| Eligibility |
Inclusion Criteria:
- Participants must satisfy all of the following criteria to be considered eligible for
the study:
- Agree to give informed consent for participation in the study.
- Aged between 18 and 60 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 GP (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 Public Health England 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 S.
Typhi carriage.
- Agree to have 24-hour contact with study staff during the four weeks post
challenge and are able to ensure that they are contactable by mobile phone for
the duration of the challenge 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 (from the time
of challenge until completion of antibiotic course). This person will be
contacted if study staff are unable to contact the participant.
- Have internet access on a daily basis 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
TOPS (The Over volunteering Prevention System) registration and for payment of
reimbursement expenses.
- Agree not to take part in another research study involving an IMP
(Investigational Medicinal Product) or challenge for the entire period of
recruitment in the current study.
Exclusion Criteria:
The participant will not be enrolled if any of the following apply:
- History of significant organ/system disease that could interfere with trial conduct or
completion. Including, for example, but not restricted to:
- Cardiovascular disease
- Respiratory disease
- Haematological disease
- Endocrine disorders
- Renal or bladder disease, including history of renal calculi
- Biliary tract disease, including biliary colic, asymptomatic gallstones or
previous cholecystectomy
- Gastro-intestinal disease including requirement for antacids, H2-receptor
antagonists, proton pump inhibitors or laxatives
- Neurological disease
- Metabolic disease
- Autoimmune disease
- Psychiatric illness requiring hospitalisation or known or suspected current drug
and/or alcohol misuse (alcohol misuse defined as an intake exceeding 42 units per
week)
- Infectious disease
- Have any known or suspected impairment of immune function, alteration of immune
function, or prior immune exposure that may alter immune function to typhoid resulting
from, for example:
- Congenital or acquired immunodeficiency, including Immunoglobulin A deficiency
- Human Immunodeficiency Virus infection or symptoms/signs suggestive of an
HIV-associated condition
- Receipt of immunosuppressive therapy such as anti-cancer chemotherapy or
radiation therapy within the preceding 12 months or long-term systemic
corticosteroid therapy
- 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).
- Screening positive for HLA B27 gene.
- Moderate or severe depression or anxiety as classified by the Hospital Anxiety and
Depression Score (score 11 or higher on either score) at screening or before challenge
that is deemed clinically significant by the study doctors .
- Weight less than 50kg .
- Presence of implants or prosthetic material.
- 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 ciprofloxacin 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 enrolment/challenge
and continue to do so until three negative stool samples, the first taken a minimum of
1 week after completion of antibiotic treatment and subsequent samples at least 48
hours apart each have been obtained.
- Occupational (unless willing and able to confirm that they are not working in the
following environment for the period of challenge to clearance confirmation):
- Full-time, part-time or voluntary occupations involving:
- Clinical or social work with direct contact with young children (defined as
those attending pre-school groups or nursery or aged under 2 years), or
- Clinical or social work with direct contact with highly susceptible patients
or persons in whom typhoid infection would have particularly serious
consequences (unless willing to avoid work for at least 6 weeks until
demonstrated not to be infected with S. Typhi 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:
- 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)
- Individual(s) who is (are) immunocompromised.
- Scheduled elective surgery (including dental work) 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 typhoid 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 (at the clinical
discretion of the study team).
- Inability to comply with any of the study requirements (at the discretion of the study
staff and the participant's General Practitioner).
- 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 typhoid vaccine within the last 3 years.
- Having been resident in an enteric fever endemic country for 6 months or more .
- Have previously been diagnosed with laboratory-confirmed typhoid or paratyphoid
infection or been given a diagnosis compatible with enteric fever.
- Have participated in previous typhoid or paratyphoid challenge studies (with ingestion
of challenge agent).
- Have a prolonged corrected QT interval (>450 milliseconds) on ECG screening.
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