QuEST - Quick and Easy Scrub Typhus Diagnostic Tools (QuEST)

Diagnostic Tools for the Direct Detection of Orientia Tsutsugamushi

Evaluate the performance of insulated isothermal polymerase chain reaction (iiPCR) in the diagnosis of scrub typhus in Chiang Rai Province

Study Overview

• Status: Completed
• Conditions: Scrub Typhus

Detailed Description

Screening and enrolment

The study team will screen patients presenting with fever at the out- and inpatient departments of study sites. A scrub typhus rapid diagnostic test (RDT) will be performed at all sites (e.g. Scrub Typhus IgM RDT, InBios International; Scrub Typhus IgM/IgA/IgG RDT, SDBioline; STANDARD Q Tsutsugamushi IgM/IgG, SDBiosensor) and insulated isothermal polymerase chain reaction (iiPCR) will be performed at Chiang Rai Clinical Research Unit (CCRU) central laboratories. Before being screened with any of the above tests for study purposes, potential participants will be asked to pre-consent to the screening test.

If participants have a positive screening test following an order form the treating physician as part of standard management (not for study purposes), this will be considered equivalent to a positive screening test; those subjects will be asked then to provide informed consent to participate in the study.

Eligible patients who agree to participate and/or their legal guardians will take part in the informed consent procedure. If the RDT or iiPCR test is positive for scrub typhus (one positive test is sufficient) or the patient has a fever and an eschar, the patient is formally enrolled into the study.

Every screened patient will receive a screening number and details are recorded into a screening log. Screening rejection is defined as patients who have been screened but are not enrolled into the study. Reasons for rejection may include any exclusion criteria, non-conformity with the inclusion criteria, or failure to obtain informed consent. Reasons will be recorded in the screening log. Patients who do not progress from screening to trial recruitment will not be assigned with a study number or have clinical data recorded in the screening log.

Inpatient stay Clinical review: Study patients will have their vital signs measured and recorded every 6 hours during hospitalisation. Details of antibiotics administered will be collected. Additional diagnostic test results (e.g. laboratory or imaging) requested by the medical team will also be collected and recorded on the case report from (CRF).

Patients admitted with scrub typhus to hospital for treatment will be discharged by the treating physician according to clinical improvement and resolution of fever.

Follow-up

Scheduled follow-up: A follow-up visits will occur at 2 weeks (+ 2 weeks). Examinations and samples are collected as outlined in the study flowchart (section 4.1.2 of the protocol).

If the patient cannot be followed-up, then the reason for loss-to-follow-up will be recorded on the CRF.

Study participants are asked to contact the study team if fever and/or symptoms and signs compatible with scrub typhus appear after hospital discharge until the patient exits the study (after the 2 week follow-up appointment). Clinical findings and samples are collected as outlined in the study flowchart.

If the patient was discharged or leaves the hospital prior to cessation of fever, the patient will be given a tympanic membrane monitor and asked to measure their temperature 4 times a day (flexible/pragmatic timings) and record the results in a diary until their fever has cleared. The diary and the thermometer will be collected by the study team at follow-up and the temperature readings used to calculate the fever clearance time.

The performance of RDTs and of iiPCR will be compared to that of reference quantitative PCR (qPCR) and indirect immunofluorescence assay (IFA) for the diagnosis of scrub typhus on acute and paired (acute and convalescent) samples. The test will also be compared to the modified scrub typhus infection criteria (Paris et al., 2011)

This study has been funded by Wellcome Trust. Grant number 315982/Z/24/Z

• Study Type: Observational
• Enrollment (Actual): 345

Contacts and Locations

Study Locations

• Thailand
  • Chiang Rai, Thailand
    • Mae Fah Luang District Hospital
  • Chiang Rai, Thailand
    • Mae Suai District Hospital
  • Changwat Chiang Rai
    • Mae Chan, Changwat Chiang Rai, Thailand
      • Mae Chan District Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Febrile patients suspected of having scrub typhus and presenting to Mae Chan or Mae Suai district hospitals

Description

INCLUSION CRITERIA:

• ≥ 7 years old AND
• Weight>15Kg AND
• The patient and/or where relevant their parent/guardian/caretaker/LAR willing and able to give informed consent /assent for participation in the study AND
• Acute (duration ≤14 days) fever (37.5°C or higher or a history of fever in the previous 24h)

For study group • Eschar OR Positivity to any of the screening tests (Immunochromatographic RDT or iiPCR)

For negative control

• Negativity to all screening tests (ten patients per hospital)

EXCLUSION CRITERIA:

• Other clear focus of infection (e.g. lobar pneumonia by chest x-ray, abscess) OR
• Other clear cause of fever (e.g. positive Dengue IgM or NS1 antigen, positive blood cultures, untreated HIV)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Suscpected scrub typhus cases; Participants with symptoms and epidemiologic risks for of scrub typhus and testing positive by: StandardQ rapid diagnostic test OR; InBios Scrub Typhus Detect IgM; Insulated isothermal PCR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Sensitivity, specificity, positive- and negative predictive values of insulated isothermal polymerase chain reaction (iiPCR) compared to reference diagnostic tests	Baseline and week two

Secondary Outcome Measures

Outcome Measure	Time Frame
G6PD deficiency estimates	Week two
Risk exposure comparisons between healthy controls and scrub typhus cases	Baseline

Collaborators and Investigators

• Sponsor: University of Oxford
• Investigators: Principal Investigator: Carlo Perrone, MD, Mahidol Oxford Tropical Medicine Research Unit

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2024
• Primary Completion (Actual): January 31, 2026
• Study Completion (Actual): February 28, 2026

Study Registration Dates

• First Submitted: November 4, 2024
• First Submitted That Met QC Criteria: November 4, 2024
• First Posted (Actual): November 5, 2024

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Scrub typhus; Orientia tsutsugamushi; insulated isothermal PCR; diagnostic evaluation
• Additional Relevant MeSH Terms: Vector Borne Diseases; Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Rickettsiaceae Infections; Scrub Typhus
• Other Study ID Numbers: OxTREC Reference: 4 - 24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After publication of main findings, or 1 year after study completion (whichever comes first) and reasonable request to MORU data access committee

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No