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Fecal-oral pathogens encounter constitutively expressed enteric alpha-defensins in the intestine during replication and transmission. Alpha-defensins can be potently antiviral and antibacterial; however, their primary sequences, the number of isoforms, and their activity against specific microorganisms often vary greatly between species, reflecting adaptation to species-specific pathogens. Therefore, alpha-defensins might influence not only microbial evolution and tissue tropism within a host but also species tropism and zoonotic potential. To investigate these concepts, we generated a panel of enteric and myeloid alpha-defensins from humans, rhesus macaques, and mice and tested their activity against group A rotaviruses, an important enteric viral pathogen of humans and animals. Rotaviral adaptation to the rhesus macaque correlated with resistance to rhesus enteric, but not myeloid, alpha-defensins and sensitivity to human alpha-defensins. While mouse rotaviral infection was increased in the presence of mouse enteric alpha-defensins, two prominent genotypes of human rotaviruses were differentially sensitive to human enteric alpha-defensins. Furthermore, the effects of cross-species alpha-defensins on human and mouse rotaviruses did not follow an obvious pattern. Thus, exposure to alpha-defensins may have shaped the evolution of some, but not all, rotaviruses. We then used a genetic approach to identify the viral attachment and penetration protein, VP4, as a determinant of alpha-defensin sensitivity. Our results provide a foundation for future studies of the VP4-dependent mechanism of defensin neutralization, highlight the species-specific activities of alpha-defensins, and focus future efforts on a broader range of rotaviruses that differ in VP4 to uncover the potential for enteric alpha-defensins to influence species tropism. IMPORTANCE Rotavirus is a leading cause of severe diarrhea in young children. Like other fecal-oral pathogens, rotaviruses encounter abundant, constitutively expressed defensins in the small intestine. These peptides are a vital part of the vertebrate innate immune system. By investigating the impact that defensins from multiple species have on the infectivity of different strains of rotavirus, we show that some rotaviral infections can be inhibited by defensins. We also found that some, but not all, rotaviruses may have evolved resistance to defensins in the intestine of their host species, and some even appropriate defensins to increase their infectivity. Because rotaviruses infect a broad range of animals and rotaviral infections are highly prevalent in children, identifying immune defenses against infection and how they vary across species and among viral genotypes is important for our understanding of the evolution, transmission, and zoonotic potential of these viruses as well as the improvement of vaccines.

Rotaviruses are important causative agents of acute gastroenteritis in children. In China, rotavirus infection has a prevalence rate of 30% and is therefore considered a serious public health problem. This study was carried out to investigate the clinical and molecular epidemiological characteristics of rotavirus infections in children under 5 years old with acute diarrhea in Shandong province, China. From July 2017 to June 2018, a total of 1211 fecal specimens were tested, and the prevalence of rotavirus infection was 32.12%. The mean age of the infected children was 12.2 ± 10.9 months, and the highest infection rate was observed in children aged 7-12 months, with a rate of 41.64%. G9P[8] (76.61%) was the most prevalent genotype combination, followed by G2P[4] (7.20%), G3P[8] (3.60%), and G9P[4] (2.06%). In addition to diarrhea, vomiting, fever, and dehydration were the most common clinical signs. In general, there was no significant difference in clinical manifestations among different age groups. However, the clinical manifestations differed significantly between vaccinated and unvaccinated children. Vaccinated children showed lower incidence and frequency of vomiting, lower incidence and degree of dehydration, and lower incidence of severe cases than unvaccinated children. These findings suggest that it is necessary to continuously monitor changes in the characteristics of rotavirus infections. Moreover, the introduction of vaccines into the national immunization program to prevent and control rotavirus infection is needed in China., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The objective of this prospective cohort study was to investigate the effect of bovine coronavirus (BCoV), bovine rotavirus (BRoV), and Cryptosporidiumparvum on dairy calf health and performance and to determine the prevalence of these pathogens. A total of 198 male dairy calves housed at a grain-fed veal facility were examined from June 11, 2018, to October 9, 2018. Calves were fed milk replacer twice daily and housed individually until weaning at 56 d. Once weaned, calves were moved into groups of 5 until they were moved to a finishing facility at 77 d. At the grain-fed veal facility, calves were scored for fecal consistency for the first 28 d and had fecal samples taken on arrival and at 7 and 14 d. Fecal samples were frozen and submitted to a commercial laboratory, where they were tested for BCoV, C.parvum, and 2 groups of BRoV: group A (BRoV A) and group B (BRoV B). Calves were weighed on arrival and at 14, 49, 56, and 77 d using a digital body scale. Treatments for disease and mortalities that occurred over the 77 d were also recorded. Statistical models, including Cox proportional hazards and repeated measures models, were built to determine the effect of infection with 1 of the pathogens. Over the 3 sampling points, 151 (85.8%), 178 (94.2%), 3 (1.5%), and 97 (57.4%) calves tested positive at least once for BCoV, BRoV A, BRoV B, and C.parvum, respectively. The source of the calves and the level of serum total protein measured on arrival were associated with testing positive for a pathogen. Calves that tested positive for C.parvum had an increased proportion of days with diarrhea and severe diarrhea; calves that tested positive for BCoV and BRoV A had an increased proportion of days with severe diarrhea. In addition, calves that tested positive for C.parvum had a higher hazard of being treated for respiratory disease. With respect to body weight, calves that had diarrhea or severe diarrhea had lower body weight at 49, 56, and 77 d. Specifically, calves that had an increased proportion of days with diarrhea showed a reduction in weight gain of up to 15 kg compared to calves without diarrhea. Calves that tested positive for C.parvum had a lower body weight at 49, 56, and 77 d; calves that tested positive for BCoV had a lower body weight at 56 and 77 d. This study demonstrates that the prevalence of BCoV, BRoV A, and C.parvum infection is high in this population of calves and has significant effects on the occurrence of diarrhea and body weight gain. Future studies should evaluate approaches for minimizing the effect of infection with these pathogens to improve the welfare, health, and productivity of dairy calves., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: A correlate of protection for rotavirus gastroenteritis would facilitate rapid assessment of vaccination strategies and the next generation of rotavirus vaccines. We aimed to quantify a threshold of postvaccine serum antirotavirus immunoglobulin A (IgA) as an individual-level immune correlate of protection against rotavirus gastroenteritis., Methods: Individual-level data on 5074 infants in 9 GlaxoSmithKline Rotarix Phase 2/3 clinical trials from 16 countries were pooled. Cox proportional hazard models were fit to estimate hazard ratios (HRs) describing the relationship between IgA thresholds and occurrence of rotavirus gastroenteritis., Results: Seroconversion (IgA ≥ 20 U/mL) conferred substantial protection against any and severe rotavirus gastroenteritis to age 1 year. In low child mortality settings, seroconversion provided near perfect protection against severe rotavirus gastroenteritis (HR, 0.04; 95% confidence interval [CI], .01-.31). In high child mortality settings, seroconversion dramatically reduced the risk of severe rotavirus gastroenteritis (HR, 0.46; 95% CI, .25-.86). As IgA threshold increased, risk of rotavirus gastroenteritis generally decreased. A given IgA threshold provided better protection in low compared to high child mortality settings., Discussion: Postvaccination antirotavirus IgA is a valuable correlate of protection against rotavirus gastroenteritis to age 1 year. Seroconversion provides an informative threshold for assessing rotavirus vaccine performance., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

A 4-year-old girl presented with an alteration of consciousness and absence of speech after a short period of vomiting, diarrhoea and fever. MRI of the brain revealed a focal lesion in the splenium of the corpus callosum. Rotavirus was detected in the faeces. We concluded that the rotavirus infection had caused mild encephalopathy with a reversible splenial lesion.

Background: Rotavirus(RV) is one of the primary causes globally of acute diarrhoea in children below 5 years of age., Aims: This literature research aims to evaluate the rotavirus diarrhoea among hospitalized children < 5 years of age in the Eastern Mediterranean Region from 2010 to 2016. Data from each country were extracted and compared., Methods: An extensive literature search was carried out using the following databases: PubMed, Google Scholar and Science Direct, with the keyword "Rotavirus". The search was limited to articles published from January 2010 to December 2016., Results: The search identified 28 studies. Rotavirus gastroenteritis (RVGE) identification in studies countries ranged from from 19%-78.2% of all tested diarrhoeal specimens, primarily in children ≤ 1 year of age. RV occurred throughout the year, with peak incidence during autumn and winter seasons. G1P[8] was the predominant circulating genotype combination followed by G9P[8] and G2P[4]. Out of 28 studies, only one examined the economic burden which ranged from US$ 245 to $345 per hospitalized child due to RV diarrhoea. Moreover, three days were the minimum duration of hospitalization. No available data on the mortality rates due to RVGE among the selected studies., Conclusions: This research documents that RV is one of the most significant pathogens that cause morbidity and mortality in the paediatric population in Eastern Mediterranean Region countries. The data from this literature research may help public healthcare workers in decreasing mortality and morbidity resulting from RVGE in the region., (Copyright © World Health Organization (WHO) 2019. Some rights reserved. This work is available under the CC BY-NC-SA 3.0 IGO license (https://creativecommons.org/licenses/by-nc-sa/3.0/igo).)

Rotavirus is a common cause of acute gastroenteritis in children. Manifestations of rotavirus gastroenteritis beyond gastrointestinal tract are rare. Rotavirus has been reported to be associated with encephalopathy, myositis and elevated liver enzymes; but simultaneous presentation of all these conditions in the same child is extremely rare. The authors report a case of 17-mo-old girl who presented with acute rotavirus gastroenteritis with G3 + G9P[8] strain associated with hypernatremia, encephalopathy, myositis, transaminitis and hypoalbuminemia. Child had complete recovery with no neurological sequalae on follow-up, and liver enzymes and albumin returned to normal. The authors suggest that rotavirus infection should be considered in the differential diagnosis of a child with encephalopathy or myositis, particularly if associated with acute diarrhea.

Rotavirus is a highly contagious viral infection that inflames the lining of the stomach and intestines, and especially affects children 2 years old and younger. In the United States, the introduction of a vaccine in 2006 helped arrest rotavirus illnesses and deaths.

Background and Purpose: Rotavirus was detected in 40-50% of patients with benign convulsions with mild gastroenteritis (CwG) before the rotavirus vaccine was introduced in late 2000. However, the rate of rotavirus positivity has decreased since 2010 while the prevalence of norovirus has gradually increased. We investigated the incidence of norovirus-associated CwG during a recent 3-year period and additionally compared the characteristics of norovirus-associated CwG with those of rotavirus-associated CwG., Methods: The medical records of CwG patients admitted to our hospital between March 2014 and February 2017 were reviewed, including the results of stool virus tests. For comparing norovirus- and rotavirus-associated CwG, data obtained between March 2005 and February 2014 that included sufficient numbers of patients with rotavirus-associated CwG were additionally reviewed. Data were collected on clinical characteristics (age, sex, seasonal distribution, enteric symptoms, and the interval to seizure onset), seizure characteristics (frequency, duration, type, and electroencephalographic findings), and laboratory findings., Results: CwG was diagnosed in 42 patients during the 3-year study period. Stool viruses were checked in 40 (95.2%) patients and were detected in 32 (80.0%) patients. Norovirus genogroup II was detected in 27 (67.5%) of the 40 patients, rotavirus was detected in 3 patients, and adenovirus was detected in 2 patients. In total, 140 CwG patients were enrolled between March 2005 and February 2017. The patients with norovirus-associated CwG (N = 44) and rotavirus-associated CwG (N = 26) were aged 18.66 ± 5.57 and 19.31 ± 7.37 months (mean ± standard deviation), respectively (P > 0.05). Norovirus-associated CwG was less prevalent than rotavirus-associated CwG during spring (13.6% vs. 34.6%, P = 0.04), while the prevalence of both types of CwG peaked during winter (63.6% and 46.2%, respectively). Vomiting was more prevalent in norovirus- than rotavirus-associated CwG (97.7% vs. 80.8%, P = 0.02) and the interval between enteric symptom onset and seizure onset was shorter in norovirus-associated CwG (2.00 ± 1.06 vs. 2.58 ± 1.21 days, P = 0.04). Most cases in both groups had seizures that lasted for less than 5 min (95.5% vs. 92.3%). Clustered seizures seemed to occur more frequently in the norovirus group (79.5% vs. 57.7%), although with borderline significance (P = 0.05). Posterior slowing was observed more frequently in norovirus-associated CwG (34.9% vs. 11.5%, P = 0.03)., Conclusion: The most common viral pathogen of CwG was norovirus during the analyzed 3-year period, with an incidence of 67.5%. In comparison with rotavirus-associated CwG, norovirus-associated CwG was less frequent during spring, more frequently seen with vomiting, had a shorter interval from enteric symptom onset to seizure onset, and more frequently showed posterior slowing in electroencephalography., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Rotaviruses (RVs) and noroviruses (NoVs) are the most common causes of severe acute gastroenteritis in children. It is generally accepted that RVs cause severe acute gastroenteritis in a higher proportion of cases compared with NoVs. To our knowledge, there are no systematic reviews and meta-analyses comparing the severity of NoV and RV disease., Methods: We searched MEDLINE for studies reporting data for NoV and RV medically attended disease severity in children. We included studies where all children had been tested for both NoV (reverse transcription polymerase chain reaction) and RV (enzyme-linked immunosorbent assay or reverse transcription polymerase chain reaction) and that reported disease severity using the Vesikari or modified Vesikari score, or provided clinical information on severity. We generated pooled estimates of the mean with 95% confidence intervals using random effects meta-analysis., Results: We identified 266 publications, of which 31 were retained for qualitative analysis and 26 for quantitative analysis. Fourteen studies provided data on severity score for the meta-analysis. The pooled mean severity scores (95% confidence interval) among outpatients were 10 (8-12) and 11 (8-14) for NoV and RV, respectively. Among inpatients, they were 11 (9-13) for NoV and 12 (10-14) for RV. The difference was statistically significant among inpatients, but relatively small (1 point in a 20-point scale). About 20% more children with RV required rehydration when compared with children with NoV., Conclusions: NoV causes moderate to severe disease similar to RV in young children. This information should be useful for future evaluations of an eventual introduction of NoV vaccines in national immunization programs.

We previously identified, by a natural-product screen, resveratrol oligomers as inhibitors of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. Here, we report the resveratrol dimer trans-ε-viniferin (TV) and tetramer r-2-viniferin (RV) as inhibitors of the intestinal calcium-activated chloride channel (CaCC) and demonstrate their antisecretory efficacy in a neonatal mouse model of rotaviral diarrhea. Short-circuit measurements show inhibition of CaCC current in the human colonic cell line HT-29 by TV and RV with IC 50 ∼1 and 20μM, respectively. TV primarily inhibited the physiologically relevant, long-term CaCC current following agonist stimulation, without effect on cytoplasmic Ca 2+ signaling. TV and RV inhibited short-circuit current in mouse colon as well. In a neonatal mouse model of rotaviral secretory diarrhea produced by oral inoculation with rotavirus, 2μg TV or 11μg RV inhibited secretory diarrhea by >50%, without effect on the rotaviral infection. Our results support the antisecretory efficacy of non-toxic, natural-product resveratrol oligomers for diarrheas produced by CaCC activation. Because these compounds also inhibit the CFTR chloride channel, they may be useful for antisecretory therapy of a wide range of diarrheas., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Our objective was to elucidate the clinical characteristics and neurodevelopmental outcomes in neonatal encephalopathy with characteristic white matter injury as compared with other injury patterns on magnetic resonance diffusion-weighted imaging. We conducted a retrospective study comparing clinical and laboratory findings, and neurologic outcomes between 17 newborns with diffuse lesions in the periventricular white matter and white matter tract (group I) and 22 newborns with other patterns (group II). Stool samples indicated that 16 neonates (94.1%) in group I were rotavirus-positive, whereas none in group II had rotavirus infection. Significantly lower calcium levels were found in group I than in group II ( P < .001). Moreover, a more favorable neurodevelopmental outcome was observed in group I than in group II. This study suggests that characteristic white matter injury in neonatal encephalopathy may be related to decreased calcium levels induced by rotavirus, and may have a better neurodevelopmental prognosis than other causes.

Rotavirus (RV)-infected piglets are presumed to be latent sources of heterologous RV infection in humans and other animals. In RVs, non-structural protein 4 (NSP4) is the major virulence factor with pleiotropic properties. In this study, we analyzed the nsp4 gene from porcine RVs isolated from diarrheic and non-diarrheic cases at different levels of protein folding to explore correlations to diarrhea-inducing capabilities and evolution of nsp4 in the porcine population. Full-length nsp4 genes were amplified, cloned, sequenced, and then analyzed for antigenic epitopes, RotaC classification, homology, genetic relationship, modeling of NSP4 protein, and prediction of post-translational modification. RV presence was observed in both diarrheic and non-diarrheic piglets. All nsp4 genes possessed the E1 genotype. Comparison of primary, secondary, and tertiary structure and the prediction of post-translational modifications of NSP4 from diarrheic and non-diarrheic piglets revealed no apparent differences. Sequence analysis indicated that nsp4 genes have a multi-phyletic evolutionary origin and exhibit species independent genetic diversity. The results emphasize the evolution of the E9 nsp4 genotype from the E1 genotype and suggest that the diarrhea-inducing capability of porcine RVs may not be exclusively linked to its enterotoxin gene.

We developed a gnotobiotic (Gn) pig model colonised with defined commensal microbiota (DMF) to provide a simplified and controlled system to study the interactions between intestinal commensals, antibiotics (ciprofloxacin, CIP), probiotics (Escherichia coli Nissle 1917, EcN) and virulent human rotavirus (VirHRV). The DMF included seven gut commensal species of porcine origin that mimic the predominant species in the infant gut. Gn piglets were divided into four groups: DMF control (non-treated), DMF+CIP (CIP treated), DMF+CIP+EcN (CIP/EcN treated), DMF+EcN (EcN treated) and inoculated orally with 10 5 cfu of each DMF strain. The pig gut was successfully colonised by all DMF species and established a simplified bacterial community by post-bacteria colonisation day (PBCD) 14/post-VirHRV challenge day (PCD) 0. Overall, Bifidobacterium adolescentis was commonly observed in faeces in all groups and time points. At PCD0, after six days of CIP treatment (DMF+CIP), we observed significantly decreased aerobic and anaerobic bacteria counts especially in jejunum (P<0.001), where no DMF species were detected in jejunum by T-RFLP. Following HRV challenge, 100% of pigs in DMF+CIP group developed diarrhoea with higher diarrhoea scores and duration as compared to all other groups. However, only 33% of pigs treated with EcN plus CIP developed diarrhoea. EcN treatment also enhanced the bacterial diversity and all seven DMF species were detected with a higher proportion of Bifidobacterium longum in jejunum in the DMF+CIP+EcN group on PBCD14/PCD0. Our results suggest that EcN increased the proportion of B. longum especially in jejunum and mitigated adverse impacts of antibiotic use during acute-infectious diarrhoea. The DMF model with a simplified gut commensal community can further our knowledge of how commensals and probiotics promote intestinal homeostasis and contribute to host health.

Rotavirus (RV) is highly endemic inside and outside hospital-settings. Immunocompromised children and adults are at risk of complicated rotavirus gastroenteritis (RVGE), but general rotavirus disease severity in this group remains poorly described and rotavirus testing is not routinely performed beyond infancy. We assessed rotavirus disease among immunocompromised hospitalized patients., Methods: Rotavirus infections at a Dutch tertiary-care centre were identified from 5-year laboratory records. Rotavirus disease course was evaluated by chart review for each immunocompromised patient. In a matched case-control analysis, we assessed whether being immunocompromised predisposed to RVGE. Rotavirus testing practice for suspected infectious gastroenteritis in our hospital was determined over a 3-years period., Results: Out of 4584 RV tests performed, 294 were positive among hospitalized patients. Immunocompromised patients represented 57% (N = 20) of adult, and 12% (N = 32) of paediatric RVGE. A complicated disease course occurred in 81% of them and 33% required adaptations in underlying disease management. Immunocompromised adults were 7.4 times more likely todevelop RVGE compared to non-immunocompromised matched hospital-controls. Rotavirus testing in adult patients with suspected infectious gastroenteritis was uncommon (12% tested)., Conclusions: In our hospital, most adults with RVGE are immunocompromised compared to a much smaller proportion in children. RVGE in immunocompromised patients is associated with significant morbidity. Routine rotavirus testing beyond infancy should be recommended for immunocompromised patients with suspected infectious gastroenteritis., (Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Rotavirus-related diarrhoea is considered one of the most important diseases in field animal production. In addition to the classic vaccine strategy, a number of studies have utilised probiotics, such as Lactobacillus rhamnosus GG (LGG), to prevent rotavirus-induced diarrhoea. Although it has been partially revealed that Toll-like receptors (TLRs) are involved in the LGG-mediated protection against rotavirus infection, the details of the underlying immunologic mechanisms remain largely unknown. In this study, three-to-four-week-old female BALB/c mice were divided into three groups and orally administered phosphate buffered saline (PBS), PBS plus rotavirus or LGG plus rotavirus, respectively. The differentiation and maturation of dendritic cells (DCs) were then determined by FACS, the expression levels of TLR-3 and nuclear factor kappa beta (NF-κB) were evaluated using real time PCR, and the production of inflammatory cytokines in mesenteric lymph nodes (MLNs) were determined by ELISA. The results demonstrated that rotavirus infection significantly increased the percentage of CD11c + CD11b + CD8a - DCs and decreased the percentage of CD11c + CD11b - CD8a + DCs in MLNs. By contrast, the presence of LGG significantly decreased the percentage of CD11c + CD11b + CD8a - DCs and increased the percentage of CD11c + CD11b - CD8a + DCs, which indicates that the differentiation of DCs is involved in the protective effects of LGG. Rotavirus infection also resulted in the increased expression of surface markers such as CD40, CD80 and MHC-II in DCs, and the administration of LGG significantly increased the expression level further. The mRNA levels of TLR-3 and NF-κB in the intestine and MLNs were also significantly increased in the presence of rotavirus, which was further increased in the presence of LGG. The production of inflammatory cytokines was also determined, and the results showed that rotavirus caused the increased production of interleukin (IL)-12 and tumour necrosis factor alpha; this effect was further enhanced by LGG. Meanwhile, although rotavirus infection led to the increased production of IL-6 and IL-10, the presence of LGG significantly decreased the mRNA levels of these cytokines. By contrast, rotavirus infection resulted in the decreased production of interferon gamma (IFN-γ), and the administration of LGG significantly increased the levels of IFN-γ. Taken together, the protective effects of LGG were partially due to the modulation of the differentiation and maturation of DCs, the increased production of TLR-3 and NF-κB, and the modulation of inflammatory cytokines.

Biliary atresia (BA) is a neonatal obstructive cholangiopathy that progresses to end-stage liver disease, often requiring transplantation. The murine model of BA, employing rhesus rotavirus (RRV), parallels human disease and has been used to elucidate mechanistic aspects of a virus induced biliary cholangiopathy. We previously reported that the RRV VP4 gene plays an integral role in activating the immune system and induction of BA. Using rotavirus binding and blocking assays, this study elucidated how RRV VP4 protein governs cholangiocyte susceptibility to infection both in vitro and in vivo in the murine model of BA. We identified the amino acid sequence on VP4 and its cholangiocyte binding protein, finding that the sequence is specific to those rotavirus strains that cause obstructive cholangiopathy. Pretreatment of murine and human cholangiocytes with this VP4-derived peptide (TRTRVSRLY) significantly reduced the ability of RRV to bind and infect cells. However, the peptide did not block cholangiocyte binding of TUCH and Ro1845, strains that do not induce murine BA. The SRL sequence within TRTRVSRLY is required for cholangiocyte binding and viral replication. The cholangiocyte membrane protein bound by SRL was found to be Hsc70. Inhibition of Hsc70 by small interfering RNAs reduced RRV's ability to infect cholangiocytes. This virus-cholangiocyte interaction is also seen in vivo in the murine model of BA, where inoculation of mice with TRTRVSRLY peptide significantly reduced symptoms and mortality in RRV-injected mice., Conclusion: The tripeptide SRL on RRV VP4 binds to the cholangiocyte membrane protein Hsc70, defining a novel binding site governing VP4 attachment. Investigations are underway to determine the cellular response to this interaction to understand how it contributes to the pathogenesis of BA. (Hepatology 2017;65:1278-1292)., (© 2016 by the American Association for the Study of Liver Diseases.)

Background: Rotavirus and HIV infection are major causes of death among children in sub-Saharan Africa. A previous study reported no association between concomitant HIV infection and rotavirus disease severity among hospitalised children in Malawi. This study examined rotavirus antigenaemia and broader immune responses among HIV-infected and uninfected children., Methods: Stored (-80°C), paired sera from acute and convalescent phases of Malawian children less than 5 years old, hospitalised for acute gastroenteritis in the primary study, collected from July 1997 to June 1999, were utilised. Among children older than 15 months, HIV infection was defined as the presence of HIV antibody in the blood, when confirmed by at least 2 established methods. For those younger than 15 months, nested polymerase chain reaction (PCR) amplification of proviral DNA was used for verification. All were followed for up to 4 weeks after hospital discharge. Rotavirus antigen levels in sera were measured with Premier™ Rotaclone® rotavirus enzyme immunoassay (EIA) kit. Acute-phase sera were examined for 17 cytokines, using Luminex fluorescent bead human cytokine immunoassay kit. Rotavirus-specific IgA and neutralising activity were determined by EIA and microneutralisation (MN) assay, respectively. Human strains and bovine-human reassortants were propagated in MA104 cells with serum-free Iscove's Modified Dulbecco's Medium (IMDM). Differences in results, from specimens with and without HIV infection, were analysed for statistical significance using the chi-square test., Results: We detected rotavirus antigen in 30% of the HIV-infected and 21% HIV-uninfected, in the acute-phase sera. HIV-infected children developed slightly prolonged rotavirus antigenaemia compared to HIV-uninfected children., Conclusions: Rotavirus-specific IgA seroconversion rates and neutralising titres were similar in HIV-infected and HIV-uninfected children, thus, HIV infection had no major effect on immune responses to rotavirus infection.

Objective: To estimate the burden of rotavirus-associated gastroenteritis in India., Methods: Hospital based surveillance network was established, with clinical evaluation and laboratory testing for rotavirus among children aged below 5 years hospitalized with acute gastroenteritis., Results: Between September 2012 and December 2014, stool samples from 10207 children were tested and rotavirus was detected in 39.6% of cases. Infections were more commonly seen among younger children (<2 years). Detection rates were higher during cooler months of September February. Among rotavirus infected children, 64.0% had severe or very severe disease. G1P[8] was the predominant rotavirus genotype (62.7%) observed during the surveillance period., Conclusions: Surveillance data highlights the high rotavirus disease burden and emphasizes the need for close monitoring to reduce morbidity and mortality associated with rotavirus gastroenteritis in India.

Background: This study aimed to explore changes in clinical epidemiology and genotype distribution and their association among hospitalized children with rotavirus gastroenteritis after the introduction of vaccines., Methods: Between November 2010 and October 2014, hospitalized children with acute gastroenteritis were enrolled. Rotavirus genotypes were confirmed through reverse transcription-polymerase chain reaction (RT-PCR), semi-nested PCR, and sequencing. Clinical information including vaccination status and the modified Vesikari scores were collected., Results: Among 179 children with rotavirus infection, nineteen (10.6 %) were completely vaccinated. During the study period, the number of children between three and 23 months of age decreased significantly compared to the number of children older than 24 months of age (P = 0.010), who showed lower diarrhea severity (duration, P = 0.042; frequency, P = 0.021) but higher vomiting severity (P = 0.007, 0.036) compared to the former. Vaccination status was also significantly associated with lower vomiting severity after adjustment for age (frequency only, P = 0.018). The predominant genotypes were G2P[4] (18.4 %), G1P[8] (14.5 %), and G1P[4]P[8] (12.8 %), and the prevalence of genotypes with uncommon and mixed combinations was more than 50 %. Children infected with G2P[4] strains tended to be older (P = 0.005) and had more severe vomiting (P = 0.018, 0.006) than those with G1P[8]., Conclusions: Increase in age of infected, hospitalized children was accompanied by change in clinical severity during 2011-2014 after the introduction of vaccines in Seoul. Clinical severity was also associated with vaccination status and genotype. Long-term large scale studies are needed to document the significance of the increase in genotypes of uncommon and mixed combinations.

ABSTRACTThis article provides a review of immunity, diagnosis, and clinical aspects of rotavirus disease. It also informs about the changes in epidemiology of diarrheal disease and genetic diversity of circulating group A rotavirus strains following the introduction of vaccines. Group A rotavirus is the major pathogen causing gastroenteritis in animals. Its segmented RNA genome can lead to the emergence of new or unusual strains in human populations via interspecies transmission and/or reassortment events.RESUMOEste artigo fornece uma revisão sobre imunidade, diagnóstico e aspectos clínicos da doença causada por rotavírus. Também aponta as principais mudanças no perfil epidemiológico da doença diarreica e na diversidade genética das cepas circulantes de rotavírus do grupo A, após a introdução vacinal. O rotavírus do grupo A é o principal patógeno associado à gastroenterite em animais. Seu genoma RNA segmentado pode levar ao surgimento de cepas novas ou incomuns na população humana, por meio de transmissão entre espécies e eventos de rearranjo.

Lactobacillus rhamnosus GG (LGG) has been regarded as a safe probiotic strain. The aim of this study was to investigate whether dietary LGG supplementation could alleviate diarrhea via improving jejunal mucosal barrier function in the weaned piglets challenged by RV, and further analyze the potential roles for apoptosis of jejunal mucosal cells and intestinal microbiota. A total of 24 crossbred barrows weaned at 21 d of age were assigned randomly to 1 of 2 diets: the basal diet and LGG supplementing diet. On day 11, all pigs were orally infused RV or the sterile essential medium. RV infusion increased the diarrhea rate, increased the RV-Ab, NSP4 and IL-2 concentrations and the Bax mRNA levels of jejunal mucosa (P<0.05), decreased the villus height, villus height: crypt depth, the sIgA, IL-4 and mucin 1 concentrations and the ZO-1, occludin and Bcl-2 mRNA levels of jejunal mucosa (P<0.05), and affected the microbiota of ileum and cecum (P<0.05) in the weaned pigs. Dietary LGG supplementation increased the villus height and villus height: crypt depth, the sIgA, IL-4, mucin 1 and mucin 2 concentrations, and the ZO-1, occludin and Bcl-2 mRNA levels of the jejunal mucosa (P<0.05) reduced the Bax mRNA levels of the jejunal mucosa (P<0.05) in weaned pigs. Furthermore, dietary LGG supplementation alleviated the increase of diarrhea rate in the weaned pigs challenged by RV (P<0.05), and relieve the effect of RV infection on the villus height, crypt depth and the villus height: crypt depth of the jejunal mucosa (P<0.05), the NSP4, sIgA, IL-2, IL-4, mucin 1 and mucin 2 concentrations of jejunal mucosa (P<0.05), the ZO-1, occludin, Bax and Bcl-2 mRNA levels of the jejunal mucosa (P<0.05), and the microbiota of ileum and cecum (P<0.05) in the weaned pigs challenged by RV. These results suggest that supplementing LGG in diets alleviated the diarrhea of weaned piglets challenged by RV via inhibiting the virus multiplication and improving the jejunal mucosal barrier function, which was possibly due to the decreasing apoptosis of jejunal mucosal cells and the improvement of intestinal microbiota.

Background: Since 1980 a form of benign convulsion during mild gastroenteritis, called Convulsion With Gastroenteritis (CWG) has been described. However diagnostic criteria have not been well defined yet given the similarity of CWG with other diseases of young age and therefore diagnosis is done by exclusion, creating anxiety in parents., Objective and Methods: We here report a series of cases admitted at our hospital and, making a review analysis of data available, propose a diagnostic score (CWGDS) in order to rapidly individuate the disease from history., Results: Five cases of seizures associated to gastrointestinal symptoms were admitted to the Pediatric Unit of Eastern Liguria Hospital in La Spezia from January 2014 to April 2015. All these cases could be defined as CWG given their characteristics and benign evolution. We then prepared CWGDS from literature's data and compared our cases with the score itself, having 100% agreement between clinical diagnosis and diagnosis done by CWGDS., Conclusion: We propose a diagnostic score to help the clinician in diagnosing a benign condition such as CWG therefore avoiding as much as possible invasive procedures and reassuring parents.

We aimed to identify whether rotavirus, human parechovirus, or enterovirus are causative or associated viral pathogens of seizures accompanied by diffuse cerebral white matter injury in neonates. Thirty neonates who presented with seizures and diffusion-restriction in the widespread bilateral cerebral white matter on diffusion-weighted magnetic resonance imaging (MRI) were included in this study. All patients were tested for rotavirus, human parechovirus, and enterovirus by using reverse transcription PCR. Stool, cerebrospinal fluid, and serum samples were examined in 30, 25, and 20 patients, respectively. Rotavirus was detected in stool samples from all 30 patients (100%). Stool samples from 5 patients (16.7%) were also positive for enterovirus. Rotavirus or human parechovirus were not detected in any cerebrospinal fluid samples from 25 patients, but 1 patient tested positive for enterovirus. No virus was detected in any of 20 patient sera. This study indicated an association between rotavirus and seizures accompanied by diffuse cerebral white matter lesions in neonates., (© The Author(s) 2015.)

Background: Norovirus is an important cause of gastroenteritis both in children and adults. In China, few studies have been conducted on adult populations. This study aimed to determine the contribution of norovirus to gastroenteritis, characterize the features of norovirus infections, compare them with other pathogens, and test the effectiveness of the surveillance system., Methods: A citywide surveillance network on diarrhea patients was established. Samples were collected with intervals from both children and adults among diarrhea outpatients in hospitals and tested for viruses using rRT-PCR and for bacteria in CDCs. Patient information was acquired through interviews and recorded into a dedicated online system. The Pearson χ2 test, multivariate logistic regression models and discriminant models were fitted into its comparisons with the non-norovirus group and other pathogens., Results: Norovirus was detected in 22.91% of sampled diarrhea patients. The seasonal distribution of norovirus infections was different from non-norovirus patients (p<0.001), with a half-year peak. Higher proportions of males (p=0.001, OR=1.303, 95% CI=1.110-1.529), local citizens (p<0.001) and officials/clerks (p=0.001, OR=1.348, 95% CI=1.124-1.618) were affected with norovirus when compared with non-norovirus patients. Diarrhea patients affected with norovirus featured nausea (p<0.001, OR=1.418, 95% CI=1.176-1.709) and vomiting (p<0.001, OR=1.969, 95% CI=1.618-2.398), while fewer manifested fever (p=0.046, OR=0.758, 95% CI=0.577-0.996) and abdominal pain (p=0.018, OR=0.815, 95% CI=0.689-0.965). Children were more vulnerable to rotavirus (p=0.008, OR=1.637, 95% CI=1.136-2.358) and bacteria (p=0.027, OR=1.511, 95% CI=1.053-2.169) than norovirus. There was a seasonal difference between the GI and GII genotypes (p<0.001). Officials or clerks were more easily affected with GI than GII (p=0.006, OR=1.888, 95% CI=1.205-2.958)., Conclusions: This study was based on a citywide hospital-sentinel surveillance system with multiple enteric pathogens included. Norovirus was recognized as the most prevalent enteric pathogen in Shanghai. The seasonal peak was from October to April. Males had a higher prevalence than females. Local citizens and officials/clerks were more vulnerable to norovirus than other pathogens. Compared with rotavirus and bacteria, children were less frequently affected by norovirus. Nausea and vomiting were typical of norovirus, whereas fever and abdominal pain were uncommon symptoms of this pathogen. GI and GII infections were centered in different seasons. Officials and clerks were more easily affected by GI than GII.

Histo-blood group antigens (HBGAs) have been proposed as rotavirus receptors. H type-1 and Lewis(b) antigens have been reported to bind VP8* from major human rotavirus genotypes P[4], P[6] and P[8], while VP8* from a rarer P[14] rotavirus recognizes A-type HBGAs. However, the role and significance of HBGA receptors in rotavirus pathogenesis remains uncertain. Here we report that P[14] rotavirus HAL1166 and the related P[9] human rotavirus K8 bind to A-type HBGAs, although neither virus engages the HBGA-specific α1,2-linked fucose moiety. Notably, human rotaviruses DS-1 (P[4]) and RV-3 (P[6]) also use A-type HBGAs for infection, with fucose involvement. However, human P[8] rotavirus Wa does not recognize A-type HBGAs. Furthermore, the common human rotaviruses that we have investigated do not use Lewis(b) and H type-1 antigens. Our results indicate that A-type HBGAs are receptors for human rotaviruses, although rotavirus strains vary in their ability to recognize these antigens.

Objectives: Because rotavirus gastroenteritis is associated with high morbidity and mortality especially in developing countries, it is necessary to develop antirotavirus drugs for the treatment of rotavirus infection. Previous studies have demonstrated that cyclosporin A (CsA) has antiviral properties against rotavirus. Its effect has not yet been evaluated against rotavirus diarrheal disease. The aim of this study was to assess the anti-rotavirus efficacy of CsA in neonatal mice after induction of rotavirus diarrhea., Methods: Suckling mice were inoculated with murine rotavirus. On the onset of diarrhea, mice were given different concentrations of CsA. To evaluate the effects of CsA on reduction of rotavirus diarrhea, diarrhea score, fecal virus shedding, and pathological lesion change in the small intestine, messenger RNA (mRNA) expression levels in the small intestine and spleen of mice were measured for type I interferon (IFN-α and IFN-β), inflammation-related cytokines (interleukin [IL]-8, IL-10, IFN-γ, and tumor necrosis factor-α), and inflammatory signaling pathways (p38, c-Jun N-terminal kinase, activator protein-1, and nuclear factor-kappa B)., Results: Among virus-inoculated and CsA-treated groups, a dose of 5 mg · kg⁻¹ · day⁻¹ of CsA inhibited diarrhea and improved fecal virus shedding and intestinal lesion changes. IFN-β mRNA expression was significantly increased in rotavirus-induced diarrhea mice treated with 5 mg · kg⁻¹ · day⁻¹ of CsA, whereas the mRNA expression levels of inflammation-related cytokines (IL-8, IL-10, IFN-γ, and tumor necrosis factor-α) and inflammatory signaling pathways (p38, c-Jun N-terminal kinase, activator protein-1, and nuclear factor-kappa B) were markedly decreased. Antiviral effects of CsA were dose dependent., Conclusions: CsA can inhibit rotavirus infection in neonatal mice through its antiviral properties. The mechanism for this may be through CsA suppression of inflammation by viral inhibition in animal models.

Diarrheal infections remain the major cause of morbidity and mortality among children under 5 years of age. The rotavirus holds the leading position among principal diarrheal pathogens that include also norovirus, enteropathogenic and enterotoxigenic Escherichia coli. Rotaviruses are transmitted by the fecal-oral route and are extremely contagious and stable in the environment. This facilitates viral transmission, particularly in daycare centers and hospitals. Rotavirus infection causes acute gastroenteritis with diarrhea and dehydration of various degrees resulting primarily from destruction of intestinal villus enterocytes with subsequent impairment of the ion transport and absorption. The incidence of rotavirus infection peaks during the winter and spring in countries with temperate climate. Many children have asymptomatic infection that supports rotavirus circulation in the popula- tion. Several vaccines have been developed for specific prophylaxis of rotavirus infections and demonstrated protection from severe acute rotavirus gastroenteritis and all-cause diarrheal mortality.

Objective: We analyzed the clinical features of seizures during gastroenteritis in children by comparing the norovirus and rotavirus pathogen, and the impact of fever, if present, during the seizure episodes., Methods: Retrospective analysis was performed on 293 consecutive pediatric patients admitted with viral gastroenteritis to Osaka General Hospital between November 2007 and May 2009. Eighteen patients developed seizures, 12 of whom were positive for norovirus and six for rotavirus, as revealed by antigen detection. Of these 18 seizure patients, eight presented without fever (the aFS group) and 10 presented with febrile episodes (FS group)., Results: Seizure patients in the rotavirus group (83%) were more likely to be febrile than those in the norovirus group (58%). Compared with the aFS group, 90% of patients in the FS group presented seizures at an early stage of gastroenteritis. The frequency of clustered seizures in the FS group was considerably higher than that of febrile seizures in general and was also as high as that of "convulsions with mild gastroenteritis (CwG)". All seizure patients, whether febrile or afebrile, presented with generalized tonic clonic seizures (GTCS), complex partial seizures (CPS), or both. Diazepam (DZP) was less effective and carbamazepine (CBZ) was completely effective for the cessation of seizures in the FS group, similar to the drug response observed in CwG., Conclusions: The causative pathogen (norovirus or rotavirus) affected the frequency of febrile episodes during gastroenteritis, but fever had little effect on the clinical features of seizures. However, seizures occurred earlier during gastroenteritis in the FS group. On the whole, the clinical features of febrile seizures during viral gastroenteritis may closely resemble those of "convulsions with mild gastroenteritis" (CwG) than those of febrile seizures in general with respect to the frequency of clustered seizures and the antiepileptic drug responses and may have a pathogenic mechanism distinct from those of febrile seizures due to other causes., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Rotaviruses are the leading cause of severe, acute, and dehydrating diarrhea affecting children under 5 years of age worldwide. Despite an important reduction in rotavirus-caused deaths as a consequence of the rotavirus vaccine, alternative or complementary strategies for preventing or treating rotavirus-associated diarrhea are needed mainly in the poorest countries. We describe the cases of four rotavirus-unvaccinated 12-13-month-old girls and a 5-year-old boy who developed rotavirus-associated diarrhea confirmed by enzyme-linked immunosorbent assay, Western blotting, and immunochemistry analyses. After the first day of diarrheal episodes, three of the five patients were immediately administered oral N-acetylcysteine (NAC) 60 mg/kg daily, divided into three equal doses every 8 hours. The other two patients did not receive NAC and served as controls. Administration of NAC resulted in a decreased number of diarrheal episodes, excretion of fecal rotavirus antigen, and resolution of symptoms after 2 days of treatment. Our results suggest that NAC treatment after the first diarrheal episode could be an efficient strategy for treating rotavirus-affected children and preventing the associated severe life-threatening accompanying dehydration., (© 2014 Pharmacotherapy Publications, Inc.)

Unlabelled: The disease mechanisms associated with onset and secondary effects of rotavirus (RV) diarrhea remain to be determined and may not be identical. In this study, we investigated whether onset of RV diarrhea is associated with increased intestinal permeability and/or motility. To study the transit time, fluorescent fluorescein isothiocyanate (FITC)-dextran was given to RV-infected adult and infant mice. Intestinal motility was also studied with an opioid receptor agonist (loperamide) and a muscarinic receptor antagonist (atropine). To investigate whether RV increases permeability at the onset of diarrhea, fluorescent 4- and 10-kDa dextran doses were given to infected and noninfected mice, and fluorescence intensity was measured subsequently in serum. RV increased transit time in infant mice. Increased motility was detected at 24 h postinfection (h p.i.) and persisted up to 72 h p.i in pups. Both loperamide and atropine decreased intestinal motility and attenuated diarrhea. Analysis of passage of fluorescent dextran from the intestine into serum indicated unaffected intestinal permeability at the onset of diarrhea (24 to 48 h p.i.). We show that RV-induced diarrhea is associated with increased intestinal motility via an activation of the myenteric nerve plexus, which in turn stimulates muscarinic receptors on intestinal smooth muscles., Importance: We show that RV-infected mice have increased intestinal motility at the onset of diarrhea, and that this is not associated with increased intestinal permeability. These new observations will contribute to a better understanding of the mechanisms involved in RV diarrhea.

Purpose: We aimed on identifying the differences of febrile and afebrile seizures associated with mild rotavirus gastroenteritis (RVGE) in the pediatric population., Method: Medical charts of pediatric patients who had been admitted between July 1999 and June 2011 due to RVGE were retrospectively reviewed. Subjects were ultimately divided into three groups; 'no seizure' (NS: patients without seizure), 'febrile seizure' (FS: patients with fever during seizure), 'afebrile seizure' (AFS: patients without fever during seizure). Comparisons between groups were carried out on demographic and clinical characteristics, laboratory test results, electroencephalogram findings, brain magnetic resonance imaging findings, antiepileptic treatment, and prognosis., Results: Among the 755 subjects who had been admitted due to mild rotavirus enteritis, 696 (90.3%) did not have any seizures, 17 (2.2%) had febrile seizures, 42 (5.5%) had afebrile seizures. The duration of gastrointestinal symptoms before the onset of seizures were significantly shorter in the FS group compared to the AFS group (1.3±0.8 vs. 2.8±1.0 days; p<0.0001). A single seizure attack was significantly higher in the AFS group (3.0±1.6 vs. 1.7±1.0 episodes; p=0.0003), and the frequency of seizures that were of focal type with or without secondary generalization were significantly higher in the AFS group (33.3% vs. 6.0%; p=0.0139). All patients among the FS and AFS group had not received further antiepileptic treatment after discharge, and none developed epilepsy during follow up period., Conclusion: Despite some differences in seizure characteristics, both febrile and afebrile seizures associated with mild RVGE were mostly benign with a favorable prognosis., (Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objectives: Biliary atresia (BA) is a rapidly progressive form of biliary fibrosis affecting neonates. We previously reported that primary cilia on the intrahepatic cholangiocytes of patients with both syndromic and nonsyndromic BA were structurally abnormal. Our objective was to determine whether extrahepatic cholangiocytes in human biliary atresia, intrahepatic and extrahepatic cholangiocytes of rhesus rotavirus (RRV)-infected neonatal mice, and RRV-infected primary neonatal extrahepatic cholangiocytes also demonstrate ciliary abnormalities., Methods: The livers of neonatal BALB/c mice injected with RRV that developed jaundice, human extrahepatic bile duct samples obtained at time of hepatoportoenterostomy, and RRV-infected primary neonatal cholangiocytes were stained with antibodies against acetylated α tubulin to identify primary cilia., Results: Extrahepatic cholangiocytes from RRV-treated mice demonstrated minimal loss of primary cilia at day 3 but almost complete loss at day 8 and partial loss at day 12. No changes were seen in mouse intrahepatic bile ducts at any of the time points. In the human BA samples, primary cilia were almost completely absent from extrahepatic duct cholangiocytes. There were, however, abundant cilia in the peribiliary glands adjacent to extrahepatic ducts in the BA sample. Cilia in RRV-infected primary neonatal cholangiocytes were significantly decreased compared with controls., Conclusions: Primary cilia are selectively lost from neonatal extrahepatic but not intrahepatic cholangiocytes after RRV infection in BALB/c mice. The cilia are also decreased in RRV-infected primary cholangiocytes and the extrahepatic ducts from human patients with BA. This suggests that ciliary abnormalities are part of the pathophysiology of BA.

Background: Rotavirus gastroenteritis is a prevalent childhood illness rarely complicated by secondary bacterial sepsis. Although there are case reports of septicemia after rotavirus infection, there are no recent reviews on this topic., Objectives: To add new cases of septicemia after rotavirus to the literature, review the few cases of septicemia after rotavirus that have been reported, calculate the incidence of septicemia in children hospitalized for rotavirus gastroenteritis, and discuss the characteristics of septicemia after rotavirus infection and implications for current pediatric practice., Methods: We identified children whose illness was complicated by septicemia from among all hospitalizations at our facility for rotavirus gastroenteritis from May 1999 through May 2010. We also review the few cases reported in the English literature., Results: We identified two cases of septicemia from among 632 hospitalizations for rotavirus gastroenteritis in this time period, for an incidence rate of 0.32%, which is comparable to other estimates in the English literature. The typical course for cases of bacterial superinfection involves a second peak of high fever; other clinical signs are variable., Conclusions: Septicemia after rotavirus gastroenteritis is a rare but dangerous entity. Early identification of a child developing bacterial superinfection after rotavirus, as in any case of sepsis, is of the utmost importance, as is obtaining blood cultures in a child with a rotavirus infection and a second fever spike.

The study was aimed at an analysis of the influence of meglumine acridonacetate--the inductor of endogenous interferon synthesis--on the clinical course of gastroenteritis caused by rotavirus in children. A group of 100 patients aged from 3 months to 14 years were involved on retrospective comparative randomized study. The obtained data showed the advantages of meglumine acridonacetate administration during early terms of treatment of the gastroenteritis caused by rotaviruses. This treatment leads to fast regression of the main clinical symptoms such as fever, diarrhea, and intoxications, which results in reduction of the clinical course duration.

This study's aim was to analyze the characteristics and severity of acute gastroenteritis related to infection with rotavirus (group R), nontyphoid Salmonella (NTS; group S), and infection with both rotavirus and Salmonella (group B) in children in southern Taiwan in order to improve diagnosis and expedite appropriate management. The medical records of children admitted between October 2002 to September 2008 for acute gastroenteritis related to rotavirus, NTS, or coinfection were collected and analyzed.Among 2040 reviewed medical records, 40 patients were infected with both pathogens, while 501 cases were infected with rotavirus alone and 189 were infected with NTS alone. There were no significant differences between the three groups in terms of age at admission or sex. The age distribution of the reviewed cases revealed that children between the ages of 12-24 months comprised the largest proportion of cases in each group. Higher concentrations of fecal leukocytes and fecal pus cells and longer hospitalizations were observed in group B in comparison with groups S and R (p < 0.05). Clinical severity was significantly higher in groups B and S than group R (p < 0.05). A proportional association was found between the monthly case number of rotavirus infections and the mean monthly temperature difference in southern Taiwan (r = 0.9248; p < 0.0001). In summary, concomitant rotavirus infection with NTS infection did not affect the clinical manifestations of the reviewed patients. Rotavirus infection was less severe in most clinical manifestations, but vomiting was more severe in rotavirus-infected patients. Positive fecal leukocytes and positive fecal pus cells were more frequent during coinfection. There was a strong positive relationship between the incidence of rotavirus gastroenteritis and the mean monthly temperature difference., (Copyright © 2012. Published by Elsevier B.V.)

Background: Antigenemia is commonly found in children with rotavirus infection, although its clinical significance is undetermined. The aim of this study was to evaluate the association of antigenemia with clinical manifestations and cytokine profiles in children infected by rotavirus., Methods: In total, 68 children hospitalized with rotavirus gastroenteritis were enrolled. Serum samples were collected for detection of antigenemia and viremia. Clinical, laboratory and demographic data were analyzed. Proinflammatory, Th1 and Th2 cytokines were evaluated by bead-based flow cytometry., Results: Antigenemia and viremia were found in 45.6% (n = 31) and 5.9% (n = 4) of the 68 rotavirus-infected children, respectively. The mean age of the antigenemia group was significantly greater than that of the non-antigenemia group (43.5 vs. 27.3 months; p = 0.034). The antigenemia group had a significantly shorter length of hospitalization (4.8 vs. 5.8 days; p = 0.0354) in comparison with the non-antigenemia group, and antigenemia was inversely associated with the length of hospitalization (β = 0.31, p = 0.021). A significantly higher tumor necrosis factor (TNF)-β level was found in the patients with antigenemia than those without (236.7 vs. 29.2 pg/mL, p = 0.026). The severity of disease and the rate of extra-intestinal manifestations did not differ between the groups. Viremia was associated with a higher fever (p = 0.012)., Conclusions: Antigenemia was positively correlated with shorter hospital stay in children with rotavirus infection. Enhanced innate and T-cell-mediated immunity evidenced by up-regulation of TNF-β was found in patients with antigenemia., (Copyright © 2012. Published by Elsevier B.V.)

Endocytosis has recently been implicated in rotavirus (RV) entry. We examined the role of Rabs, which regulate endosomal trafficking, during RV entry. Several structural proteins of neuraminidase-sensitive and -insensitive RVs colocalized with Rab5, an early endosome marker, but not Rab7, a late endosome marker. Dominant-negative and constitutively active mutants demonstrated that Rab5 but not Rab4 or Rab7 affects rhesus RV (RRV) infectivity. These data suggest that early RRV trafficking is confined to the early endosome compartment and requires Rab5.

Systemic rotavirus infection, such as rotavirus antigenemia, has been found in immunocompetent rotavirus gastroenteritis patients. However, the pathogenesis of rotavirus infection in immunocompromised transplant recipients remains unclear. Enzyme-linked immunosorbent assay was used to measure rotavirus antigen levels in serially collected serum samples obtained from 62 pediatric patients receiving allogeneic hematopoietic stem cell transplants (HSCT). Rotavirus antigen was detected in 43 (6.8%) of 633 serum samples (8 of 62 patients). The duration of rotavirus antigenemia ranged between 1 and 10 weeks, and diarrhea was concurrent with rotavirus antigenemia in Cases 3, 6, 7, and 8. The level of viral antigen in the transplant recipients (0.19 ± 0.20) was significantly lower than that observed in serum samples collected from immunocompetent patients on either day 1 (0.49 ± 0.18, P = 0.0011) or day 3 (0.63 ± 0.09, P = 0.0005). A patient who received a graft from a human leukocyte antigen (HLA)-mismatched donor was at significant risk for rotavirus antigenemia (P = 0.024; odds ratio = 9.44) in comparison to patients who received grafts from HLA-matched donors. Although the duration of antigenemia was clearly longer in HSCT patients than in immunocompetent rotavirus gastroenteritis patients, the levels of viral antigen were not as high. Therefore, mismatched HLA may be a risk factor for rotavirus antigenemia after HSCT., (© 2011 John Wiley & Sons A/S.)

The introduction of specific International Classification of Diseases-10th revision code for rotavirus in 1999 prompted us to examine the US mortality data for 1999-2007 to validate rotavirus-coded deaths. Of 38 rotavirus-coded deaths identified in the national multiple cause-of-death database, results of laboratory testing could be obtained for 21 deaths, all of which had confirmation of rotavirus by either microbiologic or histopathologic testing.

Background: Rotavirus infection is the most common cause of severe gastroenteritis in children worldwide. New rotavirus vaccines are not currently used in the five countries that make up the Central Asian region. Three of these countries, Kazakhstan, Uzbekistan, and Kyrgyzstan, have a combined total population of 48 million and an estimated 1 million annual births., Methods: We conducted prospective hospital-based surveillance for rotavirus diarrhea in three Central Asian countries (Kazakhstan, Uzbekistan, and Kyrgyzstan) during 2005-2009 to estimate the burden of rotavirus. We calculated the proportion of rotavirus among children aged <5 years hospitalized with acute diarrhea and estimated numbers of rotavirus-associated deaths, hospitalizations, outpatient visits, and home care episodes., Results: Of 20 780 children hospitalized with diarrhea and enrolled in the study, 26% (95% confidence interval (CI) 25-27) were positive for rotavirus antigen by ELISA. On an annual basis, 4007 (2.6 per 1000 child-years) rotavirus hospitalizations occur in Kazakhstan, 5491 (2.1 per 1000 child-years) in Uzbekistan, and 3883 (6.8 per 1000 child-years) in Kyrgyzstan. Rotavirus is also estimated to cause 68 (0.04 per 1000 child-years) deaths in children aged <5 years in Kazakhstan, 662 (0.25 per 1000 child-years) in Uzbekistan, and 156 (0.27 per 1000 child-years) in Kyrgyzstan., Conclusion: This study presents an epidemiological picture of rotavirus disease in Central Asia and illustrates a substantial rotavirus burden, which is preventable with rotavirus vaccination., (Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: Few methods exist to noninvasively study in vivo gastrointestinal motility in animal models of enteric infections. None have been used on mouse pups, which often display more severe symptoms during enteric infections than adult mice. This study sought to determine whether digital fluoroscopy could be used to evaluate gastrointestinal motility in mouse pups as well as adult mice., Materials and Methods: Fluoroscopic imaging studies were performed on normal 6- to 8-week-old adult mice and 12-day-old pups to develop protocols for evaluating gastric and intestinal wall movements and changes in stomach sizes. These protocols were then applied to evaluate motility in an established rotavirus mouse model. Imaging studies were performed on adult mice at 0, 2, and 4 days postinfection and on 12-day-old pups at 2 days postinfection., Results: Fluoroscopic studies revealed postnatal differences of gastric peristalsis and rates of intestinal contractions between normal mouse pups and adult mice. Studies of the rotavirus mouse model revealed that differences in gastric function occur between rotavirus-infected and control mouse pups, but no discernible difference occurs between infected and control adult mice. In contrast, there were no detectable differences in rates of intestinal wall movements between control pups with normal stools and infected pups with loose stools., Conclusions: These results demonstrate that fluoroscopy can evaluate in vivo motility in mouse pups and by doing so provide findings that are clinically relevant to the study of enteric infections in young.

Background: Acute diarrhea continues to be an important cause of hospitalization in young children, and deaths still occur as a result. We reviewed a large cohort of hospitalized children affected by gastroenteritis. The hypothesis of our study was that clinical characteristics and a limited set of laboratory data can differentiate between the different causative pathogens of diarrhea., Methods: A chart review was performed of 650 patients with pathogen-proven diarrhea treated between April 2005 and May 2008 in the children's hospital of the University of Würzburg. Clinical presentation at the time of admission and during hospital stay, laboratory findings, stool pathogen results, and epidemiological data were collected and compared. A severity score was generated., Results: Rotavirus was the most common gastroenteritis pathogen identified, followed by norovirus, adenovirus and Salmonella spp. Nosocomial infections were caused most commonly by norovirus. Rotavirus was the most common agent when there was simultaneous detection of two or more viruses. Rotavirus infections were significantly more severe, with a higher frequency of diarrhea and elevated liver enzymes. Infections due to Salmonella spp showed significantly higher values for C-reactive protein, erythrocyte sedimentation rate, and body temperature. A seasonal distribution was noted, with the peak for rotaviruses/noroviruses in winter/spring, the peak for adenoviruses in November/December, and the peak for Salmonella spp in the summer months. Younger children and toddlers had significantly higher gastroenteritis and airway inflammation scores. Of note, respiratory symptoms and parameters of systemic inflammation differed between the different pathogens., Conclusions: Gastroenteritis is a common reason for hospital admission in previously healthy children during the first years of life. Rotaviruses were found to be the most common pathogens in our cohort. On the basis of clinical and laboratory parameters it appears possible to distinguish between the different causative agents. This may have implications for hospital hygiene management and for the identification of predictive markers of a severe course., (Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Rotavirus is one of the most common causes of gastroenteritis in children and is known to accompany some neurological disorders such as encephalitis/encephalopathy and seizures. Although cerebellar disorders sometime occur as a complication of rotavirus gastroenteritis in Japan, few reports have addressed these issues. Here, we report three cases of insulted cerebellums in addition to encephalitis/encephalopathy associated with rotavirus. Similar to posterior fossa syndrome after surgery, mutism was a notable symptom that lasted about 1 month. Brain diffusion-weighted imaging (DWI) revealed chronological changes, i.e., marked hyperintensity in the bilateral dentate nucleus followed by the vermis and cerebellar hemisphere. The bilateral dentate nucleus is known to be a key lesion site for mutism, and these clinical and radiological findings may be tightly connected in rotavirus-associated cerebellitis/cerebellopathy., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: In anticipation of vaccine introduction, we assessed epidemiology of rotavirus disease among children visiting medical centre due to acute diarrhoea in Ouagadougou, Burkina Faso., Methods: Between November 2008 and February 2010, stool specimens from 447 children less than 5 years of age suffering from diarrhoea were tested for the presence of rotavirus by antigen detection using an immunochromatographic test. Sociodemographic, environmental and clinical factors were assessed during the study., Results: Rotavirus antigen was detected in 151 (33.8%) of the patients. Most of the cases (94.2%) were in children < 24 months of age. Fever and vomiting were the symptoms most commonly reported in association with rotavirus diarrhoea and the patients were often hospitalized. Rotavirus-associated diarrhoea occurred mostly during the season from December to April (dry season). Rotavirus infection was significantly less frequent in breast-fed than among bottle-fed babies., Conclusions: The results of this study underscore the need to control rotavirus infections among young children in Burkina Faso and may argue a decision on the introduction of rotavirus vaccine in Burkina Faso.

Background/purpose: Acute diarrhea is one of the most common morbidities in pediatrics worldwide. We conducted a study to investigate the incidence of norovirus in young children hospitalized with acute diarrhea in Taiwan and its clinical peculiarity compared with rotavirus gastroenteritis., Methods: Between January and December, 2009, patients younger than 5 years and admitted to hospital with acute diarrhea were randomly selected; and their stool samples were collected and tested for presence of rotavirus and norovirus by enzyme immunoassay and reverse transcription-polymerase chain reaction, respectively. The clinical manifestations and laboratory findings of the enrolled patients were analyzed., Results: A total of 989 cases were enrolled with a mean age of 21.6 ± 13.7 months and a male proportion of 56.0%. Rotavirus and norovirus was detected in 20.2% and 14.6% of all patients, respectively. Genogroup II was the predominant strain of norovirus (80.6%). Children aged 6-36 months accounted for the majority of patients positive for rotavirus and norovirus (73.0% and 81.3%, respectively). The incidences of norovirus and rotavirus infection were higher during winter and early spring. Most patients with rotavirus and norovirus diarrhea experienced vomiting (74.9%vs. 74.8%, respectively) and fever (94.7%vs. 71.3%, respectively)., Conclusion: Most young diarrheal patients presenting with vomiting were likely to have norovirus or rotavirus infection. Patients with norovirus diarrhea experienced an absence of, or low-grade fever and longer duration of vomiting compared with those positive for rotavirus infection. A family history of current gastroenteritis may suggest the possibility of norovirus infection., (Copyright © 2010 Taiwan Society of Microbiology. Published by Elsevier B.V. All rights reserved.)

Porcine group A rotaviruses (GARV) are causative agents of enteritis in piglets and are a large reservoir of genetic material for the diversification of human GARVs. Accumulation of information on the genetic heterogeneity of porcine viruses is pivotal for readily characterising unusual human strains. Screening of 292 fecal samples, collected from 4-5- to 8-9-week-old asymptomatic pigs from four herds in Ireland between 2005 and 2007 resulted in 19 (6.5%) samples testing positive by reverse-transcription PCR (RT-PCR) for GARV. The strains were molecularly characterized to collate data on the VP7 and partial VP4 outer capsid genes. By sequence analysis of the VP7 gene, the Irish strains were identified as G2, G4, G5, G9 and G11 viruses. The G11 strains were closely related to other human and porcine G11 strains, while the G2 strains resembled porcine G2 viruses detected recently in Europe and southern Asia. The G4 strains were distantly related to other G4 human and animal strains, constituting a separate G4 VP7 lineage. Analysis of the G5 strains revealed that they were similar to a selection of G5 human and porcine strains, while the G9 strains resembled other porcine G9 viruses. By sequence analysis of the VP8* fragment of the VP4, the Irish viruses were characterised as P[6], P[7], P[13], P[13]/[22], P[26] and P[32].