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      Epidemiological, Molecular, and Clinical Features of Norovirus Infections among Pediatric Patients in Qatar

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          Abstract

          Background: Norovirus (NoV) is recognized as the second most important etiological agent leading to acute gastroenteritis globally. In order to determine the burden and characteristics of NoV infections in children in Qatar, profiling of circulating genotypes and their correlation with demographics and clinical manifestations were evaluated. Methods: A total of 177 NoV-positive fecal samples were collected from children suffering from acute gastroenteritis (AGE) during two-year period between June 2016 and June 2018. The age of the subjects ranged between 3 months and 12 years (median of 15 months). Genotyping was performed by amplifying and sequencing parts of viral VP1 and RNA-dependent RNA polymerase (RdRp) regions. Phylogenetic analysis and evolutionary relationships were performed using MEGA7.0. Fisher’s exact test was used to run statistical analysis for the clinical and demographical characteristics of circulating strains. Results: Overall, NoV infections were relatively higher in males than females with a ratio of 1.3:1 ( p = 0.0073). Most of the NoV infections were reported in children between 1 and 3 years old (49.7%), followed by those <1 and >3 years of age (41.2% and 9.1%, respectively). NoV infections occurred throughout the year, with a noticeable increase in summer (36.6%) and drop in winter (25.4%). Nearly all (98.8%) NoV-infected children were positive for genogroup II (GII) compared to only two samples (1.2%) being positive for genogroup I (GI): GI.3 and GI.4. NoV genotype GII.4 (62.2%), GII.2 (15.8%), and GII.3 (13.5%) were predominant in our study. The detected strains shared >98% sequence homology with emerging recombinant strain of GII.P16-GII.4/RUS/Novosibirsk/2017 (MG892929), GII.P16-GII.4 Sydney/2012 (KY887601), GII.4 Sydney/2012, recombinant GII.P4 New Orleans /2009/GII.4 Sydney 2012 (MG585810.1), and the emerging strain GII.P16-GII.2 CHN/2017 (MH321823). Severe clinical illness (vesikari score >10) was reported in children infected with genotypes sharing homology with the above emerging strains. While GII.4 was reported in all age groups, NoV GII.3 infections were higher in children <1 year of age. Both genogroups (GII.4 and GII.3) in addition to GII.2 reported higher incidence in Qatari subjects compared to other nationalities ( p = 0.034). Conclusion: This is the first report about NoV molecular epidemiology in Qatar. The most detected NoV strain was genogroup GII, which is the dominant genotype in the Middle East region. Further, we report GII.4, GII.2, and GII.3 as the most predominant NoV genotypes in our study. Moreover, disease severity scores were higher among children genotyped with genogroup GI (GI.4) and genogroup GII (GII.4, GII.2, GII.3, GII.6, and GII.7).

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          Increase in viral gastroenteritis outbreaks in Europe and epidemic spread of new norovirus variant.

          Highly publicised outbreaks of norovirus gastroenteritis in hospitals in the UK and Ireland and cruise ships in the USA sparked speculation about whether this reported activity was unusual. We analysed data collected through a collaborative research and surveillance network of viral gastroenteritis in ten European countries (England and Wales were analysed as one region). We compiled data on total number of outbreaks by month, and compared genetic sequences from the isolated viruses. Data were compared with historic data from a systematic retrospective review of surveillance systems and with a central database of viral sequences. Three regions (England and Wales, Germany, and the Netherlands) had sustained epidemiological and viral characterisation data from 1995 to 2002. In all three, we noted a striking increase in norovirus outbreaks in 2002 that coincided with the detection and emergence of a new predominant norovirus variant of genogroup II4, which had a consistent mutation in the polymerase gene. Eight of nine regions had an annual peak in 2002 and the new genogroup II4 variant was detected in nine countries. Also, the detection of the new variant preceded an atypical spring and summer peak of outbreaks in three countries. Our data from ten European countries show a striking increase and unusual seasonal pattern of norovirus gastroenteritis in 2002 that occurred concurrently with the emergence of a novel genetic variant. In addition to showing the added value of an international network for viral gastroenteritis outbreaks, these observations raise questions about the biological properties of the variant and the mechanisms for its rapid dissemination.
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            Epidemiologic and molecular trends of "Norwalk-like viruses" associated with outbreaks of gastroenteritis in the United States.

            Between July 1997 and June 2000, fecal specimens from 284 outbreaks of nonbacterial gastroenteritis were submitted to the Centers for Disease Control and Prevention for testing for "Norwalk-like viruses" (NLVs). Specimens were examined by reverse-transcription polymerase chain reaction and direct electron microscopy for the presence of NLVs. Adequate descriptive data were available from 233 of the outbreaks, and, of these, 217 (93%) were positive for NLVs. Restaurants and events with catered food were the most common settings, and contaminated food was the most common mode of transmission. Genogroup II (GII) strains were the predominant type (73%), with genogroup I strains causing 26% of all NLV-positive outbreaks. Certain GII clusters (GII/1,4,j) were more commonly associated with outbreaks in nursing home settings than with outbreaks in other settings. Strain diversity was great: one potential new sequence cluster was implicated in multiple outbreaks, and strains belonging to a tentative new genogroup were identified.
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              A Systematic Review and Meta-Analysis of the Global Seasonality of Norovirus

              Background Noroviruses are the most common cause of acute gastroenteritis across all ages worldwide. These pathogens are generally understood to exhibit a wintertime seasonality, though a systematic assessment of seasonal patterns has not been conducted in the era of modern diagnostics. Methods We conducted a systematic review of the Pubmed Medline database for articles published between 1997 and 2011 to identify and extract data from articles reporting on monthly counts of norovirus. We conducted a descriptive analysis to document seasonal patterns of norovirus disease, and we also constructed multivariate linear models to identify factors associated with the strength of norovirus seasonality. Results The searched identified 293 unique articles, yielding 38 case and 29 outbreak data series. Within these data series, 52.7% of cases and 41.2% of outbreaks occurred in winter months, and 78.9% of cases and 71.0% of outbreaks occurred in cool months. Both case and outbreak studies showed an earlier peak in season-year 2002-03, but not in season-year 2006-07, years when new genogroup II type 4 variants emerged. For outbreaks, norovirus season strength was positively associated with average rainfall in the wettest month, and inversely associated with crude birth rate in both bivariate and multivariate analyses. For cases, none of the covariates examined was associated with season strength. When case and outbreaks were combined, average rainfall in the wettest month was positively associated with season strength. Conclusions Norovirus is a wintertime phenomenon, at least in the temperate northern hemisphere where most data are available. Our results point to possible associations of season strength with rain in the wettest month and crude birth rate.
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                Author and article information

                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                29 April 2019
                May 2019
                : 11
                : 5
                : 400
                Affiliations
                [1 ]Biomedical Research Center, Qatar University, Doha 2713, Qatar; shilu.mathew@ 123456qu.edu.qa (S.M.); msmatti@ 123456qu.edu.qa (M.K.S.); aaja@ 123456qu.edu.qa (A.A.A.T.)
                [2 ]Pediatric Emergency Center, Hamad Medical Corporation, Doha 3050, Qatar; dkmaa@ 123456hotmail.com
                [3 ]Department of Experimental Pathology, Microbiology, and Immunology, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon; hz34@ 123456aub.edu.lb
                Author notes
                [* ]Correspondence: hyassine@ 123456qu.edu.qa
                Author information
                https://orcid.org/0000-0002-7621-0130
                https://orcid.org/0000-0003-3807-6409
                https://orcid.org/0000-0001-7592-2788
                Article
                viruses-11-00400
                10.3390/v11050400
                6563317
                31035642
                997f7323-85e1-4ab3-9009-f854f83f00f3
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 08 April 2019
                : 27 April 2019
                Categories
                Article

                Microbiology & Virology
                norovirus,genotyping,age-specific,severity
                Microbiology & Virology
                norovirus, genotyping, age-specific, severity

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