Enteric fever in Phnom Penh, Cambodia
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB19906 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| ERR1877610_1.fastq.gz | Fastqsanger.gz | |||
| ERR1877610_2.fastq.gz | Fastqsanger.gz | |||
| ERR1878000_1.fastq.gz | Fastqsanger.gz | |||
| ERR1878000_2.fastq.gz | Fastqsanger.gz |
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Project description:Surveillance of Enteric Fever in India (SEFI)
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Project description:This studies describes the transcriptional response in whole blood derived from healthy adult volunteers experimentally infected with S. Paratyphi A. Samples were collected at pre-challenge baseline (Group: CTRL), at day 7 after challenge in those participants who stayed well over 14 days following challenge (Group: suspected Enteric Fever - sEF). Participants who developed signs of enteric fever were sampled at the time of inititiation of antibiotics (Group: EF).In this group diagnosis was confirmed by blood culture positive for S. Paratyphi (SPT). Antibiotic therapy commenced at time of diagnosis or at day 14 after challenge in those who did not develop symptoms. The clinical results of this study have been published in: Dobinson et al. Evaluation of the Clinical and Microbiological Response to Salmonella Paratyphi A Infection in the First Paratyphoid Human Challenge Model. Clin Infect Dis. 2017 Apr 15;64(8):1066-1073.
2019-09-02 | GSE114033 | GEO
Project description:Diagnostic host gene signature for distinguishing enteric fever from other febrile diseases
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Project description:BackgroundEnteric fever remains a major public health problem in low resource settings and antibiotic resistance is increasing. In Asia, an increasing proportion of infections is caused by Salmonella enterica serovar Paratyphi A, which for a long time was assumed to cause a milder clinical syndrome compared to Salmonella enterica serovar Typhi.MethodologyA retrospective chart review study was conducted of 254 unique cases of blood culture confirmed enteric fever who presented at a referral adult hospital in Phnom Penh, Cambodia between 2008 and 2015. Demographic, clinical and laboratory data were collected from clinical charts and antibiotic susceptibility testing was performed. Whole genome sequence analysis was performed on a subset of 121 isolates.ResultsOne-hundred-and-ninety unique patients were diagnosed with Salmonella Paratyphi A and 64 with Salmonella Typhi. In the period 2008-2012, Salmonella Paratyphi A comprised 25.5% of 47 enteric fever cases compared to 86.0% of 207 cases during 2013-2015. Presenting symptoms were identical for both serovars but higher median leukocyte counts (6.8 x 109/L vs. 6.3 x 109/L; p = 0.035) and C-reactive protein (CRP) values (47.0 mg/L vs. 36 mg/L; p = 0.034) were observed for Salmonella Typhi infections. All but one of the Salmonella Typhi isolates belonged to haplotype H58 associated with multidrug resistance (MDR) (i.e. resistance to ampicillin, chloramphenicol and co-trimoxazole).;42.9% actually displayed MDR compared to none of the Salmonella Paratyphi A isolates. Decreased ciprofloxacin susceptibility (DCS) was observed in 96.9% (62/64) of Salmonella Typhi isolates versus 11.5% (21/183) of Salmonella Paratyphi A isolates (all but one from 2015). All isolates were susceptible to azithromycin and ceftriaxone.ConclusionsIn Phnom Penh, Cambodia, Salmonella Paratyphi A now causes the majority of enteric fever cases and decreased susceptibility against ciprofloxacin is increasing. Overall, Salmonella Typhi was significantly more associated with MDR and DCS compared to Salmonella Paratyphi A.
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Project description:Genomic analysis of Salmonella enterica serotype Paratyphi A during an outbreak in Cambodia, 2013-2015
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Project description:Enteric nervous system (ENS) development relies on intestinal colonization by enteric neural crest-derived cells (ENCDCs). This is driven by a population of highly migratory and proliferative cells at the wavefront, but the unique molecular characteristics of the wavefront are unknown. ENCDCs from the wavefront and the trailing region proximal were isolated from 11.5 days post coitum (dpc) Wnt1-tdT mouse intestine and subjected to RNA-seq. Wavefront ENCDCs were transcriptionally distinct from trailing ENCDCs, and temporal modelling confirmed their relative immaturity. Wavefront ENCDCs exhibited altered expression of ECM and cytoskeletal genes, consistent with a migratory phenotype. Unlike postnatal enteric neural stem cells, wavefront ENCDCs possessed characteristics of cells undergoing epithelial-mesenchymal transition and lacked neuronal or glial commitment.
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Project description:ESBL-producing Escherichia coli in Cambodia
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Project description:BACKGROUND Enteric glia contribute to the pathophysiology of various intestinal immune-driven diseases, such as postoperative ileus (POI), a motility disorder and common complication after abdominal surgery. Enteric gliosis of the intestinal muscularis externa (ME) has been identified as part of POI development. However, the glia-restricted responses and activation mechanisms are poorly understood. The sympathetic nervous system becomes rapidly activated by abdominal surgery. It modulates intestinal immunity, innervates all intestinal layers, and directly interfaces with enteric glia. We hypothesized that sympathetic innervation controls enteric glia reactivity in response to surgical trauma. METHODS Sox10iCreERT2/Rpl22HA/+ mice were subjected to a mouse model of laparotomy or intestinal manipulation to induce POI. Histological, protein, and transcriptomic analyses were performed to analyze glia-specific responses. Interactions between the sympathetic nervous system and enteric glia were studied in mice chemically depleted of TH+ sympathetic neurons and glial-restricted Sox10iCreERT2/JellyOPfl/+/Rpl22HA/+ mice, allowing optogenetic stimulation of β-adrenergic downstream signaling and glial-specific transcriptome analyses. A laparotomy model was used to study the effect of sympathetic signaling on enteric glia in the absence of intestinal manipulation. Mechanistic studies included adrenergic receptor expression profiling in vivo and in vitro and adrenergic agonism treatments of primary enteric glial cell cultures to elucidate the role of sympathetic signaling in acute enteric gliosis and POI. RESULTS With ~4000 differentially expressed genes, the most substantial enteric glia response occurs early after intestinal manipulation. During POI, enteric glia switch into a reactive state and continuously shape their microenvironment by releasing inflammatory and migratory factors. Sympathetic denervation reduced the inflammatory response of enteric glia in the early postoperative phase. Optogenetic and pharmacological stimulation of β-adrenergic downstream signaling triggered enteric glia reactivity. Finally, distinct adrenergic agonists revealed β-1/2 adrenoceptors as the molecular targets of sympathetic–driven enteric glial reactivity. CONCLUSIONS Enteric glia act as early responders during post-traumatic intestinal injury and inflammation. Intact sympathetic innervation and active β-adrenergic receptor signaling in enteric glia is a trigger of the immediate glial postoperative inflammatory response. With immune-activating cues originating from the sympathetic nervous system as early as the initial surgical incision, adrenergic signaling in enteric glia presents a promising target for preventing POI development.
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Project description:This study was undertaken to define the molecular subtypes of cells within enteric neurospheres. Methods: We performed single-cell RNA sequencing on 3-dimensional neurosphere cultures derived from the small intestines of Plp1::GFP mice. These data show profiling results from the PLP1::GFP negative cell fraction ancillary to the positive fraction in series GSE184981. Results: We identify populations of enteric neurons and fibroblasts in the PLP1::GFP negative cell fraction of enteric neurospheres.
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