Cause Of Infectious Diarrhea Research Articles

Early treatment for Clostridioides difficile infection: retrospective cohort study.

Clostridioides difficile (CDI) is a common cause of infectious diarrhea. The current recommendation is to initiate empirical antibiotic treatment for suspected CDI who have an anticipated delay of confirmatory results or fulminant colitis. This is based on limited clinical trials. The study aims to examine the impact of early treatment on mortality and clinical outcomes. This retrospective cohort study included adult patients with CDI. Early treatment was defined as the initiation of an anti-Clostridioides medication within the first 24h following stool sampling. Outcomes were 30 and 90day mortality, length of hospital stay (LOS), recurrence, and colectomy rate. To address potential bias, propensity score matching followed by logistic regression was performed, P value less than 5% was considered statistically significant. Study cohort consisted of 796 patients; clinical characteristics were balanced following matching. There was no difference, in favor of early treatment, between the groups regarding 30day mortality and 90day mortality with HR of 0.91 (95% CI 0.56-1.47) and 0.7 (95% CI 0.45-1.08), respectively. No statistically significant difference in recurrence rate, ICU admission or colectomy rate was observed. The LOS was shorter in the early-treatment group with 6days vs. 8days. Early treatment for CDI had shortened hospital stay. However, it did not affect clinical outcomes in adult patients.

Leveraging data from a longitudinal birth cohort to improve attribution of diarrhea etiology among children in low-resource settings.

Attributing infectious causes of diarrhea is critical to inform treatment and burden estimates. The attributable fraction (AF) approach based on the association between pathogen quantity and diarrhea has been frequently used but may underestimate incidence. We leveraged data from the multisite birth-cohort Malnutrition and Enteric Disease (MAL-ED) Study, where diarrheal and non-diarrheal stools were collected from 1,715 children from 0-2 years. We compared attribution using a longitudinal AF (LAF) method that considers the temporal association between pathogen quantity and diarrhea symptoms to previously-published AF estimates. For rotavirus and Shigella, attribution did not meaningfully change. For others like adenovirus 40 & 41, astrovirus, norovirus GII, sapovirus, Campylobacter jejuni or C coli, ST ETEC, typical EPEC, and Cryptosporidium, attribution increased, demonstrating longitudinal data may be informative for pathogens with weak associations between quantity and diarrhea. We further derived accuracy-based, pathogen-specific quantity cut-offs that may improve attribution in the absence of longitudinal data.

Functional characterization of Fur from the strict anaerobe Clostridioides difficile provides insight into its redox-driven regulatory capacity.

Clostridioides (formerly Clostridium) difficile is a leading cause of infectious diarrhea associated with antibiotic therapy. The ability of this anaerobic pathogen to acquire enough iron to proliferate under iron limitation conditions imposed by the host largely determines its pathogenicity. However, since high intracellular iron catalyzes formation of deleterious reactive hydroxyl radicals, iron uptake is tightly regulated at the transcriptional level by the ferric uptake regulator Fur. Several studies relate lacking a functional fur gene in C. difficile cells to higher oxidative stress sensitivity, colonization defect and less toxigenicity, although Fur does not appear to directly regulate either oxidative stress response genes or pathogenesis genes. In this work, we report the functional characterization of C. difficile Fur and describe an additional oxidation sensing Fur-mediated mechanism independent of iron, which affects Fur DNA-binding. Using electrophoretic mobility shift assays, we show that Fur binding to the promoters of fur, feoA and fldX genes, identified as iron and Fur-regulated genes in vivo, is specific and does not require co-regulator metal under reducing conditions. Fur treatment with H2O2 produces dose-dependent soluble high molecular weight species unable to bind to target promoters. Moreover, Fur oligomers are dithiotreitol sensitive, highlighting the importance of some interchain disulfide bond(s) for Fur oligomerization, and hence for activity. Additionally, the physiological electron transport chain NADPH-thioredoxin reductase/thioredoxin from Escherichia coli reduces inactive oligomerized C. difficile Fur that recovers activity. In conjunction with available transcriptomic data, these results suggest a previously underappreciated complexity in the control of some members of the Fur regulon that is based on Fur redox properties and might be fundamental for the adaptive response of C. difficile during infection.

Infectious etiologies of persistent and chronic diarrhea in Asian developing countries: A systematic review and meta-analysis.

Infectious causes of diarrhea contribute significantly to morbidity in Asia. We conducted a systematic review and meta-analysis of the prevalence of infectious etiologies of persistent and chronic diarrhea in Asian adults. Searches were performed on PubMed and Scopus for studies from January 1, 1970, to May 30, 2023. Sixteen studies were identified and included. The meta-analysis was conducted with the random-effects method, estimating the pooled prevalence of groups of infectious pathogens as causes of persistent and chronic diarrhea among Asian adults. The findings were highly heterogeneous and indicative of publication bias. The majority of studies were conducted on persons living with human immunodeficiency virus infection (PLHIV). The studies were predominantly from low-income and middle-income Asian countries. The most common cause was parasitic, with a pooled prevalence of 0.52 (95% confidence interval 0.28-0.65, I2=99%, Cochran's Q=1027.44, P<0.01), followed by bacterial, fungal, and viral causes, which were substantially rarer. Negative microbiological testing was also common, with a pooled prevalence for a negative test being 0.37 (95% confidence interval 0.17-0.52, I2=99%, Cochran's Q=1027.44, P<0.01). Subgroup analyses of studies conducted among PLHIV, from year 2000 and among those conducted in Southeast Asia showed a similar prevalence of parasitic causes of diarrhea. In conclusion, inAsian adults with persistent and chronic diarrhea, parasitic causes were most prevalent. However, the estimate of true prevalence is limited by significant heterogeneity among the available studies. More study in this field is required, especially examining PLHIV in the post-antiretroviral therapy era and from high-income countries.

Clostridioides difficile in calves, cattle and humans from Dutch dairy farms: Predominance of PCR ribotype 695 (clade 5, sequence type 11) in cattle

BackgroundClostridioides difficile is a leading cause of infectious diarrhea in both humans and livestock. In particular, C. difficile strains belonging to sequence type (ST) 11 are common enteropathogens. The aim of this study was to determine the presence and genetic relatedness of C. difficile types in dairy cattle and calves. MethodDutch dairy farms were visited between February and December 2021. Feces was collected from adult dairy cattle and calves of two age categories (<4 weeks and 4 weeks-4 months). Fecal samples were also requested from dairy farmers, family members and employees. Fecal samples were cultured in an enrichment medium for 10–15 days and subcultured on solid media for capillary PCR ribotyping and whole genome sequencing. ResultsC. difficile was detected on 31 out of 157 (19.8%) dairy farms. The highest prevalence was found in calves <4 weeks (17.5%). None of the 99 human samples collected were positive. Thirty-seven cultured isolates belonged to 11 different PCR ribotypes (RT) of which RT695 (56.8%) and RT078/126 (16.2%) were most abundant. In the database of the Netherlands National Expertise Centre for C. difficile infections (CDI, >10.000 patient isolates), RT695 was found in only two patients with hospital-onset CDI, diagnosed in 2020 and 2021. Sequence analysis of 21C. difficile RT695 from cattle revealed that all isolates belonged to clade 5, ST11 and contained genes encoding toxin A, toxin B and binary toxin. RT695 strains carried antimicrobial resistance genes typically found in clade 5C. difficile. Groups of genetically related RT695 isolates were found between dairy farms, whereas identical strains were only present in individual farms. ConclusionsC. difficile was found in ∼20% of dairy farms with a predominance of the relatively unknown RT695. Isolates of RT695 belonged to the same clade and sequence type as RT078/126, which is recognized as an important zoonotic type.

Characteristics of Pathogenic Escherichia coli Associated with Diarrhea in Children under Five Years in Northwestern Ethiopia.

Diarrheagenic Escherichia coli (DEC) are the leading cause of infectious diarrhea and pose a significant global, regional, and national burden of disease. This study aimed to investigate the prevalence of six DEC pathotypes in children with diarrhea and determine their antibiotic resistance patterns. Samples from 107 diarrheagenic children were collected and processed for Escherichia coli (E. coli). Single-plex PCR was used to detect target virulence genes as well as characterize and categorize DEC pathotypes. Antibiotic resistance patterns were determined by the Kirby-Bauer disk diffusion method. E. coli was detected in 79 diarrheal stool samples, accounting for 73.8% of the samples collected. Additionally, 49.4% (39 out of 79) of the isolates harbored various typical virulence factors. Results revealed six pathotypes of virulence: enterotoxigenic E. coli (ETEC) (53.8%), enteropathogenic E. coli (EPEC) (12.8%), enteroaggregative E. coli (EAEC) (10.3%), Heteropathotypes (7.8%), Shiga toxin-producing E. coli (STEC), and enterohemorrhagic E. coli (EHEC) (7.7% each). The isolates exhibited high antibiotic resistance against trimethoprim/sulfamethoxazole (82.1%), amoxicillin (79.5%), ampicillin (74.4%), gentamicin (69.2%), and streptomycin (64.1%). An overall occurrence of 84.6% of multiple-drug resistance was observed in the isolates, with resistance ranging from three to four antibiotic classes. Our findings revealed a high level of pathogenic E. coli that were highly resistant to multiple categories of antibiotics among children in the Awi zone. These findings highlight the potential role of pathogenic E. coli in childhood diarrhea in tropical low-resource settings and underscore the need for continued research on the characteristics of pathogenic and antibiotic-resistant strains.

Effective treatment of Clostridioides difficile infection improves survival and affects graft-versus-host disease: a multicenter study by the Polish Adult Leukemia Group

Clostridioides difficile infection (CDI) is the most common cause of infectious diarrhea after allogeneic hematopoietic cell transplantation (allo-HCT). The impact of CDI and its treatment on allo-HCT outcomes and graft-versus-host disease (GVHD), including gastrointestinal GVHD (GI-GVHD) is not well established. This multicenter study assessed real-life data on the first-line treatment of CDI and its impact on allo-HCT outcomes. Retrospective and prospective data of patients with CDI after allo-HCT were assessed. We noted statistically significant increase in the incidence of acute GVHD and acute GI-GVHD after CDI (P = 0.005 and P = 0.016, respectively). The first-line treatment for CDI included metronidazole in 34 patients, vancomycin in 64, and combination therapy in 10. Treatment failure was more common with metronidazole than vancomycin (38.2% vs. 6.2%; P < 0.001). The need to administer second-line treatment was associated with the occurrence or exacerbation of GVHD (P < 0.05) and GI-GVHD (P < 0.001) and reduced overall survival (P < 0.05). In the multivariate analysis, the risk of death was associated with acute GVHD presence before CDI (hazard ratio [HR], 3.19; P = 0.009) and the need to switch to second-line treatment (HR, 4.83; P < 0.001). The efficacy of the initial CDI treatment affects survival and occurrence of immune-mediated GI-GVHD after allo-HCT. Therefore, agents with higher efficacy than metronidazole (vancomycin or fidaxomicin) should be administered as the first-line treatment.

Cryptosporidium parvum infection alters the intestinal mucosa transcriptome in neonatal calves: implications for immune function.

One of the leading causes of infectious diarrhea in newborn calves is the apicomplexan protozoan Cryptosporidium parvum (C. parvum). However, little is known about its immunopathogenesis. Using next generation sequencing, this study investigated the immune transcriptional response to C. parvum infection in neonatal calves. Neonatal male Holstein-Friesian calves were either orally infected (N = 5) or not (CTRL group, N = 5) with C. parvum oocysts (gp60 subtype IIaA15G2R1) at day 1 of life and slaughtered on day 7 after infection. Total RNA was extracted from the jejunal mucosa for short read. Differentially expressed genes (DEGs) between infected and CTRL groups were assessed using DESeq2 at a false discovery rate < 0.05. Infection did not affect plasma immunohematological parameters, including neutrophil, lymphocyte, monocyte, leucocyte, thrombocyte, and erythrocyte counts as well as hematocrit and hemoglobin concentration on day 7 post infection. The immune-related DEGs were selected according to the UniProt immune system process database and were used for gene ontology (GO) and pathway enrichment analysis using Cytoscape (v3.9.1). Based on GO analysis, DEGs annotated to mucosal immunity, recognizing and presenting antigens, chemotaxis of neutrophils, eosinophils, natural killer cells, B and T cells mediated by signaling pathways including toll like receptors, interleukins, tumor necrosis factor, T cell receptor, and NF-KB were upregulated, while markers of macrophages chemotaxis and cytosolic pattern recognition were downregulated. This study provides a holistic snapshot of immune-related pathways induced by C. parvum in calves, including novel and detailed feedback and feedforward regulatory mechanisms establishing the crosstalk between innate and adaptive immune response in neonate calves, which could be utilized further to develop new therapeutic strategies.

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.

Noticeable immune dysregulation-and-suppression in parvovirus affected dogs

Canine parvovirus type 2 (CPV-2) is one of the most common causes of infectious diarrhea in small animals, with high mortality and morbidity. Information on the specific treatment option(s) for CPV diseases (CPVD) is unachievably little. So, the treatment is mainly supportive one. Disruption of dog's innate immune system in viral diseases simply occurs; presumably, the CPV-2 may change the level of some TLRs, interleukins, CD4 and CD8 in the leukocytes of CPVD dogs, and disruptive activities of these immune molecules might be attributable to severe CPVD in dogs. Study on the role of the key immune molecules in CPVD is rare. Herein, by conducting and relating the clinical, para-clinical, immunological and molecular diagnostic tests, we tried to establish how some key immune molecules behave in blood of parvovirus affected dogs. As such, in the 1st study, the mRNA levels of TLR2, TLR4, TLR9, IL-1β, IL-6, CD4 and CD8 genes in the leukocytes of CPVD were assessed with quantitative (q)RT-PCR along with CPV-2 detection by rapid immunochromatography and PCR tests. In a 2nd study, the same measurements as in the 1st study were evaluated in two groups of mild versus severe clinical signs of CPVD. Both in the 1st and the 2nd studies leukopenia, much more pronounced in the severe CPVD, and immune dysregulation were observed. In the 1st study, a noticeable increase in the mRNA levels of TLR2 and TLR4 was detected with a slight decrease in TLR9 and a significant decrease in the expression of IL-1β, IL-6, CD4 and CD8 in leukocytes of CPV-infected dogs. Compared to the mild CPVD, the intense of downregulating effects on those immune molecules in the 2nd study was remarkably much more pronounced in the severe CPVD. Overall, it proves strong immune dysregulation and suppression/incompetence and potential T-cells exhaustion in severely CPV-2-affected dogs. Technically and clinically, this would be substantially applicable in canine medicine. By targeting those key immune molecules and their signaling pathways, new clinicodiagnostic approaches for CPVD can be evolved, and biotechnicoclinically this would be substantially applicable in all physiopathological conditions of dogs.

Biogeographic distribution and molecular epidemiology of Clostridioides (Clostridium) difficile in Western Australian soils.

Clostridioides (Clostridium) difficile is a leading cause of infectious diarrhea in humans and production animals and can be found in a variety of environmental sources. The prevalence and diversity of multi-locus sequence type clade 5 strains of C. difficile in Australian production animals suggest Australia might be the ancestral home of this lineage of One Health importance. To better understand the role of the environment in the colonization of humans and animals in Australia, it is important to investigate these endemic sources. This study describes the prevalence, molecular epidemiology, and biogeographic distribution of C. difficile in soils of Western Australia. A total of 321 soil samples from remote geographical locations across the eight health regions of Western Australia were screened for C. difficile and isolates characterized by PCR ribotyping and toxin gene profiling. C. difficile was isolated from 31.15% of samples, with the highest prevalence in the Perth Metropolitan Health Region (49.25%, n = 33/67). Overall, 52 different strains [PCR ribotypes (RTs)] were identified, with 14 being novel, and 38% (38/100) of isolates being toxigenic, the most common of which was RT014/020. Five unique novel isolates showed characteristics similar to C. difficile clade 5. This is the first study of C. difficile isolated from soils in Australia. The high prevalence and heterogeneity of C. difficile strains recovered suggest that soils play a role in the survival and environmental dissemination of this organism, and potentially its transmission among native wildlife and production animals, and in community and hospital settings.IMPORTANCEClostridium difficile is a pathogen of One Health importance. To better understand the role of the environment in human and animal colonization/infection, it is critical that autochthonous reservoirs/sources of C. difficile be investigated. This is the first study of C. difficile isolated from soils of Western Australia (WA). Here, the ecology of C. difficile in WA is described by examining the geographic distribution, molecular epidemiology, and diversity of C. difficile isolated from soils across WA.

Seroprevalence Study of Conserved Enterotoxigenic Escherichia coli Antigens in Globally Diverse Populations.

Enterotoxigenic Escherichia coli (ETEC) are common causes of infectious diarrhea among young children of low-and middle-income countries (LMICs) and travelers to these regions. Despite their significant contributions to the morbidity and mortality associated with childhood and traveler's diarrhea, no licensed vaccines are available. Current vaccine strategies may benefit from the inclusion of additional conserved antigens, which may contribute to broader coverage and enhanced efficacy, given their key roles in facilitating intestinal colonization and effective enterotoxin delivery. EatA and EtpA are widely conserved in diverse populations of ETEC, but their immunogenicity has only been studied in controlled human infection models and a population of children in Bangladesh. Here, we compared serologic responses to EatA, EtpA and heat-labile toxin in populations from endemic regions including Haitian children and subjects residing in Egypt, Cameroon, and Peru to US children and adults where ETEC infections are sporadic. We observed elevated IgG and IgA responses in individuals from endemic regions to each of the antigens studied. In a cohort of Haitian children, we observed increased immune responses following exposure to each of the profiled antigens. These findings reflect the wide distribution of ETEC infections across multiple endemic regions and support further evaluation of EatA and EtpA as candidate ETEC vaccine antigens.

Cryptosporidium parvum hijacks a host's long noncoding RNA U90926 to evade intestinal epithelial cell-autonomous antiparasitic defense.

Cryptosporidium is a zoonotic apicomplexan parasite that infects the gastrointestinal epithelium and other mucosal surfaces in humans. It is an important opportunistic pathogen in AIDS patients and a leading cause of infectious diarrhea and diarrheal-related death in children worldwide. The intestinal epithelial cells provide the first line of defense against Cryptosporidium infection and play a central role in activating and regulating the host's antiparasitic response. Increasing evidence suggests that long noncoding RNAs (lncRNAs) participate in host-pathogen interactions and play a regulatory role in the pathogenesis of diseases but the underlying molecular mechanisms are not fully understood. We previously identified a panel of host lncRNAs that are upregulated in murine intestinal epithelial cells following Cryptosporidium infection, including U90926. We demonstrate here that U90926 is acting in a pro-parasitic manner in regulating intestinal epithelial cell-autonomous antiparasitic defense. Inhibition of U90926 resulted in a decreased infection burden of the parasite while overexpression of U90926 showed an increase in infection burden in cultured murine intestinal epithelial cells. Induction of U90926 suppressed transcription of epithelial defense genes involved in controlling Cryptosporidium infection through epigenetic mechanisms. Specifically, transcription of Aebp1, which encodes the Aebp1 protein, a potent modulator of inflammation and NF-κB signaling, was suppressed by U90926. Gain- or loss-of-function of Aebp1 in the host's epithelial cells caused reciprocal alterations in the infection burden of the parasite. Interestingly, Cryptosporidium carries the Cryptosporidium virus 1 (CSpV1), a double-stranded (ds) RNA virus coding two dsRNA fragments, CSpV1-dsRdRp and CSpV1-dsCA. Both CSpV1-dsRdRp and CSpV1-dsCA can be delivered into infected cells as previously reported. We found that cells transfected with in vitro transcribed CSpV1-dsCA or CSpV1-dsRdRp displayed an increased level of U90926, suggesting that CSpV1 is involved in the upregulation of U90926 during Cryptosporidium infection. Our study highlights a new strategy by Cryptosporidium to hijack a host lncRNA to suppress epithelial cell-autonomous antiparasitic defense and allow for a robust infection.

Fecal microbiota transplantation for refractory immune-checkpoint-inhibitor colitis.

2657 Background: Immune-related colitis (irColitis) is associated with significant morbidity and mortality among patients treated with immune checkpoint inhibition (ICI). The gut microbiota has been implicated in the pathophysiology of irColitis. We hypothesized that abnormal fecal microbiome features would be present at the time of irColitis onset, and that restoring the microbiome to a healthy state would mitigate disease severity. Methods: We present fecal microbiota profiles from N = 18 patients with irColitis and describe our clinical experience of N = 5 patients treated with healthy donor fecal microbial transplantation (FMT). Recipients of ICI between May 2019 and June 2021 at Memorial Sloan Kettering Cancer Center whose stool samples were investigated for diarrhea were included in our dataset (N = 100). N = 18 patients with a diagnosis of irColitis were identified. Patients that had other causes of diarrhea were classified as part of the “no-colitis” comparator group (N = 32). All patients with infectious causes of diarrhea ( C. difficile, other GI pathogen) were excluded from the analysis. Stool samples were profiled by whole metagenomic shotgun sequencing. FMT products from individual healthy donors were procured from the OpenBiome fecal bank and delivered via colonoscopy. Results: There was no difference in alpha diversity between the irColitis and no-colitis groups. Patients in the irColitis group had significantly higher relative abundance of Proteobacteria at the time of symptom onset compared to the no-colitis group (p = 0.04). Escherichia spp. and Klebsiella spp. were associated with irColitis, also described in multivariate analyses. Five patients with irColitis refractory to steroids and biologics received healthy-donor FMT, with initial clinical improvement in irColitis symptoms observed in four of five (80%) patients. Two out of five subsequently exhibited recurrence of irColitis symptoms following a course of antibiotics for pneumonia and urinary tract infection, respectively. Both received a second “salvage” FMT that was, again, followed by clinical improvement of irColitis. In these two cases, fecal profiles demonstrated dysbiotic shifts in the gut microbiome post-antibiotics characterized by Proteobacteria expansion, which was salvaged post salvage FMT, mirroring clinical resolution of irColitis symptoms. Conclusions: We observed that Proteobacteria expansion is characteristic of irColitis at time of symptom onset. FMT was followed by clinical improvements in several cases of refractory irColitis. Strategies to restore or prevent microbiome injury—with a particular focus on salvage FMT after antibiotic injury—in the context of immunotherapy toxicities could be further explored in prospective clinical trials.

Cryptosporidium uses CSpV1 to activate host type I interferon and attenuate antiparasitic defenses

Cryptosporidium infects gastrointestinal epithelium and is a leading cause of infectious diarrhea and diarrheal-related death in children worldwide. There are no vaccines and no fully effective therapy available for the infection. Type II and III interferon (IFN) responses are important determinants of susceptibility to infection but the role for type I IFN response remains obscure. Cryptosporidium parvum virus 1 (CSpV1) is a double-stranded RNA (dsRNA) virus harbored by Cryptosporidium spp. Here we show that intestinal epithelial conditional Ifnar1−/− mice (deficient in type I IFN receptor) are resistant to C. parvum infection. CSpV1-dsRNAs are delivered into host cells and trigger type I IFN response in infected cells. Whereas C. parvum infection attenuates epithelial response to IFN-γ, loss of type I IFN signaling or inhibition of CSpV1-dsRNA delivery can restore IFN-γ-mediated protective response. Our findings demonstrate that type I IFN signaling in intestinal epithelial cells is detrimental to intestinal anti-C. parvum defense and Cryptosporidium uses CSpV1 to activate type I IFN signaling to evade epithelial antiparasitic response.

Climate change and imperatives to ascertain causes of infectious diarrhoea in low-income and middle-income countries

Climate change and imperatives to ascertain causes of infectious diarrhoea in low-income and middle-income countries

SG-APSIC1166: Strategies to reduce hospital-onset Clostridioides difficile infections in an acute-care hospital in Singapore

Objectives: Control of Clostridioides difficile infections (CDIs) in healthcare facilities presents significant challenges to infectious disease physicians, infection prevention and control practitioners, and environmental services staff. CDI is a common cause of infectious diarrhea and is associated with significant morbidity, mortality, and healthcare cost. A high infection rate was documented in our institution in 2017, higher than the national infection rate. Strategies to reduce hospital-onset CDI were implemented after review of international guidelines and relevant literature. The impact on hospital-onset CDI was assessed. Methods: The following strategies were implemented beginning early in 2018: (1) contact precautions for patients with diarrhea; (2) early recognition and diagnosis of C. difficile infection; (3) prompt isolation of C. difficile patients; (4) emphasis on hand hygiene and contact precautions; (5) enhanced environmental cleaning with chlorine-based disinfectant and use of UV-C and ionized hydrogen peroxide for equipment disinfection; (6) enhanced cleaning and disinfection using sporicidal wipes for shared high-risk equipment; (7) audit and feedback regarding compliance with practices and environmental cleaning; and (8) collaboration with antibiotics stewardship program (ASP) to reduce inappropriate antibiotic use. Hospital-onset CDI cases were tracked by infection prevention and control nurses using definitions from the Singapore Ministry of Health. Results: In total, 135 hospital-onset C. difficile infection cases occurred in 2017, a rate of 4.2 per 10,000 patient days. This rate gradually decreased to 3.0 in 2018 and to 2.3 in 2020, with an average of 87 infections per year. This rate further decreased to 1.8 infections per 10,000 patient days in 2021, with 61 clinical infections. Conclusions: Using multimodal strategies, CGH achieved a gradual and steady reduction in hospital-onset CDI over several years. These strategies require close collaboration among various departments to achieve the desired outcome.

Butyrate Differentiates Permissiveness to Clostridioides difficile Infection and Influences Growth of Diverse C. difficile Isolates.

A disrupted "dysbiotic" gut microbiome engenders susceptibility to the diarrheal pathogen Clostridioides difficile by impacting the metabolic milieu of the gut. Diet, in particular the microbiota-accessible carbohydrates (MACs) found in dietary fiber, is one of the most powerful ways to affect the composition and metabolic output of the gut microbiome. As such, diet is a powerful tool for understanding the biology of C. difficile and for developing alternative approaches for coping with this pathogen. One prominent class of metabolites produced by the gut microbiome is short-chain fatty acids (SCFAs), the major metabolic end products of MAC metabolism. SCFAs are known to decrease the fitness of C. difficile in vitro, and high intestinal SCFA concentrations are associated with reduced fitness of C. difficile in animal models of C. difficile infection (CDI). Here, we use controlled dietary conditions (8 diets that differ only by MAC composition) to show that C. difficile fitness is most consistently impacted by butyrate, rather than the other two prominent SCFAs (acetate and propionate), during murine model CDI. We similarly show that butyrate concentrations are lower in fecal samples from humans with CDI than in those from healthy controls. Finally, we demonstrate that butyrate impacts growth in diverse C. difficile isolates. These findings provide a foundation for future work which will dissect how butyrate directly impacts C. difficile fitness and will lead to the development of diverse approaches distinct from antibiotics or fecal transplant, such as dietary interventions, for mitigating CDI in at-risk human populations. IMPORTANCE Clostridioides difficile is a leading cause of infectious diarrhea in humans, and it imposes a tremendous burden on the health care system. Current treatments for C. difficile infection (CDI) include antibiotics and fecal microbiota transplant, which contribute to recurrent CDIs and face major regulatory hurdles, respectively. Therefore, there is an ongoing need to develop new ways to cope with CDI. Notably, a disrupted "dysbiotic" gut microbiota is the primary risk factor for CDI, but we incompletely understand how a healthy microbiota resists CDI. Here, we show that a specific molecule produced by the gut microbiota, butyrate, is negatively associated with C. difficile burdens in humans and in a mouse model of CDI and that butyrate impedes the growth of diverse C. difficile strains in pure culture. These findings help to build a foundation for designing alternative, possibly diet-based, strategies for mitigating CDI in humans.

Anti-Bacterial Activity of Shadanga Ghrita &amp; Its Ghana Vati on Diaarrhoea Causing Enteropathogens

Background: In Ayurvedic classics Diarrhoea is described with the name of Atisaar. In modern science it is closely correlated with watery Diarrhoea which is defined as having loose or watery stools at least three times per day or more frequently than normal for an individual. Diarrhoea caused by bacterial pathogens is a global health problem, especially in developing countries and enteric bacterial pathogens are the main cause of infectious Diarrhoea. Ayurvedic literature have lot of unexplored or least tested medicine, Shadanga Ghrita is one of those Ayurvedic formulation used in the management of Tridoshaja Atisaar. But it has some disadvantages such as bitterness in taste, unpalatability, feasibility and inconvenience in transportation. Considering these, here an attempt was made to transform it into a new dosage form i.e., Ghana Vati. Aim &amp; Objectives: Aim &amp; objectives of present study was to evaluate the anti-bacterial activity of Shadanga Ghrita and its new dosage form on Diarrhoea causing enteropathogens. Material and Methods: Samples of Shadanga Ghrita &amp; its Ghana Vati were prepared as per Sharangdhar Samhita Madhyama Khanda. All the samples of finished products were analyzed on organoleptic and physico-chemical parameters. Anti-bacterial study was done by using Well Diffusion Method and Muller Hinton Agar Media was used to evaluate anti-bacterial activity against S. aureus, E. coli, S. enterica, S. boydii, Y. enterolitica, A. species, and C. perfringens. Result: Both samples showed significant anti-bacterial activity against Diarrhoea causing enteropathogens. Conclusion: Shadanga Ghrita is more effective Antibacterial agent, as it was formulated by Sneha Paka Kalpana method; Gou- Ghrita has potentiated the anti- bacterial effect of it.

S2017 Double Trouble: A Case of Co-Infection With Campylobacter and Giardia in a HIV-Positive Patient

Introduction: Patients with immunosuppressed states such as uncontrolled HIV are at increased risk for opportunistic infections including acute infectious diarrhea. Here, we present a case of a noncompliant HIV patient who presented with a complaint of acute diarrhea with resulting weight loss. Work-up was significant for co-infection with giardia and campylobacter as a result of receptive anal sexual intercourse. Case Description/Methods: A 45-year-old transgender male to female patient with a past medical history of poorly controlled HIV infection not actively on antiviral therapy and chronic Hepatitis B (HBV) infection presented with initial complaint of acute diarrhea for one week with accompanying weight loss. The patient concurrently complained of a diffuse, painful, pruritic rash for 5 days. A thorough history revealed the patient had just returned from Miami, where she reported multiple sexual partners with recent unprotected oral and anal intercourse. On initial presentation, the patient was tachycardic and febrile to 104.8, with generalized abdominal tenderness and a diffuse macular rash involving scalp, torso, genitals, and extremities, including palms and soles. The patient was admitted and started on acyclovir, vancomycin and ceftriaxone. A comprehensive stool panel was positive for both campylobacter and giardia. The patient was also noted to have CMV viremia, a HIV viral load of 38,000, and a positive rapid plasma reagin. The infectious disease team was consulted and the patient was treated with a single dose of tinidazole and 2 doses of metronidazole followed by a 7-day course of ciprofloxacin. Her acute diarrhea resolved, at which point she restarted antiretroviral therapy, and completed a 14-day course of penicillin for her syphilis. She was discharged home with close follow up with her infectious disease specialist. Discussion: This case highlights the increased risk of opportunistic infections in the setting of poorly controlled HIV and unprotected sexual intercourse as highlighted by this patient’s co-infection with both giardia and campylobacter. Campylobacter and giardia are 2 commonly associated foodborne illnesses, however they can be transmitted via unprotected oral-anal sex. In addition to compliance with HIV treatment, patients should consider barrier methods during receptive sex to prevent fecal-oral transmission. In sum, our case highlights the importance of keeping a broad differential of infectious causes of diarrhea, especially in the immunocompromised population.