Cause Of Acute Gastroenteritis Research Articles

Rotavirus Vaccine Effectiveness Against Severe Acute Gastroenteritis: 2009-2022.

Rotavirus was the leading cause of acute gastroenteritis among US children until vaccine introduction in 2006, after which, substantial declines in severe rotavirus disease occurred. We evaluated rotavirus vaccine effectiveness (VE) over 13 years (2009-2022). We analyzed data from the New Vaccine Surveillance Network using a test-negative case-control design to estimate rotavirus VE against laboratory-confirmed rotavirus infections among children seeking care for acute gastroenteritis (≥3 diarrhea or ≥1 vomiting episodes within 24 hours) in the emergency department (ED) or hospital. Case-patients and control-patients were children whose stool specimens tested rotavirus positive or negative, respectively, by enzyme immunoassay or polymerase chain reaction assays. VE was calculated as (1-adjusted odds ratio)×100%. Adjusted odds ratios were calculated by multivariable unconditional logistic regression. Among 16 188 enrolled children age 8 to 59 months, 1720 (11%) tested positive for rotavirus. Case-patients were less often vaccinated against rotavirus than control-patients (62% versus 88%). VE for receiving ≥1 dose against rotavirus-associated ED visits or hospitalization was 78% (95% confidence interval [CI] 75%-80%). Stratifying by a modified Vesikari Severity Score, VE was 59% (95% CI 49%-67%), 80% (95% CI 77%-83%), and 94% (95% CI 90%-97%) against mild, moderately severe, and very severe disease, respectively. Rotavirus vaccines conferred protection against common circulating genotypes (G1P[8], G2P[4], G3P[8], G9P[8], and G12[P8]). VE was higher in children <3 years (73% to 88%); protection decreased as age increased. Rotavirus vaccines remain highly effective in preventing ED visits and hospitalizations in US children.

Prevalence and associated risk factors of Cryptosporidium infection in calves and hospitalized humans in Libo Kemkem, North Western Ethiopia.

Cryptosporidium infection is one of the major causes of acute gastroenteritis and diarrhoea caused by a protozoan parasite affecting vertebrates and humans. The disease is prevalent in cases of immunocompromised individuals. Despite the impact of the diseases in calf and hospitalized humans, well-documented studies are not available in the study area. The objectives of this study were to determine the prevalence of Cryptosporidium infection in calves and hospitalized humans and assess the major associated risk factors associated with Cryptosporidium infection in calves and hospitalized humans. A cross-sectional study was conducted from November 2020 to March 2021 on calf and human Cryptosporidium infection in Libo Kemkem District, North West Ethiopia. A total of 193 calves and 122 human stool samples admitted to the hospital were used for this study. Three kebeles were selected purposely, and individual calves were selected using a simple random sampling method. A number of sampled calves were allocated proportionally to the selected kebeles. Human samples were collected using a systematic random sampling method. Faecal and stool samples were examined using a modified Ziehl-Neelsen staining method. The overall prevalence of calf and human Cryptosporidium infection found in this study was 15.5% and 11.5%, respectively. Age of calf, breed, body condition, water source, faecal consistency and hygienic condition were found significantly (p<0.05) associated with Cryptosporidium infection in the calf. Similarly, the source of potable water, immunocompromisation and contact with domestic animals were found to be significantly (p<0.05) associated with Cryptosporidium infection in humans. There was a higher prevalence of Cryptosporidium infection in calves and humans in Libo Kemkem District. Therefore, the implementation of proper prevention methods of zoonotic Cryptosporidium infection between calf and human beings through significant risk factors is mandatory. Furthermore, additional studies to investigate the levels of economic importance of the disease should be conducted.

Epidemiology of Pediatric Astrovirus Gastroenteritis in a Nicaraguan Birth Cohort.

Astrovirus is a leading cause of acute gastroenteritis in children worldwide. However, few prospective studies have analyzed astrovirus in community-dwelling pediatric populations in low- and middle-income countries. We assessed the incidence, risk factors, clinical characteristics, genotypes, viral coinfections, and time distribution of astrovirus gastroenteritis in 443 healthy Nicaraguan children born in 2017 to 2018 who were followed for 36 months. Children were recruited from hospitals and birth records in an economically diverse neighborhood of León city. Astrovirus-positive episodes and genotypes were identified from stool with reverse transcription quantitative polymerase chain reaction and Sanger sequencing. Of 1708 total specimens tested, 80 children (18%) experienced at least 1 astrovirus episode, and 9 experienced repeat episodes, mostly during the rainy season (May-October). Initial astrovirus episodes were not associated with a lowered risk against future episodes. In exploratory analyses, home toilets were associated with a lower risk of future astrovirus episodes (hazard ratio, 0.19; 95% CI, .04-.91). Human astrovirus 5 episodes, representing 15% of all typed episodes, were associated with longer diarrhea and more symptomatic rotavirus coinfections. Astrovirus was a common cause of gastroenteritis in this cohort, and future studies should clarify the role of astrovirus genotype in clinical infection severity.

Rotavirus A Infection Prevalence and Spatio-Temporal Genotype Shift among Under-Five Children in Amhara National Regional State, Ethiopia: A Multi-Center Cross-Sectional Study.

Background: Globally, rotavirus (RV) A (RVA) is the most common cause of severe and sometimes fatal diarrhea in young children. It is also the major cause of acute gastroenteritis among children in Ethiopia. Currently, the WHO has prequalified four RVA vaccines for universal childhood immunization. Ethiopia introduced the monovalent Rotarix vaccine into its national immunization program in 2013. Since then, only a few studies on the burden and genotype distribution of RVA infection post-vaccine introduction have been conducted (mostly at sentinel surveillance sites). Therefore, this study aimed to assess RVA prevalence and genotype distribution among children under five years in Ethiopia (February 2021-December 2022). Methods: This multi-center hospital-based cross-sectional study involved 537 diarrheic children under-five years old. Rotavirus A detection was conducted using a one-step reverse-transcriptase polymerase chain reaction (RT-PCR). Genotyping was conducted by Sanger sequencing of the VP7 (complete) and VP4 (partial) genes. Descriptive analysis and Pearson's chi-squared test were carried out using SPSS version 29. Phylogenetic analysis with 1000 bootstrap replicates was performed using MEGA version 11 software. Statistical significance was set at p < 0.05 for all analyses. Results: The prevalence of RVA infection among diarrheic children was 17.5%. The most prevalent G-types identified were G3 (37%), the previously uncommon G12 (28%), and G1 (20%). The predominant P-types were P[8] (51%), P[6] (29%), and P[4] (14%). The three major G/P combinations observed were G3P[8] (32.8%), G12P[6] (28.4%), and G1P[8] (19.4%). Phylogenetic analysis revealed clustering of Ethiopian strains with the globally reported strains. Many strains exhibited amino acid differences in the VP4 (VP8* domain) and VP7 proteins compared to vaccine strains, potentially affecting virus neutralization. Conclusions: Despite the high RVA vaccination rate, the prevalence of RVA infection remains significant among diarrheic children in Ethiopia. There is an observable shift in circulating RVA genotypes from G1 to G3, alongside the emergence of unusual G/P genotype combinations such as G9P[4]. Many of these circulating RVA strains have shown amino acid substitutions that may allow for neutralization escape. Therefore, further studies are warranted to comprehend the emergence of these unusual RVA strains and the diverse factors influencing the vaccine's diminished effectiveness in developing countries.

Charting the impact of maternal antibodies and repeat exposures on sapovirus immunity in early childhood from a Nicaraguan birth cohort.

Sapovirus is an important cause of acute gastroenteritis in childhood. While vaccines against sapovirus may reduce gastroenteritis burden, a major challenge to their development is a lack of information about natural immunity. We measured sapovirus-specific IgG in serum collected, between 2017 and 2020, of mothers soon after delivery and at 6 time points in Nicaraguan children until 3 years of age (n=112 dyads) using virus-like particles representing three sapovirus genotypes (GI.1, GI.2, GV.1). Sixteen (14.3%) of the 112 children experienced at least one sapovirus gastroenteritis episode, of which GI.1 was the most common genotype. Seroconversion to GI.1 and GI.2 was most common between 5 and 12 months of age, while seroconversion to GV.1 peaked at 18 to 24 months of age. All children who experienced sapovirus GI.1 gastroenteritis seroconverted and developed genotype-specific IgG. The impact of sapovirus exposure on population immunity was determined using antigenic cartography: newborns share their mothers' broadly binding IgG responses, which declined at 5 months of age and then increased as infants experienced natural sapovirus infections. By tracking humoral immunity to sapovirus over the first 3 years of life, this study provides important insights for the design and timing of future pediatric sapovirus vaccines.

The viral trends and genotype diversity of norovirus in the wastewater of Shenzhen, China

Norovirus (NoV) is the primary cause of acute gastroenteritis (AGE) on a global scale. Numerous studies have demonstrated the immense potential of wastewater surveillance in monitoring the prevalence and spread of NoV within communities. This study employed a one-step reverse transcription-quantitative PCR to quantify NoV GI/GII in wastewater samples (n = 2574), which were collected once or twice a week from 38 wastewater treatment plants from March 2023 to February 2024 in Shenzhen. The concentrations of NoV GI and GII ranged from 5.0 × 104 to 1.7 × 106 copies/L and 4.1 × 105 to 4.5 × 106 copies/L, respectively. The concentrations of NoV GII were higher than those of NoV GI. Spearman's correlation analysis revealed a moderate correlation between the concentration of NoV in wastewater and the detection rates of NoV infections in sentinel hospitals. Baseline values were established for NoV concentrations in Shenzhen's wastewater, providing a crucial reference point for implementing early warning systems and nonpharmaceutical interventions to mitigate the impact of potential outbreaks. A total of 24 NoV genotypes were identified in 100 wastewater samples by sequencing. Nine genotypes of NoV GI were detected, with the major genotypes being GI.4 (38.6 %) and GI.3 (21.8 %); Fifteen genotypes of NoV GII were identified, with GII.4 (53.6 %) and GII.17 (26.0 %) being dominant. The trends in the relative abundance of NoV GI/GII were significantly different, and the trends in the relative abundance of NoV GII.4 over time were similar across all districts, suggesting a potential risk of cross-regional spread. Our findings underscore the effectiveness of wastewater surveillance in reflecting population-level NoV infections, capturing the diverse array of NoV genotypes, and utilizing NoV RNA in wastewater as a specific indicator to supplement clinical surveillance data, ultimately enhancing our ability to predict the timing and intensity of NoV epidemics.

Generation of single-round infectious rotavirus with a mutation in the intermediate capsid protein VP6.

Rotavirus causes severe diarrhea in infants. Although live attenuated rotavirus vaccines are available, vaccine-derived infections have been reported, which warrants development of next-generation rotavirus vaccines. A single-round infectious virus is a promising vaccine platform; however, this platform has not been studied extensively in the context of rotavirus. Here, we aimed to develop a single-round infectious rotavirus by impairing the function of the viral intermediate capsid protein VP6. Recombinant rotaviruses harboring mutations in VP6 were rescued using a reverse genetics system. Mutations were targeted at VP6 residues involved in virion assembly. Although the VP6-mutated rotavirus expressed viral proteins, it did not produce progeny virions in wild-type cells; however, the virus did produce progeny virions in VP6-expressing cells. This indicates that the VP6-mutated rotavirus is a single-round infectious rotavirus. Insertion of a foreign gene, and replacement of the VP7 gene segment with that of human rotavirus clinical isolates, was successful. No infectious virions were detected in mice infected with the single-round infectious rotavirus. Immunizing mice with the single-round infectious rotavirus induced neutralizing antibody titers as high as those induced by wild-type rotavirus. Taken together, the data suggest that this single-round infectious rotavirus has potential as a safe and effective rotavirus vaccine. This system is also applicable for generation of safe and orally administrable viral vectors.IMPORTANCERotavirus, a leading cause of acute gastroenteritis in infants, causes an annual estimated 128,500 infant deaths worldwide. Although live attenuated rotavirus vaccines are available, they are replicable and may cause vaccine-derived infections. Thus, development of safe and effective rotavirus vaccine is important. In this study, we report the development of a single-round infectious rotavirus that can replicate only in cells expressing viral VP6 protein. We demonstrated that (1) the single-round infectious rotavirus did not replicate in wild-type cells or in mice; (2) insertion of foreign genes and replacement of the outer capsid gene were possible; and (3) it was as immunogenic as the wild-type virus. Thus, the mutated virus shows promise as a next-generation rotavirus vaccine. The system is also applicable to orally administrable viral vectors, facilitating development of vaccines against other enteric pathogens.

Molecular characterization of rotavirus indicates predominance of G9P[4] genotype among children with acute gastroenteritis: First report after vaccine introduction in Pakistan

AbstractGlobally, Group A rotavirus (RVA) is the leading cause of acute gastroenteritis in children under 5 years old, with Pakistan having the highest rates of RVA‐related morbidity and mortality. The current study aims to determine the genetic diversity of rotavirus and evaluate the impact of Rotarix‐vaccine introduction on disease epidemiology in Pakistan. A total of 4749 children, hospitalized with acute gastroenteritis between 2018 and 2020, were tested at four hospitals in Lahore and Karachi. Of the total, 19.3% (918/4749) cases were tested positive for RVA antigen, with the positivity rate varying annually (2018 = 22.7%, 2019 = 14.4%, 2020 = 20.9%). Among RVA‐positive children, 66.3% were under 1 year of age. Genotyping of 662 enzyme‐linked immuno sorbent assay‐positive samples revealed the predominant genotype as G9P[4] (21.4%), followed by G1P[8] (18.9%), G3P[8] (11.4%), G12P[6] (8.7%), G2P[4] (5.7%), G2P[6] (4.8%), and 10.8% had mixed genotypes. Among vaccinated children, genotypes G9P[4] and G12P[6] were more frequently detected, whereas a decline in G2P[4] was observed. Phylogenetic analysis confirmed the continued circulation of indigenous genotypes detected earlier in the country except G9 and P[6] strains. Our findings highlight the predominance of G9P[4] genotype after the vaccine introduction thus emphasizing continual surveillance to monitor the disease burden, viral diversity, and their impact on control of rotavirus gastroenteritis in children.

Rotavirus NSP2: A Master Orchestrator of Early Viral Particle Assembly.

Rotaviruses (RVs) are 11-segmented, double-stranded (ds) RNA viruses and important causes of acute gastroenteritis in humans and other animal species. Early RV particle assembly is a multi-step process that includes the assortment, packaging and replication of the 11 genome segments in close connection with capsid morphogenesis. This process occurs inside virally induced, cytosolic, membrane-less organelles called viroplasms. While many viral and cellular proteins play roles during early RV assembly, the octameric nonstructural protein 2 (NSP2) has emerged as a master orchestrator of this key stage of the viral replication cycle. NSP2 is critical for viroplasm biogenesis as well as for the selective RNA-RNA interactions that underpin the assortment of 11 viral genome segments. Moreover, NSP2's associated enzymatic activities might serve to maintain nucleotide pools for use during viral genome replication, a process that is concurrent with early particle assembly. The goal of this review article is to summarize the available data about the structures, functions and interactions of RV NSP2 while also drawing attention to important unanswered questions in the field.

Rotavirus strains in children less than 5 years of age: A case control study

BackgroundGlobally, rotavirus A (RV) is a leading cause of acute gastroenteritis (AGE) in young children under 5 years. The main aim of this study was to describe the prevalence of RV in children with and without diarrhea whose age ranged from 3 months to 5 years from two different hospitals of Nepal. We also described the diversity of rotavirus circulating during the pre-vaccination period in Nepal between 2006–2009. Materials and methodsA total of 2400 stool samples collected from children's years with diarrhea (cases, N = 1200) and without diarrhea (controls, N = 1200) were tested for the presence of RV by both enzyme-linked immunosorbent assay and real-time reverse transcription polymerase chain reaction (RT-PCR). All samples positive for RT PCR and/or ELISA were further characterized for G and P genotypes by conventional RT-PCR. ResultsIn total, 500 of the 2398 (20.8 %) samples (424 cases and 76 controls), were positive for RV. The most frequently detected G-types were G12, G1, and G9 and P-types were P[8] and P[6]. The predominant genotypes G12P[6], G12P[8], G1P[8] and G9P[8] were identified in 27.8 %, 24.2 %, 11.8 % and 10.8 % of the samples, respectively. ConclusionThis study observed high prevalence of G12P[6] rotavirus circulating in Nepal before vaccine introduction and they may pose an emerging challenge to current and future vaccine. Therefore, continuous molecular surveillance of circulating genotypes and emerging rotavirus strain should be carried out to better understand the effectiveness of vaccination program.

Antigenic Characterization of Novel Human Norovirus GII.4 Variants San Francisco 2017 and Hong Kong 2019.

Norovirus is a major cause of acute gastroenteritis; GII.4 is the predominant strain in humans. Recently, 2 new GII.4 variants, Hong Kong 2019 and San Francisco 2017, were reported. Characterization using GII.4 monoclonal antibodies and serum demonstrated different antigenic profiles for the new variants compared with historical variants.

Evaluation of a FlpA Glycoconjugate Vaccine with Ten N-Heptasaccharide Glycan Moieties to reduce Campylobacter jejuni Colonisation in Chickens.

Campylobacter is a major cause of acute gastroenteritis in humans, and infections can be followed by inflammatory neuropathies and other sequelae. Handling or consumption of poultry meat is the primary risk factor for human campylobacteriosis, and C. jejuni remains highly prevalent in retail chicken in many countries. Control of Campylobacter in the avian reservoir is expected to limit the incidence of human disease. Toward this aim, we evaluated a glycoconjugate vaccine comprising the fibronectin-binding adhesin FlpA conjugated to up to ten moieties of the conserved N-linked heptasaccharide glycan of C. jejuni or with FlpA alone. The glycan dose significantly exceeded previous trials using FlpA with two N-glycan moieties. Vaccinated birds were challenged with C. jejuni orally or by exposure to seeder-birds colonised by C. jejuni to mimic natural transmission. No protection against caecal colonisation was observed with FlpA or the FlpA glycoconjugate vaccine. FlpA-specific antibody responses were significantly induced in vaccinated birds at the point of challenge relative to mock-vaccinated birds. A slight but significant antibody response to the N-glycan was detected after vaccination with FlpA-10×GT and challenge. As other laboratories have reported protection against Campylobacter with FlpA and glycoconjugate vaccines in chickens, our data indicate that vaccine-mediated immunity may be sensitive to host- or study-specific variables.

Recovery and Quantification of Norovirus in Air Samples from Experimentally Produced Aerosols

Norovirus is the leading cause of acute gastroenteritis in humans across all age groups worldwide. Norovirus-infected patients can produce aerosolized droplets which play a role in gastroenteritis transmission. The study aimed to assess bioaerosol sampling in combination with a virus concentrating procedure to facilitate molecular detection of norovirus genogroup (G) II from experimentally contaminated aerosols. Using a nebulizer within an experimental chamber, aerosols of norovirus GII were generated at known concentrations. Air samples were then collected in both 5 mL and 20 mL water using the SKC BioSampler at a flow rate of 12.5 L/min, 15 min. Subsequently, the virus in collected water was concentrated using speedVac centrifugation and quantified by RT-qPCR. The optimal distances between the nebulizer and the SKC BioSampler yielded high recoveries of the virus for both 5 and 20 mL collections. Following nebulization, norovirus GII RNA was detectable up to 120 min in 5 mL and up to 240 min in 20 mL collection. The concentrations of norovirus GII RNA recovered from air samples in the aerosol chamber ranged from 102 to 105 genome copies/mL, with average recoveries of 25 ± 12% for 5 mL and 22 ± 19% for 20 mL collections. These findings provide quantitative data on norovirus GII in aerosols and introduce a novel virus concentrating method for aerosol collection in water, thus enhancing surveillance of this virus.

Human norovirus cultivation systems and their use in antiviral research.

Human norovirus (HuNoV) is a major cause of acute gastroenteritis and foodborne diseases, affecting all age groups. Despite its clinical needs, no approved antiviral therapies are available. Since the discovery of HuNoV in 1972, studies on anti-norovirals, mechanism of HuNoV infection, viral inactivation, etc., have been hampered by the lack of a robust laboratory-based cultivation system for HuNoV. A recent breakthrough in the development of HuNoV cultivation systems has opened opportunities for researchers to investigate HuNoV biology in the context of de novo HuNoV infections. A tissue stem cell-derived human intestinal organoid/enteroid (HIO) culture system is one of those that supports HuNoV replication reproducibly and, to our knowledge, is most widely distributed to laboratories worldwide to study HuNoV and develop therapeutic strategies. This review summarizes recently developed HuNoV cultivation systems, including HIO, and their use in antiviral studies.

Emergence and dissemination of equine-like G3P[8] rotavirus A in Brazil between 2015 and 2021.

Rotavirus A (RVA) is a major cause of acute gastroenteritis globally that is classically genotyped by its two immunodominant outer capsid proteins, VP7 (G-) and VP4 (P-). Recent evidence suggests that the reassortant equine-like G3P[8] strain played a substantial role in RVA transmission in Brazil since 2015. To understand its global emergence and dissemination in Brazilian territory, stool samples collected from 11 Brazilian states (n = 919) were genotyped by RT-qPCR and proceeded to sequence the VP7 gene (n = 102, 79 being newly generated) of the G3P[8] samples with pronounced viral loads. Our phylogenetic genotyping showed that G3P[8] became the dominant strain in Brazil between 2017 and 2020, with equine-like variants representing 75%-100% of VP7 samples in this period. A Bayesian discrete phylogeographic analysis strongly suggests that the equine-like G3P[8] strain originated in Asia during the early 2010s and subsequently spread to Europe, the Caribbean, and South America. Multiple introductions were detected in Brazil between 2014 and 2017, resulting in five national clusters. The reconstruction of the effective population size of the largest Brazilian cluster showed an expansion until 2017, followed by a plateau phase until 2019 and subsequent contraction. Our study also supports that most mutations fixed during equine-like G3P[8] evolution were synonymous, suggesting that adaptive evolution was not an important driving force during viral dissemination in humans, potentially increasing its susceptibility to acquired immunity. This research emphasizes the need for comprehensive rotavirus genomic surveillance that allows close monitoring of its ever-shifting composition and informs more effective public health policies.IMPORTANCEOur original article demonstrated the origin and spread in a short time of equine-like G3P[8] in Brazil and the world. Due to its segmented genome, it allows numerous mechanisms including genetic drift and reassortment contribute substantially to the genetic diversity of rotavirus. Although the effectiveness and increasing implementation of vaccination have not been questioned, a matter of concern is its impact on the emergence of escape mutants or even the spread of unusual strains of zoonotic transmission that could drive epidemic patterns worldwide. This research emphasizes the need for comprehensive rotavirus genomic surveillance, which could facilitate the formulation of public policies aimed at preventing and mitigating its transmission.

Saccharomyces cerevisiae cells that display norovirus P induce both systemic and mucosal neutralizing antibodies

The human norovirus (HuNov) is the leading cause of acute gastroenteritis (AGE) worldwide. Mucosal secretory IgA (sIgA) in the gastrointestinal tract interrupts the interaction between host cells and HuNov, thus inhibiting viral infection. In this study, we constructed a recombinant Saccharomyces cerevisiae (S. cerevisiae) expressing the HuNov P protein (GII. 4) and evaluated its immunogenicity in mice after oral delivery. First, the recombinant S. cerevisiae (EBY100/pYD1-P) efficiently expressed P, as evidenced by western blotting and indirect fluorescent assay. Second, after oral administration, EBY100/pYD1-P, especially the high-dose group (5 × 109 clone formation units), elicited systemic and mucosal immune responses characterized by significant sera IgG, IgA, and mucosal sIgA. More importantly, these antibodies showed a substantial neutralization effect against P. Lastly, EBY100/pYD1-P induced significant P-specific IFN-γ-secreting T cells and IL4-secreting T cells. Collectively, the recombinant S. cerevisiae expressing HuNov P is a promising mucosal vaccine candidate against HuNov.

Current trends and new approaches for human norovirus replication in cell culture: a literature review.

Human norovirus (HuNoV) is one of the world's leading causes of acute gastroenteritis. At present, effective reproduction of the virus in cell cultures remains a challenge for virologists, as there is a lack of a permissive cell line that allows the entire viral life cycle to be reproduced. This is a barrier to the study of the HuNoV life cycle, its tropism, and virus-host interactions. It is also a major hurdle for the development of viral detection platforms, and ultimately for the development of therapeutics. The lack of an inexpensive, technically simple, and easily implemented cultivation method also negatively affects our ability to evaluate the efficacy of a variety of control measures (disinfectants, food processes) for human norovirus. In the process of monitoring this pathogen, it is necessary to detect infectious viral particles in water, food, and other environmental samples. Therefore, improvement of in vitro replication of HuNoV is still needed. In this review, we discuss current trends and new approaches to HuNoV replication in cell culture. We highlight ways in which previous research on HuNoV and other noroviruses has guided and influenced the development of new HuNoV culture systems and discuss the improvement of in vitro replication of HuNoV.

Correlates of immune protection against human rotaviruses: natural infection and vaccination.

Species A rotaviruses are the leading viral cause of acute gastroenteritis in children under 5 years of age worldwide. Despite progress in the characterization of the pathogenesis and immunology of rotavirus-induced gastroenteritis, correlates of protection (CoPs) in the course of either natural infection or vaccine-induced immunity are not fully understood. There are numerous factors such as serological responses (IgA and IgG), the presence of maternal antibodies (Abs) in breast milk, changes in the intestinal microbiome, and rotavirus structural and non-structural proteins that contribute to the outcome of the CoP. Indeed, while an intestinal IgA response and its surrogate, the serum IgA level, are suggested as the principal CoPs for oral rotavirus vaccines, the IgG level is more likely to be a CoP for parenteral non-replicating rotavirus vaccines. Integrating clinical and immunological data will be instrumental in improving rotavirus vaccine efficacy, especially in low- and middle-income countries, where vaccine efficacy is significantly lower than in high-income countries. Further knowledge on CoPs against rotavirus disease will be helpful for next-generation vaccine development. Herein, available data and literature on interacting components and proposed CoPs against human rotavirus disease are reviewed, and limitations and gaps in our knowledge in this area are discussed.

Norovirus in children under 2 years of age: an epidemiological study in Panama during the COVID-19 pandemic.

Norovirus infection is a common cause of acute gastroenteritis (AGE). Surveillance activities are important to aid investigation into effective norovirus control strategies, including vaccination. Here, we report ancillary findings related to the incidence, prevalence, and etiology of AGE caused by norovirus in Panama after adjustment of study methodology to comply with national coronavirus disease 2019 (COVID-19) mandates. In January 2020, children aged <2 years began enrolling into an epidemiological study in Panama to estimate the burden of norovirus in preparation for evaluating upcoming prevention strategies. This included an observational, longitudinal, community-based AGE surveillance study and a hospital-based AGE surveillance study. For the longitudinal study, healthy children aged 5-18 months were enrolled from January 6 through March 23, 2020, with a follow-up of approximately 6 months. The last participant was contacted on September 23, 2020. For the hospital-based study, starting on January 21, 2020, children aged <2 years who were admitted to the Hospital del Niño Dr. José Renán Esquivel in Panama City due to AGE were evaluated. The last sample was collected on September 29, 2020. Collected stool samples were tested for norovirus as well as astrovirus, sapovirus, and various enteropathogens. Unfortunately, this study was disrupted by the subsequent implementation of disease transmission control procedures for the COVID-19 pandemic, and the study methodology was revised to comply with COVID-19 mandates. In the longitudinal surveillance cohort [N = 400 (Chiriquí, n = 239; Panama, n = 161)], a total of 185 AGE episodes were documented (Chiriquí, n = 85; Panama, n = 100) resulting in an overall AGE incidence of 11.6 (95% CI: 9.99-13.4) episodes per 100 child-months. The norovirus-related AGE incidence was 0.3 (95% CI: 0.10-0.73) episodes per 100 child-months (5/185 AGE episodes) and the prevalence of norovirus was 4.6% (13/282 stool samples collected). In the hospital-based surveillance cohort, at least one pathogen was detected in 50% of samples (44/88 stool samples collected) and norovirus prevalence was 6.8% (6/88 stool samples collected). This report demonstrates how the occurrence of the COVID-19 pandemic hindered the conduct of clinical trials. However, this also created unique research opportunities to investigate the potential impact of pandemic control measures on the etiology of infectious diarrheal disease.

Comprehensive full genome analysis of norovirus strains from eastern India, 2017–2021

BackgroundWorldwide, noroviruses are the leading cause of acute gastroenteritis (AGE) in people of all age groups. In India, norovirus rates between 1.4 to 44.4% have been reported. Only a very few complete norovirus genome sequences from India have been reported.ObjectiveTo perform full genome sequencing of noroviruses circulating in India during 2017–2021, identify circulating genotypes, assess evolution including detection of recombination events.MethodologyForty-five archived norovirus-positive samples collected between October 2017 to July 2021 from patients with AGE from two hospitals in Kolkata, India were processed for full genome sequencing. Phylogenetic analysis, recombination breakpoint analysis and comprehensive mutation analysis were also performed.ResultsFull genome analysis of norovirus sequences revealed that strains belonging to genogroup (G)I were genotyped as GI.3[P13]. Among the different norovirus capsid-polymerase combinations, GII.3[P16], GII.4 Sydney[P16], GII.4 Sydney[P31], GII.13[P16], GII.16[P16] and GII.17 were identified. Phylogenetic analysis confirmed phylogenetic relatedness with previously reported norovirus strains and all viruses were analyzed by Simplot. GII[P16] viruses with multiple residue mutations within the non-structural region were detected among circulating GII.4 and GII.3 strains. Comprehensive mutation analysis and selection pressure analysis of GII[P16] viruses showed positive as well as negative selection sites. A GII.17 strain (NICED-BCH-11889) had an untypeable polymerase type, closely related to GII[P38].ConclusionThis study highlights the circulation of diverse norovirus strains in eastern India. These findings are important for understanding norovirus epidemiology in India and may have implications for future vaccine development.