Challenge Non-Typhoidal Salmonella (CHANTS) Study (CHANTS)

Inclusion Criteria: Participants must satisfy all the following criteria to be considered eligible for the study: Agree to give informed consent for participation in the study. Aged between 18 and 50 years inclusive at time of challenge. In good health as determined by medical history, physical examination, and clinical judgment of the study team. Agree (in the study team's opinion) to comply with all study requirements, including capacity to adhere to good personal hygiene and infection control precautions. Agree to allow his or her General Practitioner (and/or Consultant if appropriate), to be notified of participation in the study. Agree to allow study staff to contact his or her GP to access the participant's medical history and vaccination records. Agree to allow UKHSA and the local health protection unit to be informed of their participation in the study. Agree to give his or her close contacts written information informing them of the participant's involvement in the study and offer them voluntary screening for Salmonella carriage. Agree to a period of inpatient quarantine whilst symptomatic (In exceptional circumstances, the duration of inpatient quarantine may be extended.) Agree to have 24-hour contact with study staff during the four weeks post challenge and can ensure that they are contactable by mobile phone for the duration of the study period until antibiotic completion. Agree to allow the study team to hold the name and 24-hour contact number of a close friend, relative or housemate who will be kept informed of the study participant's whereabouts for the duration of the challenge period after quarantine (from the time of challenge until completion of antibiotic course). This person will be contacted if study staff are unable to contact the participant after discharge from inpatient quarantine. Have internet access to allow completion of the e-diary and real-time safety monitoring. Agree to avoid antipyretic/anti-inflammatory treatment from the time of challenge (Day 0) until advised by a study doctor or until 14 days after challenge. Agree to refrain from donating blood for the duration of the study. Agree to provide their National Insurance/Passport number for the purposes of Trial over-volunteering prevention system (TOPS) registration and for payment of reimbursement expenses. Participants must have received at least two doses of a SARS-CoV-2 vaccines that has been approved for use by the MHRA (or other national regulatory authority) four weeks prior to enrolment. Proficient in English at a level sufficient to understand, retain, weigh up and communicate the study details as outlined in the participant information sheet, in the opinion of the study investigator. Exclusion Criteria: The participant will not be enrolled if any of the following apply: History of microbiologically confirmed Salmonella infection. History of significant organ-specific and/or systemic disease that could interfere with trial conduct or completion. Including, for example, but not restricted to: Cardiovascular disease, including specifically Atherosclerotic disease Stable or unstable angina Previous myocardial infarction Valvular heart disease Vascular disease, including specifically Documented aneurysmal arterial disease Peripheral arterial disease Endovascular prosthesis oRespiratory disease Haematological disease including sickle cell disease and sickle cell trait. Endocrine disorders, including specifically diabetes mellitus Renal or bladder disease, including history of renal calculi Biliary tract disease, including specifically biliary colic, asymptomatic gallstones, or previous cholecystectomy Gastro-intestinal disease including specifically, a current requirement for antacids, H2-receptor antagonists, proton pump inhibitors or laxatives OR Inflammatory bowel disease OR Confirmed diagnosis of irritable bowel syndrome as defined by the Rome IV criteria. Neurological disease Metabolic disease Autoimmune disease Psychiatric illness requiring hospitalisation Known or suspected drug and/or alcohol misuse disorder Chronic/Active Infectious disease including active tuberculosis Severe infection requiring hospitalisation for intravenous antibiotics within the last 10 years. Exceptions to this would include a short course of intravenous antibiotics for appendicitis, biliary sepsis, diverticulitis, and cellulitis. History of malaria infection History of joint replacement History of any orthopaedic/osseous implanted prosthesis Presence of other internal implanted device e.g. permanent pacemaker Have any known or suspected impairment of immune function, alteration of immune function, or prior immune exposure that may alter immune function to Salmonella infection resulting from, for example: Congenital or acquired immunodeficiency, including IgA deficiency Human Immunodeficiency Virus infection or symptoms/signs suggestive of an HIV-associated condition Evidence of severe primary immunodeficiency, for example, severe combined immunodeficiency, Wiskott-Aldrich syndrome, and other combined immunodeficiency syndromes. Currently being treated for malignant disease with immunosuppressive chemotherapy or radiotherapy, or who have received such treatment within at least the last six months Individuals who have received a solid organ transplant and are currently on immunosuppressive treatment Individuals who have received a bone marrow transplant, until within 12 months of finishing all immunosuppressive treatment, Individuals receiving systemic high-dose steroids until at least three months after treatment has stopped. Individuals receiving other types of immunosuppressive drugs (alone or in combination with lower doses of steroids) until at least six months after terminating such treatment. Receipt of immunoglobulin or any blood product transfusion within 3 months of study start. History of cancer (except squamous cell or basal cell carcinoma of the skin and cervical carcinoma in situ). 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 . Weight less than 50kg . Anyone taking long-term medication (e.g. analgesia, anti-inflammatories or antibiotics) that may affect symptom reporting or interpretation of the study results. Contraindication to cephalosporin, fluroquinolone, or macrolide antibiotics. Female participants who are pregnant, lactating or who are unwilling to ensure that they or their partner use effective contraception 30 days prior to challenge and continue to do so until two negative stool samples, a minimum of 3 weeks after completion of antibiotic treatment, have been obtained. Full-time, part-time, or voluntary occupations involving: Clinical healthcare work Social work with direct contact with young children (defined as those attending pre-school groups or nursery or aged under 2 years), or other clinically vulnerable children, adolescents Clinical or social work with direct contact with highly susceptible patients or persons in whom Salmonella infection would have particularly serious consequences (unless willing to avoid work until demonstrated not to be infected with Salmonella in accordance with guidance from Public Health England and willing to allow study staff to inform their employer). Full time, part time or voluntary occupations involving: o Commercial food handling (involving preparing or serving unwrapped foods not subjected to further heating) Close household contact with: Young children (defined as those attending pre-school groups, nursery or those aged less than 2 years) Any individual who is immunocompromised. Pregnant women Household contacts aged over 70 years Scheduled elective surgery or other procedures requiring general anaesthesia during the study period. Participants who have participated in another research study involving an investigational product that might affect risk of Salmonella infection or compromise the integrity of the study within the 30 days prior to enrolment (e.g. significant volumes of blood already taken in previous study) . Detection of any abnormal results from screening investigations, unless deemed not clinically significant. Any other social, psychological or health issues which, in the opinion of the study staff, may Put the participant or their contacts at risk because of participation in the study, Adversely affect the interpretation of the primary endpoint data, Impair the participant's ability to participate in the study. Having previously received any experimental Salmonella vaccine as part of a clinical trial Have participated in previous Salmonella Typhi or Paratyphi challenge studies (with ingestion of challenge agent). Have a prolonged corrected QT interval (>450 milliseconds) on ECG screening Any employee of the sponsor or research site personnel directly affiliated with this study or their immediate family members. Inability to comply with any of the study requirements (at the discretion of the study staff). Temporary exclusion criteria at challenge Participants will be temporarily excluded from challenge if presenting at the challenge visit with the following: Positive lateral flow test for SARS-CoV-2 Significant acute or acute-on-chronic infection within the previous 7 days or have experienced fever (>37.5C) or subjective febrile symptoms within the previous 3 days. History of any antibiotic therapy during the previous 5 days. Any systemic corticosteroid (or equivalent) treatment in the previous 14 days, or for more than seven consecutive days within the past 3 months. Therapy with antacids, proton pump inhibitors or H2-receptor antagonists within 24 hours prior to challenge. Detection of gastrointestinal pathogens (other than Salmonella) in stool culture/PCR collected at the pre-challenge assessment (Day-7) including Shigella spp., Campylobacter spp., E. Coli O157, Giardia spp and Cryptosporidum spp, until two subsequent samples are negative. Detection of Salmonella spp. in stool prior to challenge (Day - 7) will result in exclusion from the study. Detection of Extended spectrum beta lactamase producing organisms or Carabapenem resistant organisms until two subsequent samples are negative.