Interaction Between Non-typhoid Salmonella, Host Microbiota, and Immune System During Acute Infection and Remission

Salmonella Infection Non-Typhoid Clinical Trial

Official title:

Interaction Between Non-typhoid Salmonella, Host Microbiota, and Immune System During Acute Infection and Remission

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03494101
• Other study ID #: SALMONELLA Study
• Status: Recruiting
• Start date: June 15, 2018
• Est. completion date: January 31, 2020

Study information

• Verified date: June 2018
• Source: University of Zurich
• Contact: Benjamin Misselwitz, PD Dr.med.
• Phone: +41 44 255 1111
• Email: benjamin.misselwitz[@]usz.ch
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: January 31, 2020
• Est. primary completion date: January 31, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• Infection
• Salmonella Infection Non-Typhoid
• Salmonella Infections

Intervention

Other:
• Blood samples
Blood samples will be collected and analyzed at different study time points
• Stool samples
Stool samples will be collected and analyzed at different study time points
• Clinical information
Clinical information will be collected at different study time points using questionnaires

Locations

Country	Name	City	State
Switzerland	Division of Gastroenterology, University Hospital Zurich	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
University of Zurich

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Genomic mutations in non-typhoid Salmonella strains	Analyze the evolution of non-typhoid Salmonella during acute infection and remission in humans. The primary variable of interest is the number of observed genomic mutations in non-typhoid Salmonella strains.	4 weeks after index stool culture
Secondary	Quantification of non-typhoid Salmonella genes associated with: tissue invasion, antibiotic resistance and virulence factors	Total number of Salmonella genes associated with tissue invasion Total number of antibiotic resistance genes Total number of virulence factor genes	4 weeks after index stool culture
Secondary	Identification of most frequently mutated surface antigenes of non-typhoid Salmonella	Identification of escape mechanisms of non-typhoid Salmonella (i.e. mutation of surface antigens) to avoid specific immune responses (i.e. antibodies) during acute infection and remission.	4 weeks after index stool culture
Secondary	Gen Cluster Expression	Identification of Salmonella gene clusters expressed during early phases of infection compared to remission.	2 weeks, 4 weeks and 6 months after index stool culture
Secondary	Mutated non-typhoid Salmonella strains	Quantification of mutated non-typhoid Salmonella strains that escape specific immune responses.	4 weeks and 6 months after index stool culture
Secondary	Microbiota changes	Composition (i.e. number of bacteria species identified) and relative diversity of the gut microbial community during acute non-typhoid Salmonella infection and remission. Findings will be compared to changes occurring in the microbiota of healthy individuals and individuals with acute, infectious diarrhea caused by microorganisms other than Salmonella.	2 weeks, 4 weeks and 6 months after index stool culture
Secondary	Antibody producing cells	Composition (i.e. number of antibody-producing cells) and relative diversity of antibody-producing cells specific for non-typhoid Salmonella.	2 weeks and 4 weeks after index stool culture
Secondary	Antibody producing B-cell clones	Number of antibody-producing cell clones (and their corresponding antibodies) against non-typhoid Salmonella isolated from peripheral blood B cells of subjects during remission. Measured variable: Number of Salmonella-specific B-cells per ml blood 4 weeks after infection.	4 weeks after index stool culture
Secondary	Antibody repertoire	Identification of the antibody repertoire against non-typhoid Salmonella during acute infection in peripheral blood. Measured variable: Antibody titers against various non-typhoid Salmonella strains.	2 weeks and 4 weeks after index stool culture
Secondary	Antigen- Antibody recognition	Number of antigens of non-typhoid Salmonella recognized by the antibodies isolated from the previous endpoint.	4 weeks and 6 months after index stool culture
Secondary	Development of irritable bowel syndrome	Number of patients who develop an irritable bowel syndrome after a non-typhoid Salmonella infection.	End of observational period (6 months)