Clinical trial NCT03494101: Interaction Between Non-typhoid Salmonella, Host Microbiota, and Immune System During Acute Infection and Remission
Official title: Interaction Between Non-typhoid Salmonella, Host Microbiota, and Immune System During Acute Infection and Remission
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Salmonella Infection Non-Typhoid
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2018-04-11
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 20 patients with a non-typhoid Salmonella infection, 10 patients with acute, infectious diarrhea without non-typhoid Salmonella infection, 10 healthy individuals

Brief summary: Stool and blood samples from patients with a non-typhoid Salmonella infection will be collected during an observation period of six months and analyzed for changes in the microbiota diversity and composition, mutation rates in the Salmonella strains and the specific immune response evoked by the infection. Findings are compared to healthy individuals and individuals with acute, infectious diarrhea caused by other microorganisms.

Detailed description: Infection processes of a non-typhoid Salmonella infection in humans are not well understood and so far, only little research has been conducted in this area. Findings from preclinical studies, using mouse models, attributed a fundamental role in infection control to the gut microbiota and the host immune system (antibody response). In mouse models a non-typhoid Salmonella infection provokes a pronounced antibody response and salmonella-inflicted gut inflammation alters the microbiota diversity and composition in the gut lumen. To date there is only scarce evidence on similar effects in humans.

During the study, longitudinal stool and blood samples will be collected from patients with a non-typhoid Salmonella infection at different study time points (2 weeks, 4 weeks and 6 months after positive Salmonella stool culture) and analyzed for changes in the microbiota, mutation rates in the Salmonella strains and the specific immune response evoked by the infection (e.g. anti-bodies). At each study time point clinical information will be investigated with a questionnaire to assess current symptoms, medication etc. Findings will be compared to healthy individuals and patients with acute, infectious diarrhea caused by other microorganisms than non-typhoid Salmonella.

Eligibility criteria: Inclusion Criteria:

General inclusion criteria:

* Signed informed consent.
* Ability to understand and follow study procedures and understand informed consent
* Age 18-75 years.

Inclusion criteria for patients with non-typhoid Salmonella infection (n=20)

* Acute diarrhea (≥3 bowel movements per day for ≤4 weeks)
* Stool cultures positive for non-typhoid Salmonella ≤4 weeks before inclusion

Inclusion criteria for patients with acute, infectious diarrhea without non-typhoid Salmonella infection (n=10)

* Acute diarrhea (≥3 bowel movements per day for ≤4 weeks)
* Stool cultures negative for non-typhoid Salmonella infection within ≤ 4 weeks

Inclusion criteria for healthy volunteers (n=10)

• No symptoms of acute or chronic diarrhea (2 bowel movements per week to 2 per day)

Exclusion Criteria:

* Current use of antibiotics
* Medication with immunosuppressants (e.g. corticoids, biological therapy).
* Major medical/surgical/psychiatric condition requiring ongoing management. Minor well controlled conditions (i.e. medically controlled arterial hypertension, occupational asthma) may be present.
* Major diagnosis known to chronically affect gut microbiota (e.g. inflammatory bowel disease, liver cirrhosis, colon carcinoma, systemic sclerosis).
* Current diagnosis of a hematological disorder (e.g. severe anemia with hemoglobin \<7 g/dl, leukemia) or any other absolute contraindication for blood donation.
* Participation in other clinical study interfering with study procedures.
* Inability to understand study procedures in order to provide inform consent.
* Previous participation in the same study.

Primary outcomes:
measure: Genomic mutations in non-typhoid Salmonella strains
timeFrame: 4 weeks after index stool culture
Secondary outcomes:
measure: Quantification of non-typhoid Salmonella genes associated with: tissue invasion, antibiotic resistance and virulence factors
timeFrame: 4 weeks after index stool culture
measure: Identification of most frequently mutated surface antigenes of non-typhoid Salmonella
timeFrame: 4 weeks after index stool culture
measure: Gen Cluster Expression
timeFrame: 2 weeks, 4 weeks and 6 months after index stool culture
measure: Mutated non-typhoid Salmonella strains
timeFrame: 4 weeks and 6 months after index stool culture
measure: Microbiota changes
timeFrame: 2 weeks, 4 weeks and 6 months after index stool culture
measure: Antibody producing cells
timeFrame: 2 weeks and 4 weeks after index stool culture
measure: Antibody producing B-cell clones
timeFrame: 4 weeks after index stool culture
measure: Antibody repertoire
timeFrame: 2 weeks and 4 weeks after index stool culture
measure: Antigen- Antibody recognition
timeFrame: 4 weeks and 6 months after index stool culture
measure: Development of irritable bowel syndrome
timeFrame: End of observational period (6 months)
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: Division of Gastroenterology, University Hospital Zurich
Study officials:
affiliation: Division of Gastroenterology, University Hospital Zurich Zurich, Switzerland, 8091
name: Benjamin Misselwitz, PD Dr.med.
role: PRINCIPAL_INVESTIGATOR
References: