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We aimed to assess the efficacy of the oral live attenuated human rotavirus vaccine Rotarix (RIX4414) for prevention of rotavirus gastroenteritis in European infants during their first 2 years of life. 3994 study participants were enrolled from six countries and were randomly assigned two oral doses of either RIX4414 (n=2646) or placebo (n=1348), which were coadministered with the first two doses of specific childhood vaccinations. Follow-up for gastroenteritis episodes was undertaken from 2 weeks post-dose two through the two consecutive rotavirus seasons following vaccinations (combined efficacy follow-up period; mean duration 17 months [SD 1·6]). Our primary endpoint was vaccine efficacy against rotavirus gastroenteritis of any severity during the first efficacy follow-up period (2 weeks post-dose two to the end of the first rotavirus season). Stool specimens obtained during gastroenteritis episodes were tested for rotavirus by ELISA and typed by RT-PCR. Episodes scoring 11 or greater on the 20-point Vesikari scale were classified as severe. Analysis was according to protocol. This study is registered with ClinicalTrials.gov, number NCT00140686 (eTrack102247). 120 infants were excluded from the according-to-protocol analysis. During the first efficacy follow-up period (mean duration 5·7 months [SD 1·2]), 24 of 2572 infants allocated RIX4414 versus 94 of 1302 given placebo had rotavirus gastroenteritis episodes of any severity, resulting in a vaccine efficacy of 87·1% (95% CI 79·6–92·1; p<0·0001). For the combined efficacy follow-up period, vaccine efficacy against severe rotavirus gastroenteritis was 90·4% (85·1–94·1; p<0·0001), for admission owing to rotavirus gastroenteritis 96·0% (83·8–99·5; p<0·0001), and for rotavirus-related medical attention 83·8% (76·8–88·9; p<0.0001), and significant protection against severe rotavirus gastroenteritis by circulating G1, G2, G3, G4, and G9 rotavirus types was shown. In a European setting, two doses of RIX4414 coadministered with childhood vaccines provided high protection against any and severe rotavirus gastroenteritis, with an overall reduction of admissions for gastroenteritis over two consecutive rotavirus epidemic seasons.

Transmissible gastroenteritis virus (TGEV) and porcine respiratory coronavirus (PRCV) are enveloped, single-stranded RNA viruses belonging to the genus Alphacoronavirus in the family Coronaviridae. PRCV, a TGEV mutant with a spike(S) gene deletion, exhibits altered tissue tropism. TGEV replicates mainly in the intestines and causes severe diarrhea and high mortality in piglets, whereas PRCV replicates mainly in the respiratory tract. PRCV causes mild or subclinical respiratory infections but may contribute to respiratory disease syndrome in pigs infected with other respiratory pathogens. As PRCV and TGEV continuously evolve, monitoring these viruses is important for disease prevention and control. In this review, we provide updated information on the prevalence and genetic characteristics of TGEV/PRCV and their phylogenetic relationships. We also discuss the impact of mutations, deletions and recombination on the virulence and tissue tropism of TGEV/PRCV and highlight the possible zoonotic potential of these viruses.

Porcine transmissible gastroenteritis virus (TGEV) is a major pathogen that causes viral enteritis and severe diarrhea in newborn piglets. TGEV strains have been isolated in the USA, Europe, and China, and their molecular characteristics are well known. However, there have been few reports of molecular analysis of TGEV strains isolated in Southeast Asia. In 2016, we isolated TGEV strain VET-16 from fecal samples collected from piglets in Vietnam and determined its complete genome sequence by Sanger sequencing. We found that, while the full genome of the VET-16 strain was 92.4-99.9% identical to those of other TGEV strains, the ORF3 gene showed very little sequence similarity. Phylogenetic analysis suggested that the VET-16 strain belongs to the Purdue subgroup. Comparison of the predicted amino acid (aa) sequence of the spike protein of strain VET-16 with those of other TGEV strains revealed three aa substitutions (V378L, S379T, and D380N) and a 3-aa insertion (F383_F387insWEK) in antigenic site D of the VET-16 strain. Also, a single aa deletion (∆F1413) was found in the transmembrane domain of the spike gene of VET-16. Like the ORF3 gene from the TGEV Miller M60 vaccine strain, the VET-16 strain has a large deletion (∆725 nt) in the ORF3 gene. Previous studies have suggested that these mutations in the spike and ORF3 genes might be associated with a reduction in pathogenicity. The data from this study will facilitate further genetic analysis and research into the evolution of TGEV in pigs in Vietnam.

Vaccination has reduced rotavirus hospitalizations by 25% in European regions with low–moderate vaccine availability. We aimed to quantify the reduction in hospital costs after the longest period in which Rotarix® and Rotateq® were simultaneously commercially available in Spain. Cases, length of stay (LOS), and diagnosis-related groups (DRGs) were retrieved from the Minimum Basic Data Set. Healthcare expenditure was estimated through the cost accounting system Gescot®. DRGs were clustered: I, non-bacterial gastroenteritis with complications; II, without complications; III, requiring surgical/other procedures or neonatal cases (highest DRG weights). Comparisons between pre (2003–2005)- and post-vaccine (2007–2009) hospital stays and costs by DRG group were made. Rotaviruses were the most common agents of specific-coded gastroenteritis (𝑁 = 1657/5012). LOS and extended LOS of rotaviruses fell significantly in 2007–2009 (𝛽-coefficient = −0·43, 95% confidence intervals (95% CI) −0·68 to −0·17; and odds ratio 0·62, 95% CI 0·50–0·76, respectively). Overall, costs attributable to rotavirus hospitalizations fell approximately €244 per patient (95% CI −365 to −123); the decrease in DRG group III was €2269 per patient (95% CI −4098 to −380). We concluded modest savings in hospital costs, largely attributable to cases with higher DRG weights, and a faster recovery. A universal rotavirus vaccination program deserves being re-evaluated, regarding its potential high impact on both at-risk children and societal costs.

Background Trends in gastroenteritis-associated mortality are changing over time with development of antibiotic resistant strains of certain pathogens, improved diagnostic methods, and changing healthcare. In 1999, ICD-10 coding was introduced for mortality records which can also affect trends. We assess trends in gastroenteritis-associated mortality and changes associated with coding. Methods Trends in gastroenteritis-associated mortality rates in the United States were examined using the National Center for Health Statistics Multiple Cause-of-Death Mortality databases for 1985–2005. All deaths with the underlying cause or any contributing cause included gastroenteritis were included. Cases were selected based on ICD9 (pre-1999) and ICD10 (1999–2005) codes and all analyses were stratified by ICD usage. Annual trends in age adjusted mortality rates were assessed using linear regression spline analysis. Relative risks and 95% confidence intervals (CIs) were calculated using Poisson regression adjusted for age group, sex, race, and region. Results There were a total of 190,674 deaths related to gastroenteritis in the U.S. from 1985–2005 with an average of 9,080 per year. During this time the percent of deaths related to gastroenteritis more than tripled, increasing from 0.25% to 0.80% of all deaths. Though the time periods varied in length, we demonstrate a significant increase in slope from a 0.0054% annual increase during the period 1985–1998, when ICD-9 coding was used, to a 0.0550% annual increase during 1999–2005, when ICD-10 coding was used. For both time periods, the oldest age group (75+ years) demonstrated the highest risk of death due to gastroenteritis. Additionally, males demonstrated higher risk than females and blacks were at higher risk than whites for death due to gastroenteritis. Conclusions This analysis demonstrates the public health burden of gastroenteritis-associated mortality in the United States and changes in trends due to change from ICD-9 to ICD-10 coding. The overall rate of gastroenteritis-associated mortality has more than tripled over the 21-year period from 1985 to 2005 and the primary burden of deaths due to gastroenteritis is in the elderly population.

Transmissible gastroenteritis virus (TGEV) is an infective coronavirus (CoV) that causes diarrhea-related morbidity and mortality in piglets. For the first time, a natural recombination strain of a TGEV Anhui Hefei (AHHF) virus between the Purdue and the Miller clusters was isolated from the small intestine content of piglets in China. A phylogenetic tree based on a complete genome sequence placed the TGEV AHHF strain between the Purdue and the Miller clusters. The results of a computational analysis of recombination showed that the TGEV AHHF strain is a natural recombinant strain between these clusters. Two breakpoints located in the open reading frame 1a (ORF1a) and spike (S) genes were identified. The pathogenicity of the TGEV AHHF strain was evaluated in piglets, and the results show that TGEV AHHF is an enteric pathogenic strain. These results provide valuable information about the recombination and evolution of CoVs and will facilitate future investigations of the molecular pathogenesis of TGEV.

In this study, a novel duplex nanoparticle-assisted polymerase chain reaction (nanoPCR) assay was developed to detect porcine epidemic diarrhea virus (PEDV) and porcine transmissible gastroenteritis virus (TGEV). Two pairs of primers were designed based on the conserved region within the N gene of PEDV and TGEV. In a screening of 114 clinical samples from four provinces in China for PEDV and TGEV, 48.2 and 3.5 % of the samples, respectively, tested positive. Under optimized conditions, the duplex nanoPCR assay had a detection limit of 7.6 × 10 1 and 8.5 × 10 1 copies μL −1 for PEDV and TGEV, respectively. The sensitivity of the duplex nanoPCR assay was ten times higher than that of a conventional PCR assay. Moreover, no fragments were amplified when the duplex nanoPCR assay was used to test samples containing other porcine viruses. Our results indicate that the duplex nanoPCR assay described here is useful for the rapid detection of PEDV and TGEV and can be applied in clinical diagnosis.

The severity of childhood gastroenteritis is generally believed to be age-related rather than aetiology-related. Rotavirus-induced gastroenteritis is more severe than gastroenteritis caused by other enteric pathogens and is also age-related. We thus addressed the question of whether the increased severity of rotavirus-induced gastroenteritis is related to age or to features intrinsic to the agent. In this multicentre, hospital-based, prospective survey, we evaluated the severity of diarrhoea in rotavirus-positive and rotavirus-negative children up to 4 years of age. Severity was assessed with a score in four groups of age-matched children. Rotavirus was detected in 381 of 911 children. Disease severity was evaluated in 589 cases for which clinical data were complete. The rotavirus-positive and rotavirus-negative groups differed with regards to diarrhoea duration, hospital stay, degree of dehydration and the number of episodes of vomiting. Gastroenteritis was more severe in rotavirus-positive than in rotavirus-negative children. In contrast, none of the main severity parameters differed in the four age groups, irrespective of the presence of rotavirus. These data provide the evidence that aetiology and not age determines diarrhoeal severity. The demonstration that diarrhoea was more severe in rotavirus-positive children supports the need for a rotavirus vaccine and for studies that address the duration of vaccine protection.

We compared gastroenteritis cases that consulted a general practitioner (GP) with those who did not in a community-based study and also with those in a GP-based study. We aimed to identify factors associated with consultation, and with inclusion of cases by GPs, and secondly to study the effects on the frequency of detection of pathogens. Furthermore, we estimated the under-ascertainment by GPs. Both studies were performed in The Netherlands in the same population in an overlapping time-period. Overall, 5% of community cases consulted a GP. Cases who consulted suffered from more severe episodes than non-consulting cases. Inclusion of cases by GPs, instead of a study team, caused a selection of more severe cases with more chronic symptoms. When extrapolating data from GP-based studies, it should be taken into account that, in general practice, gastroenteritis due to bacteria and Giardia lamblia is a relatively large proportion of that in the community and gastroenteritis due to Norwalk-like viruses is a relatively small proportion. The incidence of gastroenteritis in general practices was estimated between 14 and 35 per 1000 person years.

The aim of the study was to establish the main etiologic agents of acute viral gastroenteritis and to asses the severity of illness associated with the different viral agents of gastroenteritis in children hospitalized during spring/summer season 2008. 181 stool specimens were collected from children under 5 years of age, hospitalized with acute viral diarrhea from April to September 2008. Commercial enzyme immunoassay kits were used to detect noroviruses. The immunochromatographic tests for combined detection of rotaviruses and adenoviruses were performed routinely in our department in all in-patients suspected for viral gastroenteritis. A viral etiologic agents were detected in 108 of 181 (59.7%) samples tested. Dual viral pathogens (rotavirus and norovirus) were found in 3 of 181 (1.7%) samples. Rotavirus was the most common viral pathogen found in the study group (86/181; 47.5%), followed by NV (19/181; 10.5%) and adenoviruses (3/181; 1.7%). Approximately, 60% of acute gastroenteritis episodes occurring in children less than 5 years of age were accounted for by infection due to rotavirus and/or norovirus. Norovirus cases were clinically indistinguishable from those of rotavirus origin in children aged less than 2 years whereas they were slightly milder in older group of patients. Rotavirus infections are leading cause of children's hospitalization in spring months whereas Norovirus infections during spring/summer time. There is a great need to apply molecular diagnostic tools to determine the actual and monitoring the changing etiology of acute enteritis in Polish population.