Clinical Trial: Eschar Investigations in Scrub Typhus
Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Observational
Official Title: Eschar Investigations to Improve Diagnostics, Understand Early Immune Responses and Characterize Strains for Vaccines in Scrub Typhus
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.
Detailed Summary:
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.
Sponsor: University of Oxford
Current Primary Outcome:
- 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 ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- 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 ]
Original Secondary Outcome: Same as current
Information By: University of Oxford
Dates:
Date Received: September 22, 2016
Date Started: November 2016
Date Completion:
Last Updated: September 22, 2016
Last Verified: September 2016