are doubly magic. Time-dependent Hartree-Fock calculations predict fast equilibration of $N/Z$ in the two fragments early in the collision. This transfer of nucleons breaks the shell effect, causing this reaction to behave more like a non-magic one in the competition between fusion and quasi-fission. Future measurements of fission in reactions with exotic beams should be able to test this idea with larger $N/Z$ asymmetries.Comment: accepted for publication in Physics Letters