Acute gastroenteritis outbreak caused by a GII.6 norovirus

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.     

Virological and Epidemiological Features of Norovirus Infections in Brazil, 2017–2018

Noroviruses are considered an important cause of acute gastroenteritis (AGE) across all age groups. Here, we investigated the incidence of norovirus, genotypes circulation, and norovirus shedding in AGE stool samples from outpatients in Brazil. During a two-year period, 1546 AGE stool samples from ten Brazilian states were analyzed by RT-qPCR to detect and quantify GI and GII noroviruses. Positive samples were genotyped by dual sequencing using the ORF1/2 junction region. Overall, we detected norovirus in 32.1% of samples, with a massive predominance of GII viruses (89.1%). We also observed a significant difference between the median viral load of norovirus GI (3.4×10⁵ GC/g of stool) and GII (1.9×10⁷ GC/g). The most affected age group was children aged between 6 and 24 m old, and norovirus infection was detected throughout the year without marked seasonality. Phylogenetic analysis of partial RdRp and VP1 regions identified six and 11 genotype combinations of GI and GII, respectively. GII.4 Sydney[P16] was by far the predominant genotype (47.6%), followed by GII.2[P16], GII.4 Sydney[P31], and GII.6[P7]. We detected, for the first time in Brazil, the intergenogroup recombinant genotype GIX.1[GII.P15]. Our study contributes to the knowledge of norovirus genotypes circulation at the national level, reinforcing the importance of molecular surveillance programs for future vaccine designs.     

Burden of Norovirus and Rotavirus in Children after Rotavirus Vaccine Introduction,Cochabamba, Bolivia

The effectiveness of rotavirus vaccine in the field may set the stage for a changing landscape of diarrheal illness affecting children worldwide. Norovirus and rotavirus are the two major viral enteropathogens of childhood. This study describes the prevalence of norovirus and rotavirus 2 years after widespread rotavirus vaccination in Cochabamba, Bolivia. Stool samples from hospitalized children with acute gastroenteritis (AGE) and outpatients aged 5–24 months without AGE were recruited from an urban hospital serving Bolivia''s third largest city. Both viruses were genotyped, and norovirus GII.4 was further sequenced. Norovirus was found much more frequently than rotavirus. Norovirus was detected in 69/201 (34.3%) of specimens from children with AGE and 13/71 (18.3%) of those without diarrhea. Rotavirus was detected in 38/201 (18.9%) of diarrheal specimens and 3/71 (4.2%) of non-diarrheal specimens. Norovirus GII was identified in 97.8% of norovirus-positive samples; GII.4 was the most common genotype (71.4% of typed specimens). Rotavirus G3P[8] was the most prevalent rotavirus genotype (44.0% of typed specimens) and G2P[4] was second most prevalent (16.0% of typed specimens). This community is likely part of a trend toward norovirus predominance over rotavirus in children after widespread vaccination against rotavirus.     

Norovirus-Gastroenteritis

Viruses are the leading cause of acute gastroenteritis. In adults, noroviruses are the most common cause of gastroenteritis in sporadic cases and also in outbreaks whereas rotaviruses account for the majority of cases of viral gastroenteritis in childhood. Noroviruses are frequently associated with outbreaks in hospitals and nursing homes. The clinical manifestations of gastroenteritis include diarrhea and vomiting as the main symptoms. In immunocompromised patients clinical manifestations may be atypical, such as chronic diarrhea, weight loss and malnutrition. Nucleic acid based PCR tests are the mainstay of diagnosis; however, because of the characteristic clinical symptoms, specific viral diagnosis is usually not required. Noroviruses appear to be readily transmissible at relatively low doses, with an infectious dose even as low as 10–100 viruses and viral shedding can occur at extremely high levels up to >?10⁶ viruses/ml. Patients with symptoms consistent with norovirus gastroenteritis are placed on contact precautions or droplet precautions in case of vomiting. Hand hygiene is the most important means of preventing the spread of infection. Disinfectants with efficacy against noroviruses must be used. Norovirus gastroenteritis is usually self-limiting and is treated with supportive measures. In immunocompromised patients a reduction of immunosuppressive therapy should be considered in severe cases.     

Virus Etiology,Diversity and Clinical Characteristics in South African Children Hospitalised with Gastroenteritis

Background: Viral gastroenteritis remains a major cause of hospitalisation in young children. This study aimed to determine the distribution and diversity of enteric viruses in children ≤5 years, hospitalised with gastroenteritis at Kalafong Provincial Tertiary Hospital, Pretoria, South Africa, between July 2016 and December 2017. Methods: Stool specimens (n = 205) were screened for norovirus GI and GII, rotavirus, sapovirus, astrovirus and adenovirus by multiplex RT-PCR. HIV exposure and FUT2 secretor status were evaluated. Secretor status was determined by FUT2 genotyping. Results: At least one gastroenteritis virus was detected in 47% (96/205) of children. Rotavirus predominated (46/205), followed by norovirus (32/205), adenovirus (15/205), sapovirus (9/205) and astrovirus (3/205). Norovirus genotypes GI.3, GII.2, GII.3, GII.4, GII.7, GII.12, GII.21, and rotavirus strains G1P[8], G2P[4], G2P[6], G3P[4], G3P[8], G8P[4], G8P[6], G9P[6], G9P[8] and sapovirus genotypes GI.1, GI.2, GII.1, GII.4, GII.8 were detected; norovirus GII.4[P31] and rotavirus G3P[4] predominated. Asymptomatic norovirus infection (GI.3, GI.7, GII.4, GII.6, GII.13) was detected in 22% of 46 six-week follow up stools. HIV exposure (30%) was not associated with more frequent or severe viral gastroenteritis hospitalisations compared to unexposed children. Rotavirus preferentially infected secretor children (p = 0.143) and norovirus infected 78% secretors and 22% non-secretors. Conclusion: Rotavirus was still the leading cause of gastroenteritis hospitalisations, but norovirus caused more severe symptoms.     

Rotavirus and norovirus infections in children in Sana'a, Yemen

Objectives To describe the epidemiology of rotavirus and norovirus infection among children with acute gastroenteritis in Sana’a, Yemen. Methods A cross‐sectional study from November 2007 to March 2009 of children aged 1 month to 5 years attending the emergency and outpatient departments of two hospitals in Sana’a with acute gastroenteritis. Rotavirus was detected by ELISA and genotyped by RT‐PCR. Norovirus was detected by End Point RT‐PCR and nucleotide sequencing. Results A total of 290 children (48% in the emergency department and 52% in the outpatient department of the children respectively) were enrolled. Rotavirus infections were detected in 78 (27%) and norovirus infections in 30 (10%). Rotavirus genotypes included G1P[8] (55%), G9P[8] (21%) and G2P[4] (12%) with G12 comprising 3% of strain types. The main norovirus genotype was GII.4 (27%) with >10 other genotypes detected. Conclusions Rotavirus and norovirus infections are common causes of gastroenteritis in Yemen. Rotavirus vaccines could play a significant role in the control of acute childhood diarrhoea in this setting.     

Norovirus Infection in Young Nicaraguan Children Induces Durable and Genotype-Specific Antibody Immunity

There are significant challenges to the development of a pediatric norovirus vaccine, mainly due to the antigenic diversity among strains infecting young children. Characterizing human norovirus serotypes and understanding norovirus immunity in naïve children would provide key information for designing rational vaccine platforms. In this study, 26 Nicaraguan children experiencing their first norovirus acute gastroenteritis (AGE) episode during the first 18 months of life were investigated. We used a surrogate neutralization assay that measured antibodies blocking the binding of 13 different norovirus virus-like particles (VLPs) to histo-blood group antigens (HBGAs) in pre- and post-infection sera. To assess for asymptomatic norovirus infections, stools from asymptomatic children were collected monthly, screened for norovirus by RT-qPCR and genotyped by sequencing. Seroconversion of an HBGA-blocking antibody matched the infecting genotype in 25 (96%) of the 26 children. A subset of 13 (50%) and 4 (15%) of the 26 children experienced monotypic GII and GI seroconversion, respectively, strongly suggesting a type-specific response in naïve children, and 9 (35%) showed multitypic seroconversion. The most frequent pairing in multitypic seroconversion (8/12) were GII.4 Sydney and GII.12 noroviruses, both co-circulating at the time. Blocking antibody titers to these two genotypes did not correlate with each other, suggesting multiple exposure rather than cross-reactivity between genotypes. In addition, GII titers remained consistent for at least 19 months post-infection, demonstrating durable immunity. In conclusion, the first natural norovirus gastroenteritis episodes in these young children were dominated by a limited number of genotypes and induced responses of antibodies blocking binding of norovirus VLPs in a genotype-specific manner, suggesting that an effective pediatric norovirus vaccine likely needs to be multivalent and include globally dominant genotypes. The duration of protection from natural infections provides optimism for pediatric norovirus vaccines administered early in life.     

Epidemiological aspects of rotavirus infection in hospitalized Venezuelan children with gastroenteritis.

The prevalence of rotavirus infection in hospitalized Venezuelan children with gastroenteritis was studied during the period November 1975 to December 1976. Rotaviruses were the pathogens most frequently associated with gastroenteritis, being found in 121 of 293 (41.3%) patients and in only 3 of 66 (4.5%) controls. Other viruses (adenoviruses, enteroviruses, and small icosahedrical viruses) were detected at a lower frequency both in cases and controls. Rotaviruses were detected at a lower frequency both in cases and controls. Rotaviruses were readily detected throughout the year, which may correspond to the absence of seasonal temperature variation in a tropical country such as Venezuela. Children of all age groups examined (0-5 yr) were susceptible to rotavirus infection. The frequency of infection was slightly higher in the age group 13-24 mo, and significantly lower in children younger than 6 mo old. Rotaviruses were readily detected even after 12 days from the onset of illness. These results indicate that rotaviruses may be a major cause of infantile acute gastroenteritis in Venezuela.     

Rotavirus infections in families. A clinical and virological study.

Among 25 family members of 8 children with acute rotavirus gastroenteritis (8 siblings and 17 adults) gastroenteritis was recorded in 9 (5 siblings and 4 adults), and minor symptoms in 8 (2 siblings and 6 adults). A rotavirus infection was diagnosed in 7 of the family members with gastroenteritis and was probably the cause of the disease in the remaining 2 in this group. Four of the 8 family members with minor symptoms were infected with rotavirus, whereas no infection was detected among the 8 family members without symptoms. Serological findings sugggested that infants and young children underwent a primary infection with rotavirus, whereas older children and adults probably were reinfected. Adults as well as children with rotavirus infection excreted virus and may have served as sources of infection.     

Molecular epidemiological study of rotavirus and norovirus infections among children with acute gastroenteritis in Nha Trang, Vietnam, December 2005-June 2006

A molecular epidemiological study of rotavirus (RV) and norovirus (NoV) infections was carried out in Nha Trang city in Vietnam between December 2005 and June 2006. RV and NoV were detected in 87 (47.5%) and 12 (6.6%) of the 183 fecal specimens from children hospitalized with acute gastroenteritis, respectively. The majority of patients with RV and NoV were children younger than 2 years of age. The most frequent RV genotypes detected were G3 (n=37, 42.5%) and G1 (n=28, 32.2%) for G type, P[8] (n=61, 70.1%) for P type, and G3P[8] (n=33, 38.0%) and G1P[8] (n=18, 20.7%) for the G and P genotype combination. GII.12 was the most common genotype (6/12, 50%) for NoV, followed by GII.4 (4/12, 33.3%), and we also identified a rare type (GII.19). The results of this study highlight the increased incidence of G3P[8] and the presence of many OP354-like P[8] RVs, as well as the GII.4 2003 Asia variant of NoVs. Furthermore, the first case of GII.19 of NoV in Vietnam is reported.     

Norovirus Epidemiology and Genetic Diversity in Leipzig,Germany during 2013–2017

Globally and in all age groups, noroviruses are a main cause of gastroenteritis. To assess their local epidemiology and genetic diversity, stool samples of 7509 inpatients with gastrointestinal complaints from all age groups were analyzed. After detection of norovirus genogroup I and II RNA by real-time RT-PCR, viral capsids were genotyped by partial nucleic acid sequencing. In the case of GII.2 strains, polymerase genotypes were also assessed. Between October 2013 and September 2017, presence of norovirus RNA was shown in 611 samples (8.1%), of which 610 (99.8%) were typed successfully. Norovirus positivity rate was higher in patients aged below five years (14.8%) than in older patients (5.7%). Among the 611 norovirus positive samples, GII.4 (56.6%) strains prevailed, followed by GII.6 (11.3%), GII.3 (11.0%) and GII.2 (9.5%). The most common genogroup I (GGI) genotype was GI.3 (3.6%). In addition, rare genotypes such as GII.13, GII.14 and GII.26 were detected. Interestingly, GII.3 infections were most common in children under the age of five years. Assessment of polymerase genotypes in GII.2 viruses showed a shift from P2 to P16, with higher diversity in P2 sequences. The varying distribution of norovirus genotypes depending on season, age and setting of infection highlights the importance of frequent genotyping as a basis for vaccine development and needful adjustments.     

Epidemics of gastroenteritis during 2006 were associated with the spread of norovirus GII.4 variants 2006a and 2006b.

BACKGROUND: Acute gastroenteritis is commonly associated with norovirus genogroup II (GII) infection. Norovirus GII has 17 classified genotypes (GII.1-GII.17), but only 1 norovirus genotype (GII.4) is associated with global epidemics of gastroenteritis. In 2006, an increase in global norovirus activity was observed. METHODS: During the period from December 2005 through August 2006, a total of 231 fecal samples were obtained from patients with acute gastroenteritis from Australia and New Zealand. Norovirus RNA was amplified and sequenced to determine norovirus genotype and relatedness to known epidemic norovirus GII.4 variants. RESULTS: Two GII.4 variants, designated 2006a and 2006b, were identified in 61.8% and 11.3%, respectively, of the 186 cases investigated. Norovirus 2006a and 2006b have also been implicated as the predominant causes of norovirus-associated gastroenteritis across Europe in 2006. CONCLUSIONS: The global increase in norovirus-associated gastroenteritis in 2006 was linked to the emergence of 2 novel GII.4 variants, 2006a and 2006b.     

Approaches to immunization of infants and young children against gastroenteritis due to rotaviruses

Recent studies have shown that in developed countries rotaviruses are the single most important etiologic agents of acute gastroenteritis that requires hospitalization of infants and young children. Although deaths from gastroenteritis are, in general, infrequent in the developed countries, an effective rotavirus vaccine would clearly be of benefit to reduce the heavy toll of morbidity from gastroenteritis due to rotavirus. In the developing countries the impact of diarrheal diseases is staggering. It was recently estimated that in Asia, Africa, and Latin-America during a one-year period there would be 3.5 billion cases of diarrhea and 5-10 million deaths associated with diarrhea; in addition, diarrhea was ranked first in freqency in the categories of disease and mortality. In the developing countries rotaviruses are known to cause diarrhea, but their relative role in this high mortality rate is not yet known. epidemiologic data indicate that development of an effective rotavirus vaccine would reduce morbidity, and they suggest that a vaccine would also reduce a portion of the mortality from diarrheal disease. The prospects and approaches for the development of an effective rotavirus vaccine are presented. The recent successful propagation of rotavirus type 2 in cell culture represents an important step in this regard. In addition, the antigenic relation between human and animal strains offers another possible approach. The need for a live attenuated vaccine is indicated by the prime role played by local intestinal immunity in resistance to rotavirus disease.     

Rotavirus-associated acute gastroenteritis hospitalizations among Japanese children aged <5 years: active rotavirus surveillance in Mie Prefecture, Japan

Two effective vaccines for rotavirus infection will be available near future in Japan and data on the burden of rotavirus disease and the circulating rotavirus strains are urgently needed. To obtain these data, we set up active rotavirus hospitalization surveillance in three cities, Tsu, Matsusaka, and Ise in Mie Prefecture, Japan. From November 1, 2007 through October 31, 2009, we enrolled children <5 years of age who were hospitalized with a diagnosis of acute gastroenteritis (AGE) and collected information on age, sex, month of admission, city of residence, and symptoms at the time of hospitalization. Stool samples were also obtained for rotavirus testing and genotype investigation. Rotavirus infection accounted for approximately 40% to 50% of hospitalized AGE cases in each city, and approximately 63% of those hospitalized were 2 years of age or younger. Matsusaka had the highest incidence rate at 4.7 rotavirus hospitalizations per 1,000 children <5 years of age (95% confidence interval [CI]: 3.6-5.9), followed by Tsu City (4.4 per 1,000; 95% CI: 3.6-5.3), and Ise City (2.8 per 1,000; 95% CI: 2.0-4.0). The most dominant rotavirus genotype was G3P[8], which accounted for 73.1% of cases. Our findings confirm the substantial health burden of rotavirus AGE hospitalization among Japanese children <5 years of age.     

Prospective Study of the Burden of Acute Gastroenteritis and Rotavirus Gastroenteritis in Children Less Than 5 Years of Age, in Padova, Italy

BACKGROUND: : Data on the burden of rotavirus gastroenteritis in Europe are needed to help understand the potential impact of introducing new rotavirus vaccines. MATERIALS AND METHODS: : As part of prospective observational study (Rotavirus gastroenteritis Epidemiology and Viral types in Europe Accounting for Losses in Public Health and Society Study, REVEAL) conducted in 2004-2005 in seven European countries, we studied, the characteristics of acute gastroenteritis and rotavirus gastroenteritis in children less than 5 years in primary care, emergency room and hospital settings (Padova, Italy). RESULTS: : A total of 757 children with acute gastroenteritis were included and enzyme-linked immunoabsorbent assay (ELISA) results were available for 725 cases. The overall estimated annual incidence for rotavirus gastroenteritis was 4.7%. Overall, rotavirus gastroenteritis was estimated to account for 43.6% of acute gastroenteritis cases. Among children with acute gastroenteritis (AGE) aged 6-23 months, 61.2% were rotavirus positive. Rotavirus gastroenteritis (RVGE) was responsible for 68.8% of hospitalizations, 61% of emergency consultations, and 33% of primary care consultations. The most prevalent serotype was G9 (84.4%) followed by G1 (11.8%). The relative risk for rotavirus gastroenteritis of being referred to hospital after an initial consultation in primary care was 3.37 (95% CI: 1.77-6.43) and 3.38 (95% CI: 2.28-5.01) for emergency room referral. Children with rotavirus gastroenteritis generally had more severe disease than children with rotavirus-negative gastroenteritis. CONCLUSION: : Rotavirus accounts for a significant proportion of acute gastroenteritis cases in children less than 5 years in Italy, many of whom require frequent primary care consultations, or care in emergency room or hospital settings.     

A prospective case-control study of the role of astrovirus in acute diarrhea among hospitalized young children

This study examines the importance of astroviruses as a cause of acute diarrhea in hospitalized children <10 years old during a 5-year period. Stools were screened by electron microscopy and were tested for astrovirus, rotavirus, and enteric adenovirus by EIA. During the study, 14.6% of hospitalized children had diarrhea. Astroviruses were second only to rotaviruses as etiologic agents of both community-acquired and nosocomial diarrhea. Community-acquired astrovirus infection occurred in 6.8% of patients, and nosocomial disease occurred in 16.2%. Most cases occurred from March through June, and astrovirus type 1 was the most common. The symptoms of astrovirus-infected children were similar to those of children with rotavirus infection. However, astrovirus-infected children had a lower median age, less dehydration, and lower symptom severity scores and were less likely to have been admitted for gastroenteritis than were children with rotavirus. Astrovirus, for which only rehydration therapy is required, should be considered as another common diarrheal pathogen in children <2 years old.     

No association between histo-blood group antigens and susceptibility to clinical infections with genogroup II norovirus

Noroviruses (NoVs) are a leading cause of viral gastroenteritis in humans. In the present study, the association between NoV susceptibility and the ABO histo-blood group was studied during 2 outbreaks of acute gastroenteritis in military units in Israel caused by genogroup II (GII) NoVs. The findings demonstrate that, unlike for genogroup I of NoV, there is no association between the ABO histo-blood group and clinical infection with GII NoVs. This is the largest study to test the association between NoVs, proven clinical infection with GII, and the ABO histo-blood group.     

Noroviruses everywhere: has something changed?

PURPOSE OF REVIEW: Noroviruses causing gastroenteritis in humans have increasingly been described in both the scientific literature and the lay press. This review summarizes new information about where and why these viruses are detected as well as new developments to prevent or treat these infections. RECENT FINDINGS: Noroviruses are highly infectious and quite stable. Noroviruses infect all age groups, with particularly severe disease occurring in young children, the elderly, and persons with chronic diseases. Noroviruses also cause persistent infections in immunosuppressed patients. Host susceptibility factors have been identified, including histo-blood group antigens that likely function as initial receptors for some noroviruses. The patterns of susceptibility are complex, however, and not completely understood for all virus strains. X-ray crystallographic information on the virus capsid and other viral-encoded proteins provides targets for structure-based drug development. SUMMARY: The availability of new methods of detecting noroviruses has resulted in increased detection of these pathogens. Advances in understanding of virus replication and structure should lead to development of strategies to prevent and treat these infections. Such efforts may be challenged by the emergence of new virus strains that appear through mechanisms that remain to be understood.