Enteric FeverTRiPNCT04878549
Transcriptomic Responses for the Identification of Pathogens
An observational study of Enteric Fever and Acute Febrile Illness, run by University of Sheffield at 1 site in India.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Enteric Fever, Acute Febrile Illness, Typhoid
- What is being tested?
- 5-gene transcription signature
- How many people
- 2,000 participants
- Where
- 1 siteIndia
- Study dates
- 2 May 2022to Jun 2025
- How long will I take part?
- 14 Days
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 65 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
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.
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:
- 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
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Thomas Darton contact
About this study
Official title: A Multisite Evaluation of Functional Genomic Signatures for the Improved Diagnosis of Acute Undifferentiated Febrile Infections
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
- Being tested
- 5-gene transcription signature
- Keywords
- Gene Expression Profiling, RNA-Seq
- Medical subject headings
- Typhoid Fever, Paratyphoid Fever, Fever
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-gene transcription signatureDiagnostic 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.
| Study group | Role | What they receive |
|---|---|---|
| Febrile Adults | 1200 adult participants (15 to 65 years old) with a febrile illness without localising features and reported duration of 3-14 days. Receives: Diagnostic Test: 5-gene transcription signature | |
| Controls | 400 afebrile, healthy adult participants (15 to 65 years old). Receives: 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. Receives: Diagnostic Test: 5-gene transcription signature |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 2.5 years
Secondary outcomes (2)
Number of participants with diagnosis confirmed by laboratory testing.
Determine the frequency of other common causes of AUFI at each site.
Measured: 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.
Assess the relationship between markers of clinical illness severity, likely infection cause and level of molecular perturbation.
Measured: 2.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2021
- Study start2 May 2022
- Primary completionJun 2025 (estimated)
- Study completionJun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Enteric FeverStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 2,000 participants (estimated)
- Target duration
- 14 Days
Sponsor and investigators
- Lead sponsor
- University of Sheffield
- Sponsor type
- University, hospital or other
- Collaborators
- Christian Medical College, Vellore, India, KEMRI-Wellcome Trust Collaborative Research Program
- Responsible party
- Sponsor
- Investigators
- Thomas Darton, Study director, University of Sheffield
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04878549
- Sponsor's protocol ID
- 157365
- Acronym
- TRiP
- Status last verified
- Feb 2025
- First submitted
- 20 Jan 2021
- Last updated
- 3 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multisite Evaluation of Functional Genomic Signatures for the Improved Diagnosis of Acute Undifferentiated Febrile Infections
- ClinicalTrials.gov ID
- NCT04878549
- Acronym / sponsor ID
- TRiP / 157365
- Conditions
- Enteric Fever, Acute Febrile Illness, Typhoid, Paratyphoid Fever, Fever
- Keywords
- Gene Expression Profiling, RNA-Seq
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 2,000 participants (estimated)
- Lead sponsor
- University of SheffieldUniversity, hospital or other
- Collaborators
- Christian Medical College, Vellore, India, KEMRI-Wellcome Trust Collaborative Research Program
- Study start
- 2 May 2022 (actual)
- Primary completion
- Jun 2025 (estimated)
- Study completion
- Jun 2025 (estimated)
- First posted
- 7 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 14 Days
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Febrile Adults | – | Diagnostic Test: 5-gene transcription signature1200 adult participants (15 to 65 years old) with a febrile illness without localising features and reported duration of 3-14 days. |
| Controls | – | Diagnostic Test: 5-gene transcription signature400 afebrile, healthy adult participants (15 to 65 years old). |
| Febrile Children | – | Diagnostic Test: 5-gene transcription signature400 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. |
Who may qualify
- Ages
- 2 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 5-gene transcription signatureThis 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. | Diagnostic test | Controls, Febrile Adults, Febrile Children |
Primary outcome
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.
Time frame: 2.5 years
Evaluate the performance of a host gene transcription signature for detecting enteric fever in adults presenting with acute undifferentiated fever (AUFI)
2 secondary outcomes
Number of participants with diagnosis confirmed by laboratory testing.
Time frame: 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.
Time frame: 2.5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Thomas Darton contact
Thomas Darton study director
University of Sheffield
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Enteric Fever and Acute Febrile Illness, run by University of Sheffield at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Farah Shahi (01142159522, f.shahi@sheffield.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 2.5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2025.