Background: The role of the gut microbiota in Crohn’s disease (CD) is established and fecal microbiota transplantation (FMT) is an attractive therapeutic strategy. No randomized controlled clinical trial results are available. We performed a randomized, single-blind, sham-controlled pilot trial of FMT in adults with colonic or ileo-colonic CD. Method: Patients enrolled while in flare received oral corticosteroid. Once in clinical remission, patients were randomized to receive either FMT or sham transplantation during a colonoscopy. Corticosteroids were tapered and a second colonoscopy was performed at week 6. The primary endpoint was the implantation of the donor microbiota at week 6 (Sorensen index > 0.6). Results: Eight patients received FMT and nine sham transplantation. None of the patients reached the primary endpoint. The steroid-free clinical remission rate at 10 and 24 weeks was 44.4% (4/9) and 33.3% (3/9) in the sham transplantation group and 87.5% (7/8) and 50.0% (4/8; one patient loss of follow-up while in remission at week 12 and considered in flare at week 24) in the FMT group. Crohn’s Disease Endoscopic Index of Severity decreased 6 weeks after FMT (p = 0.03) but not after sham transplantation (p = 0.8). Conversely, the CRP level increased 6 weeks after sham transplantation (p = 0.008) but not after FMT (p = 0.5). Absence of donor microbiota engraftment was associated with flare. No safety signal was identified. Conclusion: The primary endpoint was not reached for any patient. In this pilot study, higher colonization by donor microbiota was associated with maintenance of remission. These results must be confirmed in larger studies (NCT02097797).

SUMMARY: EuroRotaNet, a laboratory network, was established in order to determine the diversity of co-circulating rotavirus strains in Europe over three or more rotavirus seasons from 2006/2007 and currently includes 16 countries. This report highlights the tremendous diversity of rotavirus strains co-circulating in the European population during three years of surveillance since 2006/2007 and points to the possible origins of these strains including genetic reassortment and interspecies transmission. Furthermore, the ability of the network to identify strains circulating with an incidence of ⩾1% allowed the identification of possible emerging strains such as G8 and G12 since the beginning of the study; analysis of recent data indicates their increased incidence. The introduction of universal rotavirus vaccination in at least two of the participating countries, and partial vaccine coverage in some others may provide data on diversity driven by vaccine introduction and possible strain replacement in Europe.

Enteric viruses represent a global public health threat and are implicated in numerous foodborne and waterborne disease outbreaks. Nonetheless, relatively little is known of their fate and stability in the environment. In this study we used carefully validated methods to monitor enteric viruses, namely adenovirus (AdV), JC polyomavirus (JCV), noroviruses (NoVs), sapovirus (SaV) and hepatitis A and E viruses (HAV and HEV) from wastewater source to beaches and shellfish beds. Wastewater influent and effluent, surface water, sediment and shellfish samples were collected in the Conwy catchment (North Wales, UK) once a month for one year. High concentrations of AdV and JCV were found in the majority of samples, and no seasonal patterns were observed. No HAV and HEV were detected and no related illnesses were reported in the area during the period of sampling. Noroviruses and SaV were also detected at high concentrations in wastewater and surface water, and their presence correlated with local gastroenteritis outbreaks during the spring and autumn seasons. Noroviruses were also found in estuarine sediment and in shellfish harvested for human consumption. As PCR-based methods were used for quantification, viral infectivity and degradation was estimated using a NoV capsid integrity assay. The assay revealed low-levels of viral decay in wastewater effluent compared to influent, and more significant decay in environmental waters and sediment. Results suggest that AdV and JCV may be suitable markers for the assessment of the spatial distribution of wastewater contamination in the environment; and pathogenic viruses can be directly monitored during and after reported outbreaks to prevent further environment-derived illnesses.

This prospective study, conducted from January 2003 to June 2005, investigated the incidence and the clinical role of various enteric viruses responsible for infantile gastroenteritis in 632 Tunisian children presenting in dispensaries (380 children) or hospitalized (252 children) for acute diarrhea. At least one enteric virus was found in each of 276 samples (43.7%). A single pathogen was observed in 234 samples, and mixed infections were found in 42 samples. In terms of frequency, rotavirus and norovirus were detected in 22.5 and 17.4% of the samples, respectively, followed by astrovirus (4.1%), Aichi virus (3.5%), adenovirus types 40 and 41 (2.7%), and sapovirus (1.0%). The seasonal distribution of viral gastroenteritis showed a winter peak but also an unusual peak from May to September. The severity of the diarrhea was evaluated for hospitalized infants. No significant differences were observed between rotavirus and norovirus infections with regard to the incidence and the clinical severity of the disease, especially in dehydration.

Noroviruses (NoVs) are one of the leading causes of gastroenteritis in children and adults. For the last 2 decades, genogroup II genotype 4 (GII.4) NoVs have been circulating worldwide. GII.4 NoVs can be divided into variants, and since 2002 they have circulated in the population before being replaced every 2 or 3 years, which raises questions about the role of their histo-blood group antigen (HBGA) ligands in their evolution. To shed light on these questions, we performed an analysis of the interaction between representative GII.4 variants and HBGAs, and we determined the role of selected amino acids in the binding profiles. By mutagenesis, we showed that there was a strict structural requirement for the amino acids, directly implicated in interactions with HBGAs. However, the ablation of the threonine residue at position 395 (ΔT395), an epidemiological feature of the post-2002 variants, was not deleterious to the binding of the virus-like particle (VLP) to the H antigen, while binding to A and B antigens was severely hampered. Nevertheless, the ΔT395 VLPs gained the capacity to bind to the Lewis x and sialyl-Lewis x antigens in comparison with the wild-type VLP, demonstrating that amino acid residues outside the HBGA binding site can modify the binding properties of NoVs. We also analyzed the attachment of baculovirus-expressed VLPs from six variants (Bristol, US95/96, Hunter, Yerseke, Den Haag, and Osaka) that were isolated from 1987 to 2007 to phenotyped saliva samples and synthetic HBGAs. We showed that the six variants could all attach to saliva of secretors irrespective of the ABO phenotype and to oligosaccharides characteristic of the secretor phenotype. Interestingly, Den Haag and Osaka variants additionally bound to carbohydrates present in the saliva of Lewis-positive nonsecretors. The carbohydrate binding profile and the genetic and mutagenesis analysis suggested that GII.4 binding to Lewis x and sialyl-Lewis x antigens might be a by-product of the genetic variation of the amino acids located in the vicinity of the binding site. Analysis of the binding properties for the six variants by surface plasmon resonance showed that only post-2002 variants (i.e., Hunter, Yerseke, Den Haag, and Osaka) presented strong binding to A and B antigens, suggesting that the GII.4 evolution could be related to an increased affinity for HBGAs for the post-2002 variants. The combination of increased affinity for ABH antigens and of a newly acquired ability to recognize glycans from Lewis-positive nonsecretors could have contributed to the epidemiological importance of strains such as the Den Haag GII.4 subtype.

The circulation of enteric viruses among the population of Cairo, Egypt, between March 2006 and February 2007 was studied. At least one virus was detected in 50% of fecal samples, 57.4% of which were positive for rotavirus, 26% for norovirus, 10.4% for adenovirus, and 1.7% for astrovirus. Over 10% of infections were mixed infections. Rotavirus typing showed that G1P[8] and G2P[4] were predominant but that the unusual G12P[4] and G12P[6] reassortants were also present. Among the noroviruses, half belonged to the predominant GGII.4 cluster. The phylogenetic analysis of the capsid gene suggested that GGII.4 strains from Cairo were similar to those circulating elsewhere. It also showed the emergence of new GGII.4 variants that were not associated with any previously known GGII.4 isolate. Further studies are required to assess the disease burden of enteric viruses in Egypt and the impact of atypical strains.