BACKGROUND In France,nitazoxanide is available through compassionate use authorization,as there is no summary of product characteristics for this medication.However,it has been marketed in the United States for severa...BACKGROUND In France,nitazoxanide is available through compassionate use authorization,as there is no summary of product characteristics for this medication.However,it has been marketed in the United States for several years,with evidence supporting its use in the treatment of chronic norovirus infections in immunocompromised individuals.Due to its limited use,data on the efficacy and safety of this drug remain sparse.CASE SUMMARY We report the case of a 79-year-old immunocompromised patient,a renal transplant recipient undergoing treatment with mycophenolate mofetil and tacrolimus,who developed toxic agranulocytosis,as absolute neutrophil count dropped from 2.93 G/L to 0.09 G/L within 17 days following the introduction of nitazoxanide for the treatment of chronic diarrhea caused by norovirus infection.Clinical and laboratory findings suggest a toxic mechanism,most likely attributable to nitazoxanide.CONCLUSION This case highlights the potential of nitazoxanide to induce dose-dependent toxic agranulocytosis.While this adverse effect does not necessarily contraindicate reintroduction of the drug,it underscores the necessity for close hematological monitoring in such cases.展开更多
AIM:To report an acute gastroenteritis outbreak caused by a genogroup 2 genotype 6(GII.6) strain norovirus in Shanghai,China.METHODS:Noroviruses are responsible for approximately half of all reported gastroenteritis o...AIM:To report an acute gastroenteritis outbreak caused by a genogroup 2 genotype 6(GII.6) strain norovirus in Shanghai,China.METHODS:Noroviruses are responsible for approximately half of all reported gastroenteritis outbreaks in many countries.Genogroup 2 genotype 4 strains are the most prevalent.Rare outbreaks caused by GII.6 strains have been reported.An acute gastroenteritis outbreak occurred in an elementary school in Shanghai in December of 2013.Field and molecular epidemiologic investigations were conducted.RESULTS:The outbreak was limited to one class in an elementary school located in southwest Shanghai.The age of the students ranged from 9 to 10 years.The first case emerged on December 10,2013,and the last case emerged on December 14,2013.The cases peaked on December 11,2013,with 21 new cases.Of 45 students in the class,32 were affected.The main symptom was gastroenteritis,and 15.6%(5/32) of the cases exhibited a fever.A field epidemiologic investigation showed the pathogen may have been transmitted to the elementary school from employees in a delicatessen via the first case student,who had eaten food from the delicatessen one day before the gastroenteritis episodes began.A molecular epidemiologic investigation identified the cause of the gastroenteritis as norovirus strain GII.6;the viral sequence of the student cases showed 100% homology with that of the shop employees.Genetic relatedness analyses showed that the new viral strain is closely related to previously reported GII.6 sequences,especially to a strain reported in Japan.CONCLUSION:This is the first report to show that norovirus strain GII.6 can cause a gastroenteritis outbreak.Thus,the prevalence of GII.6 noroviruses requires attention.展开更多
Noroviruses are the leading cause of acute gastroenteritis in humans. Real-time reverse transcription-polymerase chain reaction(real-time RT-PCR) is a promising molecular method for the detection of noroviruses. In th...Noroviruses are the leading cause of acute gastroenteritis in humans. Real-time reverse transcription-polymerase chain reaction(real-time RT-PCR) is a promising molecular method for the detection of noroviruses. In this study, the performance of three Taq Man real-time RT-PCR assays was assessed, which were one commercially available real-time RT-PCR kit(assay A:Norovirus Real Time RT-PCR kit) and two in-house real-time RT-PCR assays(assay B: Light Cycler RNA Master Hybprobe and assay C: Real Time ready RNA Virus Master). Assays A and B showed higher sensitivity than assay C for norovirus GI, while they all had the same sensitivity(103 DNA copies/m L) for GII DNA standard controls. Assay B had the highest efficiency for both genogroups.No cross-reactivity was observed among GI and GII noroviruses, rotavirus, hepatitis A virus, and poliovirus. The detection rates of these assays in GI and GII norovirus-positive fecal samples were not significantly different. However, the mean quantification cycle(Cq) value of assay B for GII was lower than assays A and C with statistical significance(P-value, 0.000). All three real-time RT-PCR assays could detect a variety of noroviruses including GI.2, GII.2, GII.3, GII.4, GII.6, GII.12, GII.17,and GII.21. This study suggests assay B as a suitable assay for the detection and quantification of noroviruses GI and GII due to good analytical sensitivity and higher performance to amplify norovirus on DNA standard controls and clinical samples.展开更多
Dear Editor,Noroviruses are positive-sense, single-stranded RNA viruses belonging to Caliciviridae and account for more than 50%of all acute gastroenteritis (AGE) outbreaks worldwide and cause an estimated 200,000 dea...Dear Editor,Noroviruses are positive-sense, single-stranded RNA viruses belonging to Caliciviridae and account for more than 50%of all acute gastroenteritis (AGE) outbreaks worldwide and cause an estimated 200,000 deaths per year among children\5 years of age, primarily in developing countries (Hall et al. 2012;Glass et al. 2009). The norovirus genome contains three open reading frames (ORFs).展开更多
Objective Shellfish are recognized as important vehicles of norovirus-associated gastroenteritis. The present study aimed to monitor norovirus contamination in oysters along the farm-to-fork continuum in Guangxi, a ma...Objective Shellfish are recognized as important vehicles of norovirus-associated gastroenteritis. The present study aimed to monitor norovirus contamination in oysters along the farm-to-fork continuum in Guangxi, a major oyster production area in Southwestern China. Methods Oyster samples were collected monthly from farms, markets, and restaurants, from January to December 2016. Norovirus was detected and quantified by one-step reverse transcription-droplet digital polymerase chain reaction（RT-ddPCR）. Results A total of 480 oyster samples were collected and tested for norovirus genogroups I and II. Norovirus was detected in 20.7% of samples, with genogroup II predominating. No significant difference was observed in norovirus prevalence among different sampling sites. The norovirus levels varied widely, with a geometric mean of 19,300 copies/g in digestive glands. Both norovirus prevalence and viral loads showed obvious seasonality, with a strong winter bias. Conclusion This study provides a systematic analysis of norovirus contamination ‘from the farm to the fork＇ in Guangxi. RT-ddPCR can be a useful tool for detection and quantification of low amounts of norovirus in the presence of inhibitors found particularly in foodstuffs. This approach will contribute to the development of strategies for controlling and reducing the risk of human illness resulting from shellfish consumption.展开更多
AIM To assess the burden of norovirus(No V) and to determine the diversity of circulating strains among hospitalized children in Lebanon. METHODS Stool samples were collected from children presenting with acute gastro...AIM To assess the burden of norovirus(No V) and to determine the diversity of circulating strains among hospitalized children in Lebanon. METHODS Stool samples were collected from children presenting with acute gastroenteritis to six major hospitals in Lebanon. A total of 739 eligible stool samples, testing negative for diarrhea caused by rotavirus as a possible viral pathogen, were collected between January 2011 and June 2013. A standardized questionnaire including demographic, epidemiological and clinical observations was used at the time of hospitalization of children presenting with diarrhea. Viral RNA was extracted from stool samples followed by reverse transcription polymerase chain reaction and nucleotide sequencing of a fragment of the viral protein 1 capsid gene. Multiple sequence alignments were carried out and phylogenetic trees were constructed using the MEGA 6 software.RESULTS Overall, 11.2% of stool samples collected from children aged < 5 years tested positive for No V genogroups Ⅰ(GⅠ) and Ⅱ(GⅡ). GⅡ accounted for 10.6% of the gastroenteritis cases with only five samples being positive for GⅠ(0.7%). The majority of hospitalized children showed symptoms of diarrhea, dehydration, vomiting and fever. Upon sequencing of positive samples and based on their clustering in the phylogenetic tree, 4/5 of GⅠ gastroenteritis cases were designated GⅠ.3 and one case as GⅠ.4. GⅡ.4 was predominantly detected in stool of our study participants(68%). We report a JB-15/KOR/2008 GⅡ.4 Apeldoorn 2008-like variant strain circulating in 2011; this strain was replaced between 2012 and 2013 by a variant sharing homology with the Sydney/NSW0514/2012/AUS GⅡ.4 Sydney 2012 and Sydney 2012/FRA GⅡ.4 strains. We also report the co-circulation of non-GⅡ.4 genotypes among hospitalized children. Our data show that No V gastroenteritis can occur throughout the year with the highest number of cases detected during the hot months.CONCLUSION The majority of No V-associated viral gastroenteritis cases among our participants are attributable to GⅡ.4, which is compatible with results reported worldwide.展开更多
Objective To clarify the epidemiological characteristics and spatial distribution patterns of human norovirus outbreaks in China, identify high-risk areas, and provide guidance for epidemic prevention and control.Meth...Objective To clarify the epidemiological characteristics and spatial distribution patterns of human norovirus outbreaks in China, identify high-risk areas, and provide guidance for epidemic prevention and control.Methods This study analyzed 964 human norovirus outbreaks involving 50,548 cases in 26 provinces reported from 2012 to 2018. Epidemiological analysis and spatiotemporal scanning analysis were conducted to analyze the distribution of norovirus outbreaks in China.Results The outbreaks showed typical seasonality, with more outbreaks in winter and fewer in summer, and the total number of infected cases increased over time. Schools, especially middle schools and primary schools, are the most common settings of norovirus outbreaks, with the major transmission route being life contact. More outbreaks occurred in southeast coastal areas in China and showed significant spatial aggregation. The highly clustered areas of norovirus outbreaks have expanded northeast over time.Conclusion By identifying the epidemiological characteristics and high-risk areas of norovirus outbreaks, this study provides important scientific support for the development of preventive and control measures for norovirus outbreaks, which is conducive to the administrative management of high-risk settings and reduction of disease burden in susceptible areas.展开更多
Norovirus(NoV)is an important cause of viral acute gastroenteritis(AGE).To gain insights into the epidemio-logical characteristics and genetic diversity of NoV among children in Hubei,1216 stool samples from children(...Norovirus(NoV)is an important cause of viral acute gastroenteritis(AGE).To gain insights into the epidemio-logical characteristics and genetic diversity of NoV among children in Hubei,1216 stool samples from children(≤5 years)obtained under AGE surveillance from January 2017 to December 2019 were analyzed.The results showed that NoV was responsible for 14.64%of AGE cases,with the highest detection rate in children aged 7-12 months(19.76%).Statistically significant differences were found between male and female infection rates(χ^(2)=8.108,P¼0.004).Genetic analysis of RdRp and VP1 sequences showed that NoV GII genotypes were GII.4 Sydney[P31](34.35%),GII.3[P12](25.95%),GII.2[P16](22.90%),GII.4 Sydney[P16](12.98%),GII.17[P17](2.29%),GII.6[P7]and GII.3[P16](each at 0.76%).GII.17[P17]variants were divided into the Kawasaki323-like lineage and the Kawasaki308-like lineage.A unique recombination event was detected between strains of GII.4 Sydney 2012 and GII.4 Sydney 2016.Significantly,all GII.P16 sequences associated with GII.4/GII.2 ob-tained in Hubei were correlated with novel GII.2[P16]variants that re-emerged in Germany in 2016.Antigenic site analysis of complete VP1 sequences from all GII.4 variants from Hubei identified notable variable residues of antibody epitopes.Genotyping under continuous AGE surveillance and observation of the antigenic sites of VP1 are important monitoring strategies for emerging NoV strains.展开更多
Norovirus(NoV)is a major pathogen that causes acute gastroenteritis(AGE)in people of all ages,especially in children.In this study,we investigated the molecular epidemiological characteristics of NoV in children with ...Norovirus(NoV)is a major pathogen that causes acute gastroenteritis(AGE)in people of all ages,especially in children.In this study,we investigated the molecular epidemiological characteristics of NoV in children with AGE in Shanghai from 2018 to 2021.The overall detection rate of NoV was 11.9%(181/1545),with annual detection rates of 9.4%(36/381),13.6%(29/213),5.8%(13/226)and 14.2%(103/725),respectively.Of note,the prevalence of NoV in 2020 was significantly lower than that in 2018-2019(10.9%,65/594)(P=0.023)and 2021(14.2%,103/725)(P=0.000).The 181 NoV strains identified in this study were classified into the GI group(1.1%,2/181),GII group(98.3%,178/181)and GIX group(0.6%,1/181)according to the VP1 gene.The most common NoV VP1 genotype was GII.4 Sydney_2012(63.5%,115/181),followed by GII.3(19.9%,36/181)and GII.2(9.4%,17/181).For P genotypes,174 strains were sequenced successfully according to the RdRp gene,and the predominant genotype was GII.P16(44.8%,78/174),followed by GII.P31(25.9%,45/174)and GII.P12(21.3%,37/174).Among the 174 cases,GII.4 Sydney_2012[P16](36.8%,64/174)was the dominant genotype,followed by GII.4 Sydney_2012[P31](25.3%,44/174),GII.3[P12](20.1%,35/174)and GII.2[P16](8.0%,14/174).In particular,the dominant genotypes in Shanghai changed from GII.4 Sydney_2012[P31]in 2018-2019 to GII.4 Sydney_2012[P16]in 2020-2021.This is the first report to describe the epidemiological changes in NoV infection before and during the COVID-19 pandemic in Shanghai.These data highlight the importance of continuous surveillance for NoV in children with AGE in Shanghai.展开更多
Noroviruses (NoVs) are widespread causes of nonbacterial gastroenteritis. Outbreaks of NoVs caused diseases are commonly ascribed to the consumption of contaminated shellfish. The concentration and RNA extraction of N...Noroviruses (NoVs) are widespread causes of nonbacterial gastroenteritis. Outbreaks of NoVs caused diseases are commonly ascribed to the consumption of contaminated shellfish. The concentration and RNA extraction of NoVs are crucial steps of detecting NoVs in shellfish. This study aimed to select a simple, rapid and highly efficient recovery method of NoVs detection with real-time RT-PCR. Four methods of recovering GI.3 and GII.4 NoVs from spiked digestive tissues of oysters and clams, respectively, were compared, of them, the method involving proteinase K and PEG 8000 was found the most efficient. With this method, 9.3% and 13.1% of GI.3 and GII.4 NoVs were recovered from oysters and 9.6% and 12.3% of GI.3 and GII.4 NoVs were recovered from clams, respectively. This method was further used to detect NoVs in 84 oysters (Crassostrea gigas) and 86 clams (Ruditapes philippinarum) collected from 10 coastal cities in China from Jan. 2011 to Feb. 2012. The NoVs isolation rates were 10.47% of clams (9/86) and 7.14% of oysters (6/84). All the detected NoVs belonged to genotype GII. The NoVs recovery method selected is efficient for NoVs detection in oysters and clams.展开更多
Norovirus(NoV)is regarded as one of the most common causes of foodborne diarrhea in the world.It is urgent to identify the pathogenic microorganism of the diarrhea in short time.In this work,we developed an electroche...Norovirus(NoV)is regarded as one of the most common causes of foodborne diarrhea in the world.It is urgent to identify the pathogenic microorganism of the diarrhea in short time.In this work,we developed an electrochemical and colorimetric dual-mode detection for NoV based on the excellent dual catalytic properties of copper peroxide/COF-NH_(2)nanocomposite(CuO_(2)@COF-NH_(2)).For the colorimetric detection,NoV can be directly detected by the naked eye based on CuO_(2)@COF-NH_(2)as a laccase-like nonazyme using“peptide-NoV-antibody”recognition mode.The colorimetric assay displayed a wide and quality linear detection range from 1 copy/mL to 5000 copies/mL of NoV with a low limit of detection(LOD)of 0.125 copy/mL.For the electrochemical detection of NoV,CuO_(2)@COF-NH_(2)showed an oxidation peak of copper ion from Cu^(+)to Cu^(2+)using“peptide-NoV-antibody”recognition mode.The electrochemical assay showed a linear detection range was 1-5000 copies/mL with a LOD of 0.152 copy/mL.It's worthy to note that this assay does not need other electrical signal molecule,which provide the stable and sensitive electrochemial detection for NoV.The electrochemical and colorimetric dual-mode detection was used to detect NoV in foods and faceal samples,which has the potential for improving food safety and diagnosing of NoV-infected diarrhea.展开更多
Noroviruses(NoVs)are the primary cause of acute gastroenteritis worldwide.Histo-blood group antigens(HBGAs)are receptors or attachment factors that affect the prevalence and host susceptibility of NoVs.GII.6 NoV is on...Noroviruses(NoVs)are the primary cause of acute gastroenteritis worldwide.Histo-blood group antigens(HBGAs)are receptors or attachment factors that affect the prevalence and host susceptibility of NoVs.GII.6 NoV is one of the predominant genotypes in humans,which recognizes the type ABO secretor of HBGAs.However,the structural basis of GII.6 NoV's interaction with HBGAs receptors remains elusive.In this study,we investigated the binding features of the GII.6 strain to HBGAs using saliva-and glycan-ELISA assays and characterized the molecular basis of the GII.6 virus that recognizes H disaccharide.We showed that the GII.6 P domain recognized some A and O secretor's saliva samples,most B secretor's saliva samples,and H disaccharide antigen,but did not bind non-secretors’saliva.Further,we determined the crystal structures of GII.6 and its complex with H disaccharides at 1.7Å,revealing that the P domain of GII.6 shares the conventional binding interface and mode of GII HBGAs.Single residue mutations at the GII.6-H binding sites could inhibit the binding of GII.6 to HBGAs,demonstrating that the interaction residues were crucial in maintaining NoV-glycan integrity.Finally,structural and sequence analyses showed that the major residues of the GII.6-H interaction were conserved among NoVs in the GII genogroup.Taken together,our study characterized the functional and structural features of GII.6 that allow it to interact with HBGAs,and shed light on NoV evolution,epidemiology,and anti-viral drug development.展开更多
Norovirus （NOV） is a pathogen that commonly causes viral diarrhea in children. Studies indicate that NoV recognizes human histo-blood group antigens （HBGAs） as cell attachment factors. In order to explore the corr...Norovirus （NOV） is a pathogen that commonly causes viral diarrhea in children. Studies indicate that NoV recognizes human histo-blood group antigens （HBGAs） as cell attachment factors. In order to explore the correlation between of NoV infection and HBGAs, a cross-sectional study was conducted in children less than five years old who were hospitalized with diarrhea in two areas of China between November 2014 and February 2015. Of the paired stool and saliva samples taken from 424 children,展开更多
Noroviruses(NoVs) are the main cause of viral gastroenteritis outbreaks worldwide, and oysters are the most common carriers of NoV contamination and transmission. NoVs bind specifically to oyster tissues through histo...Noroviruses(NoVs) are the main cause of viral gastroenteritis outbreaks worldwide, and oysters are the most common carriers of NoV contamination and transmission. NoVs bind specifically to oyster tissues through histo-blood group antigens(HBGAs), and this facilitates virus accumulation and increases virus persistence in oysters. To investigate the interaction of HBGAs in Pacific oysters with GⅡ.4 NoV, we examined HBGAs with ELISAs and investigated binding patterns with oligosaccharide-binding assays using P particles as a model of five GⅡ.4 NoV capsids. The HBGAs in the gut and gills exhibited polymorphisms. In the gut, type A was detected(100%), whereas type Leb(91.67%) and type A(61.11%) were both observed in the gills. Moreover, we found that seasonal NoV gastroenteritis outbreaks were not significantly associated with the specific HBGAs detected in the oyster gut and gills. In the gut, we found that strain-2006 b and strain-96/96 US bound to type A and H1 but only weakly bound to type Leb; in contrast, the Camberwell and Hunter strains exhibited weak binding to types H1 and Ley, and strain-Sakai exhibited no binding to any HBGA type. In the gills, strain-96/96 US and strain-2006 b bound to type Leb but only weakly bound to type H1; strains Camberwell, Hunter, and Sakai did not bind to oyster HBGAs. Assays for oligosaccharide binding to GⅡ.4 NoV P particles showed that strain-95/96 US and strain-2006 b strongly bound to type A, B, H1, Leb, and Ley oligosaccharides, while strains Camberwell and Hunter showed weak binding ability to type H1 and Ley oligosaccharides and strain-Sakai showed weak binding ability to type Leb and Ley oligosaccharides. Our study presents new information and enhances understanding about the mechanism for NoV accumulation in oysters. Further studies of multiple NoV-tissue interactions might assist in identifying new or improved strategies for minimizing contamination, including HBGA-based attachment inhibition or depuration.展开更多
Human noroviruses(HuNoVs)are major foodborne pathogens that cause nonbacterial acute gastroenteritis worldwide.As the tissue-culture system for HuNoVs is not mature enough for routine detection of the virus,detection ...Human noroviruses(HuNoVs)are major foodborne pathogens that cause nonbacterial acute gastroenteritis worldwide.As the tissue-culture system for HuNoVs is not mature enough for routine detection of the virus,detection is mainly dependent on molecular approaches such as reverse transcription polymerase chain reaction(RT-PCR)and reverse transcription quantitative real-time polymerase chain reaction(RTqPCR).The widely used primers and probes for RT-qPCR were established in the early 2000s.As HuNoVs are highly variant viruses,viral genome mutations result in previously designed primers and/or probes that were perfectly matched working less efficiently over time.In this study,a new duplex RT-qPCR(ND-RT-qPCR)was designed for the detection of genogroup Ⅰ(GⅠ)and genogroup Ⅱ(GⅡ)HuNoVs based on an analysis of viral sequences added in the database after 2010.Using long transcribed viral RNAs,the results demonstrate that the sensitivity of ND-RT-qPCR is as low as one genomic copy for both GⅠ and GⅡ HuNoVs.The performance of ND-RT-qPCR was further evaluated by a comparison with the commonly used Kageyama primer/probe sets for RT-qPCR(Kageyama RT-qPCR)for 23 HuNoV-positive clinical samples.All five GⅠ samples were registered as positive by ND-RT-qPCR,whereas only two samples were registered as positive by Kageyama RT-qPCR.All 18 GⅡ samples were registered as positive by ND-RT-qPCR,while 17 samples were registered as positive by Kageyama RT-qPCR.The sensitivity reflected by the quantification cycle(Cq)value was lower in ND-RT-qPCR than in Kageyama RT-qPCR.Our data suggest that ND-RT-qPCR could be a good fit for the detection of current strains of HuNoVs.展开更多
Objective: To determine the prevalence of astrovirus, norovirus, adenovirus in children below five years old with diarrhea by multiplex reverse transcriptase polymerase chain reaction(RT-PCR) along with rotavirus anti...Objective: To determine the prevalence of astrovirus, norovirus, adenovirus in children below five years old with diarrhea by multiplex reverse transcriptase polymerase chain reaction(RT-PCR) along with rotavirus antigen detection by enzyme linked immunosorbant assay.Methods: The study was conducted on children below five years old complaining of acute diarrhea. The study included stool examination by molecular method for detection of norovirus, adenovirus and astrovirus by multiplex RT-PCR. Rotavirus antigen was detected in the stool by enzyme linked immunosorbant assay.Results: The study included 100 children below 5 years old with acute diarrhea.Multiplex RT-PCR was positive in 34% of the children. The most frequently detected virus was rotavirus(44%), followed by norovirus(30%), adenovirus(20%) and astrovirus(14%). The clinical symptoms were more significantly associated with viral diarrhea such as fever(P = 0.03), bloody diarrhea(P = 0.025), vomiting(P = 0.000 1) and watery diarrheas(P = 0.05). The frequency of diarrhea with viral pathogen was significantly presented in winter season(39.7%). There were significant frequencies of norovirus and adenovirus in age ranging 1–2 years old(P = 0.04, P = 0.01 respectively).Conclusions: The present study spotlights on the prevalence of viral pathogens as an important etiology in diarrhea in children below five years old. Astrovirus, norovirus and adenovirus are common along with rotavirus in this group of patients. Multiplex PCR leads to improve the laboratory diagnosis of these viruses along with antigen detection method. Further longitudinal studies are required to evaluate the epidemiological data associated with these viruses and for proper management of such drastic infection.展开更多
Norovirus is one of the most common causes of viral gastroenteritis in the world,causing significant morbidity,deaths,and medical costs.In this work,we look at stochastic modelling methodologies for norovirus transmis...Norovirus is one of the most common causes of viral gastroenteritis in the world,causing significant morbidity,deaths,and medical costs.In this work,we look at stochastic modelling methodologies for norovirus transmission by water,human to human transmission and food.To begin,the proposed stochastic model is shown to have a single global positive solution.Second,we demonstrate adequate criteria for the existence of a unique ergodic stationary distribution R0 s>1 by developing a Lyapunov function.Thirdly,we find sufficient criteria Rs<1 for disease extinction.Finally,two simulation examples are used to exemplify the analytical results.We employed optimal control theory and examined stochastic control problems to regulate the spread of the disease using some external measures.Additional graphical solutions have been produced to further verify the acquired analytical results.This research could give a solid theoretical foundation for understanding chronic communicable diseases around the world.Our approach also focuses on offering a way of generating Lyapunov functions that can be utilized to investigate the stationary distribution of epidemic models with nonlinear stochastic disturbances.展开更多
The efficacy of an activated sludge (modified Ludzack-Ettinger (MLE)) UV disinfection processes in removing human noroviruses and E. coli from sewage were compared with the prevalence of these microorganisms in a sett...The efficacy of an activated sludge (modified Ludzack-Ettinger (MLE)) UV disinfection processes in removing human noroviruses and E. coli from sewage were compared with the prevalence of these microorganisms in a settled storm discharge from the same sewage treatment works. Both discharges impacted a designated oyster production area. The treatment process delivered average NoV and E. coli reductions of 2.9log10 and 5.2log10, respectively. Most E. coli reductions occurred during the UV disinfection process whereas the MLE process was comparatively more important in reducing NoV levels. A positive relationship was found between NoV removal and measured applied UV dose. The average levels of total NoV in the settled storm tank were of the same order of magnitude of those in screened raw influent at the works. These results highlight the importance of measures to reduce the impact of stormwater discharges to minimise the risk of NoV gastroenteritis associated with the consumption of oysters.展开更多
Norovirus(NoV)infection is a major cause of gastroenteritis worldwide.The virus poses great challenges in developing vaccines with broad immune protection due to its genetic and antigenic diversity.To date,there are n...Norovirus(NoV)infection is a major cause of gastroenteritis worldwide.The virus poses great challenges in developing vaccines with broad immune protection due to its genetic and antigenic diversity.To date,there are no approved NoV vaccines for clinical use.Here,we aimed to develop a broad-acting quadrivalent NoV vaccine based on a chimpanzee adenovirus vector,AdC68,carrying the major capsid protein(VP1)of noroviral GI and GII genotypes.Compared to intramuscular(i.m.),intranasal(i.n.),or other prime-boost immunization regimens(i.m.t i.m.,i.m.t i.n.,i.n.t i.m.),AdC68-GI.1-GII.3(E1)-GII.4-GII.17(E3),administered via i.n.t i.n.induced higher titers of serum IgG antibodies and higher IgA antibodies in bronchoalveolar lavage fluid(BALF)and saliva against the four homologous VP1s in mice.It also significantly stimulated the production of blocking antibodies against the four genotypes.In response to re-stimulation with virus-like particles(VLP)-GI.1,VLP-GII.3,VLP-GII.4,and VLP-GII.17,the quadrivalent vaccine administered according to the i.n.t i.n.regimen effectively triggered specific cell-mediated immune responses,primarily characterized by IFN-γsecretion.Furthermore,the preparation of this novel quadrivalent NoV vaccine requires only a single recombinant adenovirus to provide broad preventive immunity against the major GI/GII epidemic strains,making it a promising vaccine candidate for further development.展开更多
Noroviruses are the most common cause of acute gastroenteritis. Annually, 21 million Americans are infected with norovirus. Recent advances in molecular diagnostics have helped to establish norovirus as the most commo...Noroviruses are the most common cause of acute gastroenteritis. Annually, 21 million Americans are infected with norovirus. Recent advances in molecular diagnostics have helped to establish norovirus as the most common cause of outbreaks of acute gastroenteritis across all ages. However, there is no effective or efficient treatment/control against norovirus infection. Conventional intervention techniques used to inactivate norovirus have shown lack of efficacy against human norovirus. Currently, effective treatment or control measures against human norovirus have not been identified. In this study, murine norovirus acts as a model to human norovirus to evaluate the inhibitory effects of crude extracts of Zanthoxylum armatum and Hibiscus sabdariffa. The study also separated, identified and quantified the selected compounds using the ultra-liquid chromatography (UPLC). To study the antiviral activities of crude extracts and its fractionated portions of Z. armatum and H. sabdariffa against norovirus surrogate, RAW 264.7 cells were infected with Murine norovirus surrogate virus of human norovirus and incubated at 37?C. Phytochemicals were extracted from the seeds and calyces of the plants using methanolic extraction. Fractionated portions of the crude extracts were subsequently used in both chromatographic and microbiological studies. Our data indicated that there was reduction of viruses, when treated with the 60% aqueous methanol extracts. Amongst the four selected phenolic compounds (myricetin, quercetin, kaempferol and luteolin), quercetin showed the most significant logarithmic viral reductions. These compounds were identified, purified and quantified using UPLC. Extracts of Zanthoxylum armatum and Hibiscus sabdariffa showed antiviral effects. Phenolic compounds are virucidal. Extracts of Hibiscus sabdariffa also exhibits anti-norovirus activities. The results are anticipated to control/prevent the human norovirus infections.展开更多
文摘BACKGROUND In France,nitazoxanide is available through compassionate use authorization,as there is no summary of product characteristics for this medication.However,it has been marketed in the United States for several years,with evidence supporting its use in the treatment of chronic norovirus infections in immunocompromised individuals.Due to its limited use,data on the efficacy and safety of this drug remain sparse.CASE SUMMARY We report the case of a 79-year-old immunocompromised patient,a renal transplant recipient undergoing treatment with mycophenolate mofetil and tacrolimus,who developed toxic agranulocytosis,as absolute neutrophil count dropped from 2.93 G/L to 0.09 G/L within 17 days following the introduction of nitazoxanide for the treatment of chronic diarrhea caused by norovirus infection.Clinical and laboratory findings suggest a toxic mechanism,most likely attributable to nitazoxanide.CONCLUSION This case highlights the potential of nitazoxanide to induce dose-dependent toxic agranulocytosis.While this adverse effect does not necessarily contraindicate reintroduction of the drug,it underscores the necessity for close hematological monitoring in such cases.
文摘AIM:To report an acute gastroenteritis outbreak caused by a genogroup 2 genotype 6(GII.6) strain norovirus in Shanghai,China.METHODS:Noroviruses are responsible for approximately half of all reported gastroenteritis outbreaks in many countries.Genogroup 2 genotype 4 strains are the most prevalent.Rare outbreaks caused by GII.6 strains have been reported.An acute gastroenteritis outbreak occurred in an elementary school in Shanghai in December of 2013.Field and molecular epidemiologic investigations were conducted.RESULTS:The outbreak was limited to one class in an elementary school located in southwest Shanghai.The age of the students ranged from 9 to 10 years.The first case emerged on December 10,2013,and the last case emerged on December 14,2013.The cases peaked on December 11,2013,with 21 new cases.Of 45 students in the class,32 were affected.The main symptom was gastroenteritis,and 15.6%(5/32) of the cases exhibited a fever.A field epidemiologic investigation showed the pathogen may have been transmitted to the elementary school from employees in a delicatessen via the first case student,who had eaten food from the delicatessen one day before the gastroenteritis episodes began.A molecular epidemiologic investigation identified the cause of the gastroenteritis as norovirus strain GII.6;the viral sequence of the student cases showed 100% homology with that of the shop employees.Genetic relatedness analyses showed that the new viral strain is closely related to previously reported GII.6 sequences,especially to a strain reported in Japan.CONCLUSION:This is the first report to show that norovirus strain GII.6 can cause a gastroenteritis outbreak.Thus,the prevalence of GII.6 noroviruses requires attention.
基金supported by research grant from the Thailand Research Fund (TRF) through the Royal Golden Jubilee Ph.D. program (Grant No. PHD/0085/2554)the Thai Government Budget through Mahidol University, fiscal year 2015-2017
文摘Noroviruses are the leading cause of acute gastroenteritis in humans. Real-time reverse transcription-polymerase chain reaction(real-time RT-PCR) is a promising molecular method for the detection of noroviruses. In this study, the performance of three Taq Man real-time RT-PCR assays was assessed, which were one commercially available real-time RT-PCR kit(assay A:Norovirus Real Time RT-PCR kit) and two in-house real-time RT-PCR assays(assay B: Light Cycler RNA Master Hybprobe and assay C: Real Time ready RNA Virus Master). Assays A and B showed higher sensitivity than assay C for norovirus GI, while they all had the same sensitivity(103 DNA copies/m L) for GII DNA standard controls. Assay B had the highest efficiency for both genogroups.No cross-reactivity was observed among GI and GII noroviruses, rotavirus, hepatitis A virus, and poliovirus. The detection rates of these assays in GI and GII norovirus-positive fecal samples were not significantly different. However, the mean quantification cycle(Cq) value of assay B for GII was lower than assays A and C with statistical significance(P-value, 0.000). All three real-time RT-PCR assays could detect a variety of noroviruses including GI.2, GII.2, GII.3, GII.4, GII.6, GII.12, GII.17,and GII.21. This study suggests assay B as a suitable assay for the detection and quantification of noroviruses GI and GII due to good analytical sensitivity and higher performance to amplify norovirus on DNA standard controls and clinical samples.
基金supported by the Special National Project on Research and Development of Key Biosafety Technologies (2016YFC1201900)the National Natural Science Foundation of China (31500139)
文摘Dear Editor,Noroviruses are positive-sense, single-stranded RNA viruses belonging to Caliciviridae and account for more than 50%of all acute gastroenteritis (AGE) outbreaks worldwide and cause an estimated 200,000 deaths per year among children\5 years of age, primarily in developing countries (Hall et al. 2012;Glass et al. 2009). The norovirus genome contains three open reading frames (ORFs).
文摘Objective Shellfish are recognized as important vehicles of norovirus-associated gastroenteritis. The present study aimed to monitor norovirus contamination in oysters along the farm-to-fork continuum in Guangxi, a major oyster production area in Southwestern China. Methods Oyster samples were collected monthly from farms, markets, and restaurants, from January to December 2016. Norovirus was detected and quantified by one-step reverse transcription-droplet digital polymerase chain reaction（RT-ddPCR）. Results A total of 480 oyster samples were collected and tested for norovirus genogroups I and II. Norovirus was detected in 20.7% of samples, with genogroup II predominating. No significant difference was observed in norovirus prevalence among different sampling sites. The norovirus levels varied widely, with a geometric mean of 19,300 copies/g in digestive glands. Both norovirus prevalence and viral loads showed obvious seasonality, with a strong winter bias. Conclusion This study provides a systematic analysis of norovirus contamination ‘from the farm to the fork＇ in Guangxi. RT-ddPCR can be a useful tool for detection and quantification of low amounts of norovirus in the presence of inhibitors found particularly in foodstuffs. This approach will contribute to the development of strategies for controlling and reducing the risk of human illness resulting from shellfish consumption.
基金Supported by an investigator-initiated research grant from Merck Sharpe and Dohme(MSD)University Review Board Grant,American University of Beirut
文摘AIM To assess the burden of norovirus(No V) and to determine the diversity of circulating strains among hospitalized children in Lebanon. METHODS Stool samples were collected from children presenting with acute gastroenteritis to six major hospitals in Lebanon. A total of 739 eligible stool samples, testing negative for diarrhea caused by rotavirus as a possible viral pathogen, were collected between January 2011 and June 2013. A standardized questionnaire including demographic, epidemiological and clinical observations was used at the time of hospitalization of children presenting with diarrhea. Viral RNA was extracted from stool samples followed by reverse transcription polymerase chain reaction and nucleotide sequencing of a fragment of the viral protein 1 capsid gene. Multiple sequence alignments were carried out and phylogenetic trees were constructed using the MEGA 6 software.RESULTS Overall, 11.2% of stool samples collected from children aged < 5 years tested positive for No V genogroups Ⅰ(GⅠ) and Ⅱ(GⅡ). GⅡ accounted for 10.6% of the gastroenteritis cases with only five samples being positive for GⅠ(0.7%). The majority of hospitalized children showed symptoms of diarrhea, dehydration, vomiting and fever. Upon sequencing of positive samples and based on their clustering in the phylogenetic tree, 4/5 of GⅠ gastroenteritis cases were designated GⅠ.3 and one case as GⅠ.4. GⅡ.4 was predominantly detected in stool of our study participants(68%). We report a JB-15/KOR/2008 GⅡ.4 Apeldoorn 2008-like variant strain circulating in 2011; this strain was replaced between 2012 and 2013 by a variant sharing homology with the Sydney/NSW0514/2012/AUS GⅡ.4 Sydney 2012 and Sydney 2012/FRA GⅡ.4 strains. We also report the co-circulation of non-GⅡ.4 genotypes among hospitalized children. Our data show that No V gastroenteritis can occur throughout the year with the highest number of cases detected during the hot months.CONCLUSION The majority of No V-associated viral gastroenteritis cases among our participants are attributable to GⅡ.4, which is compatible with results reported worldwide.
基金supported by the National Natural Science Foundation of China[grant number 81903377]Young Scholar Foundation of NIEH[grant number 19qnjj]。
文摘Objective To clarify the epidemiological characteristics and spatial distribution patterns of human norovirus outbreaks in China, identify high-risk areas, and provide guidance for epidemic prevention and control.Methods This study analyzed 964 human norovirus outbreaks involving 50,548 cases in 26 provinces reported from 2012 to 2018. Epidemiological analysis and spatiotemporal scanning analysis were conducted to analyze the distribution of norovirus outbreaks in China.Results The outbreaks showed typical seasonality, with more outbreaks in winter and fewer in summer, and the total number of infected cases increased over time. Schools, especially middle schools and primary schools, are the most common settings of norovirus outbreaks, with the major transmission route being life contact. More outbreaks occurred in southeast coastal areas in China and showed significant spatial aggregation. The highly clustered areas of norovirus outbreaks have expanded northeast over time.Conclusion By identifying the epidemiological characteristics and high-risk areas of norovirus outbreaks, this study provides important scientific support for the development of preventive and control measures for norovirus outbreaks, which is conducive to the administrative management of high-risk settings and reduction of disease burden in susceptible areas.
基金the sub-project of Major National Science and Technology Projects(grant number 2017ZX10103005)the Natural Science Foundation of Hubei Province(grant number 2018CFB716,2022CFB015)the Health and Family Planning Scientific Research Project of Hubei Province(grant number WJ2017M137,WJ2023M107).
文摘Norovirus(NoV)is an important cause of viral acute gastroenteritis(AGE).To gain insights into the epidemio-logical characteristics and genetic diversity of NoV among children in Hubei,1216 stool samples from children(≤5 years)obtained under AGE surveillance from January 2017 to December 2019 were analyzed.The results showed that NoV was responsible for 14.64%of AGE cases,with the highest detection rate in children aged 7-12 months(19.76%).Statistically significant differences were found between male and female infection rates(χ^(2)=8.108,P¼0.004).Genetic analysis of RdRp and VP1 sequences showed that NoV GII genotypes were GII.4 Sydney[P31](34.35%),GII.3[P12](25.95%),GII.2[P16](22.90%),GII.4 Sydney[P16](12.98%),GII.17[P17](2.29%),GII.6[P7]and GII.3[P16](each at 0.76%).GII.17[P17]variants were divided into the Kawasaki323-like lineage and the Kawasaki308-like lineage.A unique recombination event was detected between strains of GII.4 Sydney 2012 and GII.4 Sydney 2016.Significantly,all GII.P16 sequences associated with GII.4/GII.2 ob-tained in Hubei were correlated with novel GII.2[P16]variants that re-emerged in Germany in 2016.Antigenic site analysis of complete VP1 sequences from all GII.4 variants from Hubei identified notable variable residues of antibody epitopes.Genotyping under continuous AGE surveillance and observation of the antigenic sites of VP1 are important monitoring strategies for emerging NoV strains.
基金This work was supported by grants from the Key Development Program of the Children's Hospital of Fudan University(grant no.EK2022ZX05).
文摘Norovirus(NoV)is a major pathogen that causes acute gastroenteritis(AGE)in people of all ages,especially in children.In this study,we investigated the molecular epidemiological characteristics of NoV in children with AGE in Shanghai from 2018 to 2021.The overall detection rate of NoV was 11.9%(181/1545),with annual detection rates of 9.4%(36/381),13.6%(29/213),5.8%(13/226)and 14.2%(103/725),respectively.Of note,the prevalence of NoV in 2020 was significantly lower than that in 2018-2019(10.9%,65/594)(P=0.023)and 2021(14.2%,103/725)(P=0.000).The 181 NoV strains identified in this study were classified into the GI group(1.1%,2/181),GII group(98.3%,178/181)and GIX group(0.6%,1/181)according to the VP1 gene.The most common NoV VP1 genotype was GII.4 Sydney_2012(63.5%,115/181),followed by GII.3(19.9%,36/181)and GII.2(9.4%,17/181).For P genotypes,174 strains were sequenced successfully according to the RdRp gene,and the predominant genotype was GII.P16(44.8%,78/174),followed by GII.P31(25.9%,45/174)and GII.P12(21.3%,37/174).Among the 174 cases,GII.4 Sydney_2012[P16](36.8%,64/174)was the dominant genotype,followed by GII.4 Sydney_2012[P31](25.3%,44/174),GII.3[P12](20.1%,35/174)and GII.2[P16](8.0%,14/174).In particular,the dominant genotypes in Shanghai changed from GII.4 Sydney_2012[P31]in 2018-2019 to GII.4 Sydney_2012[P16]in 2020-2021.This is the first report to describe the epidemiological changes in NoV infection before and during the COVID-19 pandemic in Shanghai.These data highlight the importance of continuous surveillance for NoV in children with AGE in Shanghai.
基金supported by the China-Australia Bilateral Research Program (No. 2010DFA31720)the National Key Technology R&D Program (2012BAD28B05)
文摘Noroviruses (NoVs) are widespread causes of nonbacterial gastroenteritis. Outbreaks of NoVs caused diseases are commonly ascribed to the consumption of contaminated shellfish. The concentration and RNA extraction of NoVs are crucial steps of detecting NoVs in shellfish. This study aimed to select a simple, rapid and highly efficient recovery method of NoVs detection with real-time RT-PCR. Four methods of recovering GI.3 and GII.4 NoVs from spiked digestive tissues of oysters and clams, respectively, were compared, of them, the method involving proteinase K and PEG 8000 was found the most efficient. With this method, 9.3% and 13.1% of GI.3 and GII.4 NoVs were recovered from oysters and 9.6% and 12.3% of GI.3 and GII.4 NoVs were recovered from clams, respectively. This method was further used to detect NoVs in 84 oysters (Crassostrea gigas) and 86 clams (Ruditapes philippinarum) collected from 10 coastal cities in China from Jan. 2011 to Feb. 2012. The NoVs isolation rates were 10.47% of clams (9/86) and 7.14% of oysters (6/84). All the detected NoVs belonged to genotype GII. The NoVs recovery method selected is efficient for NoVs detection in oysters and clams.
基金financially supported by National Key Research and Development Program of China(2022YFC2601604)Major science and technology project of Yunnan Province(202202AE090085)+9 种基金the National Natural Science Foundation of China(3216059732160236)Science and technology talent and platform plan of YunnanKey Scientific and Technology Project of Yunnan(202203AC100010)Spring City Plan:the High-level Talent Promotion and Training Project of Kunming(2022SCP001)the second phase of“Double-First Class”program construction of Yunnan Universitygrants from State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan,Yunnan University(2021KF005)Key Scientific and Technology Project of Yunnan(202002AE320005)Program for Excellent Young Talents of Yunnan Universitythe Program for Donglu Scholars of Yunnan University。
文摘Norovirus(NoV)is regarded as one of the most common causes of foodborne diarrhea in the world.It is urgent to identify the pathogenic microorganism of the diarrhea in short time.In this work,we developed an electrochemical and colorimetric dual-mode detection for NoV based on the excellent dual catalytic properties of copper peroxide/COF-NH_(2)nanocomposite(CuO_(2)@COF-NH_(2)).For the colorimetric detection,NoV can be directly detected by the naked eye based on CuO_(2)@COF-NH_(2)as a laccase-like nonazyme using“peptide-NoV-antibody”recognition mode.The colorimetric assay displayed a wide and quality linear detection range from 1 copy/mL to 5000 copies/mL of NoV with a low limit of detection(LOD)of 0.125 copy/mL.For the electrochemical detection of NoV,CuO_(2)@COF-NH_(2)showed an oxidation peak of copper ion from Cu^(+)to Cu^(2+)using“peptide-NoV-antibody”recognition mode.The electrochemical assay showed a linear detection range was 1-5000 copies/mL with a LOD of 0.152 copy/mL.It's worthy to note that this assay does not need other electrical signal molecule,which provide the stable and sensitive electrochemial detection for NoV.The electrochemical and colorimetric dual-mode detection was used to detect NoV in foods and faceal samples,which has the potential for improving food safety and diagnosing of NoV-infected diarrhea.
基金supported by grants from the National Natural Science Foundation of China(no.32100111,21934005)Guangdong Basic and Applied Basic Reuter Foundation(no.2019A1515110220)+1 种基金China Postdoctoral Science Foundation(no.2020M682900)Shenzhen High-level Hospital Construction Fund.
文摘Noroviruses(NoVs)are the primary cause of acute gastroenteritis worldwide.Histo-blood group antigens(HBGAs)are receptors or attachment factors that affect the prevalence and host susceptibility of NoVs.GII.6 NoV is one of the predominant genotypes in humans,which recognizes the type ABO secretor of HBGAs.However,the structural basis of GII.6 NoV's interaction with HBGAs receptors remains elusive.In this study,we investigated the binding features of the GII.6 strain to HBGAs using saliva-and glycan-ELISA assays and characterized the molecular basis of the GII.6 virus that recognizes H disaccharide.We showed that the GII.6 P domain recognized some A and O secretor's saliva samples,most B secretor's saliva samples,and H disaccharide antigen,but did not bind non-secretors’saliva.Further,we determined the crystal structures of GII.6 and its complex with H disaccharides at 1.7Å,revealing that the P domain of GII.6 shares the conventional binding interface and mode of GII HBGAs.Single residue mutations at the GII.6-H binding sites could inhibit the binding of GII.6 to HBGAs,demonstrating that the interaction residues were crucial in maintaining NoV-glycan integrity.Finally,structural and sequence analyses showed that the major residues of the GII.6-H interaction were conserved among NoVs in the GII genogroup.Taken together,our study characterized the functional and structural features of GII.6 that allow it to interact with HBGAs,and shed light on NoV evolution,epidemiology,and anti-viral drug development.
基金supported by the National Natural Science Foundation of China(81472003 and 31500139)
文摘Norovirus （NOV） is a pathogen that commonly causes viral diarrhea in children. Studies indicate that NoV recognizes human histo-blood group antigens （HBGAs） as cell attachment factors. In order to explore the correlation between of NoV infection and HBGAs, a cross-sectional study was conducted in children less than five years old who were hospitalized with diarrhea in two areas of China between November 2014 and February 2015. Of the paired stool and saliva samples taken from 424 children,
基金Supported by the National Natural Science Foundation of China(No.31471663)the Qingdao Postdoctoral Application Research Project
文摘Noroviruses(NoVs) are the main cause of viral gastroenteritis outbreaks worldwide, and oysters are the most common carriers of NoV contamination and transmission. NoVs bind specifically to oyster tissues through histo-blood group antigens(HBGAs), and this facilitates virus accumulation and increases virus persistence in oysters. To investigate the interaction of HBGAs in Pacific oysters with GⅡ.4 NoV, we examined HBGAs with ELISAs and investigated binding patterns with oligosaccharide-binding assays using P particles as a model of five GⅡ.4 NoV capsids. The HBGAs in the gut and gills exhibited polymorphisms. In the gut, type A was detected(100%), whereas type Leb(91.67%) and type A(61.11%) were both observed in the gills. Moreover, we found that seasonal NoV gastroenteritis outbreaks were not significantly associated with the specific HBGAs detected in the oyster gut and gills. In the gut, we found that strain-2006 b and strain-96/96 US bound to type A and H1 but only weakly bound to type Leb; in contrast, the Camberwell and Hunter strains exhibited weak binding to types H1 and Ley, and strain-Sakai exhibited no binding to any HBGA type. In the gills, strain-96/96 US and strain-2006 b bound to type Leb but only weakly bound to type H1; strains Camberwell, Hunter, and Sakai did not bind to oyster HBGAs. Assays for oligosaccharide binding to GⅡ.4 NoV P particles showed that strain-95/96 US and strain-2006 b strongly bound to type A, B, H1, Leb, and Ley oligosaccharides, while strains Camberwell and Hunter showed weak binding ability to type H1 and Ley oligosaccharides and strain-Sakai showed weak binding ability to type Leb and Ley oligosaccharides. Our study presents new information and enhances understanding about the mechanism for NoV accumulation in oysters. Further studies of multiple NoV-tissue interactions might assist in identifying new or improved strategies for minimizing contamination, including HBGA-based attachment inhibition or depuration.
基金supported by the Ministry of Science and Technology of China(2017YFC1601200)the National Natural Science Foundation of China(31772078)the Agri-X Interdisciplinary Fund of Shanghai Jiao Tong University(2017).
文摘Human noroviruses(HuNoVs)are major foodborne pathogens that cause nonbacterial acute gastroenteritis worldwide.As the tissue-culture system for HuNoVs is not mature enough for routine detection of the virus,detection is mainly dependent on molecular approaches such as reverse transcription polymerase chain reaction(RT-PCR)and reverse transcription quantitative real-time polymerase chain reaction(RTqPCR).The widely used primers and probes for RT-qPCR were established in the early 2000s.As HuNoVs are highly variant viruses,viral genome mutations result in previously designed primers and/or probes that were perfectly matched working less efficiently over time.In this study,a new duplex RT-qPCR(ND-RT-qPCR)was designed for the detection of genogroup Ⅰ(GⅠ)and genogroup Ⅱ(GⅡ)HuNoVs based on an analysis of viral sequences added in the database after 2010.Using long transcribed viral RNAs,the results demonstrate that the sensitivity of ND-RT-qPCR is as low as one genomic copy for both GⅠ and GⅡ HuNoVs.The performance of ND-RT-qPCR was further evaluated by a comparison with the commonly used Kageyama primer/probe sets for RT-qPCR(Kageyama RT-qPCR)for 23 HuNoV-positive clinical samples.All five GⅠ samples were registered as positive by ND-RT-qPCR,whereas only two samples were registered as positive by Kageyama RT-qPCR.All 18 GⅡ samples were registered as positive by ND-RT-qPCR,while 17 samples were registered as positive by Kageyama RT-qPCR.The sensitivity reflected by the quantification cycle(Cq)value was lower in ND-RT-qPCR than in Kageyama RT-qPCR.Our data suggest that ND-RT-qPCR could be a good fit for the detection of current strains of HuNoVs.
文摘Objective: To determine the prevalence of astrovirus, norovirus, adenovirus in children below five years old with diarrhea by multiplex reverse transcriptase polymerase chain reaction(RT-PCR) along with rotavirus antigen detection by enzyme linked immunosorbant assay.Methods: The study was conducted on children below five years old complaining of acute diarrhea. The study included stool examination by molecular method for detection of norovirus, adenovirus and astrovirus by multiplex RT-PCR. Rotavirus antigen was detected in the stool by enzyme linked immunosorbant assay.Results: The study included 100 children below 5 years old with acute diarrhea.Multiplex RT-PCR was positive in 34% of the children. The most frequently detected virus was rotavirus(44%), followed by norovirus(30%), adenovirus(20%) and astrovirus(14%). The clinical symptoms were more significantly associated with viral diarrhea such as fever(P = 0.03), bloody diarrhea(P = 0.025), vomiting(P = 0.000 1) and watery diarrheas(P = 0.05). The frequency of diarrhea with viral pathogen was significantly presented in winter season(39.7%). There were significant frequencies of norovirus and adenovirus in age ranging 1–2 years old(P = 0.04, P = 0.01 respectively).Conclusions: The present study spotlights on the prevalence of viral pathogens as an important etiology in diarrhea in children below five years old. Astrovirus, norovirus and adenovirus are common along with rotavirus in this group of patients. Multiplex PCR leads to improve the laboratory diagnosis of these viruses along with antigen detection method. Further longitudinal studies are required to evaluate the epidemiological data associated with these viruses and for proper management of such drastic infection.
基金supported by the Fundamental Research Funds for the Central Universities,Sun Yat-sen University(Grant No.34000-31610293)。
文摘Norovirus is one of the most common causes of viral gastroenteritis in the world,causing significant morbidity,deaths,and medical costs.In this work,we look at stochastic modelling methodologies for norovirus transmission by water,human to human transmission and food.To begin,the proposed stochastic model is shown to have a single global positive solution.Second,we demonstrate adequate criteria for the existence of a unique ergodic stationary distribution R0 s>1 by developing a Lyapunov function.Thirdly,we find sufficient criteria Rs<1 for disease extinction.Finally,two simulation examples are used to exemplify the analytical results.We employed optimal control theory and examined stochastic control problems to regulate the spread of the disease using some external measures.Additional graphical solutions have been produced to further verify the acquired analytical results.This research could give a solid theoretical foundation for understanding chronic communicable diseases around the world.Our approach also focuses on offering a way of generating Lyapunov functions that can be utilized to investigate the stationary distribution of epidemic models with nonlinear stochastic disturbances.
文摘The efficacy of an activated sludge (modified Ludzack-Ettinger (MLE)) UV disinfection processes in removing human noroviruses and E. coli from sewage were compared with the prevalence of these microorganisms in a settled storm discharge from the same sewage treatment works. Both discharges impacted a designated oyster production area. The treatment process delivered average NoV and E. coli reductions of 2.9log10 and 5.2log10, respectively. Most E. coli reductions occurred during the UV disinfection process whereas the MLE process was comparatively more important in reducing NoV levels. A positive relationship was found between NoV removal and measured applied UV dose. The average levels of total NoV in the settled storm tank were of the same order of magnitude of those in screened raw influent at the works. These results highlight the importance of measures to reduce the impact of stormwater discharges to minimise the risk of NoV gastroenteritis associated with the consumption of oysters.
基金supported by the National Natural Science Foundation of China(82241065,32070926)to D.Z.the Sichuan Science and Technology Program(2023JDRC0090)to H.L.
文摘Norovirus(NoV)infection is a major cause of gastroenteritis worldwide.The virus poses great challenges in developing vaccines with broad immune protection due to its genetic and antigenic diversity.To date,there are no approved NoV vaccines for clinical use.Here,we aimed to develop a broad-acting quadrivalent NoV vaccine based on a chimpanzee adenovirus vector,AdC68,carrying the major capsid protein(VP1)of noroviral GI and GII genotypes.Compared to intramuscular(i.m.),intranasal(i.n.),or other prime-boost immunization regimens(i.m.t i.m.,i.m.t i.n.,i.n.t i.m.),AdC68-GI.1-GII.3(E1)-GII.4-GII.17(E3),administered via i.n.t i.n.induced higher titers of serum IgG antibodies and higher IgA antibodies in bronchoalveolar lavage fluid(BALF)and saliva against the four homologous VP1s in mice.It also significantly stimulated the production of blocking antibodies against the four genotypes.In response to re-stimulation with virus-like particles(VLP)-GI.1,VLP-GII.3,VLP-GII.4,and VLP-GII.17,the quadrivalent vaccine administered according to the i.n.t i.n.regimen effectively triggered specific cell-mediated immune responses,primarily characterized by IFN-γsecretion.Furthermore,the preparation of this novel quadrivalent NoV vaccine requires only a single recombinant adenovirus to provide broad preventive immunity against the major GI/GII epidemic strains,making it a promising vaccine candidate for further development.
文摘Noroviruses are the most common cause of acute gastroenteritis. Annually, 21 million Americans are infected with norovirus. Recent advances in molecular diagnostics have helped to establish norovirus as the most common cause of outbreaks of acute gastroenteritis across all ages. However, there is no effective or efficient treatment/control against norovirus infection. Conventional intervention techniques used to inactivate norovirus have shown lack of efficacy against human norovirus. Currently, effective treatment or control measures against human norovirus have not been identified. In this study, murine norovirus acts as a model to human norovirus to evaluate the inhibitory effects of crude extracts of Zanthoxylum armatum and Hibiscus sabdariffa. The study also separated, identified and quantified the selected compounds using the ultra-liquid chromatography (UPLC). To study the antiviral activities of crude extracts and its fractionated portions of Z. armatum and H. sabdariffa against norovirus surrogate, RAW 264.7 cells were infected with Murine norovirus surrogate virus of human norovirus and incubated at 37?C. Phytochemicals were extracted from the seeds and calyces of the plants using methanolic extraction. Fractionated portions of the crude extracts were subsequently used in both chromatographic and microbiological studies. Our data indicated that there was reduction of viruses, when treated with the 60% aqueous methanol extracts. Amongst the four selected phenolic compounds (myricetin, quercetin, kaempferol and luteolin), quercetin showed the most significant logarithmic viral reductions. These compounds were identified, purified and quantified using UPLC. Extracts of Zanthoxylum armatum and Hibiscus sabdariffa showed antiviral effects. Phenolic compounds are virucidal. Extracts of Hibiscus sabdariffa also exhibits anti-norovirus activities. The results are anticipated to control/prevent the human norovirus infections.
