Shigellosis caused by Shigella sonnei
Conditions
Interventions
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Healthy adults between 18 and 45 years of age (inclusive) Kilifi County residents. 2. Able and willing (in the Investigator’s opinion) to comply with all study requirements. 3. Provide informed consent. 4. Demonstrate comprehension of the protocol procedures and knowledge of study by passing a test of understanding (pass grade 100%). 5. Use of effective method of contraception for the entire duration of study (prior to study start and up to study completion) (women only). Female volunteers will be asked to provide their family planning records to verify. Effective contraception is defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly, in accordance with the product label. Examples of these include: combined oral contraceptives; injectable progestogen; implants of etenogestrel or levonorgestrel; intrauterine device or intrauterine system; male partner sterilisation at least 6 months prior to the female volunteer’s entry into the study, and the relationship is monogamous; male condom combined with a vaginal spermicide (foam, gel, film, cream or suppository); and male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository). 6. Willingness to participate for an inpatient stay lasting approximately 12 days or longer and an outpatient follow-up lasting about 12 months from challenge. 7. Available for all planned follow-up visits.
Exclusion criteria
Exclusion criteria: 1. Presence of a significant medical condition (e.g., psychiatric conditions, alcohol or illicit drug abuse/dependency, or gastrointestinal disease, such as peptic ulcer, symptoms or evidence of active gastritis or gastroesophageal reflux disease, inflammatory bowel disease), or other laboratory abnormalities which in the opinion of the investigator precludes participation in the study. 2. Known immunosuppressive illness for example those with cancer, on immunosuppressive therapy, HIV etc. 3. Positive serology results for HIV, HBsAg, or HCV antibodies. 4. Evidence of inflammatory arthritis on exam and/or HLA-B27 positive. 5. Family history of inflammatory arthritis. 6. Clinically significant abnormalities in screening lab haematology or serum chemistry, as determined by PI or PI in consultation with the research monitor and Sponsor. 7. Known allergies to fluoroquinolones, ß-lactams or trimethoprim-sulfamethoxazole (any of the three are exclusionary). 8. Fewer than 3 stools per week or more than 3 stools per day as the usual frequency. 9. History of diarrhoea in the 2 weeks prior to planned inpatient phase. 10. Use of antibiotics during the 7 days before receiving the challenge inoculum dosing. 11. Use of prescription and/or OTC medications that contain imodium, acetaminophen, aspirin, ibuprofen, and/or other non-steroidal anti-inflammatory drugs, during the 48 hours prior to investigational product administration. 12. Confirmed PCR positive for SARS-COV-2 three days before challenge i.e., Day -3. 13. Use of any medication known to affect the immune function within 30 days preceding receipt of the challenge inoculum or planned use during the active study period. 14. Serologic evidence of prior S. sonnei infection as determined by ELISA. 15. A chronic disease for which doses of prescription medications are not stable for at least the past 3 months. 16. Have known immunocompromised household contacts for example those with cancer, on immunosuppressive therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety of increasing doses of lyophilised S. sonnei 53G in Kenyan adults;Safe dose of lyophilised S. sonnei 53G that consistently yields a shigellosis attack rate of =60% in Kenyan adults. | — |
Secondary
| Measure | Time frame |
|---|---|
| Effects of lyophilized S. sonnei 53G on stool output and clinical symptoms;Qualitative and quantitative faecal shedding patterns of the S. sonnei 53G challenge strain following experimental infection.;Mucosal and systemic immune responses to O antigen (O-Ag) on the lipopolysaccharide (LPS) “O” LPS, and invasion protein antigens IpaB and IpaC (both IgA and IgG) following challenge with 53G. | — |
Countries
Kenya
Contacts
Public ContactPhilip Bejon
KEMRI CGMRC
Outcome results
None listed