Salmonella Paratyphoid A Infections and Infestations
Conditions
Interventions
This is an inpatient dose-finding controlled human infection model (CHIM) study of Salmonella Paratyphi A infection in healthy adult participants in Pakistan. In total, up to 60 participants will be r
OVG 2014/01, REC Ref: 14/SC/1204, OVG 2018/07, REC Ref: 21/SC/0330). Because of pre-existing immunity in an endemic country, we anticipate that a higher dose of challenge may be required to successful
the programme will therefore run as a dose-escalation study, increasing a log of the dose at a time for each cohort of 3-5 participants enrolled. Given this study is the first SPA CHIM in Pakistan, we
Sponsors
Aga Khan University
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Inclusion criteria
Inclusion criteria: 1. Willing and able to give informed consent. 2. Aged 18 -55yrs. 3. In good health as determined by medical history, physical examination and clinical judgment of the study team. 4. Available for all required appointments (agree to being residential in Karachi until confirmed clearance). 5. Able to comply with all study requirements, including infection control precautions. 6. Agree to medical record review. 7. Agree to avoid antipyretic/anti-inflammatory treatment from challenge until advised by a study doctor or until 14 days after challenge. 8. Agree to refrain from donating blood for the duration of the study. 9. Agree to avoid vaccination during the study period. 10. For participants of childbearing potential, they should be willing to ensure that they or their partner use effective contraception until confirmed clearance. 11. Agree to remaining admitted in the hospital and take leave from work for a period of 10-20 days
Exclusion criteria
Exclusion criteria: 1. History of significant organ/system disease that could interfere with study conduct or completion, in the opinion of the study team. Including, for example, but not restricted to: 1.1 Cardiovascular disease 1.2 Respiratory disease 1.3 Haematological disease 1.4 Endocrine disorders 1.5 Renal or bladder disease, including history of renal calculi 1.6 Biliary tract disease, including biliary colic, asymptomatic gallstones or polyps or previous cholecystectomy 1.7 Gastro-intestinal disease including chronic diarrhoea, inflammatory bowel disease, irritable bowel syndrome or diseases requiring use of regular antacids, H2-receptor antagonists, proton pump inhibitors, laxatives or prokinetic agents 1.8 Neurological disease 1.9 Metabolic disease 1.10 Psychiatric illness requiring hospitalisation, or other mental health condition 1.11 Known or suspected drug abuse 1.12 Known or suspected alcohol misuse 1.13 Infectious disease 1.14 Coagulation disorder 2. Known or suspected impairment of immune function, alteration of immune function, or prior immune exposure that may alter immune function to paratyphoid, resulting from, for example: 2.1 Congenital or acquired immunodeficiency, including IgA deficiency 2.2 History of auto-immune disease 2.3 Human Immunodeficiency Virus or symptoms/signs suggestive of an HIV-associated condition 2.4 Receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 12 months or long-term systemic corticosteroid therapy 2.5 Receipt of immunoglobulin or any blood product transfusion within 3 months of study start 2.6 History of cancer (except squamous cell or basal cell carcinoma of the skin and cervical carcinoma in situ) 3. HLA-B27 positive. 4. Moderate or severe depression or anxiety as classified by the Hospital Anxiety and Depression Score at screening or challenge that is deemed clinically significant by the study doctors. 5. Weight less than 50 kg. 6. Presence of implants or prosthetic material. 7. Anyone taking long-term medication (e.g. analgesia, anti-inflammatories or antibiotics) that may affect symptom reporting or interpretation of the study results or that may interact with antibiotics used for treatment of paratyphoid A (in particular drugs that could prolong corrected QT interval). 8. Contraindication to fluoroquinolones, macrolide antibiotics, co-trimoxazole, cefixime or ceftriaxone. 9. Family history of aneurysmal disease. 10. Participants who are pregnant, lactating or unwilling to ensure that they or their partner use effective contraception from 30 days until three negative stool samples confirm clearance. 11. Scheduled elective surgery or other procedures requiring general anaesthesia during the study period. 12. Participants who have participated in another research study involving an investigational product that might affect risk of paratyphoid infection or compromise the integrity of the study within the 30 days prior to enrolment, or who plan to enrol in another research study during the follow-up study period. 13. Significant blood donation or planned blood donation prior to enrolment. 14. Detection of any abnormal results from screening investigations (at the clinical discretion of the study team). 15. Prolonged corrected QT interval (>450 milliseconds) or significant clinical abnormality on ECG screening. 16. Evidence
Countries
Pakistan
Contacts
Public ContactFarah Naz Qamar
Outcome results
None listed