Outbreak Of Gastroenteritis Research Articles

Influence of herd immunity on norovirus: a long-term field study of repeated viral gastroenteritis outbreaks at the same facilities

BackgroundViral acute gastroenteritis (AG) is detected worldwide annually. Outbreaks caused by viruses associated with gastroenteritis have been reported repeatedly at the same facilities in Yokohama, Japan over several years. We investigated the statuses of these repeated outbreaks to consider herd immunity at the facility level.MethodsBetween September 2007 and August 2017, 1459 AG outbreaks were reported at 1099 facilities. Stool samples were collected for virological testing, and the norovirus gene was amplified and sequenced to determine the genotype using the N-terminal region of the capsid.ResultsThe outbreaks were caused by norovirus, sapovirus, rotavirus A, and rotavirus C. Norovirus was consistently predominant over the 10-year period. Of 1099 facilities, 227 reported multiple outbreaks, of which norovirus-only combinations accounted for 76.2%. More outbreaks were due to different genotype combinations than the same genotype combinations. For facilities that experienced two norovirus outbreaks, the average interval between outbreaks was longer for groups with the same combinations than for groups with different genogroup or genotype combinations, although no statistically significant differences were observed. At 44 facilities, outbreaks occurred repeatedly during the same AG season, and most exhibited combinations of different norovirus genotypes or viruses. Among 49 combinations with the same norovirus genotype at the same facilities over 10 years, the most prevalent genotypes were combinations of genogroup II genotype 4 (GII.4), followed by GII.2, GII.6, GII.3, GII.14, and GI.3. The mean interval between outbreaks was 31.2 ± 26.8 months for all combinations, and the mean intervals were longer for non-GII.4 genotype cases than for GII.4 cases, and statistically significant differences were observed (t-test, P < 0.05). Additionally, these average intervals were longer for kindergarten/nursery schools and primary schools than for nursing homes for older adults (t-test, P < 0.05).ConclusionsRepeated AG outbreaks at the same facilities in Yokohama during the 10-year study period included mainly norovirus combinations. Herd immunity at the facility level was maintained for at least the same AG season. Norovirus genotype-specific herd immunity was maintained for an average of 31.2 months during the study period, and these intervals differed depending on genotype.

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.

Genome characterisation of norovirus GII.P17-GII.17 detected during a large gastroenteritis outbreak in Romania in 2021.

Norovirus (NoV) is one of the leading causes of acute gastroenteritis worldwide. Genotype GII.P17-G.II.17 emerged in Asia between 2013 and 2015 and transiently replaced the GII.4 Sydney 2012 variant circulating at that time. We present the genome characterisation of a GII.P17-GII.17 strain causing a large outbreak in Romania in 2021. Our study shows that the 2021 strain belongs to a novel cluster of genotype GII.17, different from the two previously recognised P.17 clusters. Distinctive substitutions in predicted conformational epitopes of VP1 were identified for this new cluster. Also, our phylogenetic analysis showed the existence of another P.17 cluster grouping strains from France and Canada.

Use of Zebrafish Embryos To Reproduce Human Norovirus and To Evaluate Human Norovirus Infectivity Decay after UV Treatment.

This study reports an essential improvement of the method for replication of human norovirus (HNoV) with the use of zebrafish (Danio rerio) embryos. With three HNoV genotypes and P-types GII.2[P16], GII.4[P16], and GII.17[P31], we demonstrated that this tool had higher efficiency and robustness than the zebrafish larvae as reported previously. When zebrafish larvae were injected with virus (1.6 ± 0.3 log genome copies/10 larvae), a significant increase of virus genome copies was detected at 2 days postinfection (dpi; 4.4 ± 0.8 log genome copies/10 larvae, P < 0.05) and the viral loads started to decrease gradually from 3 dpi. In comparison, when the viruses were injected into the zebrafish embryos, significant virus replication was noticed from 1 dpi and lasted to 6 dpi (P < 0.05). The virus levels detected at 3 dpi had the highest mean value and the smallest variation (7.7 ± 0.2 log genome copies/10 larvae). The high levels of virus replication enabled continuous passaging for all three strains up to four passages. The zebrafish embryo-generated HNoVs showed clear patterns of binding to human histo-blood group antigens (HBGAs) in human saliva by a simple saliva-binding reverse transcription-quantitative PCR (RT-qPCR). Last, in a disinfection study, it was shown that a dose of 6 mJ/cm2 UV254 was able induce a >2-log reduction in HNoV infectivity for all three HNoV strains tested, suggesting that HNoVs were more UV susceptible than multiple enteric viruses and commonly used HNoV surrogates as tested before. IMPORTANCE HNoVs are a leading cause of gastroenteritis outbreaks worldwide. The zebrafish embryo tool as developed in this study serves as an efficient way to generate viruses with high titers and clean background and a straightforward platform to evaluate HNoV inactivation efficacies. It is expected that this tool will not only benefit epidemiological research on HNoV but also be used to generate HNoV inactivation parameters which are highly needed by the water treatment and food industries.

Excess acute diarrhoea cases attributed to norovirus variants in Beijing, China between 2011 and 2018.

New norovirus (NoV) variants emerge often leading to increased acute gastroenteritis outbreaks and outpatient visits. However, these increases are rarely quantified. Between September 2011 and August 2018, we included a total of 133 131 acute diarrhoea cases in 11 enteric disease outpatient clinics which were open all year round in Beijing. Over the same period, the etiology surveillance for acute diarrhoea was conducted, a total of 13 139 specimens were collected and tested, and 16.84% (2213/13 139) of all specimens were NoV-positive. The partial VP1 genes were successfully sequenced in 965 NoV strains. GII.4 Sydney, GII.17, and GII.2 predominated in 2012-2013, 2014-2015, and 2016-2017, respectively. We estimated the excess NoV-associated acute diarrhoea cases using the adjusted Serfling regression model, and three excess periods were found, corresponding to the predominance periods of GII.4 Sydney, GII.17 and GII.2, respectively, represented increases of 180.5% (95% confidence interval [CI]: 115.0%-246.0%), 114.7% (95% CI: 66.4%-163.1%) and 152.6% (95% CI: 100.2%-205.0%), compared with the baseline level. New NoV variants often caused an excess in their first year of predominance, and the excess periods of NoV-associated acute diarrhoea cases coincided with the predominance periods of NoV variants.

Interrupted time series segmented regression analysis for detecting waterborne disease outbreaks by syndromic surveillance.

Pathogens can enter the drinking water supply and cause gastroenteritis outbreaks. Such events can affect many people in a short time, making them a high risk for public health. In Australia, the Victoria State Government Department of Health is deploying a syndromic surveillance system for drinking water contamination events. We assessed the utility of segmented regression models for detecting such events and determined the number of excess presentations needed for such methods to signal a detection. The study involved an interrupted time series study of a past lapse in water treatment. The baseline period comprised the four weeks before the minimum incubation period of suspected pathogens, set at two days post-event. The surveillance period comprised the week after. We used segmented linear regression to compare the count of gastroenteritis presentations to public hospital emergency departments (EDs) between the surveillance and baseline periods. We then simulated events resulting in varying excess presentations. These were superimposed onto the ED data over fifty different dates across 2020. Using the same regression, we calculated the detection probability at p < 0.05 for each outbreak size. In the retrospective analysis, there was strong evidence for an increase in presentations shortly after the event. In the simulations, with no excess presentations (i.e., with the ED data as is) the models signalled 8% probability of detection. The models returned 50% probability of detection with 28 excess presentations and 100% probability of detection with 78 excess presentations. The transient increase in presentations after the event may be attributed to microbiological hazards or increased health-seeking behaviour following the issuing of boil water advisories. The simulations demonstrated the ability for segmented regressions to signal a detection, even without a large excess in presentations. The approach also demonstrated high specificity and should be considered for informing Victoria's syndromic surveillance system.

Rare Recombinant GI.5[P4] Norovirus That Caused a Large Foodborne Outbreak of Gastroenteritis in a Hotel in Spain in 2021.

Noroviruses are among the most important causes of acute gastroenteritis (AGE). In summer 2021, a large outbreak of norovirus infections affecting 163 patients, including 15 norovirus-confirmed food handlers, occurred in a hotel in Murcia in southeast Spain. A rare GI.5[P4] norovirus strain was identified as the cause of the outbreak. The epidemiological investigation determined that norovirus transmission might have been initiated through an infected food handler. The food safety inspection found that some symptomatic food handlers continued working during illness. Molecular investigation with whole-genome and ORF1 sequencing provided enhanced genetic discrimination over ORF2 sequencing alone and enabled differentiation of the GI.5[P4] strains into separate subclusters, suggesting different chains of transmission. These recombinant viruses have been identified circulating globally over the last 5 years, warranting further global surveillance. IMPORTANCE Due to the large genetic diversity of noroviruses, it is important to enhance the discriminatory power of typing techniques to differentiate strains when investigating outbreaks and elucidating transmission chains. This study highlights the importance of (i) using whole-genome sequencing to ensure genetic differentiation of GI noroviruses to track chains of transmission during outbreak investigations and (ii) the adherence of symptomatic food handlers to work exclusion rules and strict hand hygiene practices. To our knowledge, this study provides the first full-length genome sequences of GI.5[P4] strains apart from the prototype strain.

An Outbreak Investigation of a Cluster of Gastroenteritis Following a Marriage Function in Wayanad District, Kerala, India

Foodborne diseases are a significant cause of morbidity and mortality, especially in low-resource settings. This paper describes the investigation conducted in response to a cluster of acute gastroenteritis outbreak in the Wayanad district of Kerala. House-to-house visits were undertaken to identify the case patients, along with laboratory and environmental investigations. The attack rate was 41.2% among those who consumed chicken biriyani compared to 6.9% among those who consumed vegetarian meals. The risk difference (95% CI) was 34.34 % (22.8-45.6), and the risk ratio (95% CI) was 6 (1.6-23) for chicken biriyani compared to vegetarian meals. The attributable fraction (95% CI) among those who ate chicken biriyani was 83.3% (35.6-95.6), and the population attributable fraction was 81.2%. We recommend strengthening of laboratory capacity for detecting foodborne pathogens and active surveillance of all food handlers and food preparation areas with the coordination of food safety, health and local self government departments.

A Point Source Gastroenteritis Outbreak in a High School Putatively Due to Clostridium perfringens: Timely Investigation Is Everything.

On May 28, 2021, several gastroenteritis cases were reported among students and staff of a high school on a Greek island. Lunches were delivered daily at the school by a catering company. We conducted a retrospective cohort study. Cases were defined as students or school staff presenting with diarrhea and abdominal pain between May 27 and 29, 2021. We used a self-administered questionnaire to collect the data. In the univariate analysis, we calculated food-specific attack rates (ARs), relative risks (RRs), and confidence intervals (95% CIs). Statistically significant variables (p < 0.05) were included in the multivariable model. Stool samples were collected from students on the same day of notification and were tested for bacteria, viruses, and parasites. The local food safety authority also inspected the school and the catering company premises. The food samples were sent to the reference laboratory for analysis. We received 129 responses from 174 students and staff members (response rate: 74%). Thirty cases were identified (AR, 23%). Of the 11 significant food items in the univariate analysis, the consumption of spaghetti with minced meat on May 27 (odds ratio 53.40, 95% CI: 3.9-736.1, 97% of cases exposed) was independently associated with the onset of gastroenteritis. Clostridium perfringens was detected in two of the three students' stool samples. Six samples from spaghetti with minced meat were positive for C. perfringens and four of those also tested positive for Bacillus cereus. Environmental investigation revealed non-compliances concerning food personnel training and Hazard Analysis and Critical Control Points (HACCP) plan implementation in the food establishment. Timely investigation and samples collection allowed the identification of the probable source of the outbreak. Changes, regarding the reception and distribution of meals in the school, were applied. Recommendations were given to the catering establishment focusing on adequate personnel training and HACCP issues, especially regarding temperature/time controls during all production, handling, and distribution phases.

Epidemiology of GII.4 and GII.2 norovirus outbreaks in closed and semi-closed institutions in 2017 and 2018

Norovirus infections are a leading cause of acute gastroenteritis outbreaks worldwide, with genotypes GII.2 and GII.4 being the most prevalent. The aim of this study was to compare the characteristics of GII.2 and GII.4 norovirus outbreaks reported in Catalonia in closed or semi-closed institutions in 2017 and 2018. The epidemiological and clinical characteristics of GII.2 and GII.4 outbreaks were compared using the chi-square test or Fisher's exact test for categorical variables and the Mann–Whitney U test for continuous variables. Odds ratios and their 95% confidence intervals were estimated. 61 outbreaks were reported: GII.4 was the causative agent in 12 outbreaks (30%) and GII.2 in 9 outbreaks (22.5%). GII.2 outbreaks were detected more frequently in schools or summer camps (66.7%) and GII.4 outbreaks in nursing homes (91.7%) (p = 0.01). Ninety-three people were affected in GII.2 outbreaks and 94 in GII.4 outbreaks. The median age was 15 years (range: 1–95 years) in GII.2 outbreaks and 86 years (range: 0–100 years) in GII.4 outbreaks (p < 0.001). Nausea, abdominal pain, and headache were observed more frequently in persons affected by GII.2 outbreaks (p < 0.05). Symptomatic cases presented a higher viral load suggestive of greater transmission capacity, although asymptomatic patients presented relevant loads indicative of transmission capacity.

Prevalence and Abundance of Bacterial Pathogens of Concern in Shrimp, Catfish and Tilapia Obtained at Retail Stores in Maryland, USA

Outbreaks of human gastroenteritis have been linked to the consumption of contaminated domestic and imported seafood. This study investigated the microbiological quality of seafood obtained from retail stores on the Eastern Shore of Maryland. A total of 440 samples of domestic and imported frozen shrimp, catfish and tilapia samples were analyzed for aerobic plate count (APC), total coliforms, Escherichia coli and seafood-borne-pathogens (Vibrio parahaemolyticus, Vibrio vulnificus, Salmonella, Campylobacter jejuni). The prevalence of APC, coliforms and E. coli positive samples was 100%, 43% and 9.3%, respectively. Approximately 3.2%, 1.4%, 28.9% and 3.6% of the samples were positive for V. parahaemolyticus, V. vulnificus, Salmonella and Campylobacter jejuni, respectively. The MPN/g ranges were 150-1100 MPN/g for vibrios, 10-1100 MPN/g for Salmonella and 93-460 MPN/g for C. jejuni in seafood, respectively. Comparing bacterial prevalence by type or source of seafood, the only significant difference identified was Salmonella-positive imported tilapia (33.3%) versus domestic tilapia (19.4%). The quantitative data on pathogen levels in the present study provide additional information for quantitative risk assessment not available in previous surveys. The findings of this study suggest the association of potential food safety hazards with domestic and imported seafood and warrant further large-scale studies and risk assessment.

Factors driving norovirus transmission in long-term care facilities: A case-level analysis of 107 outbreaks

Norovirus is the most common cause of gastroenteritis outbreaks in long-term care facilities (LTCFs) in the United States, causing a high burden of disease in both residents and staff. Understanding how case symptoms and characteristics contribute to norovirus transmission can lead to more informed outbreak control measures in LTCFs. We examined line lists for 107 norovirus outbreaks that took place in LTCFs in five U.S. states from 2015 to 2019. We estimated the individual effective reproduction number, Ri, to quantify individual case infectiousness and examined the contribution of vomiting, diarrhea, and being a resident (vs. staff) to case infectiousness. The associations between case characteristics and Ri were estimated using a multivariable, log-linear mixed model with inverse variance weighting. We found that cases with vomiting infected 1.28 (95 % CI: 1.11, 1.48) times the number of secondary cases compared to cases without vomiting, and LTCF residents infected 1.31 (95 % CI: 1.15, 1.50) times the number of secondary cases compared to staff. There was no difference in infectiousness between cases with and without diarrhea (1.07; 95 % CI: 0.90, 1.29). This suggests that vomiting, particularly by LTCF residents, was a primary driver of norovirus transmission. These results support control measures that limit exposure to vomitus during norovirus outbreaks in LTCFs.

A Large Acute Gastroenteritis Outbreak Associated with Both Campylobacter coli and Human Sapovirus - Beijing Municipality, China, 2021.

Campylobacter is a significant foodborne pathogen that leads to global outbreaks of acute gastroenteritis (AGE) usually affecting less than 30 individuals. Human sapovirus (HuSaV) is an enteric virus responsible for sporadic cases and outbreaks of AGE worldwide. In a study conducted in Beijing, HuSaV detection ranked second after norovirus. We present a discussion of the first large-scale outbreak of AGE caused by both Campylobacter coli (C. coli) and HuSaV. The outbreak involved a total of 996 patients and exhibited two distinct peaks over a period of 17 days. Through case-control studies, we identified exposure to raw water from a secondary water supply system as a significant risk factor. Among 83 patients, 49 samples tested positive for C. coli, 39 samples tested positive for HuSaV, and 27 samples tested positive for both pathogens using real-time polymerase chain reaction detection. Furthermore, whole-genome sequencing of 17 C. coli isolates obtained from 17 patients revealed that all isolates belonged to a highly clonal strain of C. coli. Outbreaks of AGE resulting from multiple pathogen infections warrant increased attention. This report emphasizes the significance of ensuring the safety of drinking water, particularly in secondary supply systems.

Genotypes Diversity of Acute Gastroenteritis Outbreaks Caused by Human Sapovirus - Beijing Municipality, China, 2015-2021.

Human sapovirus (HuSaV) is an enteric virus responsible for sporadic cases and outbreaks of acute gastroenteritis (AGE) globally. A seven-year active surveillance study was conducted to investigate the molecular epidemiology of HuSaVs associated with AGE outbreaks in Chaoyang District of Beijing Municipality, China from January 2015 to December 2021. Fecal and anal swab samples were obtained from patients experiencing AGE outbreaks. HuSaVs were identified through reverse transcription polymerase chain reaction (RT-PCR), and partial viral protein 1 (VP1) sequences (approximately 434 base pairs) were utilized for genotyping, single nucleotide polymorphism (SNP) analysis, and phylogenetic examination. HuSaVs were identified in 71 AGE outbreaks, demonstrating a detection rate of 10.5%, second only to norovirus. The primary demographic affected by HuSaV were children under the age of 5 in kindergarten settings. Infection rates tended to peak during two distinct periods: May to June and September to December. Upon genotyping, seven distinct genotypes emerged. GII.3 was the most prevalent, accounting for 54.9% of cases, followed by GI.1 (12.7%), GI.2 (9.9%), GII.5 (7.0%), GI.5 (2.8%), GI.6 (1.4%), GII.1 (1.4%), and untyped cases (9.9%). A phylogenetic analysis of GII.3 identified three distinct groups, with 15 notable SNPs observed. This study offers a comprehensive analysis of the persistent prevalence of HuSaV outbreaks in Chaoyang District, Beijing Municipality, China. Over time, the diversity of HuSaV subtypes has shifted, and it is now recognized as the second leading viral agent responsible for AGE outbreaks. This highlights the importance of ongoing surveillance in the future.

Simultaneous on-site visual identification of norovirus GI and GII genogroups with point-of-care molecular lateral flow strip

Norovirus (NoV) possesses a significant risk for outbreaks of acute gastroenteritis all over the world.

Asymptomatic Norovirus Infection Among Children in Kindergartens and Primary Schools - Beijing Municipality, China, 2021.

Children in kindergartens and primary schools are the high-incidence groups of norovirus acute gastroenteritis. However, asymptomatic norovirus infection among them is seldom reported. The norovirus positive rate was 3.48% among asymptomatic children in kindergartens and primary schools in Beijing Municipality in June 2021, the most common genotype was GII.4 Sydney, and no acute gastroenteritis outbreak was reported over the study period. The asymptomatic norovirus infection was relatively low among kindergarten children and primary school students in summer. Norovirus genotypes in asymptomatic children were similar to those circulating in the symptomatic cases. Asymptomatic norovirus infection may play a limited role in causing acute gastroenteritis outbreaks.

Structural Investigations on Novel Non-Nucleoside Inhibitors of Human Norovirus Polymerase.

Human norovirus is the first cause of foodborne disease worldwide, leading to extensive outbreaks of acute gastroenteritis, and causing around 200,000 children to die annually in developing countries. No specific vaccines or antiviral agents are currently available, with therapeutic options limited to supportive care to prevent dehydration. The infection can become severe and lead to life-threatening complications in young children, the elderly and immunocompromised individuals, leading to a clear need for antiviral agents, to be used as treatments and as prophylactic measures in case of outbreaks. Due to the key role played by the viral RNA-dependent RNA polymerase (RdRp) in the virus life cycle, this enzyme is a promising target for antiviral drug discovery. In previous studies, following in silico investigations, we identified different small-molecule inhibitors of this enzyme. In this study, we rationally modified five identified scaffolds, to further explore structure-activity relationships, and to enhance binding to the RdRp. The newly designed compounds were synthesized according to multiple-step synthetic routes and evaluated for their inhibition of the enzyme in vitro. New inhibitors with low micromolar inhibitory activity of the RdRp were identified, which provide a promising basis for further hit-to-lead optimization.

Diversity of human astroviruses in Germany 2018 and 2019

Aim of this study was to investigate the molecular diversity of human astroviruses (HAstV) in Germany. A follow-up study was performed with human stool samples collected in 2018–2019, which were genotyped retrospectively. A total of 2645 stool samples, collected between January 2018 and December 2019 from sporadic cases and outbreaks of acute gastroenteritis were analyzed. An algorithm of PCR systems was used to characterize human astrovirus. Human astroviruses were found in 40 samples (positive rate: 1.6%). During the study period, children aged 1–2 years (48%) were most affected by HAstV. Genotyping revealed a number of nine circulating genotypes representing four human Mamastrovirus species. Strain MLB1 was predominant in the study population with a detection rate of 25% followed by HAstV1 with a positive rate of 20%. The diversity of astrovirus genotypes seems to be rather stable in Germany in the last years. A clustering of regionally and/or temporally linked human astroviruses in Germany was not detectable.