Norovirus Outbreaks Research Articles

Study of Risk Factors for Total Attack Rate and Transmission Dynamics of Norovirus Outbreaks, Jiangsu Province, China, From 2012 to 2018.

Objective: To describe the epidemiological characteristics of norovirus outbreaks in Jiangsu Province, utilize the total attack rate (TAR) and transmissibility (Runc) as the measurement indicators of the outbreak, and a statistical difference in risk factors associated with TAR and transmissibility was compared. Ultimately, this study aimed to provide scientific suggestions to develop the most appropriate prevention and control measures.Method: We collected epidemiological data from investigation reports of all norovirus outbreaks in Jiangsu Province from 2012 to 2018 and performed epidemiological descriptions, sequenced the genes of the positive specimens collected that were eligible for sequencing, created a database and calculated the TAR, constructed SEIAR and SEIARW transmission dynamic models to calculate Runc, and performed statistical analyses of risk factors associated with the TAR and Runc.Results: We collected a total of 206 reported outbreaks, of which 145 could be used to calculate transmissibility. The mean TAR in was 2.6% and the mean Runc was 12.2. The epidemiological characteristics of norovirus outbreaks showed an overall increasing trend in the number of norovirus outbreaks from 2012 to 2018; more outbreaks in southern Jiangsu than northern Jiangsu; more outbreaks in urban areas than in rural areas; outbreaks occurred mostly in autumn and winter. Most of the sites where outbreaks occurred were schools, especially primary schools. Interpersonal transmission accounted for the majority. Analysis of the genotypes of noroviruses revealed that the major genotypes of the viruses changed every 3 years, with the GII.2 [P16] type of norovirus dominating from 2016 to 2018. Statistical analysis of TAR associated with risk factors found statistical differences in all risk factors, including time (year, month, season), location (geographic location, type of settlement, type of premises), population (total number of susceptible people at the outbreak site), transmission route, and genotype (P < 0.05). Statistical analysis of transmissibility associated with risk factors revealed that only transmissibility was statistically different between sites.Conclusions: The number of norovirus outbreaks in Jiangsu Province continues to increase during the follow-up period. Our findings highlight the impact of different factors on norovirus outbreaks and identify the key points of prevention and control in Jiangsu Province.

Improper handling of vomitus as a risk factor in the human norovirus outbreak in a kindergarten in Wuyi County, Zhejiang Province, China.

This study investigated an outbreak in a kindergarten in Wuyi County of acute gastroenteritis concerning a large number of students and teachers. We performed a case-control study, and collected information on the layout of the school, symptoms, onset time of all cases and vomiting sites. A total of 62 individuals fit the definition of probable cases; among these, there were 19 cases of laboratory-confirmed norovirus infection. Nausea and vomiting were the most common symptoms in the outbreak. Seven student norovirus patients vomited in the school. The odds ratio (OR) of norovirus illness was 15.75 times higher among teachers who handled or interacted with student vomitus without respiratory protection than compared to those without this type of exposure (OR 15.75, 95% CI 1.75-141.40). Nine samples were successfully genotyped; eight samples were norovirus GII.2[P16], one sample was norovirus GII.4 Sydney[P16]. This study revealed that improper handling of vomitus is a risk factor of norovirus infection. Therefore, more attention should be given to train school staff in knowledge of disinfection.

Detection of Norovirus Using Paper-Based Cell-Free Systems.

Norovirus infections are the leading cause of foodborne illness and human gastroenteritis, afflicting hundreds of millions of people each year. Molecular assays with the capacity to detect norovirus without expensive equipment and with high sensitivity and specificity represent useful tools to track and contain future outbreaks. Here we describe how norovirus can be detected in low-cost paper-based cell-free reactions. These assays combine freeze-dried, thermostable cell-free transcription-translation reactions with toehold switch riboregulators designed to target the norovirus genome, enabling convenient colorimetric assay readouts. Coupling cell-free reactions with synbody-based viral enrichment and isothermal amplification enables detection of norovirus from clinical samples down to concentrations as low as 270zM. These diagnostic tests are promising assays for confronting norovirus outbreaks and can be adapted to a variety of other human pathogens.

Assessment of Food and Waterborne Viral Outbreaks by Using Field Epidemiologic, Modern Laboratory and Statistical Methods-Lessons Learnt from Seven Major Norovirus Outbreaks in Finland.

Seven major food- and waterborne norovirus outbreaks in Western Finland during 2014–2018 were re-analysed. The aim was to assess the effectiveness of outbreak investigation tools and evaluate the Kaplan criteria. We summarised epidemiological and microbiological findings from seven outbreaks. To evaluate the Kaplan criteria, a one-stage meta-analysis of data from seven cohort studies was performed. The case was defined as a person attending an implicated function with diarrhoea, vomiting or two other symptoms. Altogether, 22% (386/1794) of persons met the case definition. Overall adjusted, 73% of norovirus patients were vomiting, the mean incubation period was 44 h (4 h to 4 days) and the median duration of illness was 46 h. As vomiting was a more common symptom in children (96%, 143/149) and diarrhoea among the elderly (92%, 24/26), symptom and age presentation should drive hypothesis formulation. The Kaplan criteria were useful in initial outbreak assessments prior to faecal results. Rapid food control inspections enabled evidence-based, public-health-driven risk assessments. This led to probability-based vehicle identification and aided in resolving the outbreak event mechanism rather than implementing potentially ineffective, large-scale public health actions such as the withdrawal of extensive food lots. Asymptomatic food handlers should be ideally withdrawn from high-risk work for five days instead of the current two days. Food and environmental samples often remain negative with norovirus, highlighting the importance of research collaborations. Electronic questionnaire and open-source novel statistical programmes provided time and resource savings. The public health approach proved useful within the environmental health area with shoe leather field epidemiology, combined with statistical analysis and mathematical reasoning.

Investigation and analysis on an outbreak of norovirus infection in a health school in Guangdong Province, China.

Our objective was to describe the epidemiological features of an outbreak of norovirus infection in a health school in Guangdong province, China, to identify the cause of such a large scale outbreak of norovirus among older students, to simulate the transmission dynamics, and to evaluate the effect of intervention measures of GII.17 [P17] genotype norovirus infection. We identified all cases during the outbreak. Descriptive epidemiological, analytical epidemiological and hygiene survey methods were used to described the outbreak epidemic course and identify the cause of the outbreak of norovirus infection. We also used dynamical model to simulate the transmission dynamics of norovirus infection and evaluate the effect of intervention measures. Norovirus genotyping was assigned to the newly obtained strains, with a maximum likelihood phylogenetic analysis conducted. There were 360 cases of 42 classes in five grades with a 12.99% attack rate. Proportionally, more students were in contact with sick students and vomit in the suspected case group than the control group (χ2=5.535, P=0.019 and χ2=5.549, P=0.019, respectively). The basic reproduction number was 8.32 before and 0.49 after the intervention. Dynamical modeling showed that if the isolation rate was higher or case isolation began earlier, the total attack rate would decrease. Molecular characterization identified the GII.17 [P17] genotype in all stains obtained from the health school, which were clustered with high support in the phylogenetic tree. This was an outbreak of norovirus infection caused by contact transmission. The main reasons for the spread of the epidemic were the later control time, irregular treatment of vomit and no case isolation. The transmission dynamics of contact transmission was high, more efficient control measures should be employed.

Norovirus outbreaks in long-term care facilities in Catalonia from 2017 to 2018

Norovirus is the leading cause of outbreaks of acute viral gastroenteritis. We carried out this study to investigate outbreaks in long-term care facilities reported in 2017 and 2018 in Catalonia (Spain). The characteristics of the centers, exposed persons and the genogroups responsible were analyzed. Viral loads were estimated. The attack rate (AR) of the outbreaks studied, and the rate ratio (RR) and the odds ratio (OR) and their 95% confidence intervals as measures of association were calculated. The mean cycle thresholds were compared using the t-test for independent means. We included 30 outbreaks (4631 exposed people). The global AR was 25.93%. The RR of residents vs. staff was 2.28 (95% CI 2.0–2.6). The RR between AR in residents with total or severe dependence vs. residents with moderate, low or no-dependence was 1.23 (95% CI 1.05–1.45). The AR were higher in smaller centers than in larger ones (38.47% vs. 19.25% and RR 2; 95% CI 1.82–2.2). GII was responsible for 70% of outbreaks. No association was found between the genogroup and presenting symptoms (OR 0.96; 95% CI 0.41–2.26). Viral loads were higher in symptomatic than in asymptomatic patients (p = 0.001).

Epidemiological characteristics and genetic diversity of norovirus infections among outpatient children with diarrhea under 5\xa0years of age in Beijing, China, 2011\u20132018

BackgroundHuman noroviruses are the leading cause of sporadic cases and outbreaks of viral acute gastroenteritis in all age groups worldwide.MethodsEpidemiological data and fecal specimens were collected between January 2011 and December 2018 from 4911 children < 5 years of age with diarrhea in three districts of Beijing. From 2011 to 2013, One-Step Reverse Transcription Polymerase Chain Reaction (RT-PCR) was used to detect noroviruses, and from January 2014 to December 2018, norovirus GI and GII were screened using duplex quantitative real-time RT-PCR (qRT-PCR). One-Step RT-PCR and RT-seminested PCR were performed to amplify the RNA-dependent polymerase and capsid genes of noroviruses in positive sample. Amplified products were sequenced directly; norovirus was typed using the online Norovirus Genotyping Tool v2.0 and phylogenetic analyses were conducted using MEGA-X.ResultsFrom 2011 to 2018, noroviruses were detected in 16.5% of specimens from children with diarrhea. The highest prevalence was observed in children aged 12 to 23 months (22.4%, 319/1421), followed by children aged 6 to 11 months (17.6%, 253/1441). The highest prevalence of norovirus infections occurred in autumn followed by winter, spring, and summer. From 2011 to 2018, the most prevalent dual types (genotype and polymerase type) were GII.4 Sydney[P31] (51.6%, 239/463), followed by GII.3[P12] (24.0%, 111/463), GII.4 2006b[P4 2006b] (7.3%, 34/463), GII.2[P16] (5.0%, 23/463), GII.17[P17] (2.6%, 12/463) and GII.6[P7] (2.6%, 12/463). GII.4 2006b[P4 2006b] predominated in 2011 and 2012. GII.4 Sydney[P31] predominated from 2013 to 2018. In total, 15 genotypes, 15 P-types and 19 dual types were detected in this study, reflecting the genetic diversity.ConclusionsThere were significant epidemiological characteristics and genetic diversity among outpatient children with norovirus infections < 5 years of age in Beijing from 2011 to 2018. These characteristics differ from those of norovirus outbreaks in Beijing. The complete genome sequences of each genotype are needed to better understand norovirus evolutionary mechanisms.

Norovirus outbreak amid COVID-19 in the United Kingdom; priorities for achieving control.

Norovirus, an enteric virus primarily responsible for gastroenteritis outbreaks worldwide, is currently causing outbreaks around the United Kingdom during the COVID‐19 pandemic. With an already exhausted health care system, the significant burden norovirus can have on the National Health Service, including economic and social burdens, is immense and cannot be tolerated. Primary challenges and priorities to be focused on due to the increase in norovirus outbreaks include a further depletion of health care services, increase cases in schools, nurseries, and care facilities, underreporting of the cases, and no effective vaccine being available. Therefore, it is essential to increase awareness about norovirus and its transmission in public, take necessary precautions, and increase reporting of cases. This article discusses the impact norovirus has during the COVID‐19 pandemic, and the challenges, and recommendations to achieve control before it reaches epidemic levels.

A norovirus gastroenteritis outbreak in an Australian child-care center: A household-level analysis.

There is a large burden of norovirus disease in child-care centers in Australia and around the world. Despite the ubiquity of norovirus outbreaks in child-care centers, little is known about the extent of this burden within the child-care center and the surrounding household clusters. Therefore, we performed an in-depth analysis of a gastroenteritis outbreak to examine the patterns of transmissions, household attack rates and the basic reproduction number (R0) for Norovirus in a child-care facility. We used data from parental interviews of suspected cases sent home with gastroenteritis at a child-care center between 24th of August and 18th of September 2020. A total of 52 persons in 19 household clusters were symptomatic in this outbreak investigation. Of all transmissions, 23 (46.9%) occurred in the child-care center, the rest occurring in households. We found a household attack rate of 36.5% (95% CI 27.3, 47.1%). Serial intervals were estimated as mean 2.5 ± SD1.45 days. The R0, using time-dependent methods during the growth phase of the outbreak (days 2 to 8) was 2.4 (95% CI 1.50, 3.50). The count of affected persons of a child-care center norovirus outbreak is approximately double the count of the total symptomatic staff and attending children. In the study setting, each symptomatic child-care attendee likely infected one other child-care attendee or staff and just over one household contact on average.

Spatiotemporal distribution of norovirus infection outbreaks in Chengdu

Objective To analyze the spatiotemporal distribution of norovirus infection outbreaks in Chengdu with the geographic information system (GIS) and provide evidence for the prevention and control of norovirus infection. Methods A database of the outbreaks of norovirus infection in Chengdu from 2014 to 2019 was established. The concentration ratio and circular distribution method were used to analyze the temporal clustering of the epidemic, and the Moran’s Ⅰ method was used to analyze spatial autocorrelation. Results The M value of norovirus outbreaks in Chengdu was 0.3927872, which showed the temporal clustering of norovirus infection with higher incidence in winter and the incidence peak during November - March. The incidence was higher in central urban area than in suburban area, with different “hot spot” or “cold spot” in different seasons. Conclusion There was obvious spatiotemporal clustering of norovirus infection outbreaks in Chengdu, suggesting that the prevention and control of norovirus infection should be strengthened in key area and period.

Epidemiologic Features and Influencing Factors of Norovirus Outbreaks in the City of Wuxi, China from 2014 to 2018.

ABSTRACT.The study investigated the genotypic changes and epidemiologic features of norovirus outbreaks and factors influencing the attack rate and outbreak duration in Wuxi from 2014 to 2018. Norovirus outbreaks, monitored through surveillance system, were investigated. The norovirus-positive specimens from outbreaks were collected and genotyped using a dual polymerase-capsid genotyping protocol based on a one-step polymerase chain reaction (PCR) amplicon. The genotypes were analyzed by Norovirus Typing Tool Version 2.0. A total of 74 norovirus outbreaks were reported in Wuxi from 2014 to 2018. Most (93.2%) norovirus outbreaks were caused by GII genotypes. The predominant norovirus genotypes in outbreaks have changed from GII.17 (20.3%) in 2014–2015 to GII.P16/GII.2 (40.5%) in 2017–2018. GII.P16/GII.2 in 2017–2018 season were more prevalent than GII.17 in 2014–2015 season (χ2 = 4.741, P = 0.029). 56.7% of the outbreaks occurred in primary schools. The re-outbreak rate was 16.2%. 66.7% of re-outbreaks were caused by norovirus variants different from previous genotypes. Outbreaks in nonprimary school settings (odds ratio [OR]: 4.007; 95% CI: 1.247–12.876) and those leading to temporary school or institution closure (OR: 20.510; 95% CI: 1.806–232.937) were reported with a higher attack rate. The outbreaks in primary schools (OR: 4.248; 95% CI: 1.211–14.903), re-outbreaks (OR: 6.433; 95% CI: 1.103–37.534) and longer report timing (OR: 8.380; 95% CI: 2.259–31.089) declared a significantly longer duration. It is of great importance that the monitoring of norovirus outbreaks for the emergence of novel strains, along with responsive prevention and control intervention should be strengthened in adults and school-age population, especially in primary students and preschool children.

Receptor profile and immunogenicity of the non-epidemic norovirus GII.8 variant

Noroviruses are causative agents of acute nonbacterial gastroenteritis epidemics worldwide. There are various genotypes, among which the non-epidemic genotype GII.8 can cause norovirus outbreaks. We previously demonstrated that the immunogenicity of GII.8 differed from that of epidemic variants. This study aimed to comprehensively compare the receptor profile and immunogenicity of the GII.8 variant with those of the epidemic variants. Using the baculovirus-insect cell expression system, we observed that recombinant capsid protein VP1 of the norovirus GII.8 GZ2017-L601 strain formed virus-like particles (VLPs) with a diameter of approximately 30 nm, as evidenced by transmission electron microscopy analysis. The GII.8 VLPs showed weak or moderate binding with all secretor histo-blood group antigens (HBGAs), but not with non-secretors, as evidenced by the HBGA-VLP binding test. The GII.8 VLP antiserum obtained from immunized BALB/c mice was tested for cross-reactivity with other norovirus genotypes (n = 28). The results showed that this antiserum demonstrated moderate cross-reactivity with GI.1, GII.3, and GII.15; however, no cross-reactivity with the epidemic variants of GII.2, GII.4, and GII.17 was observed. Additionally, the blocking-antibody activity of GII.8 antisera against GII.4 VLP-HBGAs and GII.17 VLP-HBGAs interactions and the cross-blocking of GII.8 VLP-HBGAs interactions by GI.1 and GII.4 antisera were evaluated using the HBGAs-VLP blocking test. However, no cross-blocking effect was observed. In summary, the characterization of norovirus GII.8 VLPs and derived antisera revealed that the GII.8 immunogenicity differed from that of epidemic variants.

Surveillance To Prevent the Spread of Norovirus Outbreak from Asymptomatic Food Handlers during the PyeongChang 2018 Olympics

Human noroviruses are major causes of nonbacterial gastroenteritis and are transmitted by both food and water, as well as person-to-person. Asymptomatic norovirus infection of food handlers may play a role in transmission. The outbreak of norovirus infections was recognized in the PyeongChang Winter Olympics, starting with security staff on 3 February 2018. The Ministry of Food and Drug Safety in the Republic of Korea conducted norovirus surveillance from asymptomatic food handlers of food-catering facilities related to the Olympics to prevent the spread of noroviruses. Rectal swab samples (707) from food handlers were collected and examined for noroviruses by using real-time reverse transcription PCR and conventional reverse transcription PCR. Five of 707 samples were identified as noroviruses. Genotypes of the norovirus-positive samples were determined with sequencing analysis. Identified genotypes of norovirus in asymptomatic food handlers included GI.3, GII.4, and GII.17. The GII.17 strain was prevalent among the genotypes, accounting for three of five detections. Food handlers with noroviruses detected in rectal swabs were excluded from cooking, and all food handled by infected food handlers was discarded. Surveillance of norovirus infection for food handlers contributed to preventing norovirus spread.

Predicting Norovirus in the United States Using Google Trends: Infodemiology Study.

BackgroundNorovirus is a contagious disease. The transmission of norovirus spreads quickly and easily in various ways. Because effective methods to prevent or treat norovirus have not been discovered, it is important to rapidly recognize and report norovirus outbreaks in the early phase. Internet search has been a useful method for people to access information immediately. With the precise record of internet search trends, internet search has been a useful tool to manifest infectious disease outbreaks.ObjectiveIn this study, we tried to discover the correlation between internet search terms and norovirus infection.MethodsThe internet search trend data of norovirus were obtained from Google Trends. We used cross-correlation analysis to discover the temporal correlation between norovirus and other terms. We also used multiple linear regression with the stepwise method to recognize the most important predictors of internet search trends and norovirus. In addition, we evaluated the temporal correlation between actual norovirus cases and internet search terms in New York, California, and the United States as a whole.ResultsSome Google search terms such as gastroenteritis, watery diarrhea, and stomach bug coincided with norovirus Google Trends. Some Google search terms such as contagious, travel, and party presented earlier than norovirus Google Trends. Some Google search terms such as dehydration, bar, and coronavirus presented several months later than norovirus Google Trends. We found that fever, gastroenteritis, poison, cruise, wedding, and watery diarrhea were important factors correlated with norovirus Google Trends. In actual norovirus cases from New York, California, and the United States as a whole, some Google search terms presented with, earlier, or later than actual norovirus cases.ConclusionsOur study provides novel strategy-based internet search evidence regarding the epidemiology of norovirus.

Norovirus Outbreaks in Long-term Care Facilities in the United States, 2009-2018: A Decade of Surveillance.

In the United States, norovirus is the leading cause of healthcare-associated gastroenteritis outbreaks. To inform prevention efforts, we describe the epidemiology of norovirus outbreaks in long-term care facilities (LTCFs). The Centers for Disease Control and Prevention (CDC) collect epidemiologic and laboratory data on norovirus outbreaks from US health departments through the National Outbreak Reporting System (NORS) and CaliciNet. Reports from both systems were merged, and norovirus outbreaks in nursing homes, assisted living, and other LTCFs occurring in 2009-2018 were analyzed. Data from the Centers for Medicare and Medicaid Services and the National Center for Health Statistics were used to estimate state LTCF counts. During 2009-2018, 50 states, Washington D.C., and Puerto Rico reported 13 092 norovirus outbreaks and 416 284 outbreak-associated cases in LTCFs. Participation in NORS and CaliciNet increased from 2009 to 2014 and median reporting of LTCF norovirus outbreaks stabilized at 4.1 outbreaks per 100 LTCFs (interquartile range [IQR]: 1.0-7.1) annually since 2014. Most outbreaks were spread via person-to-person transmission (90.4%), and 75% occurred during December-March. Genogroup was reported for 7292 outbreaks with 862 (11.8%) positive for GI and 6370 (87.3%) for GII. Among 4425 GII outbreaks with typing data, 3618 (81.8%) were GII.4. LTCF residents had higher attack rates than staff (median 29.0% vs 10.9%; P < .001). For every 1000 cases, there were 21.6 hospitalizations and 2.3 deaths. LTCFs have a high burden of norovirus outbreaks. Most LTCF norovirus outbreaks occurred during winter months and were spread person-to-person. Outbreak surveillance can inform development of interventions for this vulnerable population, such as vaccines targeting GII.4 norovirus strains.

Enteric Illness Outbreaks Reported Through the National Outbreak Reporting System-United States, 2009-2019.

The National Outbreak Reporting System (NORS) captures data on foodborne, waterborne, and enteric illness outbreaks in the United States. This study describes enteric illness outbreaks reported during 11 years of surveillance. We extracted finalized reports from NORS for outbreaks occurring during 2009-2019. Outbreaks were included if caused by an enteric etiology or if any patients reported diarrhea, vomiting, bloody stools, or unspecified acute gastroenteritis. A total of 38 395 outbreaks met inclusion criteria, increasing from 1932 in 2009 to 3889 in 2019. Outbreaks were most commonly transmitted through person-to-person contact (n = 23 812; 62%) and contaminated food (n = 9234; 24%). Norovirus was the most commonly reported etiology, reported in 22 820 (59%) outbreaks, followed by Salmonella (n = 2449; 6%) and Shigella (n = 1171; 3%). Norovirus outbreaks were significantly larger, with a median of 22 illnesses per outbreak, than outbreaks caused by the other most common outbreak etiologies (P < .0001, all comparisons). Hospitalization rates were higher in outbreaks caused by Salmonella and Escherichia coli outbreaks (20.9% and 22.8%, respectively) than those caused by norovirus (2%). Case fatality rate was highest in E. coli outbreaks (0.5%) and lowest in Shigella and Campylobacter outbreaks (0.02%). Norovirus caused the most outbreaks and outbreak-associated illness, hospitalizations, and deaths. However, persons in E. coli and Salmonella outbreaks were more likely to be hospitalized or die. Outbreak surveillance through NORS provides the relative contributions of each mode of transmission and etiology for reported enteric illness outbreaks, which can guide targeted interventions.

Structure-Activity Relationship Studies on Novel Antiviral Agents for Norovirus Infections.

Human norovirus is the leading cause of acute gastroenteritis worldwide, affecting every year 685 million people. Norovirus outbreaks are associated with very significant economic losses, with an estimated societal cost of 60 billion USD per year. Despite this, no therapeutic options or vaccines are currently available to treat or prevent this infection. An antiviral therapy that can be used as treatment and as a prophylactic measure in the case of outbreaks is urgently needed. We previously described the computer-aided design and synthesis of novel small-molecule agents able to inhibit the replication of human norovirus in cell-based systems. These compounds are non-nucleoside inhibitors of the viral polymerase and are characterized by a terminal para-substituted phenyl group connected to a central phenyl ring by an amide-thioamide linker, and a terminal thiophene ring. Here we describe new modifications of these scaffolds focused on exploring the role of the substituent at the para position of the terminal phenyl ring and on removing the thioamide portion of the amide-thioamide linker, to further explore structure-activity relationships (SARs) and improve antiviral properties. According to three to four-step synthetic routes, we prepared thirty novel compounds, which were then evaluated against the replication of both murine (MNV) and human (HuNoV) norovirus in cells. Derivatives in which the terminal phenyl group has been replaced by an unsubstituted benzoxazole or indole, and the thioamide component of the amide-thioamide linker has been removed, showed promising results in inhibiting HuNoV replication at low micromolar concentrations. Particularly, compound 28 was found to have an EC50 against HuNoV of 0.9 µM. Although the most active novel derivatives were also associated with an increased cytotoxicity in the human cell line, these compounds represent a very promising starting point for the development of new analogues with reduced cytotoxicity and improved selectivity indexes. In addition, the experimental biological data have been used to create an initial 3D quantitative structure-activity relationship model, which could be used to guide the future design of novel potential anti-norovirus agents.

Quantitative microbial risk assessment of human norovirus infection in environmental service workers due to healthcare-associated fomites

Healthcare-associated norovirus outbreaks place a large burden on healthcare staff. Environmental service workers (ESWs), however, remain understudied despite high contact with potentially contaminated surfaces. Understanding the magnitude of the risk of norovirus infection in healthcare ESWs can protect workers and improve infection control. This study simulated the risk of norovirus infection for unprotected ESWs after a single fomite contact, assuming no disinfection or protective equipment, in norovirus-positive patient rooms. In addition, the risk of secondary surface transmission from norovirus-exposed ESWs was simulated. A quantitative microbial risk assessment employing two-dimensional Monte Carlo simulation with parameters extracted from the literature was used to estimate norovirus infection from multiple fomite contact scenarios defined by: norovirus source (patient vomit/diarrhoea), location (bathroom/patient room) and target outcome (ESW/secondary illness). Unprotected ESWs have a maximum estimated risk of norovirus infection of 33% (1:3) for a single fomite contact in a room where a norovirus-positive patient had a diarrhoeal event. Patient vomit events lead to fomite contact risk estimates that are four orders of magnitude lower than those for diarrhoeal events. The estimated risk of secondary illness from touching a common surface is as high as 25% (1:4) after single fomite exposure following a diarrhoeal event. A single fomite contact may lead to sizable risk of norovirus infection in ESWs if personal protective equipment and disinfection are not used appropriately. ESWs can also transfer virus to secondary surfaces, initiating further infections. Interventions are needed to reduce fomite transfer of norovirus, and protect patients and staff from nosocomial infections.

Development of a Specific Anti-capsid Antibody- and Magnetic Bead-Based Immunoassay to Detect Human Norovirus Particles in Stool Samples and Spiked Mussels via Flow Cytometry.

Human noroviruses impose a considerable health burden globally. Here, a flow cytometry approach designed for their detection in biological waste and food samples was developed using antibody-coated magnetic beads. Antipeptide antibodies against murine norovirus and various human norovirus genotypes were generated for capture and coated onto magnetic beads. A flow cytometry assay was then implemented to detect bead-bound human norovirus GI.3 in patient stool samples and in norovirus-spiked mussel digestive tissues. The detection limit for stool samples was 105gc/mL, thus bettering detection limits of commercially available norovirus diagnosis quick kits of 100-fold; the detection limit in spiked mussels however was ten-fold higher than in stool samples. Further assays showed a decrease in fluorescence intensity for heat- or UV-inactivated virus particles. Overall, we demonstrate the application of a flow cytometry approach for direct detection of small non-enveloped virus particles such as noroviruses. An adaptation of the technology to routine diagnostics has the potential to contribute a rapid and sensitive tool to norovirus outbreak investigations. Further improvements to the method, notably decreasing the detection limit of the approach, may allow the analysis of naturally contaminated food and environmental samples.

Norovirus Foodborne Outbreak Associated With the Consumption of Ice Pop, Southern Brazil, 2020.

Norovirus is a major cause of foodborne-associated acute gastroenteritis (AGE) outbreaks worldwide. Usually, food products are contaminated either during harvesting or preparation, and the most common products associated to norovirus outbreaks are raw or undercooked bivalve shellfish, fruits (frozen berries) and ready-to-eat produce. In the present study, we investigated an AGE outbreak caused by norovirus associated with the consumption of ice pops in southern Brazil. Clinical stool samples from patients and ice pops samples were collected and analyzed for viruses' detection. By using RT-qPCR and sequencing, we detected the uncommon genotype GII.12[P16] in clinical samples and GII.12 in samples of ice pop. Strains shared identity of 100% at nucleotide level strongly suggesting the consumption of ice pops as the source of the outbreak.