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Background Human Adenoviruses (HAdVs) are highly contagious pathogens of clinical importance, especially among the pediatric population. Studies on comparative viral genomic analysis of cases associated with severe and mild infections due to HAdV are limited. Using whole-genome sequencing (WGS), we investigated whether there were any differences between circulating HAdV strains associated with severe infections (meningitis, sepsis, convulsion, sudden infant death syndrome, death, and hospitalization) and mild clinical presentations in pediatric patients hospitalized between the years 1998 and 2017 in a tertiary care hospital group in Bern, Switzerland covering a population base of approx. 2 million inhabitants. The HAdV species implicated in causing severe infections in this study included HAdV species C genotypes (HAdV1, HAdV2, and HAdV5). Clustering of the HAdV whole-genome sequences of the severe and mild cases did not show any differences except for one sample (isolated from a patient presenting with sepsis, meningitis, and hospitalization) that formed its own cluster with HAdV species C genotypes. This isolate showed intertypic recombination events involving four genotypes, had the highest homology to HAdV89 at complete genome level, but possessed the fiber gene of HAdV1, thereby representing a novel genotype of HAdV species C. The incidence of potential recombination events was higher in severe cases than in mild cases. Our findings confirm that recombination among HAdVs is important for molecular evolution and emergence of new strains. Therefore, further research on HAdVs, particularly among susceptible groups, is needed and continuous surveillance is required for public health preparedness including outbreak investigations.
Joyce Odeke Akello; Richard Kamgang; Maria Teresa Barbani; Franziska Suter-Riniker; Christoph Aebi; Christian Beuret; Daniel H. Paris; Stephen L Leib; Alban Ramette. Genomic analyses of human adenoviruses unravel novel recombinant genotypes associated with severe infections in pediatric patients. 2021, 1 .
AMA StyleJoyce Odeke Akello, Richard Kamgang, Maria Teresa Barbani, Franziska Suter-Riniker, Christoph Aebi, Christian Beuret, Daniel H. Paris, Stephen L Leib, Alban Ramette. Genomic analyses of human adenoviruses unravel novel recombinant genotypes associated with severe infections in pediatric patients. . 2021; ():1.
Chicago/Turabian StyleJoyce Odeke Akello; Richard Kamgang; Maria Teresa Barbani; Franziska Suter-Riniker; Christoph Aebi; Christian Beuret; Daniel H. Paris; Stephen L Leib; Alban Ramette. 2021. "Genomic analyses of human adenoviruses unravel novel recombinant genotypes associated with severe infections in pediatric patients." , no. : 1.
Pneumococcal conjugate vaccines (PCVs) have lowered the incidence of invasive pneumococcal disease (IPD) worldwide. However, the influence of regional vaccine uptake differences on the changing epidemiology of IPD remains unclear. We aimed to examine the overall impact of both seven- and 13-valent PCVs (PCV7 and PCV13) on IPD in Switzerland. Three-year periods from 2005–2010 and 2011–2019 were considered, respectively, as (early and late) PCV7 eras and (early, mid and late) PCV13 eras. Vaccine coverage was estimated from a nationwide survey according to east (German-speaking) and west (French/Italian-speaking) regions for each period. Reported incidence rate ratios (IRRs) were compared between successive periods and regions using nationwide IPD surveillance data. Overall IPD incidence across all ages was only 16% lower in the late PCV13 era compared to the early PCV7 era (IRR 0.83, 95% CI 0.79–0.88), due to increasing incidence of non-PCV-type IPD (2.59, 2.37–2.83) in all age groups, except children <5 years. PCV uptake rates in swiss children were slightly higher in the west than the east (p< 0.001), and were accompanied by lower IPD incidences across all age groups in the former region. Post-PCV13, non-PCV serotypes 8, 22F and 9N were the major cause of IPD in adults ≥65 years. Increased PCV coverage in both areas of Switzerland resulted in a decrease in vaccine-type and overall IPD incidence across all age groups, in a regionally dependent manner. However, the rising incidence of non-vaccine-type IPD, exclusive to older adults, may undermine indirect beneficial effects.
Oluwaseun Oyewole; Phung Lang; Werner Albrich; Kerstin Wissel; Stephen Leib; Carlo Casanova; Markus Hilty. The Impact of Pneumococcal Conjugate Vaccine (PCV) Coverage Heterogeneities on the Changing Epidemiology of Invasive Pneumococcal Disease in Switzerland, 2005–2019. Microorganisms 2021, 9, 1078 .
AMA StyleOluwaseun Oyewole, Phung Lang, Werner Albrich, Kerstin Wissel, Stephen Leib, Carlo Casanova, Markus Hilty. The Impact of Pneumococcal Conjugate Vaccine (PCV) Coverage Heterogeneities on the Changing Epidemiology of Invasive Pneumococcal Disease in Switzerland, 2005–2019. Microorganisms. 2021; 9 (5):1078.
Chicago/Turabian StyleOluwaseun Oyewole; Phung Lang; Werner Albrich; Kerstin Wissel; Stephen Leib; Carlo Casanova; Markus Hilty. 2021. "The Impact of Pneumococcal Conjugate Vaccine (PCV) Coverage Heterogeneities on the Changing Epidemiology of Invasive Pneumococcal Disease in Switzerland, 2005–2019." Microorganisms 9, no. 5: 1078.
The rapid spread of the SARS-CoV-2 lineages B.1.1.7 (N501Y.V1) throughout the UK, B.1.351 (N501Y.V2) in South Africa, and P.1 (B.1.1.28.1; N501Y.V3) in Brazil has led to the definition of variants of concern (VoCs) and recommendations for lineage specific surveillance. In Switzerland, during the last weeks of December 2020, we established a nationwide screening protocol across multiple laboratories, focusing first on epidemiological and microbiological definitions. In January 2021, we validated and implemented an N501Y-specific PCR to rapidly screen for VoCs, which are then confirmed using amplicon sequencing or whole genome sequencing (WGS). A total of 13,387 VoCs have been identified since the detection of the first Swiss case in October 2020, with 4194 being B.1.1.7, 172 B.1.351, and 7 P.1. The remaining 9014 cases of VoCs have been described without further lineage specification. Overall, all diagnostic centers reported a rapid increase of the percentage of detected VOCs, with a range of 6 to 46% between 25 to 31 of January 2021 increasing towards 41 to 82% between 22 to 28 of February. A total of 739 N501Y positive genomes were analysed and show a broad range of introduction events to Switzerland. In this paper, we describe the nationwide coordination and implementation process across laboratories, public health institutions, and researchers, the first results of our N501Y-specific variant screening, and the phylogenetic analysis of all available WGS data in Switzerland, that together identified the early introduction events and subsequent community spreading of the VoCs.
Ana Goncalves Cabecinhas; Tim Roloff; Madlen Stange; Claire Bertelli; Michael Huber; Alban Ramette; Chaoran Chen; Sarah Nadeau; Yannick Gerth; Sabine Yerly; Onya Opota; Trestan Pillonel; Tobias Schuster; Cesar Metzger; Jonas Sieber; Michael Bel; Nadia Wohlwend; Christian Baumann; Michel Koch; Pascal Bittel; Karoline Leuzinger; Myrta Brunner; Franziska Suter-Riniker; Livia Berlinger; Kirstine Søgaard; Christiane Beckmann; Christoph Noppen; Maurice Redondo; Ingrid Steffen; Helena Seth-Smith; Alfredo Mari; Reto Lienhard; Martin Risch; Oliver Nolte; Isabella Eckerle; Gladys Martinetti Lucchini; Emma Hodcroft; Richard Neher; Tanja Stadler; Hans Hirsch; Stephen Leib; Lorenz Risch; Laurent Kaiser; Alexandra Trkola; Gilbert Greub; Adrian Egli. SARS-CoV-2 N501Y Introductions and Transmissions in Switzerland from Beginning of October 2020 to February 2021—Implementation of Swiss-Wide Diagnostic Screening and Whole Genome Sequencing. Microorganisms 2021, 9, 677 .
AMA StyleAna Goncalves Cabecinhas, Tim Roloff, Madlen Stange, Claire Bertelli, Michael Huber, Alban Ramette, Chaoran Chen, Sarah Nadeau, Yannick Gerth, Sabine Yerly, Onya Opota, Trestan Pillonel, Tobias Schuster, Cesar Metzger, Jonas Sieber, Michael Bel, Nadia Wohlwend, Christian Baumann, Michel Koch, Pascal Bittel, Karoline Leuzinger, Myrta Brunner, Franziska Suter-Riniker, Livia Berlinger, Kirstine Søgaard, Christiane Beckmann, Christoph Noppen, Maurice Redondo, Ingrid Steffen, Helena Seth-Smith, Alfredo Mari, Reto Lienhard, Martin Risch, Oliver Nolte, Isabella Eckerle, Gladys Martinetti Lucchini, Emma Hodcroft, Richard Neher, Tanja Stadler, Hans Hirsch, Stephen Leib, Lorenz Risch, Laurent Kaiser, Alexandra Trkola, Gilbert Greub, Adrian Egli. SARS-CoV-2 N501Y Introductions and Transmissions in Switzerland from Beginning of October 2020 to February 2021—Implementation of Swiss-Wide Diagnostic Screening and Whole Genome Sequencing. Microorganisms. 2021; 9 (4):677.
Chicago/Turabian StyleAna Goncalves Cabecinhas; Tim Roloff; Madlen Stange; Claire Bertelli; Michael Huber; Alban Ramette; Chaoran Chen; Sarah Nadeau; Yannick Gerth; Sabine Yerly; Onya Opota; Trestan Pillonel; Tobias Schuster; Cesar Metzger; Jonas Sieber; Michael Bel; Nadia Wohlwend; Christian Baumann; Michel Koch; Pascal Bittel; Karoline Leuzinger; Myrta Brunner; Franziska Suter-Riniker; Livia Berlinger; Kirstine Søgaard; Christiane Beckmann; Christoph Noppen; Maurice Redondo; Ingrid Steffen; Helena Seth-Smith; Alfredo Mari; Reto Lienhard; Martin Risch; Oliver Nolte; Isabella Eckerle; Gladys Martinetti Lucchini; Emma Hodcroft; Richard Neher; Tanja Stadler; Hans Hirsch; Stephen Leib; Lorenz Risch; Laurent Kaiser; Alexandra Trkola; Gilbert Greub; Adrian Egli. 2021. "SARS-CoV-2 N501Y Introductions and Transmissions in Switzerland from Beginning of October 2020 to February 2021—Implementation of Swiss-Wide Diagnostic Screening and Whole Genome Sequencing." Microorganisms 9, no. 4: 677.
Background and Purpose: Endovascular aneurysm treatment relies on a biological process, including cell migration for thrombus organization and growth of a neointima. To better understand aneurysm healing, our study explores the origin of neointima-forming and thrombus-organizing cells in a rat saccular sidewall aneurysm model. Methods: Saccular aneurysms were transplanted onto the abdominal aorta of male Lewis rats and endovascularly treated with coils (n=28) or stents (n=26). In 34 cases, GFP+ (green fluorescent protein)-expressing vital aneurysms were sutured on wild-type rats, and in 23 cases, decellularized wild-type aneurysms were sutured on GFP+ rats. Follow-up at 3, 7, 14, 21, and 28 days evaluated aneurysms by fluorescence angiography, macroscopic inspection, and microscopy for healing and inflammation status. Furthermore, the origin of cells was tracked with fluorescence histology. Results: In animals with successful functional healing, histological studies showed a gradually advancing thrombus organization over time characterized by progressively growing neointima from the periphery of the aneurysm toward the center. Cell counts revealed similar distributions of GFP+ cells for coil or stent treatment in the aneurysm wall (54.4% versus 48.7%) and inside the thrombus (20.5% versus 20.2%) but significantly more GFP+ cells in the neointima of coiled (27.2 %) than stented aneurysms (10.4%; P =0.008). Conclusions: Neointima formation and thrombus organization are concurrent processes during aneurysm healing. Thrombus-organizing cells originate predominantly in the parent artery. Neointima formation relies more on cell migration from the aneurysm wall in coiled aneurysms but receives greater contributions from cells originating in the parent artery in stent-treated aneurysms. Cell migration, which allows for a continuous endothelial lining along the parent artery’s lumen, may be a prerequisite for complete aneurysm healing after endovascular therapy. In terms of translation into clinical practice, these findings may explain the variability in achieving complete aneurysm healing after coil treatment and the improved healing rate in stent-assisted coiling.
Basil E. Grüter; Stefan Wanderer; Fabio Strange; Gwendoline Boillat; Dominik Täschler; Jeannine Rey; Davide M. Croci; Denis Grandgirard; Stephen L. Leib; Michael von Gunten; Stefano Di Santo; Hans Rudolf Widmer; Luca Remonda; Lukas Andereggen; Edin Nevzati; Daniel Coluccia; Javier Fandino; Serge Marbacher. Patterns of Neointima Formation After Coil or Stent Treatment in a Rat Saccular Sidewall Aneurysm Model. Stroke 2021, 52, 1043 -1052.
AMA StyleBasil E. Grüter, Stefan Wanderer, Fabio Strange, Gwendoline Boillat, Dominik Täschler, Jeannine Rey, Davide M. Croci, Denis Grandgirard, Stephen L. Leib, Michael von Gunten, Stefano Di Santo, Hans Rudolf Widmer, Luca Remonda, Lukas Andereggen, Edin Nevzati, Daniel Coluccia, Javier Fandino, Serge Marbacher. Patterns of Neointima Formation After Coil or Stent Treatment in a Rat Saccular Sidewall Aneurysm Model. Stroke. 2021; 52 (3):1043-1052.
Chicago/Turabian StyleBasil E. Grüter; Stefan Wanderer; Fabio Strange; Gwendoline Boillat; Dominik Täschler; Jeannine Rey; Davide M. Croci; Denis Grandgirard; Stephen L. Leib; Michael von Gunten; Stefano Di Santo; Hans Rudolf Widmer; Luca Remonda; Lukas Andereggen; Edin Nevzati; Daniel Coluccia; Javier Fandino; Serge Marbacher. 2021. "Patterns of Neointima Formation After Coil or Stent Treatment in a Rat Saccular Sidewall Aneurysm Model." Stroke 52, no. 3: 1043-1052.
Translational research organizations (TROs) face specific challenges to secure resilience and longevity. This perspective article provides the rationale for six hands-on recommendations for the management of legitimacy building in TROs.
Christian Rosser; Fritz Sager; Stephen L. Leib. Six Recommendations to Build Legitimacy for Translational Research Organizations. Frontiers in Medicine 2020, 7, 1 .
AMA StyleChristian Rosser, Fritz Sager, Stephen L. Leib. Six Recommendations to Build Legitimacy for Translational Research Organizations. Frontiers in Medicine. 2020; 7 ():1.
Chicago/Turabian StyleChristian Rosser; Fritz Sager; Stephen L. Leib. 2020. "Six Recommendations to Build Legitimacy for Translational Research Organizations." Frontiers in Medicine 7, no. : 1.
Background: Microglia initiates and sustains the inflammatory reaction that drives the pathogenesis of pneumococcal meningitis. The expression of the G-protein cannabinoid receptor type 2 (CB2) in the brain is low, but is upregulated in glial cells during infection. Its activation down-regulates pro-inflammatory processes, driving microglia towards an anti-inflammatory phenotype. CB2 agonists are therefore therapeutic candidates in inflammatory conditions like pneumococcal meningitis. We evaluated the effects of JWH-133, a specific CB2 agonist on microglial cells, inflammation, and damage driven by S. pneumoniae in vitro and in experimental pneumococcal meningitis. Materials/methods: Primary mixed glial cultures were stimulated with live or heat-inactivated S. pneumoniae, or lipopolysaccharide and treated with JWH-133 or vehicle. Nitric oxide and cytokines levels were measured in the supernatant. In vivo, pneumococcal meningitis was induced by intracisternal injection of live S. pneumoniae in 11 days old Wistar rats. Animals were treated with antibiotics (Ceftriaxone, 100 mg/kg, s.c. bid) and JWH-133 (1 mg/kg, i.p. daily) or vehicle (10% Ethanol in saline, 100 µl/25g body weight) at 18 h after infection. Brains were harvested at 24 and 42 h post infection (hpi) for histological assessment of hippocampal apoptosis and cortical damage and determination of cyto/chemokines in tissue homogenates. Microglia were characterized using Iba-1 immunostaining. Inflammation in brain homogenates was determined using membrane-based antibody arrays. Results: In vitro, nitric oxide and cytokines levels were significantly lowered by JWH-133 treatment. In vivo, clinical parameters were not affected by the treatment. JWH-133 significantly lowered microglia activation assessed by quantification of cell process length and endpoints per microglia. Animals treated with JWH-133 demonstrated significantly lower parenchymal levels of chemokines (CINC-1, CINC-2α/β, and MIP-3α), TIMP-1, and IL-6 at 24 hpi, and CINC-1, MIP-1α, and IL-1α at 42 hpi. Quantitative analysis of brain damage did not reveal an effect of JWH-133. Conclusions: JWH-133 attenuates microglial activation and downregulates the concentrations of pro-inflammatory mediators in pneumococcal infection in vitro and in vivo. However, we didn’t observe a reduction in cortical or hippocampal injury. This data provides evidence that inhibition of microglia by adjuvant CB2 agonists therapy effectively downmodulates neuroinflammation but does not reduce brain damage in experimental pneumococcal meningitis
Steven D. Pan; Denis Grandgirard; Stephen L. Leib. Adjuvant Cannabinoid Receptor Type 2 Agonist Modulates the Polarization of Microglia Towards a Non-Inflammatory Phenotype in Experimental Pneumococcal Meningitis. Frontiers in Cellular and Infection Microbiology 2020, 10, 1 .
AMA StyleSteven D. Pan, Denis Grandgirard, Stephen L. Leib. Adjuvant Cannabinoid Receptor Type 2 Agonist Modulates the Polarization of Microglia Towards a Non-Inflammatory Phenotype in Experimental Pneumococcal Meningitis. Frontiers in Cellular and Infection Microbiology. 2020; 10 ():1.
Chicago/Turabian StyleSteven D. Pan; Denis Grandgirard; Stephen L. Leib. 2020. "Adjuvant Cannabinoid Receptor Type 2 Agonist Modulates the Polarization of Microglia Towards a Non-Inflammatory Phenotype in Experimental Pneumococcal Meningitis." Frontiers in Cellular and Infection Microbiology 10, no. : 1.
Background: L. monocytogenes meningoencephalitis has a mortality rate of up to 50% and neurofunctional sequelae are common. Type I restriction-modification systems (RMS) are capable of adding methyl groups to the host genome. Some contain multiple sequence recognition (hsdS) genes that recombine, resulting in distinct DNA methylation patterns and patterns of gene expression. These phenotypic switches have been linked to virulence and have recently been discovered in multiple clonal complexes of L. monocytogenes. In the present study, we investigated the significant of RMS on L. monocytogenes virulence during the acute phase of experimental meningitis. Methods: L. monocytogenes strains containing RMS systems were identified, and purified clones enriched for single hsdS alleles were isolated. In vivo, 11-day old Wistar rats were infected with an inoculum containing (a) one of 4 single RMS allele variants (A, B, C, D) treated with amoxicillin (AMX 50 mg/kg/dosis, q8h), (b) a mixture of all 4 variants with or without AMX treatment, or (c) different mixtures of 2 RMS allele variants. At selected time points after infection, clinical and inflammatory parameters, bacterial titers and brain damage were determined. Changes in the relative frequency of the occurring RMS alleles in the inoculum and in CSF or cerebellum of infected animals were analyzed by capillary electrophoresis. Results: We have identified a phase variable RMS locus within L. monocytogenes CC4 and generated stocks that stably expressed each of the possible hsdS genes within that loci. Generation of these allele variants (A, B, C, D) allowed us to determine the methylation pattern associated with each hsdS through SMRT sequencing. In vivo infections with these single allele variants revealed differences in disease severity in that C induced the worst clinical outcome and more pronounced hippocampal apoptosis; D showed the most pronounced weight loss and the highest bacterial titer in the cerebellum. A caused the least severe disease. Conclusion: We identified that L. monocytogenes expressing hsdS (A) causes less damage than when other hsdS genes are expressed. While expression of hsdSC and D worsened the outcome in L. monocytogenes meningitis. We also demonstrate a competitive advantage of variants C and B over variant A in this model. Phenotypical switching may therefore represent a mechanism of virulence regulation during the acute phase of CNS infections with L. monocytogenes.
Florian R. Zbinden; Megan De Ste Croix; Denis Grandgirard; Richard D. Haigh; Irene Vacca; Roxana Zamudio; Emily C. A. Goodall; Roger Stephan; Marco R. Oggioni; Stephen L. Leib. Pathogenic Differences of Type 1 Restriction-Modification Allele Variants in Experimental Listeria monocytogenes Meningitis. Frontiers in Cellular and Infection Microbiology 2020, 10, 590657 .
AMA StyleFlorian R. Zbinden, Megan De Ste Croix, Denis Grandgirard, Richard D. Haigh, Irene Vacca, Roxana Zamudio, Emily C. A. Goodall, Roger Stephan, Marco R. Oggioni, Stephen L. Leib. Pathogenic Differences of Type 1 Restriction-Modification Allele Variants in Experimental Listeria monocytogenes Meningitis. Frontiers in Cellular and Infection Microbiology. 2020; 10 ():590657.
Chicago/Turabian StyleFlorian R. Zbinden; Megan De Ste Croix; Denis Grandgirard; Richard D. Haigh; Irene Vacca; Roxana Zamudio; Emily C. A. Goodall; Roger Stephan; Marco R. Oggioni; Stephen L. Leib. 2020. "Pathogenic Differences of Type 1 Restriction-Modification Allele Variants in Experimental Listeria monocytogenes Meningitis." Frontiers in Cellular and Infection Microbiology 10, no. : 590657.
Background Pneumococcal meningitis (PM) remains a global public health concern and affects all age groups. If acquired during infancy or childhood, permanent neurofunctional deficits including cognitive impairment, cerebral palsy, and secondary epilepsy are typical sequelae of neuronal injury. Determination of patients at risk for the development of brain injury and subsequent neurofunctional sequelae could help to identify patients for focused management. Neurofilament light chain (NfL) is an axonal cytoskeletal protein released upon neuronal injury into the cerebrospinal fluid (CSF) and blood. As little is known about the course of neurofilament release in the course of PM, we measured CSF and serum NfL levels longitudinally in experimental PM (ePM). Methods Eleven-day-old infant Wistar rats were infected intracisternally with Streptococcus pneumoniae and treated with ceftriaxone. At 18 and 42 h post-infection (hpi), the blood and CSF were sampled for NfL measurements by a single molecule array technology. Inflammatory cytokines and MMP-9 in CSF were quantified by magnetic bead multiplex assay (Luminex®) and by gel zymography, respectively. Results In ePM, CSF and serum NfL levels started to increase at 18 hpi and were 26- and 3.5-fold increased, respectively, compared to mock-infected animals at 42 hpi (p < 0.0001). CSF and serum NfL correlated at 18 hpi (p < 0.05, r = 0.4716) and 42 hpi (p < 0.0001, r = 0.8179). Both CSF and serum NfL at 42 hpi strongly correlated with CSF levels of IL-1β, TNF-α, and IL-6 and of MMP-9 depending on their individual kinetics. Conclusion Current results demonstrate that during the peak inflammatory phase of ePM, NfL levels in CSF and serum are the highest among CNS disease models studied so far. Given the strong correlation of CSF versus serum NfL, and its CNS-specific signal character, longitudinal measurements to monitor the course of PM could be performed based on blood sample tests, i.e., without the need of repetitive spinal taps. We conclude that NfL in the serum should be evaluated as a biomarker in PM.
Ngoc Dung Le; Lukas Muri; Denis Grandgirard; Jens Kuhle; David Leppert; Stephen L. Leib. Evaluation of neurofilament light chain in the cerebrospinal fluid and blood as a biomarker for neuronal damage in experimental pneumococcal meningitis. Journal of Neuroinflammation 2020, 17, 1 -9.
AMA StyleNgoc Dung Le, Lukas Muri, Denis Grandgirard, Jens Kuhle, David Leppert, Stephen L. Leib. Evaluation of neurofilament light chain in the cerebrospinal fluid and blood as a biomarker for neuronal damage in experimental pneumococcal meningitis. Journal of Neuroinflammation. 2020; 17 (1):1-9.
Chicago/Turabian StyleNgoc Dung Le; Lukas Muri; Denis Grandgirard; Jens Kuhle; David Leppert; Stephen L. Leib. 2020. "Evaluation of neurofilament light chain in the cerebrospinal fluid and blood as a biomarker for neuronal damage in experimental pneumococcal meningitis." Journal of Neuroinflammation 17, no. 1: 1-9.
Pneumococcal meningitis (PM) causes damage to the hippocampus, a brain structure critically involved in learning and memory. Hippocampal injury–which compromises neurofunctional outcome–occurs as apoptosis of progenitor cells and immature neurons of the hippocampal dentate granule cell layer thereby impairing the regenerative capacity of the hippocampal stem cell niche. Repetitive transcranial magnetic stimulation (rTMS) harbours the potential to modulate the proliferative activity of this neuronal stem cell niche. In this study, specific rTMS protocols–namely continuous and intermittent theta burst stimulation (cTBS and iTBS)–were applied on infant rats microbiologically cured from PM by five days of antibiotic treatment. Following two days of exposure to TBS, differential gene expression was analysed by whole transcriptome analysis using RNAseq. cTBS provoked a prominent effect in inducing differential gene expression in the cortex and the hippocampus, whereas iTBS only affect gene expression in the cortex. TBS induced polarisation of microglia and astrocytes towards an inflammatory phenotype, while reducing neurogenesis, neuroplasticity and regeneration. cTBS was further found to induce the release of pro-inflammatory cytokines in vitro. We conclude that cTBS intensified neuroinflammation after PM, which translated into increased release of pro-inflammatory mediators thereby inhibiting neuroregeneration.
Lukas Muri; Simone Oberhänsli; Michelle Buri; Ngoc Dung Le; Denis Grandgirard; Rémy Bruggmann; René M. Müri; Stephen L. Leib. Repetitive transcranial magnetic stimulation activates glial cells and inhibits neurogenesis after pneumococcal meningitis. PLOS ONE 2020, 15, e0232863 .
AMA StyleLukas Muri, Simone Oberhänsli, Michelle Buri, Ngoc Dung Le, Denis Grandgirard, Rémy Bruggmann, René M. Müri, Stephen L. Leib. Repetitive transcranial magnetic stimulation activates glial cells and inhibits neurogenesis after pneumococcal meningitis. PLOS ONE. 2020; 15 (9):e0232863.
Chicago/Turabian StyleLukas Muri; Simone Oberhänsli; Michelle Buri; Ngoc Dung Le; Denis Grandgirard; Rémy Bruggmann; René M. Müri; Stephen L. Leib. 2020. "Repetitive transcranial magnetic stimulation activates glial cells and inhibits neurogenesis after pneumococcal meningitis." PLOS ONE 15, no. 9: e0232863.
Enteroviruses are small RNA viruses that affect millions of people each year by causing an important burden of disease with a broad spectrum of symptoms. In routine diagnostic laboratories, enteroviruses are identified by PCR-based methods, often combined with partial sequencing for genotyping. In this proof-of-principle study, we assessed direct RNA sequencing (DRS) using nanopore sequencing technology for fast whole-genome sequencing of viruses directly from clinical samples. The approach was complemented by sequencing the corresponding viral cDNA via Illumina MiSeq sequencing. DRS of total RNA extracted from three different enterovirus-positive stool samples produced long RNA fragments, covering between 59% and 99.6% of the most similar reference genome sequences. The identification of the enterovirus sequences in the samples was confirmed by short-read cDNA sequencing. Sequence identity between DRS and Illumina MiSeq enterovirus consensus sequences ranged between 94% and 97%. Here, we show that nanopore DRS can be used to correctly identify enterovirus genotypes from patient stool samples with high viral load and that the approach also provides rich metatranscriptomic information on sample composition for all life domains.
Carole Grädel; Miguel A. Terrazos Miani; Christian Baumann; Maria Teresa Barbani; Stefan Neuenschwander; Stephen L. Leib; Franziska Suter-Riniker; Alban Ramette. Whole-Genome Sequencing of Human Enteroviruses from Clinical Samples by Nanopore Direct RNA Sequencing. Viruses 2020, 12, 841 .
AMA StyleCarole Grädel, Miguel A. Terrazos Miani, Christian Baumann, Maria Teresa Barbani, Stefan Neuenschwander, Stephen L. Leib, Franziska Suter-Riniker, Alban Ramette. Whole-Genome Sequencing of Human Enteroviruses from Clinical Samples by Nanopore Direct RNA Sequencing. Viruses. 2020; 12 (8):841.
Chicago/Turabian StyleCarole Grädel; Miguel A. Terrazos Miani; Christian Baumann; Maria Teresa Barbani; Stefan Neuenschwander; Stephen L. Leib; Franziska Suter-Riniker; Alban Ramette. 2020. "Whole-Genome Sequencing of Human Enteroviruses from Clinical Samples by Nanopore Direct RNA Sequencing." Viruses 12, no. 8: 841.
Meningococcal meningitis (MM) is a life-threatening disease associated with approximately 10% case fatality rates and neurological sequelae in 10–20% of the cases. Recently, we have shown that the matrix metalloproteinase (MMP) inhibitor BB-94 reduced brain injury in a mouse model of MM. The present study aimed to assess whether doxycycline (DOX), a tetracycline that showed a neuroprotective effect as adjuvant therapy in experimental pneumococcal meningitis (PM), would also exert a beneficial effect when given as adjunctive therapy to ceftriaxone (CRO) in experimental MM. BALB/c mice were infected by the intracisternal route with a group C Neisseria meningitidis strain. Eighteen h post infection (hpi), animals were randomised for treatment with CRO [100 mg/kg subcutaneously (s.c.)], CRO plus DOX (30 mg/kg s.c.) or saline (control s.c.). Antibiotic treatment was repeated 24 and 40 hpi. Mouse survival and clinical signs, bacterial counts in cerebella, brain damage, MMP-9 and cyto/chemokine levels were assessed 48 hpi. Analysis of bacterial load in cerebella indicated that CRO and CRO + DOX were equally effective at controlling meningococcal replication. No differences in survival were observed between mice treated with CRO (94.4%) or CRO + DOX (95.5%), (p > 0.05). Treatment with CRO + DOX significantly diminished both the number of cerebral hemorrhages (p = 0.029) and the amount of MMP-9 in the brain (p = 0.046) compared to untreated controls, but not to CRO-treated animals (p > 0.05). Levels of inflammatory markers in the brain of mice that received CRO or CRO + DOX were not significantly different (p > 0.05). Overall, there were no significant differences in the parameters assessed between the groups treated with CRO alone or CRO + DOX. Treatment with CRO + DOX showed similar bactericidal activity to CRO in vivo, suggesting no antagonist effect of DOX on CRO. Combined therapy significantly improved mouse survival and disease severity compared to untreated animals, but addition of DOX to CRO did not offer significant benefits over CRO monotherapy. In contrast to experimental PM, DOX has no adjunctive activity in experimental MM.
Susanna Ricci; Denis Grandgirard; Ilias Masouris; Tiziana Braccini; Gianni Pozzi; Marco R. Oggioni; Uwe Koedel; Stephen L. Leib. Combined therapy with ceftriaxone and doxycycline does not improve the outcome of meningococcal meningitis in mice compared to ceftriaxone monotherapy. BMC Infectious Diseases 2020, 20, 1 -8.
AMA StyleSusanna Ricci, Denis Grandgirard, Ilias Masouris, Tiziana Braccini, Gianni Pozzi, Marco R. Oggioni, Uwe Koedel, Stephen L. Leib. Combined therapy with ceftriaxone and doxycycline does not improve the outcome of meningococcal meningitis in mice compared to ceftriaxone monotherapy. BMC Infectious Diseases. 2020; 20 (1):1-8.
Chicago/Turabian StyleSusanna Ricci; Denis Grandgirard; Ilias Masouris; Tiziana Braccini; Gianni Pozzi; Marco R. Oggioni; Uwe Koedel; Stephen L. Leib. 2020. "Combined therapy with ceftriaxone and doxycycline does not improve the outcome of meningococcal meningitis in mice compared to ceftriaxone monotherapy." BMC Infectious Diseases 20, no. 1: 1-8.
Adipose tissue eosinophils (ATEs) are important in the control of obesity-associated inflammation and metabolic disease. However, the way in which ageing impacts the regulatory role of ATEs remains unknown. Here, we show that ATEs undergo major age-related changes in distribution and function associated with impaired adipose tissue homeostasis and systemic low-grade inflammation in both humans and mice. We find that exposure to a young systemic environment partially restores ATE distribution in aged parabionts and reduces adipose tissue inflammation. Approaches to restore ATE distribution using adoptive transfer of eosinophils from young mice into aged recipients proved sufficient to dampen age-related local and systemic low-grade inflammation. Importantly, restoration of a youthful systemic milieu by means of eosinophil transfers resulted in systemic rejuvenation of the aged host, manifesting in improved physical and immune fitness that was partially mediated by eosinophil-derived IL-4. Together, these findings support a critical function of adipose tissue as a source of pro-ageing factors and uncover a new role of eosinophils in promoting healthy ageing by sustaining adipose tissue homeostasis.
Daniel Brigger; Carsten Riether; Robin Van Brummelen; Kira I. Mosher; Alicia Shiu; Zhaoqing Ding; Noemi Zbären; Pascal Gasser; Pascal Guntern; Hanadie Yousef; Joseph M. Castellano; Federico Storni; Neill Graff-Radford; Markus Britschgi; Denis Grandgirard; Magdalena Hinterbrandner; Mark Siegrist; Norman Moullan; Willy Hofstetter; Stephen L. Leib; Peter M. Villiger; Johan Auwerx; Saul A. Villeda; Tony Wyss-Coray; Mario Noti; Alexander Eggel. Eosinophils regulate adipose tissue inflammation and sustain physical and immunological fitness in old age. Nature Metabolism 2020, 2, 688 -702.
AMA StyleDaniel Brigger, Carsten Riether, Robin Van Brummelen, Kira I. Mosher, Alicia Shiu, Zhaoqing Ding, Noemi Zbären, Pascal Gasser, Pascal Guntern, Hanadie Yousef, Joseph M. Castellano, Federico Storni, Neill Graff-Radford, Markus Britschgi, Denis Grandgirard, Magdalena Hinterbrandner, Mark Siegrist, Norman Moullan, Willy Hofstetter, Stephen L. Leib, Peter M. Villiger, Johan Auwerx, Saul A. Villeda, Tony Wyss-Coray, Mario Noti, Alexander Eggel. Eosinophils regulate adipose tissue inflammation and sustain physical and immunological fitness in old age. Nature Metabolism. 2020; 2 (8):688-702.
Chicago/Turabian StyleDaniel Brigger; Carsten Riether; Robin Van Brummelen; Kira I. Mosher; Alicia Shiu; Zhaoqing Ding; Noemi Zbären; Pascal Gasser; Pascal Guntern; Hanadie Yousef; Joseph M. Castellano; Federico Storni; Neill Graff-Radford; Markus Britschgi; Denis Grandgirard; Magdalena Hinterbrandner; Mark Siegrist; Norman Moullan; Willy Hofstetter; Stephen L. Leib; Peter M. Villiger; Johan Auwerx; Saul A. Villeda; Tony Wyss-Coray; Mario Noti; Alexander Eggel. 2020. "Eosinophils regulate adipose tissue inflammation and sustain physical and immunological fitness in old age." Nature Metabolism 2, no. 8: 688-702.
The "One Health" framework emphasizes the ecological relationships between soil, plant, animal and human health. Microbiomes play important roles in these relationships, as they modify the health and performance of the different compartments and influence the transfer of energy, matter and chemicals between them. Standardized methods to characterize microbiomes along food chains are, however, currently lacking. To address this methodological gap, we evaluated the performance of DNA extraction kits and commonly recommended primer pairs targeting different hypervariable regions (V3‐V4, V4, V5‐V6, V5‐V6‐V7) of the 16S rRNA gene, on microbiome samples along a model food chain, including soils, maize roots, cattle rumen, and cattle and human faeces. We also included faeces from gnotobiotic mice colonized with defined bacterial taxa and mock communities to confirm the robustness of our molecular and bioinformatic approaches on these defined low microbial diversity samples. Based on Amplicon Sequence Variants, the primer pair 515F‐806R led to the highest estimates of species richness and diversity in all sample types and offered maximum diversity coverage of reference databases in in silico primer analysis. The influence of the DNA extraction kits was negligible compared to the influence of the choice of primer pairs. Comparing microbiomes using 515F‐806R revealed that soil and root samples have the highest estimates of species richness while lowest richness was observed in human faeces. Primer pair choice directly influenced the estimation of community changes within and across compartments and may give rise to preferential detection of specific taxa. This work demonstrates why a standardized approach is necessary to analyse microbiomes within and between source compartments along food chains in the context of the One Health framework.
Wasim. Uddin; Klaus Schlaeppi; Francesca Ronchi; Stephen L. Leib; Matthias Erb; Alban Ramette. Evaluation of primer pairs for microbiome profiling from soils to humans within the One Health framework. Molecular Ecology Resources 2020, 20, 1558 -1571.
AMA StyleWasim. Uddin, Klaus Schlaeppi, Francesca Ronchi, Stephen L. Leib, Matthias Erb, Alban Ramette. Evaluation of primer pairs for microbiome profiling from soils to humans within the One Health framework. Molecular Ecology Resources. 2020; 20 (6):1558-1571.
Chicago/Turabian StyleWasim. Uddin; Klaus Schlaeppi; Francesca Ronchi; Stephen L. Leib; Matthias Erb; Alban Ramette. 2020. "Evaluation of primer pairs for microbiome profiling from soils to humans within the One Health framework." Molecular Ecology Resources 20, no. 6: 1558-1571.
Enteroviruses are small RNA viruses that affect millions of people each year by causing an important burden of disease with a broad spectrum of symptoms. In routine diagnostic laboratories, those viruses are identified by PCR based methods, often combined with partial sequencing for genotyping. In this proof-of-principle study, we assessed direct RNA sequencing (DRS) using nanopore sequencing technology for fast whole-genome sequencing of viruses directly from clinical samples. Results of the approach were complemented with those obtained by sequencing the corresponding viral cDNA via Illumina MiSeq sequencing. DRS of total RNA extracted from three different enterovirus-positive stool samples produced long RNA fragments, covering between 59% to 99.6 % of the best reference genomes. The identification of the enterovirus sequences in the sample was confirmed by the short-read cDNA sequencing. Sequence identity between DRS and Illumina MiSeq enterovirus consensus sequences ranged between 94-97%. Here we show that nanopore DRS can be used to correctly identify the genotypes of enteroviruses from patient stool samples with high viral load.
Carole Grädel; Miguel A Terrazos Miani; Christian Baumann; Maria Teresa Barbani; Stefan Neuenschwander; Stephen L Leib; Franziska Suter-Riniker; Alban Ramette. Whole genome sequencing of human enteroviruses from clinical samples by nanopore direct RNA sequencing. 2020, 1 .
AMA StyleCarole Grädel, Miguel A Terrazos Miani, Christian Baumann, Maria Teresa Barbani, Stefan Neuenschwander, Stephen L Leib, Franziska Suter-Riniker, Alban Ramette. Whole genome sequencing of human enteroviruses from clinical samples by nanopore direct RNA sequencing. . 2020; ():1.
Chicago/Turabian StyleCarole Grädel; Miguel A Terrazos Miani; Christian Baumann; Maria Teresa Barbani; Stefan Neuenschwander; Stephen L Leib; Franziska Suter-Riniker; Alban Ramette. 2020. "Whole genome sequencing of human enteroviruses from clinical samples by nanopore direct RNA sequencing." , no. : 1.
Amplicon sequencing of the 16S rRNA gene is commonly used for the identification of bacterial isolates in diagnostic laboratories and mostly relies on the Sanger sequencing method. The latter, however, suffers from a number of limitations, with the most significant being the inability to resolve mixed amplicons when closely related species are coamplified from a mixed culture. This often leads to either increased turnaround time or absence of usable sequence data. Short-read next-generation sequencing (NGS) technologies could solve the mixed amplicon issue but would lack both cost efficiency at low throughput and fast turnaround times.
Stefan Moritz Neuenschwander; Miguel Angel Terrazos Miani; Heiko Amlang; Carmen Perroulaz; Pascal Bittel; Carlo Casanova; Sara Droz; Jean-Pierre Flandrois; Stephen L. Leib; Franziska Suter-Riniker; Alban Ramette. A Sample-to-Report Solution for Taxonomic Identification of Cultured Bacteria in the Clinical Setting Based on Nanopore Sequencing. Journal of Clinical Microbiology 2020, 58, 1 .
AMA StyleStefan Moritz Neuenschwander, Miguel Angel Terrazos Miani, Heiko Amlang, Carmen Perroulaz, Pascal Bittel, Carlo Casanova, Sara Droz, Jean-Pierre Flandrois, Stephen L. Leib, Franziska Suter-Riniker, Alban Ramette. A Sample-to-Report Solution for Taxonomic Identification of Cultured Bacteria in the Clinical Setting Based on Nanopore Sequencing. Journal of Clinical Microbiology. 2020; 58 (6):1.
Chicago/Turabian StyleStefan Moritz Neuenschwander; Miguel Angel Terrazos Miani; Heiko Amlang; Carmen Perroulaz; Pascal Bittel; Carlo Casanova; Sara Droz; Jean-Pierre Flandrois; Stephen L. Leib; Franziska Suter-Riniker; Alban Ramette. 2020. "A Sample-to-Report Solution for Taxonomic Identification of Cultured Bacteria in the Clinical Setting Based on Nanopore Sequencing." Journal of Clinical Microbiology 58, no. 6: 1.
Identification and characterization of viral genomes in vectors including ticks and mosquitoes positive for pathogens of great public health concern using metagenomic next generation sequencing (mNGS) has challenges. One such challenge is the ability to efficiently recover viral RNA which is typically dependent on sample processing. We evaluated the quantitative effect of six different extraction methods in recovering viral RNA in vectors using negative tick homogenates spiked with serial dilutions of tick-borne encephalitis virus (TBEV) and surrogate Langat virus (LGTV). Evaluation was performed using qPCR and mNGS. Sensitivity and proof of concept of optimal method was tested using naturally positive TBEV tick homogenates and positive dengue, chikungunya, and Zika virus mosquito homogenates. The amount of observed viral genome copies, percentage of mapped reads, and genome coverage varied among different extractions methods. The developed Method 5 gave a 120.8-, 46-, 2.5-, 22.4-, and 9.9-fold increase in the number of viral reads mapping to the expected pathogen in comparison to Method 1, 2, 3, 4, and 6, respectively. Our developed Method 5 termed ROVIV (Recovery of Viruses in Vectors) greatly improved viral RNA recovery and identification in vectors using mNGS. Therefore, it may be a more sensitive method for use in arbovirus surveillance.
Joyce Odeke Akello; Stephen L. Leib; Olivier Engler; Christian Beuret. Evaluation of Viral RNA Recovery Methods in Vectors by Metagenomic Sequencing. Viruses 2020, 12, 562 .
AMA StyleJoyce Odeke Akello, Stephen L. Leib, Olivier Engler, Christian Beuret. Evaluation of Viral RNA Recovery Methods in Vectors by Metagenomic Sequencing. Viruses. 2020; 12 (5):562.
Chicago/Turabian StyleJoyce Odeke Akello; Stephen L. Leib; Olivier Engler; Christian Beuret. 2020. "Evaluation of Viral RNA Recovery Methods in Vectors by Metagenomic Sequencing." Viruses 12, no. 5: 562.
Hypoxic-ischemic brain injury is the leading cause of disability and death after successful resuscitation from cardiac arrest, and, to date, no specific treatment option is available to prevent subsequent neurofunctional impairments. The hippocampal cornu ammonis segment 1 (CA1) is one of the brain areas most affected by hypoxia, and its degeneration is correlated with memory deficits in patients and corresponding animal models. The aim of the present work was to evaluate the feasibility of neural progenitor cell (NPC) transplantation into the hippocampus in a refined rodent cardiac arrest model. Adult rats were subjected to 12 minutes of potassium-induced cardiac arrest and followed up to 6 weeks. Histological analysis showed extensive neuronal cell death specifically in the hippocampal CA1 segment, without any spontaneous regeneration. Neurofunctional assessment revealed transient memory deficits in ischemic animals compared to controls, detectable after 4, but not after 6 weeks. Using stereotactic surgery, embryonic NPCs were transplanted in a subset of animals 1 week after cardiac arrest and their survival, migration and differentiation were assessed histologically. Transplanted cells showed a higher persistence in the CA1 segment of animals after ischemia. Glia in the damaged CA1 segment expressed the chemotactic factor SDF-1, while transplanted NPCs expressed its receptor CXCR4, suggesting that the SDF-1/CXCR4 pathway, known to be involved in the migration of neural stem cells towards injured brain regions, directs the observed retention of cells in the damaged area. Using immunostaining, we could demonstrate that transplanted cells differentiated into mature neurons. In conclusion, our data document the survival, persistence in the injured area and neuronal differentiation of transplanted NPCs, and thus their potential to support brain regeneration after hypoxic-ischemic injury. This may represent an option worth further investigation in order to improve the outcome of patients after cardiac arrest.
Patricia Meyer; Denis Grandgirard; Marika Lehner; Matthias Haenggi; Stephen L. Leib. Grafted Neural Progenitor Cells Persist in the Injured Site and Differentiate Neuronally in a Rodent Model of Cardiac Arrest-Induced Global Brain Ischemia. Stem Cells and Development 2020, 29, 574 -585.
AMA StylePatricia Meyer, Denis Grandgirard, Marika Lehner, Matthias Haenggi, Stephen L. Leib. Grafted Neural Progenitor Cells Persist in the Injured Site and Differentiate Neuronally in a Rodent Model of Cardiac Arrest-Induced Global Brain Ischemia. Stem Cells and Development. 2020; 29 (9):574-585.
Chicago/Turabian StylePatricia Meyer; Denis Grandgirard; Marika Lehner; Matthias Haenggi; Stephen L. Leib. 2020. "Grafted Neural Progenitor Cells Persist in the Injured Site and Differentiate Neuronally in a Rodent Model of Cardiac Arrest-Induced Global Brain Ischemia." Stem Cells and Development 29, no. 9: 574-585.
Pneumococcal meningitis (PM) causes damage to the hippocampus, a brain structure critically involved in learning and memory. Hippocampal injury – which compromises neurofunctional outcome – occurs as apoptosis of progenitor cells and immature neurons of the hippocampal dentate granule cell layer thereby impairing the regenerative capacity of the hippocampal stem cell niche. Repetitive transcranial magnetic stimulation (rTMS) harbours the potential to modulate the proliferative activity of this neuronal stem cell niche. In this study, specific rTMS protocols – namely continuous and intermittent theta burst stimulation (cTBS and iTBS) – were applied on infant rats microbiologically cured from PM by five days of antibiotic treatment. Following two days of exposure to TBS, differential gene expression was analysed by whole transcriptome analysis using RNAseq. cTBS provoked a prominent effect in inducing differential gene expression in the cortex and the hippocampus, whereas iTBS only affect gene expression in the cortex. TBS induced polarisation of microglia and astrocytes towards an inflammatory phenotype, while reducing neurogenesis, neuroplasticity and regeneration. cTBS was further found to induce the release of pro-inflammatory cytokines in vitro. We conclude that cTBS intensified neuroinflammation after PM, which translated into increased release of pro-inflammatory mediators thereby inhibiting neuroregeneration.
Lukas Muri; Simone Oberhänsli; Michelle Buri; Ngoc Dung Le; Denis Grandgirard; Rémy Bruggmann; René M. Müri; Stephen L. Leib; Muri Lukas. Repetitive Transcranial Magnetic Stimulation Activates Glial Cells and Inhibits Neurogenesis after Pneumococcal Meningitis. 2020, 1 .
AMA StyleLukas Muri, Simone Oberhänsli, Michelle Buri, Ngoc Dung Le, Denis Grandgirard, Rémy Bruggmann, René M. Müri, Stephen L. Leib, Muri Lukas. Repetitive Transcranial Magnetic Stimulation Activates Glial Cells and Inhibits Neurogenesis after Pneumococcal Meningitis. . 2020; ():1.
Chicago/Turabian StyleLukas Muri; Simone Oberhänsli; Michelle Buri; Ngoc Dung Le; Denis Grandgirard; Rémy Bruggmann; René M. Müri; Stephen L. Leib; Muri Lukas. 2020. "Repetitive Transcranial Magnetic Stimulation Activates Glial Cells and Inhibits Neurogenesis after Pneumococcal Meningitis." , no. : 1.
Background: Human adenovirus (HAdV) is an important pathogen seen in clinical practice. Long-term studies may help better understand epidemiological trends and changes in circulating genotypes over time. Purpose: Using a large biobank of samples from hospitalized, adenovirus-positive patients over a 20-year period, we aimed to analyze long-term epidemiological trends and genotypic relatedness among circulating HAdV strains. Methods: Based on samples from hospitalized patients confirmed to be HAdV positive in Bern, Switzerland, from 1998 to 2017, and on their associated demographic and clinical data, we identified epidemiological trends and risk factors associated with HAdV infection. HAdV genotyping was performed by PCR amplification and sequencing of the hypervariable hexon gene. The obtained sequences were phylogenetically compared with sequences from international HAdV strains. Results: HAdV was identified in 1302 samples tested. Cases of HAdV infection were reported throughout the years with no clear seasonality. Upper respiratory tract samples, conjunctivitis swabs, and stool had the highest positivity rate (56.2%, 18.7%, and 14.2% of the cases, respectively). HAdV infection was highest among children ≤ 4 years old. Increased number of HAdV cases were observed in years 2009 (n = 110) and 2010 (n =112). HAdV8 was the predominant genotype among patients older than 20 years, and was mostly associated with ophthalmic infection. Predominant genotypes among children ≤ 4 years old were HAdV1, HAdV2, and HAdV3, which were mostly associated with respiratory tract infections. Recurring peaks of increased HAdV cases were evidenced every 4 years among children ≤ 4 years old. Conclusion: Our study gives novel insights on long-term epidemiological trends and phylogenetic relatedness among circulating HAdV strains in Switzerland, country in which little data on HAdV prevalence and diversity was so far available.
Joyce Odeke Akello; Richard Kamgang; Maria Teresa Barbani; Franziska Suter-Riniker; Stephen L Leib; Alban Ramette. Epidemiology of Human Adenoviruses: A 20-Year Retrospective Observational Study in Hospitalized Patients in Bern, Switzerland. Clinical Epidemiology 2020, ume 12, 353 -366.
AMA StyleJoyce Odeke Akello, Richard Kamgang, Maria Teresa Barbani, Franziska Suter-Riniker, Stephen L Leib, Alban Ramette. Epidemiology of Human Adenoviruses: A 20-Year Retrospective Observational Study in Hospitalized Patients in Bern, Switzerland. Clinical Epidemiology. 2020; ume 12 ():353-366.
Chicago/Turabian StyleJoyce Odeke Akello; Richard Kamgang; Maria Teresa Barbani; Franziska Suter-Riniker; Stephen L Leib; Alban Ramette. 2020. "Epidemiology of Human Adenoviruses: A 20-Year Retrospective Observational Study in Hospitalized Patients in Bern, Switzerland." Clinical Epidemiology ume 12, no. : 353-366.
The “One Health” framework emphasizes the ecological relationships between soil, plant, animal and human health. Microbiomes play important roles in these relationships, as they modify the health and performance of the different compartments and influence the transfer of energy, matter and chemicals between them. Standardized methods to characterize microbiomes along food chains are, however, currently lacking. To address this methodological gap, we evaluated the performance of DNA extractions kits and commonly recommended primer pairs targeting different hypervariable regions (V3-V4, V4, V5-V6, V5-V6-V7) of the 16S rRNA gene, on microbiome samples along a model food chain, including soils, maize roots, cattle rumen, and cattle and human faeces. We also included faeces from gnotobiotic mice colonized with defined bacterial taxa and mock communities to confirm the robustness of our molecular and bioinformatic approaches on these defined low microbial diversity samples. Based on Amplicon Sequence Variants, the primer pair 515F-806R led to the highest estimates of species richness and diversity in all sample types and offered maximum diversity coverage of reference databases in in silico primer analysis. The influence of the DNA extraction kits was negligible compared to the influence of the choice of primer pairs. Comparing microbiomes using 515F-806R revealed that soil and root samples have the highest estimates of species richness and inter-sample variation. Species richness decreased gradually along the food chain, with the lowest richness observed in human faeces. Primer pair choice directly influenced the estimation of community changes (beta diversity) within and across compartments and may give rise to preferential detection of specific taxa. This work demonstrates why a standardized approach is necessary to analyse microbiomes within and between source compartments along food chains in the context of the One Health framework.
Wasimuddin Wasimuddin; Klaus Schlaeppi; Francesca Ronchi; Stephen L Leib; Matthias Erb; Alban Ramette. Evaluation of primer pairs for microbiome profiling across a food chain from soils to humans within the One Health framework. 2019, 843144 .
AMA StyleWasimuddin Wasimuddin, Klaus Schlaeppi, Francesca Ronchi, Stephen L Leib, Matthias Erb, Alban Ramette. Evaluation of primer pairs for microbiome profiling across a food chain from soils to humans within the One Health framework. . 2019; ():843144.
Chicago/Turabian StyleWasimuddin Wasimuddin; Klaus Schlaeppi; Francesca Ronchi; Stephen L Leib; Matthias Erb; Alban Ramette. 2019. "Evaluation of primer pairs for microbiome profiling across a food chain from soils to humans within the One Health framework." , no. : 843144.