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Introduction: Shigellosis is an intestinal disease and is one of the main causes of morbidity and mortality among children in India. The study aims to analyze the effect of the designed formulation on the hematological parameters in shigellosis-induced rats and assess the in vivo toxicity of this formulation. Methods: Male Wistar rats were housed in different groups. Group 1 is normal control; group 2 is diseased control; group 3 and group 4 diseased rats received 250 mg/kg formulation and 20 mg/kg body weight norfloxacin, respectively, orally once a day. Shigellosis was induced by a single intraperitoneal injection of Shigella flexneri, and bacterial load was calculated using the Shigella agar plate. On completion of the study, blood was collected for hematological as well as electrolyte analysis. Results: The in vivo acute toxicity results indicate that the formulation is safe up to 2000 mg/kg. Furthermore, formulation significantly (p

Global travel patterns are on a rebound and so to the perennial threat of gastrointestinal infections associated with travellers' diarrhoea (TD) and acute gastroenteritis (AGE) in those who journey to many parts of the world. In a second report out of the Netherlands, a large cohort ( I N i = 1519) of travellers were assessed before during, and after travel for the development of PI-IBS in relation to whether or not they experienced TD during travel.[8] Among the 35% within the cohort who experienced TD, 12.1% developed PI-IBS; whereas, only 3.4% who did not experience TD developed PI-IBS (relative risk: 3.5, 95%CI 2.3-5.3). Risk factors for development of PI-IBS after TD were prolonged duration of travel, prolonged diarrhoea and parasitic aetiology. [Extracted from the article]

Shigellosis is one of the acute bowel infections and remains a serious public health problem in resource-poor countries. The present study aimed to survey the distribution of extended-spectrum β-lactamase (ESBL)-producing Shigella strains isolated from patients with diarrhea in northwest Iran. In the present cross-sectional study, from January 2019 to December 2020, 1280 fecal samples were collected from children with diarrhea in Ardabil, Iran. Multiplex PCR assay was applied for the presence of ipaH, invC, wbgZ, rfpB, and rfc genes to detect Shigella spp., Shigella sonnei, Shigella dysenteriae, Shigella flexneri, and Shigella boydii, respectively. Phenotypic detection of ESBL-producing isolates was carried out using the Double Disc Test (DDT). The frequency of main ESBL encoding genes including blaCTX-M, blaSHV, and blaTEM was detected using multiplex PCR. The genetic similarity of S. sonnei isolates was determined using ERIC PCR. A total of 49 Shigella isolates (3.8%; 49/1280) including 42 (85.7%) S. sonnei, 5 (10.2%) S. flexneri, and 2 (4%) S. dysenteriae were identified. S. boydii was not detected in any fecal samples. ESBLs were produced by 10.2% of Shigella spp. including 3 S. sonnei, 1 S. flexneri, and 1 S. dysenteriae. The ESBL encoding genes include blaCTX-M and blaTEM found in 65.3% and 61.2% of isolates, respectively. blaSHV gene was not detected in any isolates. The ERIC-PCR profiles allowed the differentiation of 42 S. sonnei strains into 6 clusters. Our study revealed a high frequency of ESBL-encoding genes among Shigella spp. in northwest Iran. The high prevalence of S. sonnei harboring ESBL genes, in the present work, is the main challenge for dysentery treatment, and this concern justifies the need for effective and regular monitoring of antibiotic usage among patients. [ABSTRACT FROM AUTHOR]

Background: Shigella spp. are common enteric pathogens in captive non‐human primates. Treatment of symptomatic infections involves supportive care and antibiotic therapy, typically with an empirical choice of antibiotic. Methods: Twenty‐four clinically ill, Shigella PCR‐positive animals were randomly assigned to one of four treatment groups: single‐dose ceftiofur crystalline free acid (CCFA), single‐dose azithromycin gavage, a 5‐day tapering azithromycin dose, or 7‐day course of enrofloxacin. We hypothesized that all antimicrobial therapies would have similar efficacy. Results: Animals in all groups cleared Shigella, based on fecal PCR, and had resolution of clinical signs 2 weeks after treatment. Eight out of nine clinically ill and PCR‐positive animals tested negative by fecal culture. Conclusions: Single‐dose CCFA, single‐dose azithromycin, and a 5‐day tapering course of azithromycin all performed as well as a 7‐day course of enrofloxacin in eliminating Shigella infection. Fecal PCR may be a better diagnostic than culture for Shigella. [ABSTRACT FROM AUTHOR]

Introduction: Shigella continues to cause significant morbidity and mortality each year, mostly in under-five children living in developing countries. We investigated the association between Shigella virulence genes and shigellosis. Methodology: We randomly selected 61 S. flexneri strains isolated from patients in Bangladesh between 2009 and 2013, and evaluated the presence of 140 MDa large-virulence-plasmid (p140), and 22 virulence genes including ipaH, ial, toxin, and T3SS-related genes. Results: We found p140 in 79% (n = 48) and ipaBCD in 90% (n = 55) strains, while seven strains were missing the p140. The prevalence of ial was 89%, ipgC and ipgE was 85%, and the prevalence for the remaining genes was < 85%. During the multivariate analysis, we found that instead of sen, the Shigella enterotoxin gene set along with several other virulence genes such as ipgA, icsB, ipgB1, spa15, and mxiC, were significantly influencing multiple clinical features relevant to shigellosis, including bloody stool, mucoid stool, and rectal straining. Conclusions: We believe our model will help to determine the actual disease burden by directly looking for the genetic material in clinically suggestive patients, especially when detecting the causative organisms by traditional means is difficult. [ABSTRACT FROM AUTHOR]

Objectives: This study investigates the amino acid sequence and identifies antigenic epitopes of 49.8 kilodalton (kDa) pili protein Shigella flexneri, which will be used as candidates for the shigellosis vaccine. Materials and Methods: Our study is a prospectively descriptive laboratory. We used bacterial isolate of S. flexneri pili isolation was performed using a pili cutter and sodium dodecyl-sulfate polyacrylamide gel electrophoresis. The amino acid sequences were analyzed using liquid chromatography dual mass spectrometry (LC-MS/MS) method in the proteomic laboratory. The target epitope antigenicity analysis was tested using Kolaskar and Tongaonkar Antigenicity software. The Bepired Linear Epitope Prediction software is used for epitope mapping. PymOL software was used for the visualization of proteins and molecular docking. Peptides and antibodies were applied to hemagglutination test and immune response was tested using the dot blot method. Results: LC-MS/MS analysis results from the mascot server showed that the 49.8 kDa pili protein is S. flexneri similar to the flagellin protein of S. flexneri 1235-66 (ID I6H2T2). The results of antigenicity analysis and epitope mapping showed that areas of protein that has the most potential and antigenic epitopes are the regions 98-111 and 263-290 with the amino acid sequences, QSSTGTNSQSDLDS (Q-S) and DTTITKAETKTVTKNQVVDTPVTTDAAK (D-K). The results of the molecular docking interaction test between the peptide and the B-cell receptor have a low binding energy. Peptide Q-S and peptide D-K antigens are hemagglutinin molecules because they can agglutinate erythrocytes. The immune response between peptide antigens and anti-peptide antibodies can react based on color gradations in the dotblot method. Conclusion: The amino acid sequences Q-S and D-K are potentially antigenic epitopes. These peptides can be used to develop candidates for shigellosis vaccine. [ABSTRACT FROM AUTHOR]

Introduction: Rotavirus is the leading cause of severe, life threatening gastroenteritis in infants and young children. As rotavirus strains vary between geographic areas, region specific genotyping information is highly vital to study rotavirus epidemiology and to monitor strain variation after vaccine introduction. Aim: To estimate the prevalence of rotavirus diarrhoea and strains causing the infection among children younger than five years of age and to study the clinical profile of rotavirus diarrhoea to ascertain factors associated with rotavirus infection in them. Materials and Methods: This hospital-based cross-sectional study was carried out on 150 children under five years with diarrhoea in the Department of Paediatrics, Government Medical College, Chennai, Tamil Nadu, India from November 2017 to August 2018. The clinical severity was assessed by using Vesikari score. By using PremierTM Rotaclone ELISA Kit rotavirus antigen was detected. Positive samples were tested for RNA identification by Reverese Transcriptase-Polymerase Chain Reaction (RT-PCR). The IBM Statistical Package for the Social Sciences (SPSS) version 22 was used for statistical analysis. Results: The prevalence of rotavirus diarrhoea was 17.3% and positive samples belonged to G3 type. Prevalence of rotavirus diarrhoea among the vaccinated children was less when compared to unvaccinated children (p-value 0.034). Clinical severity score (Vesikari score) indicated that patients infected with rotavirus had severe disease as compared to rotavirus non infected patients (p-value 0.011). The duration of hospital stay was longer in rotavirus-positive children as compared to rotavirus-negative children (p-value <0.001). Conclusion: This study highlights the serotype specific prevalence of rotavirus diarrhoea in under five children. Rotavirus has been found to have more severe and prolonged illness among unimmunised under five children; thereby, reinforcing the need for routine rotavirus vaccination. [ABSTRACT FROM AUTHOR]

Introduction: Shigellosis is a reportable infectious disease. It can present as a severe bloody diarrhoea but is often asymptomatic. Shigella can be sexually transmissible. We performed a study among symptomatic and asymptomatic men who have sex with men (MSM) to assess the prevalence of Shigella, Salmonella and Campylobacter.Methods: From March to June 2020, MSM attending the Amsterdam centre for sexual health were consecutively included. Predefined minimal numbers of inclusion of 150, 100 and 50 were determined, respectively, for MSM who reported no diarrhoea, diarrhoea during last month or diarrhoea on the day of visit to clinic. Anal samples were tested for the presence of Shigella, Salmonella and Campylobacter. During the same period, the frequency of these bacteria was assessed in routinely tested samples requested by general physicians or nursing home physicians. Characteristics of included MSM were compared between the men with different diarrhoea anamnesis, and the prevalence of shigellosis was estimated in each group.Results: We included 212 MSM without diarrhoea, 109 MSM who recently had diarrhoea and 68 MSM who reported diarrhoea on the day of clinic visit. Thirteen (3.3%, 95% CI 1.7% to 5.6%) MSM were infected with Shigella, none with Salmonella and 7 (1.8%, 95% CI 0.7% to 3.7%) with Campylobacter. Shigella prevalence was 2.8% (95% CI 1.0% to 6.1%) in asymptomatic men, 3.7% (95% CI 1.0% to 9.1%) in men who recently had diarrhoea and 4.4% (95% CI 0.9% to 12.4%) in men with current diarrhoea (p=0.799). Shigella was more frequently found in MSM who had used pre-exposure prophylaxis (PrEP) in the preceding 3 months (10/151), compared with those not having used PrEP (2/146) or being HIV positive (1/75) (p=0.038). Shigella was significantly more often detected among MSM compared with routinely obtained faecal samples being 11/770 (1.4%) (p=0.031).Conclusion: Shigella infections are relatively common in both symptomatic and asymptomatic MSM. Future studies should focus on the risk of onward transmission via asymptomatic persons. SamenvattingIntroductie Shigellose is een meldingsplichtige infectieziekte. Het kan zich presenteren als een ernstige bloederige diarree, maar is vaak asymptomatisch. Shigella kan seksueel overdraagbaar zijn. We hebben een onderzoek uitgevoerd onder symptomatische en asymptomatische mannen die seks hebben met mannen (MSM) om de prevalentie van Shigella, Salmonella en Campylobacter te bepalen. Methoden Van maart tot juni 2020 werden achtereenvolgens MSM van het Amsterdamse centrum voor seksuele gezondheid opgenomen. Vooraf gedefinieerde minimale aantallen van inclusie van respectievelijk 150, 100 en 50 waren bepaald voor MSM die geen diarree, diarree in de afgelopen maand of diarree op de dag van bezoek aan de kliniek meldden. Anale monsters werden getest op de aanwezigheid van Shigella, Salmonella en Campylobacter. In dezelfde periode werd de frequentie van deze bacteriën bepaald in routinematig geteste monsters aangevraagd door huisartsen of verpleeghuisartsen. Kenmerken van geïncludeerde MSM werden vergeleken tussen mannen met verschillende diarree anamnese, en de prevalentie van shigellose werd in elke groep geschat. Resultaten We includeerden 212 MSM zonder diarree, 109 MSM die onlangs diarree hadden en 68 MSM die diarree meldden op de dag van het bezoek aan de kliniek. Dertien (3,3%, 95% CI 1,7-5,6%) MSM waren geïnfecteerd met Shigella, geen enkele met Salmonella, en 7 (1,8%, 95% CI 0,7-3,7%) met Campylobacter. De prevalentie van Shigella was 2,8% (95%CI 1,0-6,1%) bij asymptomatische mannen, 3,7% (95%CI 1,0-9,1%) bij mannen die recent diarree hadden en 4,4% (95%CI 0,9-12,4%) bij mannen met huidige diarree (P=0,799). Shigella werd vaker gevonden bij MSM die in de voorgaande drie maanden (10/151) PrEP hadden gebruikt dan bij mensen die geen PrEP hadden gebruikt (2/146) of hiv-positief waren (1/75) (p=0,038). Shigella werd significant vaker gedetecteerd bij MSM in vergelijking met routinematig verkregen fecale monsters, namelijk 11/770 (1,4%) (p=0,031). ConclusieShigella infecties komen relatief vaak voor bij zowel symptomatische als asymptomatische MSM. Toekomstige studies moeten zich richten op het risico van verdere overdracht via asymptomatische personen. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance of Shigella sonnei has become a global concern. Here, we report a phylogenetic group of S. sonnei with extensive drug resistance, including a combination of multidrug resistance, coresistance to ceftriaxone and azithromycin (cefRaziR), reduced susceptibility to fluoroquinolones, and even colistin resistance (colR). This distinct clone caused six waterborne shigellosis outbreaks in China from 2015 to 2020. We collect 155 outbreak isolates and 152 sporadic isolates. The cefRaziR isolates, including outbreak strains, are mainly distributed in a distinct clade located in global Lineage III. The outbreak strains form a recently derived monophyletic group that may have emerged circa 2010. The cefRaziR and colR phenotypes are attributed to the acquisition of different plasmids, particularly the IncB/O/K/Z plasmid coharboring the blaCTX-M-14, mphA, aac(3)-IId, dfrA17, aadA5, and sul1 genes and the IncI2 plasmid with an mcr-1 gene. Genetic analyses identify 92 accessory genes and 60 single-nucleotide polymorphisms associated with the cefRaziR phenotype. Surveillance of this clone is required to determine its dissemination and threat to global public health. Shigella sonnei is a major contributor to the global burden of dysenteric diarrhoea in developed countries. In this work, authors report a S. sonnei clone which has caused numerous waterborne shigellosis outbreaks in China from 2015 to 2020. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance against shigellosis is increasingly alarming. However, evidence-based knowledge gaps regarding the changing trends of shigellosis in Bangladesh exist due to the scarcity of longitudinal data on antimicrobial resistance. Our study evaluated the last 20 years antimicrobial resistance patterns against shigellosis among under-5 children in the urban and rural sites of Bangladesh. Data were extracted from the Diarrheal Disease Surveillance System (DDSS) of Dhaka Hospital (urban site) and Matlab Hospital (rural site) of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b) between January 2001 and December 2020. We studied culture-confirmed shigellosis cases from urban Dhaka Hospital (n = 883) and rural Matlab Hospital (n = 1263). Since 2001, a declining percentage of shigellosis in children observed in urban and rural sites. Moreover, higher isolation rates of Shigella were found in the rural site [1263/15684 (8.1%)] compared to the urban site [883/26804 (3.3%)] in the last 20 years. In both areas, S. flexneri was the predominant species. The upward trend of S. sonnei in both the study sites was statistically significant after adjusting for age and sex. WHO-recommended 1st line antibiotic ciprofloxacin resistance gradually reached more than 70% in both the urban and rural site by 2020. In multiple logistic regression after adjusting for age and sex, ciprofloxacin, azithromycin, mecillinam, ceftriaxone, and multidrug resistance (resistance to any two of these four drugs) among under-5 children were found to be increasing significantly (p<0.01) in the last 20 years in both sites. The study results underscore the importance of therapeutic interventions for shigellosis by appropriate drugs based on their current antibiogram for under-5 children. These observations may help policymakers in formulating better case management strategies for shigellosis. [ABSTRACT FROM AUTHOR]

Aims: This study represents the first analysis from Iran for both the frequency of the most common causes of infectious diarrhoea and their antibiotic resistance patterns in adult patients. Methods: Adult stool specimens (n = 211) were analyzed. Stool specimens were analyzed using standard microbiological, polymerase chain reaction, and reverse transcription polymerase chain reaction tests to identify bacterial, parasitic, and viral enteropathogens. Antibiotic resistance profiles were determined. Results: Enteropathogens were identified in 46.4% (98/211) of the surveyed samples. This included 33.1% (70/211) bacterial infections, including 9.9% (21/211) diarrheagenic Escherichia coli (DEC) and 8.5% (18/211) Shigella spp. We detected 7.1% (15/211) parasitic infections (mostly Giardia lamblia) and 6.1% (13/211) viral infections (mostly adenovirus). The DEC and Shigella spp. isolates included many multi-drug resistant (MDR) isolates (95.2% and 77.7%, respectively), and extended spectrum-β-lactamase (ESBL) genes were often present (57.1% and 61.1%, respectively). The most commonly identified ESBL genes in the DEC and Shigella spp. isolates were blaTEM (100% in both species), blaCTX-M15 (91.6% and 100%, respectively), AmpC blaCIT (80% and 100%, respectively), and blaDHA (80% and 100%, respectively). Conclusions: Bacterial infection was the primary cause of infectious diarrhea, affecting one-third of the adults. The frequency of DEC and Shigella spp. was higher than for other enteropathogens. The high prevalence of MDR, the elevated incidence of ESBL genes among Shigella spp. and DEC isolates, and the presence of quinolone resistance in the Salmonella spp. isolates represent a significant challenge for gastroenteritis diagnosis and treatment in this region. [ABSTRACT FROM AUTHOR]

Shigella, the causative agent of bacillary dysentery, subvert cytoskeletal and trafficking processes to invade and replicate in epithelial cells using an arsenal of bacterial effectors translocated through a type III secretion system. Here, we review the various roles of the type III effector IpgD, initially characterized as phosphatidylinositol 4,5 bisphosphate (PI4,5P2) 4-phosphatase. By decreasing PI4,5P2 levels, IpgD triggers the disassembly of cortical actin filaments required for bacterial invasion and cell migration. PI5P produced by IpgD further stimulates signaling pathways regulating cell survival, macropinosome formation, endosomal trafficking and dampening of immune responses. Recently, IpgD was also found to exhibit phosphotransferase activity leading to PI3,4P2 synthesis adding a new flavor to this multipotent bacterial enzyme. The substrate of IpgD, PI4,5P2 is also the main substrate hydrolyzed by endogenous phospholipases C to produce inositoltriphosphate (InsP2), a major Ca2+ second messenger. Hence, beyond the repertoire of effects associated with the direct diversion of phoshoinositides, IpgD indirectly down-regulates InsP3-mediated Ca2+ release by limiting InsP3 production. Furthermore, IpgD controls the intracellular lifestyle of Shigella promoting Rab8/11-dependent recruitment of the exocyst at macropinosomes to remove damaged vacuolar membrane remnants and promote bacterial cytosolic escape. IpgD thus emerges as a key bacterial effector for the remodeling of host cell membranes. [ABSTRACT FROM AUTHOR]

Background: Rotavirus is the leading global pathogen of diarrhea-associated mortality and poses a great threat to public health in all age groups. This study aimed to explore the global burden and 30-year change patterns of rotavirus infection-associated deaths. Methods: Based on the Global Burden of Disease 2019 Study (GBD 2019), we analyzed the age-standardized death rate (ASDR) of rotavirus infection by sex, geographical region, and sociodemographic index (SDI) from 1990 to 2019. A Joinpoint regression model was used to analyze the global trends in rotavirus infection over the 30 years, SaTScan software was used to detect the spatial and temporal aggregations, and a generalized linear model to explore the relationship between sociodemographic factors and death rates of rotavirus infection. Results: Globally, rotavirus infection was the leading cause of diarrheal deaths, accounting for 19.11% of deaths from diarrhea in 2019. Rotavirus caused a higher death burden in African, Oceanian, and South Asian countries in the past three decades. The ASDR of rotavirus declined from 11.39 (95% uncertainty interval [95% UI] 5.46–19.48) per 100,000 people in 1990 to 3.41 (95% UI 1.60–6.01) per 100,000 people in 2019, with an average annual percentage change (AAPC) (− 4.07%, P < 0.05). However, a significant uptrend was found in high-income North America (AAPC = 1.79%, P < 0.05). The death rate was the highest among children under 5 years worldwide. However, the death rates of elderly individuals over 70 years were higher than those of children under 5 years in 2019 among high, high-middle, middle, and low-middle SDI regions. Current health expenditure, gross domestic product per capita, and the number of physicians per 1000 people were significantly negatively correlated with death rates of rotavirus. Conclusions: Although the global trends in the rotavirus burden have decreased substantially over the past three decades, the burden of rotavirus remained high in Africa, Oceania, and South Asia. Children under 5 years and elderly individuals over 70 years were the populations most at risk for rotavirus infection-associated deaths, especially elderly individuals over 70 years in relatively high SDI regions. More attention should be paid to these areas and populations, and effective public health policies should be implemented in the future. [ABSTRACT FROM AUTHOR]

Escherichia coli is one of the commensal species most represented in the intestinal microbiota. However, there are some strains that can acquire new virulence factors that enable them to adapt to new intestinal niches. These include enteroinvasive E. coli (EIEC) that is responsible for the bacillary dysentery that causes severe diarrheal symptoms in both children and adults. Due to the increasing onset of antibiotic resistance phenomena, scientific research is focused on the study of other therapeutic approaches for the treatment of bacterial infections. A promising alternative could be represented by antimicrobial peptides (AMPs), that have received widespread attention due to their broad antimicrobial spectrum and low incidence of bacterial resistance. AMPs modulate the immune defenses of the host and regulate the composition of microbiota and the renewal of the intestinal epithelium. With the aim to investigate an alternative therapeutic approach, especially in the case of antibiotic resistance, in this work we created a line of intestinal epithelial cells able to express high concentrations of AMP human β-defensin-2 (HBD-2) in order to test its ability to interfere with the pathogenicity mechanisms of EIEC. The results showed that HBD-2 is able to significantly reduce the expression of the proinflammatory cytokines by intestinal epithelial cells, the invasiveness ability of EIEC and the expression of invasion-associated genes. [ABSTRACT FROM AUTHOR]

Food-borne disease due to intestinal parasites (IPs) and enteric bacterial infections (EBIs) remain a major public health problem. Food handlers, individuals involved in preparing and serving food, working with poor personal hygiene could pose a potential threat of spreading IPs and EBIs to the public. The aim of this study was to examine the overall prevalence and risk factors of IPs and EBIs among food handlers in four selected regions of Ethiopia. Scientific articles written in English were recovered from PubMed, ScienceDirect, Web of Science, Google Scholar, Cochrane Library, and other sources from Google Engine and University Library Databases. "Prevalence," "Intestinal Parasites," "Enteric Bacterial Infections," "Associated Factors," "Food Handlers," and "Ethiopia" were the search terms used for this study. For critical appraisal, PRISMA 2009 was applied. Stata software version 16 was used to perform the meta-analysis. Heterogeneity and publication bias were evaluated using Cochran's Q, inverse variance (I2), and funnel plot asymmetry tests. A random-effects model was used to calculate the pooled burden of IPs and EBIs and its associated factors among food handlers, along with the parallel odds ratio (OR) and 95% confidence interval (CI). For this meta-analysis, a total of 5844 food handlers were included in the 20 eligible studies. The overall pooled prevalence of IPs and EBIs among food handlers in four selected regions of Ethiopia was 29.16% (95% CI: 22.61, 35.71), with covering (25.77%) and (3.39%) by IPs and EBIs, respectively. Ascaris lumbricoides, Entamoeba histolytica/dispar, Giardia lamblia, and hookworm were the most prevalent IPs among food handlers with a pooled prevalence of 7.58%, 6.78%, 3.67%, and 2.70%, respectively. Salmonella and Shigella spp. were the most prevalent EBIs among food handlers with a pooled prevalence of 2.78% and 0.61%, respectively. A high prevalence of IPs and EBIs among food handlers was observed in Oromia (38.56%; 95% CI: 29.98, 47.14), while a low prevalence was observed in the Tigray region (19.45%; 95% CI: 6.08, 32.82). Food handlers who had not taken food hygiene training (OR: 0.68, 95% CI: -0.34, 1.69), untrimmed finger nail (OR: 2.23, 95% CI: 1.47, 2.99), lack of periodic medical checkup (OR: 1.52, 95% CI: 0.41, 2.64), lack of handwashing habits (OR: 1.97, 95% CI: 0.53, 3.41), and eating raw vegetables and meat (OR: 2.63, 95% CI: 0.92, 4.34) were factors significantly associated with the prevalence of IPs and EBIs. The prevalence of IPs and EBIs was high in the selected Ethiopian region (Amhara, Oromia, SNNPR, and Tigray) food handlers along an increasing prevalence trend from 2014 to 2022. Therefore, this study recommends the provision of proper health education and training regarding personal hygiene, hand washing, food handling, medical checks, as well as raw vegetable and meat safety. [ABSTRACT FROM AUTHOR]

Campylobacter spp. are a major cause of bacterial diarrhea worldwide and are associated with high rates of mortality and linear growth faltering in children living in low- to middle-income countries (LMICs). Campylobacter jejuni and Campylobacter coli are most often the causative agents of enteric disease among children in LMICs. However, previous work on a collection of stool samples from children under 2 years of age, living in a low resource community in Peru with either acute diarrheal disease or asymptomatic, were found to be qPCR positive for Campylobacter species but qPCR negative for C. jejuni and C. coli. The goal of this study was to determine if whole-genome shotgun metagenomic sequencing (WSMS) could identify the Campylobacter species within these samples. The Campylobacter species identified in these stool samples included C. jejuni, C. coli, C. upsaliensis, C. concisus, and the potential new species of Campylobacter, "Candidatus Campylobacter infans". Moreover, WSMS results demonstrate that over 65% of the samples represented co-infections with multiple Campylobacter species present in a single stool sample, a novel finding in human populations. Author summary: Analysis of shotgun metagenomic data obtained from fecal samples of children living in a low resource tropical community of Peru revealed multiple Campylobacter species. Co-infections with more than one Campylobacter specie within the same sample was a common finding. A potential new species of Campylobacter was also detected within these samples. [ABSTRACT FROM AUTHOR]

Introduction: Diarrhea is a global leading cause of morbidity and mortality among children under five, with rotaviruses being the most common cause. This study aimed to determine the genotypes of rotavirus in children under 5 years with diarrhea in Bandung, Indonesia. Methods: This cross-sectional study was conducted from 2014 to 2018 on 450 children under five with acute diarrhea in primary health centers in Bandung, Indonesia. Fecal samples were examined for rotavirus antigen using an enzyme-linked immunosorbent assay method, and genotype was determined through sequencing using polymerase chain reaction. Results were statistically analyzed using Pearson Chi-square in Epi Info version 3.5.4, with P < 0.05 considered statistically significant. Results: Rotavirus was identified in 8.9% of the subjects, slightly higher in boys (n = 24, 9.8%) than girls (n = 16, 7.8%). We found that the most rotavirus positive in age group is >12–24 months and >24–59 months, while the highest percentage is at the age of ≤6 months (11.8%). Moderate malnutrition was observed in more subjects (12.8%). Vomiting was more frequent in patients positive (55%, P = 0.013) and fever was seen in 32.5% (P = 0.645). No signs of dehydration were seen in most subjects (75%), P = 0.227. Rotavirus genotypes identified were G1P[8] (18, 45%), G3P[8] (14, 35%), G3P[6] (4, 10%), G3P[9] (2, 5%), G2P[4] (1, 2.5%), and nontypeable (NT) (1, 2.5%). Conclusions: The dominant rotavirus genotype is G1P[8], followed by G3P[8], G3P[6], G3P[9], G2P[4], and NT. The most common rotavirus positive in age group is >12–24 months and >24–59 months, while the highest percentage is at the age of ≤6 months. [ABSTRACT FROM AUTHOR]

Background: Shigellosis, traditionally a foodborne and waterborne infection, causes substantial morbidity globally. It is now a leading cause of sexually transmitted gastroenteritis among gay, bisexual, and other men who have sex with men (MSM). We describe an ongoing outbreak of extensively drug-resistant (XDR) Shigella sonnei in the UK.Methods: Routine laboratory surveillance (Second Generation Surveillance System, Gastrointestinal Data Warehouse) identified an exceedance of S sonnei clade 5 in England, first detected in September, 2021. Cases within this clade were subsequently reported from Scotland, Wales, and Northern Ireland. Confirmed cases in this outbreak were defined as individuals diagnosed with S sonnei clade 5 in the UK, with a specimen date between Sept 1, 2021, and Feb 9, 2022, who were genomically confirmed as part of a ten-single nucleotide polymorphism (SNP) linkage cluster. We used whole-genome sequencing with SNP typing to identify genomic clusters and antimicrobial-resistance determinants, analysing cases across the UK. We collected demographic, epidemiological, and clinical data from people infected with S sonnei clade 5 in England using questionnaires (standard and bespoke outbreak questionnaires). We used descriptive summary statistics to characterise cases.Findings: 72 cases (70 [97%] male, median age 34 years [IQR 27-39]) belonging to the ten-SNP single linkage cluster of S sonnei clade 5 were identified between Sept 4, 2021, and Feb 9, 2022. Isolates were predominantly XDR, with 66 (92%) of 72 harbouring blaCTX-M-27, a plasmid-mediated gene for production of extended-spectrum β-lactamases (ESBLs). Of 33 cases with clinical data, 19 (58%) received antibiotics and eight (24%) were hospitalised. 21 (78%) of 27 cases with completed bespoke outbreak questionnaires were HIV-negative MSM taking HIV pre-exposure prophylaxis (PrEP) who reported sexual contacts in the UK and Europe within the incubation period.Interpretation: We highlight the rapid dissemination of XDR ESBL-producing S sonnei in sexual networks of MSM. We recommend strengthening shigella testing where clinically indicated, antimicrobial-resistance surveillance, and integrated health promotion messaging among all MSM, including PrEP users, to reduce the burden of shigellosis.Funding: National Institute for Health Research Health Protection Research Unit in Gastrointestinal Infections at the University of Liverpool in partnership with the UK Health Security Agency. [ABSTRACT FROM AUTHOR]

Background: The importance of accurate diagnosis of infectious diseases is central and crucial to the effectiveness of treatment and prevention of the associated long-term complications of such infections. The objective of this study was therefore to determine the accuracy of the Widal antibody titre test in the diagnosis of typhoid fever relative to the gold standard blood culture technique. Methodology: A total of 40 students attending the Olabisi Onabanjo University Health Services, Ago-Iwoye, Ogun State, Nigeria on account of suspected typhoid fever by positive Widal test (= 1/80) and not on antibiotic therapy, were recruited for the study. Stool and blood samples were collected from each participant and analysed at the medical laboratory of the health center using conventional culture techniques and confirmation of isolates by simplex and multiplex polymerase chain reaction (PCR) amplification assays of hilA (Salmonella enterica), ipaH (Shigella spp), rfc (Shigella flexneri) and wbgZ (Shigella sonnei) genes. Antibiotic susceptibility testing (AST) of isolated bacteria to 10 panel of antibiotics was done using the Kirby Bauer disk diffusion test and interpreted according to the Clinical and Laboratory Standards Institute (CSLI) guideline. Results: Of the 40 patients with suspected typhoid fever by the Widal test, 9 yielded Salmonella enterica giving a 22.5% isolation rate, with Salmonella enterica serovar Typhi (Salmonella Typhi) confirmed as sole bacterium from blood cultures in 5 (12.5%) patients and co-infection of Salmonella and Shigella from stool samples in 4 (10.0%) patients. A total of 52 enteric bacteria isolates were recovered from blood and stool samples of the 40 patients made of Salmonella enterica 9 (17.3%), Shigella spp 20 (38.5%), S. flexneri 9 (17.3%) and S. sonnei 14 (26.9%). All the enteric isolates were multi-drug resistant (MDR), with resistance rates to the antibiotic panel ranging from 33.3%-100%, and all the isolates were resistant to ceftriaxone and pefloxacin. Salmonella isolates were also 100% resistant to nitrofurantoin, ofloxacin and ciprofloxacin; S. flexneri were 100% resistant to nitrofurantoin, amoxicillin, cotrimoxazole, ofloxacin and ciprofloxacin; and S. sonnei were 100% resistant to nitrofurantoin and cotrimoxazole. Conclusion: These results showed that only 12.5% of typhoid fever diagnosis by Widal test had Salmonella Typhi isolated from their blood cultures while Salmonella enterica and Shigella spp were isolated from stool samples of other cases. There is need to adopt culture techniques for laboratory diagnosis of febrile illnesses in order to improve treatment regimen. The fact that AST can also be performed with culture technique could further guide antibiotic prescription and reduce the risk of emergence of resistant bacteria. [ABSTRACT FROM AUTHOR]

Ixekizumab is one of the three biologic agents including Secukinumab and Brodalumab that targets the Interleukin-17 (IL-17) pathway to reduce inflammation in psoriasis and ankylosing spondylitis. In this report we present the case of 42-year-old woman, who was diagnosed with psoriasis and psoriatic arthritis. One week after first administration of Ixekizumab, she developed diffuse abdominal pain, bloody diarrhea (7-8 stools/day) and fever. Following imaging (colonoscopy, computed tomography) and laboratory investigations, she was diagnosed with acute severe ulcerative colitis complicated with toxic megacolon. The medical treatment (first corticotherapy, then infliximab) has failed and the patient needed emergency colectomy. Based on the immunological mechanisms and the observation from other studies, Ixekizumab should be considered an etiology for new-onset inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Background: Intestinal parasites are one of the most common causes of diarrhea in children and it has almost global prevalence with high prevalence rates in developing countries. Objective: The aim of this study was to compare between the prevalence of Entamoeba histolytica (E. histolytica) and Giardia lamblia (G. lamblia) as a cause of diarrhea in children in AL-Kufa City, Iraq. Patients and methods: Four hundred children with age ranged between 1-10 years old that had diarrhea and were admitted to the General Hospital in AL-Kufa City from June 2021 to February 2022. Parasites were diagnosed according to stool microscopic examination. Results: Out of 400 children, there were 325 infected by parasites (190 E. histolytica and 135 G. lamblia), age group 4-6 yeas was the most infected with 80 and 54 cases by E. histolytica and G. lamblia respectively. The rural area was the highest infected than urban with 105 and 85 cases by E. histolytica respectively, and 90 and 45 by G. lamblia respectively. Conclusion: There were high prevalence of diarrheal infections in children caused by E. histolytica and G. lamblia, and the most infections were more in rural than urban. [ABSTRACT FROM AUTHOR]

Background: Diarrheal disease is considered as the second most common cause of death among under-5 children globally. Objective: The aim of this article is to determine mothers' knowledge and practices regarding diarrhea causes and principles of management. Materials and Methods: A cross-sectional study was conducted on 200 mothers of under-5 children who attended the pediatric outpatient department for diarrhea. The correlation between mothers' age and level of education with their knowledge regarding signs of dehydration and their awareness of the use of oral rehydration solution (ORS) and management of diarrhea was done. The χ2 test was used, and a P-value of 0.05 was considered significant. Results: Nearly half (45%) of the mothers believed intestinal infection caused that diarrhea, whereas (37.5%) blamed the teething process. Mothers rated the severity of diarrhea as increased frequency (70%), change in consistency (62.5%), foul smell stool (13.5%), and change in stool color (7%). The study showed that 45% of the mothers did not know any sign of dehydration and indicated poor mothers' adherence to ORS use (4%), despite their awareness of ORS (66.5%). The study showed a significant correlation between mothers' education and initial management of diarrhea at home (P <0.05), but not with their awareness of ORS or their knowledge about signs of dehydration. There was no significant relation between mothers' age and their awareness of ORS, their knowledge regarding the signs of dehydration, and their initial action to manage diarrhea at home. Conclusion: Most respondents lack satisfactory knowledge of diarrheal diseases. Therefore, mothers need health education to create a better attitude toward the prevention and management of diarrheal diseases. [ABSTRACT FROM AUTHOR]

The escalating prevalence of bacterial infections and the rapid emergence of multidrug-resistant Gram-negative bacterial pathogens highlight an urgent demand for effective antibacterial agents. In this study, we report our findings on IITR00210, a small molecule belonging to the nitrile class. The small molecule demonstrates broad-spectrum activity against bacterial pathogens, specifically against enteric pathogens, and exhibits antibiofilm activity. IITR00210 displays potent bactericidal activity against enteropathogens, resulting in a reduction of bacterial counts greater than 3 Log 10 CFU in time-kill kinetic assays. Mechanistic investigations revealed that IITR00210 induces bacterial cell envelope stress, leading to the alteration of the overall proton motive force (PMF). The disruption of PMF causes intracellular ATP dissipation and ultimately promotes cell death. The cell envelope stress generated in the presence of IITR00210 leads to a translational aberration. Importantly, IITR00210 exhibits a safe profile in in vitro and in vivo settings. The small molecule further showed potent intracellular antibacterial activity in polymorphonuclear cells infected with enteric pathogens and antiadhesion activity in mammalian cell lines. IITR00210 proves to be a promising therapeutic candidate, displaying a lack of stable resistance development, and it exhibited efficacy in the treatment of bacterial infections in a shigellosis murine model.

Background: Shigella sonnei has caused sexually transmitted enteric infections in men who have sex with men (MSM) in Vancouver. We recently observed a high rate of multidrug-resistant (MDR) S. sonnei bacteremia among persons experiencing homelessness (PEH). We aim to describe the wider epidemiology, clinical outcomes, and genomics of S. sonnei infections over time., Methods: A retrospective review of 163 patients with S. sonnei infections was undertaken from 2015 -2022. We collected demographic, clinical, and microbiological data over two time periods: historical (2015-2020) and recent (2021-2022). Severe shigellosis definition included hospitalization, bacteremia, or death. Whole genome sequencing was performed to identify genotype, infer relatedness, and predict antimicrobial resistance., Results: S. sonnei infections rose from 8.3 (historical-period) to 56.5 cases/year (recent-period). Over time, the primary population characteristics associated with shigellosis shifted from MSM (45, 98%) to PEH (86,77%). The population intersection between MSM and PEH historically and recently was similar and occurred in three (6%) and ten (9%) of patients, respectively. Severe shigellosis was significantly higher in the recent compared to historical period (69 [61%] versus 7 [14%], p<0.001). A dominant clone of MDR S. sonnei, 3.6.1.1.2 (CipR.MSM5), emerged with resistance to all first and second-line agents yet with susceptibility to ceftriaxone., Conclusion: We observed a substantial increase in severe shigellosis and shift from sexually transmitted S. sonnei infections in MSM to likely environmental transmission among PEH. More severe disease associated with the 3.6.1.1.2 clone of MDR S. sonnei in PEH could be a result of underlying vulnerabilities of the affected population., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Shigellosis continues to pose a significant public health problem in Africa; however, there is a lack of comprehensive knowledge regarding its prevalence, serogroup distribution, and antimicrobial resistance profiles. Therefore, the objective of this systematic review and meta-analysis was to determine the overall prevalence of Shigella, the distribution of species, and the patterns of antimicrobial resistance across Africa., Methods: Following PRISMA guidelines, a systematic search strategy was conducted using the PubMed, Web of Science and Scopus databases from January 31, 2024 to February 10, 2024. The study quality was assessed using the Joanna Briggs Institute checklist, and data were analyzed using the R statistical language and the R package 'meta'. The random effects model was employed to estimate the pooled prevalence, while heterogeneity was assessed using the I 2 statistic and prediction interval., Results: A total of 116 studies from 29 African countries were included in this meta-analysis, involving the examination of 99,510 samples. The overall pooled estimate of Shigella prevalence was determined to be 5.9% (95% CI: 4.9 - 7.0%). Regional prevalence showed prevalences of Southern Africa (6.9 [95% CI: 3.0 - 12.2%]), Northern Africa (6.7% [95% CI: 4.1 - 9.8%]), Eastern Africa (6.2% [95% CI: 4.9 - 7.6%]), Central Africa (4.5% [95% CI: 2.6 - 6.8%]) and Western Africa (4.0% [95% CI: 2.5 - 5.9%]). Shigella prevalence was found to be higher in children (6.6%, 95% CI: 3.2 - 11.1%) than in adults (3.6%, 95% CI: 1.6 - 6.3%). The most prevalent species was S. flexneri (53.6%, 95% CI: 46.1%-61.0%), followed by S. sonnei (11.5%, 95% CI: 7.7%-15.7%), S. dysenteriae (10.1%, 95% CI: 6.2 - 14.5%) and S. boydii (7.7%, 95% CI: 4.7 - 11.1%). Among the currently recommended first-line antibiotics, ciprofloxacin and ceftriaxone showed resistance prevalences of 10.0% (95% CI: 4.5%-16.9%) and 8.5% (95% CI: 2.4-16.9%) respectively., Conclusion: This review highlights the burden of shigellosis in Africa. S. flexneri remains the most prevalent species associated with shigellosis cases with S. sonnei being the second most dominant. The antimicrobial resistance patterns observed in the study suggest local antimicrobial patterns in choosing antibiotics for the treatment of Shigellosis., Recommendation: There is the need to explore alternative treatments for shigellosis with particular focus on vaccine development. There is also the need for more genomic epidemiology studies exploring the dissemination and risk of drug-resistant S. sonnei clones in Africa., (© 2024. The Author(s).)

We reviewed all diagnoses of Shigella species notified to the UK Health Security Agency from January 2016 to March 2023. An overall increase in notifications of shigellosis was seen between 2016 ( n = 415/quarter) and 2023 ( n = 1 029/quarter). However, notifications dramatically declined between March 2020 and September 2021 during the COVID-19 pandemic ( n = 208/quarter) highlighting the impact of travel and social distancing restrictions on transmission. S. sonnei diagnoses were more affected by lockdown restrictions than S. flexneri , most likely due to a combination of species-specific characteristics and host attributes. Azithromycin resistance continued to be associated with epidemics of sexually transmissible S. flexneri (adult males = 45.6% vs. adult females = 8.7%) and S. sonnei (adult males = 59.5% vs. adult females = 14.6%). We detected resistance to ciprofloxacin in S. sonnei from adult male cases not reporting travel at a higher frequency (79.4%) than in travel-associated cases (61.7%). Extensively drug-resistant Shigella species associated with sexual transmission among men almost exclusively had ESBL encoded by bla CTX-M-27 , whereas those associated with returning travellers had bla CTX-M-15 . Given the increasing incidence of infections and AMR, we recommend that enhanced surveillance is used to better understand the impact of travel and sexual transmission on the acquisition and spread of MDR and XDR Shigella species.

The range of differential diagnostic search in the development of hemorrhagic colitis (hemocolitis) is wide enough and includes infectious and non-infectious factors. Purpose: clinical, laboratory and etiological analysis of bacterial diarrhea occurring with hemorrhagic colitis in the infectious diseases department.Materials and methods: a retrospective study of 141 case histories of those hospitalized in the infectious diseases department of the2 Children's City Clinical Hospital No. 9 named after G.N. Speransky of Moscow in 2019—2021 patients with clinical picture of hemocolitis. Hemocolitis was determined on the basis of macroscopic and microscopic signs (in scatology — mucus, leukocytes, erythrocytes) signs. All patients underwent routine laboratory examinations. The etiology was verified using modern methods of laboratory diagnostics (bacteriological analysis of feces, Latex test, ICA, ELISA, PCR, IHR).Results. There were 137 patients with infectious hemocolitis. Inflammatory bowel disease was diagnosed in 3 children, anus fissure — in 1 child. Young children under 3 years of age prevailed (77%). The etiology of infectious hemocolitis was deciphered in 47 patients (34%). Salmonellosis (36%) and shigellosis (36%) prevailed. Campylobacteriosis, clostridiosis-dificile and klebsiellosis accounted for 11%, 9% and 6% of cases, respectively. Yersiniosis was detected in 1 child at the age of 5 months. The severe form was found in 5.8% of cases, in most cases with shigellosis. Symptoms of intoxication and febrile fever were expressed in all patients, vomiting — in 28.5%, abdominal pain — in 94%, mesenteric adenitis on ultrasound — in 15%, diarrhea with a frequency of more than 5 times a day — in 84%, dehydration — in 64%, intercurrent diseases (ARVI, pneumonia) — in 41.3% of cases. Inflammatory changes in infectious hemocolitis were manifested by an increase in C-reactive protein in 71% (23.91 ± 24.17 mg/l), leukocytosis — in 69% (11.58 ± 3.52 х103 / μl), thrombocytosis — in 26%, an increase in the relative number of stab neutrophils in the general blood test in 78% of cases (10.95 ± 0.4%).Conclusions. Differential diagnostic search in the development of hemocolitis should include modern diagnostic methods, if necessary, additional instrumental studies and specialist consultations to exclude inflammatory bowel diseases.

Background: Shigellosis is an infectious intestinal disease common in rural communities. In developing countries, shigellosis is caused predominantly by Shigella flexneri and has been determined as a major cause of morbidity and mortality. Objective: The study investigates the anti-biofilm, anti-microbial, and anti-shigellosis activity of a designed formulation. Materials and methods: The potential of the formulation against S. flexneri (MTCC 1457) was investigated using a well-diffusion assay. Further, the effect of the designed formulation on bacterial growth and biofilm formation was analyzed by the spectrophotometry method. Anti-quorum sensing activity was analyzed using Chromobacterium violaceum CV026, a bacterial strain. Finally, the cytotoxicity of the formulation was examined by using cell line and brine shrimp lethality assay. Results: The MIC value of the aqueous extract of the formulation was 2.4 mg ml−1 and an inhibitory zone of 23 mm was observed. On the other side, the formulation significantly inhibited the bacterial growth, biofilm formation (23.78%), violacein inhibition (27.68%) at 0.6 mg ml−1 concentration (did not significantly affect the growth curves) and was found non-toxic in cell assay and brine shrimp lethality assay. Conclusion: According to the result obtained, the designed formulation was found effective and non-toxic, so it can be used to treat shigellosis and Shigella-related infections.

No doubts that shigellosis severity directly depends on the spread of the gut specific lesion. There are some data published on the basis of autopsy records and pointing to shigella caused lesion spreading both to colon and ileum in adult cases especially in those older than 60 y.o. or with any immunosuppressive premorbid background. Obviously, the gut mucosa condition determines the local resistance potential and moreover it's shown that in shigellosis cases, the histologic pattern of gut mucosa depends on quantity and quality of neutrophils, extremely important to control the intensity of agent invasion. Viral infections with concomitant neutropenia are commonly considered as immune suppressive conditions. As to Herpes virus infection, it's well known as the large mucosa lesion disease that can subsequently lead to aggravation of any forthcoming acute bacterial infection. The paper suggests the description of shigellosis case confirmed with the use of PCR test (PCR kit Amplisens All-bacto-screen-FL Lab, Interlabservice) and developed by young woman with unfavorable premorbid condition. The disease course turned to be severe and complicated by the peritonitis development. The aggravating factors in the proposed case were likely such immune modulating concurrent conditions as Herpes virus infection and pregnancy. The clinical example demonstrates that young people can develop severe complicated shigellosis course given burdened premorbid background availability.

This article discusses the misdiagnosis and management of Hirschsprung-associated enterocolitis (HAEC) in infants. HAEC is a condition characterized by intestinal inflammation and can occur in patients with Hirschsprung Disease (HD) or as the onset of previously undetected HD. The article emphasizes the importance of recognizing red flags for HAEC, such as a history of HD, delayed passage of meconium, and signs of sepsis. Prompt interruption of enteral feeding and treatment with antibiotics are recommended to improve prognosis. The article concludes by highlighting the need for further research on effective therapies and improved diagnostic criteria and treatment guidelines for HAEC. [Extracted from the article]

Background: Shigella infections cause inflammation, which has been hypothesized to mediate the associations between Shigella and child development outcomes among children in low-resource settings. We aimed to assess whether early life inflammation and Shigella infections affect school-aged growth and cognitive outcomes from 6–8 years of age. Methodology/principal findings: We conducted follow-up assessments of anthropometry, reasoning skills, and verbal fluency in 451 children at 6–8 years of age in the Brazil, Tanzania, and South Africa sites of MAL-ED, a longitudinal birth cohort study. We estimated the associations between Shigella burden and inflammation with linear growth at 2, 5, and 6–8 years of age, and with the cognitive test scores using linear regression and adjusting for potential confounding variables. We also assessed whether inflammation mediated the associations between Shigella and school-aged outcomes using a regression-based approach to mediation analysis. A high prevalence of Shigella was associated with a 0.32 (95% CI: 0.08, 0.56) z-score lower height-for-age z-score (HAZ) at 6–8 years compared to a low prevalence of Shigella. Intestinal inflammation had a smaller association with HAZ at 6–8 years. Shigella burden had small and consistently negative associations with cognitive outcomes in Brazil and Tanzania, but not South Africa, and the estimates were not statistically significant. Systemic inflammation was strongly associated with lower verbal fluency scores in Brazil (semantic fluency z-score difference: -0.57, 95% CI: -1.05, -0.10; phonemic fluency z-score difference: -0.48, 95% CI: -0.93, -0.03). There was no evidence that intestinal inflammation mediated the association between Shigella and HAZ or cognitive outcomes. Conclusions/significance: While Shigella infections were consistently associated with long-term deficits in linear growth, the estimates of the negative associations between Shigella and cognitive outcomes were imprecise and only observed in the Brazil and Tanzania sites. Systemic inflammation was strongly associated with lower semantic and phonemic fluency scores in Brazil only, highlighting the site-specificity of effects. Author summary: Shigella infections are common among children in low-resource settings and cause inflammation, which may contribute to poor child development outcomes. We studied children from birth to 6–8 years of age in Brazil, Tanzania, and South Africa to assess whether Shigella infections and markers of inflammation in the first 2 years of life were associated with child development outcomes at school age, including height and cognitive assessment scores. Shigella infections were consistently associated with long-term deficits in linear growth. However, the associations between Shigella and cognitive outcomes were smaller, not statistically significant, and inconsistent across the three sites. There was no evidence that inflammation caused by Shigella explained the associations between Shigella and school-aged outcomes. Systemic inflammation was strongly associated with lower cognitive assessment scores in Brazil but not in the other sites, highlighting the differences in determinants of child development across settings. Quantifying the impact and understanding mechanisms for the effect of early life exposures to Shigella on long-term cognitive outcomes remains challenging. [ABSTRACT FROM AUTHOR]

To eliminate the influences of excipients and interference of dead bacterial DNA on the detection of Escherichia coli, Pseudomonas aeruginosa, Salmonella paratyphoid B, and Shigella dysentery in live Bacillus licheniformis capsules, a polymerase chain reaction (PCR) method with high sensitivity and specificity was established. By combining bromide with propidium monoazide (PMA) -real-time quantitative PCR (qPCR) with microporous membrane filtration, excipients were removed, the filtrate was collected, and the bacteria were enriched using the centrifugal method. The optimal PMA working concentration, dark incubation time, and exposure time were determined. Specific E. coli, P. aeruginosa, S. paratyphoid B, and S. dysentery primers were selected to design different probes and a multiplex qPCR reaction system was established. The PMA-qPCR method was verified using different concentrations of dead and live bacteria. This method is efficient and accurate and can be widely applied to the detection of aforementioned pathogenic bacterial strains in live Bacillus licheniformis products. [ABSTRACT FROM AUTHOR]

Background: Human immunodeficiency virus (HIV) and enteric parasite co-infection not only aggravates the clinical symptoms of parasites but also accelerates acquired immunodeficiency syndrome (AIDS) progression. However, co-infection research on men who have sex with men (MSM), the predominant high-risk population of HIV/AIDS in China, is still limited. In this study, we investigated the epidemiology of enteric parasites, risk factors, and associations with clinical significance in an MSM HIV/AIDS population in Heilongjiang Province, northeast China. Methods: We recruited 308 MSMs HIV/AIDS patients and 199 HIV-negative individuals in two designated AIDS hospitals in Heilongjiang between April 2016 and July 2017. Fresh stool samples were collected. DNA extraction, molecular identification, and genotyping of Cryptosporidium species, Entamoeba histolytica, Cyclospora cayetanensis, Enterocytozoon bieneusi, and Blastocystis hominis were performed. Fourteen diarrhea-related pathogens were examined to exclude the influence of other bacterial pathogens on diarrhea incidence. Results: 31.5% of MSM HIV/AIDS participants were infected with at least one parasite species, a significantly higher proportion than that found in the HIV-negative individuals (2.5%). E. bieneusi presented the highest prevalence, followed by B. hominis, E. histolytica, Cryptosporidium spp., and C. cayetanensis. Warm seasons were the risk factor for parasitic infections in this population [odds ratio (OR) = 2.6, 95% CI: 1.47–4.57]. In addition, these individuals showed a higher proportion (35.8%) of present diarrhea (PD) compared with men who have sex with women (MSW) with HIV/AIDS (16.7%). The infection proportions of both Cryptosporidium spp. and E. histolytica were significantly higher in the PD. E. bieneusi infection was more prevalent in the historic diarrhea (HD) group. CD4+ T cell counts in the MSM patients with the above three parasites were significantly lower. New species and genotypes were found, and MSM patients had a wider range of species or genotypes. Conclusions: Enteric parasitic infection was prevalent in the MSM HIV/AIDS population, especially in patients with present diarrhea during warm seasons. E. histolytica and B. hominis should also be considered high-risk parasites for opportunistic infections in AIDS patients in addition to Cryptosporidium spp. Author summary: Human immunodeficiency virus (HIV) and enteric parasite co-infection not only aggravates the clinical symptoms of parasites but also accelerates acquired immunodeficiency syndrome (AIDS) progression. In China, despite a large number of HIV-infected people, the data regarding co-infection with enteric intracellular parasites in this population is still sparse. In the present study, we investigated the epidemiology of Cryptosporidium spp., Enterocytozoon bieneusi, Blastocystis hominis, Entamoeba histolytica and Cyclospora cayetanensis in 384 HIV/AIDS including 308 MSM HIV/AIDS populations in two designated AIDS hospitals in Heilongjiang Province, North-East China between April 2016 and July 2017 by polymerase chain reaction. We also try to track the possible sources, risk factors, and any associations, with clinical significance, of human parasitic infections. Such knowledge will provide insights into prognosis, treatment, and preventive strategies against infections with such pathogens. The findings in this study have important implications for public health, the control of AIDS progression and control of parasitic infections. [ABSTRACT FROM AUTHOR]

Globally, obesity is a serious health concern that causes numerous diseases, including type 2 diabetes, hypertension, cardiovascular diseases, etc. Medicinal plants have been used to aid in weight loss since ancient times. Thus, this research is focused on the exploration of pancreatic lipase inhibitory activity and secondary metabolite profiling of Bergenia ciliata, Mimosa pudica, and Phyllanthus emblica, selected based on an ethnobotanical survey. The lipase inhibition was investigated using 4-nitrophenyl butyrate (p-NPB) as a substrate. To uncover further therapeutic potentials of these medicinal plants, antimicrobial activity and minimum inhibitory concentration (MIC) of the extracts were also determined. The ethyl acetate plant extracts showed higher antimicrobial activity against Staphylococcus aureus, Escherichia coli, Salmonella typhi, and Shigella sonnei. The MIC of ethyl acetate extracts of medicinal plants considered in this study ranges from 1.56 to 6.25 mg/mL. The hexane fraction of Mimosa pudica and Phyllanthus emblica showed a higher lipase inhibitory activity as compared to others, with IC50 values of 0.49 ± 0.02 and 2.45 ± 0.003 mg/mL, respectively. In the case of Bergenia ciliata, the methanolic extract inhibited lipase more effectively than others, with an IC50 value of 1.55 ± 0.02 mg/mL (IC50 value of orlistat was 179.70 ± 3.60 µg/mL). A mass spectrometry analysis of various solvent/solvent partition fractions (extracts) revealed 29 major secondary metabolites. The research offers a multitude of evidence for using medicinal plants as antiobesity and antimicrobial agents. [ABSTRACT FROM AUTHOR]

Shigellosis represents a major public health problem worldwide. The morbidity of the disease, especially in children in developing countries, together with the increase of antimicrobial resistance make a vaccine against Shigella an urgent medical need. Several vaccines under development are targeting Shigella lipopolysaccharide (LPS), whose extreme diversity renders necessary the development of multivalent vaccines. Immunity against Shigella LPS can elicit antibodies capable of killing bacteria in a serotype-specific manner. Therefore, although a correlation of protection against shigellosis has not been established, demonstration of vaccine-elicited antibody bactericidal activity may provide one means of vaccine protection against Shigella. To facilitate Shigella vaccine development, we have set up a high-throughput serum bactericidal assay based on luminescence readout (L-SBA), which has been already used to determine the functionality of antibodies against S. sonnei in multiple clinical trials. Here we present the setup and intra-laboratory characterization of L-SBA against three epidemiologically relevant Shigella flexneri serotypes using human sera. We assessed the linearity, repeatability and reproducibility of the method, demonstrating high assay specificity to detect the activity of antibodies against each homologous strain without any heterologous aspecificity against species-related and non-species-related strains; this assay is ready to be used to determine bactericidal activity of clinical sera raised by multivalent vaccines and in sero-epidemiological studies. [ABSTRACT FROM AUTHOR]

Clostridioides difficile infections (CDI) are traditionally attributed to adults, but children can also be affected. In children, when indicated, laboratory diagnosis of CDI should be combined with testing for the presence of other gastrointestinal pathogens that are a common cause of diarrhoea, particularly in younger children. This was also confirmed in a cohort of 652 children with diarrhoea admitted to the Motol University Hospital, where 71 PCR positive tests for toxigenic C. difficile revealed another infectious cause in 33.8% (n = 24) by multiplex PCR. The detection of toxigenic C. difficile by PCR does not distinguish between colonisation and active infection, so the stool sample with a positive PCR test should be tested also for the presence of toxins A/B. Of the above 71 PCR-positive stools, 65 were further tested with the immunoenzymatic assay, and simultaneous positivity of C. difficile GDH and A/B toxins was detected only in 44.6% of stools (n = 24), but in almost half of these samples (n = 10), another infectious cause of diarrhoea was detected. In recurrent CDI, as in the first episode, emphasis should be placed on combined laboratory diagnostics to exclude co-infection with another intestinal pathogen or colonization with C. difficile. Compared with adult inpatients, available clinical data in children are limited and further prospective studies are needed to determine the prevalence of CDI and the efficacy of treatment regimens. [ABSTRACT FROM AUTHOR]

In recent years, there has been a resurgence of interest in the development of vaccines against I Shigella i driven by the growing awareness of the impact of this pathogen on global health. This is now being assessed in a Phase 3 study in China and is the most advanced I Shigella i vaccine and, as far as we are aware, the only multivalent I Shigella i vaccine to be assessed in a Phase 3 study to date [[17]]. Finally, we provide, in a separate article, a description of the I Shigella i vaccine pipeline putting the various current candidates covered in this Special Issue in context with vaccines whose development has been halted for one or other reason [[31]]. As a result, the development of many I Shigella i vaccines has been described piecemeal over several years and in multiple papers, none providing the full story of the vaccine they relate to. [Extracted from the article]

Shigella is the leading cause of global diarrheal deaths that currently lacks a licensed vaccine. Shigellosis drives antimicrobial resistance and leads to economic impact through linear growth faltering. Today, there is a robust pipeline of vaccines in clinical development which are broadly divided into parenteral glycoconjugate vaccines, consisting of O-antigen conjugated to carrier proteins, and oral live attenuated vaccines, which incorporate targeted genetic mutations seeking to optimize the balance between reactogenicity, immunogenicity and ultimately protection. Proof of efficacy has previously been shown with both approaches but for various reasons no vaccine has been licensed to date. In this report, we outline the requirements for a Shigella vaccine and describe the current pipeline in the context of the many candidates that have previously failed or been abandoned. The report refers to papers from individual vaccine developers in this special supplement of Vaccines which is focused on Shigella vaccines. Once readouts of safety and immunogenicity from current trials of lead candidate vaccines among the target population of young children in low- and middle-income countries are available, the likely time to licensure of a first Shigella vaccine will become clearer. [ABSTRACT FROM AUTHOR]

Zoonotic Cryptosporidium parvum infections are mainly caused by IIa and IId subtypes. As most biological characterizations have been performed on IIa subtypes, the biological and genetic characteristics of IId subtypes in China are not clear. We evaluated the infection and genetic characteristics of IId isolates in interferon-γ-knockout mice using qPCR to quantify oocyst shedding, histological examination to monitor pathological changes and comparative genomic analyses to identify infectivity and virulence-associated differences. Compared with the reference IIa isolate, mice infected with the IId isolates had significantly higher and longer oocyst shedding and lower body weight gain. In addition, the four IId isolates examined differed significantly in infectivity (as indicated by the half infective dose), oocyst shedding duration, and pathogenicity. Comparative genomic analysis indicated that the IId isolates had three more subtelomeric genes than the reference IIa isolate and 5385–5548 nucleotide substitutions, with the hypervariable genes mostly in two blocks on chromosome 1. In contrast, the four IId isolates differed from each other by 77–1,452 nucleotides, with virulence-associated sequence differences mainly in nine genes within a 28-kb block on chromosome 6. These data indicate the newly emerged C. parvum IId subtypes in China have high animal infectivity and unique genomic characteristics. Author summary: Cryptosporidiosis is the most important waterborne disease in industrialized nations and a primary cause of severe diarrhea in children in low- and middle-income countries. While the IIa subtype family of Cryptosporidium parvum is responsible for most zoonotic cryptosporidiosis, its IId subtype family has emerged in China in recent years. To understand the biological differences between the two major zoonotic subtype families, we have compared the infection patterns, virulence, and genetic characteristics of IIa and IId isolates using a newly established mouse model and whole genome sequencing. We have shown that IId isolates induce significantly higher infection intensity, longer infection duration, and more severe pathogenicity than the reference IIa isolate. They also have three more invasion-associated genes and substantial nucleotide sequence differences. In contrast, the four IId isolates with different virulence differ from each other mainly in sequences of nine genes within a small area on chromosome 6. We conclude that C. parvum isolates in China have high infectivity and unique genomic characteristics, and the productive infection model developed in the study should be useful in evaluations of potential therapeutics and studies of pathogenesis of C. parvum. [ABSTRACT FROM AUTHOR]

Background: Enterotoxigenic Escherichia coli (ETEC) is one of the top aetiologic agents of diarrhea in children under the age of 5 in low-middle income countries (LMICs). The lack of point of care diagnostic tools for routine ETEC diagnosis results in limited data regarding the actual burden and epidemiology in the endemic areas. We evaluated performance of the novel Rapid LAMP based Diagnostic Test (RLDT) for detection of ETEC in stool as a point of care diagnostic assay in a resource-limited setting. Methods: We conducted a cross-sectional study of 324 randomly selected stool samples from children under 5 presenting with moderate to severe diarrhea (MSD). The samples were collected between November 2012 to September 2013 at selected health facilities in Zambia. The RLDT was evaluated by targeting three ETEC toxin genes [heat labile toxin (LT) and heat stable toxins (STh and STp)]. Quantitative PCR was used as the "gold standard" to evaluate the diagnostic sensitivity and specificity of RLDT for detection of ETEC. We additionally described the prevalence and seasonality of ETEC. Results: The study included 324 participants, 50.6% of which were female. The overall prevalence of ETEC was 19.8% by qPCR and 19.4% by RLDT. The children between 12 to 59 months had the highest prevalence of 22%. The study determined ETEC toxin distribution was LT 28/321(9%), ST 18/321(6%) and LT/ST 16/321(5%). The sensitivity and specificity of the RLDT compared to qPCR using a Ct 35 as the cut-off, were 90.7% and 97.5% for LT, 85.2% and 99.3% for STh and 100% and 99.7% for STp, respectively. Conclusion: The results of this study suggest that RLDT is sufficiently sensitive and specific and easy to implement in the endemic countries. Being rapid and simple, the RLDT also presents as an attractive tool for point-of-care testing at the health facilities and laboratories in the resource-limited settings. Author summary: ETEC is one of the top causes of diarrheal diseases in low and middle income countries. The advancement of molecular diagnosis has made it possible to accurately detect ETEC in endemic areas. However, the complexity, infrastructure and cost implication of these tests has made it a challenge to routinely incorporate them in health facilities in endemic settings. The ETEC RLDT is a simple and cost-effective molecular tool that can be used to screen for ETEC in resource limited settings. Here, we described the performance of the RLDT against a qPCR as the gold standard. Our findings showed that the ETEC RLDT performs comparable to the qPCR and would be a suitable screening tool in health facilities in recourse limited settings. [ABSTRACT FROM AUTHOR]

Shigella causes moderate to severe diarrhea or dysentery after invading the colon mucosa. Long Pentraxin 3 (PTX3) is recognized as the humoral component of the innate immune response to bacterial pathogens. We examined the interplay between levels of PTX3 and levels of anti-Shigella lipopolysaccharide (LPS) and anti-Shigella type 3 secretion system protein-IpaB antibodies in children during acute shigellosis and after recovery. PTX3 concentrations in serum and stool extracts were determined by sandwich ELISA using commercial anti-PTX3 antibodies. Serum IgG, IgM, and IgA anti-S. sonnei LPS or anti-S. sonnei IpaB were measured using in house ELISA. Children with acute shigellosis (n = 60) had elevated PTX3 levels in serum and stools as compared with recovered subjects (9.6 ng/mL versus 4.7 ng/mL, p < 0.009 in serum and 16.3 ng/g versus 1.1 ng/g in stool, p = 0.011). Very low levels of PTX3 were detected in stools of healthy children (0.3 ng/g). Increased serum levels of PTX3 correlated with high fever accompanied by bloody or numerous diarrheal stools characteristic of more severe shigellosis while short pentraxin; C-Reactive Protein (CRP) did not show such a correlation. PTX3 decreased in convalescence while anti-Shigella antibodies increased, switching the response from innate to adaptive toward the eradication of the invasive organism. These data can inform the development of Shigella vaccines and treatment options. [ABSTRACT FROM AUTHOR]

Lethal infectious disease epidemics have historically occurred in military, refugee and mining camps where crowded conditions promote the spread of enteric, respiratory and insect‐borne infections. The early history of gold mines around Palmer River, Queensland in the 1870s, Kalgoorlie, Western Australia in the 1890s and Papua on the island of New Guinea in the 1910s are recounted specifically as it relates to infectious disease deaths. Despite large diagnostic gaps, it is likely that malaria was the predominant problem in Palmer River, typhoid in Kalgoorlie and bacillary dysentery in Papua. Nearly two‐thirds of all recorded deaths in the Palmer River district from 1873 to 1883 were due to infections, predominately 'fevers'. Typhoid fever likely killed >2000 Australians in the early phases of the Western Australian goldfields in the 1890s. Severe dysentery outbreaks killed up to a majority of the local workforce in the Lakekema goldfields of Papua resulting in the colonial authorities stopping mining activity in the second decade of the 20th century. In the absence of public health measures and specific chemotherapy, large mortality rates in miners reflected the over‐riding economic drivers of gold miners and their lack of any understanding of microbial disease and its interruption by public health measures. Similar infectious disease epidemics are likely to reoccur when large numbers of impoverished miners use low‐technology methods to work alluvial gold deposits in conflict areas as has been seen in modern Africa. [ABSTRACT FROM AUTHOR]

Enzymes from pathogens often modulate host protein post-translational modifications (PTMs), facilitating survival and proliferation of pathogens. Shigella virulence factors IpaJ and IcsB induce proteolytic cleavage and lysine fatty acylation on host proteins, which cause Golgi stress and suppress innate immunity, respectively. However, it is unknown whether host enzymes could reverse such modifications introduced by pathogens' virulence factors to suppress pathogenesis. Herein, we report that SIRT2, a potent lysine defatty-acylase, is upregulated by the transcription factor CREB3 under Golgi stress induced by Shigella infection. SIRT2 in turn removes the lysine fatty acylation introduced by Shigella virulence factor IcsB to enhance host innate immunity. SIRT2 knockout mice are more susceptible to Shigella infection than wildtype mice, demonstrating the importance of SIRT2 to counteract Shigella infection. Here the authors revealed a role for the protein deacetylase SIRT2 in Golgi stress, particularly induced by bacterial infection. Shigella secrete effector proteins such as IcsB, which transfers fatty acyl groups to modify host proteins to evade host immune surveillance. The upregulated SIRT2 counteracts this function by removing the fatty acyl groups and enhancing the killing of Shigella. [ABSTRACT FROM AUTHOR]

Rotaviruses (RVs) are one of the main causes of severe gastroenteritis, diarrhea, and death in children and young animals. While suckling mice prove to be highly useful small animal models of RV infection and pathogenesis, direct visualization tools are lacking to track the temporal dynamics of RV replication and transmissibility in vivo. Here, we report the generation of the first recombinant murine-like RV that encodes a Nano-Luciferase reporter (NLuc) using a newly optimized RV reverse genetics system. The NLuc-expressing RV was replication-competent in cell culture and both infectious and virulent in neonatal mice in vivo. Strong luciferase signals were detected in the proximal and distal small intestines, colon, and mesenteric lymph nodes. We showed, via a noninvasive in vivo imaging system, that RV intestinal replication peaked at days 2 to 5 post infection. Moreover, we successfully tracked RV transmission to uninoculated littermates as early as 3 days post infection, 1 day prior to clinically apparent diarrhea and 3 days prior to detectable fecal RV shedding in the uninoculated littermates. We also observed significantly increased viral replication in Stat1 knockout mice that lack the host interferon signaling. Our results suggest that the NLuc murine-like RV represents a non-lethal powerful tool for the studies of tissue tropism and host and viral factors that regulate RV replication and spread, as well as provides a new tool to facilitate the testing of prophylactic and therapeutic interventions in the future. [ABSTRACT FROM AUTHOR]

Enterotoxigenic Escherichia coli (ETEC) is a primary causative agent of diarrhea in travelers and young children in low-to-middle-income countries (LMICs). ETEC adhere to intestinal epithelia via colonization factors (CFs) and secrete heat-stable toxin (ST) and/or heat-labile toxin (LT), causing dysregulated cellular ion transport and water secretion. ETEC isolates often harbor genes encoding more than one CF that are targets as vaccine antigens. CFA/I is a major CF that is associated with ETEC that causes moderate-to-severe diarrhea and plays an important role in pathogenesis. The Global Enteric Multicenter Study finding that 78% of CFA/I-expressing ETEC also encode the minor CF CS21 prompted investigation of the combined role of these two CFs. Western blots and electron microscopy demonstrated growth media-dependent and strain-dependent differences in CFA/I and CS21 expression. The critical role of CFA/I in adherence by ETEC strains expressing CFA/I and CS21 was demonstrated using the human enteroid model and a series of CFA/I- and CS21-specific mutants. Furthermore, only anti-CFA/I antibodies inhibited adherence by global ETEC isolates expressing CFA/I and CS21. Delivery of ST and resulting cGMP secretion was measured in supernatants from infected enteroid monolayers, and strain-specific ST delivery and time-dependent cGMP production was observed. Interestingly, cGMP levels were similar across wildtype and CF-deficient strains, reflecting a limitation of this static aerobic infection model. Despite adherence by ETEC and delivery of ST, the enteroid monolayer integrity was not disrupted, as shown by the lack of decrease in transepithelial electrical resistance and the lack of IL-8 cytokines produced during infection. Taken together, these data demonstrate that targeting CFA/I in global clinical CFA/I-CS21 strains is sufficient for adherence inhibition, supporting a vaccine strategy that focuses on blocking major CFs. In addition, the human enteroid model has significant utility for the study of ETEC pathogenesis and evaluation of vaccine-induced functional antibody responses. Author summary: Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea in travelers and in young children in low-to-middle-income countries (LMIC). ETEC infects the small intestine using surface located adhesins called colonization factors (CFs) and delivers toxins to the intestine. These CFs are optimal targets for ETEC vaccine development for the induction of colonization-blocking responses. In the current study we investigated the role of 2 CFs, namely CFA/I and CS21 when they are simultaneously expressed in geographically diverse ETEC clinical isolates, in infection using the human enteroid model. This system is the most human relevant and sensitive model to study enteric pathogens. We determined that CFA/I was important for adherence to the human enteroid by ETEC strains expressing CFA/I and CS21. Strain-specific levels of toxin delivery were quantified but there was no difference between wildtype and CF-deficient mutant strains. This result highlights the opportunity to consider the effects of intestinal movement and oxygen levels in the model. Infected enteroids did not have disrupted cell monolayers or produce inflammatory signals. This study supports the strategy to target CFA/I in ETEC vaccine development and underscores the enteroid as a significant model system. [ABSTRACT FROM AUTHOR]

Background: Mild encephalitis with reversible splenial lesion of the corpus callosum (MERS) is a clinical/radiological syndrome characterized by hyperintense signal changes in the splenium of the corpus callosum visible on diffusion weighted imaging (DWI) in the brain Magnetic Resonance Imaging (MRI) associated with various neurological symptoms. Progression is usually favorable with disappearance of the MRI brain lesion and regression of clinical symptoms over a few days to a few weeks. The exact pathophysiology remains unclear. MERS can be associated with various pathogens.Case Presentation: We report here a paediatric case of MERS associated with Shigella flexneri infection. A five-year-old boy with no relevant past medical history presented with symptoms such as headache, fever, profuse diarrhea and hallucinations. A brain Magnetic Resonance Imaging performed on Day 2 of the symptoms revealed hyperintense signal changes of the splenium of the corpus callosum in T2 FLAIR sequence. This infection had a favorable outcome after antibiotic therapy. No further recurrence of symptoms was observed and a follow-up clinical examination eight weeks later was normal. A follow-up brain Magnetic Resonance Imaging three months after discharge was also normal and the hyperintense signal changes of the splenium of the corpus callosum had disappeared completely.Conclusions: MERS is a clinical/radiological syndrome with a generally good prognosis. We believe that this is the first description of a case of Shigella-associated MERS. It is useful to know about this condition to help distinguish it from acute disseminated encephalomyelitis. [ABSTRACT FROM AUTHOR]

Antibiotic treatment plays an essential role in preventing Shigella infection. However, incidences of global rise in antibiotic resistance create a major challenge to treat bacterial infection. In this context, there is an urgent need for newer approaches to reduce S. flexneri burden. This study largely focuses on the role of the herbal compound capsaicin (Caps) in inhibiting S. flexneri growth and evaluating the molecular mechanism behind bacterial clearance. Here, we show for the first time that Caps inhibits intracellular S. flexneri growth by inducing autophagy. Activation of autophagy by Caps is mediated through transcription factor TFEB, a master regulator of autophagosome biogenesis. Caps induced the nuclear localization of TFEB. Activation of TFEB further induces the gene transcription of autophagosomal genes. Our findings revealed that the inhibition of autophagy by silencing TFEB and Atg5 induces bacterial growth. Hence, Caps-induced autophagy is one of the key factors responsible for bacterial clearance. Moreover, Caps restricted the intracellular proliferation of S. flexneri-resistant strain. The efficacy of Caps in reducing S. flexneri growth was confirmed by an animal model. This study showed for the first time that S. flexneri infection can be inhibited by inducing autophagy. Overall observations suggest that Caps activates TFEB to induce autophagy and thereby combat S. flexneri infection. [ABSTRACT FROM AUTHOR]

• New-onset diarrhea was common (1.7/100 inpatient-days, 0.6/100 LTCF-resident-days) • Stool specimen collection and Clostridioides difficile testing frequency was low (32%) • Low C. difficile testing frequency is indicative of potential C. difficile infection (CDI) underdiagnosis • Further studies are needed to confirm the extent of CDI underdiagnosis This study aimed to determine the stool specimen collection and Clostridioides difficile (C. difficile) testing frequency from inpatients and long-term care facility (LTCF) residents with new-onset diarrhea. A cross-sectional study was conducted in all wards of 9 adult hospitals (3532 beds) and 14 LTCFs (1205 beds) in Louisville, Kentucky to identify new-onset diarrhea (≥3 loose stools in the past 24 h and not present in the preceding 24 h) among Louisville adults via electronic medical record review, nurse interviews, and patient interviews during a 1–2 week observation period in 2018–2019. Among Louisville-resident inpatients, 167 patients with 9731 inpatient-days had new-onset diarrhea (1.7/100 inpatient-days). Stool specimens were collected from 32% (53/167); 12 (23%) specimens were laboratory-confirmed for C. difficile infection (CDI) (12.3 cases/10,000 inpatient-days). Among LTCF residents, 63 with 10,402 LTCF resident-days had new-onset diarrhea (0.6/100 LTCF resident-days). Stool specimens were collected from 32% (20/63); 9 (45%) specimens were laboratory-confirmed for CDI (8.6 cases/10,000 LTCF resident-days). New-onset diarrhea was common among inpatients and LTCF residents. Only one-third of patients with new-onset diarrhea had a stool specimen collected and tested for C. difficile —indicative of a potential CDI underdiagnosis—although, further studies are needed to confirm the extent of CDI underdiagnosis. [ABSTRACT FROM AUTHOR]