Transcriptomic Responses for the Identification of Pathogens

NCT ID: NCT04878549

Last Updated: 2025-03-03

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 2000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-05-02
• Study Completion Date: 2025-06-30

Brief Summary

Acute undifferentiated febrile infection (AUFI) is a common presenting syndrome in low-resource settings and better diagnostics are urgently needed to improve patient management and guide disease prevention interventions. Assessment of the host gene expression response to infection in endemic populations has demonstrated significant promise as a new approach to identifying patients with enteric fever and for potential in differentiating between other causes of AUFI. Signatures identified through new data analytic techniques could be developed into a point-of-care test for use in endemic settings.

In this multisite diagnostic evaluation study we will collect prospective clinical, laboratory and diagnostic data from two endemic settings to evaluate host gene expression signatures for detecting enteric fever and for determining the cause of AUFI in LMIC settings.

Conditions

Enteric Fever; Acute Febrile Illness; Typhoid; Paratyphoid Fever; Fever

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Febrile Adults

1200 adult participants (15 to 65 years old) with a febrile illness without localising features and reported duration of 3-14 days.

5-gene transcription signature

Intervention Type: DIAGNOSTIC_TEST

This is a prospective multisite diagnostic evaluation study to assess a novel approach to the diagnosis of enteric fever. The index test of host gene transcription responses by a 5 gene-signature will be compared to the reference test of blood culture confirmation for a diagnosis of enteric fever in patients with AUFI.

Controls

400 afebrile, healthy adult participants (15 to 65 years old).

5-gene transcription signature

Intervention Type: DIAGNOSTIC_TEST

This is a prospective multisite diagnostic evaluation study to assess a novel approach to the diagnosis of enteric fever. The index test of host gene transcription responses by a 5 gene-signature will be compared to the reference test of blood culture confirmation for a diagnosis of enteric fever in patients with AUFI.

Febrile Children

400 child participants (2 to 14 years old) with a febrile illness without localising features and reported duration of 3-14 days. This is an exploratory arm of the study.

5-gene transcription signature

Intervention Type: DIAGNOSTIC_TEST

This is a prospective multisite diagnostic evaluation study to assess a novel approach to the diagnosis of enteric fever. The index test of host gene transcription responses by a 5 gene-signature will be compared to the reference test of blood culture confirmation for a diagnosis of enteric fever in patients with AUFI.

Interventions

5-gene transcription signature

This is a prospective multisite diagnostic evaluation study to assess a novel approach to the diagnosis of enteric fever. The index test of host gene transcription responses by a 5 gene-signature will be compared to the reference test of blood culture confirmation for a diagnosis of enteric fever in patients with AUFI.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

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:

• 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).

• Age greater than or equal to 2 years and less than 15 years
• As above for adult participants.

Exclusion Criteria

• 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.

• 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.'

• 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.

• 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.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Christian Medical College, Vellore, India

OTHER

Sponsor Role: collaborator

KEMRI-Wellcome Trust Collaborative Research Program

OTHER

Sponsor Role: collaborator

University of Sheffield

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas Darton

Role: STUDY_DIRECTOR

University of Sheffield

Locations

Christian Medical Centre

Vellore, , India

Site Status: RECRUITING

Countries

India

Central Contacts

Farah Shahi

Role: CONTACT

f.shahi@sheffield.ac.uk

01142159522

Thomas Darton

Role: CONTACT

t.darton@sheffield.ac.uk

Other Identifiers

157365

Identifier Type: -

Identifier Source: org_study_id