Transcriptomic Responses for the Identification of Pathogens

NCT04878549 | Recruiting

• 1 other identifier: 157365
• Study Type: observational
• Target: 2,000
• Locations: 1 country
• Sites: 1

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

Keywords

Gene Expression Profiling; RNA-Seq

Outcome Measures

Primary Outcomes (1)

• Sensitivity and specificity (AUROC) of a diagnostic score derived from transcriptional responses by a 5-gene transcription signature (STAT1, SLAMF8, PSME2, WARS, ALDH1A1) in classifying patients with blood culture-confirmed enteric fever.

  Evaluate the performance of a host gene transcription signature for detecting enteric fever in adults presenting with acute undifferentiated fever (AUFI)

  2.5 years

Secondary Outcomes (2)

• Number of participants with diagnosis confirmed by laboratory testing.

  2.5 years

• Number of participants presenting with mild, moderate or severe illness by clinical diagnosis according to validated prognostic scores such as sepsis scoring systems.

  2.5 years

Study Arms (3)

Febrile Adults

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

Diagnostic Test: 5-gene transcription signature

Controls

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

Diagnostic Test: 5-gene transcription signature

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.

Diagnostic Test: 5-gene transcription signature

Interventions

5-gene transcription signature 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; Febrile Adults; Febrile Children

Eligibility Criteria

• Age: 2 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

We will recruit adults aged 15 to 65 years presenting to hospital with fever at 2 sites: 1 in Asia and 1 in Africa where enteric fever is endemic. All included febrile participants will have a (documented) tympanic/rectal temperature of ≥ 38°C or an axillary/oral temperature of ≥ 37.8°C on presentation and will report a history of fever within the last 24 hours lasting 3 to 14 days. In parallel, healthy community control participants will be recruited from each site catchment area during the course of the study with enrolment designed to result in an even representation of age groups and seasonal variation. Identified signatures of infection will be explored in a cohort of febrile children aged 2 to 14 years at each site. 600 febrile adults, 200 febrile children and 200 afebrile adult controls will be recruited at each site.

You may qualify if:

• 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:

You may not qualify if:

• 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
• 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.'

Sponsors & Collaborators

• University of Sheffield: lead
• Christian Medical College, Vellore, India: collaborator
• KEMRI-Wellcome Trust Collaborative Research Program: collaborator

Study Sites (1)

Christian Medical Centre

Vellore, India

RECRUITING

MeSH Terms

Conditions

Typhoid Fever; Paratyphoid Fever; Fever

Condition Hierarchy (Ancestors)

Salmonella Infections; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Thomas Darton

  University of Sheffield

  STUDY DIRECTOR

Central Study Contacts

Farah Shahi

CONTACT

01142159522; f.shahi@sheffield.ac.uk

Thomas Darton

CONTACT

t.darton@sheffield.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 14 Days
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2021
• First Posted: May 7, 2021
• Study Start: May 2, 2022
• Primary Completion: June 1, 2025
• Study Completion: June 1, 2025
• Last Updated: March 3, 2025

Record last verified: 2025-02

Locations

IN (1)