Acute Febrile Illness, Enteric Fever, Fever, Paratyphoid Fever, Typhoid
Conditions
Keywords
Gene Expression Profiling, RNA-Seq
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.
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.
Sponsors
Christian Medical College, Vellore, India
KEMRI-Wellcome Trust Collaborative Research Program
University of Sheffield
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
2 Years to 65 Years
Healthy volunteers
Yes
Inclusion 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-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 2.5 years | Evaluate the performance of a host gene transcription signature for detecting enteric fever in adults presenting with acute undifferentiated fever (AUFI) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with diagnosis confirmed by laboratory testing. | 2.5 years | Determine the frequency of other common causes of AUFI at each site. |
| 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 | Assess the relationship between markers of clinical illness severity, likely infection cause and level of molecular perturbation. |
Countries
India
Contacts
Primary ContactFarah Shahi
Backup ContactThomas Darton
Outcome results
None listed