Scrub Typhus Pediatric Immunology Study (NIRPS)

September 18, 2018 updated by: University of Oxford

The Natural Immune Response In Pediatric Scrub Typhus In Chiangrai

This is an observational study of the natural immune response to scrub typhus in patients recruited from Chiangrai Prachanukroh Hospital, N-Thailand. Febrile patients with a positive IgM rapid diagnostic test will be asked if they wish to take part in a study to improve the understanding of how the body responds to scrub typhus. Blood samples will be collected from each participant ("STP", n=60) at baseline (the day of presentation to hospital), 2 weeks later in hospital, 12 weeks after baseline at the clinic visit and 1 year later. Data on clinical presentation and relapses will be recorded. Control subjects are scrub typhus exposed patients from a rural village in the caption area of Prachanukroh Hospital ("STE", n=80; approx. 40 children and 40 adults), and healthy adults blood donors from Bangkok ("STH" n=30) - these subjects will be enrolled for one single blood sample. The study team will also collect eschar swab specimens from STP group and a non-invasive specimen of the dark crust on the day of enrollment.

Funder: Li Ka Shing Foundation [Grant C13004]

Study Overview

Detailed Description

Primary Objective:

o To measure and characterize the memory and effector T-cell responses, as well as the humoral response in young patients with acute scrub typhus and to compare theseThese acute responses will be compared to responses in the convalescent phase of the same individuals at 2, 12 and 52 weeks later, as well as to scrub typhus-exposed controls and to healthy controls.

Secondary Objectives:

  • To establish ELISpot and flow cytometer based immunology assays using human samples collected in rural areas of high scrub typhus endemicity.
  • To set up a prospective cohort study of paediatric scrub typhus in a region of high endemicity

Description of the Study Sites and Population Chiangrai Prachanukroh Hospital in Chiangrai province, N-Thailand is ideally suited for this study. We have a well-established collaboration, due to a previously completed multi-year fever study and an excellent relationship with local senior doctors, staff and the hospital-based laboratory. There is a very high rate of scrub typhus cases admitted to the infectious diseases ward and the recent establishment of a MORU (Mahidol Oxford Tropical Medicine Research Unit) satellite laboratory within the hospital facilities, make this study site unique and highly suited for performing this research project. This study will contribute significantly towards the long-term aim of developing the Chiangrai study site towards an immunogenicity monitoring field site for vaccine trials.

The 'scrub typhus' patients (STP) are febrile children recruited from the ID and/or pediatric wards at Prachanukroh hospital during an acute hospitalization due to scrub typhus, and followed up as described above.

The scrub typhus 'exposed' cohort (STE) will consist of children and adults recruited from two villages in an area where scrub typhus is reported as a common disease. This cohort has a high risk of previous contact with scrub typhus, and it is unknown if they had an asymptomatic or sub-clinical infection in the past, but we expect the presence of some form of immune memory regarding cellular and/or humoral immunity in a large proportion of these subjects.

The healthy scrub typhus naïve control group (STH) does not necessarily need to include children, as the principle is to compare a non-exposed immune response to previously exposed and/or acute cellular responses. Thus, the 'Healthy Cohort' will be recruited from the staff at MORU and/or the Faculty of Tropical Medicine in Bangkok.

Study Type

Observational

Enrollment (Actual)

170

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

      • 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

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Cases: Male and female patients ≤ 18 years of age with acute scrub typhus (n=60). Controls: people exposed to scrub typhus (approx. 40 children and 40 adults from Chiangrai, total n=80) preferably age-matched, healthy and non-febrile, and healthy adult scrub typhus-naïve controls from Bangkok (n=30), total n=170.

Description

Inclusion Criteria:

Scrub Typhus Patients (STP) Cohort inclusion criteria

  • Age >6 months to ≤18 years (STP consist of pediatrics only)
  • Scrub Typhus Rapid test positivity (SDm Standard Diagnostics RDT, Korea)
  • O. tsutsugamushi PCR-positivity (if PCR capability is available by the start of the study)
  • Fever in ≤ 14 days of presentation to Hospital
  • Willingness to participate in the study and written informed assent previously obtained from the patient, and written informed consent obtained from the patient's parent(s), guardian(s) or representative(s)

Scrub Typhus Exposed (STE) Cohort inclusion criteria

  • Age >6 months to ≤18 years and age >18 years (STE consist of paediatrics and adult )
  • Historical diagnosis of scrub typhus, as defined by rapid diagnostic test, serology and/or PCR positivity (more than 2 years ago), or living in an endemic area with high risk of previous exposure.
  • Currently well and healthy
  • Willingness to participate in the study and written informed assent previously obtained from the patient, and written informed consent obtained from the patient's parent(s), guardian(s) or representative(s)

Scrub Typhus Healthy (STH) Cohorts inclusion criteria

  • Age >18 years (STH consist of adults only)
  • Currently well, no medical problems requiring hospital specialist supervision
  • Willingness to participate in the study and written, informed consent previously obtained
  • Residing in Bangkok for at least the 2 past recent years

Exclusion Criteria:

Scrub Typhus Patients (STP) Cohort exclusion criteria:

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

Scrub Typhus Exposed (STE) Cohort exclusion criteria:

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

Scrub Typhus Healthy (STH) Cohorts exclusion criteria:

  • Previous history of scrub typhus
  • Significant acute intercurrent illness at the time of blood draw including fever >37.5°C or infection (including TB) requiring antibiotics
  • Documented HIV infection, use of steroids, chemotherapy, other immunosuppressant therapy 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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
STP
Scrub Typhus Patients (STP, n=60) Cohort. Blood samples will be collected at baseline (the day of presentation to hospital), 2 weeks later in hospital, 12 weeks after baseline at the clinic visit and 1 year later. Data on clinical presentation and relapses will be recorded. Eschar swab specimens and a non-invasive specimen of the dark crust will be also collected from STP group on the day of enrollment.
At baseline (the day of presentation to hospital), 2 weeks, 12 weeks and 1 year later.
STE
Scrub Typhus Exposed (STE, n=80) Cohort. Single blood sample collection.
On the enrollment day
STH
Scrub Typhus Healthy (STH, n=30) Cohort. Single blood sample collection
On the enrollment day

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cellular immune response to Orientia tsutsugamushi
Time Frame: 2 years
Characterize the cellular immune response to Orientia tsutsugamushi, based on immune cell phenotyping and quantitation of effector, memory & regulatory T cell functions.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
T-cell subsets during the scrub typhus infection
Time Frame: 2 years
Identification of T-cell subsets affected by apoptosis during the course of acute scrub typhus.
2 years
Antibody isotypes during the scrub typhus infection
Time Frame: 2 years
Determination of the antibody isotypes and their dynamics involved in natural scrub typhus infection.
2 years
Adaptive immune response to Orientia tsutsugamushi
Time Frame: 2 years
Characterisation of the adaptive immune response to Orientia tsutsugamushi, measured by ex vivo interferon-gamma ELISPOT in spot forming cells per million peripheral blood mononuclear cells (SFC/106PBMC), using four Orientia antigens (whole cell antigen, 56kDa, 47kDa and scaC) in samples of acute disease and long term follow up.
2 years

Collaborators and Investigators

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

Investigators

  • Principal Investigator: Dr.Daniel Paris, MD, Mahidol Oxford Tropical Medicine Research Unit

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)

July 15, 2015

Primary Completion (ACTUAL)

October 17, 2017

Study Completion (ACTUAL)

October 17, 2017

Study Registration Dates

First Submitted

February 27, 2015

First Submitted That Met QC Criteria

March 19, 2015

First Posted (ESTIMATE)

March 25, 2015

Study Record Updates

Last Update Posted (ACTUAL)

September 20, 2018

Last Update Submitted That Met QC Criteria

September 18, 2018

Last Verified

August 1, 2018

More Information

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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