Cause Of Acute Gastroenteritis Research Articles

Quercetin, a flavonoid, combats rotavirus infection by deactivating rotavirus-induced pro-survival NF-κB pathway

Rotavirus (RV) is the leading cause of acute gastroenteritis and watery diarrhea in children under 5 years accounting for high morbidity and mortality in countries with poor socioeconomic status. Although vaccination against RV has been implemented in more than 100 countries, the efficacy of vaccine has been challenged in low-income settings. The lack of any FDA-approved drug against RV is an additional concern regarding the treatment associated with rotavirus-induced infantile death. With the purpose for the discovery of anti-RV therapeutics, we assessed anti-rotaviral potential of quercetin, a well-characterized antioxidant flavonoid. In vitro study revealed that quercetin treatment resulted in diminished production of RV-SA11 (simian strain) viral particles in a concentration-dependent manner as estimated by the plaque assay. Consistent with this result, Western blot analysis also revealed reduced synthesis of viral protein in quercetin-treated RV-SA11-infected MA104 cells compared to vehicle (DMSO) treated controls. Not surprisingly, infection of other RV strains A5-13 (bovine strain) and Wa (Human strain) was also found to be abridged in the presence of quercetin compared to DMSO. The IC50 of quercetin against three RV strains ranges between 2.79 and 4.36 Mm, and S.I. index is greater than 45. Concurrent to the in vitro results, in vivo study in mice model also demonstrated reduced expression of viral proteins and viral titer in the small intestine of quercetin-treated infected mice compared to vehicle-treated infected mice. Furthermore, the result suggested anti-rotaviral activity of quercetin to be interferon-independent. Mechanistic study revealed that the antiviral action of quercetin is co-related with the inhibition of RV-induced early activation of NF-κB pathway. Overall, this study delineates the strong anti-RV potential of quercetin and also proposes it as future therapeutics against rotaviral diarrhea.

Differentiation between Wild-Type Group A Rotaviruses and Vaccine Strains in Cases of Suspected Horizontal Transmission and Adverse Events Following Vaccination.

Human group A rotaviruses (RVA) are important enteric pathogens, as they are a leading cause of acute gastroenteritis (AGE) in children worldwide. Since 2013, the German Standing Committee on vaccination recommended the routine rotavirus vaccination for infants in Germany. While vaccination has significantly decreased RVA cases and worldwide mortality, in some cases, infants can develop acute gastroenteritis as an adverse reaction after immunization with an attenuated live vaccine. Pediatricians, as well as clinicians and diagnostic laboratories, contacted the Consultant Laboratory for Rotaviruses and inquired whether cases of RVA-positive AGE after vaccination were associated with vaccine or with wild-type RVA strains. A testing algorithm based on distinguishing PCRs and confirmative sequencing was designed, tested, and applied. Diagnostic samples from 68 vaccinated children and six cases where horizontal transmission was suspected were investigated in this study. Using a combination of real-time PCR, fragment-length analysis of amplicons from multiplex PCRs and confirmative sequencing, vaccine-like virus was detected in 46 samples and wild-type RVA was detected in 6 samples. Three mixed infections of vaccine and wild-type RVA were detectable, no RVA genome was found in 19 samples. High viral loads (>1.0 × 107 copies/g stool) were measured in most RVA-positive samples. Furthermore, information on co-infections with other AGE pathogens in the vaccinated study population was of interest. A commercial multiplex PCR and in-house PCRs revealed three co-infections of vaccinated infants with bacteria (two samples with Clostridioides difficile and one sample with enteropathogenic E. coli) and six co-infections with norovirus in a subset of the samples. Human astrovirus was detected in one sample, with suspected horizontal transmission. The cases of suspected horizontal transmission of vaccine RVA strains could not be confirmed, as they either involved wild-type RVA or were RVA negative. This study shows that RVA-positive AGE after vaccination is not necessarily associated with the vaccine strain and provides a reliable workflow to distinguish RVA vaccine strains from wild-type strains.

Rotavirus and Norovirus Infections in Children Under 5 Years Old with Acute Gastroenteritis in Southwestern China, 2018–2020

ObjectiveRotaviruses and noroviruses are important causes of acute gastroenteritis in children. While previous studies in China have mainly focused on rotavirus, we investigated the incidence of norovirus in addition to rotavirus in Southwestern China.MethodsFrom January 2018 to December 2020, cases of rotavirus or norovirus infections among children under five ages with acute gastroenteritis were evaluated retrospectively.ResultsThe detection rate of rotavirus was 24.5% (27,237/111,070) and norovirus was 26.1% (4649/17,797). Among 17,113 cases submitted for dual testing of both rotavirus and norovirus, mixed rotavirus/norovirus infections were detected in 5.0% (859/17,113) of cases. While there was no difference in norovirus incidence in outpatient compared to hospitalized cases, rotavirus was detected two times more in outpatients compared to hospitalized cases (26.6% vs.13.6%; P < 0.001). Both rotavirus and norovirus infections peaked in children aged 12–18 months seeking medical care with acute gastroenteritis (35.6% rotavirus cases; 8439/23,728 and 32.5% norovirus cases; 1660/5107). Rotavirus infections were frequent between December and March of each year while norovirus was detected earlier from October to December. Our results showed significant correlation between virus detection and environmental factors such as average monthly temperature but not relative humidity. In addition, we observed a reduction in the detection rates of rotavirus and norovirus at the beginning of the SARS-CoV-2 pandemic in 2020.ConclusionOur results indicate that rotavirus and norovirus are still important viral agents in pediatric acute gastroenteritis in Southwestern China.

Epidemiological portrait of noroviral infection

Introduction. Noroviruses are a common cause of acute gastroenteritis with significant public health burden, including outbreaks in health facilities, closed and semi-closed settings. This study aims to present a global overview and trends in noroviral epidemiology and highlights the important biological properties of norovirus. Materials and methods. The bibliographic databases (PubMed and Russian Science Citation Index) were searched based on the keyword “norovirus” (in English and Russian languages respectively) without restrictions and 338 papers were retrieved. Results and Discussion. Human noroviruses are highly genetically diverse and evolve rapidly, evading the host's immune response. In addition to being highly contagious, the lack of a robust cell culture system complicates vaccine development for noroviral infection prevention. This highlights the importance of surveillance and infection control measures, for efficient use of available healthcare resources for maximizing health benefits. Common preventive measures include providing the public with safe water and food (i.e. decontamination), improvement of hand hygiene, early detection, and isolation of infected individuals. Current surveillance techniques include sentinel surveillance, molecular surveillance, disease modeling, and prediction. Further investigations in the field of norovirus prevention and control and its economics are needed, since some studies demonstrate inconsistent results (i.e. effectiveness of hand sanitizers). Conclusion. Noroviral infections represent a significant public health burden and current surveillance techniques require further improvement in terms of sensitivity and accuracy. There is a need to push research in the field of prevention and control measures (safety of water and food supply, early isolation of infected patients, sufficient hand hygiene) and their effectiveness.

Human enteric adenovirus F40/41 as a major cause of acute gastroenteritis in children in Brazil, 2018 to 2020

Human adenovirus (HAdV) types F40/41 have long been recognized as major viral agents of acute gastroenteritis (AGE) in children. Despite this, studies on HAdV molecular epidemiology are sparse, and their real impact is likely under-estimated. Thus, our goal was to investigate HAdV incidence, enteric and non-enteric types circulation, co-detections with rotavirus and norovirus and DNA shedding in stool samples from inpatients and outpatients from eleven Brazilian states. During the three-year study, 1012 AGE stool samples were analysed by TaqMan-based qPCR, to detect and quantify HAdV. Positive samples were genotyped by partial sequencing of the hexon gene followed by phylogenetic analysis. Co-detections were accessed by screening for rotavirus and norovirus. Overall, we detected HAdV in 24.5% of single-detected samples (n = 248), with a prevalence of type F41 (35.8%). We observed a higher incidence in children between 6 to 24 months, without marked seasonality. Additionally, we observed a statistically higher median viral load among single-detections between enteric and non-enteric types and a significantly lower HAdV viral load compared to rotavirus and norovirus in co-detections (p < 0.0001). Our study contributes to the knowledge of HAdV epidemiology and reinforces the need for the inclusion of enteric types F40/41 in molecular surveillance programs.

Antigenic Site Immunodominance Redirection Following Repeat Variant Exposure.

Human norovirus is a leading cause of acute gastroenteritis, driven by antigenic variants within the GII.4 genotype. Antibody responses to GII.4 vaccination in adults are shaped by immune memory. How children without extensive immune memory will respond to GII.4 vaccination has not been reported. Here, we characterized the GII.4 neutralizing antibody (nAb) landscape following natural infection using a surrogate assay and antigenic site chimera virus-like particles. We demonstrate that the nAb landscape changes with age and virus exposure. Among sites A, C, and G, nAbs from first infections are focused on sites A and C. As immunity develops with age/exposure, site A is supplemented with antibodies that bridge site A to sites C and G. Cross-site nAbs continue to develop into adulthood, accompanied by an increase in nAb to site G. Continued exposure to GII.4 2012 Sydney correlated with a shift to co-dominance of sites A and G. Furthermore, site G nAbs correlated with the broadening of nAb titer across antigenically divergent variants. These data describe fundamental steps in the development of immunity to GII.4 over a lifetime, and illustrate how the antigenicity of one pandemic variant could influence the pandemic potential of another variant through the redirection of immunodominant epitopes.

Natural extracts, honey, and propolis as human norovirus inhibitors

Norovirus is the most important cause of acute gastroenteritis, yet there are still no antivirals, vaccines, or treatments available. Several studies have shown that norovirus-specific monoclonal antibodies, Nanobodies, and natural extracts might function as inhibitors. Therefore, the objective of this study was to determine the antiviral potential of additional natural extracts, honeys, and propolis samples. Norovirus GII.4 and GII.10 virus-like particles (VLPs) were treated with different natural samples and analyzed for their ability to block VLP binding to histo-blood group antigens (HBGAs), which are important norovirus co-factors. Of the 21 natural samples screened, date syrup and one propolis sample showed promising blocking potential. Dynamic light scattering indicated that VLPs treated with the date syrup and propolis caused particle aggregation, which was confirmed using electron microscopy. Several honey samples also showed weaker HBGA blocking potential. Taken together, our results found that natural samples might function as norovirus inhibitors.

Whole genome sequence of an uncommon G9P[4] species A rotavirus containing DS-1-like (genotype 2) genes in Japan

Species A rotaviruses (RVAs) have been recognized as one of the leading causes of acute gastroenteritis in humans worldwide. Here, the complete coding sequences of 11 RNA segments of an uncommon G9P[4] RVA strain, which was detected in feces of a diarrheal child in Japan, were determined by next-generation sequencing technology. Its genomic constellation, VP7-VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5, was determined as G9-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2. This work reports the complete coding sequences of a G9P[4] RVA strain containing DS-1-like (genotype 2) genes that was isolated in Japan in 2013.

Atomic Structure of the Human Sapovirus Capsid Reveals a Unique Capsid Protein Conformation in Caliciviruses.

ABSTRACTSapovirus (SaV) is a member of the Caliciviridae family, which causes acute gastroenteritis in humans and animals. Human sapoviruses (HuSaVs) are genetically and antigenically diverse, but the lack of a viral replication system and structural information has hampered the development of vaccines and therapeutics. Here, we successfully produced a self-assembled virus-like particle (VLP) from the HuSaV GI.6 VP1 protein, and the first atomic structure was determined using single-particle cryo-electron microscopy (cryo-EM) at a 2.9-Å resolution. The atomic model of the VP1 protein revealed a unique capsid protein conformation in caliciviruses. All N-terminal arms in the A, B, and C subunits interacted with adjacent shell domains after extending through their subunits. The roof of the arched VP1 dimer was formed between the P2 subdomains by the interconnected β strands and loops, and its buried surface was minimized compared to those of other caliciviruses. Four hypervariable regions that are potentially involved in the antigenic diversity of SaV formed extensive clusters on top of the P domain. Potential receptor binding regions implied by tissue culture mutants of porcine SaV were also located near these hypervariable clusters. Conserved sequence motifs of the VP1 protein, “PPG” and “GWS,” may stabilize the inner capsid shell and the outer protruding domain, respectively. These findings will provide the structural basis for the medical treatment of HuSaV infections and facilitate the development of vaccines, antivirals, and diagnostic systems.IMPORTANCE SaV and norovirus, belonging to the Caliciviridae family, are common causes of acute gastroenteritis in humans and animals. SaV and norovirus infections are public health problems in all age groups, which occur explosively and sporadically worldwide. HuSaV is genetically and antigenically diverse and is currently classified into 4 genogroups consisting of 18 genotypes based on the sequence similarity of the VP1 proteins. Despite these detailed genetic analyses, the lack of structural information on viral capsids has become a problem for the development of vaccines or antiviral drugs. The 2.9-Å atomic model of the HuSaV GI.6 VLP presented here not only revealed the location of the amino acid residues involved in immune responses and potential receptor binding sites but also provided essential information for the design of stable constructs needed for the development of vaccines and antivirals.

Evaluation of a New Norovirus Genogroups GI and GII In Vitro Molecular Diagnostic Assay Using Clinical Specimens Collected from Acute Diarrheal Outbreaks.

Norovirus is a leading cause of acute gastroenteritis (AGE) in Taiwan. To improve diagnosis as part of laboratory surveillance, AGE surveillance was conducted using a new fluorescent probe hydrolysis-based insulated isothermal polymerase chain reaction (PCR) method, the POCKIT system, and the results were compared with those obtained from conventional methods. A total of 119 clinical stool samples from reported AGE outbreaks were collected for this study. From 83 real-time reverse transcription PCR (rRT-PCR) norovirus-positive cases, the POCKIT system identified 78 with a sensitivity of 90.3% in GI genogroup and 96.7% in GII genogroup. The specificity for both GI and GII genogroups was 100%. Overall, the POCKIT system is faster and easier to use than the conventional rRT-PCR method, and because of its high sensitivity and specificity, this system is a promising alternative for the detection of norovirus in patients with AGE, and would benefit public health laboratories for near real-time surveillance of AGE epidemic outbreaks.

Studies on Detection, Prevalence and Molecular Characterization of Avian Rotavirus

Rotaviruses are the foremost cause of acute gastroenteritis. Outbreaks of rotavirus infection can lead to significant economic losses in livestock and poultry industry. Group A and D rotavirus are the predominant enteric viruses groups in birds. Limited prevalence studies are available to date in India. Poultry samples consisting of 20 fecal samples and 80 intestinal content samples were screened by VP6 gene based diagnostic PCR for AvRVA and AvRVD. All samples were negative for group A rotavirus. Five fecal samples and 22 intestinal samples were positive for AvRVD-VP6 gene giving an amplicon of 185 bp giving a prevalence of 27%. Positive samples screened for VP4, VP7, NSP4 and NSP5 genes of AvRVD were negative for VP4, VP7 and NSP4 but six samples were positive for NSP5 gene giving an amplicon of 652 bp size. Cloning and sequencing showed 99.4 to 100% sequence similarity among all six isolates at nucleotide level. The percent nucleotide similarity with chicken RVD isolates was in the range 78.2-85.1%. All isolates showed highest similarity of 85% with chicken isolate from South Korea followed by Germany (81.5%) and Australia (78.2%). The phylogenetic analysis exhibited all six isolates clustered together in a separate clade with isolates from Australia, Germany and South Korea.

Rotavirus-Induced Lipid Droplet Biogenesis Is Critical for Virus Replication.

A variety of pathogens, including viruses, bacteria and parasites, target cellular lipid droplets for their replication. Rotaviruses (RVs) infect the villous epithelium of the small intestine and are a major cause of acute gastroenteritis in infants and young children worldwide. RVs induce and require lipid droplets for the formation of viroplasms, sites of virus genome replication, and nascent particle assembly. Here we review the role of lipid droplets in RV replication. Inhibitors of fatty acid synthesis or chemicals that interfere with lipid droplet homeostasis decrease the number and size of viroplasms and the yield of infectious virus. We used a genetically engineered RV, delayed in viroplasm assembly, to show an early interaction of RV nonstructural protein NSP2 and the lipid droplet-associated protein phospho-PLIN1. The interaction between NSP2 and phospho-PLIN1 suggests that we have identified part of the mechanism of RV-induced lipid droplet formation. These studies demonstrate that RV is an excellent model to dissect the cellular process of lipid droplet formation and to determine how RV induces and usurps lipid droplet biogenesis to form viroplasm/lipid droplets for virus replication.

Experience with the use of the drug cycloferon in the treatment of rotaviral infection in children

Introduction. Rotavirus infection is the leading cause of acute gastroenteritis in young children. Due to the lack of etiotropic treatment of viral gastroenteritis, the interest of scientists and practitioners in the use of antiviral drugs is increasing. Studies of domestic authors have proven that the low molecular weight interferon inductor – meglumine acridonacetate has antiviral, immunoregulatory and anti-inflammatory activity.Aim. Evaluation of the efficacy and safety of the antiviral drug meglumine acridonacenate in the treatment of acute gastroenteritis of rotavirus etiology in children aged 4–7 years in a hospital setting.Materials and methods. A prospective analysis of cases of treatment with meglumine acridonacetate for moderately severe rotavirus gastroenteritis in preschool children (n = 29, group I) was carried out. The comparison group consisted of patients receiving standard therapy (n = 31, group II). The presence of rotavirus infection was confirmed by the detection of the pathogen antigen in the feces. Meglumine acridonacetate was prescribed according to the scheme, parenterally, every other day.Results and discussion. The effectiveness of therapy with an antiviral drug on the 3rd day of treatment of moderately severe rotavirus gastroenteritis was 79.3% (p &lt; 0.05). The elimination of the main clinical symptoms of the disease was noted on days 2–3: a decrease in the symptoms of intoxication, fever, a significant decrease in the duration of vomiting and diarrhea (p &lt; 0.05), a reduction in the pathogen elimination period by 2.67 days (p &lt; 0.01), meglumine acridonacetate was well tolerated, no side effects of the drug were detected.Conclusions. Meglumine acridonacetate can be recommended for the complex treatment of moderate rotavirus infection from the first days of the disease.

Knowledge, Awareness, and Prevention of Norovirus Infection among Kindergarten Parents in Chengdu, China.

Human noroviruses (HuNoVs) are a leading cause of acute gastroenteritis among children in China. However, little is known about parents’ knowledge of HuNoV infection and their understanding of how to prevent and control the disease. Therefore, we performed an exploratory survey to assess the level of knowledge of HuNoV infection among kindergarten parents. A cross-sectional survey was conducted by investigating kindergarteners’ parents through an online self-administered questionnaire between October 2020 and November 2020 in Chengdu, China. A total of 771 questionnaires were received with valid responses, and 81.97% of respondents had heard about NoV before. Among parents who had heard about HuNoV before, they had a poor awareness of incubation period, duration, and high-incidence seasons of HuNoV infection. The respondents also had a low-level awareness of how to clean the places contaminated by vomitus or stool. The multiple-regression analysis confirmed that factors associated with good knowledge regarding HuNoV infection were level of education, occupation, history of infection, and HuNoV learning experience. The most expected approach to learn about HuNoV among parents was the internet, followed by knowledge training in kindergartens, community information, and television. This is the first study to assess kindergarten parents’ knowledge and awareness of HuNoV infection. The survey results provide insights that would help in developing effective strategies and educational materials to prevent and control the disease.

Review of Over 15 Years Postmarketing Safety Surveillance Spontaneous Data for the Human Rotavirus Vaccine (Rotarix) on Intussusception

IntroductionRotavirus (RV) is the most common cause of acute gastroenteritis in children <5 years of age worldwide, and vaccination reduces the disease burden. Evidence from postmarketing surveillance studies suggested an increased risk of intussusception (IS) in infants post-RV vaccination. An overall positive benefit–risk balance for the human RV vaccine (HRV) Rotarix (GlaxoSmithKline [GSK], Belgium) has been established and recent findings indicate an indirect effect of reduced IS over the long term.ObjectiveThe aim of this study was to discuss spontaneous data from the GSK worldwide safety database on IS post-Rotarix administration.MethodsThe database was reviewed for all spontaneous IS cases from 2004 to 2020. Additionally, an observed versus expected (O/E) analysis was done for adverse events attributed to IS. Data were reviewed as overall worldwide and stratified by region (Europe/USA/Japan) and dose.ResultsA male predominance of IS patients was observed, consistent with earlier reports. The most frequently reported events in confirmed IS cases (Brighton Collaboration Working Group [BCWG] level 1) with time to onset ≤ 30 days post-vaccination were vomiting (55.8%), haematochezia (47.2%), and crying (21.1%). The observations from the IS spontaneous cases review and results of the O/E analysis are consistent with the known IS safety profile of RV vaccines: a transient increased incidence of IS post-vaccination (primarily in Europe/Japan/worldwide), mostly within 7 days postdose 1.ConclusionSince the outcomes of early IS management are favourable over delayed management, healthcare professionals should inform parents about the importance of seeking immediate medical advice in case of unusual behaviour of the vaccinated infant. GSK continues to monitor the IS risk post-Rotarix administration through routine pharmacovigilance activities.Graphic abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s40264-021-01141-4.

Effects of Epigallocatechin-3-Gallate-Palmitate (EC16) on In Vitro Norovirus Infection.

Norovirus is the world-leading cause of acute gastroenteritis associated with severe symptoms and deaths. However, vaccines against norovirus are currently not available, and medications that specifically target human norovirus infection are still under development. The current study evaluated the virucidal and antiviral activities of epigallocatechin-3-gallate-palmitate (EC16), a compound derived from green tea polyphenols, against murine norovirus (MNV S99, a surrogate for human norovirus). Initially, formulation suitability tests were conducted to compare EGCG (epigallocatechin-3-gallate), EC16 and tea polyphenol-palmitate in alcohol solution and hand hygiene formulations. The virucidal activity of EC16 was then tested in hand sanitizer gel and hand sanitizer foam formulations using a TCID50 time-kill suspension assay. In vitro treatment and prevention tests were performed using a 1-hour incubation of EC16 or EGCG with RAW264.7 cells, either post-infection or pre-infection with MNV. Statistical analysis employed two-tailed student t test (alpha=0.05). Unlike EC16, both EGCG and tea polyphenol-palmitate showed auto-oxidation (color change) and precipitation in alcohol solution and hand hygiene formulations, and thus less suitable for potential hand hygiene product or new drug development. The time-kill suspension test results demonstrated that EC16 in both sanitizer gel and foam formulations reduced MNV by >99.99% (>log10 4) after 60 sec direct contact. One-hour incubation of EC16 with RAW264.7 cells either before or after MNV infection (i.e., without direct contact with MNV), resulted in >99% (>log10 2) reduction of MNV infectivity. EC16 is a candidate for use as a virucidal and antiviral compound to prevent and treat norovirus infection, with potential to be developed as a new drug against norovirus, pending in vivo and clinical tests.

The Role of Host Glycobiology and Gut Microbiota in Rotavirus and Norovirus Infection, an Update.

Rotavirus (RV) and norovirus (NoV) are the leading causes of acute gastroenteritis (AGE) worldwide. Several studies have demonstrated that histo-blood group antigens (HBGAs) have a role in NoV and RV infections since their presence on the gut epithelial surfaces is essential for the susceptibility to many NoV and RV genotypes. Polymorphisms in genes that code for enzymes required for HBGAs synthesis lead to secretor or non-secretor and Lewis positive or Lewis negative individuals. While secretor individuals appear to be more susceptible to RV infections, regarding NoVs infections, there are too many discrepancies that prevent the ability to draw conclusions. A second factor that influences enteric viral infections is the gut microbiota of the host. In vitro and animal studies have determined that the gut microbiota limits, but in some cases enhances enteric viral infection. The ways that microbiota can enhance NoV or RV infection include virion stabilization and promotion of virus attachment to host cells, whereas experiments with microbiota-depleted and germ-free animals point to immunoregulation as the mechanism by which the microbiota restrict infection. Human trials with live, attenuated RV vaccines and analysis of the microbiota in responder and non-responder individuals also allowed the identification of bacterial taxa linked to vaccine efficacy. As more information is gained on the complex relationships that are established between the host (glycobiology and immune system), the gut microbiota and intestinal viruses, new avenues will open for the development of novel anti-NoV and anti-RV therapies.

Emergence of Multiple Novel Inter-Genotype Recombinant Strains of Human Astroviruses Detected in Pediatric Patients With Acute Gastroenteritis in Thailand.

Objective: Human astrovirus (HAstV) is recognized as an important cause of acute gastroenteritis in children. Recombination between different genotypes of HAstV can contribute to diversity and evolution of the virus. This study aimed to investigate the emergence of HAstV recombinant strains in pediatric patients hospitalized with acute gastroenteritis in Chiang Mai, Thailand, spanning 2011–2020.Methods: A total of 92 archival HAstV strains collected from pediatric patients with acute gastroenteritis during 2011–2020 were further characterized to identify the recombinant strains. The ORF1b and ORF2 junction region of each strain was amplified and sequenced. The obtained sequences were analyzed in comparison with the reference sequences retrieved from GenBank database. Their genotypes were assigned using MEGA X software based on the partial ORF1b (RdRp) and ORF2 (capsid) regions, and the recombination breakpoints of recombinant strains were determined by SimPlot and RDP4 analyses.Results: Five inter-genotype recombinant strains with three recombination patterns of ORF1b/ORF2 of classic HAstV, HAstV8/HAstV1, HAstV8/HAstV3, and HAstV3/HAstV2, were detected. The recombination breakpoints of all strains were located at the 3′-end region of ORF1b close to the ORF1b/ORF2 junction.Conclusion: Several novel inter-genotype recombinant strains of classic HAstV genotypes were detected in pediatric patients with acute gastroenteritis in Chiang Mai, Thailand, during the period of 10 years from 2011 to 2020.

Norovirus strains among children aged 0-18 years hospitalized with acute gastroenteritis in Estonia 2015-2016.

Norovirus (NoV) is the leading cause of acute gastroenteritis (AGE) in many countries that have introduced universal rotavirus mass vaccination. This is the first study to report data on NoV strains in Estonia. We recruited 2249 children aged 0-18 years hospitalized for AGE in Estonian hospitals from February 1, 2015 to August 31, 2016. Norovirus gastroenteritis (NoVGE) was diagnosed in 14.5% (n = 325) cases. Stool sample for RNA extraction and genotyping was available in 86% (n = 280) of NoVGE cases (2015, n = 91; 2016, n = 189). Dominant capsid types detected in 75% (n = 210) samples were, GII.4 (63.8%, n = 134), GII.3 (15.2%, n = 32), GII.17 (6.7%, n = 14), and GII.6 (5.2%, n = 11). Prevailing RNA polymerase types found in 77% (n = 215) samples were GII.P31 (51.1%, n = 110), GII.P21 (17.7%, n = 38), GII.P4 (11.2%, n = 24), and GII.P7 (6.5%, n = 14). Both regions were typeable for 67% (n = 189) of samples. Most prevalent strains were GII.4Sydney_2012[P31] (48.7%, n = 92), GII.3[P21] (15.3%, n = 29), GII.4Sydney_2012[P4] (5.8%, n = 11) and GII.17[P17] (5.8%, n = 11). Simpson's diversity index showed a significant difference between the age groups 1-4 and 5-9 years: D 0.64 (95% confidence interval [CI]: 0.55-0.73) versus 0.83 (95% CI: 0.81-0.86), respectively (p = 0.03). An accurate understanding of NoV strain diversity is important for control and preventive measures, especially in the postrotavirus vaccine era.

Genetic diversity of rotavirus strains circulating in Norway before and after the introduction of rotavirus vaccination in children.

Globally, rotavirus (RV) is the leading cause of acute gastroenteritis (AGE) in young children under 5 years of age. Implementation of RV vaccination is expected to result in fewer cases of RV in the target population, but it is unknown if this also results in vaccine-induced virus strain replacement. Rotarix, a monovalent vaccine based on G1P[8] RV, was introduced in Norway in the children's immunization program in September 2014. The main aim of this study was to describe the diversity of RV circulating pre and post introduction of the RV vaccine in Norway and investigate changes in genotype distribution during the first 4 years after implementation. A total of 1108 samples were collected from children under 5 years enrolled with AGE from five large hospitals in Norway and were analyzed for RV by enzyme immunoassay (EIA). All positive results were genotyped by multiplex semi-nested reverse transcription PCR for identification of G and P types. In total, 487 of the 1108 (44%) samples, collected from the enrolled children, were positive for RV by EIA method which were further genotyped. G1P[8] was found to be the most common type of RV pre and post RV vaccine implementation followed by G9P[8]. There were neither geographical nor temporal differences in genotype dominance. Also, no apparent changes were shown in the genotype distribution in the postvaccine era for years from 2015 to 2018. In 21.4% of the cases, vaccine strains were detected. Continuous RV genotype surveillance is vital for assessing the effectiveness of a vaccine program and monitoring for any emergence of vaccine-escape strains. Genotyping is also necessary to detect vaccine strains to avoid reporting false-positive cases of active RV infection in newly vaccinated cases.