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Enteric viruses, particularly rotaviruses and noroviruses, are a leading cause of gastroenteritis worldwide. Rotaviruses primarily affect young children, accounting for almost 40% of hospital admissions for diarrhoea and 200 000 deaths worldwide, with the majority of deaths occurring in developing countries. Two vaccines against rotavirus were licensed in 2006 and have been implemented in 95 countries as of April, 2018. Data from eight high-income and middle-income countries showed a 49–89% decline in rotavirus-associated hospital admissions and a 17–55% decline in all-cause gastroenteritis-associated hospital admissions among children younger than 5 years, within 2 years of vaccine introduction. Noroviruses affect people of all ages, and are a leading cause of foodborne disease and outbreaks of gastroenteritis worldwide. Prevention of norovirus infection relies on frequent hand hygiene, limiting contact with people who are infected with the virus, and disinfection of contaminated environmental surfaces. Norovirus vaccine candidates are in clinical trials; whether vaccines will provide durable protection against the range of genetically and antigenically diverse norovirus strains remains unknown. Treatment of viral gastroenteritis is based primarily on replacement of fluid and electrolytes.

Human Norovirus is currently the main viral cause of acute gastroenteritis (AGEs) in most countries worldwide. Nearly 50 years after the discovery of the “Norwalk virus” by Kapikian and colleagues, the scientific and medical community continue to generate new knowledge on the full biological and disease spectrum of Norovirus infection. Nevertheless, several areas remain incompletely understood due to the serious constraints to effectively replicate and propagate the virus. Here, we present a narrated historic perspective and summarize our current knowledge, including insights and reflections on current points of interest for a broad medical community, including clinical and molecular epidemiology, viral–host–microbiota interactions, antivirals, and vaccine prototypes. We also include a reflection on the present and future impacts of the COVID-19 pandemic on Norovirus infection and disease.

With candidate norovirus (NV) vaccines in a rapid phase of development, assessment of the potential economic value of vaccine implementation will be necessary to aid health officials in vaccine implementation decisions. To date, no evaluations have been performed to evaluate the benefit of adopting NV vaccines for use in the childhood immunization programs of low- and middle-income countries. We used a Markov decision model to evaluate the cost-effectiveness of adding a two-dose NV vaccine to Peru's routine childhood immunization schedule using two recent estimates of NV incidence, one for a peri-urban region and one for a jungle region of the country. Using the peri-urban NV incidence estimate, the annual cost of vaccination would be $13.0 million, offset by $2.6 million in treatment savings. Overall, this would result in 473 total DALYs averted; 526,245 diarrhea cases averted;153,735 outpatient visits averted; and 414 hospitalizations averted between birth and the fifth year of life. The incremental cost-effectiveness ratio would be $21,415 per DALY averted; $19.86 per diarrhea case; $68.23 per outpatient visit; and $26,298 per hospitalization. Using the higher jungle NV incidence rates provided a lower cost per DALY of $10,135. The incremental cost per DALY with per-urban NV incidence is greater than three times the 2012 GDP per capita of Peru but the estimate drops below this threshold using the incidence from the jungle setting. In addition to the impact of incidence, sensitivity analysis showed that vaccine price and efficacy play a strong role in determining the level of cost-effectiveness. The introduction of a NV vaccine would prevent many healthcare outcomes in the Peru and potentially be cost-effective in scenarios with high NV incidence. The vaccine cost-effectiveness model could also be applied to the evaluation of NV vaccine cost-effectiveness in other countries in resource-poor settings, where NV incidence rates are expected to be higher.

Human noroviruses (NoVs) are the primary cause of acute gastroenteritis and are characterized by antigenic variation between genogroups and genotypes and antigenic drift of strains within the predominant GII.4 genotype. In the context of this diversity, an effective NoV vaccine must elicit broadly protective immunity. We used an antibody (Ab) binding blockade assay to measure the potential cross-strain protection provided by a multivalent NoV virus-like particle (VLP) candidate vaccine in human volunteers. Sera from ten human volunteers immunized with a multivalent NoV VLP vaccine (genotypes GI.1/GII.4) were analyzed for IgG and Ab blockade of VLP interaction with carbohydrate ligand, a potential correlate of protective immunity to NoV infection and illness. Immunization resulted in rapid rises in IgG and blockade Ab titers against both vaccine components and additional VLPs representing diverse strains and genotypes not represented in the vaccine. Importantly, vaccination induced blockade Ab to two novel GII.4 strains not in circulation at the time of vaccination or sample collection. GII.4 cross-reactive blockade Ab titers were more potent than responses against non-GII.4 VLPs, suggesting that previous exposure history to this dominant circulating genotype may impact the vaccine Ab response. Further, antigenic cartography indicated that vaccination preferentially activated preexisting Ab responses to epitopes associated with GII.4.1997. Study interpretations may be limited by the relevance of the surrogate neutralization assay and the number of immunized participants evaluated. Vaccination with a multivalent NoV VLP vaccine induces a broadly blocking Ab response to multiple epitopes within vaccine and non-vaccine NoV strains and to novel antigenic variants not yet circulating at the time of vaccination. These data reveal new information about complex NoV immune responses to both natural exposure and to vaccination, and support the potential feasibility of an efficacious multivalent NoV VLP vaccine for future use in human populations. ClinicalTrials.gov NCT01168401.

Feline calicivirus (FCV) is a common pathogen in domestic cats that is highly contagious, resistant to many disinfectants and demonstrates a high genetic variability. FCV infection can lead to serious or even fatal diseases. In this review, the European Advisory Board on Cat Diseases (ABCD), a scientifically independent board of experts in feline medicine from 11 European countries, presents the current knowledge of FCV infection and fills gaps with expert opinions. FCV infections are particularly problematic in multicat environments. FCV-infected cats often show painful erosions in the mouth and mild upper respiratory disease and, particularly in kittens, even fatal pneumonia. However, infection can be associated with chronic gingivostomatitis. Rarely, highly virulent FCV variants can induce severe systemic disease with epizootic spread and high mortality. FCV can best be detected by reverse-transcriptase PCR. However, a negative result does not rule out FCV infection and healthy cats can test positive. All cats should be vaccinated against FCV (core vaccine); however, vaccination protects cats from disease but not from infection. Considering the high variability of FCV, changing to different vaccine strain(s) may be of benefit if disease occurs in fully vaccinated cats. Infection-induced immunity is not life-long and does not protect against all strains; therefore, vaccination of cats that have recovered from caliciviral disease is recommended.

Singapore has seen an increase in norovirus outbreaks in preschools from 2019 to 2022 primarily due to person-to-person transmission. This study describes the use of compartmental susceptible-exposed-infectious-recovered (SEIR) modelling to simulate the spread of norovirus among preschool children in a classroom setting. Different intervention measures, such as isolation of infected preschoolers, handwashing and surface decontamination were modelled to quantify their effectiveness at reducing the number of children infected. We found that isolation of the sick child was the most effective single intervention to reduce transmission risk, which was 5 times more effective than handwashing. Coupled with handwashing and surface decontamination, transmission risk could be further reduced, close to zero. Findings from our study can be used to reiterate to parents and teachers on the importance of recognizing the symptoms exhibited by their unwell children and refraining from sending them to school, as this action poses a risk of transmitting norovirus to other children. In addition, our findings can be used to educate children and staff in preschools on the importance of practising good personal hygiene and regular environmental cleaning. Through this study, decision makers would be better informed on the effectivness of various risk mitigation measures at reduce the risk of norovirus transmission in preschool settings.

Norovirus (NoV) is an enteric non-enveloped virus which is the leading cause of gastroenteritis across all age groups. It is responsible for around 200,000 deaths annually and outbreaks are common in small communities such as educational and care facilities. 40% of all NoV outbreaks occur in long-term and acute-care facilities, forming the majority of outbreaks. Nosocomial settings set ideal environments for ease of transmission, especially due to the presence of immunocompromised groups. It is estimated to cost global economies around £48 billion a year, making it a global issue. NoV is transmitted via the faecal-oral route and infection with it results in asymptomatic cases or gastrointestinal disease. It has high mutational rates and this allows for new variants to emerge and be more resistant. The classification system available divides NoV into 10 genogroups and 49 genotypes based on whole amino acid sequencing of VP1 capsid protein and partial sequencing of RdRp, respectively. The most predominant genotypes which cause gastroenteritis in humans include GI.1 and GII.4, where GII.4 is responsible for more extreme clinical implications such as hospitalisation. In addition, GII.4 has been responsible for 6 pandemic strains, the last of which is the GII.4 Sydney (2012) variant. In recent years, the successful cultivation of HuNoV was reported in stem cell-derived human intestinal enteroids (HIEs), which promises to assist in giving a deeper understanding of its underlying mechanisms of infection and the development of more personalized control measures. There are no specific control measures against NoV, therefore common practices are used against it such as hand washing. No vaccine is available, but the HIL-214 candidate passed clinical phase 2b and shows promise.

Noroviruses, in the genus Norovirus, are a significant cause of viral gastroenteritis in humans and animals. For almost 50 years, the lack of a cultivation system for human noroviruses (HuNoVs) was a major barrier to understanding virus biology and the development of effective antiviral strategies. This review presents a historical perspective of the development of a cultivation system for HuNoVs in human intestinal epithelial cell cultures. Successful cultivation was based on the discovery of genetically-encoded host factors required for infection, knowledge of the site of infection in humans, and advances in the cultivation of human intestinal epithelial cells achieved by developmental and stem cell biologists. The human stem cell-derived enteroid cultivation system recapitulates the multicellular, physiologically active human intestinal epithelium, and allows studies of virus-specific replication requirements, evaluation of human host-pathogen interactions, and supports the pre-clinical assessment of methods to prevent and treat HuNoV infections.

Norovirus, primarily transmitted via fomite route, poses a significant threat to global public health and the economy. Airports, as critical transportation hubs connecting people from around the world, has high potential risk of norovirus transmission due to large number of public surfaces. A total of 21.3 hours of video episodes were recorded across nine functional areas at the airport, capturing 25,925 touches. A surface transmission model based on a Markov chain was developed. Using the beta-Poisson dose-response model, the infection risk of norovirus and the effectiveness of various interventions in different airports’ areas were quantified. Without any preventive measures, restaurants at airports exhibited the highest risk of norovirus transmission, with an infection probability of 8.8×10 −3 % (95% CI, 1.5×10 −3 % -2.1×10 −2 %). This means approximately 4.6 (95% CI, 0.8–10.9) out of 51,494 passengers who entered the restaurants would be infected by an infected passenger. Comparing with no surface disinfection, disinfecting public surfaces every 2 hours can reduce the risk of norovirus infection per visit to the airport by 83.2%. In contrast, comparing with no hand washing, handwashing every 2 hours can reduce the infection risk per visit to the airport by only 2.0%, making public surface disinfection significantly more effective than handwashing. If the mask-wearing rate increases from 0% to 50%, the infection risk of norovirus would be decreased by 48.0% (95% CI, 43.5–52.3%). Furthermore, using antimicrobial copper/copper-nickel alloy coatings for most public surfaces could reduce the infection risk by 15.9%-99.2%.

Norovirus is a highly contagious virus and the leading cause of acute gastroenteritis worldwide. The World Health Organization (WHO) estimates that approximately 685 million cases of norovirus infection occur each year, with around 200 million affecting children under the age of five. The impact of this virus is substantial, contributing to roughly 200,000 deaths annually—about 50,000 of which are among young children—mostly in low-income countries. In addition to the human toll, norovirus imposes a significant economic burden, with global costs reaching approximately $60 billion each year due to healthcare expenses and lost productivity. In this paper, we present a fractional-order mathematical analysis of the norovirus epidemic model, focusing on its transmission dynamics, incorporating memory effects. The total population, denoted as N(t), is categorized into four compartments: susceptible, exposed, infected, and recovered. We analytically derive the equilibrium points and the basic reproduction number of the model. Furthermore, we discuss the properties of positivity, boundedness, uniqueness, and existence to ensure the model’s validity. The non-linear model is linearized around its equilibrium points, and local stability is analyzed using the eigenvalues of the Jacobian matrix. In addition, global stability is examined using the Lyapunov function and LaSalle’s invariance principle. To validate the theoretical findings, a numerical scheme based on the GL-Non-Standard Finite Difference (NSFD) method is developed, which serves to verify the theoretical analysis of the norovirus epidemic model.