Tropism of Puumala orthohantavirus and endoparasite coinfection in the bank vole reservoir

In Europe, most cases of human hantavirus disease are caused by Puumala orthohantavirus (PUUV) transmitted by bank voles (Clethrionomys glareolus, syn. Myodes glareolus), in which PUUV causes inconspicuous infection. Little is known about tropism and endoparasite coinfections in PUUV-infected reservoir and spillover-infected rodents. Here, we characterized PUUV tropism, pathological changes and endoparasite coinfections. The voles and some non-reservoir rodents were examined histologically, immunohistochemically, by in situ hybridization, indirect IgG enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction. PUUV RNA and anti-PUUV antibodies were detected simultaneously in a large proportion of the bank voles, indicating persistent infection. Although PUUV RNA was not detected in non-reservoir rodents, the detection of PUUV-reactive antibodies suggests virus contact. No specific gross and histological findings were detected in the infected bank voles. A broad organ tropism of PUUV was observed: kidney and stomach were most frequently infected. Remarkably, PUUV was detected in cells lacking the typical secretory capacity, which may contribute to the maintenance of virus persistence. PUUV-infected wild bank voles were found to be frequently coinfected with Hepatozoon spp. and Sarcocystis (Frenkelia) spp., possibly causing immune modulation that may influence susceptibility to PUUV infection or vice versa. The results are a prerequisite for a deeper understanding of virus–host interactions in natural hantavirus reservoirs

Zoonotic pathogen screening of striped field mice (Apodemus agrarius) from Austria

The striped field mouse (Apodemus agrarius) is known to carry several zoonotic pathogens, including Leptospira spp. and Dobrava-Belgrade orthohantavirus (DOBV). Since its first detection in 1996 in south-east Austria, the striped field mouse has further expanded its range in Austria. Here, we screened 35 striped field mice collected in an Austrian region near the Hungarian border for DOBV, Leptospira spp. and seven vector-borne pathogens. Hantavirus RT-PCR screening and DOBV IgG ELISA analysis led to the detection of two DOBV-positive striped field mice. The complete coding sequences of all three genome segments of both strains were determined by a combination of target enrichment and next-generation sequencing. Both complete coding S segment sequences clustered within the DOBV genotype Kurkino clade with the highest similarity to a sequence from Hungary. In one of 35 striped field mice, Leptospira borgpetersenii sequence type (ST) 146 was detected. Bartonella spp., Borrelia miyamotoi and Neoehrlichia mikurensis DNA was detected in four, one and two of 32 mice, respectively. Babesia, Anaplasma, Ehrlichia and Rickettsia specific DNA was not detected. Future investigations will have to determine the prevalence and invasion of these pathogens with the ongoing range expansion of the striped field mouse in Austria

Zoonotic pathogen screening of striped field mice (Apodemus agrarius) from Austria

The striped field mouse (Apodemus agrarius) is known to carry several zoonotic pathogens, including Leptospira spp. and Dobrava–Belgrade orthohantavirus (DOBV). Since its first detection in 1996 in south-east Austria, the striped field mouse has further expanded its range in Austria. Here, we screened 35 striped field mice collected in an Austrian region near the Hungarian border for DOBV, Leptospira spp. and seven vector-borne pathogens. Hantavirus RT-PCR screening and DOBV IgG ELISA analysis led to the detection of two DOBV-positive striped field mice. The complete coding sequences of all three genome segments of both strains were determined by a combination of target enrichment and next-generation sequencing. Both complete coding S segment sequences clustered within the DOBV genotype Kurkino clade with the highest similarity to a sequence from Hungary. In one of 35 striped field mice, Leptospira borgpetersenii sequence type (ST) 146 was detected. Bartonella spp., Borrelia miyamotoi and Neoehrlichia mikurensis DNA was detected in four, one and t wo of 32 mice, respectively. Babesia, Anaplasma, Ehrlichia and Rickettsia specific DNA was not detected. Future investigations will have to determine the prevalence and invasion of these pathogens with the ongoing range expansion of the striped field mouse in Austria

Cluster of human Puumala orthohantavirus infections due to indoor exposure?—An interdisciplinary outbreak investigation

Puumala orthohantavirus (PUUV) is the most important hantavirus species in Europe, causing the majority of human hantavirus disease cases. In central and western Europe, the occurrence of human infections is mainly driven by bank vole population dynamics influenced by beech mast. In Germany, hantavirus epidemic years are observed in 2- to 5-year intervals. Many of the human infections are recorded in summer and early autumn, coinciding with peaks in bank vole populations. Here, we describe a molecular epidemiological investigation in a small company with eight employees of whom five contracted hantavirus infections in late 2017. Standardized interviews with employees were conducted to assess the circumstances under which the disease cluster occurred, how the employees were exposed and which counteractive measures were taken. Initially, two employees were admitted to hospital and serologically diagnosed with hantavirus infection. Subsequently, further investigations were conducted. By means of a self-administered questionnaire, three additional symptomatic cases could be identified. The hospital patients' sera were investigated and revealed in one patient a partial PUUV L segment sequence, which was identical to PUUV sequences from several bank voles collected in close proximity to company buildings. This investigation highlights the importance of a One Health approach that combines efforts from human and veterinary medicine, ecology and public health to reveal the origin of hantavirus disease clusters.Peer Reviewe

The Bank Vole (Clethrionomys glareolus) - Small Animal Model for Hepacivirus Infection

Many people worldwide suffer from hepatitis C virus (HCV) infection, which is frequently persistent. The lack of efficient vaccines against HCV and the unavailability of or limited compliance with existing antiviral therapies is problematic for health care systems worldwide. Improved small animal models would support further hepacivirus research, including development of vaccines and novel antivirals. The recent discovery of several mammalian hepaciviruses may facilitate such research. In this study, we demonstrated that bank voles (Clethrionomys glareolus) were susceptible to bank vole-associated Hepacivirus F and Hepacivirus J strains, based on the detection of hepaciviral RNA in 52 of 55 experimentally inoculated voles. In contrast, interferon α/β receptor deficient C57/Bl6 mice were resistant to infection with both bank vole hepaciviruses (BvHVs). The highest viral genome loads in infected voles were detected in the liver, and viral RNA was visualized by in situ hybridization in hepatocytes, confirming a marked hepatotropism. Furthermore, liver lesions in infected voles resembled those of HCV infection in humans. In conclusion, infection with both BvHVs in their natural hosts shares striking similarities to HCV infection in humans and may represent promising small animal models for this important human disease

Hantavirus Brno loanvirus is highly specific to the common noctule bat (Nyctalus noctula) and widespread in Central Europe.

Bat-associated hantaviruses have been detected in Asia, Africa and Europe. Recently, a novel hantavirus (Brno loanvirus, BRNV) was identified in common noctule bats (Nyctalus noctula) in the Czech Republic, but nothing is known about its geographical range and prevalence. The objective of this study was to evaluate the distribution and host specificity of BRNV by testing bats from neighbouring countries Germany, Austria and Poland. One thousand forty-seven bats representing 21 species from Germany, 464 bats representing 18 species from Austria and 77 bats representing 12 species from Poland were screened by L segment broad-spectrum nested reverse transcription-polymerase chain reaction (RT-PCR) or by BRNV-specific real-time RT-PCR. Three common noctules from Germany, one common noctule from Austria and three common noctules from Poland were positive in the hantavirus RNA screening. Conventional RT-PCR and primer walking resulted in the amplification of partial L segment and (almost) complete S and M segment coding sequences for samples from Germany and partial L segment sequences for samples from Poland. Phylogenetic analysis of these nucleotide sequences showed highest similarity to BRNV from Czech Republic. The exclusive detection of BRNV in common noctules from different countries suggests high host specificity. The RNA detection rate in common noctules ranged between 1 of 207 (0.5%; Austria), 3 of 245 (1.2%; Germany) and 3 of 20 (15%; Poland). In conclusion, this study demonstrates a broader distribution of BRNV in common noctules in Central Europe, but at low to moderate prevalence. Additional studies are needed to prove the zoonotic potential of this hantavirus and evaluate its transmission within bat populations

United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU)

Background:There have been substantial improvements in the management of chronic pancreatitis, leading to the publication of several national guidelines during recent years. In collaboration with United European Gastroenterology, the working group on Harmonizing diagnosis and treatment of chronic pancreatitis across Europe' (HaPanEU) developed these European guidelines using an evidence-based approach. Methods: Twelve multidisciplinary review groups performed systematic literature reviews to answer 101 predefined clinical questions. Recommendations were graded using the Grading of Recommendations Assessment, Development and Evaluation system and the answers were assessed by the entire group in a Delphi process online. The review groups presented their recommendations during the 2015 annual meeting of United European Gastroenterology. At this one-day, interactive conference, relevant remarks were voiced and overall agreement on each recommendation was quantified using plenary voting (Test and Evaluation Directorate). After a final round of adjustments based on these comments, a draft version was sent out to external reviewers. Results: The 101 recommendations covered 12 topics related to the clinical management of chronic pancreatitis: aetiology (working party (WP)1), diagnosis of chronic pancreatitis with imaging (WP2 and WP3), diagnosis of pancreatic exocrine insufficiency (WP4), surgery in chronic pancreatitis (WP5), medical therapy (WP6), endoscopic therapy (WP7), treatment of pancreatic pseudocysts (WP8), pancreatic pain (WP9), nutrition and malnutrition (WP10), diabetes mellitus (WP11) and the natural course of the disease and quality of life (WP12). Using the Grading of Recommendations Assessment, Development and Evaluation system, 70 of the 101 (70%) recommendations were rated as strong' and plenary voting revealed strong agreement' for 99 (98%) recommendations. Conclusions:The 2016 HaPanEU/United European Gastroenterology guidelines provide evidence-based recommendations concerning key aspects of the medical and surgical management of chronic pancreatitis based on current available evidence. These recommendations should serve as a reference standard for existing management of the disease and as a guide for future clinical research

Rock glaciers and mountain hydrology: A review

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.In mountainous regions, climate change threatens cryospheric water resources, and understanding all components of the hydrological cycle is necessary for effective water resource management. Rockglaciers are climatically more resilient than glaciers and contain potentially hydrologically valuable ice volumes, and yet havereceived lessattention, even though rock glacier hydrologicalimportance may increase under future climate warming. In synthesising data from a range of global studies, we provide the first compre-hensive evaluation of the hydrological role played by rock glaciers. Weevaluate hydrological significanceover a range of temporal and spatial scales, alongsidethe complex multiple hydrological processes with which rock glaciers can interact diurnally, seasonally, annually, decadally and both at local and regional extents.We report that although no global-extent, complete inventory for rock glaciers exists currently, recent research efforts have greatly elaborated spatialcoverage.Using these research papers,we synthe-sise information on rock glacier spatial distribution, morphometric characteristics, surface and subsurface features, ice-storage and hydrological flow dynamics, water chemistry, and future resilience, from which we provide the first comprehensive evaluation of their hydrological contribution. We identify and discuss long-, intermediate-and short-term timescales for rock glacier storage, allowing a more balanced assess-ment of the contrasting perspectives regarding the relative significance of rock glacier-derived hydrological contributions compared to other water sources.We show that further empirical observations are required to gain a deeper hydrological understanding of rock glaciers, in terms of(i) their genesis and geomorpho-logical dynamics (ii) total ice/water volume; (iii) water discharge; and (iv) water quality. Lastly, we hypothesisethat at decadal and longer timescales, under future climate warming, degradation of ice within rock glaciers may represent an increasing hydrological contribution to downstream regions, and thus in-creased hydrological significance while rock glacier water stores persist.Royal Geographical SocietyNatural Environment Research Council (NERC

Cellular anatomy of the mouse primary motor cortex.

An essential step toward understanding brain function is to establish a structural framework with cellular resolution on which multi-scale datasets spanning molecules, cells, circuits and systems can be integrated and interpreted1. Here, as part of the collaborative Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based anatomical description of one exemplar brain structure, the mouse primary motor cortex, upper limb area (MOp-ul). Using genetic and viral labelling, barcoded anatomy resolved by sequencing, single-neuron reconstruction, whole-brain imaging and cloud-based neuroinformatics tools, we delineated the MOp-ul in 3D and refined its sublaminar organization. We defined around two dozen projection neuron types in the MOp-ul and derived an input-output wiring diagram, which will facilitate future analyses of motor control circuitry across molecular, cellular and system levels. This work provides a roadmap towards a comprehensive cellular-resolution description of mammalian brain architecture