Transcriptomic Responses for the Identification of Pathogens

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Brief Title

Transcriptomic Responses for the Identification of Pathogens

Official Title

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

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.
    



Study Type

Observational [Patient Registry]


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.

Secondary Outcome

 Number of participants with diagnosis confirmed by laboratory testing.

Condition

Enteric Fever

Intervention

5-gene transcription signature

Study Arms / Comparison Groups

 Febrile Adults
Description:  1200 adult participants (15 to 45 years old) with a febrile illness without localising features and reported duration of 3-14 days.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Diagnostic Test

Estimated Enrollment

2000

Start Date

June 2021

Completion Date

December 2023

Primary Completion Date

June 2023

Eligibility Criteria

        FEBRILE ADULTS- INCLUSION CRITERIA

          -  Age greater than or equal to 15 years and less than or equal to 45 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

          -  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 and

               -  Reported duration of fever 3-14 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.

          -  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)

          -  Hospitalisation within 4 weeks prior to current admission

          -  Vaccination within 8 weeks prior to current admission

          -  They live outside of the normal/local catchment area for each hospital site

          -  Localising signs or symptoms of infection sufficient to diagnose the likely cause of
             acute febrile illness and thus prevent it from being 'undifferentiated' (see Section
             8.4 'Screening and Eligibility').

        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 45 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 8 weeks prior to recruitment

          -  Antimicrobial use within 4 weeks of recruitment

          -  They live outside of the normal/local catchment area for each hospital site

          -  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.
      

Gender

All

Ages

2 Years - 45 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

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Administrative Informations


NCT ID

NCT04878549

Organization ID

157365


Responsible Party

Sponsor

Study Sponsor

University of Sheffield

Collaborators

 Christian Medical College, Vellore, India

Study Sponsor

, , 


Verification Date

January 2021