Rotavirus and norovirus cause acute gastroenteritis with severe diarrhoea and vomiting, symptoms that may lead to severe dehydration and death. The objective of this randomized double-blinded ...placebo-controlled study was to investigate whether ondansetron, a serotonin receptor antagonist could attenuate rotavirus- and norovirus-induced vomiting and diarrhoea, which would facilitate oral rehydration and possibly accelerate recovery and reduce need for hospitalization.
Children with acute gastroenteritis, aged 6 months to 16 years where enrolled (n = 104) and randomized to one single oral dose (0.15mg/kg) of ondansetron (n = 52) or placebo (n = 52). The number of diarrhoea and vomiting episodes during the 24 hours following treatment was reported as well as the number of days with symptoms. Pathogens in faeces were diagnosed by real-time PCR. Outcome parameters were analyzed for rotavirus- and norovirus-positive children.
One dose of oral ondansetron reduced duration of rotavirus clinical symptoms (p = 0.014), with a median of two days. Furthermore, ondansetron reduced diarrhea episodes, most pronounced in children that had been sick for more than 3 days before treatment (p = 0.028).
Ondansetron may be a beneficial treatment for children with rotavirus gastroenteritis.
European Clinical Trial Database EudraCT 2011-005700-15.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tick-borne encephalitis virus (TBEV) infections can be asymptomatic or cause moderate to severe injuries of the nervous system. We previously reported that a nonfunctional chemokine receptor 5 (CCR5) ...and a functional Toll-like receptor 3 (TLR3) predispose adults to clinical tick-borne encephalitis (TBE). This study expands our previous findings and further examines polymorphisms in CCR5 and TLR3 genes in different age and disease severity groups.
117 children and 129 adults, stratified into mild, moderate and severe forms of TBE, and 103 adults with severe TBE were analyzed. 135 healthy individuals and 79 patients with aseptic meningoencephalitis served as controls. CCR5 delta 32 and rs3775291 TLR3 genotypes were established by pyrosequencing, and their frequencies were analyzed using recessive genetic, genotype and allelic models.
The prevalence of CCR5Δ32 homozygotes was higher in children (2.5%), in adults with severe TBE (1.9%), and in the combined cohort of TBE patients (2.3%) than in controls (0%) (p<0.05). The nonfunctional homozygous TLR3 genotype was less prevalent among the combined TBE cohort (11.5%) than among controls (19.9%) (p = 0.025), but did not differ between children TBE and controls. The genotype and allele prevalence of CCR5 and TLR3 did not differ in children nor adult TBE cohorts stratified by disease severity. However, in the severe adult TBE cohort, homozygous functional TLR3 genotype and wt allele were less prevalent compared to the adult cohort with the whole disease severity spectrum (44.4% vs 59.8% p = 0.022 and 65.2% vs 76.4% p = 0.009; respectively).
Independently of age, nonfunctional CCR5Δ32 mutation is a significant risk factor for development of clinical TBE, but not for disease severity. The polymorphism of TLR3 gene predisposes to clinical TBE in adults only and may be associated with disease severity. Further studies are needed to clarify the role of these polymorphisms in susceptibility to TBEV infection.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Increased intestinal permeability has been proposed as a mechanism of rotavirus-induced diarrhea. Studies with humans and mice have, however, shown that rotavirus leaves intestinal permeability ...unaffected or even reduced during diarrhea, in contrast to most bacterial infections. Gastrointestinal permeability is regulated by the vagus nerve and the enteric nervous system, which is composed of neurons and enteric glial cells (EGCs). We investigated whether the vagus nerve, serotonin (5-HT), EGCs, and neurotropic factors contribute to maintaining gut barrier homeostasis during rotavirus infection. Using subdiaphragmatic vagotomized and 5-HT
receptor knockout mice, we found that the unaffected epithelial barrier during rotavirus infection is independent of the vagus nerve but dependent on 5-HT signaling through enteric intrinsic 5-HT
receptors. Immunofluorescence analysis showed that rotavirus-infected enterocytes were in close contact with EGCs and enteric neurons and that the glial cell-derived neurotrophic factor (GDNF) was strongly upregulated in enterocytes of infected mice. Moreover, rotavirus and 5-HT activated EGCs (
0.001). Using Ussing chambers, we found that GDNF and
-nitrosoglutathione (GSNO) led to denser epithelial barriers in small intestinal resections from noninfected mice (
0.01) and humans (
0.001) and that permeability was unaffected in rotavirus-infected mice. GSNO made the epithelial barrier denser in Caco-2 cells by increasing the expression of the tight junction protein zona occludens 1 (
0.001), resulting in reduced passage of fluorescein isothiocyanate dextran (
0.05) in rotavirus-infected monolayers. This is the first report to show that neurotropic factors contribute to maintaining the gut epithelial barrier during viral insult.
Human and mouse studies have shown that rotavirus infection is associated with low inflammation and unaffected intestinal barrier at the time of diarrhea, properties different from most bacterial and inflammatory diseases of the gut. We showed by
,
, and
experiments that neurotrophic factors and 5-HT have barrier protective properties during rotavirus insult. These observations advance our understanding of how the gut barrier is protected against rotavirus and suggest that rotavirus affects the gut barrier differently from bacteria. This is the first report to show that neurotrophic factors contribute to maintain the gut epithelial barrier during viral insult.
The ongoing SARS-CoV-2 pandemic has spread rapidly worldwide and disease prevention is more important than ever. In the absence of a vaccine, knowledge of the transmission routes and risk areas of ...infection remain the most important existing tools to prevent further spread. Here we investigated the presence of the SARS-CoV-2 virus in the hospital environment at the Uppsala University Hospital Infectious Disease ward by RT-qPCR and determined the infectivity of the detected virus in vitro on Vero E6 cells. SARS-CoV-2 RNA was detected in several areas, although attempts to infect Vero E6 cells with positive samples were unsuccessful. However, RNase A treatment of positive samples prior to RNA extraction did not degrade viral RNA, indicating the presence of SARS-CoV-2 nucleocapsids or complete virus particles protecting the RNA as opposed to free viral RNA. Our results show that even in places where a moderate concentration (Ct values between 30 and 38) of SARS-CoV-2 RNA was found; no infectious virus could be detected. This suggests that the SARS-CoV-2 virus in the hospital environment subsides in two states; as infectious and as non-infectious. Future work should investigate the reasons for the non-infectivity of SARS-CoV-2 virions.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Norovirus (NoV) is an important cause of nosocomial gastroenteric outbreaks. This 5-month study was designed to characterize NoV contamination and airborne dispersal in patient rooms during hospital ...outbreaks. Air vents, overbed tables, washbasins, dust, and virus traps designed to collect charged particles from the air were swabbed to investigate the possibility of NoV contamination in patient rooms during outbreaks in seven wards and in an outbreak-free ward. Symptomatic inpatients were also sampled. Nucleic acid extracts of the samples were examined for NoV RNA using genogroup I (GI) and GII real-time reverse transcription-PCR (RT-PCR). The NoV strains were characterized by RT-PCR, sequencing, and phylogenetic analysis of the RNA-dependent RNA-polymerase-N/S capsid-coding region (1,040 nucleotides nt). Patient strains from two outbreaks in one ward were sequenced across the RNA-dependent-RNA-polymerase major capsid-coding region (2.5 kb), including the hypervariable P2 domain. In the outbreak wards, NoV GII was detected in 48 of 101 (47%) environmental swabs and 63 of 108 patients (58%); NoV genotype II.4 was sequenced from 18 environmental samples, dust (n = 8), virus traps (n = 4), surfaces (n = 6), and 56 patients. In contrast, NoV GII was detected in 2 (GII.4) of 28 (7%) environmental samples and in 2 (GII.6 and GII.4) of 17 patients in the outbreak-free ward. Sequence analyses revealed a high degree of similarity (>99.5%, 1,040 nt) between NoV GII.4 environmental and patient strains from a given ward at a given time. The strains clustered on 11 subbranches of the phylogenetic tree, with strong correlations to time and place. The high nucleotide similarity between the NoV GII.4 strains from patients and their hospital room environment provided molecular evidence of GII.4 dispersal in the air and dust; therefore, interventional cleaning studies are justified.
Viral Gastroenteritis Svensson, Lennart; Desselberger, Ulrich; Estes, Mary K ...
2016, 2016-07-13
eBook
Viral Gastroenteritis: Molecular Epidemiology and Pathogenesis provides a comprehensive review of research on viruses causing acute gastroenteritis in infants and young children, including coverage ...of rotaviruses, human caliciviruses, astroviruses, enteric adenoviruses, and viruses causing gastroenteritis more rarely. Includes general chapters on gastrointestinal physiology and pathophysiology, gastrointestinal immune mechanisms, immunodeficiencies and host genetics influencing susceptibility to viral gastroenteritis, and therapeutic and preventative approaches. The book also includes special sections on virus particle structures, replication cycles, pathogenesis, immunology, epidemiology, and preventative measures. This book covers both basic science and translational applications and is an appropriate resource for virologists, molecular biologists, epidemiologists, gastroenterologists, vaccinologists, and those with an interest in public health.
Features new approaches in diagnosis and characterization of viral gastroenteritis pathogensIncludes coverage of therapeutic and preventative methodsCovers recent advances in characterizing the molecular biology and immune responses of rotaviruses and norovirusesCovers both basic science and translational applications and is an appropriate resource for virologists, molecular biologists, epidemiologists, gastroenterologists, vaccinologists, and those with an interest in public health.
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