Association between Norovirus and Rotavirus Infection and Histo-Blood Group Antigen Types in Vietnamese Children

Norovirus and rotavirus are the two most important causes of acute gastroenteritis in children worldwide. Both norovirus and rotavirus recognize human histo-blood group antigens (HBGAs), and multiple binding patterns for HBGAs have been reported. To explore the role of HBGAs in host susceptibility to norovirus and rotavirus, we conducted a cross-sectional study in children hospitalized with diarrhea in northern Vietnam from September 2010 through September 2012. Of 260 children with paired stool and saliva samples, 158 (61%) were classified as HBGA secretors (Le^a−b+), 31 (12%) were nonsecretors (Le^a+b−), and 71 (27%) were partial secretors (Le^a+b+). Norovirus was detected in 50 patients (19%), with viral genotypes GII.3 (n = 28) and GII.4 (n = 22) being the most common. All children infected with norovirus strains of genotype GII.4 were either HBGA secretors or partial secretors. Of the 28 GII.3 cases, 12 involved HBGA secretors, 11 partial secretors, and 5 nonsecretors. A total of 85 children tested positive for rotavirus, 74 of whom were infected with genotype P[8], 5 with P[4], and 6 with P[6]; all were HBGA secretors or partial secretors. This is the first epidemiological study demonstrating in a population that HBGA phenotype is a key susceptibility factor for both norovirus and rotavirus infections in children.     

Sequential evolution of genotype GII.4 norovirus variants causing gastroenteritis outbreaks from 2001 to 2006 in Eastern Spain

Noroviruses are the most common cause of outbreaks of viral gastroenteritis worldwide. Norovirus outbreaks were surveyed in Catalonia and the region of Valencia (Eastern Spain) between January 2001 and December 2006 as part of the European Union funded network "Food-borne viruses in Europe". During this time the etiology and epidemiological features of 194 outbreaks of acute non-bacterial gastroenteritis were investigated and norovirus was identified as causing 169 (87.1%) of them. Molecular epidemiology of viral strains was studied by RT-PCR and sequencing part of the RNA polymerase gene in ORF1 from 153 outbreak strains. The most commonly identified norovirus genotype was GII.4 (71.9% of the characterized outbreak strains), which is also the predominant genotype worldwide. During this survey five genetic variants of GII.4 genotype have been sequentially detected and identified as 1996, 2002, 2004, 2006a, and 2006b variants. The transition from one variant to a new one always took place over a short period of time, and thereafter the replacement of strains circulating previously was observed. These new GII.4 variants may have arisen as a consequence of viral evasion from the host immune responses, although apparently there is a lack of long-term immunity after norovirus infections.     

Norovirus contamination found in oysters worldwide

Noroviruses (Norwalk-like viruses) are recognized as major causes of acute gastroenteritis worldwide. Outbreaks of norovirus gastroenteritis are often associated with consumption of oysters. In this study, oysters imported into Hong Kong from 11 countries over a 3-year period were screened by RT-PCR. Overall, 53 out of 507 (10.5%) samples were positive for norovirus-RNA, and a wide variety of strains were found. Two novel genetic clusters were detected, which could indicate novel human or animal norovirus strains. However, whether these two new clusters are of human or animal origin is not known. Thirteen outbreaks, in which oysters were implicated as the source of infection were investigated: Norovirus RNA sequences could be detected in oysters from six outbreaks, but only in one outbreak the strains isolated from patients and oysters matched (>98% homology). Therefore, RT-PCR was of use in detecting norovirus contamination of oysters implicated in an outbreak, but was less useful in demonstrating an actual molecular epidemiological link with human cases. It was shown that contamination by noroviruses could be demonstrated in oysters worldwide, and therefore oysters may serve as an important vehicle for introducing novel norovirus strains.     

Genetic drift of norovirus genotype GII-4 in seven consecutive epidemic seasons in Hungary.

BACKGROUND: Noroviruses are common pathogens in human gastroenteritis outbreaks worldwide. They belong to a genetically diverse group of RNA viruses with multiple genogroups (G) and genotypes. Genotype GII-4 norovirus (Lordsdale) is the predominant agent in epidemics. OBJECTIVES: To investigate the genetic variation in GII-4 strains isolated during seven epidemic seasons in Hungary from November 2000 to June 2007. STUDY DESIGN: Using the prospective epidemiological surveillance of norovirus outbreaks in Hungary, GII-4 strains were selected for further genetic analysis. After phylogenetic analysis, RNA-polymerase (open reading frame 1; ORF1), capsid (ORF2) and the ORF1/ORF2 junction were analysed by RT-PCR and sequencing. RESULTS: Three hundred and seventy-seven (76.8%) of 491 confirmed norovirus outbreaks were caused by genotype GII-4. GII-4 was the predominant genotype in six of the seven epidemic seasons. Four main GII-4 variants--epidemic point mutants--(GII-4-2000, GII-4-2002, GII-4-2004 and GII-4-2006b) were detected, with each variant predominating in two consecutive epidemic seasons. CONCLUSIONS: Genotype GII-4 was confirmed as the predominant genetic type in epidemic norovirus seasons in Hungary. Genetic drift successfully promotes the re-emergence of GII-4 variants in the population. The elevated number of norovirus outbreaks in the population predicts the emergence of new GII-4 genetic variants as part of an international epidemic.     

Molecular epidemiology of noroviruses associated with acute sporadic gastroenteritis in children: Global distribution of genogroups,genotypes and GII.4 variants

Noroviruses are a leading cause of epidemic and sporadic acute gastroenteritis worldwide. The development of sensitive molecular diagnostic techniques has revolutionized our understanding of norovirus epidemiology over the past two decades, but norovirus strain types associated with sporadic gastroenteritis remain poorly described. Therefore, we conducted a systematic review of studies performed after 2000 to clarify the genotypic distribution of noroviruses in children (≤18 years of age) with sporadic acute gastroenteritis. Genogroup GII norovirus was the most prevalent, accounting for 96% of all sporadic infections. GII.4 was the most prevalent genotype, accounting for 70% of the capsid genotypes and 60% of the polymerase genotypes, followed by the capsid genotype GII.3 (16%) and the polymerase genotype GII.b (14%). The most common ORF1/ORF2 inter-genotype recombinants were GII.b, GII.12, and GII.4 polymerase genotypes combined with the capsid genotype GII.3, accounting for 19% of all genotyped strains. The distribution of GII.4 variants over the last decade was dominated by successive circulation of GII.4/2002, GII.4/2004, GII.4/2006b, and GII.4/2008 with GII.4/2006b continuing to date. Genotypes GII.4 and GII.3 have predominated in children during the past decade; this is most notable in the global emergence of GII.4 variant noroviruses. As the burden of rotavirus disease decreases following the introduction of childhood immunization programs, the relative importance of norovirus in the etiology of acute childhood gastroenteritis will likely increase. In order for a successful norovirus vaccine to be developed, it should provide immunity against strains with capsid genotypes GII.4 and GII.3.     

Norovirus infections in children under 5?years of age hospitalized due to the acute viral gastroenteritis in northeastern Poland

The primary aim of this study was to evaluate the frequency and seasonality of norovirus infection in hospitalized Polish children under 5 years of age, and a secondary aim was to compare the clinical severity of norovirus and rotavirus disease. The prospective surveillance study was carried out from July 2009 through June 2010. Stool samples from 242 children hospitalized due to acute viral gastroenteritis were tested for rotavirus group A and adenovirus with commercial immunochromatographic test and for norovirus with EIA assay. Single norovirus infection was found in 35/242 (14.5%) patients and in a further 5 (2.1%) children as co-infection with rotavirus. Overall, norovirus was detected in 16.5% of stool specimens. Norovirus infections tended to peak from October to November and again from February to March. In autumn months and in February, the proportion of norovirus gastroenteritis cases was equal or even surpassed those of rotavirus origin. Both norovirus and rotavirus infections most commonly affected children between 12 and 23 months of age. The low-grade or no fever was significantly more common in children infected with norovirus (94.3%) compared to rotavirus cases (52.9%). Overall, norovirus gastroenteritis was less severe than rotavirus disease with regard to 20-point severity scale (p < 0.05). Noroviruses have emerged as a relevant cause of acute gastroenteritis in Polish children. There is a great need for introducing routine norovirus testing of hospitalized children with gastroenteritis.     

Norovirus genotypes causing gastroenteritis outbreaks in Finland 1998-2002.

BACKGROUND: Outbreak investigation methods for enteric viruses were improved in 1990s when gene amplification techniques were established in viral laboratories. OBJECTIVES: The objective of the study was to determine the causative agents for Finnish viral gastroenteritis outbreaks. Our aim was also to further characterise the norovirus strains, reveal the temporal occurrence of norovirus (NV) genotypes and to study some epidemiological aspects concerning the outbreaks. STUDY DESIGN: A total of 416 Finnish viral gastroenteritis outbreaks that occurred during 5 years (1998-2002), excluding those among hospitalised children, were investigated for enteric viruses. Stool samples were screened by electron microscopy as well as analyzed by specific noro- and astrovirus RT-PCR tests. Amplicon sequence analysis was used to find out norovirus genotypes. RESULTS: Noroviruses caused 252 (60.6%) of the outbreaks; other viruses, astro- or rotavirus, caused four epidemics. Norovirus epidemics occurred in all kinds of settings, most often in hospitals (30.6%) and in restaurants and canteens (14.3%). Both NV genogroups were found every year, but NV GGII outbreaks always outnumbered those of GGI. All but one outbreak at hospitals and nursing homes were of genotype GII. Polymerase sequence analysis revealed a variety of NV genotypes; six GI and at least eight GII genotypes. The GI.3 Birmingham-like and GII.4 Bristol-like genotype appeared every year, whereas the other types were circulating for shorter periods or sporadically. During the study period the genotypes GII.4 (Bristol), GII.1 (Hawaii), an emerging genotype GIIb, and a new variant of GII.4 predominated in that order. Indication for rapid genetic changes in the genotype GII.4 was also noticed. CONCLUSIONS: Noroviruses were the most prevalent causative agents in the outbreaks. Many NV genotypes were circulating, and a shift in the predominant genotypes was evident between epidemic seasons.     

Detection and molecular characterisation of rotavirus and norovirus infections in Jordanian children with acute gastroenteritis

Rotavirus and norovirus are globally important causes of paediatric gastroenteritis, but no studies of viral genotypes have been reported from Jordan. We undertook a molecular epidemiological study in children hospitalised with acute gastroenteritis in Jordan between January 2006 and December 2007. Among 368 children, rotavirus and norovirus infections were detected in 49.5% and 11.4% of children, respectively. Rotavirus genotypes P[8],G1 (56%), P[4],G2 (14%) and P[8],G9 (13%) were most commonly identified, consistent with results of global rotavirus surveillance studies. Norovirus GII.3 was the most commonly detected genotype, followed by GII.4, contrasting with most studies in which GII.4 has predominated.     

Detection of a novel recombinant strain of norovirus in an African-descendant community from the Amazon region of Brazil in 2008

Noroviruses, a major cause of acute gastroenteritis outbreaks worldwide, are constantly evolving. This ability is reflected in the speed and efficiency with which these viruses spread and remain in the human population. The present study reports the detection of a novel recombination event among norovirus genotypes in Brazil in 2008. A strain detected in a stool sample from a child with norovirus-associated gastroenteritis, residing in an African-descendant semi-closed community of Pará State, was characterized as a novel intergenotype recombinant, GII.7/GII.20, as determined by partial sequencing and SimPlot analysis.     

Epidemiology of norovirus gastroenteritis in hospitalized children under five years old in western China, 2015–2019

ObjectivesNorovirus is associated with one-fifth of all gastroenteritis cases, but basic epidemiological data is lacking, especially in developing countries. As long-term surveillance on norovirus gastroenteritis is scarce in western China, this study aims to update the epidemiological knowledge of norovirus gastroenteritis and to characterize the genotypes of norovirus strains.MethodsStool samples were collected from hospitalized children under 5 years old with gastroenteritis in Chengdu, China. All samples were tested for norovirus as well as rotavirus, sapovirus, enteric adenovirus, and astrovirus by real-time RT-PCR. RdRp and VP1 genes were sequenced in norovirus-positive samples to investigate viral phylogenies.ResultsOf the 1181 samples collected from 2015 to 2019, 242 (20.5%) were positive for norovirus.Among norovirus-positive cases, 65 cases had co-infection with another virus; norovirus/enteric adenovirus was most frequently detected (50.8%, 33/65). The highest positive rate was observed in children aged 13–18 months (23.7%, 68/287). Norovirus infection peaked in autumn (36.6%, 91/249), followed by summer (20.3%, 70/345). Pearson correlation analysis showed significant correlation between the norovirus-positive rate and humidity (r = 0.773, P < 0.05). GII.4 Sydney 2012 [P31] (48.5%, 79/163) and GII.3 [P12] (35.6%, 58/163) were the dominant norovirus strains.ConclusionsNorovirus has become one of the most common causes of viral gastroenteritis in children under 5 years old in western China. Continuous monitoring is imperative for predicting the emergence of new epidemic strains and for current vaccine development.     

Enteric viruses in wastewaters: an interesting approach to evaluate the potential impact of rotavirus vaccination on viral circulation

Rotavirus and norovirus are the leading causes of acute gastroenteritis worldwide. Both viruses share features such as low infectious dose, high stool concentration and prolonged survival in the environment, including water. However, they differ in several aspects, reflecting potential differences in their interactive capacities with the environment and host. This work, which is a 13-month prospective study in a developing country with high rotavirus vaccine coverage demonstrated a high (44%) PCR detection of norovirus in 84 wastewater samples compared with a relatively low (11%) detection of rotavirus. These results suggest that rotavirus circulation may be positively affected by vaccination and support the use of enteric viral detection in wastewaters as a useful tool to measure the impact of specific interventions.     

Genetic characterization of rotavirus subtypes in Pakistan-first report of G12 genotype from Pakistan under WHO-Eastern Mediterranean region

Rotaviruses are among the major causes of gastroenteritis and diarrhea among children in developed as well as the developing countries. The rapidly evolving strain prevalence and circulation have resulted in the emergence of novel strains over the period worldwide. The introduction of G12 prototype in 1987 from Philippines and subsequently re-emergence among most of the Asian countries along with USA and Europe has provoked new research horizons to address the global distribution of rotavirus serotypes. These newly emerging subtypes and their sustenance among the population have posed tremendous challenge to the development of an effectual vaccine with heterotypic protective efficacy. In Pakistan, no data is available regarding the prevalent rotavirus serotypes; therefore, this is the first study to report the prevalence of G12 strain in Pakistan in hospitalized children with diarrhea addressing a dire need of further large-scale epidemiological surveys to resolve the underlying rotavirus isolates in both the hospitalized and the community neonatal and child population before formulating the vaccine introduction policies in the country's routine immunization program.     

Prevalence of norovirus GII-4 antibodies in Finnish children

Noroviruses (NoVs) are the second most common cause of viral gastroenteritis after rotavirus in children. NoV genotype GII-4 has emerged as the major type not only in outbreaks of NoV gastroenteritis but also endemic gastroenteritis among infants and young children worldwide. Using baculovirus-insect cell system virus-like particles (VLPs) of NoV genotype GII-4 and an uncommon genotype GII-12 were produced. These VLPs were used in enzyme-linked immunosorbent assays (ELISA) for detection of NoV-specific immunoglobulin G (IgG) and IgA antibodies in 492 serum specimens from Finnish children 0-14 years of age collected between 2006 and 2008. NoV IgG antibody prevalence was 47.3% in the age group 7-23 months and increased up to 91.2% after the age of 5 years. Avidity of NoV IgG antibodies was low in the primary infections while high avidity antibodies were detected in the recurrent infections of the older children. In GII-4 infections, the homologous antibody response to GII-4 VLPs was stronger than to GII-12 VLPs but cross-reactivity between GII-4 and GII-12 was observed. Binding of GII-4 VLPs to a putative carbohydrate antigen receptor H-type 3 could be blocked by sera from children not infected with NoV during a waterborne outbreak of acute gastroenteritis. Therefore, protection against NoV infection correlated with strong blocking activity.     

High prevalence of enteric viruses associated with acute gastroenteritis in pediatric patients in a low-income area in Vitória,Southeastern Brazil

Acute gastroenteritis (AGE) is a significant cause of child mortality worldwide. In Brazil, despite the reduction in infant mortality achieved in recent years, many children still die because of undiagnosed AGE. The prevalence, viral load, and circulating genotypes of rotavirus A (RVA), human adenovirus (HAdV), and norovirus GII (NoV GII) were investigated in children with AGE during 12 months in Vitoria, Espírito Santo, Southeastern Brazil. Enteric viruses were detected in stool samples, quantified by quantitative polymerase chain reaction, sequenced, and compared phylogenetically. The overall prevalence was 93.3% (125/134). Cases of single infection (41.8%) and mixed infection (51.5%) were observed; in 21.6% of cases, all the three viruses were detected. RVA had the highest number of copies in all infections. Phylogenetic analysis revealed predominantly the presence of RVA genotype G3, followed by G2 and G9. HAdV clustered within subgroup C, but some samples harbored subgroups A, D, or F. All sequenced NoV-positive samples clustered within the prevalent genotype GII.4. The high prevalence of RVA, HAdV, and NoV in diarrheal feces clarifies the etiology of AGE in this population, and the presence of RVA in vaccinated children reinforces the importance of monitoring programs to identify the causes of gastroenteritis and contribute to the reliability of diagnosis.     

Prevalence and molecular epidemiology of noroviruses detected in outbreak and sporadic cases of acute gastroenteritis in Bulgaria

Noroviruses constitute a genetically diverse group of viruses in the Caliciviridae family, and are recognized as an important cause of acute non‐bacterial gastroenteritis worldwide. To date there are no data on the incidence of noroviruses as a cause of gastroenteritis in Bulgaria. Fecal samples from an outbreak, and sporadic cases of diarrhea that occurred between December 2006 and April 2007 were tested for the presence of noroviruses. From a total of 474 stools (341 from sporadic cases and 133 cases from a single outbreak) examined, 72 samples (37 from sporadic cases and 35 from the outbreak) were positive using a norovirus‐specific enzyme immunoassay. Fifty‐nine specimens were confirmed and genotyped by RT‐PCR and sequencing of regions of the RNA‐dependent RNA polymerase and/or capsid. Sequence and phylogenetic analyses of 29 norovirus strains revealed a great diversity of norovirus genotypes among the sporadic cases including: GGII.3, GGII.4/2006a, GGII.4/2006b, GGII.20, and GGII.Karachi. A single norovirus genotype (GGII.4/2006b) was identified as the causative agent of the outbreak. This first investigation on the prevalence and molecular epidemiology of noroviruses demonstrates the significant role of these viruses as etiologic agents in acute gastroenteritis in Bulgaria. J. Med. Virol. 80:2161–2168, 2008. © 2008 Wiley‐Liss, Inc.     

Characterization of norovirus strains in Australian children from 2006 to 2008: prevalence of recombinant strains

Noroviruses are highly infectious and are the most common cause of gastroenteritis outbreaks. Genotype II.4 strains have been the dominant type identified in adults, however the genotype distribution in children is less clearly defined. This study aimed to detect and genotype norovirus strains infecting children hospitalized with acute gastroenteritis in Melbourne, Australia from 2006 to 2008. Stool samples were collected from 272 children admitted to the Royal Children's Hospital, Melbourne, Australia, with non-rotavirus acute gastroenteritis between April 2006 and December 2008. Using RT-PCR, norovirus was detected in 36% of samples. Strains were genetically characterized via analysis of regions from both the capsid gene and the RNA dependent RNA polymerase (RdRp) gene, to investigate genotype distribution and incidence of recombination. Typing based on the capsid gene (n = 70) detected GII.4 (49%) and GII.3 (46%) as the most predominant genotypes. Strains with a GII.4 capsid were usually assigned a GII.4 RdRp, whereas most strains identified as GII.3 based on capsid typing were assigned a GIIb RdRp (71%). The GII.3/GIIb represent recombinant strains. Sequence analysis of the putative recombination breakpoint was performed for three representative suspected recombinants: GII.3/GIIb (n = 2) and GII.3/GII.12 (n = 1). Recombination analysis confirmed these strains as recombinants and identified putative breakpoints adjacent to the ORF1/ORF2 junction. This study highlights the importance of norovirus infection as a cause of pediatric gastroenteritis. It also reinforces the high circulation of recombinant strains causing disease in children, particularly the GII.3/GIIb strain.