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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Non-typhoid Salmonella infection | Patients with a non-typhoid Salmonella infection. Blood samples, stool samples and clinical information will be collected. |
| |
| Acute, infectious diarrhea | Patients with acute, infectious diarrhea without non-typhoid Salmonella infection. Blood samples, stool samples and clinical information will be collected. |
| |
| Healthy individuals | Healthy individuals with no symptoms of acute or chronic diarrhea. Blood samples, stool samples and clinical information will be collected. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Blood samples | Other | Blood samples will be collected and analyzed at different study time points |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
General inclusion criteria:
Inclusion criteria for patients with non-typhoid Salmonella infection (n=20)
Inclusion criteria for patients with acute, infectious diarrhea without non-typhoid Salmonella infection (n=10)
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:
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20 patients with a non-typhoid Salmonella infection, 10 patients with acute, infectious diarrhea without non-typhoid Salmonella infection, 10 healthy individuals
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Benjamin Misselwitz, PD Dr.med. | Contact | +41 44 255 1111 | benjamin.misselwitz@usz.ch |
| Name | Affiliation | Role |
|---|---|---|
| Benjamin Misselwitz, PD Dr.med. | Division of Gastroenterology, University Hospital Zurich Zurich, Switzerland, 8091 | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Division of Gastroenterology, University Hospital Zurich | Recruiting | Zurich | 8091 | Switzerland |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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Blood and stool samples
| Stool samples | Other | Stool samples will be collected and analyzed at different study time points |
|
| Clinical information | Other | Clinical information will be collected at different study time points using questionnaires |
|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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) |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |