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  1. Article ; Online: Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?

    Miriam Cebey-López / Jethro Herberg / Jacobo Pardo-Seco / Alberto Gómez-Carballa / Nazareth Martinón-Torres / Antonio Salas / José María Martinón-Sánchez / Antonio Justicia / Irene Rivero-Calle / Edward Sumner / Colin Fink / Federico Martinón-Torres

    PLoS ONE, Vol 11, Iss 4, p e

    2016  Volume 0152481

    Abstract: Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear.To correlate the presence of viral co-infection with clinical phenotype in children admitted ... ...

    Abstract Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear.To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI).We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011-2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK.204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort.The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective role.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Viral Co-Infections in Pediatric Patients Hospitalized with Lower Tract Acute Respiratory Infections.

    Miriam Cebey-López / Jethro Herberg / Jacobo Pardo-Seco / Alberto Gómez-Carballa / Nazareth Martinón-Torres / Antonio Salas / José María Martinón-Sánchez / Stuart Gormley / Edward Sumner / Colin Fink / Federico Martinón-Torres / GENDRES network

    PLoS ONE, Vol 10, Iss 9, p e

    2015  Volume 0136526

    Abstract: Molecular techniques can often reveal a broader range of pathogens in respiratory infections. We aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (LT-ARI), using ...

    Abstract Molecular techniques can often reveal a broader range of pathogens in respiratory infections. We aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (LT-ARI), using molecular techniques.A nested polymerase chain reaction approach was used to detect Influenza (A, B), metapneumovirus, respiratory syncytial virus (RSV), parainfluenza (1-4), rhinovirus, adenovirus (A-F), bocavirus and coronaviruses (NL63, 229E, OC43) in respiratory samples of children with acute respiratory infection prospectively admitted to any of the GENDRES network hospitals between 2011-2013. The results were corroborated in an independent cohort collected in the UK.A total of 204 and 97 nasopharyngeal samples were collected in the GENDRES and UK cohorts, respectively. In both cohorts, RSV was the most frequent pathogen (52.9% and 36.1% of the cohorts, respectively). Co-infection with multiple viruses was found in 92 samples (45.1%) and 29 samples (29.9%), respectively; this was most frequent in the 12-24 months age group. The most frequently observed co-infection patterns were RSV-Rhinovirus (23 patients, 11.3%, GENDRES cohort) and RSV-bocavirus / bocavirus-influenza (5 patients, 5.2%, UK cohort).The presence of more than one virus in pediatric patients admitted to hospital with LT-ARI is very frequent and seems to peak at 12-24 months of age. The clinical significance of these findings is unclear but should warrant further analysis.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Bacteremia in Children Hospitalized with Respiratory Syncytial Virus Infection.

    Miriam Cebey-López / Jacobo Pardo-Seco / Alberto Gómez-Carballa / Nazareth Martinón-Torres / José María Martinón-Sánchez / Antonio Justicia-Grande / Irene Rivero-Calle / Elli Pinnock / Antonio Salas / Colin Fink / Federico Martinón-Torres / GENDRES network

    PLoS ONE, Vol 11, Iss 2, p e

    2016  Volume 0146599

    Abstract: The risk of bacteremia is considered low in children with acute bronchiolitis. However the rate of occult bacteremia in infants with RSV infection is not well established. The aim was to determine the actual rate and predictive factors of bacteremia in ... ...

    Abstract The risk of bacteremia is considered low in children with acute bronchiolitis. However the rate of occult bacteremia in infants with RSV infection is not well established. The aim was to determine the actual rate and predictive factors of bacteremia in children admitted to hospital due to confirmed RSV acute respiratory illness (ARI), using both conventional culture and molecular techniques.A prospective multicenter study (GENDRES-network) was conducted between 2011-2013 in children under the age of two admitted to hospital because of an ARI. Among those RSV-positive, bacterial presence in blood was assessed using PCR for Meningococcus, Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus, in addition to conventional cultures.66 children with positive RSV respiratory illness were included. In 10.6% patients, bacterial presence was detected: H. influenzae (n = 4) and S. pneumoniae (n = 2). In those patients with bacteremia, there was a previous suspicion of bacterial superinfection and had received empirical antibiotic treatment 6 out of 7 (85.7%) patients. There were significant differences in terms of severity between children with positive bacterial PCR and those with negative results: PICU admission (100% vs. 50%, P-value = 0.015); respiratory support necessity (100% vs. 18.6%, P-value < 0.001); Wood-Downes score (mean = 8.7 vs. 4.8 points, P-value < 0.001); GENVIP scale (mean = 17 vs. 10.1, P-value < 0.001); and length of hospitalization (mean = 12.1 vs. 7.5 days, P-value = 0.007).Bacteremia is not frequent in infants hospitalized with RSV respiratory infection, however, it should be considered in the most severe cases.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?

    Miriam Cebey-López / Jethro Herberg / Jacobo Pardo-Seco / Alberto Gómez-Carballa / Nazareth Martinón-Torres / Antonio Salas / José María Martinón-Sánchez / Antonio Justicia / Irene Rivero-Calle / Edward Sumner / Colin Fink / Federico Martinón-Torres / GENDRES network

    PLoS ONE, Vol 11, Iss 4, p e

    2016  Volume 0152481

    Abstract: BACKGROUND:Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. OBJECTIVES:To correlate the presence of viral co-infection with clinical ... ...

    Abstract BACKGROUND:Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. OBJECTIVES:To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI). METHODS:We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011-2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK. RESULTS:204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort. CONCLUSION:The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective role.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

    Lisa Borghini / Eileen Png / Alexander Binder / Victoria J. Wright / Ellie Pinnock / Ronald de Groot / Jan Hazelzet / Marieke Emonts / Michiel Van der Flier / Luregn J. Schlapbach / Suzanne Anderson / Fatou Secka / Antonio Salas / Colin Fink / Enitan D. Carrol / Andrew J. Pollard / Lachlan J. Coin / Taco W. Kuijpers / Federico Martinon-Torres /
    Werner Zenz / Michael Levin / Martin L. Hibberd / Sonia Davila / EUCLIDS consortium

    Scientific Reports, Vol 9, Iss 1, Pp 1-

    2019  Volume 15

    Abstract: Abstract Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more ... ...

    Abstract Abstract Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA – a NF-kB subunit, master regulator of the response to infection – under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2019-05-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Plasma lipid profiles discriminate bacterial from viral infection in febrile children

    Xinzhu Wang / Ruud Nijman / Stephane Camuzeaux / Caroline Sands / Heather Jackson / Myrsini Kaforou / Marieke Emonts / Jethro A. Herberg / Ian Maconochie / Enitan D. Carrol / Stephane C. Paulus / Werner Zenz / Michiel Van der Flier / Ronald de Groot / Federico Martinon-Torres / Luregn J. Schlapbach / Andrew J. Pollard / Colin Fink / Taco T. Kuijpers /
    Suzanne Anderson / Matthew R. Lewis / Michael Levin / Myra McClure / EUCLIDS consortium

    Scientific Reports, Vol 9, Iss 1, Pp 1-

    2019  Volume 13

    Abstract: Abstract Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The ‘ ... ...

    Abstract Abstract Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The ‘omics’ approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics.
    Keywords Medicine ; R ; Science ; Q
    Subject code 572
    Language English
    Publishing date 2019-11-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens

    Esther Willems / Jolein Gloerich / Anouk Suppers / Michiel van der Flier / Lambert P. van den Heuvel / Nicole van de Kar / Ria H.L.A. Philipsen / Maurice van Dael / Myrsini Kaforou / Victoria J. Wright / Jethro A. Herberg / Federico Martinon Torres / Michael Levin / Ronald de Groot / Alain J. van Gool / Dirk J. Lefeber / Hans J.C.T. Wessels / Marien I. de Jonge / Amina Abdulla /
    Christoph Aebi / Koen van Aerde / Rachel Agbeko / Philipp Agyeman / Umberto D’alessandro / Ladan Ali / Wynand Alkema / Karen Allen / Fernando Álvez González / Suzanne Anderson / Imran Ansari / Tasnim Araf / Tanja Avramoska / Bryan Baas / Natalija Bahovec / Cristina Balo Farto / Anda Balode / A.M. Barendregt / Ruth Barral-Arca / María Barreiro Castro / Arta Bārzdiņa / David Bath / Sebastian Bauchinger / Lucas Baumard / Hinrich Baumgart / Frances Baxter / Ashley Bell / Kathryn Bell / Xabier Bello / Evangelos Bellos / Martin Benesch / Mirian Ben García / Joshua Bennet / Christoph Berger / J.M. van den Berg / Sara Bernhard-Stirnemann / Sagida Bibi / Christoph Bidlingmaier / Alexander Binder / Vera Binder / Kalifa Bojang / Dorine M. Borensztajn / Ulrich von Both / Karen Brengel-Pesce / Bryan van den Broek / Judith Buschbeck / Leo Calvo-Bado / Sandra Carnota / Enitan D. Carrol / Michael J. Carter / Miriam Cebey-López / Samba Ceesay / Astrid Ceolotto / Adora Chan / Elizabeth Cocklin / Kalvin Collings / Stephen Crulley / Aubrey Cunnington / María José Curras-Tuala / Katharina Danhauser / Saffiatou Darboe / Sarah Darnell / Tisham De / Dārta Deksne / Kirsty Devine / Juan Emmanuel Dewez / Julia Dudley / Carlos Durán Suárez / Ernst Eber / Irini Eleftheriou / Marieke Emonts / Daniel Fabian / Tobias Feuchtinger / Katy Fidler / Colin Fink / A.M. van Furth / Rachel Galassini / Siegfried Gallistl / Luisa García Vicente / Dace Gardovska / J. Geissler / G.P.J.M. Gerrits / Eric Giannoni / Ilona van der Giessen / Alberto Gómez-Carballa / Jose Gómez Rial / Gunther Gores / Dagne Grāvele / Matthias Griese / Ilze Grope / Meeru Gurung / L. de Haan / Nikolaus Haas / Dominic Habgood-Coote / Nienke N. Hagedoorn / Harald Haidl / Shea Hamilton / Almuthe Hauer / J. Heidema / Ulrich Heininger / Stefanie Henriet / Jethro Herberg / Clive Hoggart / Susanne Hösele / Sara Hourmat / Christa Hude / Martijn Huijnen / Heather Jackson / Rebecca Jennings / Joanne Johnston / Ilse Jongerius / Rikke Jorgensen / Christian Kahlert / Rama Kandasamy / Matthias Kappler / Julia Keil / Markus Keldorfer / Dominic F. Kell / Eunjung Kim / Sharon King / Lieke Kloosterhuis / Daniela S. Kohlfürst / Benno Kohlmaier / Laura Kolberg / Mojca Kolnik / Larissa Krenn / Taco Kuijpers / M. van der Kuip / Pilar Leboráns Iglesias / Simon Leigh / Manuel Leitner / M. van Leur / Emma Lim / Naomi Lin / Ching-Chuan Liu / Sabine Löffler / Eberhard Lurz / Ian Maconochie / Christine Mackerness / François Mallet / Federico Martinón-Torres / Antonis Marmarinos / Alex Martin / Mike Martin / José María Martinón Sánchez / Nazareth Martinón-Torres / Paul McAlinden / Anne McDonnell / Sam McDonald / C.J. Miedema / Anija Meiere / Stephanie Menikou / G. van Mierlo / Alec Miners / Ravi Mistry / Henriëtte A. Moll / Marine Mommert / Belén Mosquera Pérez / David R. Murdoch / Sobia Mustafa / Giancarlo Natalucci / C. Neeleman / Karen Newall / Samuel Nichols / Tobias Niedrist / Anita Niederer-Loher / Ruud Nijman / Ieva Nokalna / Urzula Nora Urbāne / Gudrun Nordberg / C.C. Obihara / Daniel O'Connor / Wilma Oosthoek / Veronika Osterman / Alexandre Pachot / D. Pajkrt / Jacobo Pardo-Seco / Stéphane Paulus / Jana Pavāre / Ivonne Pena Paz / Salina Persand / Andreas Pfleger / Klaus Pfurtscheller / Ria Philipsen / Ailsa Pickering / Benjamin Pierce / Heidemarie Pilch / Lidia Piñeiro Rodríguez / Sara Pischedda / Tina Plankar Srovin / Marko Pokorn / Andrew J. Pollard / Lena Pölz / Klara M. Posfay-Barbe / Petra Prunk / Zanda Pučuka / Glorija Rajic / Aqeela Rashid / Lorenzo Redondo-Collazo / Christa Relly / Irene Rivero Calle / Sara Rey Vázquez / Mathew Rhodes / Vivien Richmond / Thomas Riedel / Anna RocaIsatou Sarr / Siegfried Rödl / Carmen Rodríguez-Tenreiro / Sam Romaine / Emily Rowlands / Miguel Sadiki Ora / Manfred G. Sagmeister / Momodou Saidykhan / Antonio Salas / Luregn J. Schlapbach / D. Schonenberg / Fatou Secka / Katrīna Selecka / Sonia Serén Fernández / Cristina Serén Trasorras / Priyen Shah / Ching-Fen Shen / Shrijana Shrestha / Aleksandra Sidorova / Andrea Skrabl-Baumgartner / Giselle D’Souza / Matthias Sperl / Evelien Sprenkeler / Nina A. Schweintzger / Laura Stampfer / Molly Stevens / Martin Stocker / Volker Strenger / Dace Svile / Kelly Syggelou / Maria Tambouratzi / Chantal Tan / Emma Tavliavini / Evelyn Thomson / Stephen Thorson / Holger Till / G.A. Tramper-Stranders / Andreas Trobisch / Maria Tsolia / Effua Usuf / Lucille Valentine / Clementien L. Vermont / Marisol Vilas Iglesias / Katarina Vincek / Marie Voice / Gabriella de Vries / Diane Wallia / Shih-Min Wang / Clare Wilson / Amanda Wood / Phil Woodsford / Victoria Wright / Marietta Xagorari / Shunmay Yeung / Joany Zachariasse / Dace Zavadska / Syed M.A. Zaman / Judith Zandstra / Werner Zenz / Christoph Zurl / Manuela Zwerenz

    iScience, Vol 26, Iss 8, Pp 107257- (2023)

    2023  

    Abstract: Summary: Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an ... ...

    Abstract Summary: Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection.
    Keywords Health sciences ; Glycobiology ; Immunology ; Glycomics ; Science ; Q
    Subject code 572
    Language English
    Publishing date 2023-08-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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