Eschar Investigations in Scrub Typhus

NCT02915861 | Completed

• 1 other identifier: MICRO1504
• Study Type: observational
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Scrub Typhus

Keywords

immune responses; vaccines

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  2 years

Secondary Outcomes (3)

• Establishing the usefulness of non-invasive eschar samples from patients with acute scrub typhus for diagnostics for OT and for genotyping +/- whole-genome sequencing.

  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.

  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.

  2 years

Study Arms (4)

EXPa

Scrub typhus patients: Group A

Other: Non-invasive eschar samples + blood

EXPb

Scrub typhus patients: Group B

Other: Non-invasive eschar samples+eschar biopsy+blood

EXPc

Scrub typhus patients: Group C

Other: Non-invasive eschar samples+eschar biopsy+lymph node fine-needle aspiration biopsy+blood

EXC

Control group

Other: Blood+Skin sample

Interventions

Non-invasive eschar samples + blood OTHER

EXPa (n=12) will have blood and non-invasive eschar samples collected (consent to study, declined biopsy).

EXPa

Non-invasive eschar samples+eschar biopsy+blood OTHER

EXPb (n=12) will have blood, non-invasive eschar samples, and an eschar biopsy collected (consent to study, draining LN inaccessible).

EXPb

Non-invasive eschar samples+eschar biopsy+lymph node fine-needle aspiration biopsy+blood OTHER

EXPc (n=12) will have blood, non-invasive eschar samples, eschar biopsy, and LN FNA collected (consent to study, draining LN accessible).

EXPc

Blood+Skin sample OTHER

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.

EXC

Eligibility Criteria

• Age: 7 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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).

You may qualify if:

• 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).
• 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).

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Oxford: lead
• Chiangrai Prachanukroh Hospital: collaborator

Study Sites (1)

Chiangrai Prachanukroh Hospital

Chiang Rai, Thailand

Location

Biospecimen

Retention: SAMPLES WITH DNA

1. Non-invasive eschar samples 2. Eschar biopsy 3. Lymph node fine-needle aspiration biopsy (LN FNA) 4. Blood

MeSH Terms

Conditions

Scrub Typhus

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Rickettsiaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Dr. Tri Wangrangsimakul, MD

  Chiangrai Prachanukroh Hospital, Chiangrai, Thailand

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2016
• First Posted: September 27, 2016
• Study Start: June 30, 2017
• Primary Completion: May 31, 2021
• Study Completion: May 31, 2021
• Last Updated: August 5, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)