Cause Of Diarrhea Research Articles

Clinical decision support for gastrointestinal panel testing.

This study aimed to assess the impact of clinical decision support (CDS) to improve ordering of multiplex gastrointestinal polymerase chain reaction (PCR) testing panel ("GI panel"). Single-center, retrospective, before-after study. Tertiary care Veteran's Affairs (VA) Medical Center provides inpatient, outpatient, and residential care. All patients tested with a GI panel between June 22, 2022 and April 20, 2023. We designed a CDS questionnaire in the electronic medical record (EMR) to guide appropriate ordering of the GI panel. A "soft stop" reminder at the point of ordering prompted providers to confirm five appropriateness criteria: 1) documented diarrhea, 2) no recent receipt of laxatives, 3) C. difficile is not the leading suspected cause of diarrhea, 4) time period since a prior test is >14 days or prior positive test is >4 weeks and 5) duration of hospitalization <72 hours. The CDS was implemented in November 2022. Compared to the pre-implementation period (n = 136), fewer tests were performed post-implementation (n = 92) with an IRR of 0.61 (p = 0.003). Inappropriate ordering based on laxative use or undocumented diarrhea decreased (IRR 0.37, p = 0.012 and IRR 0.25, p = 0.08, respectively). However, overall inappropriate ordering and outcome measures did not significantly differ before and after the intervention. Implementation of CDS in the EMR decreased testing and inappropriate ordering based on use of laxatives or undocumented diarrhea. However, inappropriate ordering of tests overall remained high post-intervention, signaling the need for continued diagnostic stewardship efforts.

Epidemiologia molecular do Clostridioides difficile obtido de amostras de fezes de animais selvagens no Brasil

ABSTRACT: Clostridioides difficile is a strictly anaerobic, spore-forming Gram-positive bacterium associated with diarrhea, known as C. difficile infection (CDI). In domestic animals, C. difficile is considered an important pathogen mostly in pigs and horses, but there are also reports in other domestic species. In wild animals, the epidemiology of C. difficile is largely unknown, and the role of the bacterium as a cause of diarrhea is unclear. The aim of this study was to determine the prevalence of C. difficile in the feces of wild animals referred to the Center of Medicine and Research in Wild Animals (CEMPAS). Fecal samples obtained from 100 animals of 34 different species were subjected to qPCR for the detection of the C. difficile 16S rRNA gene and two major toxin genes (tcdA and tcdB) and to anaerobic bacterial isolation. A total of 63 animals (63%) were positive for C. difficile by qPCR, and 16 isolates were recovered. The opossum (Didelphis spp.) had the highest number of positive animals in both tests (from 21 samples, 19 were qPCR positive, and four isolates were recovered). Three toxigenic strains (RT 002, 004, and 014), all previously described as infecting humans and animals, were isolated in the following species: bearded dragon (Pogona vitticeps), pampas fox (Lycalopex vetulus), and marmoset (Callithrix sp.). The presence of C. difficile in the feces of wild animals highlights the importance of wildlife as potential carriers of infection for production animals or humans.

Food Hygiene and Sanitation at the Jakarta Pondok Gede Hajj Embarkation Dormitory: Food Safety Efforts for the Hajj Pilgrims

Several health risks are associated with performing Hajj pilgrimage. Food poisoning is a major cause of diarrhea and vomiting during Hajj. Food hygiene is an effort to control aspects of food, people, places, and equipment that could cause disease or health problems. This study aimed to describe food hygiene and sanitation efforts implemented in 2023 at the Jakarta Pondok Gede Hajj Embarkation Dormitory in Jakarta, implemented in 2023 to safeguard foods for the Hajj pilgrims. Using a descriptive qualitative design with a document analysis approach, this study examined activities during the pre-embarkation and embarkation periods. Pre-embarkation efforts included inspecting the kitchen environment and coaching the catering team, while during the embarkation period, activities involved checking the hygiene of catering services, inspecting foods brought by pilgrims, and assessing the quality of food and drink. This study found that the dormitory kitchen did not meet the necessary facilities and infrastructure requirements, affecting food safety. Additionally, food handlers did not fully comply with hygiene and sanitation standards. This study emphasized the necessity of meeting hygiene requirements in the kitchen, food handling, equipment, and ingredients since the pre-embarkation period.

Phylogenetic Analysis of Attaching and Effacing E. coli Strains Isolated From Pet Birds in Iran

Background: Enteropathogenic E. coli (EPEC) and Shiga toxin-producing E. coli (STEC) are categorized as attaching and effacing E. coli (AEEC) due to their eae gene. One of the essential causes of diarrhea in humans is AEEC, which affects birds, too, thereby being considered a zoonotic pathogen. Objectives: Our study aimed to determine AEEC and evaluate its antibiotic resistance and phylogroups. Methods: A total of 200 fecal samples were collected from pet birds referred to the Veterinary Medicine Hospital, University of Tehran. PCR methods were used to detect AEEC using uspA, eae, bfpA, stx1, and stx2 gene-specific primers. The antimicrobial susceptibility of the recovered isolates was determined by the agar disk diffusion and MIC methods. Their phylogroups were analyzed based on Clermont phylotyping methods. Results: Of 200 samples, we isolated 26 (13%) E. coli strains, 9 harbor eae genes. None of the ease-positive samples possessed the bfpA gene, but 4 had stx2, and 5 had stx1 and stx2 genes. Phylogenetic analysis identified the phylogenetic groups of all AEEC isolated strains but 2 (duck and cockatiel). Detected phylogroups include four B2 and three D. Based on our results, 7 out of 9 AEEC isolated strains showed multi-drug resistance. Conclusion: The discovery of common phylogroups of AEEC in pet birds (a common companion animal in Iran with intimate contact with their owners, especially children) and humans, as well as their resistance to a wide range of antibiotics used in human medicine, verifies AEEC as a serious public health threat.

Antibacterial Ingredients That Cause Diarrhea Can Be Made from Black, Green, and White Tea Extract (Camellia sinensis L.)

One cause of diarrhea is a bacterial infection. Tea (Camellia sinensis) is a steeping drink that has the efficacy of treating diarrhea. This looks at goals to decide the effect of formulations of three tea extracts that act as antibacterial causes of diarrhea and decide the most appropriate maceration temperature. Extraction was carried out with water solvents at temperatures 70oC, 100oC, and 121oC. The disc method conducted an antibacterial test against E. coli and S. aureus. The most optimal temperature for producing the highest inhibitory zone is the temperature of 100oC. Tea extract temperatures of 100oC are used for antibacterial testing. BSLT test showed the LC50 value of 1800 µg/mL. Tests on E. coli bacteria showed the highest results in a single white tea extract with a diameter of 9.750 mm, and tests on S. aureus showed the highest results in the three tea extract formula with a diameter of 9.65 mm. The inhibitory area evaluation of the system changed into finished using the simplex-centroid design method. It showed a non-huge linear model in the antibacterial test in opposition to E. coli and S. aureus.

Pathogenicity of enterotoxigenic Escherichia coli in Caenorhabditis elegans as an alternative model host.

Enterotoxigenic Escherichia coli (ETEC), one of the diarrheagenic E. coli, is the most common cause of diarrhea in developing country and in travelers to those areas. In this study, Caenorhabditis elegans was used as an alternative model host to evaluate ETEC infections. The ETEC strain ETEC1, which was isolated from a patient with diarrhea, possessed enterotoxins STh, LT1, and EAST1 and colonization factors CS2 and CS3. Live ETEC1 shortened the life span and body size of C. elegans in association with increased expression of enterotoxin genes and intestinal colonization. In contrast, heat-killed ETEC1 did not affect the life span of C. elegans. Caenorhabditis elegans infected with ETEC1 showed upregulated expression of genes related to insulin-like peptides and host defense responses. These results suggest that ETEC1 exhibits pathogenicity through intestinal colonization and enterotoxin production in C. elegans. This system is useful as an ETEC infection model.

Analysis of Knowledge and Attitudes of Mothers with Toddlers at Risk of Diarrhea in the Moramo Health Center Working Area South Konawe Regency

Background: The incidence of diarrhea in Indonesia is the second leading cause of death in children under 5 (five) years of age. Data on the number of cases of diarrhea in children in 15 districts and 2 (two) cities in Southeast Sulawesi Province. South Konawe Regency is in second place with the most cases of diarrhea in toddlers, totaling 77 cases. South Konawe Regency has 24 Community Health Center working areas. In the Moramo Community Health Center area, there were 41 cases of diarrhea in 2021.&#x0D; Method: The type of research used in this research is quantitative with an observational method with a Case Control Study Design approach. This research was carried out in August 2022. This research will be carried out in the Moramo Health Center Work Area, South Konawe Regency, Southeast Sulawesi Province. With a sample of 76 respondents. The sampling technique used in this research was Simple Random Sampling.&#x0D; Result: The results of the research are known from the results of the analysis X2Hit 15.221 &gt; Hit 10,344&gt; df=1), ϕ = 0.504.&#x0D; Conclusion: It is hoped that parents, especially mothers who have toddlers, can increase their knowledge about the causes of diarrhea, improve their attitudes to avoid diarrheal disease, especially in toddlers.

Prevalence and risk estimates of Cryptosporidium oocysts infection associated with consumption of raw-eaten vegetables in Maiduguri metropolis LGAs, Northeast Nigeria

Cryptosporidium is one of the most important protozoan parasitic pathogens, and it is a common cause of diarrhoea in humans, domestic animals, and wild vertebrates and has serious public health threats. A cross-sectional study was designed to determine the prevalence of Cryptosporidium oocysts in raw-eaten vegetables in Maiduguri Metropolitan Council (MMC) and Jere Local Government Areas (LGAs). A total of 400 samples were collected from four (4) different locations, namely Tashan Bama, Gomboru, and Monday Markets (n = 100), while fifty (n = 50) each from 202-Vegetable-Vendors and Unimaid Commercials. A total of 16 visits were conducted in all the sampling areas (twenty-five samples per visit). The Cryptosporidium oocysts were detected using the Modified Ziehl–Neelsen Staining Technique. The locations, sources, and types of raw-eaten vegetables were also assessed. The oocysts were confirmed (100×) as bright pink spherules. Data generated were analyzed using IBM-SPSS V23.0, and p ≤ 0.05 was considered significant. Out of the total samples (n = 400) analyzed, cabbage appeared to have the highest number of 10 (12.5%) of Cryptosporidium oocysts detected, while Tomato and garden egg had 9 (11.3%) and 1 (1.2%), respectively. There was a statistically significant association (χ2 = 12.5, P = 0.014) between the presence of Cryptosporidium oocysts in raw-eaten vegetables and vegetable types. Among the sources of the vegetables sampled, Alau had the highest number of Cryptosporidium oocysts, 15 (12.5%), followed by Kilari-Abdullahi and Zabarmari sources with 4 (10.0%) and 4 (5.0%), respectively. However, Jetete appeared to have the least number 2 (2.5%) of oocysts, and there was a statistically significant association (χ2= 10.4, P = 0.034) between the presence of Cryptosporidium oocysts and the sources of vegetables and fruits. The study concludes that the raw-eaten vegetables sampled from Maiduguri Metropolis were contaminated with Cryptosporidium oocysts. The study recommends that all raw-eaten vegetables should be from cleaned sources and washed before consumption. Consumers should be enlightened on the hygienic measures in the food chain in line with the Hazard Analysis and Critical Control Points (HACCP) principles.

Genomic Profiling of Multidrug-Resistant Swine Escherichia coli and Clonal Relationship to Human Isolates in Peru.

The misuse of antibiotics is accelerating antimicrobial resistance (AMR) in Escherichia coli isolated from farm animals. The genomes of ten multidrug-resistant (MDR) E. coli isolates from pigs were analyzed to determine their sequence types, serotypes, virulence, and AMR genes (ARGs). Additionally, the relationship was evaluated adding all the available genomes of Peruvian E. coli from humans using the cgMLST + HierCC scheme. Two aEPEC O186:H11-ST29 were identified, of which H11 and ST29 are reported in aEPEC isolates from different sources. An isolate ETEC-O149:H10-ST100 was identified, considered a high-risk clone that is frequently reported in different countries as a cause of diarrhea in piglets. One ExPEC O101:H11-ST167 was identified, for which ST167 is an international high-risk clone related to urinary infections in humans. We identified many ARGs, including extended-spectrum β-lactamase genes, and one ETEC harboring the mcr-1 gene. CgMLST + HierCC analysis differentiated three clusters, and in two, the human isolates were grouped with those of swine in the same cluster. We observed that Peruvian swine MDR E. coli cluster with Peruvian E. coli isolates from healthy humans and from clinical cases, which is of great public health concern and evidence that AMR surveillance should be strengthened based on the One Health approach.

Shigella as a Cause of Diarrhea Hospitalization in Children Under Five: Evaluation by Conventional and Molecular Methods.

Shigella is an important cause of diarrhea in children under five, often missed by conventional laboratory methods. Blood in stools has always been a syndromic indicator for Shigella diarrhea, but most cases present with watery diarrhea without blood. This study aimed to determine the frequency of Shigella detected by molecular and conventional methods in children under five. Additionally, we aimed to study the clinical profile and outcome of children with Shigella diarrhea managed as per current diarrhea treatment guidelines. In this hospital-based prospective observational study, stool samples from 150 children (age range: one month to five years) with acute diarrhea (duration < seven days) were subjected to routine microscopic examination, stool culture, and DNA extraction. The extracted DNA from stored stool samples was subjected to polymerase chain reaction (PCR) amplification using a specific primer for the invasion plasmid antigen Hgenesequence (ipaH) gene at 424 bp. Results were interpreted in the context of the percentage of isolation of Shigella by molecular (PCR) and conventional methods (stool microscopy and culture) and the follow-up outcome in terms of recurrence of diarrhea or dysentery and growth faltering over three months after discharge. Shigella infection was diagnosed in stool samples by PCR from 13 (8.7%) children, whereas it was isolated by conventional stool culture in only one (0.7%) child. The sensitivity of culture was only 7.7% against PCR for the diagnosis of Shigella infection, whereas blood in stools had a sensitivity of 15.4%. The majority of Shigella PCR-positive cases (11 out of 13) presented with non-bloody diarrhea. None of the evaluated clinical predictors had a significant association with the Shigella infection. No statistically significant difference was found between PCR-positive and PCR-negative children at the end of follow-up (P>0.05). The majority of children with Shigella infection present with watery diarrhea rather than bloody diarrhea, and a history of blood in stools is a poor marker for the diagnosis of shigellosis. The diagnostic performance of stool culture is also very low compared to stool PCR for the diagnosis of Shigella diarrhea.

HANDWASHING BEHAVIOR, SNACK EATING HABITS AND E.COLI CONTAMINATION WITH DIARRHEA IN ELEMENTARY SCHOOL STUDENTS IN TANJUNGPINANG CITY AND CIMAHI CITY

Diarrhea is an endemic disease that has the potential to cause pandemic and is still a contributor to the mortality rate in Indonesia. The behavior of elementary school students in choosing snacks and hand washing with soap is often the cause of diarrhea. The purpose of this study was to determine the relationship between the habit of consuming snacks, hand washing behavior and E.coli contamination in snacks with the incidence of diarrhea in public elementary school students in Tanjungpinang and Cimahi, Indonesia. This study was a cross sectional design. The population in this study were all public primary school students in grades 4, 5 and 6 from 15 public primary schools in Bukit Bestari sub-district and 18 public primary schools in Cimahi Utara sub-district. Sampling was conducted using quota sampling method (30 students per school) so that the minimum number of samples reached 990 students. Based on the results of data analysis, it can be concluded that there is no relationship between hand washing and diarrhea in elementary school students. There is a relationship between the habit of eating snacks and consumption of snacks containing E.coli with the incidence of diarrhea in elementary school students

Enteric parasites and associated factors in cancer patients in Nepal.

Infection with intestinal parasites is widespread worldwide, especially in developing countries. Intestinal parasites are a major cause of diarrhea in both immunocompetent and immunocompromised people, but cancer patients are more prone to infection. This study aimed to investigate the prevalence and risk factors of intestinal parasitic infections (IPIs) among cancer patients undergoing chemotherapy at Nepal Cancer Hospital and Research Center (NCHRC) in Nepal. One hundred individuals were selected with a convenience sampling strategy. The stool samples were examined by direct wet mount, sedimentation, flotation, and acid-fast methods to determine the prevalence and intensity of IPIs in this population. The overall prevalence of IPIs was 8% (4% protozoan and 4% helminths). Altogether, three species of intestinal parasites were detected. Cryptosporidium (4%) was predominant followed by Trichuris trichiura (2%) and Ancylostoma duodenale (2%). Multivariable regression analysis revealed that "not using soap for handwashing" was significantly associated with the prevalence of overall IPIs. None of the other evaluated risk factors indicated an association with IPIs infection. In this study, the IPIs were attributable to individual hygiene behaviors, but not to nutritional status or socio-demographic characteristics. Yet, significant numbers of males reported anemia and undernutrition in this study population.

Burden of diarrhea and antibiotic use among children in low-resource settings preventable by Shigella vaccination: A simulation study.

Shigella is a leading cause of diarrhea and dysentery in children in low-resource settings, which is frequently treated with antibiotics. The primary goal of a Shigella vaccine would be to reduce mortality and morbidity associated with Shigella diarrhea. However, ancillary benefits could include reducing antibiotic use and antibiotic exposures for bystander pathogens carried at the time of treatment, specifically for fluoroquinolones and macrolides (F/M), which are the recommended drug classes to treat dysentery. The aim of the study was to quantify the reduction in Shigella attributable diarrhea, all diarrhea, and antibiotic use in the first 2 years of life that could be prevented by a Shigella vaccine. We used data from the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study, a birth cohort study that followed 1,715 children with twice weekly surveillance for enteric infections, illnesses, and antibiotic use for the first 2 years of life from November 2009 to February 2014 at 8 sites. We estimated the impact of 2 one-dose (6 or 9 months) and 3 two-dose (6 and 9 months, 9 and 12 months, and 12 and 15 months) Shigella vaccines on diarrheal episodes, overall antibiotic use, and F/M use. Further, we considered additional protection through indirect and boosting effects. We used Monte Carlo simulations to estimate the absolute and relative reductions in the incidence of diarrhea and antibiotic use comparing each vaccination scenario to no vaccination. We analyzed 9,392 diarrhea episodes and 15,697 antibiotic courses among 1,715 children in the MAL-ED birth cohort study. There were 273.8 diarrhea episodes, 30.6 shigellosis episodes, and 457.6 antibiotic courses per 100 child-years. A Shigella vaccine with a mean vaccine efficacy of 60% against severe disease given at 9 and 12 months prevented 10.6 (95% CI [9.5, 11.5]) Shigella diarrhea episodes of any severity per 100 child-years (relative 34.5% reduction), 3.0 (95% CI [2.5, 3.5]) F/M courses for Shigella treatment per 100 child-years (relative 35.8% reduction), and 5.6 (95% CI [5.0, 6.3]) antibiotic courses of any drug class for Shigella treatment per 100 child-years (relative 34.5% reduction). This translated to a relative 3.8% reduction in all diarrhea, a relative 2.8% reduction in all F/M courses, a relative 3.1% reduction in F/M exposures to bystander pathogens, and a relative 0.9% reduction in all antibiotic courses. These results reflect Shigella incidence and antibiotic use patterns at the 8 MAL-ED sites and may not be generalizable to all low-resource settings. Our simulation results suggest that a Shigella vaccine meeting WHO targets for efficacy could prevent about a third of Shigella diarrhea episodes, antibiotic use to treat shigellosis, and bystander exposures due to shigellosis treatment. However, the reductions in overall diarrhea episodes and antibiotic use are expected to be modest (<5%).

Comparison of Shigella GMMA and glycoconjugate four-component formulations in animals.

Shigellosis is leading bacterial cause of diarrhea with high prevalence in children younger than 5years in low- and middle-income countries, and increasing number of reports of Shigella cases associated to anti-microbial resistance. No vaccines against Shigella are still licensed, but different candidates based on the O-antigen portion of lipopolysaccharides are in clinic. Generalized Modules for Membrane Antigens (GMMA) have been proposed as an alternative delivery system for the O-antigen, and a 4-component vaccine candidate (altSonflex1-2-3), containing GMMA from S. sonnei and S. flexneri 1b, 2a and 3a is being tested in a phase 1/2 clinical trial, with the aim to elicit broad protection against the most prevalent Shigella serotypes. Here, the 4-component GMMA vaccine candidate has been compared to a more traditional glycoconjugate formulation for the ability to induce functional antibodies in mice and rabbits. In mice, in the absence of Alhydrogel, GMMA induce higher IgG antibodies than glycoconjugates and stronger bactericidal titers against all Shigella serotypes. In the presence of Alhydrogel, GMMA induce O-antigen specific IgG levels similar to traditional glycoconjugates, but with a broader range of IgG subclasses, resulting in stronger bactericidal activity. In rabbits, GMMA elicit higher functional antibodies than glycoconjugates against S. sonnei, and similar responses to S. flexneri 1b, 2a and 3a, independently from the presence of Alhydrogel. Different O-antigen based vaccines against Shigella are now in clinical stage and it will be of particular interest to understand how the preclinical findings in the different animal models translate in humans.

First identification and coinfection detection of Enterocytozoon bieneusi, Encephalitozoon spp., Cryptosporidium spp. and Giardia duodenalis in diarrheic pigs in Southwest China

BackgroundEnterocytozoon bieneusi, Encephalitozoon spp., Cryptosporidium spp., and Giardia duodenalis (G. intestinalis) are enteric pathogens that cause diarrhea in pigs. This study aimed to determine the prevalence of these enteric parasites and their coinfection with E. bieneusi in diarrheic pigs in Southwest China (Chongqing and Sichuan) using nested polymerase chain reaction (nPCR) based methods.ResultsA total of 514 fecal samples were collected from diarrheic pigs from 14 pig farms in Chongqing (five farms) and Sichuan (nine farms) Provinces. The prevalence of Encephalitozoon spp., Cryptosporidium spp. and G. duodenalis was 16.14% (83/514), 0% (0/514), and 8.95% (46/514), respectively. Nested PCR revealed 305 mono-infections of E. bieneusi, six of E. cuniculi, two of E. hellem, and nine of G. duodenalis and 106 concurrent infections of E. bieneusi with the other enteric pathogens. No infections of E. intestinalis and Cryptosporidium species were detected. The highest coinfection was detected between E. bieneusi and E. cuniculi (10.5%, 54/514), followed by E. bieneusi and G. duodenalis (5.8%, 30/514) and E. bieneusi and E. hellem (2.9%, 15/514). E. bieneusi was the most frequently detected enteric pathogen, followed by E. cuniculi, G. duodenalis and E. hellem. There was a significant age-related difference in the prevalence of E. cuniculi in fattening pigs (χ2 = 15.266, df = 3, P = 0.002) and G. duodenalis in suckling pigs (χ2 = 11.92, df = 3, P = 0.008) compared with the other age groups. Sequence analysis of the ITS region of Encephalitozoon species showed two genotypes (II and III) for E. cuniculi and one (TURK1B) for E. hellem. Only G. duodenalis assemblage A was identified in all nested PCR-positive samples. E. bieneusi was found more often than other enteric pathogens.ConclusionsThis study showed that E. bieneusi, Encephalitozoon spp. [E. cuniculi and E. hellem] and G. duodenalis were common enteric parasites in diarrheic pigs in Chongqing and Sichuan Provinces. In case of both mono-infection and coinfection, E. bieneusi was the most common enteric pathogen in diarrheic pigs. Thus, it may be a significant cause of diarrhea in pigs. Precautions should be taken to prevent the spread of these enteric parasites.

Identification and characterization of porcine Rotavirus A in Chilean swine population.

Rotavirus A (RVA) is a common cause of diarrhea in newborn pigs, leading to significant economic losses. RVA is considered a major public health concern due to genetic evolution, high prevalence, and pathogenicity in humans and animals. The objective of this study was to identify and characterize RVA in swine farms in Chile. A total of 154 samples (86 oral fluids and 68 fecal samples) were collected, from 22 swine farms. 58 (38%) samples belonging to 14 farms were found positive for RVA by real-time RT-PCR. The samples with low Ct values (21) and the two isolates were selected for whole genome sequencing. Nearly complete genomes were assembled from both isolates and partial genomes were assembled from five clinical samples. BLAST analysis confirmed that these sequences are related to human and swine-origin RVA. The genomic constellation was G5/G3-P[7]-I5-R1-C1-M1-A8-N1-T1-E1-H1. Phylogenetic analysis showed that VP4, VP1, VP2, NSP2, NSP3, NSP4, and NSP5 sequences were grouped in monophyletic clusters, suggesting a single introduction. The phylogenies for VP7, VP6, VP3, and NSP1 indicated two different origins of the Chilean sequences. The phylogenetic trees showed that most of the Chilean RVA sequences are closely related to human and swine-origin RVA detected across the world. The results highlight the potential zoonotic nature of RVA circulating in Chilean swine farms. Therefore, it is important to continue RVA whole genome sequencing globally to fully understand its complex epidemiology and early detection and characterization of zoonotic strains.

A First in Human Clinical Trial Assessing the Safety and Immunogenicity of Two Intradermally Delivered Enterotoxigenic Escherichia coli CFA/I Fimbrial Tip Adhesin Antigens with and without Heat-Labile Enterotoxin with Mutation LT(R192G).

Enterotoxigenic E. coli (ETEC) is a leading cause of diarrhea in travelers as well as for children living in low- to middle-income countries. ETEC adhere to intestinal epithelium via colonization factors (CFs). CFA/I, a common CF, is composed of a polymeric stalk and a tip-localized minor adhesive subunit, CfaE. Vaccine delivery by the transcutaneous immunization of dscCfaE was safe but was poorly immunogenic in a phase 1 trial when administered to volunteers with LTR(192G) and mLT. To potentially enhance the immunogenicity of CfaE while still delivering via a cutaneous route, we evaluated the safety and immunogenicity of two CfaE constructs administered intradermally (ID) with or without mLT. CfaE was evaluated as a donor strand-complemented construct (dscCfaE) and as a chimeric construct (Chimera) in which dscCfaE replaces the A1 domain of the cholera toxin A subunit and assembles non-covalently with the pentamer of heat-labile toxin B (LTB). Subjects received three ID vaccinations three weeks apart with either dscCfaE (1, 5, and 25 µg) or Chimera (2.6 and 12.9 µg) with and without 0.1 µg of mLT. Subjects were monitored for local and systemic adverse events. Immunogenicity was evaluated by serum and antibody-secreting cell (ASC) responses. The vaccine was well-tolerated with predominantly mild and moderate local vaccine site reactions characterized by erythema, induration and post-inflammatory hyperpigmentation. High rates of serologic and ASC responses were seen across study groups with the most robust responses observed in subjects receiving 25 µg of dscCfaE with 0.1 mcg of LT(R192G). Both ETEC adhesin vaccine prototypes were safe and immunogenic when co-administered with mLT by the ID route. The observed immune responses induced with the high dose of dscCfaE and mLT warrant further assessment in a controlled human infection model.

How I approach diarrhea in hematological transplant patients: A practical tool.

Diarrhea in hematopoietic stem-cell transplantation (HSCT) remains a multifactorial challenge that demands a nuanced diagnostic approach. The causes of infectious diarrhea in HSCT recipients are diverse and influenced by patient-specific risk factors, the post-transplant timeline, and local epidemiology. During the past decade, our understanding of diarrhea in HSCT has witnessed a transformative shift through the incorporation of gastrointestinal (GI) multiplex polymerase chain reaction (PCR) panels. However, the judicious application of these panels is imperative to avoid overtesting and prevent adverse outcomes. The challenge lies in distinguishing between the diverse causes of diarrhea, ascertaining the clinical significance of detected pathogens, and navigating the diagnostic uncertainty presented by several non-infectious conditions such as mucositis, intestinal dysbiosis, and acute graft-versus-host disease (aGvHD), all of which mimic infection. This review examines the landscape of infectious diarrhea in the HSCT population, encompassing both established (e.g., Cytomegalovirus, Clostridioides difficile, and norovirus) and emerging pathogens (e.g., sapoviruses, astroviruses). We propose a multifaceted diagnostic algorithm that combines clinical assessment, risk stratification, and tailored utilization of molecular platforms. While multiplex GI panels present invaluable opportunities for rapid and comprehensive pathogen detection, their judicious use is pivotal in preserving diagnostic stewardship. Customization of diagnostic algorithms tailored to local epidemiology ensures optimal patient care and resource utilization.

Structure and immunogenicity of the murine astrovirus capsid spike.

Human astroviruses (HAstVs) are small, non-enveloped icosahedral RNA viruses that are a significant cause of diarrhoea in young children. Despite their worldwide prevalence, HAstV pathogenesis studies and vaccine development remain challenging due to the lack of an animal model for HAstV infection. The recent development of a murine astrovirus (MuAstV) infection model in mice provides the opportunity to test proof-of-concept vaccines based on MuAstV antigens. To help establish a system in which an astrovirus capsid spike-based vaccine could be tested in vivo, we designed and produced a recombinant MuAstV capsid spike protein based on predicted secondary structure homology to HAstV spike proteins. The recombinant MuAstV spike can be expressed with high efficiency in Escherichia coli and retains antigenicity to polyclonal antibodies elicited by MuAstV infection. We determined the crystal structure of the MuAstV spike to 1.75 Å and assessed its structural conservation with HAstV capsid spike. Despite low sequence identity between the MuAstV and HAstV spikes and differences in their overall shapes, they share related structural folds. Additionally, we found that vaccination with MuAstV spike induced anti-MuAstV-spike antibodies, highlighting that the recombinant spike is immunogenic. These studies lay a foundation for future in vivo MuAstV challenge studies to test whether MuAstV spike can be the basis of an effective vaccine.

Mckittrick-Wheelock syndrome: An infrequent cause of diarrhea in a patient with complicated necrotizing acute pancreatitis

Mckittrick-Wheelock syndrome: An infrequent cause of diarrhea in a patient with complicated necrotizing acute pancreatitis