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Tian Tian,1,* Xiaobo Zhang,1,* Tao Luo,1 Duolao Wang,2 Yuping Sun,3 Jianghong Dai1 1Department of Epidemiology and Biostatistics, School of Public Health, Xinjiang Medical University, Urumqi, 830001, People’s Republic of China; 2Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, L35QAUK, UK; 3School of Basic Medicine, Xinjiang Medical University, Urumqi, 830001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianghong Dai Tel +86-991-4365530Email epidjh@163.comAbstract: Gut microbiota are critical to many aspects of human health including immune and metabolic health. Long-term diet influences the community structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how the human gut microbiome responds to short-term intervention with dietary fiber. This study explored the effects of mixed dietary fibers on gut microbiota in young, healthy people. Twelve healthy, young adults participated in a randomized, crossover trial comparing the effects of polyglucan, inulin and resistant malt dextrin on gut microbiota composition and bacterial abundances. During the study, the subjects followed their normal diets without any constraints. Microbial community profiles were determined by absolute quantification 16S rRNA gene amplicon sequencing. Mixed model analysis did not reveal an effect of dietary intervention on microbial community structure. At the genus level, dietary fiber intervention for 4 days significantly promoted the growth of Alloprevotella, Parabacteroides and Parasutterella and inhibited the growth of Adlercreutzia, Anaerovorax, Enterococcus, Intestinibacter and Ruminococcus 2 compared with the baseline. Addition of whey albumen powder for 4 days promoted the growth of Corynebacterium, Collinsella, Olsenella and Lactococcus but interfered with the growth of Megasphaera. Our results should be corroborated by randomized clinical trials with large sample size.Keywords: dietary fiber, gut microbiota, short-term intervention

Background/purpose The current standard care for acute pancreatitis with acute necrotic collections (ANC) is to postpone invasive intervention for 4 weeks when indicated. However, in patients with persistent organ failure (POF), this delayed approach may prolong organ failure. In this study, we aimed to assess the feasibility and safety of earlier drainage for acute pancreatitis patients with ANC and POF. Methods A single-center, randomized controlled trial was conducted. Eligible patients were randomly assigned to either the early on-demand (EOD) group or the standard management (SM) group. Within 21 days of randomization, early drainage was triggered by unremitted or worsening organ failure in the EOD group. The primary endpoint was a composite of major complications/death during 90-days follow-up. Results Thirty patients were randomized. Within 21 days of randomization, eight of the 15 patients (53%) in the EOD group underwent percutaneous drainage compared to four of the 15 patients (27%) in the SM group (P = 0.26). The primary outcome occurred in three of the 15 (20%) patients in the EOD group and seven of the 15(46.7%) in the controls (P = 0.25, relative risk 0.43, 95%CI 0.14 to 1.35). Conclusions Although the EOD approach did not result in significant differences between groups, the primary outcome assessed in this trial demonstrated the potential for clinical benefits favoring early drainage.

Introduction/aim: The supraphysiologic chloride concentration of normal saline may contribute to acute kidney injury (AKI). Balanced crystalloids can decrease chloride concentration and AKI in critically ill patients. We aim to test the hypothesis that, in patients with predicted severe acute pancreatitis (pSAP), compared with saline, fluid therapy with balanced crystalloids will decrease plasma chloride concentration.Methods/Design: This is a multicenter, stepped-wedge, cluster-randomized, controlled trial. All eligible patients presenting to the 11 participating sites across China during the study period will be recruited. All sites will use saline for the first month and sequentially change to balanced crystalloids at the pre-determined and randomly allocated time point. The primary endpoint is the plasma chloride concentration on day 3 of enrollment. Secondary endpoints will include major adverse kidney events on hospital discharge or day 30 (MAKE 30) and free and alive days to day 30 for intensive care admission, invasive ventilation, vasopressors, and renal replacement therapy. Additional endpoints include daily serum chloride and sequential organ failure assessment (SOFA) score over the first seven days of enrollment.Discussion: This study will provide data to define the impact of normal saline vs. balanced crystalloids on plasma chloride concentration and clinical outcomes in pSAP patients. It will also provide the necessary data to power future large-scale randomized trials relating to fluid therapy.Ethics and Dissemination: This study was approved by the ethics committee of Jinling Hospital, Nanjing University (2020NZKY-015-01) and all the participating sites. The results of this trial will be disseminated in peer-reviewed journals and at scientific conferences.Trial registration: The trial has been registered at the Chinese Clinical Trials Registry (ChiCTR2100044432).

Sickle cell anaemia (SCA) is a chronic haemolytic anaemia associated with vaso-occlusive painful crises which may affect several systems including the gastro-intestinal system, resulting in abdominal pain. The concurrence of inflammatory bowel disease and haemoglobinopathy is rare. No previously reported concurrent cases of both SCA and ulcerative colitis (UC) in sub-Saharan Africa were found in the literature. A 16-year-old girl with concurrent SCA and UC is presented. She was admitted to University College Hospital, Ibadan with a 1-year history of recurrent peri-umbilical pain and bloody stools. These symptoms were mainly attributed to SCA at the referring hospital, and she was managed for chronic tropical diarrhoea without a remarkable clinical response. This case illustrates the concurrent presentation of SCA and ulcerative colitis which led to the missed and delayed diagnosis of ulcerative colitis.

Background: The relationship between asymptomatic Salmonella exposure within the gastrointestinal tract and Salmonella bacteraemia is poorly understood, in part due to the low sensitivity of stool culture and the lack of validated molecular diagnostic tests for the detection of Salmonella in the stool. The study aimed to determine a reliable molecular diagnostic test for Salmonella in stool specimens. Methods: We optimised an in-house monoplex real-time polymerase chain reaction (PCR) for the detection of Salmonella ttr and InvA genes in stool by including a selenite broth pre-culture step for Salmonella before DNA extraction and validated their specificity against other local common pathogens. Then we assessed their performance against a well-validated multiplex PCR targeting the same ttr and InvA genes and against stool culture using clinical stool specimens collected from a cohort of 50 asymptomatic healthy Malawian children that were sampled at 1-month intervals over 12 months. We employed a latent Markov model to estimate the specificities and sensitivities of PCR methods. Results: Ttr and InvA primers were both able to detect all the different Salmonella serovars tested and had superior limits of detection when DNA was extracted after selenite pre-culture. Ttr sensitivity and specificity for monoplex-PCR were (99.53%, 95.46%) and for multiplex-PCR (90.30%, 99.30%) respectively. InvA specificity and specificity for using monoplex-PCR was (95.06%, 90.31%) and multiplex-PCRs (89.41%, 98.00%) respectively. Sensitivity and specificity for standard stool culture were 62.88% and 99.99%, respectively. Culture showed the highest PPV (99.73%), and monoplex-ttr had the highest NPV (99.67%). Conclusion: Test methods demonstrated high concordance, although stool culture and monoplexed ttr primers had superior specificity and sensitivity, respectively. The use of selenite pre-enrichment step increased Salmonella detection rate. Taken together, molecular detection methods used here could be used to reveal the true extent of both asymptomatic and symptomatic Salmonella exposure events.

Since December 2019, COVID-19 has caused huge global\ud morbidity and mortality.1 Although the disease is primarily\ud a respiratory illness, gastrointestinal (GI) symptoms are\ud increasingly recognised.2 However, reported literature on\ud the prevalence of these symptoms is conflicting, as is their\ud relationship with disease course and outcome.3,4\ud We aimed to identify the prevalence of GI symptoms among a\ud cohort of UK hospitalised adults with confirmed SARS-CoV-2\ud and to describe the association of GI symptoms with patient\ud characteristics, clinical course and outcome.

Non-typhoidal Salmonella (NTS) usually cause gastroenteritis in humans, but in recent years NTS have begun to cause epidemics of bloodstream infections in Africa. Salmonella Enteritidis is the second most common serovar associated with this invasive form of NTS disease (iNTS) in Africa. To establish a systemic infection, Salmonella must survive and replicate within host cells, with macrophages being a primary target. Genomic characterisation of S. Enteritidis isolates from human bloodstream has identified two new clades that are unique to Africa and distinct from the Global Epidemic clade. The African S. Enteritidis clades exhibit genomic degradation, and possess a distinct prophage repertoire and are multi-drug resistant. However, little is known about the virulence factors that allow African S. Enteritidis to cause systemic infection in susceptible hosts. We screened libraries of random insertion mutants of African and Global S. Enteritidis by transposon insertion sequencing (TIS), and identified about 280 genes belonging to each clade that contribute to bacterial survival and replication in murine macrophages. The genes were associated with 5 pathogenicity-islands, or encoded the global regulators PhoPQ and OmpR-EnvZ. Experiments are ongoing to investigate the role in intra-macrophage replication of genes that are uniquely identified in African Salmonella. It is hoped that our findings will contribute to a greater understanding of African Salmonella infection biology, and that some of the virulence-associated genes could be potential targets for novel therapeutics.

Background Intestinal schistosomiasis was not considered endemic in Lake Malawi until November 2017 when populations of Biomphalaria pfeifferi were first reported; in May 2018, emergence of intestinal schistosomiasis was confirmed. This emergence was in spite of ongoing control of urogenital schistosomiasis by preventive chemotherapy. Our current study sought to ascertain whether intestinal schistosomiasis is transitioning from emergence to outbreak, to judge if stepped-up control interventions are needed. Methods During late-May 2019, three cross-sectional surveys of primary school children for schistosomiasis were conducted using a combination of rapid diagnostic tests, parasitological examinations and applied morbidity-markers; 1) schistosomiasis dynamics were assessed at Samama (n = 80) and Mchoka (n = 80) schools, where Schistosoma mansoni was first reported, 2) occurrence of S. mansoni was investigated at two non-sampled schools, Mangochi Orphan Education and Training (MOET) (n = 60) and Koche (n = 60) schools, where B. pfeifferi was nearby, and 3) rapid mapping of schistosomiasis, and B. pfeifferi, conducted across a further 8 shoreline schools (n = 240). After data collection, univariate analyses and Chi-square testing were performed, followed by binary logistic regression using generalized linear models, to investigate epidemiological associations. Results In total, 520 children from 12 lakeshore primary schools were examined, mean prevalence of S. mansoni by ‘positive’ urine circulating cathodic antigen (CCA)-dipsticks was 31.5% (95% confidence interval [CI]: 27.5–35.5). Upon comparisons of infection prevalence in May 2018, significant increases at Samama (relative risk [RR] = 1.7, 95% CI: 1.4–2.2) and Mchoka (RR = 2.7, 95% CI: 1.7–4.3) schools were observed. Intestinal schistosomiasis was confirmed at MOET (18.3%) and Koche (35.0%) schools, and in all rapid mapping schools, ranging from 10.0 to 56.7%. Several populations of B. pfeifferi were confirmed, with two new eastern shoreline locations noted. Mean prevalence of urogenital schistosomiasis was 24.0% (95% CI: 20.3–27.7). Conclusions We notify that intestinal schistosomiasis, once considered non-endemic in Lake Malawi, is now transitioning from emergence to outbreak. Once control interventions can resume after coronavirus disease 2019 (COVID-19) suspensions, we recommend stepped-up preventive chemotherapy, with increased community-access to treatments, alongside renewed efforts in appropriate environmental control.

Inflammatory Bowel Disease (IBD) describes a group of conditions that includes Crohn’s disease and ulcerative colitis. Unlike some chronic conditions, to a greater or lesser extent, IBD is hidden from or invisible to others which enables concealment of the condition, especially when stigma is associated with the condition. Concealment or nondisclosure allows a means of identity management. Disclosure of a chronic condition is not a single event, and it is dependent on many factors. There is little literature that specifically addresses stigma and/or disclosure in relation to children and young people with IBD. An in-depth qualitative study was undertaken, framed by Interpretive Description and using interviews, friendship maps, and photographs within a participatory framework. Public and patient involvement and engagement (PPIE) was undertaken throughout (inception to dissemination) the study. Young people aged 14-25 years with IBD who had participated in the survey phase of the larger study self-selected to participate in interviews that focused broadly on friendship and feelings of social connectedness. Data were analysed using an iterative, interpretive approach. Preliminary themes were developed and these were explored further, and then tentative theoretical connections about friendship were developed. One superordinate theme focused on disclosure. Thirty-one young people (16 males, 15 females, mean age 18.7 years; 24 Crohn’s, 7 colitis) participated in the interviews (of these, five created friendship maps and six utilised photographs). Three discrete, but interlinked, themes were generated, revealing young people’s experiences of disclosure: to tell or not to tell; controlling the flow: the who, when, what, and how of telling; and reactions and responses to telling: anticipated and actual. Decisions about telling friends about having IBD are challenging for many young people. Having control over disclosure is not always possible, and the potential consequences can feel risky. However, most young people had positive experiences of disclosure and gained support from friends and romantic partners. Most young people downplayed the seriousness of their IBD, revealing some facets of their condition, aiming to sustain their self-identity. Only one young person had been given professional support to disclose. Provision of support and opportunities to discuss whether, when, who, and how to tell friends and what the risks and benefits may be is something that could be woven into an ongoing and wider person-centred dialogue between young people and health professionals within routine clinic visits.

INTRODUCTION: \ud Thetanix (gastroresistant capsules containing lyophilized Bacteroides thetaiotaomicron) is a live biotherapeutic, under development for Crohn's disease, that antagonizes transcription factor nuclear factor kappa B, reducing proinflammatory cytokines, particularly tumor necrosis factor alpha. We aimed to assess safety and tolerability in adolescents with Crohn's disease in remission.\ud \ud METHODS: \ud Subjects who were 16–18 years with Crohn's in remission (weighted pediatric Crohn's disease activity index 99% in part B. Two subjects reported adverse events deemed related—one in part A with eructation, flatulence, and reflux; one in part B with dizziness, abdominal pain, and headache. No serious adverse events were reported. There was no significant change in median calprotectin across part B (87.8 [4.4–447] to 50.5 [5.3–572], P = 0.44 by the Fisher exact test in the active group). No significant differences were found in microbiota profiles, but diversity seemed to increase in treated subjects.\ud \ud DISCUSSION: \ud Thetanix, after single and multiple doses, was well tolerated. Although the numbers in this study were small, the safety profile seems good. Future studies should explore efficacy.

IntroductionNoroviruses are the leading cause of acute gastroenteritis in all age groups, but illness is more severe and causes excess mortality in the elderly, particularly those in long-term care. The total burden of norovirus disease in the elderly in the UK is poorly defined; no current surveillance programmes systematically or accurately quantify norovirus infection in those living in care homes. The aim of this study is to evaluate an enhanced surveillance system for acute gastroenteritis among the elderly in care homes.Methods and analysisWe will conduct this prospective cohort study in care homes in North West England; residents and staff at study care homes will be asked to participate. We will prospectively enrol a cohort of participants in an enhanced surveillance system to capture the incidence of acute gastroenteritis and use multiplex PCR to detect pathogens. We will sample symptomatic and non-symptomatic participants to understand characteristics of norovirus disease and susceptibility to infection. We will generate novel data on transmission dynamics by collecting data on the pattern of interactions within care homes using electronic proximity sensors. Comparisons of outbreak and non-outbreak periods will be used to quantify the impact of norovirus outbreaks on care homes.Ethics and disseminationThe study has been approved by the North West–Greater Manchester South NHS Research Ethics Committee (REC Reference: 16/NW/0541). Study outputs will be disseminated through scientific conferences and peer-reviewed publications. This study will provide detailed insight on the burden and aetiology of acute gastroenteritis in care homes, in addition to generating novel data on transmission dynamics and risks. The study will identify areas for improving infection control practice and allow more accurate modelling of the introduction of interventions such as vaccination.

ObjectivesTo estimate the incidence of gastroenteritis in individuals in care homes.DesignProspective cohort study.SettingFive participating care homes in North West England, UK.ParticipantsResidents and staff present at the five study care homes between 15 August 2017 and 30 May 2019 (n=268).Outcome measuresWe calculated incidence rates for all gastroenteritis cases per 1000 person-years at risk and per 1000 bed-days at risk. We also calculated the incidence rate of gastroenteritis outbreaks per 100 care homes per year.ResultsIn total 45 cases were reported during the surveillance period, equating to 133.7 cases per 1000 person-years at risk. In residents the incidence rate was 0.62 cases per 1000 bed-days. We observed seven outbreaks in all care homes included in surveillance, a rate of 76.4 outbreaks per 100 care homes per year. 15 stool samples were tested; three were positive for norovirus, no other pathogens were detected.ConclusionsWe found that surveillance of infectious gastroenteritis disease in care homes based on outbreaks, the current general approach, detected a majority of cases of gastroenteritis. However, if policymakers are to estimate the burden of infectious gastroenteritis in this setting using only routine outbreak surveillance data and not accounting for non-outbreak cases, this study implies that the total burden will be underestimated.

Typhoid fever is usually a mild clinical disease, but it can have potentially serious complications. Here, we describe a case of an adolescent male who presented with severe illness and multi-organ involvement from typhoid fever. He required follow-up after discharge but eventually recovered. Clinicians should be aware of the spectrum of clinical manifestations as early recognition will improve monitoring and management of typhoid disease.

We report a case of a tubo-ovarian abscess infected with Salmonella enterica serotype typhi A 19-year-old Nepalese woman presented to a hospital in Kathmandu with lower abdominal pain, constipation, fever and a non-healing, suppurative surgical wound from an emergency caesarian section performed 2 months previously at 37 weeks of pregnancy. She also had an exploratory laparotomy for an appendix perforation with peritonitis at 25 weeks of gestation. Her wound infection did not respond to cloxacillin and she had an exploratory laparotomy, and a tubo-ovarian abscess was found from which S. typhi was isolated. She had a bilateral salpingo-oophorectomy and responded to 14 days of chloramphenicol. A tubo-ovarian abscess is a rare complication of enteric fever. [Abstract copyright: © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.]

Background Persistent diarrhoea in children is a common problem in low and middle income countries. To help target appropriate treatment for specific pathogens in the absence of diagnostic tests, we systematically reviewed pathogens most commonly associated with persistent diarrhoea in children. Methods We sought all descriptive studies of pathogens in the stool of children with diarrhoea of over 14 days duration in low and middle income countries with a comprehensive search of the MEDLINE, EMBASE, LILACS and WEB OF SCIENCE databases. We described the study designs and populations, assessed the quality of the laboratory tests, and extracted and summarised data on pathogens. For Escherichia coli, we calculated high and low prevalence estimates of all enteropathic types combined. Results across studies were compared for geographical patterns. Results Nineteen studies were included. Some used episodes of diarrhoea as the unit of analysis, others used children. The quality of reporting of laboratory procedures varied, and pathogens (particularly E. coli types) were classified in different ways. As there were no apparent regional differences in pathogen prevalence, we aggregated data between studies to give a guide to overall prevalence. Enteropathic E. coli types were commonly found in children with persistent diarrhoea (up to 63%). Various other organisms, including viruses, bacteria and parasites, were detected but across all studies their prevalence was under 10%. However, these pathogens were also found in similar frequencies in children without diarrhoea. Conclusion A number of pathogens are commonly associated with persistent diarrhoea in children, but in children without diarrhoea the pathogens are found with similar frequencies. New research with carefully selected controls and standardised laboratory investigations across countries will help map causes and help explore effective options for presumptive treatment.

Background A high proportion of children with persistent diarrhoea in middle and low income countries die. The best treatment is not clear. We conducted a systematic review to evaluate the effectiveness of antimicrobial drug treatment for persistent diarrhoea of unknown or non-specific cause. Methods We included randomized comparisons of antimicrobial drugs for the treatment of persistent diarrhoea of unknown or non-specific cause in children under the age of six years in low and middle income countries. We searched the electronic databases MEDLINE, EMBASE, LILACS, WEB OF SCIENCE, and the Cochrane Central Register of Controlled Trials (CENTRAL) to May 2008 for relevant randomized or quasi randomized controlled trials. We summarised the characteristics of the eligible trials, assessed their quality using standard criteria, and extracted relevant outcomes data. Where appropriate, we combined the results of different trials. Results Three trials from South East Asia and one from Guatemala were included, all were small, and three had adequate allocation concealment. Two were in patients with diarrhoea of unknown cause, and two were in patients in whom known bacterial or parasitological causes of diarrhoea had been excluded. No difference was demonstrated for oral gentamicin compared with placebo (presence of diarrhoea at 6 or 7 days; 2 trials, n = 151); and for metronidazole compared with placebo (presence of diarrhoea at 3, 5 and 7 days; 1 trial, n = 99). In one small trial, sulphamethoxazole-trimethoprim appeared better than placebo in relation to diarrhoea at seven days and total stool volume (n = 55). Conclusion There is little evidence as to whether or not antimicrobials help treat persistent diarrhoea in young children in low and middle income countries.