ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03494101
Recruitment Status : Not yet recruiting
First Posted : April 11, 2018
Last Update Posted : April 11, 2018
Sponsor:
Information provided by (Responsible Party):
University of Zurich

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.

Condition or disease Intervention/treatment
Salmonella Infection Non-Typhoid Other: Blood samples Other: Stool samples Other: Clinical information

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.


Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Interaction Between Non-typhoid Salmonella, Host Microbiota, and Immune System During Acute Infection and Remission
Estimated Study Start Date : April 15, 2018
Estimated Primary Completion Date : January 31, 2020
Estimated Study Completion Date : January 31, 2020

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Non-typhoid Salmonella infection
Patients with a non-typhoid Salmonella infection. Blood samples, stool samples and clinical information will be collected.
Other: Blood samples
Blood samples will be collected and analyzed at different study time points

Other: Stool samples
Stool samples will be collected and analyzed at different study time points

Other: Clinical information
Clinical information will be collected at different study time points using questionnaires

Acute, infectious diarrhea
Patients with acute, infectious diarrhea without non-typhoid Salmonella infection. Blood samples, stool samples and clinical information will be collected.
Other: Blood samples
Blood samples will be collected and analyzed at different study time points

Other: Stool samples
Stool samples will be collected and analyzed at different study time points

Other: Clinical information
Clinical information will be collected at different study time points using questionnaires

Healthy individuals
Healthy individuals with no symptoms of acute or chronic diarrhea. Blood samples, stool samples and clinical information will be collected.
Other: Blood samples
Blood samples will be collected and analyzed at different study time points

Other: Stool samples
Stool samples will be collected and analyzed at different study time points

Other: Clinical information
Clinical information will be collected at different study time points using questionnaires




Primary Outcome Measures :
  1. Genomic mutations in non-typhoid Salmonella strains [ Time Frame: 4 weeks after index stool culture ]
    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.


Secondary Outcome Measures :
  1. Quantification of non-typhoid Salmonella genes associated with: tissue invasion, antibiotic resistance and virulence factors [ Time Frame: 4 weeks after index stool culture ]
    Total number of Salmonella genes associated with tissue invasion Total number of antibiotic resistance genes Total number of virulence factor genes

  2. Identification of most frequently mutated surface antigenes of non-typhoid Salmonella [ Time Frame: 4 weeks after index stool culture ]
    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.

  3. Gen Cluster Expression [ Time Frame: 2 weeks, 4 weeks and 6 months after index stool culture ]
    Identification of Salmonella gene clusters expressed during early phases of infection compared to remission.

  4. Mutated non-typhoid Salmonella strains [ Time Frame: 4 weeks and 6 months after index stool culture ]
    Quantification of mutated non-typhoid Salmonella strains that escape specific immune responses.

  5. Microbiota changes [ Time Frame: 2 weeks, 4 weeks and 6 months after index stool culture ]
    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.

  6. Antibody producing cells [ Time Frame: 2 weeks and 4 weeks after index stool culture ]
    Composition (i.e. number of antibody-producing cells) and relative diversity of antibody-producing cells specific for non-typhoid Salmonella.

  7. Antibody producing B-cell clones [ Time Frame: 4 weeks after index stool culture ]
    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.

  8. Antibody repertoire [ Time Frame: 2 weeks and 4 weeks after index stool culture ]
    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.

  9. Antigen- Antibody recognition [ Time Frame: 4 weeks and 6 months after index stool culture ]
    Number of antigens of non-typhoid Salmonella recognized by the antibodies isolated from the previous endpoint.

  10. Development of irritable bowel syndrome [ Time Frame: End of observational period (6 months) ]
    Number of patients who develop an irritable bowel syndrome after a non-typhoid Salmonella infection.


Biospecimen Retention:   Samples With DNA
Blood and stool samples


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03494101


Contacts
Contact: Benjamin Misselwitz, PD Dr.med. +41 44 255 1111 benjamin.misselwitz@usz.ch

Locations
Switzerland
Division of Gastroenterology, University Hospital Zurich
Zurich, Switzerland, 8091
Sponsors and Collaborators
University of Zurich
Investigators
Principal Investigator: Benjamin Misselwitz, PD Dr.med. Division of Gastroenterology, University Hospital Zurich Zurich, Switzerland, 8091

Responsible Party: University of Zurich
ClinicalTrials.gov Identifier: NCT03494101     History of Changes
Other Study ID Numbers: SALMONELLA Study
First Posted: April 11, 2018    Key Record Dates
Last Update Posted: April 11, 2018
Last Verified: April 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Infection
Communicable Diseases
Salmonella Infections
Enterobacteriaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections