RecruitingNCT04878549

Transcriptomic Responses for the Identification of Pathogens

A Multisite Evaluation of Functional Genomic Signatures for the Improved Diagnosis of Acute Undifferentiated Febrile Infections

Sponsor

University of Sheffield

Enrollment

2,000 participants

Start Date

May 2, 2022

Study Type

OBSERVATIONAL

Conditions

Fever Enteric Fever Acute Febrile Illness Typhoid Paratyphoid Fever

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.

Eligibility

Min Age: 2 YearsMax Age: 65 Years

Inclusion Criteria9

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 Criteria30

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.'
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.

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Interventions

DIAGNOSTIC_TEST5-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.