Targeting pediatric versus elderly populations for norovirus vaccines: a model-based analysis of mass vaccination options
Molly SteeleJustin V. RemaisManoj GambhirJohn W. GlasserAndreas HandelUmesh D. ParasharBenjamin A. Lopman
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Abstract:
Noroviruses are the leading cause of acute gastroenteritis and foodborne diarrheal disease in the United States. Norovirus vaccine development has progressed in recent years, but critical questions remain regarding which age groups should be vaccinated to maximize population impact.We developed a deterministic, age-structured compartmental model of norovirus transmission and immunity in the U.S.The model was fit to age-specific monthly U.S. hospitalizations between 1996 and 2007. We simulated mass immunization of both pediatric and elderly populations assuming realistic coverages of 90% and 65%, respectively. We considered two mechanism of vaccine action, resulting in lower vaccine efficacy (lVE) between 22% and 43% and higher VE (hVE) of 50%.Pediatric vaccination was predicted to avert 33% (95% CI: 27%, 40%) and 60% (95% CI: 49%, 71%) of norovirus episodes among children under five years for lVE and hVE, respectively. Vaccinating the elderly averted 17% (95% CI: 12%, 20%) and 38% (95% CI: 34%, 42%) of cases in 65+ year olds for lVE and hVE, respectively. At a population level, pediatric vaccination was predicted to avert 18-21 times more cases and twice as many deaths per vaccinee compared to elderly vaccination.The potential benefits are likely greater for a pediatric program, both via direct protection of vaccinated children and indirect protection of unvaccinated individuals, including adults and the elderly. These findings argue for a clinical development plan that will deliver a vaccine with a safety and efficacy profile suitable for use in children.Keywords:
Acute gastroenteritis
Vaccine efficacy
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Acute gastroenteritis
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Objectives: For our survey of the incidence of norovirus infections and the genogroup distribution of norovirus in Seoul, Republic of Korea, we evaluated through regular surveillance the prevalence of norovirus infections in patients with acute gastroenteritis occurring in Seoul from January 2007 to July 2011. Methods: For norovirus detection, we conducted epidemiological analyses on the basis of the junction of ORF1 and ORF2 (approximately 314 bp). 11,202 fecal specimens were collected from patients in Seoul with acute gastroenteritis between January 2007 and July 2011 and then tested for the presence of NoV via reverse transcription (RT) - polymerase chain reaction (PCR). Results: 16.6% (1,861/11,202) of the fecal specimens were determined to be positive for noroviruses. The incidences of norovirus infection in Seoul in the case of acute gastroenteritis with regular surveillance were 28.0% in 2007, 14.6% in 2008, 9.1% in 2009, 14.1% in 2010, and 12.9% in 2011, which shows that noroviruses constituted a major causative agent of acute gastroenteritis. Also, the incidence of noroviral infection in patients with acute gastroenteritis increased after the large-scale new influenza in 2009. Conclusions: The genetic characteristics of norovirus and the epidemiologic patterns of a viral pathogen in acute gastroenteritis patients may provide potentially effective data for epidemiological studies in Seoul, Korea.
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Acute gastroenteritis
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Noroviruses are a major cause of epidemic gastroenteritis in children and adults. The aim of the present study was to investigate the molecular epidemiology of norovirus gastroenteritis in Japan.A total of 954 fecal specimens collected from infants and children with acute gastroenteritis from five different regions (Tokyo, Sapporo, Saga, Osaka, and Maizuru) of Japan during 2007-2009 were identified by multiple RT-PCR and semi-nested PCR.Norovirus was detected in a relatively high detection rate (26.6%; 254 of 954). Of the identified NoV, 9.5% (91 of 954) were positive by semi-nested PCR. Norovirus GII (97.3%) was more prevalent than GI (2.7%). Norovirus infections were very common in the patients aged 12-23 months (44.5%; 113 of 254). Winter month seasonality supported norovirus infection in Japan. All 7 GI sequences (100%) detected only in 2007-2008 clustered with Chiba 407 known as GI.4 genotype. Most of the norovirus GII sequences in 2007-2008 belonged to GII.4 (77.9%), followed by GII.14 (11.9%), and GII.3 and GII.6 (5.1% each). In 2008-2009, norovirus sequences were classified into eight distinct genotypes (GII.1, GII.2, GII.3, GII.4, GII.6, GII.7, GII12, and GII.14). GII.4/2006b variant was responsible for 100% among the detected GII.4 strains in both seasons. Interestingly, GII.6/GII.14 recombinant strains emerged, for the first time in Japanese children, as the second prevalent genotype (11.9%) in 2007-2008 and then dropped rapidly to 2.3% in a year after. In addition, GII.b/GII.3 and GII.4/GII.3 recombinant strains that had been described previously were also found in this study.This is the first report to demonstrate the co-circulation of the predominant GII.4/2006b variant and the emerging GII.6/GII.14 recombinant strains and supports the importance of norovirus as a causative agent of diarrhea in Japanese children with acute gastroenteritis.
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Human noroviruses are the leading cause of non-bacterial gastroenteritis in children worldwide. The objectives of this study are to determine the frequency and importance of norovirus in diarrheal illness among children below 5 years of age and to investigate the most affected age, seasonal distribution and the major clinical symptoms associated with norovirus infections; 400 stool samples (200 symptomatic cases and 200 asymptomatic healthy children) were investigated during the period from March 2011 to March 2012.Norovirus was detected in 8% of symptomatic children whereas all the control groups were norovirus negative. Norovirus was highly prevalent among children of 18-23 months of age (P=0.05). Noroviruses were continuously detected throughout the year except in May and October, but the principle peaks of detection were in November. The most common clinical symptoms beside diarrhea observed among norovirus infected children were vomiting (94%), fever (69%), dehydration (50%) and abdominal pain found in 31%.
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Noroviruses belonging to the family of Caliciviridae are a major cause of acute gastroenteritis in both children and adults. In the current study incidence of norovirus gastroenteritis was estimated in children hospitalized for acute gastroenteritis using commercially available ELISA tests. Epidemiological data were correlated with basic demographic findings. A hundred and forty nine children with acute gastroenteritis were enrolled in the study. Screening for common viruses causing gastroenteritis: rotavirus and adenovirus was performed and than stool samples were frozen and stored in <20 degrees C for future simultaneous testing with IDEIA Norovirus (Dakocytomation). Group I noroviruses were found in one child when 16 children were tested positive for Norowirus group two. In total noroviruses were found in 11.4% of children included in the study. Children with norovirus infection were 3 weeks to 15 years old (mean age 5.9 years). Seasonal peak of norovirus infection was seen in September through December. The infectious agent has not been identified in 43% of investigated children. Our results support important role of noroviruses as a causing agent of gastroenteritis in children in Northeastern Poland. The importance of noroviruses may grow as rotavirus infections are likely to be eliminated due to wide introduction of vaccine in the nearest future. Routine testing for noroviruses should be considered in clinical practice.
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Acute gastroenteritis associated with human norovirus infection was reported in Phuket, Thailand, in June 2023. We amplified GII.8[P8] from the outbreak stool specimens. Retrospective sample analysis identified infrequent GII.8[P8] in the country beginning in 2018. In all, the 10 whole-genome GII.8[P8] sequences from Thailand we examined had no evidence of genotypic recombination.
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Background: Norovirus is one of the most prevalent pathogens causing acute gastroenteritis in children. We compared the clinical features of noroviral gastroenteritis to those of rotaviral gastroenteritis and analyzed the noroviruses'genotype frequencies. Materials and Methods: Stool samples were ob...
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Rotavirus gastroenteritis
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BackgroundThe genogroups GI and GII of norovirus (NoV) ribonucleic acid (RNA) genetic variants are the most prevalent cause of acute gastroenteritis outbreaks, especially in children, worldwide. A fast, accurate and convenient tool for diagnosis of NoV may be preferable to the more complicated performance of real-time reverse transcription-polymerase chain reaction (RT-PCR).MethodsIn this study, we developed and evaluated a tool using insulated isothermal PCR (iiPCR)-mediated POCKIT Central NoV GI and NoV GII assay systems for diagnosis of NoV infection in pediatric patients suspected with gastroenteritis.ResultsPerformance of POCKIT Central Norovirus GI and GII assays using RT-iiPCR, compared to regular real-time RT-PCR showed the same diagnosis rate to NoV GI (100% of total percent agreement and 1.0 of Cohen's kappa value) and a similar detection rate to norovirus GII (96.3% of total percent agreement and 0.92 of Cohen's kappa value). In exclusivity tests, the POCKIT Central NoV GI and GII assays showed negative results to other viruses, indicating that the assays may be a NoV-specific detection tool.ConclusionPOCKIT Central NoV GI and GII Assay systems can provide a simple, rapid, sensitive, and specific point-of-need diagnostic tool for the detection of NoV GI and GII RNAs in clinical specimens from children with acute gastroenteritis. The genogroups GI and GII of norovirus (NoV) ribonucleic acid (RNA) genetic variants are the most prevalent cause of acute gastroenteritis outbreaks, especially in children, worldwide. A fast, accurate and convenient tool for diagnosis of NoV may be preferable to the more complicated performance of real-time reverse transcription-polymerase chain reaction (RT-PCR). In this study, we developed and evaluated a tool using insulated isothermal PCR (iiPCR)-mediated POCKIT Central NoV GI and NoV GII assay systems for diagnosis of NoV infection in pediatric patients suspected with gastroenteritis. Performance of POCKIT Central Norovirus GI and GII assays using RT-iiPCR, compared to regular real-time RT-PCR showed the same diagnosis rate to NoV GI (100% of total percent agreement and 1.0 of Cohen's kappa value) and a similar detection rate to norovirus GII (96.3% of total percent agreement and 0.92 of Cohen's kappa value). In exclusivity tests, the POCKIT Central NoV GI and GII assays showed negative results to other viruses, indicating that the assays may be a NoV-specific detection tool. POCKIT Central NoV GI and GII Assay systems can provide a simple, rapid, sensitive, and specific point-of-need diagnostic tool for the detection of NoV GI and GII RNAs in clinical specimens from children with acute gastroenteritis.
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