Episode Of Acute Gastroenteritis Research Articles

8721 A Case of Congenital Hyperinsulinism Manifesting as Transient Hypoglycemia During Illness Due to Mosaic Variant of Unknown Significance in ABCC8

Abstract Disclosure: E.E. Bell-Sambataro: None. L. Mamilly: None. Background: Congenital hyperinsulinism (CHI) is characterized by inappropriate secretion of insulin during periods of low blood glucose. CHI can lead to significant complications such as seizures, developmental delays and neurologic damage. CHI can be caused by multiple genetic variants. The most common genetic etiologies are loss of function mutations in the genes ABCC8 and KCNJ11 encoding the pancreatic Beta (β)-cell ATP-sensitive potassium channel causing over secretion of insulin from the β-cells. We report a challenging pediatric case with a clinical presentation of CHI in an infant with a de novo mosaic ABCC8 gene variant of unknown significance manifesting only during times of illness. Clinical Case: A male infant born at 36 weeks gestational age was transferred to a tertiary center NICU secondary to seizure activity and hypoglycemia after the 24 hours of life with glucose levels as low as 32 mg/dL. His birth weight was normal and there was not maternal history of diabetes mellitus. The hypoglycemia persisted throughout the first week of life and required a glucose infusion rate of 11 mg/kg/min, without success in obtaining a critical sample. He had multiple seizures and MRI brain showed signs of hypoglycemic encephalopathy. Subsequently, he was weaned off IV dextrose and completed a 6 hour safety fast prior to discharge. Rapid genome testing resulted in a de novo, mosaic variant of unknown significance in ABCC8 (C.3622G>A resulting in amino acid substitution p.Glu1208Lys). His family reported significant but transient hypoglycemia during times of illness. At the age of 11 months, he was hospitalized for significant hypoglycemia during an episode of acute gastroenteritis and was treated with dextrose-containing fluids for 36 hours. A subsequent diagnostic fasting study resulted in hypoglycemia within 5.5 hours with capillary glucose of 49 mg/dL. At the time of hypoglycemia, beta hydroxybutyrate was inappropriately low at 0.78 mm, insulin level was suppressed <2 mcIU/mL. Glucagon (30 mcg/Kg) was administered after the initial sample was drawn with a significant increase in glucose from 49 mg/dL to 103 mg/dL. Based on the positive glucagon response and low serum ketone, the clinical diagnosis of CHI was made and diazoxide was initiated while awaiting other results. After the second dose of diazoxide, all glucose levels remained above 80 mg/dL. He was sent home on a continuous glucose monitor and diazoxide. Conclusion: CHI can occur due to autosomal recessive or autosomal dominant ABCC8 loss-of-function mutations of which more than half are not responsive to diazoxide. In this case report, we describe the diagnosis of hyperinsulinemic hypoglycemia in an infant with an ABCC8 variant classified with unknown significance. We describe a good initial response to diazoxide in normalizing blood glucose levels in this infant. Presentation: 6/2/2024

Pericardial effusion in a patient of celiac disease and hypothyroidism: A case report

Celiac disease (CD) can be defined as an autoimmune chronic disorder in gluten-intolerant individuals producing malabsorption of nutrients and vitamins. The presence of CD in individuals causes an alteration in the absorption and pharmacokinetics of certain drugs. This poses a great challenge in maintaining serum thyrotropin levels in hypothyroidism patients on replacement therapy with levothyroxine (LT4). In this report, we present the case of a 39-year-old woman with hypothyroidism, pericardial effusion, and (previously unrecognized) CD. Our patient was a known case of hypothyroidism with a history of previous hospitalization for an episode of acute gastroenteritis. In our clinic, after an initial workup, the patient was continued on LT4 supplement, oral iron, and multivitamins. During her follow-up visit, when an anti-tissue transglutaminase IgA-positive report was available, a gluten-free diet was advised. Following this, the clinical condition of the patient improved drastically, accompanied by a fall in elevated thyroid-stimulating hormone (TSH) levels. This case highlights the necessity of understanding the etiology of rising serum TSH levels, hence ruling out malabsorption. Pericardial effusion, being a rare complication of hypothyroidism and CD, may lead to adverse cardiac events, hence resulting in hospitalization and patient disability.

Lack of detection of HPyV12 DNA using real-time PCR in Italian infants with diarrhea.

HPyV12 was found in organs of the digestive tract, in particular the liver but also in colon, rectum and feces. Until now, the prevalence of HPyV12 is not well characterized. In this study, we investigate the presence of this novel polyomavirus DNA in stool specimens collected from under-five-year-old children with gastroenteritis compared to healthy infants. A total of 190 fecal specimens previously screened for rotavirus (RV) and adenovirus (ADV) and 80 fecal samples from healthy infants, were tested for HPyV12 DNA using a home-made real time PCR. All fecal specimens were tested for the presence of HPyV12 with specific primers and probes. None of 190 (0%) episodes of acute gastroenteritis was associated with HPyV12. We did not detect HPyV12 DNA in any of 80 control subjects, as well. Our study represents a pilot study aiming to clarify the current epidemiological pattern in pediatric Italian patients regarding the novel and rare HPyV12. Based on our negative data and the recent observations reported in literature, doubts remain on human tropism of the HPyV12 and epidemiology: these issues need further investigations.

Human Bocavirus in children with acute gastroenteritis in Piedmont, Italy.

Gastroenteritis is a common disease in children, characterized by diarrhea, vomiting, abdominal pain, and fever. Co-detection of human Bocavirus (HBoV) with other gastroenteric viruses was reported a lot in patients with acute gastroenteritis. This paper presents the real-time RT-PCR Taqman assay for the detection and quantification of HBoV for clinical fecal samples collected from hospitalized children with acute gastroenteritis in Piedmont. All fecal specimens were tested for the presence of HBoV with specific primers and probe. A total of 17 out of 123 (13.92%) episodes of acute gastroenteritis were associated with HBoV genomic detection with median viral load 6864.75±19784.79 genomes/mg fecal specimens. Among the 17 HBoV-positive cases, 11 were also positive for other viral pathogens, including Rotavirus (N.=2), astrovirus (N.=1), norovirus GII (N.=6), norovirus GI (N.=2). Two cases were positive for more than one virus including norovirus GII and norovirus GI (N.=1) and Rotavirus, sapovirus and astrovirus (N.=1). A higher detection of HBoV infections was observed in winter, and peaking in February. Although HBoV is suspected to be responsible for gastroenteritis in children, our data showed that this association was uncertain since no difference was observed in term of viral load in the group with single infection of HBoV and group of coinfections with other viral agent.

Prevalence of human Cosavirus and Saffold virus in young children with gastroenteritis in Northern Italy.

Gastroenteritis is a common disease in children, characterized by diarrhea, vomiting, abdominal pain, and fever. Human Cosavirus (HCoSV) and Saffold virus (SAFV) both have a worldwide distribution. Both viruses have been detected in the stools of patients with acute gastroenteritis in several countries. In order to provide more insights into the epidemiology of enteric viruses that are not included usually in routine diagnostic tests, cases of childhood sporadic gastroenteritis of unknown etiology requiring hospital admission in Turin, Italy, during December 2014 to November 2015, were screened for HCoSV and SAFV. A total of 1 out of 164 (0.6%) episodes of acute gastroenteritis were associated with SAFV genomic detection. Among the 1 SAFV-positive cases, 1 were also positive for Adenovirus. The patient positive for SAFV do not present diarrheal episodes but vomiting. HCoSV was not detected in any of the samples. In conclusion, this study presents the current epidemiological data regarding the two viruses, HCoSV and SAFV, circulating in pediatric patients admitted to hospital with acute gastroenteritis in Turin, Italy.

A Theoretical Approach on the Action of Vilwadi Agada in Relieving the Symptoms of Acute Gastroenteritis

Ayurveda a unique science of life, which emphasized on the principle of protecting the health of a healthy individual and eradicating the disease in diseased persons. Now a days, people living in the midst of diseases that disturb them to achieve a good health. The people are trying to overcome this situation by developing an art of medicine and science of healing. Agadatantra is one of the branches in Ayurveda. Literally’ Agada’ means a disease-free condition. It deals with different type of poisoning from animate and inanimate objects with its management. The poisoning from the bite of snakes, spiders, insects, rodents and from the combination of different poisons with their management are included in this branch. Vilwadi agada is a polyherbal combination can be used in various toxicological conditions, GIT problems, concocted poisoning, systemic symptoms like fever, infectious conditions. Today Vilwady agada is marketing as Vilwady gutika by different pharmaceutical companies. Classical reference of Vilwadi agada mentioned in Ashtangahridaya, Ashtangasamgraha, Sahasrayogam, Visha Jyotsnika and Kriyakoumudhi. Acute gastroenteritis (stomach flu) is an infection characterised by diarrhoea, cramps, nausea, vomiting and fever with inflammation of gastric mucosa. Viruses are the important causative factors for 70% of the episodes of acute gastroenteritis in children especially the rota virus. In contemporary science the first choice is oral rehydration therapy and then gives anti diarrhoeal drugs, antiemetics, antispasmodic drugs according to the condition of the patient. The drugs in Vilwadi agada having antimicrobial, antiviral, analgesic, anti- inflammatory, antioxidant, carminative properties. These attributes of this combination is very effective in relieving the cardinal symptoms such as abdominal cramps, nausea, vomiting diarrhoea and fever in acute gastroenteritis.

Investigating association between inflammatory bowel disease and rotavirus vaccination in a paediatric cohort in the UK.

In the UK, the incidence and prevalence of inflammatory bowel disease (IBD) is increasing in paediatric populations. Environmental factors including acute gastroenteritis episodes (AGE) may impact IBD development. Infant rotavirus vaccination has been shown to significantly reduce AGE. This study aims to explore the association between vaccination with live oral rotavirus vaccines and IBD development. A population-based cohort study was used, analysing primary care data from the Clinical Practice Research Datalink Aurum. Participants included children born in the UK from 2010 to 2015, followed from a minimum of 6months old to a maximum of 7years old. The primary outcome was IBD, and the primary exposure was rotavirus vaccination. Cox regression analysis with random intercepts for general practices was undertaken, with adjustment for potential confounding factors. In a cohort of 907,477 children, IBD was recorded for 96 participants with an incidence rate of 2.1 per 100,000 person-years at risk. The univariable analysis hazard ratio (HR) for rotavirus vaccination was 1.45 (95% confidence interval (CI) 0.93-2.28). Adjustment in the multivariable model attenuated the HR to 1.19 (95% CI 0.53-2.69). This study shows no statistically significant association between rotavirus vaccination and development of IBD. However, it provides further evidence for the safety of live rotavirus vaccination.

Chronic Diarrhea and Weight Loss in an 18-month-old Boy.

Chronic Diarrhea and Weight Loss in an 18-month-old Boy.

Longer Term Follow-up on the First Patients with Severe Hemoglobinopathies Treated with Lentiglobin Gene Therapy

Background: LentiGlobin Drug Product (DP) contains autologous CD34+ cells transduced with the betibeglogene darolentivec (BB305) lentiviral vector, encoding a human β-globin gene with a point mutation (AT87Q) that confers anti-sickling properties similar to those with γ-globin. Human proof of concept for LentiGlobin treatment in transfusion-dependent β-thalassemia (TDT) and severe sickle cell disease (SCD) has been established in HGB-205 (NCT02151526), the original clinical study of gene therapy for hemoglobinopathies. Here, we provide an update on 5 previously-reported patients (4 TDT, 1 SCD) as well as early data from 2 additional treated patients with SCD.Methods: HGB-205 enrolled patients (5−35 years old) with TDT (≥100 mL/kg of packed red blood cells [pRBCs] per year) or severe SCD (e.g., failed hydroxyurea treatment and ≥2 acute chest syndrome episodes [ACS] or ≥2 vaso-occlusive crises [VOC] in the preceding year/year prior to regular transfusions). Following mobilization/apheresis for TDT or bone marrow harvest for SCD, autologous CD34+ cells were transduced with the BB305 lentiviral vector. Patients underwent myeloablative conditioning with busulfan, were infused with transduced cells and monitored for hematologic engraftment, vector copy number (VCN), transgenic hemoglobin (HbAT87Q) levels, and adverse events (AEs). Transfusion requirements and biological markers for TDT, and VOCs for SCD were also assessed.Results: As of June 2, 2017, 4 patients with TDT and 3 patients with severe SCD have received LentiGlobin DP; median follow-up is 23.4 (range, 3.4 - 42.2) months. Patient and DP characteristics and key outcomes for these 7 patients are shown in Table 1. All patients engrafted successfully. The toxicity profile was consistent with myeloablative conditioning with single-agent busulfan, with no DP-related ≥ grade 3 AEs or serious AEs and no evidence of clonal dominance reported to date. For patients with TDT, VCN, total Hb and HbAT87Q levels in peripheral blood remain stable, with no evidence of decreasing efficacy (Table 1). All patients with TDT remain free of RBC transfusions. In all 3 β0/βE patients, Hb levels are stable near or within the normal range. Importantly, iron burden and biological hallmarks of dyserythropoiesis have largely returned to normal. Two patients with TDT have discontinued iron chelation therapy and transitioned to therapeutic phlebotomy while the third patient (1202) has been able to discontinue both.All 3 patients with SCD showed increase in HbAT87Q production through 6 months or last follow-up. The first treated patient with severe SCD (1204) had no clinical symptoms or complications of SCD until, at about 30 months post-treatment, the patient developed a VOC following an episode of acute gastroenteritis with fever and dehydration, and was subsequently hospitalized. His total Hb levels (12.4 g/dL), HbAT87Q (6.1 g/dL) and peripheral blood VCN levels (2.3) have remained stable at 30 months of follow-up. The 2 recently treated patients with SCD (1207 and 1208) have 6 and 3 months of follow-up, have not undergone transfusions since Day 21 and 15 post-infusion, and have total Hb of 8.8 g/dL and 9.8 g/dL and HbAT87Q of 1.8 and 1.5 g/dL, respectively as of last follow-up. At approximately 6 months post-treatment, patient 1207 experienced an episode of ACS and was hospitalized. Total % anti-sickling Hb ([HbAT87Q + HbF + HbA2]/Total Hb * 100) in the 3 patients with SCD was 52%, 39% and 36% as of last follow-up. Levels of unconjugated bilirubin, lactate dehydrogenase and reticulocyte count had improved compared to screening in the 2 patients with SCD (1204 and 1207) who had ≥ 6 months follow-up.Summary: Data from this pioneering phase 1/2 clinical study continue to suggest that treatment with LentiGlobin DP elicits sustained HbAT87Q levels which may be sufficient to alleviate the clinical and biochemical effects of severe SCD and TDT, with an acceptable safety profile. In patients with TDT, sustained levels of HbAT87Q with longer term follow-up, abatement of dyserythropoeisis and discontinuation of iron chelation therapy confirm the results seen to date. For patients with SCD, the marked clinical improvement in 1 patient with nearly 2.5 years of follow-up and increasing HbAT87Q levels in recently treated patients suggest gene therapy may be a promising option. Follow-up data on the 3 patients with SCD and 2-year primary follow-up for patients with TDT will be presented. [Display omitted] DisclosuresPayen:bluebird bio: Honoraria, Research Funding. Brousse:Add Medica: Membership on an entity's Board of Directors or advisory committees. Bartolucci:Novartis: Consultancy; AddMedica: Consultancy, Research Funding. Beuzard:bluebird bio: Consultancy, Equity Ownership. Asmal:bluebird bio: Employment, Equity Ownership. Miller:bluebird bio: Employment, Equity Ownership. De Montalembert:Addmedica: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Leboulch:bluebird bio: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Ribeil:Addmedica: Membership on an entity's Board of Directors or advisory committees; Vitalaire: Other: Non-financial support; Novartis: Other: Non-financial support.

Changing trends in rotavirus detection, genotypes and clinical severity among children

Background: Rotavirus is a major cause of acute gastroenteritis in developing countries like India. Rotavirus causes approximately 11.37 million episodes of acute gastroenteritis (AGE), 872,000 inpatient admissions and 78,000 deaths in children <5 years annually in India. This study aims to detect rotavirus among children <5 years admitted with acute gastroenteritis and to determine the common circulating genotypes and assess their clinical severity. Methods and materials: A total of 772 stool samples were collected from children <5years who were admitted for acute gastroenteritis (AGE) during February 2014 to October 2019. Rotavirus antigen was detected using a commercial enzyme immunoassay kit, Rotaclone®). RNA was extracted from stool samples using viral RNA mini kit (Qiagen, Germany). The extracted RNA was converted into cDNA by MMLV-RT enzyme. The cDNA is used for genotyping by a semi-nested RT-PCR targeting VP7 and VP4. Modified Vesikari scale was used to analyse the severity of acute gastroenteritis and Modified Kuppuswamy scale was used to assess the socio-economic class. Results: Rotavirus was detected in 23.6% of children with AGE. The year-wise detection rate of rotavirus was 33.8% (2014), 29.8% (2015), 26.1% (2016), 19.7% (2017), 17.7% (2018) and 20.9% (2019). Based on Vesikari score rotavirus G2P [4] infected children had more vomiting and episodes (56%) than those infected with G1P [8] (29%) and G3P [8] (32%). Children aged 12–24 months had a higher detection rate of 27.9%. Rotavirus was detected significantly higher among lower-middle class 26.7% in contrast to upper-middle class 17.4% (p = 0.006). G1P [8] (42%) and G3P [8] (32%) were the predominant circulating genotypes. G1P [8] was initially the predominant genotype (2014–2016) and it has been replaced by G3P [8] (2017–2019). Conclusion: Rotavirus shows a declining trend since 2017 and this could probably because of the introduction of rotavirus vaccine in National immunisation schedule. There is a change in genotype distribution of rotavirus G3P [8] replaced G1P [8] as the predominant circulating genotype in the past 3 years however less circulating G2P [4] genotype was associated with longer duration of vomiting and more episodes leads to severe gastroenteritis.

Attribution of Pediatric Acute Gastroenteritis Episodes and Emergency Department Visits to Norovirus Genogroups I and II

Norovirus is a leading cause of acute gastroenteritis. With vaccines in development, population-based estimates of norovirus burden are needed to identify target populations, quantify potential benefits, and understand disease dynamics. We estimated the attributable fraction (AF) for norovirus infections in children, defined as the proportion of children testing positive for norovirus whose gastroenteritis was attributable to norovirus. We calculated the standardized incidence and emergency department (ED) visit rates attributable to norovirus using provincial gastroenteritis visit administrative data. From 3731 gastroenteritis case patients and 2135 controls we determined that the AFs were 67.0% (95% confidence interval [CI], 31.5%-100%) and 91.6% (88.8%-94.4%) for norovirus genogroups I (GI) and II (GII), respectively. Norovirus GII AF varied by season but not age. We attributed 116 episodes (95% CI, 103-129) and 59 (51-67) ED visits per 10 000 child-years to norovirus GII across all ages, accounting for 20% and 18% of all medically attended gastroenteritis episodes and ED visits, respectively. In children, a large proportion of norovirus GII detections reflect causation, demonstrating significant potential for norovirus GII vaccines. Seasonal variation in the norovirus GII AF may have implications for understanding the role asymptomatic carriage plays in disease dynamics.

Lack of detection of HPyV12 DNA using real-time PCR in Italian infants with diarrhea.

HPyV12 was found in organs of the digestive tract, in particular the liver but also in colon, rectum and faeces. Until now, the prevalence of HPyV12 is not well.characterized. In this study, we investigate the presence of this novel polyomavirus DNA in stool specimens collected from under-five-year-old children with gastroenteritis compared to healthy infants. A total of 190 fecal specimens previously screened for Rotavirus (RV) and Adenovirus (ADV) and 80 fecal samples from healthy infants, were tested for HPyV12 DNA using a home-made real time PCR. All fecal specimens were tested for the presence of HPyV12 with specific primers and probes. None of 190 (0%) episodes of acute gastroenteritis was associated with HPyV12. We did not detect HPyV12 DNA in any of 80 control subjects, as well. Our study represents a pilot study aiming to clarify the current epidemiological pattern in pediatric italian patients regarding the novel and rare HPyV12. On the basis of our negative data and the recently observations reported in literature, doubts remain on human tropism of the HPyV12 and epidemiology: these issues need further investigations.

Effect of Definitions of Acute Gastroenteritis Episodes Using Symptom Diaries in Paediatric Cohorts: A Systematic Review.

Estimates of acute gastroenteritis (AGE) burden are difficult to compare between studies because of inconsistent definitions describing this illness. AGE definitions used in prospective, community-based childhood cohort studies were identified by searching databases for studies that collected daily observations of AGE symptoms. Disease definitions and refractory periods were extracted. Data from the Australian community-based Observational Research in Childhood Infectious Diseases birth cohort were used to calculate AGE incidence and duration using identified AGE definitions, and the World Health Organization definition for diarrhoea. Eight distinct AGE definitions were identified. All included loose stools and 7 included vomiting as symptoms. The refractory period separating episodes ranged from 1 to 21 days. When applied to the Observational Research in Childhood Infectious Diseases dataset, AGE incidence ranged from 0.8 to 2.6 episodes per child-year-at-risk, a 3-fold relative difference. Direct comparisons of rates from different cohorts can only be undertaken if a standard definition for AGE is adopted.

Community burden and transmission of acute gastroenteritis caused by norovirus and rotavirus in the Netherlands (RotaFam): a prospective household-based cohort study

Norovirus and rotavirus are the dominant pathogens causing acute gastroenteritis in children. To quantify their natural disease burden and transmission, we prospectively monitored households in an endemic setting in the Netherlands, a high-income country that does not have a rotavirus vaccination programme. We did a prospective, household survey-based cohort study in the Netherlands. Randomly selected households from the Dutch Population Register were invited to participate if they had at least three household members, including a child younger than 2 years. A member of each household was asked to record the gastrointestinal symptoms of all household members every day for 10 consecutie weeks using an interactive smartphone application. Real-time detection of acute gastroenteritis onset on the basis of entered symptoms activated requests for the case and one other household member to complete disease questionnaires and provide stool samples. Stool samples were analysed by real-time PCR for norovirus, rotavirus, adenovirus 40/41, and astrovirus. We calculated the per-pathogen proportion of households with at least one secondary acute gastroenteritis episode (epidemiologically but not microbiologically linked), the probability of a secondary episode in household members at risk (secondary attack rate), and the microbiologically confirmed symptomatic and asymptomatic transmission rates. During two seasons (January to March) in 2016 and 2017, 30 660 households were invited to participate, of which 604 households including 2298 individuals were enrolled. 697 acute gastroenteritis episodes were detected in 358 households, with samples obtained from 609 (87%) of 697 episodes. Norovirus (150 [25%] of 609 cases) and rotavirus (91 [15%] cases) were most frequently detected. Astrovirus was detected in 50 (8%) samples and adenovirus 40/41 in 24 (4%) samples. Overall disease severity was higher in patients with rotavirus-positive acute gastroenteritis than those with norovirus-positive acute gastroenteritis. Norovirus led to higher disease burden in adults than did rotavirus. Following an index case, a secondary acute gastroenteritis episode occurred in 34 (35%) of 96 households for norovirus and 26 (46%) of 56 households for rotavirus. Secondary attack rates were 15% (37 of 244 participants) for norovirus and 28% (33 of 120 participants) for rotavirus and asymptomatic transmission rates were 51% (52 of 102 household members) for norovirus and 22% (12 of 55 household members) for rotavirus. The microbiologically confirmed symptomatic transmission rate for norovirus was 10% (25 of 254 household members) and 18% for rotavirus (21 of 119 household members). In households with young family members in a setting without rotavirus vaccination, norovirus is the dominant acute gastroenteritis pathogen, but rotavirus is associated with more severe disease. There was substantial within-household transmission, both symptomatic and asymptomatic. The study provides key quantities on transmission, which can inform vaccine policy decisions and act as a baseline for impact evaluations in high-income settings. The Netherlands Organisation for Health Research and Development (grant 91616158).

172 Multiplex Polymerase Chain Reaction Stool Testing Detects Pathogens Not Frequently Detected on Concurrent Stool Culture With Ova and Parasite Exam

INTRODUCTION: Rapid, highly sensitive and specific multiplex polymerase chain reaction-based stool assays for gastrointestinal pathogens (GI PCR) are increasingly being used alternatively to conventional stool culture. We investigated the concordance between simultaneous GI PCR and stool culture with an ova and parasite (O&amp;P) exam in outpatients presenting with symptoms of infectious gastroenteritis. METHODS: We performed a cross-sectional study of outpatients who received a FilmArray GI PCR test for acute diarrhea at an academic medical center from September 2015 to February 2019 to identify patients who had a concomitant stool culture with an ova and parasite exam (conventional testing) at the same time, on the same stool sample. The primary outcome was detection of an infection on GI PCR or conventional stool testing. Correlation was evaluated using McNemar's test for pathogens detected on both tests. Other categorical variables were compared with Chi-square analysis. RESULTS: We identified 150 outpatients who received GI PCR and stool culture with an ova and parasite exam for an episode of acute gastroenteritis. 106 (71%) patients had a pathogen isolated on GI PCR for 144 total pathogens including 128 (88%) bacteria, 13 (9%) viruses, and 3 (2%) parasites; 21 (14%) patients had a pathogen isolated on conventional testing for 18 total pathogens including 9 (50%) bacteria and 9 (50%) parasites (Table 1). Multiple pathogens were found in 38 (26%) GI PCR tests. PCR testing most commonly identified Enteropathogenic Escherichia coli (EPEC), representing 42 (33%) positive PCR tests. Conventional testing most commonly identified Campylobacter jejuni with 13 (54%) positive tests. Of 28 total C. jejuni infections, 15 (54%) were positive only on PCR, 3 (10%) only on conventional testing, and 10 (36%) on both modalities, showing that conventional testing missed 54% of all infections (P = 0.008). Conventional testing missed 4/6 (67%, P = 0.125) Salmonella infections and 9/14 (64%, P = 0.0215) Yersinia infections, nor did it detect any viral or diarrheagenic E. coli infections. Overall, PCR detected 144 of 191 (75%) of possible pathogens whereas conventional testing detected 47 of 179 possible pathogens (26%). CONCLUSION: GI PCR testing identified multiple pathogens unidentified by conventional testing, such as enteric viruses and pathogenic strains of E. coli. Conventional testing missed 88% of enteric bacteria showing poor concordance between simultaneous GI PCR testing and stool culture with an ova and parasite exam.

Clinical Characterisation of Rota Virus Infection Associated with Most Commonly Circulating Genotypes in Children Hospitalised in Children’s University Hospital: A Cross-Sectional Study in Latvia

Abstract In developed and developing countries, most cases of acute gastroenteritis in children are caused by viruses, and rotaviruses are known as the leading cause. The aim of our study was to estimate the main circulating serotypes of rotavirus before the introduction of routine immunisation in Latvia, and to search for their possible correlation with clinical symptoms and circulating genotypes. A cross-sectional study was carried out among children who had been hospitalised in the Children’s Clinical University Hospital from April 2013 to December 2015. Genotyping was done for 462 stool samples. Among G/P combinations, the most predominant genotypes were G4P[8] (61.3%), G9P[8] (12.4%) and G2P[4] (10.0%) in children of age &lt; 5 years, G4P[8] (45.5%), G2P[4] (18.2%), G9P[8], G3P[8], and G1P[8] (9.1%) in children of age &gt; 5 years. There was a statistically significant correlation (p &lt; 0.05) between clinical signs (vomiting, dehydration, chronic diseases) and G1P[8] and G8P[8] genotypes. Infants infected with genotype G4P[4] had a statistically significant negative correlation with severity of acute gastroenteritis episodes (p &lt; 0.05). We detected nine different rotavirus G genotypes, and two different P genotypes. G4P[8], G9P[8], and G2P[8] were predominant. We observed correlation between the dominant genotypes and clinical manifestations of rotavirus infection.

PF441 RED BLOOD CELLS PROPERTIES IN PATIENTS WITH SICKLE CELL DISEASE TREATED WITH LENTIGLOBIN GENE THERAPY IN THE HGB‐205 TRIAL

Background:Sickle cell disease (SCD) is one of the most prevalent inherited disorders worldwide. The ex vivo gene therapy phase 1/2 study HGB‐205 conducted in France, evaluates the treatment of SCD and TDT (Transfusion Dependent Thalassemia) with LentiGlobin Drug Product (DP) containing autologous CD34+ cells transduced with the BB305 lentiviral vector encoding a human β‐globin gene with a single substitution (βA‐T87Q).Aims:We evaluated the clinical impact and the production of gene therapy‐derived hemoglobin (HbAT87Q) in the 3 HGB‐205 SCD patients (1204, 1207 and 1208).Methods:As of May 2018, the 3 patients had a follow‐up of 42, 18 and 15 months respectively. HbS polymerization level was evaluated by O2 dissociation/association curves and cell morphology; membrane properties by red blood cells (RBCs) density curves, deformability under increasing osmolality and level of adherence to surfaces coated with thrombospondin (TSP). Hemoglobin contents of RBCs and reticulocytes were assessed by RP‐HPLC.Results:Two (1204 and 1208) of the 3 patients with SCD were free of any SCD‐related treatment, with stable peripheral blood vector copy numbers and total anti‐sickling haemoglobin (HbAT87Q + HbF) at 45–50% of total Hb. Both patients have less‐common SCD genotypes: 1204 has a βS/βS genotype with an alpha‐thalassemia trait and 1208 has a β0/βS genotype. At approximately 30 months post‐infusion, patient 1204 developed vaso‐occlusive pain following an episode of acute gastroenteritis; since then the patient has not had any vaso‐occlusive episodes or acute chest syndrome (ACS). Patient 1208 had no episodes of vaso‐occlusive crisis or ACS post LentiGlobin gene therapy. Patient 1207 had 2 episodes of ACS approximately 6 and 8 months after LentiGlobin gene therapy and re‐started chronic transfusions and hydroxyurea treatment; the patient subsequently experienced 1 Grade ≥3 vaso‐occlusive pain episode. Total Hb and % HbAT87Q contribution to total Hb for patients 1204, 1207 and 1208 at last visit were: 12.2, 8.4, and 10.2 g/dL, and 50.4, 4.4 and 26.4%, respectively. Dissociation and association of O2 curves for RBCs isolated from the 2 patients free of chronic transfusions (1204 and 1208) and performed 36‐ and 8‐months post infusion, respectively, showed only a slight increase in P50 during re‐oxygenation, indicating anti‐sickling capability of transgenic HbAT87Q and low levels of HbS polymerization. Density curves showed an overall normal RBC hydration at multiple time points during follow‐up, with dense cells contributing 0–4% compared to a mean (±SD) of 12.8% (±7.8) in untreated patients. The deformability of RBCs from the 2 patients (1204 and 1208) was lower than observed for healthy donors but higher than for untreated SCD patients. Under controlled shear stress, thrombospondin adherence was consistently lower for RBCs isolated from the 2 patients (1204 and 1208) compared to untreated patients with SCD. Slight intravascular hemolysis was observed for the 3 HGB‐205 patients during follow‐up, but the hemolytic levels improved compared to baseline. RP‐HPLC analysis of total RBCs isolated at last visit showed an increase in βA‐T87Q and a decrease in βS in comparison to reticulocytes, indicating an improved survival of RBCs expressing more anti‐sickling β‐globin transgene. A longer follow‐up and data on deformability, distribution of fetal Hb and additional adhesion markers will be presented.Summary/Conclusion:Further investigations are needed to better define the sickle cell disease phenotype which could most benefit from a gene therapy approach.

Cross-validation of an algorithm detecting acute gastroenteritis episodes from prescribed drug dispensing data in France: comparison with clinical data reported in a primary care surveillance system, winter seasons 2014/15 to 2016/17

BackgroundThis study compares an algorithm to detect acute gastroenteritis (AG) episodes from drug dispensing data to the validated data reported in a primary care surveillance system in France.MethodsWe used drug dispensing data collected in a drugstore database and data collected by primary care physicians involved in a French surveillance network, from season 2014/15 to 2016/17. We used an adapted version of an AG discrimination algorithm to identify AG episodes from the drugstore database. We used Pearson’s correlation coefficient to evaluate the agreement between weekly AG signals obtained from the two data sources during winter months, in the overall population, by specific age-groups and by regions.ResultsCorrelations between AG signals for all ages were 0.84 [95%CI 0.69; 0.92] for season 2014/15, 0.87 [95%CI 0.75; 0.93] for season 2015/16 and 0.94 [95%CI 0.88; 0.97] for season 2016/17. The association between AG signals estimated from two data sources varied significantly across age groups in season 2016/17 (p-value < 0.01), and across regions in all three seasons studied (p-value < 0.01).ConclusionsThere is a strong agreement between the dynamic of AG activity estimated from drug dispensing data and from validated primary care surveillance data collected during winter months in the overall population but the agreement is poorer in several age groups and in several regions. Once automated, the reuse of drug dispensing data, already collected for reimbursement purposes, could be a cost-efficient method to monitor AG activity at the national level.

Human bocavirus in children with acute gastroenteritis in Piedmont, Italy.

Gastroenteritis is a common disease in children, characterized by diarrhea, vomiting, abdominal pain, and fever. Co-detection of HBoV with other gastroenteric viruses was reported a lot in patients with acute gastroenteritis. This paper presents the real-time RT-PCR Taqman assay for the detection and quantification of HBoV for clinical fecal samples collected from hospitalized children with acute gastroenteritis in Piedmont. All fecal specimens were tested for the presence of HBoV with specific primers and probe. A total of 17 out of 123 (13.92%) episodes of acute gastroenteritis were associated with HBoV genomic detection with median viral load 6864.75±19784.79 genomes/mg fecal specimens. Among the 17 HBoV-positive cases, 11 were also positive for other viral pathogens, including rotavirus (n = 2), astrovirus (n=1), norovirus GII (n=6), norovirus GI (n=2) . Two cases were positive for more than one virus including norovirus GII and norovirus GI (n=1) and rotavirus, sapovirus and astrovirus (n=1). A higher detection of HBoV infections was observed in winter, and peaking in February. Although HBoV is suspected to be responsible for gastroenteritis in children, our data showed that this association was uncertain since none difference was observed in term of viral load in the group with single infection of HBoV and group of coinfections with other viral agent.

Tumour necrosis factor-α gene -308 G>A and -238 G>A polymorphisms are associated with susceptibility to irritable bowel syndrome and drug efficacy in children.

An imbalance in the genetically controlled pro- and anti-inflammatory cytokine production could potentially promote ongoing low-grade inflammation following an episode of acute gastroenteritis and, subsequently, could result in irritable bowel syndrome (IBS; post-infectious IBS, PI-IBS). Since there is very little known on the impact of pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α) on IBS, we conducted the present study with aims of determining the correlation between TNF-α gene polymorphisms (-308 G>A and -238 G>A) and susceptibility to IBS and drug efficacy in children. Diarrhoea-predominant IBS patients and healthy subjects were recruited for DNA extraction. The genotypes were tested using polymerase chain reaction-restriction fragment length polymorphism. In addition to conventional symptomatic treatments, Live Combined Bifidobacterium, Lactobacillus and Enterococcus Powder and Montmorillonite Powder were administered to all the patients participating in the study for consecutive 4weeks. The efficacy was evaluated 2weeks after the withdrawal of the drugs. The association between gene polymorphism and drug efficacy was analysed by means of binary logistic regression analysis. Patients in the IBS group were susceptible to IBS with GA genotype and A allele of -308 G>A so were those with AA genotype and A allele of -238 G>A. The symptoms were also alleviated following treatment. The cure rate of patients with GA genotype of -308 G>A and AA genotype of -238 G>A was low. These findings suggested that the haplotype AA could potentially be associated with the cure rate of IBS patients. GA genotype of -308 G>A, AA genotype of -238 G>A, enterobacteria and 5-hydroxytryptamine in serum may act adversely, whereas bifidobacterial may be beneficial to the efficacy of IBS treatment. The above findings evidently suggest that the frequency of TNF-α gene -308 G>A carrying GA genotype and A allele and -238 G>A carrying AA genotype and A allele is higher in children with IBS. Additionally, GA genotype of -308 G>A and AA genotype of -238 G>A may act adversely to the efficacy of IBS treatment, which may be a reference index for predicting the curative effect of IBS.