Identifying pathogens in febrile patients using gene expression
A Multisite Evaluation of Functional Genomic Signatures for the Improved Diagnosis of Acute Undifferentiated Febrile Infections
This study is trying to find out if looking at gene responses in feverish patients can help doctors quickly tell if they have enteric fever or another infection, especially in places with limited resources.
Quick facts
| Study type | Observational |
|---|---|
| Enrollment | 2000 (estimated) |
| Ages | 2 Years to 65 Years |
| Sex | All |
| Sponsor | University of Sheffield Academic / other |
| Locations | 1 site (Vellore) |
| Trial ID | NCT04878549 on ClinicalTrials.gov |
What this trial studies
This observational study aims to improve diagnostics for acute undifferentiated febrile infections (AUFI) by evaluating host gene expression responses in endemic populations. By collecting clinical and laboratory data from febrile adults in low-resource settings, the study seeks to identify gene expression signatures that can differentiate enteric fever from other causes of AUFI. The ultimate goal is to develop a point-of-care test based on these signatures to enhance patient management and disease prevention in low- and middle-income countries.
Who should consider this trial
Good fit: Ideal candidates for this study are febrile adults aged 15 to 65 who present with fever without localizing features or have recently confirmed enteric fever.
Not a fit: Patients who are unable to provide informed consent or do not have a next of kin willing to assist will not benefit from this study.
Why it matters
Potential benefit: If successful, this study could lead to more accurate and timely diagnoses of enteric fever, improving patient outcomes and guiding effective treatment.
How similar studies have performed: Other studies have shown promise in using gene expression profiling for pathogen identification, indicating that this approach may be effective.
Eligibility criteria
Show full inclusion / exclusion criteria
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.
Where this trial is running
Vellore
- Christian Medical Centre — Vellore, India (Recruiting)
Study contacts
- Study coordinator: Farah Shahi
- Email: f.shahi@sheffield.ac.uk
- Phone: 01142159522
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.