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Objectives: Although enteric disease case interviews are critical for control measures and education, not all case-patients are interviewed. We evaluated systematic differences between people with an enteric disease in Colorado who were and were not interviewed to identify ways to increase response rates and reduce biases in the surveillance data used to guide public health interventions., Methods: We obtained data from the Colorado Electronic Disease Reporting System from March 1, 2017, through December 31, 2019. Among case-patients not interviewed and interviewed, we used univariate analyses to describe sociodemographic characteristics, timing of contact attempts, and effect of additional funding., Results: As compared with case-patients who were interviewed, case-patients who were not interviewed were significantly more likely to be aged 18 to 39 years (35.7% vs 31.7%; P  < .001); identify as male, Hispanic, or Black; be experiencing homelessness or hospitalization; reside in rural/frontier areas or an institution; or live in areas with lower levels of education, life expectancy, and income. Time to first contact attempt was longer for case-patients who were not interviewed than for those who were (mean days from specimen collection to first contact attempt, 9.8 vs 6.8; P  < .001). Residing in a jurisdiction with additional funding for interviewing was associated with increased interview rates (87.7% vs 68.8%) and timeliness of public health report and first contact attempt (2.3 vs 4.4 days; P  < .001)., Conclusion: Findings can guide efforts to improve response rates in groups least likely to be interviewed, resulting in reduced biases in surveillance data, better disease mitigation, and increased efficiency in case investigations. Timeliness of case interviews and additional funding to conduct case investigations were factors in increasing response rates., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Children under-5 years of age are particularly vulnerable to severe acute malnutrition (SAM), and the risk factors associated with relapse to SAM are poorly understood. Possible causes are asymptomatic or symptomatic infection with enteric pathogens, with contaminated food as a critical transmission route. This cross-sectional study comprised a household survey with samples of child food (n = 382) and structured observations of food preparation (n = 197) among children aged 6-59 months that were discharged from treatment in community management of acute malnutrition (CMAM) programmes in South Sudan. We quantified Escherichia coli and total coliforms (TCs), measured in colony forming units per g of food (CFU/g), as indicators of microbial contamination of child food. A modified hazard analysis critical control point (HACCP) approach was utilised to determine critical control points (CCPs) followed by multivariate logistic regression analysis to understand the risk factors associated with contamination. Over 40% (n = 164) of samples were contaminated with E. coli (43% >0 E. coli CFU/g, 95% CI 38%-48%), and 90% (n = 343) had >10 TCs (CFU/g) (>10 TC CFU/g, 95% CI 87%-93%). Risk factors associated (p < 0.05) with child food contamination included if the child fed themselves (9.05 RR, 95% CI [3.18, 31.16]) and exposure to animals (2.63 RR, 95% CI [1.33, 5.34]). This study highlights the risk factors and potential control strategies that can support interventions that reduce food contamination exposure in young children and help further protect those that are highly vulnerable to recurrent exposure to enteric pathogens., (© 2023 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

l-Glutamine supplementation improves gastrointestinal and immune function in dairy calves during controlled immune and stress challenges. However, it is unknown whether supplementing milk replacer (MR) with l-glutamine improves preweaning dairy calf health and welfare under production conditions. Therefore, the study objective was to evaluate the effects of supplementing MR with l-glutamine on gastrointestinal permeability, immune function, growth performance, postabsorptive metabolic biomarkers, and physiological stress response in preweaning dairy calves. In 3 repetitions, Holstein heifer calves (n = 30; 1.5 ± 0.5 d old; 37.1 ± 0.86 kg body weight) were blocked by serum total protein, body weight, and age, and provided MR (3.8 L/calf per d; 24% CP, 17% fat, 12.5% solids) supplemented with l-glutamine (GLN; 10g/kg MR powder; n = 5 calves/repetition) or nonsupplemented (NSMR; n = 5 calves/repetition). Calves were individually housed with ad libitum starter grain and water access until weaning (56.4 ± 0.5 d old). At 1 and 6 wk of age, urinary catheters were placed, and calves were orally dosed with 1 L of chromium (Cr)-EDTA. Urine samples were collected over a 24-h period for Cr output analysis as an in vivo biomarker of gastrointestinal permeability. Blood was collected on study d 1, 5, 7, 14, 21, 42, and 56 to measure white blood cell counts, cortisol, insulin, glucose, nonesterified fatty acids, serum amyloid A, haptoglobin, and neutrophil: lymphocytes. Two study intervals were used in the statistical analyses, representing greater (P1; wk 1-3) and reduced (P2; wk 4-8) enteric disease susceptibility. Data were analyzed using PROC GLIMMIX in SAS 9.4 (SAS Institute Inc.) with calf as the experimental unit. Overall, total urinary Cr output was reduced in GLN versus NSMR calves. Total Cr output was reduced at 1 wk of age in GLN versus NSMR calves, but no differences were detected at 6 wk of age. Neutrophil:lymphocyte was decreased both overall and during P2 in GLN versus NSMR calves, and neutrophil counts tended to be reduced in GLN versus NSMR calves during P2. No MR treatment differences were detected for average daily feed intake, average daily gain, body measurements, postabsorptive metabolic biomarkers, disease scores, and therapeutic treatments between GLN and NSMR calves. In summary, l-glutamine supplementation reduced gastrointestinal permeability and biomarkers of physiological stress in preweaning Holstein heifer calves., (Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Typhoid and emerging paratyphoid fever are a severe enteric disease worldwide with high morbidity and mortality. Licensed typhoid vaccines are in the market, but no paratyphoid vaccine is currently available. In the present study we developed a bivalent vaccine against Salmonella Typhi and Paratyphi A using a bacterial ghost platform. Bacterial ghost cells (BGs) are bacteria-derived cell membranes without cytoplasmic contents that retain their cellular morphology, including all cell surface features. Furthermore, BGs have inherent adjuvant properties that promote an enhanced humoral and cellular immune reaction to the target antigen. Sodium hydroxide was used to prepare ghost cells of Salmonella Typhi and Paratyphi A. The bacterial ghost cells were characterised using electron microscopy. Then BALB/c mice were immunized three times (0 th , 14 th and 28 th day) with the bivalent typhoidal bacterial ghost cells. Haematological study of adult mice throughout immunization period reflected that the immunogen was safe to administer and does not affect the animals' health. After complete immunization, we found significant serum antibody titter against whole cell lysate, outer membrane protein and lipopolysaccharide of both bacteria, and cell-mediated immunity was observed in an ex-vivo experiment. CD4+, CD8a+ and CD19+ splenic cell populations were increased in immunized animals. Bivalent Typhoidal ghost cell immunized mice showed better survival, less bacterial colonization in systemic organs, and less inflammation and/or destruction of tissue in histopathological analysis than non-immunized control mice.Serum antibodies of immunized animals can significantly inhibit bacterial motility and mucin penetration ability with better killing properties against Salmonella Typhi and Paratyphi A. Furthermore, significant passive protection was observed through the adoptive transfer of serum antibody and lymphocytes of immunized animals to naïve animals after bacterial infection. In summary, Bivalent Typhoidal Bacterial Ghost cells (BTBGs) enhances immunogenic properties and serves as a safe and effective prevention strategy against Salmonella Typhi and Paratyphi A., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: Clostridioides difficile is an etiological agent of enteric diseases in humans and animals. Animals are considered a potential reservoir due to the genetic and antimicrobial resistance similarities between human and animal C. difficile isolates. In this study, we evaluated the genetic characteristics and antimicrobial resistance profiles of C. difficile isolated from 942 fecal samples collected from horses in South Korea during 2019-2020., Methods: The C. difficile isolates were tested for toxin genes including tcdA (A), tcdB (B), and cdtAB (CDT) and deletions of the tcdC gene by PCR. In addition, ribotyping, multilocus sequence typing, and antimicrobial susceptibility tests were performed., Results: Twenty-three (2.4%) C. difficile isolates were associated with diarrhea in foals under 1 year old during the spring-summer period. Of these, 82.6% were toxigenic strains, determined to be A + B + CDT + (52.1%) or A + B + CDT ‒ (30.4%). All isolates were susceptible to metronidazole and vancomycin, and resistant to cefotaxime and gentamicin, and 76.2% were multidrug resistant (MDR). RT078/ST11/Clade 5 was the most common genotype (47.8%), which was also found in animals and humans worldwide. All RT078/ST11/Clade 5 strains were toxigenic and had deletions of the tcdC gene. About half of these strains were resistant to moxifloxacin, and 63.6% were MDR., Conclusions: C. difficile isolates in this study consisted mostly of toxigenic and MDR strains, and their genetic properties were highly similar to human C. difficile isolates. These results suggest high possibilities of zoonotic transmission and can provide knowledge for establishing strategies for the treatment and prevention of C. difficile infection., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest related to this study., (Copyright © 2023. Published by Elsevier Ltd.)

Pre-weaned dairy calves are very susceptible to disease in the first months of life due to having a naïve immune system and because of the numerous physiological stressors they face. Hygiene management is a key element in minimizing enteric disease risk in calves by reducing their exposure to pathogens. Samples of milk, concentrate feed and drinking water, boot swabs of bedding and swabs of feed equipment were collected from 66 dairy farms as part of a survey of calf rearing practice and housing design. All the samples were cultured to determine total viable counts (TVC), total coliforms (TCC) and Escherichia coli as indicators of hygiene. Target ranges for levels of TVC, TCC and E. coli were defined from the literature and the sample results compared against them. The TVC targets in milk, MR and water were <4.0 log 10 CFU/mL. TCC and E. coli targets of <1.1 log 10 CFU/mL (the detection limit) were used for milk, MR, concentrate feed and feeding equipment. For water, the TCC and E. coli targets were <1.0 log 10 CFU/100 mL. The targets used for bedding boot swabs were <6.3 log 10 TVC CFU/mL and <5.7 log 10 TCC or E. coli CFU/mL. Farm management factors were included as fixed effects in a generalized linear mixed model to determine the probability of samples being within each hygiene indicator target range. Milk replacer samples obtained from automatic feeders were more likely to be within the TVC target range (0.63 probability) than those prepared manually (0.34) or milk samples taken from the bulk tank (0.23). Concentrate feed samples taken from buckets in single-calf pens were more likely to have E. coli detected (0.89) than samples taken from group pen troughs (0.97). A very small proportion of water samples were within the indicator targets (TVC 9.8%, TCC 6.0%, E. coli 10.2%). Water from self-fill drinkers had a lower likelihood of being within the TVC target (0.03) than manually filled buckets (0.14), and water samples from single pens were more likely to be within TCC target ranges (0.12) than those from group pens (0.03). However, all self-fill drinkers were located in group pens so these results are likely confounded. Where milk feeders were cleaned after every feed, there was a greater likelihood of being within the TVC target range (0.47, compared with 0.23 when not cleaned after every feed). Detection of coliforms in milk replacer mixing utensils was linked with reduced probability of TVC (0.17, compared with 0.43 when coliforms were not detected) and TCC (0.38, compared with 0.62), which was within target in feeders. Key factors related to increased probability of bedding samples being within TCC target range were use of group calf pens (0.96) rather than single-calf pens (0.80), use of solid floors (0.96, compared with 0.76 for permeable floors) and increased space allowance of calves (0.94 for pens with ≥2 m 2 /calf, compared with 0.79 for pens with <2 m 2 /calf). Bedding TVC was more likely to be within the target range in group (0.84) rather than in single pens (0.66). The results show that hygiene levels in the calf rearing environment vary across farms and that management and housing design impact hygiene.

Fowl adenoviruses are a group of pathogens that cause large economic losses worldwide in the poultry industry, in addition to producing a wide range of diseases, such as IBH, HHS, and enteric and respiratory diseases. The objective of this study was to quantify, identify, and molecularly characterize the types of FAdV circulating in commercial poultry farms (broilers, breeders, and layers) in Ecuador from 2019 to 2021. Molecular characterization was performed by PCR, quantification by qPCR, and subsequent sequencing for each positive sample. The results indicated that the FAdV genotypes circulating in our country are FAdV-2/D2, FAdV-6/E1, FAdV-8a/E2, and FAdV-11/D3; the samples were grouped into different groups that contain sequences that were obtained from countries in Africa, Asia, and America, and that are found in birds at different ages, since early age where can cause different clinical signs, such as diarrhea, ruffled feathers and dwarfism. Therefore, these results indicate that several genotypes of the virus are circulating in commercial poultry flocks, suggesting that biosecurity measures on farms should be improved, in addition to carrying out new or improved vaccination plans.

Postweaning diarrhoea caused by Enterotoxigenic Escherichia coli (ETEC) is a threat to the pig industry. With an intensified focus on finding alternatives to the use of medical zinc oxide and antibiotics in newly weaned pigs, the objective of this study was to investigate the effect of early inoculation of probiotics to suckling piglets on subsequently ETEC faecal shedding and immune parameters in ETEC F18-challenged weaned piglets. Sixty pigs weaned on day 28 of age were assigned to three treatment groups: (i) Negative Control (non-challenged), (ii) Positive Control (challenged) and (iii) Probiotic (challenged and inoculated with a multi-species probiotic product during suckling). On days 1 and 2 postweaning, pigs in the Positive Control and Probiotic groups were challenged with 5 × 10 8 colony-forming unit ETEC F18/pig/day, whereas pigs in the Negative Control group were provided with NaCl. Growth and diarrhoea incidence were not significantly affected by ETEC challenge or probiotic administration. ETEC F18 shedding and C-reactive protein concentration in plasma were significantly lower in the Negative Control group, confirming a successful challenge model. Pigs in the Probiotic group had a significantly reduced number of pigs shedding ETEC F18 and STb toxin in faeces compared with the Positive Control group. Probiotic application did not significantly impact the concentration of C-reactive protein, haptoglobin and cytokines in plasma nor haematology numbers. In conclusion, weaned pigs administered with a multi-species probiotic product early in life had a more rapid response towards the pathogen challenge and a faster clearance of ETEC compared with the Positive Control group. Administration of a multi-species probiotic to newborn piglets may thus promote resilience in the newly weaned pig. However, further studies with pigs subjected to a more severe pathogen challenge are needed to confirm these results and to investigate the mechanism of action of the probiotic intervention., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

In early 2018, we investigated a large national multiple-serotype Salmonella outbreak linked to contaminated kratom, a raw minimally processed botanical substance. Kratom is a plant consumed for its stimulant effects and as an opioid substitute. A case was defined as a laboratory-confirmed Salmonella infection with one of the outbreak strains (serotypes I 4,[5],12:b:-, Heidelberg, Javiana, Okatie, Weltevreden, or Thompson) with illnesses onset during January 11, 2017-May 8, 2018. State and local officials collected detailed information on product consumption and sources. Suspected products were tested for Salmonella and traceback was conducted to determine product distribution chains and suppliers. We identified 199 cases from 41 states; 54 patients were hospitalized. Early interviews indicated kratom was an exposure of interest. Seventy-six (74%) of 103 people interviewed reported consuming kratom in pills, powders, or teas. Multiple serotypes of Salmonella were detected in samples of kratom collected from the homes of the patients and from retail locations. Several companies issued recalls of kratom products due to Salmonella contamination. To the authors' knowledge, this investigation is the first to establish kratom as a vehicle for Salmonella infection. Our findings underscore the serious safety concerns regarding minimally processed botanical substances intended for oral consumption and the challenges in investigating outbreaks linked to novel outbreak vehicles.

Several biologic therapies have been approved for enteric diseases. We evaluate each biologic's role based on their mechanism of action in treating these conditions. This review examines data on efficacy and safety, as well as considerations for using these therapies in clinical practice in inflammatory bowel diseases, enteric infections-specifically Clostridioides difficile colitis-and potentially in the increasingly prevalent disorder of eosinophilic esophagitis. When choosing an appropriate therapy, it is important to assess patient severity, as most biologics are approved for those with moderate to severe disease activity. With many years of data from clinical trials and real-world experience, these therapies have been shown to improve outcomes overall in enteric diseases, contributing to more options for our patients., Competing Interests: Dr. Abraham reports research funding from Janssen, Celgene, Genentech, Gilead, AbbVie, Takeda, and Lilly, and has been a paid consultant/speaker for AbbVie, BMS, Takeda, Janssen, Pfizer, Lilly, and Medtronics. The authors report no other conflicts of interest in this work., (© 2022 Saleh et al.)

The Salmonella enterica serotype Paratyphi B complex causes a wide range of diseases, from gastroenteritis to paratyphoid fever, depending on the biotypes Java and sensu stricto . The burden of Paratyphi B biotypes in Bangladesh is still unknown, as these are indistinguishable by Salmonella serotyping. Here, we conducted the first whole-genome sequencing (WGS) study on 79 Salmonella isolates serotyped as Paratyphi B that were collected from 10 nationwide enteric disease surveillance sites in Bangladesh. Placing these in a global genetic context revealed that these are biotype Java, and the addition of these genomes expanded the previously described PG4 clade containing Bangladeshi and UK isolates. Importantly, antimicrobial resistance (AMR) genes were scarce amongst Bangladeshi S . Java isolates, somewhat surprisingly given the widespread availability of antibiotics without prescription. This genomic information provides important insights into the significance of S . Paratyphi B biotypes in enteric disease and their implications for public health.

Background: Fecal calprotectin is largely applied as a non-invasive intestinal inflammation biomarker in human medicine. Previous studies in pigs investigated the levels of fecal calprotectin in healthy animals only. Thus, there is a knowledge gap regarding its application during infectious diarrhea. This study investigated the usefulness of fecal calprotectin as a biomarker of intestinal inflammation in Brachyspira hyodysenteriae and Salmonella Typhimurium infected pigs., Results: Fecal samples from pigs with colitis (n = 18) were collected from animals experimentally inoculated with B. hyodysenteriae (n = 8) or from sham-inoculated controls (n = 3). Fecal samples from pigs with enteritis (n = 14) were collected from animals inoculated with Salmonella enterica serovar Typhimurium (n = 8) or from sham-inoculated controls (n = 4). For both groups, fecal samples were scored as: 0 = normal; 1 = soft, wet cement; 2 = watery feces; 3 = mucoid diarrhea; and 4 = bloody diarrhea. Fecal calprotectin levels were assayed using a sandwich ELISA, a turbidimetric immunoassay and a point-of-care dipstick test. Fecal calprotectin levels were greater in colitis samples scoring 4 versus ≤ 4 using ELISA, and in feces scoring 3 and 4 versus ≤ 1 using immunoturbidimetry (P < 0.05). No differences were found in calprotectin concentration among fecal scores for enteritis samples, regardless of the assay used. All samples were found below detection limits using the dipstick method., Conclusions: Fecal calprotectin levels are increased following the development of colitis, but do not significantly change due to enteritis. While practical, the use of commercially available human kits present sensitivity limitations. Further studies are needed to validate the field application of calprotectin as a marker of intestinal inflammation., (© 2021. The Author(s).)

Background: Older children and adults are susceptible to rotavirus, but the extent to which rotavirus affects this population is not fully understood, hindering accuracy of global rotavirus estimations., Objective: To determine what proportion of diarrhea cases are due to rotavirus among persons ≥ 5 years old and to estimate this proportion by age strata., Methods: We conducted a systematic review and meta-analysis using the PRISMA guidelines. We included studies that reported on conditional rotavirus prevalence (i.e., percent of diarrhea due to rotavirus) in persons ≥ 5 years old who were symptomatic with diarrhea/gastroenteritis and had laboratory confirmation for rotavirus infection. Studies on nosocomial infections and outbreak investigations were excluded. We collected age group-specific conditional rotavirus prevalence and other variables, such as study geography, study setting, and study type. We calculated pooled conditional rotavirus prevalence, corresponding 95% confidence intervals (95% CI), heterogeneity (I 2 ) estimates, and prediction intervals (PI)., Results: Sixty-six studies from 32 countries met the inclusion criteria. Conditional rotavirus prevalence ranged from 0% to 30% across the studies. The total pooled prevalence of rotavirus among persons ≥ 5 years old with diarrhea was 7.6% (95% CI: 6.2-9.2%, I 2  = 99.6%, PI: 0-24%). The pooled prevalence of rotavirus among older children and adolescents was 8.7% (95% CI: 6.2-11.7%, I 2  = 96%, PI:0-27%), among younger adults was 5.4% (95% CI: 1.4-11.8%, I 2  = 96%, PI:0-31%), and among older adults was 4.7% (95% CI: 2.8-7.0%, I 2  = 96%, PI:0-16%). Pooled conditional rotavirus prevalences did not differ by other variables., Conclusion: In this systematic review and meta-analysis of rotavirus among persons ≥ 5 years old with diarrhea, we found relatively low pooled conditional rotavirus prevalence compared to what is typically reported for children < 5 years; however, results should be interpreted with caution as the wide prediction intervals suggest large heterogeneity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Equine coronavirus (ECoV) infection is the cause of an emerging enteric disease of adult horses. Outbreaks have been reported in the USA, EU and Japan, as well as sporadic cases in the UK and Saudi Arabia. Infection of ECoV in horses in Israel has never been reported, and the risk of exposure is unknown. Importation and exportation of horses from and into Israel may have increased the exposure of horses in Israel to ECoV. While the disease is mostly self-limiting, with or without supportive treatment, severe complications may occur in some animals, and healthy carriers may pose a risk of infection to other horses. This study was set to evaluate the risk of exposure to ECoV of horses in Israel by using a previously validated, S1-based enzyme-linked immunosorbent assay (ELISA). A total of 41 out of 333 horses (12.3%) were seropositive. Exposure to ECoV was detected in 17 of 29 farms (58.6%) and the seroprevalence varied between 0 and 37.5% amongst farms. The only factor found to be significantly associated with ECoV exposure in the multivariable model was the geographical area ( p < 0.001). ECoV should be included in the differential diagnosis list of pathogens in cases of adult horses with anorexia, lethargy, fever and gastrointestinal signs in Israel.

Controlled human infection models (CHIMs) are useful for vaccine development. To improve on existing models, we developed a CHIM using a lyophilized preparation of Shigella sonnei strain 53G produced using current good manufacturing practice (cGMP). Healthy adults were enrolled in an open-label dose-ranging study. Following administration of a dose of rehydrated S. sonnei strain 53G, subjects were monitored for development of disease. The first cohort received 500 CFU of 53G, and dosing of subsequent cohorts was based on results from the previous cohort. Subjects were administered ciprofloxacin on day 5 and discharged home on day 8. Subjects returned as outpatients for clinical checks and sample collection. Attack rates increased as the dose of S. sonnei was increased. Among those receiving the highest dose (1,760 CFU), 70% developed moderate to severe diarrhea, 50% had dysentery, and 40% had fever. Antilipopolysaccharide responses were observed across all cohorts. An S. sonnei CHIM using a lyophilized lot of strain 53G was established. A dose in the range of 1,500 to 2,000 CFU of 53G was selected as the dose for future challenge studies using this product. This model will enable direct comparison of study results between institutions and ensure better consistency over time in the challenge inoculum. IMPORTANCE Controlled human infection models (CHIMs) are invaluable tools utilized to understand the human response to infection, potentially leading to protective immune mechanisms and allowing efficacy testing of enteric countermeasures, including vaccines, antibiotics, and other products. The development of an improved Shigella CHIM for both Shigella sonnei and Shigella flexneri is consistent with international efforts, supported by international donors and the World Health Organization, focused on standardizing Shigella CHIMs and using them to accelerate Shigella vaccine development. The use of lyophilized Shigella challenge strains rather than plate-grown inoculum preparations is considered an important step forward in the standardization process. Furthermore, the results of studies such as this justify the development of lyophilized preparations for additional epidemiologically important S. flexneri serotypes, including S. flexneri 3a and S. flexneri 6.

The concept of open data has been gaining traction as a mechanism to increase data use, ensure that data are preserved over time, and accelerate discovery. While epidemiology data sets are increasingly deposited in databases and repositories, barriers to access still remain. ClinEpiDB was constructed as an open-access online resource for clinical and epidemiologic studies by leveraging the extensive web toolkit and infrastructure of the Eukaryotic Pathogen Database Resources (EuPathDB; a collection of databases covering 170+ eukaryotic pathogens, relevant related species, and select hosts) combined with a unified semantic web framework. Here we present an intuitive point-and-click website that allows users to visualize and subset data directly in the ClinEpiDB browser and immediately explore potential associations. Supporting study documentation aids contextualization, and data can be downloaded for advanced analyses. By facilitating access and interrogation of high-quality, large-scale data sets, ClinEpiDB aims to spur collaboration and discovery that improves global health., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Ruhamyankaka E et al.)

The role of type A Clostridium perfringens in canine acute hemorrhagic diarrhea syndrome and foal necrotizing enteritis is poorly characterized. However, a highly significant association between the presence of novel toxigenic C. perfringens and these specific enteric diseases has been described. These novel toxigenic strains produce 3 novel putative toxins, which have been designated NetE, NetF, and NetG. Although not conclusively demonstrated, current evidence suggests that NetF is likely the major virulence factor in strains responsible for canine acute hemorrhagic diarrhea syndrome and foal necrotizing enteritis. NetF is a beta-pore-forming toxin that belongs to the same toxin superfamily as CPB and NetB toxins produced by C. perfringens . The netF gene is encoded on a conjugative plasmid that, in the case of netF , also carries another putative toxin gene, netE . In addition, these strains consistently also carry a cpe tcp -conjugative plasmid, and a proportion also carry a separate netG tcp -conjugative plasmid. The netF and netG genes form part of a locus with all the features of the pathogenicity loci of tcp -conjugative plasmids. The netF -positive isolates are clonal in origin and fall into 2 clades. Disease in dogs or foals can be associated with either clade. Thus, these are strains with unique virulence-associated characteristics associated with serious and sometimes fatal cases of important enteric diseases in 2 animal species.

The concept of open data has been gaining traction as a mechanism to increase data use, ensure that data are preserved over time, and accelerate discovery. While epidemiology data sets are increasingly deposited in databases and repositories, barriers to access still remain. ClinEpiDB was constructed as an open-access online resource for clinical and epidemiologic studies by leveraging the extensive web toolkit and infrastructure of the Eukaryotic Pathogen Database Resources (EuPathDB; a collection of databases covering 170+ eukaryotic pathogens, relevant related species, and select hosts) combined with a unified semantic web framework. Here we present an intuitive point-and-click website that allows users to visualize and subset data directly in the ClinEpiDB browser and immediately explore potential associations. Supporting study documentation aids contextualization, and data can be downloaded for advanced analyses. By facilitating access and interrogation of high-quality, large-scale data sets, ClinEpiDB aims to spur collaboration and discovery that improves global health., Competing Interests: No competing interests were disclosed., (Copyright: © 2019 Ruhamyankaka E et al.)

The objective of this study was to investigate the presence of equine coronavirus (ECoV) in clinical samples submitted to a diagnostic laboratory in Ireland. A total of 424 clinical samples were examined from equids with enteric disease in 24 Irish counties between 2011 and 2015. A real-time reverse transcription polymerase chain reaction was used to detect ECoV RNA. Nucleocapsid, spike and the region from the p4.7 to p12.7 genes of positive samples were sequenced, and sequence and phylogenetic analyses were conducted. Five samples (1.2%) collected in 2011 and 2013 tested positive for ECoV. Positive samples were collected from adult horses, Thoroughbred foals and a donkey foal. Sequence and/or phylogenetic analysis showed that nucleocapsid, spike and p12.7 genes were highly conserved and were closely related to ECoVs identified in other countries. In contrast, the region from p4.7 and the non-coding region following the p4.7 gene had deletions or insertions. The differences in the p4.7 region between the Irish ECoVs and other ECoVs indicated that the Irish viruses were distinguishable from those circulating in other countries. This is the first report of ECoV detected in both foals and adult horses in Ireland., Competing Interests: The authors declare no conflict of interest.

Background: Humans are susceptible to over 1400 pathogens. Co-infection by multiple pathogens is common, and can result in a range of neutral, facilitative, or antagonistic interactions within the host. Soil-transmitted helminths (STH) are powerful immunomodulators, but evidence of the effect of STH infection on the direction and magnitude of concurrent enteric microparasite infections is mixed., Methods: We collected fecal samples from 891 randomly selected children and adults in rural Laos. Samples were analyzed for 5 STH species, 6 viruses, 9 bacteria, and 5 protozoa using a quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay. We utilized logistic regression, controlling for demographics and household water, sanitation, and hygiene access, to examine the effect of STH infection on concurrent viral, bacterial, and protozoal infection., Results: We found that STH infection was associated with lower odds of concurrent viral infection [odds ratio (OR): 0.48, 95% confidence interval (CI): 0.28-0.83], but higher odds of concurrent bacterial infections (OR: 1.81, 95% CI: 1.06-3.07) and concurrent protozoal infections (OR: 1.50, 95% CI: 0.95-2.37). Trends were consistent across STH species., Conclusions: The impact of STH on odds of concurrent microparasite co-infection may differ by microparasite taxa, whereby STH infection was negatively associated with viral infections but positively associated with bacterial and protozoal infections. Results suggest that efforts to reduce STH through preventive chemotherapy could have a spillover effect on microparasite infections, though the extent of this impact requires additional study. The associations between STH and concurrent microparasite infection may reflect a reverse effect due to the cross-sectional study design. Additional research is needed to elucidate the exact mechanism of the immunomodulatory effects of STH on concurrent enteric microparasite infection.

Purpose of Review: Waterborne enteric pathogens remain a global health threat. Increasingly, quantitative microbial risk assessment (QMRA) and infectious disease transmission modeling (IDTM) are used to assess waterborne pathogen risks and evaluate mitigation. These modeling efforts, however, have largely been conducted independently for different purposes and in different settings. In this review, we examine the settings where each modeling strategy is employed., Recent Findings: QMRA research has focused on food contamination and recreational water in high-income countries (HICs) and drinking water and wastewater in low- and middle-income countries (LMICs). IDTM research has focused on large outbreaks (predominately LMICs) and vaccine-preventable diseases (LMICs and HICs). Human ecology determines the niches that pathogens exploit, leading researchers to focus on different risk assessment research strategies in different settings. To enhance risk modeling, QMRA and IDTM approaches should be integrated to include dynamics of pathogens in the environment and pathogen transmission through populations.

Background: Environmental enteric dysfunction (EED), frequently seen in rural Malawian children, causes chronic inflammation and increases the risk of stunting. Legumes may be beneficial for improving nutrition and reducing the risk of developing EED in weaning children. Objective: The objectives of this study were to determine the nutritional value, verify the food safety, and identify metabolite profiles of 3 legume-based complementary foods: common bean (CB), cowpea (CP), and traditional corn-soy blend (CSB). Methods: Foods were prepared by using local ingredients and analyzed for nutrient composition with the use of Association of Official Analytical Chemists (AOAC) standards (950.46, 991.43, 992.15, 996.06, and 991.36) for macro- and micronutrient proximate analysis. Food safety analysis was conducted in accordance with the Environmental Protection Agency (7471B) and AOAC (2008.02) standards. The metabolite composition of foods was determined with nontargeted ultra-performance LC-tandem mass spectrometry metabolomics. Results: All foods provided similar energy; CB and CP foods contained higher protein and dietary fiber contents than did the CSB food. Iron and zinc were highest in the CSB and CP foods, whereas CB and CP foods contained higher amounts of magnesium, phosphorus, and potassium. A total of 652 distinct metabolites were identified across the 3 foods, and 23, 14, and 36 metabolites were specific to the CSB, CB, and CP foods, respectively. Among the potential dietary biomarkers of intake to distinguish legume foods were pipecolic acid and oleanolic acid for CB; arabinose and serotonin for CSB; and quercetin and α- and γ-tocopherol acid for CP. No heavy metals were detected, and aflatoxin was measured only in the CSB (5.2 parts per billion). Conclusions: Legumes in the diet provide a rich source of protein, dietary fiber, essential micronutrients, and phytochemicals that may reduce EED. These food metabolite analyses identified potential dietary biomarkers of legume intake for stool, urine, and blood detection that can be used in future studies to assess the relation between the distinct legumes consumed and health outcomes. This trial was registered at clinicaltrials.gov as NCT02472262 and NCT02472301.

Intestinal disease has a major impact on the broiler industry due to economic and welfare reasons. Intestinal disease might occur due to a large number of reasons varying from well-defined pathogens to non-specific enteritis and complex syndromes. However, knowledge about the nature of intestinal disease and presence of enteric viruses in the Dutch broiler industry is largely absent. Therefore, a large-scale field study, in which 98 broiler flocks from 86 farms were sampled weekly, was started to assess the prevalence of histopathological lesions in the jejunum, a number of enterotropic viruses by real-time quantitative reverse transcriptase PCR (RT-qPCR) and coccidia by lesion scoring. Histopathological lesions indicative of intestinal disease were found in all flocks examined. The pathogens investigated were chicken astrovirus (99% of flocks positive), avian nephritis virus 3 (100%), rotavirus A (95%), rotavirus D (52%), reovirus (100%), Eimeria acervulina (94%), E. maxima (49%) and E. tenella (40%). The enteric viruses were more prevalent in the first weeks of the growing period, while coccidiosis was more frequently found at 4 and 5 weeks of age. The abundant presence of the enteric viruses and enteric disorders stresses the need to elucidate the role of these viruses in intestinal disease. Furthermore, the high prevalence of coccidiosis despite the use of anticoccidials shows that the current coccidial management programmes might be insufficient in controlling this disease.

The aim of this study was to investigate the effect of a soy diet on the excretion of Brachyspira hyodysenteriae in five farms with subclinically infected pigs. The effects on general health, faecal consistency and dry matter were analysed. In total, 200 pigs of different ages (group 1 <100 days of age (n=120) and group 2 ≥100 days (n=80)) were randomly assigned to the control (C) and the treatment (T) groups. Group C received the farm's standard diet. In group T half of the daily feed ration was replaced by pure soy on two consecutive days. Faecal scores were used to determine faecal consistency and a microwave method to assess faecal dry matter content (FDMC). In age group 1, soy feeding resulted in a statistically significant decrease of the FDMC of 2.5 per cent compared with group C and in age group 2 in a significant increase of 2.2 per cent compared with group C at day 2. Overall seven (T: 5, C: 2) out of 597 faecal samples tested positive for B hyodysenteriae by PCR. In conclusion, a high soy diet applied over two days influenced the faecal consistency and the FDMC in growers, finishers and sows under field conditions. Further investigations with more sensitive diagnostic methods are needed to prove a potential influence of a high soy diet on the detection rate of B hyodysenteriae in subclinically infected herds.

Porcine epidemic diarrhea virus (PEDV) is a main etiology causing severe enteric disease in piglets with clinical signs of anorexia, vomiting, diarrhea and dehydration resulting in loss of condition and death within a few days. Historically, PED is one of major causes of loss in swine and remains prevalent in some parts of the world. Even with increase in the available tests for PED diagnosis, which include histological diagnosis; virological diagnosis and serological diagnosis, there is no vaccine or specific treatment for this disease yet. In this mini review, the overview and current situation of PED is described with updated techniques, in an effort to comprehensively discuss and understand the disease characteristics., (© Korean Society of Environmental Risk Assessment and Health Science and Springer Science+Business Media Dordrecht 2016.)

Vibrio cholerae is the agent of cholera, a potentially lethal diarrheal disease that remains a significant threat to populations in developing nations. The infant rabbit model of cholera is the only non-surgical small animal model system that closely mimics human cholera. Following orogastric inoculation, V. cholerae colonizes the intestines of infant rabbits, and the animals develop severe cholera-like diarrhea. In this unit, we provide a detailed description of the preparation of the V. cholerae inoculum, the inoculation process and the collection and processing of tissue samples. This infection model is useful for studies of V. cholerae factors and mechanisms that promote its intestinal colonization and enterotoxicity, as well as the host response to infection. The infant rabbit model of cholera enables investigations that will further our understanding of the pathophysiology of cholera and provides a platform for testing new therapeutics., (Copyright © 2015 John Wiley & Sons, Inc.)

Performance and mortality of hares were evaluated for 2 consecutive years in a large farm in Veneto Region (Northern Italy). On average, fertile reproductive pairs (n=318) gave birth 4.8 times and produced 11.4 live leverets, weaned 8.4 leverets and produced 7.0 growing hares (60 days) every year. Mean mortality was 3.6%, 22.9%, 9.7% and 2.5% in newborn (0 to 2 days of age), suckling (3 to 25 days), growing (26 to 60 days) and sub-adult (61 days until sale) hares, respectively. The main causes of mortality were enteric diseases (75.5%, 75.9% and 12.1% in suckling, growing and sub-adult hares, respectively), followed by respiratory diseases (3.4%, 8.0% and 36.2% in suckling, growing and sub-adult hares, respectively), starvation (11.3% and 8.8% in suckling and growing hares, respectively) and trauma (7.1%, 2.3% and 30.2% in suckling, growing and sub-adult hares, respectively). In reproducing hares, mortality was 24.7% and 15.4% in 2010 and 2011, respectively. Respiratory diseases (34.8%) and ulcerative pododermatitis (18.9%) were the most common pathological changes detected in reproducing hares. Farmed hares seem to be affected by diseases resembling those of rabbits reared under intensive conditions. It seems necessary to improve the husbandry of hares to reach satisfactory technical standards and to preserve their health.

Bovine coronavirus (BoCV; Betacoronavirus 1) infections are associated with varied clinical presentations including neonatal diarrhea, winter dysentery in dairy cattle, and respiratory disease in various ages of cattle. The current report presents information on BoCV infections associated with enteric disease of postweaned beef cattle in Oklahoma. In 3 separate accessions from a single herd, 1 in 2012 and 2 in 2013, calves were observed with bloody diarrhea. One calf in 2012 died and was necropsied, and 2 calves from this herd died in 2013 and were necropsied. A third calf from another herd died and was necropsied. The gross and histologic diagnosis was acute, hemorrhagic colitis in all 4 cattle. Colonic tissues from all 4 animals were positive by fluorescent antibody testing and/or immunohistochemical staining for BoCV antigen. Bovine coronavirus was isolated in human rectal tumor cells from swabs of colon surfaces of all animals. The genomic information from a region of the S envelope region revealed BoCV clade 2. Detection of BoCV clade 2 in beef cattle in Oklahoma is consistent with recovery of BoCV clade 2 from the respiratory tract of postweaned beef calves that had respiratory disease signs or were healthy. Further investigations on the ecology of BoCV in cattle are important, as BoCV may be an emerging disease beyond the initial descriptions. Challenge studies are needed to determine pathogenicity of these strains, and to determine if current BoCV vaccines are efficacious against the BoCV clade 2 strains., (© 2014 The Author(s).)

Innovative vaccines against typhoid and other Salmonella diseases that are safe, effective, and inexpensive are urgently needed. In order to address this need, buoyant, self-adjuvating gas vesicle nanoparticles (GVNPs) from the halophilic archaeon Halobacterium sp. NRC-1 were bioengineered to display the highly conserved Salmonella enterica antigen SopB, a secreted inosine phosphate effector protein injected by pathogenic bacteria during infection into the host cell. Two highly conserved sopB gene segments near the 3'-coding region, named sopB4 and B5, were each fused to the gvpC gene, and resulting GVNPs were purified by centrifugally accelerated flotation. Display of SopB4 and B5 antigenic epitopes on GVNPs was established by Western blotting analysis using antisera raised against short synthetic peptides of SopB. Immunostimulatory activities of the SopB4 and B5 nanoparticles were tested by intraperitoneal administration of recombinant GVNPs to BALB/c mice which had been immunized with S. enterica serovar Typhimurium 14028 ΔpmrG-HM-D (DV-STM-07), a live attenuated vaccine strain. Proinflammatory cytokines IFN-γ, IL-2, and IL-9 were significantly induced in mice boosted with SopB5-GVNPs, consistent with a robust Th1 response. After challenge with virulent S. enterica serovar Typhimurium 14028, bacterial burden was found to be diminished in spleen of mice boosted with SopB4-GVNPs and absent or significantly diminished in liver, mesenteric lymph node, and spleen of mice boosted with SopB5-GVNPs, indicating that the C-terminal portions of SopB displayed on GVNPs elicit a protective response to Salmonella infection in mice. SopB antigen-GVNPs were found to be stable at elevated temperatures for extended periods without refrigeration in Halobacterium cells. The results all together show that bioengineered GVNPs are likely to represent a valuable platform for the development of improved vaccines against Salmonella diseases., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Previous research suggests that enteric disease and poor gut health interact to decrease pig performance. Our objective was to determine if light birth weight pigs or those from the bottom 10th percentile of transition ADG (tADG) have a higher incidence of pathogen presence or enteric lesions than heavier or faster-growing contemporaries. A total of 1,500 pigs were weighed at birth and divided into 5 birth weight (BRW) categories: <1, 1 to 1.25, 1.26 to 1.5, 1.51 to 1.75, and >1.76 kg. At weaning, 1,054 random pigs were moved to a commercial wean-to-finish barn. Pigs were weighed individually at 0 and 3 wk postweaning. Transition ADG was calculated as the ADG between wk 0 and 3 postweaning. One pig from each of the 10th, 30th, and 70th percentiles of tADG was used to create 1 set of 3 pigs with the same litter size and from the same parity sow. Forty pigs from each of the 3 tADG percentiles were matched for sex, litter size, and sow parity but not BRW to create 20 matched sets of 60 pigs. This allowed for the main effects of BRW and tADG to be studied as a 5 × 3 factorial design. At 3 and 22 wk postweaning, pigs were euthanized for organ system tissue evaluation. Lung, lymph node, and digesta were analyzed for presence of pathogens and for severity of microscopic lesions (0 = not present, 1 = present, with slight erosion, 2 = present, with moderate erosion, and 3 = present and severe erosion). Data were analyzed using PROC GENMOD and GLIMMIX, where pig served as the experimental unit. The fixed effects were BRW and tADG and the random effects were pen and set. There were no BRW × tADG interactions (P = 0.16). There was no correlation (P = 0.12) between tADG and pathogen presence at either 3 or 22 wk postweaning. Incidence and severity of microscopic lesions in the large intestine at 3 wk postweaning decreased linearly with increasing tADG (P = 0.01). Lesion incidence and severity were also affected (P < 0.04) by tADG at 22 wk postweaning, with greater stomach incidence in the 10th percentile. Birth weight affected (P = 0.02) haemolytic Escherichia coli and Salmonella spp. B (includes Salmonella typhimurium) isolation at 3 wk postweaning as well as Brachyspira spp. isolation at 22 wk postweaning (P = 0.05) but in mixed directions. There were no effects (P = 0.21) of BRW or tADG on serum or ileum mucosa immune markers. In summary, it is apparent from this research that neither BRW nor tADG are likely causes of pathogen or lesion incidence.

Shigella sonnei is a human-adapted pathogen that is emerging globally as the dominant agent of bacterial dysentery. To investigate local establishment, we sequenced the genomes of 263 Vietnamese S. sonnei isolated over 15 y. Our data show that S. sonnei was introduced into Vietnam in the 1980s and has undergone localized clonal expansion, punctuated by genomic fixation events through periodic selective sweeps. We uncover geographical spread, spatially restricted frontier populations, and convergent evolution through local gene pool sampling. This work provides a unique, high-resolution insight into the microevolution of a pioneering human pathogen during its establishment in a new host population.

During the 10 days commencing April 29, 2013, the Iowa State University Veterinary Diagnostic Laboratory received the first 4 of many submissions from swine farms experiencing explosive epidemics of diarrhea and vomiting affecting all ages, with 90-95% mortality in suckling pigs. Histology revealed severe atrophy of villi in all segments of the small intestines with occasional villus-epithelial syncytial cells, but testing for rotaviruses and Transmissible gastroenteritis virus (Alphacoronavirus 1) were negative. Negative-staining electron microscopy of feces revealed coronavirus-like particles and a pan-coronavirus polymerase chain reaction (PCR) designed to amplify a conserved region of the polymerase gene for all members in the family Coronaviridae produced expected 251-bp amplicons. Subsequent sequencing and analysis revealed 99.6-100% identity among the PCR amplicons from the 4 farms and 97-99% identity to the corresponding portion of the polymerase gene of Porcine epidemic diarrhea virus (PEDV) strains, with the highest identity (99%) to strains from China in 2012. Findings were corroborated at National Veterinary Services Laboratories using 2 nested S-gene and 1 nested N-gene PCR tests where the sequenced amplicons also had the highest identity with 2012 China strains. Whole genome sequence for the virus from 2 farms in 2 different states using next-generation sequencing technique was compared to PEDV sequences available in GenBank. The 2013 U.S. PEDV had 96.6-99.5% identity with all known PEDV strains and the highest identity (>99.0%) to some of the 2011-2012 Chinese strains. The nearly simultaneous outbreaks of disease, and high degree of homology (99.6-100%) between the PEDV strains from the 4 unrelated farms, suggests a common source of virus.

Objective: In Vietnam, shigellosis/dysentery, typhoid fever, and cholera are important enteric diseases. To better understand their epidemiology, we determined temporal trends, seasonal patterns, and climatic factors associated with high risk periods in eight regions across Vietnam., Methods: We quantified monthly cases and incidence rates (IR) for each region from national surveillance data (1991-2001). High- and low-disease periods were defined from the highest and lowest IRs (1 SD above and below the mean) and from outbreaks from positive outliers (4 SDs higher in 1 month or 2 SDs higher in > or = 2 consecutive months). We used general linear models to compare precipitation, temperature, and humidity between high- and low-risk periods., Results: Shigellosis/dysentery was widespread and increased 2.5 times during the study period, with the highest average IRs found between June and August (2.1/100,000-26.2/100,000). Typhoid fever was endemic in the Mekong River Delta and emerged in the Northwest in the mid-1990s, with peaks between April and August (0.38-8.6). Cholera was mostly epidemic along the central coast between May and November (0.07-2.7), and then decreased dramatically nationwide from 1997 onward. Significant climate differences were found only between high- and low-disease periods. We were able to define 4 shigellosis/dysentery, 14 typhoid fever, and 8 cholera outbreaks, with minimal geotemporal overlap and no significant climatic associations., Conclusions: In Vietnam, bacterial enteric diseases have distinct temporal trends and seasonal patterns. Climate plays a role in defining high- and low-disease periods, but it does not appear to be an important factor influencing outbreaks.