Scrub TyphusNIRPSNCT02398162
Scrub Typhus Pediatric Immunology Study
An observational study of Scrub Typhus, run by University of Oxford at 1 site in Thailand.
Trial summary
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… Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Scrub Typhus
- What is being tested?
- Multi Blood Collections and Single Blood Collection
- Type of treatment
- Surgery or procedure
- How many people
- 170 participants
- Where
- 1 siteThailand
- Study dates
- 15 Jul 2015to 17 Oct 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
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.
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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]
Read the detailed description
Primary Objective:
- 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.
- Conditions
- Scrub Typhus
- Being tested
- Multi Blood Collections, Single Blood Collection
- Keywords
- Scrub Typhus in Pediatric, Immunology
- Medical subject headings
- Scrub Typhus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multi Blood CollectionsProcedure or surgery
At baseline (the day of presentation to hospital), 2 weeks, 12 weeks and 1 year later.
Single Blood CollectionProcedure or surgery
On the enrollment day
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Multi Blood Collections | |
| STE | Scrub Typhus Exposed (STE, n=80) Cohort. Single blood sample collection. Receives: Procedure: Single Blood Collection | |
| STH | Scrub Typhus Healthy (STH, n=30) Cohort. Single blood sample collection Receives: Procedure: Single Blood Collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cellular immune response to Orientia tsutsugamushi
Characterize the cellular immune response to Orientia tsutsugamushi, based on immune cell phenotyping and quantitation of effector, memory \& regulatory T cell functions.
Measured: 2 years
Secondary outcomes (3)
T-cell subsets during the scrub typhus infection
Identification of T-cell subsets affected by apoptosis during the course of acute scrub typhus.
Measured: 2 years
Antibody isotypes during the scrub typhus infection
Determination of the antibody isotypes and their dynamics involved in natural scrub typhus infection.
Measured: 2 years
Adaptive immune response to Orientia tsutsugamushi
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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2015 (estimated)
- Study start15 Jul 2015
- Primary completion17 Oct 2017
- Study completion17 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Scrub TyphusStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 170 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Li Ka Shing Foundation, Mahidol University, Chiangrai Prachanukroh Hospital
- Responsible party
- Sponsor
- Investigators
- Dr.Daniel Paris, MD, Principal investigator, Mahidol Oxford Tropical Medicine Research Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02398162
- Sponsor's protocol ID
- MICRO1402
- Acronym
- NIRPS
- Status last verified
- Aug 2018
- First submitted
- 27 Feb 2015
- Last updated
- 20 Sep 2018
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Natural Immune Response In Pediatric Scrub Typhus In Chiangrai
- ClinicalTrials.gov ID
- NCT02398162
- Acronym / sponsor ID
- NIRPS / MICRO1402
- Conditions
- Scrub Typhus
- Keywords
- Scrub Typhus in Pediatric, Immunology
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 170 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Li Ka Shing Foundation, Mahidol University, Chiangrai Prachanukroh Hospital
- Study start
- 15 Jul 2015 (actual)
- Primary completion
- 17 Oct 2017 (actual)
- Study completion
- 17 Oct 2017 (actual)
- First posted
- 25 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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]
Detailed description
Primary Objective:
- 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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| STP | – | Procedure: Multi Blood CollectionsScrub 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. |
| STE | – | Procedure: Single Blood CollectionScrub Typhus Exposed (STE, n=80) Cohort. Single blood sample collection. |
| STH | – | Procedure: Single Blood CollectionScrub Typhus Healthy (STH, n=30) Cohort. Single blood sample collection |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (16 listed)
- 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
Key exclusion criteria (10 listed)
- 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
- 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
- Previous history of scrub typhus
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Multi Blood CollectionsAt baseline (the day of presentation to hospital), 2 weeks, 12 weeks and 1 year later. | Procedure or surgery | STP |
| Single Blood CollectionOn the enrollment day | Procedure or surgery | STE, STH |
Primary outcome
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.
3 secondary outcomes
T-cell subsets during the scrub typhus infection
Time frame: 2 years
Antibody isotypes during the scrub typhus infection
Time frame: 2 years
Adaptive immune response to Orientia tsutsugamushi
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr.Daniel Paris, MD principal investigator
Mahidol Oxford Tropical Medicine Research Unit
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Scrub Typhus, run by University of Oxford at 1 site in Thailand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cellular immune response to Orientia tsutsugamushi (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2018.