Acute Infectious Gastroenteritis: The Causative Agents, Omics-Based Detection of Antigens and Novel Biomarkers

Acute infectious gastroenteritis (AGE) is among the leading causes of mortality in children less than 5 years of age worldwide. There are many causative agents that lead to this infection, with rotavirus being the commonest pathogen in the past decade. However, this trend is now being progressively replaced by another agent, which is the norovirus. Apart from the viruses, bacteria such as Salmonella and Escherichia coli and parasites such as Entamoeba histolytica also contribute to AGE. These agents can be recognised by their respective biological markers, which are mainly the specific antigens or genes to determine the causative pathogen. In conjunction to that, omics technologies are currently providing crucial insights into the diagnosis of acute infectious gastroenteritis at the molecular level. Recent advancement in omics technologies could be an important tool to further elucidate the potential causative agents for AGE. This review will explore the current available biomarkers and antigens available for the diagnosis and management of the different causative agents of AGE. Despite the high-priced multi-omics approaches, the idea for utilization of these technologies is to allow more robust discovery of novel antigens and biomarkers related to management AGE, which eventually can be developed using easier and cheaper detection methods for future clinical setting. Thus, prediction of prognosis, virulence and drug susceptibility for active infections can be obtained. Case management, risk prediction for hospital-acquired infections, outbreak detection, and antimicrobial accountability are aimed for further improvement by integrating these capabilities into a new clinical workflow.

Minimally Invasive Image-Guided Gut Transport Function Measurement Probe

Introduction: Diseases such as celiac disease, environmental enteric dysfunction, infectious gastroenteritis, type II diabetes and inflammatory bowel disease are associated with increased gut permeability. Dual sugar absorption tests, such as the lactulose to rhamnose ratio (L:R) test, are the current standard for measuring gut permeability. Although easy to administer in adults, the L:R test has a number of drawbacks. These include an inability to assess for spatial heterogeneity in gut permeability that may distinguish different disease severity or pathology, additional sample collection for immunoassays, and challenges in carrying out the test in certain populations such as infants and small children. Here, we demonstrate a minimally invasive probe for real-time localized gut permeability evaluation through gut potential difference (GPD) measurement.Materials and Methods: The probe has an outer diameter of 1.2 mm diameter and can be deployed in the gut of unsedated subjects via a transnasal introduction tube (TNIT) that is akin to an intestinal feeding tube. The GPD probe consists of an Ag/AgCl electrode, an optical probe and a perfusion channel all housed within a transparent sheath. Lactated Ringer’s (LR) solution is pumped through the perfusion channel to provide ionic contact between the electrodes and the gut lining. The optical probe captures non-scanning (M-mode) OCT images to confirm electrode contact with the gut lining. A separate skin patch probe is placed over an abraded skin area to provide reference for the GPD measurements. Swine studies were conducted to validate the GPD probe. GPD in the duodenum was modulated by perfusing 45 ml of 45 mM glucose.Results: GPD values of −13.1 ± 2.8 mV were measured in the duodenum across four swine studies. The change in GPD in the duodenum with the addition of glucose was −10.5 ± 2.4 mV (p < 0.001). M-mode OCT images provided electrode-tissue contact information, which was vital in ascertaining the probe’s proximity to the gut mucosa.Conclusion: We developed and demonstrated a minimally invasive method for investigating gastrointestinal permeability consisting of an image guided GPD probe that can be used in unsedated subjects.

Leaked genomic and mitochondrial DNA contribute to the host response to noroviruses in a STING-dependent manner

The cGAS-STING pathway is central to the IFN response against DNA viruses. However, recent studies are increasingly demonstrating its role in the restriction of some RNA viruses. Here we show that the cGAS-STING pathway also contributes to the IFN response against noroviruses, positive-sense single-stranded RNA viruses that are now one of the most common causes of infectious gastroenteritis world-wide. We show a significant reduction in IFN-β induction and a corresponding increase in viral replication in norovirus-infected cells following STING inhibition, knockdown or deletion. Upstream of STING, we show that cells lacking either cGAS or IFI16 also have severely impaired IFN responses. Further, we demonstrate that immunostimulatory host genome-derived DNA, and to a lesser extent mitochondrial DNA, accumulate in the cytosol of norovirus-infected cells. And lastly, overexpression of the viral NS4 protein was sufficient to drive the accumulation of cytosolic DNA. Together, our data elucidate a role for cGAS, IFI16 and STING in the restriction of noroviruses, and demonstrate for the first time the utility of host genomic DNA as a damage-associated molecular pattern in cells infected with an RNA virus.HighlightscGAS, IFI16 and STING are required for a robust IFN response against norovirusesNuclear and mitochondrial DNA accumulate in the cytosols of infected cellsViral NS4 mediates accumulation of cytosolic DNA

Prevalence of Clinical Factors before Inflammatory Bowel Disease Diagnosis among 380,000 Girls Scheduled for Papillomavirus Vaccination: A Cohort Study

Background: As potentially auto-immune, human papillomavirus vaccination safety surveillance includes Inflammatory Bowel Disease (IBD). We aimed to assess other risk factors among girls scheduled to vaccinate during 2007-2016 Methods: Cohort study including girls aged 9-18 years using the Spanish Primary Care Database for Pharmacoepidemiological Research (BIFAP). Adjusted Hazard ratios (HR; reported in brackets) of IBD associated with (gastroenterological and others) clinical factors were estimated. Results: Out of 388,669 girls, 185 IBD cases occurred (43.78% Crohn’s disease, 37.84% Ulcerative colitis, 18.38% undetermined). IBD increased with age, IBD family history (HR: 10.64), thyroiditis (5.07), herpesvirus infection (4.96), asthenia (1.74), while decreased with inhaled budesonide (0.38) or meningococcus B-C vaccination (0.33). Abnormal bowel movement (25.26), lower gastrointestinal bleeding (8.74), dyspepsia (7.69), abdominal pain (1.49) and spasmolytic (3.89) or antisecretory drugs (2.43) were more recorded among cases. Contraceptives (3.07), fever (2.57), infectious gastroenteritis (2.48), growth problems (2.12), chronic diarrhoea (5.37) and coeliac disease (2.07) showed almost statistical increased risk while depression or allergy showed no risk. Conclusions: The relationship between potential immune diseases and IBD varied, being high for thyroiditis, just suggested for celiac disease and lacking for allergy. The important prevalence of family history, gastrointestinal or growth conditions on IBD was confirmed.

Probiotics in Pediatrics. A Review and Practical Guide

The potential benefit of the administration of probiotics in children has been studied in many settings globally. Probiotics products contain viable micro-organisms that confer a health benefit on the host. Beneficial effects of selected probiotic strains for the management or prevention of selected pediatric conditions have been demonstrated. The purpose of this paper is to provide an overview of current available evidence on the efficacy of specific probiotics in selected conditions to guide pediatricians in decision-making on the therapeutic or prophylactic use of probiotic strains in children. Evidence to support the use of certain probiotics in selected pediatric conditions is often available. In addition, the administration of probiotics is associated with a low risk of adverse events and is generally well tolerated. The best documented efficacy of certain probiotics is for treatment of infectious gastroenteritis, and prevention of antibiotic-associated, Clostridioides difficile-associated and nosocomial diarrhea. Unfortunately, due to study heterogeneity and in some cases high risk of bias in published studies, a broad consensus is lacking for specific probiotic strains, doses and treatment regimens for some pediatric indications. The current available evidence thus limits the systematic administration of probiotics. The most recent meta-analyses and reviews highlight the need for more well-designed, properly powered, strain-specific and dedicated-dose response studies.

Detection of Rotavirus Vaccine Strains in Oysters and Sewage and Their Relationship with the Gastroenteritis Epidemic

Rotavirus is one of the major causes of infectious gastroenteritis among infants and children, and live attenuated vaccines for rotavirus A (RVA), namely Rotarix and RotaTeq, have become recently available in Japan. Rotavirus is known to be excreted from patients and accumulated in oysters similar to norovirus; however, the vaccine strains in aquatic environments or oysters have not yet been analyzed. In this study, we focused on wild-type RVA, which is highly important in considering the risk of infectious diseases. We quantified total RVA, Rotarix, and RotaTeq strains in oyster and sewage samples collected between September 2014 and July 2016 to assess the contamination levels of wild-type RVA by subtracting the quantitative value of rotavirus vaccine strains from that of total RVA. The positive rates of wild-type RVA, Rotarix, and RotaTeq in oysters were 54, 14, and 31%, respectively. These rates were comparable with those of wild-type RVA (57%) and RotaTeq (35%) in sewage; however, Rotarix was not detected in any sewage samples. The comparison of viral concentrations in oysters and sewage suggested more efficient accumulation of the vaccine strains in oysters than the wild-type RVA. The concentration of wild-type RVA in oysters was significantly correlated with that in sewage with a lag-time of -6 to 0 weeks which is required for viral transportation from wastewater treatment plants to oysters. On the other hand, no significant correlation was observed between wild-type RVA concentration in sewage and the number of rotavirus-associated gastroenteritis cases, implying the existence of asymptomatic RVA-infected individuals. Importance We quantified rotavirus A (RVA), Rotarix, and RotaTeq strains in oyster and sewage samples during two gastroenteritis seasons, and revealed the exact contamination of wild-type RVA by subtracting the quantitative value of rotavirus vaccine strains from that of RVA. The concentration of wild-type RVA was significantly correlated between oysters and sewage, although no significant correlation was seen between wild-type RVA concentration in sewage and the number of rotaviruses detected in patients with gastroenteritis. This finding suggested the existence of asymptomatic patients and that monitoring of rotavirus vaccine strain could be useful to understand the trend of wild-type RVA and rotavirus outbreak in detail. We believe that our study makes a significant contribution to the literature because it is the first report of detection of rotavirus vaccine strains in oysters.

Etiological structure of acute gastrointestinal infections in children and analysis of their clinical features depending on etiology

Acute gastroenteritis (AGE) often causes different complications in younger children, which can lead to hospital admission. Purpose — to explore the etiological structure of infectious gastroenteritis in children under 5 years and severity clinical features of the disease depending on the pathogen. Materials and methods. 978 children with AGE were enrolled in the study. The age of participants was 0–5 years, they all were patients of infectious diseases department of Kyiv city children's hospital No.1 during 2014–2018 years. The division into groups was based on the detected pathogen. Determination of rotavirus antigen was performed by enzyme$linked immunosorbent assay (ELISA), other pathogens were identified by nucleic acid extraction and testing by TAC (TaqMan Array Cards). The clinical features severity according to Vesicari's scale were analyzed during the study. Results. Among children who were enrolled in the study the most common pathogen was rotavirus, which was present in 47% of all cases. Norovirus took the second place. Campylobacter was the most common among bacterial pathogens. Rotavirus was more common among children of older age group. Shigella and Campylobacter were two the most common pathogens in younger age group. In group non-rotavirus pathogens the most common were mild and moderate course of the disease, but in group with rotavirus mild course wasn't common. None of children with adenoviral or noroviral infection had mild disease. The most part of AGEs caused by bacterial pathogens had severe course. Conclusions. The leadership of rotavirus infection and an important change in the majority of infections, the introduction of vaccination into the national calendar is highly relevant. Norovirus took the second place in etiological structure of AGE after rotavirus, and that's why developing vaccine against it is an actual problem. According to severity of disease depending on the pathogen, the biggest value for prophylaxis will have development of vaccines against salmonellosis, norovirus and adenovirus. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of these Institutes. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: causative agents of acute gastroenteritis, rotavirus, noravirus, severity.