Eschar Investigations in Scrub Typhus (EXIST)
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|ClinicalTrials.gov Identifier: NCT02915861|
Recruitment Status : Completed
First Posted : September 27, 2016
Last Update Posted : August 5, 2021
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.
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
|Condition or disease||Intervention/treatment|
|Scrub Typhus||Other: Non-invasive eschar samples + blood Other: Non-invasive eschar samples+eschar biopsy+blood Other: Non-invasive eschar samples+eschar biopsy+lymph node fine-needle aspiration biopsy+blood Other: Blood+Skin sample|
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|
|Actual Enrollment :||44 participants|
|Official Title:||Eschar Investigations to Improve Diagnostics, Understand Early Immune Responses and Characterize Strains for Vaccines in Scrub Typhus|
|Actual Study Start Date :||June 30, 2017|
|Actual Primary Completion Date :||May 31, 2021|
|Actual Study Completion Date :||May 31, 2021|
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).
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).
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).
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.
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
Biospecimen Retention: Samples With DNA
- Non-invasive eschar samples
- Eschar biopsy
- Lymph node fine-needle aspiration biopsy (LN FNA)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02915861
|Chiangrai Prachanukroh Hospital|
|Chiang Rai, Thailand|
|Principal Investigator:||Dr. Tri Wangrangsimakul, MD||Chiangrai Prachanukroh Hospital, Chiangrai, Thailand|