An assessment of potential biomarkers of environment enteropathy and its association with age and microbial infections among children in Bangladesh.

Interventional studies targeting environment enteropathy (EE) are impeded by the lack of appropriate, validated, non-invasive biomarkers of EE. Thus, we aimed to validate the association of potential biomarkers for EE with enteric infections and nutritional status in a longitudinal birth cohort study. We measured endotoxin core antibody (EndoCab) and soluble CD14 (sCD14) in serum, and myeloperoxidase (MPO) in feces using commercially available enzyme-linked immunosorbent assay (ELISA) kits. We found that levels of serum EndoCab and sCD14 increase with the cumulative incidence of enteric infections. We observed a significant correlation between the fecal MPO level in the children at 24 months of age with the total number of bacterial and viral infections, the total number of parasitic infections, and the total number of diarrheal episodes and diarrheal duration. We observed that the levels of serum EndoCab, sCD14, and fecal MPO at 3 months of age were significantly associated with whether children were malnourished at 18 months of age or not. Biomarkers such as fecal MPO, serum EndoCab and sCD14 in children at an early age may be useful as a measure of cumulative burden of preceding enteric infections, which are predictive of subsequent malnutrition status and may be useful non-invasive biomarkers for EE.

Coronavirus disease-2019: implications for the gastroenterologist.

PURPOSE OF REVIEW: The COVID-19 pandemic has impacted the practicing gastroenterologist in several ways. Although majority of COVID-19 patients present with respiratory symptoms, gastrointestinal symptoms are also seen. COVID-19 has also disrupted gastrointestinal endoscopy services in numerous ways. There are also concerns regarding the impact of these changes on gastrointestinal cancer screening and management of chronic gastrointestinal diseases. The purpose of this review is to provide an overview of the implications of COVID-19 for the practicing gastroenterologist. RECENT FINDINGS: COVID-19 patients can have gastrointestinal symptoms including diarrhea, nausea and vomiting, abdominal pain and anorexia. Separate from the management of COVID-19 patients, there has been a reduction in endoscopy volume worldwide. This has also resulted in reduction/cessation of in-person clinic visits and an increasing use of telemedicine services. In addition, patients with certain chronic diseases like chronic liver disease or inflammatory bowel disease may have worse outcomes during the COVID-19 pandemic. SUMMARY: Gastroenterologists need to rapidly adapt to the challenges being faced and need to make both systems and practice-based changes to the endoscopy unit and outpatient clinic practices. Gastroenterologists should stay up-to-date with the rapidly evolving literature regarding gastrointestinal symptoms in COVID-19 patients as well as its impact on chronic gastrointestinal illnesses.

Gastrointestinal coronavirus disease 2019: epidemiology, clinical features, pathogenesis, prevention, and management.

INTRODUCTION: The new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the etiologic agent of coronavirus disease 2019. Some authors reported pieces of evidence that patients with SARS-CoV-2 infection could have direct involvement of the gastrointestinal tract, and in symptomatic cases, gastrointestinal symptoms (diarrhea, nausea/vomiting, abdominal pain) could be very common. AREA COVERED: In this article, we reviewed current-published data of the gastrointestinal aspects involved in SARS-CoV-2 infection, including prevalence and incidence of specific symptoms, the presumptive biological mechanism of GI infection, prognosis, clinical management, and public health-related concerns on the possible risk of oral-fecal transmission. EXPERT OPINION: Different clues point to direct virus infection and replication in mucosal cells of the gastrointestinal tract. In vitro studies showed that SARS-CoV-2 could enter into the gastrointestinal epithelial cells by the Angiotensin-Converting enzyme two membrane receptor. These findings, coupled with the identification of viral RNA found in stools of patients, clearly suggest that direct involvement of the gastrointestinal tract is very likely. This can justify most of the gastrointestinal symptoms but also suggest a risk for an oral-fecal route for transmission, additionally or alternatively to the main respiratory route.

Guía de práctica clínica para el diagnóstico y manejo de la infección por Helicobacter Pylori en enfermedades gastroduodenales / Clinical practice guideline for the diagnosis and management of Helicobacter Pylori infection in gastroduodenal diseases

La infección por Helicobacter pylori (HP) es la infección crónica más común en humanos (1, 2). Se trata de una bacteria gram negativa espiralada, microaerofílica (3) que por su contenido en ureasa, motilidad y capacidad para adherirse al epitelio gástrico puede sobrevivir y proliferar en el medio gástrico (4). Esta bacteria generalmente no invade el tejido gástrico, pero lo hace más susceptible al daño del ácido péptico al romper la capa mucosa y liberar enzimas y toxinas que, al ser reconocidas por el huésped, generan una reacción inflamatoria más perjudicial aún. La inflamación crónica del tejido altera la fisiología de la secreción gástrica y produce una gastritis crónica que en muchos casos no causa síntomas ni progresa, pero en otros, produce úlcera péptica, o gastritis atrófica que luego avanza a metaplasia intestinal y eventualmente a carcinoma gástrico (5-7). La prevalencia de infección por HP a nivel global es estimada en alrededor de 50% de la población, en el Perú, esta cifra llega al 45.5% (8). Debido a la alta prevalencia de la infección y las complicaciones de la misma es necesario realizar una Guía de Práctica Clínica que optimice el diagnóstico y manejo de esta infección. Por ello, el Seguro Social de Salud (EsSalud) priorizó la realización de la presente guía de práctica clínica (GPC) para establecer lineamientos basados en evidencia para gestionar de la mejor manera los procesos y procedimientos asistenciales de la presente condición. Esta GPC fue realizada por la Dirección de Guías de Práctica Clínica, Farmacovigilancia y Tecnovigilancia del Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) de EsSalud.

[Comparing traditional and commercial molecular biology detection of gastrointestinal pathogens with AusDiagnostics panels in Motol University Hospital].

BACKGROUND: The aim was to do an internal audit of gastrointestinal pathogen detection at the Department of Medical Microbiology, Motol University Hospital between the years 2014 and 2018 and to test two commercial multiplex molecular biology assays potentially improving the diagnostic process and reducing costs. MATERIAL AND METHODS: Based on data from a laboratory information system (LIS), a total of 45,888 samples were identified which had been tested for the presence of gastrointestinal pathogens using culture, immunochromatographic, microscopic and molecular biology techniques between 2014-2018. Novel multiplex molecular biology detection was used to test 182 nucleic acid isolates obtained from stool samples with the Enteric Viruses (8-well) assay (Viral Panel, EVP) or Faecal Pathogens M (16-well) assay (Microbial Panel, FPM) manufactured by AusDiagnostics. RESULTS: The LIS data showed 6.2 % of positive pathogens causing diarrhea from all tested samples (detection rates: 4.5 % for bacterial agents, 21.6 % for viral agents and 0.4 % for parasitic agents). Valid samples (98.9 % of all tested samples) tested by the molecular biology technique yielded, in descending order: C. difficile toxin B (19 %), norovirus (9 %), astrovirus (8 %), Campylobacter (7 %), sapovirus (6 %), Yersinia enterocolitica (6 %), rotavirus (4 %), enterovirus (3 %), Aeromonas (3 %), adenovirus (2 %) and Salmonella (1 %). There was found at least 1 additional new positive detection in 27 % of stools tested by the Viral Panel and in 40 % of stools tested by the Microbial Panel in comparison with the traditional approach. Introducing the panels into routine diagnostic practice will not reduce the costs. CONCLUSIONS: The introduction of novel multiplex molecular biology assays for detecting gastrointestinal pathogens will considerably increase pathogen detection rates even though the costs will be higher for the Department of Medical Microbiology.

Malaria Coinfections in Febrile Pediatric Inpatients: A Hospital-Based Study From Ghana.

Background: The epidemiology of pediatric febrile illness is shifting in sub-Saharan Africa, but malaria remains a major cause of childhood morbidity and mortality. The present study describes causes of febrile illness in hospitalized children in Ghana and aims to determine the burden of malaria coinfections and their association with parasite densities. Methods: In a prospective study, children (aged ≥30 days and ≤15 years) with fever ≥38.0°C were recruited after admission to the pediatric ward of a primary hospital in Ghana. Malaria parasitemia was determined and blood, stool, urine, respiratory, and cerebrospinal fluid specimens were screened for parasitic, bacterial, and viral pathogens. Associations of Plasmodium densities with other pathogens were calculated. Results: From November 2013 to April 2015, 1238 children were enrolled from 4169 admissions. A clinical/microbiological diagnosis could be made in 1109/1238 (90%) patients, with Plasmodium parasitemia (n = 728/1238 [59%]) being predominant. This was followed by lower respiratory tract infections/pneumonia (n = 411/1238 [34%]; among detected pathogens most frequently Streptococcus pneumoniae, n = 192/299 [64%]), urinary tract infections (n = 218/1238 [18%]; Escherichia coli, n = 21/32 [66%]), gastrointestinal infections (n = 210 [17%]; rotavirus, n = 32/97 [33%]), and invasive bloodstream infections (n = 62 [5%]; Salmonella species, n = 47 [76%]). In Plasmodium-infected children the frequency of lower respiratory tract, gastrointestinal, and bloodstream infections increased with decreasing parasite densities. Conclusions: In a hospital setting, the likelihood of comorbidity with a nonmalarial disease is inversely correlated with increasing blood levels of malaria parasites. Hence, parasite densities provide important information as an indicator for the probability of coinfection, in particular to guide antimicrobial medication.

Epidemiologic evaluation of multiple alternate microbial water quality monitoring indicators at three California beaches.

INTRODUCTION: Advances in molecular methods provide new opportunities for directly measuring pathogens or host-associated markers of fecal pollution instead of relying on fecal indicator bacteria (FIB) alone for beach water quality monitoring. Adoption of new indicators depends on identifying relationships between either the presence or concentration of the indicators and illness among swimmers. Here we present results from three epidemiologic studies in which a broad range of bacterial and viral indicators of fecal contamination were measured simultaneously by either culture or molecular methods along with Enterococcus to assess whether they provide better health risk prediction than current microbial indicators of recreational water quality. METHODS: We conducted prospective cohort studies at three California beaches -- Avalon Bay (Avalon), Doheny State Beach (Doheny), Surfrider State Beach (Malibu) -- during the summers of 2007, 2008 and 2009. The studies enrolled 10,785 swimmers across the beaches and recorded each swimmer's water exposure. Water and sand samples were collected several times per day at multiple locations at each beach and analyzed for up to 41 target indicators using 67 different methodologies. Interviewers contacted participants by phone 10-14 days later and recorded symptoms of gastrointestinal illness occurring after their beach visit. Regression models were used to evaluate the association between water quality indicators and gastrointestinal illness among swimmers at each beach. RESULTS: F+ coliphage (measured using EPA Method 1602) exhibited a stronger association with GI illness than did EPA Method 1600 at the two beaches where it was measured, while a molecular method, F+ RNA Coliphage Genotype II, was the only indicator significantly associated with GI illness at Malibu. MRSA, a known pathogen, had the strongest association with GI illness of any microbe measured at Avalon. There were two methods targeting human-associated fecal anaerobic bacteria that were more strongly associated with GI illness than EPA Method 1600, but only at Avalon. No indicator combinations consistently had a higher odds ratio than EPA Method 1600, but one composite indicator, based on the number of pathogens detected at a beach, was significantly associated with gastrointestinal illness at both Avalon and Doheny when freshwater flow was high. DISCUSSION: While EPA Method1600 performed adequately at two beaches based on its consistency of association with gastrointestinal illness and the precision of its estimated associations, F+ coliphage measured by EPA Method 1602 had a stronger association with GI illness under high risk conditions at the two beaches where it was measured. One indicator, F+ Coliphage Genotype II was the only indicator significantly associated with GI illness at Malibu. Several indicators, particularly those targeting human associated bacteria, exhibited relationships with GI illness that were equal to or greater than that of EPA Method 1600 at Avalon, which has a focused human fecal source. Our results suggest that site-specific conditions at each beach determine which indicator or indicators best predict GI illness.

Integrating bacterial and viral water quality assessment to predict swimming-associated illness at a freshwater beach: a cohort study.

BACKGROUND & OBJECTIVE: Recreational waters impacted by fecal contamination have been linked to gastrointestinal illness in swimmer populations. To date, few epidemiologic studies examine the risk for swimming-related illnesses based upon simultaneous exposure to more than one microbial surrogate (e.g. culturable E. coli densities, genetic markers). We addressed this research gap by investigating the association between swimming-related illness frequency and water quality determined from multiple bacterial and viral genetic markers. METHODS: Viral and bacterial genetic marker densities were determined from beach water samples collected over 23 weekend days and were quantified using quantitative polymerase chain reaction (qPCR). These genetic marker data were paired with previously determined human exposure data gathered as part of a cohort study carried out among beach users at East Fork Lake in Ohio, USA in 2009. Using previously unavailable genetic marker data in logistic regression models, single- and multi-marker/multi-water quality indicator approaches for predicting swimming-related illness were evaluated for associations with swimming-associated gastrointestinal illness. RESULTS: Data pertaining to genetic marker exposure and 8- or 9-day health outcomes were available for a total of 600 healthy susceptible swimmers, and with this population we observed a significant positive association between human adenovirus (HAdV) exposure and diarrhea (odds ratio  = 1.6; 95% confidence interval: 1.1-2.3) as well as gastrointestinal illness (OR  = 1.5; 95% CI: 1.0-2.2) upon adjusting for culturable E. coli densities in multivariable models. No significant associations between bacterial genetic markers and swimming-associated illness were observed. CONCLUSIONS: This study provides evidence that a combined measure of recreational water quality that simultaneously considers both bacterial and viral densities, particularly HAdV, may improve prediction of disease risk than a measure of a single agent in a beach environment likely influenced by nonpoint source human fecal contamination.

Assessment of antigenemia assay for the diagnosis of cytomegalovirus gastrointestinal diseases in HIV-infected patients.

We conducted a single-center prospective study to evaluate the utility of cytomegalovirus (CMV) antigenemia assay for the diagnosis of CMV-gastrointestinal disease (GID). The study subjects were HIV-infected patients with CD4 count ≤200 µL/cells who had undergone endoscopy. A definite diagnosis of CMV-GID was made by histological examination of endoscopic biopsied specimen. CMV antigenemia assay (C10/C11 monoclonal antibodies), CD4 count, HIV viral load, history of HAART, and gastrointestinal symptoms as measured by 7-point Likert scale, were assessed on the same day of endoscopy. One hundred cases were selected for analysis, which were derived from 110 cases assessed as at high-risk for CMV-GID after endoscopy screening of 423 patients. Twelve patients were diagnosed with CMV-GID. Among the gastrointestinal symptoms, mean bloody stool score was significantly higher in patients with CMV-GID than in those without (2.5 vs. 1.7, p=0.02). The area under the receiver-operating characteristic curve of antigenemia was 0.80 (95%CI 0.64-0.96). The sensitivity, specificity, positive likelihood ratio (LR), and negative LR of antigenemia were 75.0%, 79.5%, 3.7, and 0.31, respectively, when the cutoff value for antigenemia was ≥1 positive cell per 300,000 granulocytes, and 50%, 92.0%, 5.5, and 0.55, respectively, for ≥5 positive cells per 300,000 granulocytes. In conclusion, CMV antigenemia seems a useful diagnostic test for CMV-GID in patients with HIV infection. The use of ≥5 positive cells per 300,000 granulocytes as a cutoff value was associated with high specificity and high positive LR. Thus, a positive antigenemia assay with positive endoscopic findings should allow the diagnosis of CMV-GID without biopsy.

Microbial quality assessment of household greywater.

A monitoring program was undertaken to assess the microbial quality of greywater collected from 93 typical households in Melbourne, Australia. A total of 185 samples, comprising 75 washing machine wash, 74 washing machine rinse and 36 bathroom samples were analysed for the faecal indicator Escherichia coli. Of these, 104 were also analysed for genetic markers of pathogenic E coli and 111 for norovirus (genogroups GI and GII), enterovirus and rotavirus using RT-PCR. Enteric viruses were detected in 20 out of the 111 (18%) samples comprising 16 washing machine wash water and 4 bathroom samples. Eight (7%) samples were positive for enterovirus, twelve (11%) for norovirus genogroup GI, one (1%) for norovirus genogroup GII and another (1%) for rotavirus. Two washing machine samples contained more than one virus. Typical pathogenic E. coli were detected in 3 out of 104 (3%) samples and atypical enteropathogenic E. coli in 11 (11%) of samples. Levels of indicator E. coli were highly variable and the presence of E. coli was not associated with the presence of human enteric viruses in greywater. There was also little correlation between reported gastrointestinal illness in households and detection of pathogens in greywater.

Swimmer risk of gastrointestinal illness from exposure to tropical coastal waters impacted by terrestrial dry-weather runoff.

This study used molecular methods to measure concentrations of four enteric viruses (adenovirus, enterovirus, norovirus GI, and norovirus GII) and fecal source tracking markers (human, ruminant, and pig Bacteroidales) in land-based runoff from 22 tropical streams on O'ahu, Hawai'i. Each stream was sampled twice in the morning and afternoon during dry weather. Viruses and human Bacteroidales were widespread in the streams. Watershed septic tank densities were positively associated with higher occurrence of human Bacteroidales and norovirus. There were no associations between occurrence of viruses and fecal indicator concentrations. Virus concentrations and previously reported culturable Salmonella and Campylobacter were used as inputs to a quantitative microbial risk assessment (QMRA) model to estimate the risk of acquiring gastrointestinal (GI) illness from swimming in tropical marine waters adjacent to discharging streams. Monte Carlo methods were used to incorporate uncertainties in the dilution of stream discharge with seawater, swimmer ingestion volumes, pathogen concentrations, and dose-response parameters into the model. Median GI illness risk to swimmers from exposure to coastal waters adjacent to the 22 streams ranged from 0 to 21/1000. GI illness risks from viral exposures were generally orders of magnitude greater than bacterial exposures. Swimming adjacent to streams positive for norovirus or adenovirus resulted in the highest risks. The median risk adjacent to each stream was positively, significantly correlated to the concentration of Clostridium perfringens in the stream. Although a number of important assumptions were made to complete the QMRA, results suggest land-based runoff in the tropics as a potential source of GI illness risk, with pathogens coming from both human and nonhuman nonpoint sources including septic tanks.

Foodborne proportion of gastrointestinal illness: estimates from a Canadian expert elicitation survey.

The study used a structured expert elicitation survey to derive estimates of the foodborne attributable proportion for nine illnesses caused by enteric pathogens in Canada. It was based on a similar study conducted in the United States and focused on Campylobacter, Escherichia coli O157:H7, Listeria monocytogenes, nontyphoidal Salmonella enterica, Shigella spp., Vibrio spp., Yersinia enterocolitica, Cryptosporidium parvum, and Norwalk-like virus. For each pathogen, experts were asked to provide their best estimate and low and high limits for the proportion of foodborne illness relative to total cases. In addition, they provided background information with regard to food safety experience, including self-evaluated expertise for each pathogen on a 5-point scale. A snowball approach was used to identify 152 experts within Canada. The experts' background details were summarized using descriptive statistics. Factor analysis was used to determine whether the variability in best estimates was related to self-assessed level of expertise or other background information. Cluster analysis followed by beta function fitting was undertaken on best estimates from experts who self-evaluated their expertise 3 or higher. In parallel, Monte Carlo resampling was run using triangular distributions based on each expert's best estimate and its limits. Sixty-six experts encompassing various academic backgrounds, fields of expertise, and experiences relevant to food safety provided usable data. Considerable variation between experts in their estimated foodborne attributable proportions was observed over all diseases, without any relationship to the expert's background. Uncertainty about their estimate (measured by the low and high limits) varied between experts and between pathogens as well. Both cluster analysis and Monte Carlo resampling clearly indicated disagreement between experts for Campylobacter, E. coli O157, L. monocytogenes, Salmonella, Vibrio, and Y. enterocolitica. In the absence of more reliable estimates, the observed discrepancy between experts must be explored and understood before one can judge which opinion is the best.

Microbial risk assessment: don't forget the children.

Quantitative microbial risk assessment is a rapidly developing field with a purpose to quantify risks of infection, disease and mortality from the environmental exposure of pathogens. It is currently being applied to the development of standards for drinking water, wastewater re-use and foods. A growing body of evidence indicates that the greatest risk of infection for enteric pathogens is for persons less than 19 years of age. Children are more likely to become ill from consumption of contaminated drinking water and recreational activities. These increased risks may be because immunological, neurological and digestive systems are still developing. In addition, children are more environmentally exposed to pathogens. For some enteric pathogens children may be the greatest at risk population.