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Transcriptomic Responses for the Identification of Pathogens

ConditionsEnteric FeverAcute Febrile IllnessTyphoidParatyphoid FeverFever
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age2-65
SponsorUniversity of Sheffield

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

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

Febrile illness without localising features (see '

Disqualifiers

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.

Trial 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.

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

  • 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.

Treatment groups

2,000 Participants
are divided into 3 treatment groups
Group A: Febrile Adults1 intervention
Group B: Controls1 intervention
Group C: Febrile Children1 intervention

Trial outcomes

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)

Time frame
2.5 years

Secondary outcomes

1

Number of participants with diagnosis confirmed by laboratory testing.

Determine the frequency of other common causes of AUFI at each site.

Time frame
2.5 years
2

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

Assess the relationship between markers of clinical illness severity, likely infection cause and level of molecular perturbation.

Time frame
2.5 years

Other outcomes

Sponsors and contacts

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University of Sheffield

Lead sponsor

Christian Medical College, Vellore, India

Collaborator

KEMRI-Wellcome Trust Collaborative Research Program

Collaborator

Source ClinicalTrials.gov
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