Eschar Investigations in Scrub Typhus (EXIST)

July 29, 2021 updated by: University of Oxford

Eschar Investigations to Improve Diagnostics, Understand Early Immune Responses and Characterize Strains for Vaccines in Scrub Typhus

This is an observational study of patients with scrub typhus (rapid diagnostic test/quantitative polymerase chain reaction (RDT/qPCR) positive) and an inoculation eschar present on examination, recruited from Chiangrai Prachanukroh Hospital, North of Thailand.

In this study, we aim to:

  • Investigate relevant pathogen dissemination dynamics, early innate immune response, and pathogen-host interactions in scrub typhus using a minimal set of easily accessible samples; the inoculation eschar (crust or biopsy), whole blood and - where possible - a lymph node fine-needle aspiration (FNA).
  • Determine the potential use of the inoculation eschar for improving early diagnostics and assessing the diversity of human pathogenic strains; by evaluating non-invasive swabs and scrapings, as well as biopsies for molecular diagnostics templates.
  • Dissect the underlying patho-biology associated with the inoculation eschar and in a subgroup, including the draining lymph node; by defining the spectrum of infected cells via microscopy and double-immune labeling; by determining cytokine and RNA gene expression profiles in blood peripheral blood mononuclear cell (PBMCs) and eschar samples.

Data sharing:

No future analysis or study of legacy data/specimens including data sharing for purposes not specified in the protocol will be done without seeking further regulatory (EC/IRB) approval

  • Any requests for data sharing will be considered by MORU's data sharing committee
  • Any data subsequently shared will be anonymised and will not include personal identifiers

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Scrub typhus patients will be recruited into the scrub typhus patient (EXP) arm of the study. There will be 3 sub-groups:

  • EXPa (n=12) will have blood and non-invasive eschar samples collected (consent to study, declined biopsy).
  • EXPb (n=12) will have blood, non-invasive eschar samples, and an eschar biopsy collected (consent to study, draining lymph node (LN) inaccessible).
  • EXPc (n=12) will have blood, non-invasive eschar samples, eschar biopsy, and LN FNA collected (consent to study, draining LN accessible).

Samples will be collected at baseline (all) and 2 weeks (blood only).

Control participants will be recruited into the scrub typhus control.

- EXC (n=12) are healthy individuals, attending hospital for elective/minor surgery or treatment of minor skin injury, and normally reside in a scrub typhus endemic region. Blood and a skin sample will be collected at baseline only.

Study Type

Observational

Enrollment (Actual)

44

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Thailand
      • Chiang Rai, Thailand
        • Chiangrai Prachanukroh Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

7 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

EXP: Male and female patients ≥7 years old with confirmed acute scrub typhus and an eschar present on examination (N=36).

EXC: Healthy individuals ≥7 years old who normally reside in a scrub typhus endemic region, attending hospital for elective/minor surgery or treatment of minor skin injury, and preferably age and sex-matched (N=12).

Description

Scrub Typhus Patients (EXP) inclusion criteria:

  • Age ≥7 years old.
  • Presentation to hospital with fever in ≤14 days and a clinical suspicion of typhus.
  • Eschar observed on examination.
  • Scrub typhus RDT positive or OT qPCR positive (if qPCR available at local site by time of study initiation).
  • Willingness to participate in the study. Written informed consent obtained from the patient (≥18 years old) or, written informed assent from participant (≥7 to <18years old) along with written informed consent from participant's parent(s)/legal guardian(s).

Scrub Typhus Controls (EXC) inclusion criteria:

  • Age ≥7 years old.
  • Clinically well, attending elective/minor surgery or for treatment of minor skin injury.
  • Historical diagnosis of scrub typhus (RDT, serology, and/or PCR positivity) more than 2 years ago or living in an endemic area with high risk of previous exposure.
  • Willingness to participate in the study. Written informed consent obtained from the patient (≥18 years old) or written informed assent from participant (≥7 to <18years old) along with written informed consent from participant's parent(s)/legal guardian(s).

Scrub Typhus Patients (EXP) exclusion criteria:

  • Current TB or TB treatment in ≤6 months (contains OT-effective antimicrobials)
  • Documented HIV infection, use of steroids, chemotherapy, other immunosuppressants, or herbal remedies containing steroids, and/or pregnancy

Scrub Typhus Controls (EXC) exclusion criteria:

  • Significant acute intercurrent illness at the time of admission including fever >37.5˚C or infection (including TB) requiring antibiotics
  • Documented HIV infection, use of steroids, chemotherapy, other immunosuppressants, or herbal remedies containing steroids, and/or pregnancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
EXPa
Scrub typhus patients: Group A
Other: Non-invasive eschar samples + blood
EXPa (n=12) will have blood and non-invasive eschar samples collected (consent to study, declined biopsy).
EXPb
Scrub typhus patients: Group B
Other: Non-invasive eschar samples+eschar biopsy+blood
EXPb (n=12) will have blood, non-invasive eschar samples, and an eschar biopsy collected (consent to study, draining LN inaccessible).
EXPc
Scrub typhus patients: Group C
Other: Non-invasive eschar samples+eschar biopsy+lymph node fine-needle aspiration biopsy+blood
EXPc (n=12) will have blood, non-invasive eschar samples, eschar biopsy, and LN FNA collected (consent to study, draining LN accessible).
EXC
Control group
Other: Blood+Skin sample
Controls (EXC, n=12) are healthy individuals, attending hospital for elective/minor surgery or treatment of minor skin injury, and normally reside in a scrub typhus endemic region. Blood and a skin sample will be collected at baseline only.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Phenotypic characterisation of the major subset of Orientia tsutsugamushi (OT) infected leucocytes within eschar, lymph node, and blood during the dissemination phase of OT in vivo.
Time Frame: 2 years
2 years
Characterisation of cytokine and RNA gene expression profiles within the eschar, lymph node, and blood in vivo and comparisons with profiles of uninfected target cells.
Time Frame: 2 years
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Establishing the usefulness of non-invasive eschar samples from patients with acute scrub typhus for diagnostics for OT and for genotyping +/- whole-genome sequencing.
Time Frame: 2 years
2 years
Define and contrast the eschar histo-pathological findings in this study in Thailand to previous findings from Laos, where the Gilliam strain predominates.
Time Frame: 2 years
2 years
Comparisons to parallel studies in the non-human primate model with emphasis on dissemination dynamics, immunomodulation, and the innate and adaptive immune responses to OT; contributing to vaccine development.
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Oxford

Collaborators

Chiangrai Prachanukroh Hospital

Investigators

  • Principal Investigator: Dr. Tri Wangrangsimakul, MD, Chiangrai Prachanukroh Hospital, Chiangrai, Thailand

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 30, 2017

Primary Completion (Actual)

May 31, 2021

Study Completion (Actual)

May 31, 2021

Study Registration Dates

First Submitted

September 22, 2016

First Submitted That Met QC Criteria

September 22, 2016

First Posted (Estimate)

September 27, 2016

Study Record Updates

Last Update Posted (Actual)

August 5, 2021

Last Update Submitted That Met QC Criteria

July 29, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MICRO1504

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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