Outbreaks Of Acute Gastroenteritis Research Articles

Diverse genotypes of norovirus genogroup I and II contamination in environmental water in Thailand during the COVID-19 outbreak from 2020 to 2022

Noroviruses (NoVs) are the most significant viral pathogens associated with waterborne and foodborne outbreaks of nonbacterial acute gastroenteritis in humans worldwide. This study aimed to investigate the prevalence and diversity of NoVs contaminated in the environmental water in Chiang Mai, Thailand. A total of 600 environmental water samples were collected from ten sampling sites in Chiang Mai from July 2020 to December 2022. The presence of NoV genogroups I (GI), GII, and GIV were examined using real-time RT-PCR assay. The genotype of the virus was determined by nucleotide sequencing and phylogenetic analysis. The results showed that NoV GI and GII were detected at 8.5% (51/600) and 11.7% (70/600) of the samples tested, respectively. However, NoV GIV was not detected in this study. NoV circulated throughout the year, with a higher detection rate during the winter season. Six NoV GI genotypes (GI.1-GI.6) and eight NoV GII genotypes (GII.2, GII.3, GII.7, GII.8, GII.10, GII.13, GII.17, and GII.21) were identified. Among 121 NoV strains detected, GII.17 was the most predominant genotype (24.8%, 30 strains), followed by GII.2 (21.5%, 26 strains), GI.3 (17.4%, 21 strains), and GI.4 (16.5%, 20 strains). Notably, NoV GII.3, GII.7, GII.8, and GII.10 were detected for the first time in water samples in this area. This study provides insight into the occurrence and seasonal pattern of NoV along with novel findings of NoV strains in environmental water in Thailand during the COVID-19 outbreak. Our findings emphasize the importance of further surveillance studies to monitor viral contamination in environmental water.

Acute Gastroenteritis Outbreak Among Colorado River Rafters and Backpackers in the Grand Canyon, 2022.

From April 1 to May 31, 2022, Grand Canyon National Park received increased acute gastroenteritis reports. Pooled portable toilet specimens identified norovirus genogroups I and II. We sought to determine outbreak transmission contributors and individual risk factors while rafting or backpacking in the park. Grand Canyon rafters and backpackers were surveyed online from June 13-July 8, 2022, and a Cox proportional hazards model was used to identify predictors associated with illness and adjusted for potential confounding factors. Among 762 surveys, 119 cases and 505 well persons submitted complete survey data. Illness among rafters was associated with interaction with ill persons during the trip (adjusted hazard ratio [adjHR] = 3.4 [95%CI 2.3-5.0]) and lack of any hand hygiene (1.2 [0.7-1.9]) or use of only sanitizer or water (1.6 [1.04-2.6]) before snacks. Younger rafters had higher illness rates compared to those ≥60 y (1.5 [1.2-1.8] for ages 40-59 and 2.2 [1.4-3.5] for ages <40 y). Person-to-person transmission likely accounted for the widespread outbreak. Future outbreak mitigation efforts on river trips could focus on symptom screening before the trip starts, prompt separation of ill and well passengers, strict adherence to hand hygiene with soap and water, minimizing social interactions among rafting groups, and widespread outbreak notices and education to all park users.

Acute Gastroenteritis Outbreak in a Rural Area in Perak, Malaysia, 2022

An outbreak of acute gastroenteritis was identified in a rural village in Perak, Malaysia, on 22 Jun 2022, following the detection of 20 cases. The Larut, Matang, and Selama District Health Office implemented public health measures to control the outbreak. We detected 25 cases during 22–24 Jun 2022, among private boarding school students and residents. Half (52%) of the cases were aged between 11 and 15 years, 68% were male, and 44% were students. Common symptoms included vomiting (88%), abdominal pain (76%), and diarrhoea (72%). No food was suspected based on food diaries, as there was no common food eaten by all cases. The epidemic curve showed a point-source pattern. Mapping of cases demonstrated that all cases used water for drinking, cooking, and other domestic usages that were supplied by the same gravity feed system. Several empty containers of carbofuran-containing insecticide and nematicide, used for agriculture, were found near the gravity feed system route at an altitude higher than its inlet. No known pathogen was isolated from the rectal swabs of cases. This acute gastroenteritis outbreak was suspected to have occurred from drinking water contaminated with chemicals such as carbofuran. After excluding other possible causes, health education to the villagers, particularly on the appropriate use of insecticides nearby the source of water supply with good cooperation from the local communities had helped successfully controlling the outbreak.

Aerosol Transmission of Norovirus.

Norovirus (NoV) is a major cause of acute gastroenteritis outbreaks worldwide. A comprehensive understanding of the transmission mode is of great significance for the prevention and control of the NoV infection. Currently, the transmission modes of NoV include contact, food-borne, water-borne and aerosol transmission. The first three modes are more common, while aerosol transmission is seldom reported. In this paper, the source, generation mechanism, infectivity, sampling and related outbreaks of NoV aerosol are summarized and discussed.

Asymptomatic norovirus infection during outbreaks in China: A systematic review and meta-analysis.

Acute gastroenteritis outbreaks may be caused by the excretion of norovirus (NoV) from asymptomatic individuals. Despite numerous studies involving asymptomatic NoV infection during outbreaks in China, a comprehensive assessment of its role has not been conducted, which is critical for emergency management. Our objective was to assess the prevalence of asymptomatic NoV infection during outbreaks in China. We conducted a comprehensive search of multiple databases, including PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, China Wanfang, and China Weipu, between January 1, 1997 and June 19, 2023. The retrieved articles and their references underwent screening, which utilized polymerase chain reaction-based assays for the detection of NoV in asymptomatic individuals during outbreaks that occurred in China. The primary summary data were the prevalence of asymptomatic NoV infection in outbreaks. We generated pooled estimates of asymptomatic prevalence in the population as a whole and in subgroups by using random-effect models. Of the 97 articles included, the pooled asymptomatic prevalence of NoV among 5117 individuals in outbreaks was 17.6% (95% confidence interval [CI]: 14.1-21.3). The asymptomatic prevalence of NoV GII (17.1%, 95% CI: 12.9-21.5) was similar to that of NoV GI (22.0%, 95% CI: 12.8-32.4). However, the proportion of asymptomatic individuals involved in NoV GII (57.44%) was significantly higher than that of NoV GI (5.12%), and NoV GII (75.26%) was reported much more frequently than NoV GI (14.43%) in the included articles. Meta-regression analysis of 11 possible influencing factors (geographic region, setting, season, sample type, genotype, transmission route, occupation, age, per capita income, study quality, and cases definition) showed that the source of heterogeneity might be related to the outbreak settings, per capita income, and study quality (p = 0.037, 0.058, and 0.026, respectively). Of particular note was the asymptomatic prevalence peaked in preschoolers (27.8%), afterward, it fell into trough in elementary and junior school children (10.5%), before the second peak located in adults (17.8%), and the elderly (25.2%). Prevalent genotypes reported include GII.4, followed by GII.17, GII.2, GII.3, GII.6, and so forth. The estimated asymptomatic prevalence of NoV during outbreaks in China was as high as 17.6%, with NoV GII dominating. In addition, genetic subtypes of NoV in outbreaks should be detected whenever possible. The role of asymptomatic individuals in NoV outbreaks cannot be ignored. This knowledge will help governments develop public health policies and emergency response strategies for outbreaks, assess the burden, and develop vaccines.

The impact of COVID-19 pandemic on the incidence of acute gastroenteritis outbreaks in Catalonia (Spain).

We carried out a retrospective study of acute gastroenteritis (AGE) outbreaks reported between 1 January 2015 and 31 December 2021 in Catalonia (Spain) to compare the incidence from 2015 to 2019 with that observed from 2020 to 2021. We observed a higher incidence rate of outbreaks during the prepandemic period (16.89 outbreaks/1,000,000 person-years) than during the pandemic period (6.96 outbreaks/1,000,000 person-years) (rate ratio (RR) 0.41; 95% confidence interval (CI) 0.34 to 0.51). According to the aetiology of the outbreak, those of viral aetiology decreased from 7.82 to 3.38 outbreaks/1,000,000 person-years (RR 2.31; 95% CI 1.72 to 3.12), and those of bacterial aetiology decreased from 5.01 to 2.78 outbreaks/1,000,000 person-years (RR 1.80; 95% CI 1.29 to 2.52). There was a great reduction in AGE outbreaks in Catalonia. This reduction may have been due to the effect of the nonpharmaceutical measures applied to reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the collapse of the healthcare system and epidemiological surveillance services may also have had a strong influence.

Acute gastroenteritis outbreak associated with multiple and rare norovirus genotypes after storm events in Santa Catarina, Brazil.

Norovirus is a major cause of acute diarrheal disease (ADD) outbreaks worldwide. In the present study, we investigated an ADD outbreak caused by norovirus in several municipalities of Santa Catarina state during the summer season, southern Brazil in 2023. As of the 10th epidemiological week of 2023, approximately 87 000 ADD cases were reported, with the capital, Florianópolis, recording the highest number of cases throughout the weeks. By using RT-qPCR and sequencing, we detected 10 different genotypes, from both genogroups (G) I and II. Some rare genotypes were also identified. Additionally, rotavirus and human adenovirus were sporadically detected among the ADD cases. Several features of the outbreak suggest that sewage-contaminated water could played a role in the surge of ADD cases. Storm events in Santa Catarina state that preceded the outbreak likely increased the discharge of contaminated wastewater and stormwater into water bodies, such as rivers and beaches during a high touristic season in the state. Climate change-induced extreme weather events, including intensified rainfall and frequent floods, can disturb healthcare and sanitation systems. Implementing public policies for effective sanitation, particularly during peak times, is crucial to maintain environmental equilibrium and counter marine pollution.

Vaccine value profile for norovirus

Norovirus is attributed to nearly 1 out of every 5 episodes of diarrheal disease globally and is estimated to cause approximately 200,000 deaths annually worldwide, with 70,000 or more among children in developing countries. Noroviruses remain a leading cause of sporadic disease and outbreaks of acute gastroenteritis even in industrialized settings, highlighting that improved hygiene and sanitation alone may not be fully effective in controlling norovirus. Strengths in global progress towards a Norovirus vaccine include a diverse though not deep pipeline which includes multiple approaches, including some with proven technology platforms (e.g., VLP-based HPV vaccines). However, several gaps in knowledge persist, including a fulsome mechanistic understanding of how the virus attaches to human host cells, internalizes, and induces disease.

Genotypic diversity and recombination of norovirus GI.6[P11] associated acute gastroenteritis outbreaks in Beijing, China, from 2016 to 2019.

Norovirus (NoV) is the leading pathogen responsible for global acute gastroenteritis (AGE) outbreaks and sporadic cases. NoV evolves through gene mutation and recombination, leading to the emergence of new strains capable of causing global epidemics. This study aimed to learn the epidemiological characteristics of 39 GI.6[P11] NoV outbreaks in Beijing, China, from 2016 to 2019 and to analyze the genetic diversity and phylogenetic process of GI.6[P11] strains. The Bayesian phylogenetic analysis of partial VP1 and RNA-dependent RNA polymerase (RdRp) genes showed that GI.6[P11] strains were clustered into four subclades. Eleven whole genome sequences were obtained through the amplicon sequencing with 16 pairs of newly designed primers. The phylogenetic trees based on the whole genome and ORF1, 2, and 3 showed that the clustering of the 11 strains was consistent with that of partial VP1 and RdRp genes. The Bayesian inference revealed that the most recent ancestor (TMRCA) for the four subclades of the phylogenetic tree based on the whole genome sequences was 2012.42, 2014.81, 2011.74, and 2015.53, respectively. The recombination sites of GI.6[P11] strains in Beijing were located near the ORF1/2 junction. The histo-blood group antigens (HBGA) binding sites of GI.6[P11] strains in Beijing were conserved and there were some unique amino acid mutations in non-structural proteins in the ORF1 region.

Two successive outbreaks of acute gastroenteritis due to norovirus GII.6 in a holiday camp house

When two outbreaks occur in the same institution within a short period of time, an important health and social concern is generated. Two gastroenteritis outbreaks occurring a week apart in the same facility were reported in Lleida, Spain, in 2018. The objective of this study was to describe the clinical, epidemiological and microbiological investigation carried out and to determine the risk factors. Demographic data, food consumption and symptoms were collected. Health inspections of the facility were carried out. Risk ratio and their 95% confidence intervals were estimated for the implication of each food consumed. The attack rate was 89.7% in the first outbreak and 69.6% in the second outbreak. The most frequent symptoms in the first and second outbreak were abdominal pain (88.5% and 100%, respectively), vomiting (80.8% and 87.5%, respectively) and nausea (69.2% and 81.3%, respectively). The first outbreak was associated with the consumption of a salad and the second with a cheese omelet. Norovirus GII.6 was detected by RT-PCR and sequenced in both groups of students and in the food handlers who prepared the meals. These results highlight the importance of exclusion from work of food handlers with gastroenteritis, the adequate availability of mechanisms for correct hand washing and the correct cleaning of surfaces.

Surveillance of SARS-CoV-2, rotavirus, norovirus genogroup II, and human adenovirus in wastewater as an epidemiological tool to anticipate outbreaks of COVID-19 and acute gastroenteritis in a city without a wastewater treatment plant in the Peruvian Highlands

The coronavirus disease 2019 (COVID-19) pandemic has demonstrated that Wastewater Based Epidemiology is a fast and economical alternative for monitoring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the community level in high-income countries. In the present study, wastewater from a city in the Peruvian Highlands, which lacks a wastewater treatment plant, was monitored for one year to assess the relationship between the concentration of SARS-CoV-2 and the reported cases of COVID-19 in the community. Additionally, we compared the relationship between rotavirus (RV), norovirus genogroup II (NoV GGII), and human adenovirus (HAdV) with the number of reported cases of acute gastroenteritis. Before commencing the analysis of the samples, the viral recovery efficacy of three processing methods was determined in spiked wastewater with SARS-CoV-2. This evaluation demonstrated the highest recovery rate with direct analysis (72.2 %), as compared to ultrafiltration (50.8 %) and skimmed milk flocculation (5.6 %). Wastewater monitoring revealed that 72 % (36/50) of the samples tested positive for SARS-CoV-2, with direct analysis yielding the highest detection frequency and quantification of SARS-CoV-2. Furthermore, a strong correlation was observed between the concentration of SARS-CoV-2 in wastewater and the reported cases of COVID-19, mainly when we shift the concentration of SARS-CoV-2 by two weeks, which allows us to anticipate the onset of the fourth and fifth waves of the pandemic in Peru up to two weeks in advance. All samples processed using the skimmed milk flocculation method tested positive and showed high concentrations of RV, NoV GGII, and HAdV. In fact, the highest RV concentrations were detected up to four weeks before outbreaks of acute gastroenteritis reported in children under four years of age. In conclusion, the results of this study suggest that periodic wastewater monitoring is an excellent epidemiological tool for surveillance and can anticipate outbreaks of infectious diseases, such as COVID-19, in low- and middle-income countries.

From Foodborne Disease Outbreak (FBDO) to Investigation: The Plant Toxin Trap, Brittany, France, 2018.

On 6 July 2018, the Center for Epidemiology and Public Health of the French Armed Forces was informed of an outbreak of acute gastroenteritis among customers of a dining facility at a military base in Brittany, France. A total of 200 patients were reported out of a population of 1700 (attack rate: 12%). The symptoms were mainly lower digestive tract disorders and occurred rapidly after lunch on 5 July (median incubation period: 3.3 h), suggesting a toxin-like pathogenic process. A case-control survey was carried out (92 cases and 113 controls). Statistical analysis pointed to the chili con carne served at lunch on 5 July as the very likely source of poisoning. Phytohaemagglutinin, a plant lectin, was found in the chili con carne at a concentration above the potentially toxic dose (400 HAU/gram). The raw kidney beans incorporated in the chili con carne presented a high haemagglutination activity (66,667 HAU/gram). They were undercooked, and the phytohaemagglutinin was not completely destroyed. FBDOs due to PHA are poorly documented. This study highlights the need to develop methods for routine testing of plant toxins in food matrices. Improved diagnostic capabilities would likely lead to better documentation, epidemiology, and prevention of food-borne illnesses caused by plant toxins.

Trends on Human Norovirus Virus-like Particles (HuNoV-VLPs) and Strategies for the Construction of Infectious Viral Clones toward In Vitro Replication.

Most acute gastroenteritis (AGE) outbreaks and sporadic cases in developing countries are attributable to infection by human norovirus (HuNoV), the enteric virus mainly transmitted via fecal-contaminated water. However, it has been challenging to study HuNoV due to the lack of suitable systems to cultivate and replicate the virus, hindering the development of treatments and vaccines. Researchers have been using virus-like particles (VLPs) and infectious viral clones to overcome this challenge as alternatives to fresh virus isolates in various in vitro and ex vivo models. VLPs are multiprotein structures that mimic the wild-type virus but cannot replicate in host cells due to the lack of genetic materials for replication, limiting downstream analysis of the virus life cycle and pathogenesis. The development of in vitro cloning systems has shown promise for HuNoV replication studies. This review discusses the approaches for constructing HuNoV-VLPs and infectious viral clones, the techniques involved, and the challenges faced. It also highlights the relationship between viral genes and their protein products and provides a perspective on technical considerations for producing efficient HuNoV-VLPs and infectious viral clones, which could substitute for native human noroviruses in future studies.

Nanocellulose-Based Passivated-Carbon Quantum Dots (P-CQDs) for Antimicrobial Applications: A Practical Review.

Passivated-carbon quantum dots (P-CQDs) have been attracting great interest as an antimicrobial therapy tool due to their bright fluorescence, lack of toxicity, eco-friendly nature, simple synthetic schemes, and possession of photocatalytic functions comparable to those present in traditional nanometric semiconductors. Besides synthetic precursors, CQDs can be synthesized from a plethora of natural resources including microcrystalline cellulose (MCC) and nanocrystalline cellulose (NCC). Converting MCC into NCC is performed chemically via the top-down route, while synthesizing CODs from NCC can be performed via the bottom-up route. Due to the good surface charge status with the NCC precursor, we focused in this review on synthesizing CQDs from nanocelluloses (MCC and NCC) since they could become a potential source for fabricating carbon quantum dots that are affected by pyrolysis temperature. There are several P-CQDs synthesized with a wide spectrum of featured properties, namely functionalized carbon quantum dots (F-CQDs) and passivated carbon quantum dots (P-CQDs). There are two different important P-CQDs, namely 2,2'-ethylenedioxy-bis-ethylamine (EDA-CQDs) and 3-ethoxypropylamine (EPA-CQDs), that have achieved desirable results in the antiviral therapy field. Since NoV is the most common dangerous cause of nonbacterial, acute gastroenteritis outbreaks worldwide, this review deals with NoV in detail. The surficial charge status (SCS) of the P-CQDs plays an important role in their interactions with NoVs. The EDA-CQDs were found to be more effective than EPA-CQDs in inhibiting the NoV binding. This difference may be attributed to their SCS as well as the virus surface. EDA-CQDs with surficial terminal amino (-NH2) groups are positively charged at physiological pH (-NH3+), whereas EPA-CQDs with surficial terminal methyl groups (-CH3) are not charged. Since the NoV particles are negatively charged, they are attracted to the positively charged EDA-CQDs, resulting in enhancing the P-CQDs concentration around the virus particles. The carbon nanotubes (CNTs) were found to be comparable to the P-CQDs in the non-specific binding with NoV capsid proteins, through complementary charges, π-π stacking, and/or hydrophobic interactions.

Assessment of the aetiology of acute gastroenteritis outbreaks in infants reveals rotavirus, noroviruses and adenovirus prevalence and viral coinfections in Nsukka, Nigeria.

The online version contains supplementary material available at 10.1007/s13337-023-00821-2.

Epidemiological characteristics of norovirus acute gastroenteritis outbreaks and influencing factors in China, 2007-2021

Objective: To analyze the epidemiological characteristics of norovirus-caused acute gastroenteritis outbreaks in China, identify the factors influencing the scale of outbreaks, and provide scientific evidences for early control of norovirus infection outbreaks. Methods: The descriptive epidemiological analysis approach was applied to analyze the incidence of national norovirus infection outbreaks by using the data from the Public Health Emergency Event Surveillance System in China from January 1, 2007 to December 31, 2021. The unconditional logistic regression model was applied to analyze the risk factors that affected the outbreaks' scale. Results: A total of 1 725 norovirus infection outbreaks were recorded in China from 2007 to 2021, with an upward trend in the number of the reported outbreaks. The southern provinces had their annual outbreak peaks from October to March; the northern provinces had two outbreak peaks from October to December and from March to June annually. The outbreaks occurred mainly in southeastern coastal provinces with a trend of gradual spread to central, northeastern and western provinces. The outbreaks mainly occurred in schools and childcare setting (1 539 cases, 89.22%), followed by enterprises and institutions (67 cases, 3.88%) and community households (55 cases, 3.19%). Human to human transmission was the main infection route (73.16%), and norovirus GⅡ genotype was the predominate pathogen causing the outbreaks (899 cases, 81.58%). The time interval between the onset of the primary case and the outbreak reporting M (Q1, Q3) was 3 (2, 6) days and the case number of the outbreak M (Q1, Q3) was 38 (28, 62). The timeliness of outbreak reporting was improved in recent years and the scale of the outbreaks showed a decreasing trend over the years, the differences in reporting timeliness and outbreak scale among different settings were significant (P<0.001). The factors that affected outbreaks' scale included the outbreak setting, transmission route, outbreak reporting timeliness and type of living areas (P<0.05). Conclusions: From 2007 to 2021, the number of the norovirus-caused acute gastroenteritis outbreaks increased in China and the more areas were affected. However, the outbreak scale showed a decreasing trend and the outbreak reporting timeliness was improved. It is important to further improve the surveillance sensitivity and reporting timeliness for the effective control of the outbreak scale.

An unusual outbreak of acute infectious gastroenteritis

An unusual outbreak of acute infectious gastroenteritis

An Intermittent Gastroenteritis Outbreak of Rotavirus Genotype G9P[8] in a Hotel in Songkhla Province, Thailand, April–May 2019

A series of acute gastroenteritis outbreaks occurred among participants of two seminars at a hotel in Songkhla Province during 26–29 Apr 2019 and 8–10 May 2019. Investigations were done to determine the causes of the outbreaks and recommend control measures. A case was defined as a participant who developed diarrhea, vomiting, nausea or abdominal pain between 26–30 April (Seminar 1) or 8–13 May (Seminar 2). Samples of the drinking and cooking water used during the seminars were taken and rectal swabs from cases and food handlers were collected for bacterial culture and viral reverse transcription polymerase chain reaction tests. A retrospective cohort study was conducted to identify risk factors. Of 349 participants interviewed, 237 were cases, giving an attack rate of 67.9%. The ages of the cases ranged from 11–57 years (median 15 years). The most common symptoms were watery diarrhea (94.1%), abdominal pain (81.0%) and nausea (57.8%). Rotavirus was detected in five cases, three food handlers and a sample of water used for cooking. All were of the same genotype G9P[8]. Implicated dishes included spicy seafood salad (adjusted odds ratio (AOR) 4.5, 95% confidence interval (CI) 1.7–11.8), shrimp in sauce (AOR 2.9, 95% CI 1.0-8.2), roast duck with vegetables (AOR 2.9, 95% CI 1.2–7.3) and water from a cooler (AOR 2.0, 95% CI 1.0–3.9). Contaminated water and infected food handlers were probable sources of cross-contamination. After the hotel’s water system was repaired and the food handlers were educated on safe food handling practices and good personal hygiene, no other outbreaks associated with the hotel were reported.

Direct Blockade of the Norovirus Histo-Blood Group Antigen Binding Pocket by Nanobodies.

Noroviruses are the leading cause of outbreaks of acute gastroenteritis. These viruses usually interact with histo-blood group antigens (HBGAs), which are considered essential cofactors for norovirus infection. This study structurally characterizes nanobodies developed against the clinically important GII.4 and GII.17 noroviruses with a focus on the identification of novel nanobodies that efficiently block the HBGA binding site. Using X-ray crystallography, we have characterized nine different nanobodies that bound to the top, side, or bottom of the P domain. The eight nanobodies that bound to the top or side of the P domain were mainly genotype specific, while one nanobody that bound to the bottom cross-reacted against several genotypes and showed HBGA blocking potential. The four nanobodies that bound to the top of the P domain also inhibited HBGA binding, and structural analysis revealed that these nanobodies interacted with several GII.4 and GII.17 P domain residues that commonly engaged HBGAs. Moreover, these nanobody complementarity-determining regions (CDRs) extended completely into the cofactor pockets and would likely impede HBGA engagement. The atomic level information for these nanobodies and their corresponding binding sites provide a valuable template for the discovery of additional "designer" nanobodies. These next-generation nanobodies would be designed to target other important genotypes and variants, while maintaining cofactor interference. Finally, our results clearly demonstrate for the first time that nanobodies directly targeting the HBGA binding site can function as potent norovirus inhibitors. IMPORTANCE Human noroviruses are highly contagious and a major problem in closed institutions, such as schools, hospitals, and cruise ships. Reducing norovirus infections is challenging on multiple levels and includes the frequent emergence of antigenic variants, which complicates designing effective, broadly reactive capsid therapeutics. We successfully developed and characterized four norovirus nanobodies that bound at the HBGA pockets. Compared with previously developed norovirus nanobodies that inhibited HBGA through disrupted particle stability, these four novel nanobodies directly inhibited HBGA engagement and interacted with HBGA binding residues. Importantly, these new nanobodies specifically target two genotypes that have caused the majority of outbreaks worldwide and consequently would have an enormous benefit if they could be further developed as norovirus therapeutics. To date, we have structurally characterized 16 different GII nanobody complexes, a number of which block HBGA binding. These structural data could be used to design multivalent nanobody constructs with improved inhibition properties.

Epidemiological Characteristics of Norovirus Outbreaks in Shenyang from 2017 to 2021.

Norovirus is one of the leading causes of acute gastroenteritis outbreaks worldwide. This study aimed to identify the epidemiological characteristics of norovirus outbreaks and to provide evidence for public health entities. Specimens and epidemiological survey data were collected to determine if there were differences in the attack rate of norovirus in terms of the year, season, transmission route, exposure setting, and region and to determine whether there were relationships between the reporting interval, the number of illnesses in a single outbreak and the duration of the outbreak. Norovirus outbreaks were reported throughout the year, with seasonal characteristics (i.e., high rates in spring and winter). Among all regions in Shenyang with the exception of Huanggu and Liaozhong, norovirus outbreaks had been reported, and the primary genotype was GII.2[P16]. Vomiting was the most common symptom. The main places of occurrence were childcare institutions and schools. The person-to-person route was the main transmission route. The median duration of norovirus was 3 days (IQR [interquartile range]: 2-6 days), the median reporting interval was 2 days (IQR: 1-4 days), the median number of illnesses in a single outbreak was 16 (IQR: 10-25); there was a positive correlation between these parameters. Norovirus surveillance and genotyping studies still need to be further strengthened to increase knowledge regarding the pathogens and their variant characteristics, to better characterize the patterns of norovirus outbreaks and to provide information for outbreak prevention. Norovirus outbreaks should be detected, reported and handled early. Public health entities and the government should develop corresponding measures for different seasons, transmission routes, exposure settings, and regions.