Transcriptomic Responses for the Identification of Pathogens

FEBRILE ADULTS- INCLUSION CRITERIA

• Age greater than or equal to 15 years and less than or equal to 65 years

• Participant is willing and they and/or an appropriate guardian/relative/representative is able to give informed consent for participation in the study and a follow-up (telephone) discussion at 14 days

• And either:

1. Febrile illness without localising features (see 'exclusion criteria' and 'screening' sections) where fever is defined as:

• documented tympanic/rectal temperature of ≥ 38°C or an axillary/oral temperature of ≥ 37.8°C, or a reported fever within the last 24 hours and

• Reported duration of fever 3-14 days or

2. Recently confirmed blood culture indicating enteric fever (confirmed within the previous 5 days)

• They may have had recent exposure to antimicrobials.

FEBRILE ADULTS- EXCLUSION CRITERIA

• The participant may not enter the study if ANY of the following apply:

• Unable to provide informed consent and no next of kin is willing and able to provide informed consent.

• For patients with febrile illness (included in (1) above): Any history or clinical suspicion of:

• Rheumatological or connective tissue disorder (e.g. Rheumatoid arthritis)

• Autoimmune condition (e.g. Autoimmune Hepatitis)

• Malignancy

• Active treatment with immunomodulating medications, or for tuberculosis (pulmonary or extrapulmonary) or any other chronic infection.

• Pregnancy (breast feeding mothers will NOT be excluded)

• No hospitalisation for more than 48 hours in the last 4 weeks

• Vaccination within 4 weeks prior to current admission

• Localising signs or symptoms of infection sufficient to diagnose the likely cause of acute febrile illness and thus prevent it from being 'undifferentiated.'

CONTROLS- INCLUSION CRITERIA

• Participant is willing and they are (and in 15-18 year olds, a guardian is) able to give informed consent for participation in the study

• Age greater than or equal to 15 years and less than or equal to 65 years

• They live outside of the normal/local catchment area for each hospital site

• Afebrile (as defined by no reported fever and temperature ≤ 38°C or an axillary/oral temperature of ≤ 37.8°C).

CONTROLS- EXCLUSION CRITERIA

• The participant may not enter the study if ANY of the following apply:

• Unable to provide informed consent and no next of kin (or parent/guardian in the case of a minor) is willing and able to provide informed consent.

• Current treatment for or prior history, or clinical suspicion of:

• Rheumatological or connective tissue disorder

• Autoimmune condition

• Malignancy

• Active treatment for tuberculosis (pulmonary or extrapulmonary) or clinical suspicion of active tuberculosis. Previous completed treatment is not a reason for exclusion.

• Active treatment with immunomodulating medications or any other chronic infection.

• Pregnant (breast feeding mothers will NOT be excluded)

• Hospitalisation within 4 weeks of recruitment

• Vaccination within 4 weeks prior to recruitment

• Antimicrobial use within 4 weeks of recruitment

• Participant reports feeling more unwell than usual on the day of enrolment.

EXPLORATORY AIMS- PAEDIATRIC CRITERIA; INCLUSION CRITERIA

• Age greater than or equal to 2 years and less than 15 years

• As above for adult participants.

EXPLORATORY AIMS- PAEDIATRIC CRITERIA; EXCLUSION CRITERIA

• Parent/guardian is unwilling, and/or patient aged 8 to 14 years is unwilling to assent to provide informed consent.

• As above for adult participants.