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      Molecular epidemiology and clinical characteristics of norovirus gastroenteritis with seizures in children in Taiwan, 2006–2015

      research-article
      , MD a , , MD, PhD b , , MD, PhD c , , MD b , , MD d , , MD, PhD e ,
      Medicine
      Wolters Kluwer Health
      children, gastroenteritis, norovirus, seizures, Taiwan

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          Abstract

          This study examined the characteristics of norovirus (NoV) gastroenteritis associated with convulsions in children and its molecular epidemiology. From July 2006 through December 2015, NoV infection was confirmed by the genome detection using reverse transcriptase polymerase chain reaction. Viral genotyping with strain validation was achieved using sequence analyses with Basic Local Alignment Search Tool genome identification. The patients’ clinical features were assessed retrospectively, focusing on convulsive disorders. The diagnosis of encephalitis followed the International Encephalitis Consortium. Seizures occurred in 52 (20.9%) of 249 NoV infections. GII.4 Den_Haag_2006b (n = 22, 42.3%) and GII.4 Sydney 2012 (n = 10, 19.2%) were major variants correlated with convulsions. Patient with convulsions tend to have GII.4 genotype infection ( P < .001), short vomiting (≤2 days) ( P < .001), and no fever ( P = .002). Compared to GII.4 Den_Haag_2006b, the GII.4 Sydney 2012-associated convulsions had similar manifestations except without significant winter preponderance ( P = .049). The NoV infection with convulsions had less febrile course, specific genotype (GII.4) infections, and with shorter symptom of vomiting. Continuous surveillance is important for uncommon disease associated with emerging NoV strain infections. The prevention of NoV diseases requires the development of vaccines targeting highly virulent variants.

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          Most cited references25

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          Major reduction of rotavirus, but not norovirus, gastroenteritis in children seen in hospital after the introduction of RotaTeq vaccine into the National Immunization Programme in Finland

          Universal rotavirus (RV) vaccination is expected to reduce hospitalizations for acute gastroenteritis (GE) of children by eliminating most of severe RVGE, but it does not have any effect on norovirus (NV), the second most common causative agent of GE in children. After the introduction of the RV vaccine into the National Immunization Programme (NIP) of Finland in 2009, we conducted a prospective 2-year survey of GE in children seen in Tampere University Hospital either as outpatients or inpatients and compared the results with a similar 2-year survey conducted prior to NIP in the years 2006–2008. Compared with the pre-NIP 2-year period, in 2009–2011, hospitalizations for RVGE were reduced by 76 % and outpatient clinic visits were reduced by 81 %. NVGE showed a slight decreasing trend and accounted for 34 % of all cases of GE seen in hospital in pursuance of RVGE having decreased to 26 % (down from 52 %). In cases admitted to the hospital ward, RV accounted for 28 % and NV accounted for 37 %.The impact of RV vaccination was reflected as a 57 % decrease in all hospital admissions and 62 % decrease in all outpatient clinic visits for GE of any cause. Conclusion: RV vaccination in NIP has led to a major reduction of hospital admissions and clinic visits due to RVGE, but has had no effect on NVGE. After 2 years of NIP, NV has become the leading cause of acute GE in children seen in hospital.
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            Structural basis for the receptor binding specificity of Norwalk virus.

            Noroviruses are positive-sense, single-stranded RNA viruses that cause acute gastroenteritis. They recognize human histo-blood group antigens as receptors in a strain-specific manner. The structures presented here were analyzed in order to elucidate the structural basis for differences in ligand recognition of noroviruses from different genogroups, the prototypic Norwalk virus (NV; GI-1) and VA387 (GII-4), which recognize the same A antigen but differ in that NV is unable to bind to the B antigen. Two forms of the receptor-binding domain of the norovirus coat protein, the P domain and the P polypeptide, that were previously shown to differ in receptor binding and P-particle formation properties were studied. Comparison of the structures of the NV P domain with and without A trisaccharide and the NV P polypeptide revealed no major ligand-induced changes. The 2.3-A cocrystal structure reveals that the A trisaccharide binds to the NV P domain through interactions with the residues Ser377, Asp327, His329, and Ser380 in a mode distinct from that previously reported for the VA387 P-domain-A-trisaccharide complex. Mutational analyses confirm the importance of these residues in NV P-particle binding to native A antigen. The alpha-GalNAc residue unique to the A trisaccharide is buried deeply in the NV binding pocket, unlike in the structures of A and B trisaccharides bound to VA387 P domain, where the alpha-fucose residue forms the most protein contacts. The A-trisaccharide binding mode seen in the NV P domain complex cannot be sterically accommodated in the VA387 P domain.
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              Outbreak of Necrotizing Enterocolitis Caused by Norovirus in a Neonatal Intensive Care Unit

              Objectives To investigate an outbreak of necrotizing enterocolitis (NEC) in a neonatal intensive care unit (NICU) and to identify the etiology, describe illness risk factors, and develop control measures. Study design A retrospective case-control study was performed including newborns with NEC and newborns without NEC, examining demographic factors and exposures to medications, staff members, and procedures before illness. Stool samples from affected newborns were collected and tested for bacteria, parasites, and viruses. Results We confirmed a NEC outbreak in the NICU in January 1998 with 8 cases, including 2 deaths, clustered in time and space. Norovirus-like particles were identified in all available stools from cases; norovirus (NoV) was confirmed with reverse transcriptase polymerase chain reaction in 4 of 6 samples. NEC cases were younger, had lower Apgar scores, and received antibiotics longer than 25 control subjects. Three NICU health care personnel had more contact with cases than control subjects; 1 staff member recalled having gastroenteritis symptoms around the time of the outbreak. Conclusions This report associates NoV with NEC. NoV appeared to precipitate NEC in predisposed infants. Spatial clustering and epidemiologic links between cases and a health care worker with gastroenteritis suggests that NoV should be investigated among the etiologies of NEC outbreaks and that interventions targeted to interruption of NoV transmission should be considered.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                October 2019
                04 October 2019
                : 98
                : 40
                : e17269
                Affiliations
                [a ]Division of Neonatology, Department of Pediatrics, Taipei Medical University Shuang Ho Hospital, New Taipei City
                [b ]Division of Pediatric Neurology, Department of Pediatrics, Taipei Medical University Shuang Ho Hospital, New Taipei City
                [c ]Division of Pediatric Infectious Diseases, Department of Pediatrics, Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan
                [d ]Division of Pediatric Gastroenterology, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan
                [e ]Division of Pediatric Gastroenterology, Department of Pediatrics, Taipei Medical University Shuang Ho Hospital, New Taipei City, Taiwan.
                Author notes
                []Correspondence: Shih Yen Chen, Division of Pediatric Gastroenterology, Department of Pediatrics, Taipei Medical University Shuang Ho Hospital, New Taipei City, Taiwan (e-mail: 18159@ 123456s.tmu.edu.tw ).
                Article
                MD-D-19-01370 17269
                10.1097/MD.0000000000017269
                6783164
                31577718
                bcdc956e-3c46-4707-8871-2f4ac0143716
                Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

                History
                : 16 February 2019
                : 30 July 2019
                : 28 August 2019
                Categories
                6200
                Research Article
                Observational Study
                Custom metadata
                TRUE

                children,gastroenteritis,norovirus,seizures,taiwan
                children, gastroenteritis, norovirus, seizures, taiwan

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