Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03269266 |
| Other study ID # |
OXTREC 18-17 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
December 4, 2017 |
| Est. completion date |
December 26, 2019 |
Study information
| Verified date |
January 2019 |
| Source |
Myanmar Oxford Clinical Research Unit |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Fever is one of most common presenting complaints in clinics in tropical countries.
Rickettsial infections, enteric fever and leptospirosis are common and important causes of
undifferentiated fever in Southeast Asia. Scrub typhus is caused by Orientia tsutsugamushi
and humans are typically infected by a bite of an infected chigger (trombiculid mite larva).
Clinical diagnosis is unreliable for identifying scrub typhus, unless a tick eschar is
present which is almost pathognomonic for the disease in Southeast Asia. A combination of
culture, paired serology and PCR has been proposed as the gold-standard method for detection.
As a result laboratory confirmation is not widely available and the diagnosis is missed
frequently in clinical practice. Some progress has been made in developing such a test and
one promising candidate is the Scrub Typhus Detect IgM Rapid Test (InBios International Inc).
We plan to use to this test in this study to estimate the prevalence of scrub typhus in
selected febrile patients presenting to clinics in Myanmar .
Patients will be followed up for one week to check for resolution of symptoms.
Description:
Title: A multicenter observational study to describe the prevalence of scrub typhus defined
as s positive rapid diagnostic test among selected patients presenting with fever to clinics
in Myanmar.
Rational and objectives of the study Fever is one of most common presenting complaints in
clinics in tropical countries. Rickettsial infections, enteric fever and leptospirosis are
common and important causes of undifferentiated fever in Southeast Asia. The largest and
earliest reports of scrub typhus in Myanmar were made during World War II when this disease
afflicted numerous troops, particularly those serving close to the border with India. Scrub
typhus is caused by Orientia tsutsugamushi and humans are typically infected by a bite of an
infected chigger (trombiculid mite larva). Clinical diagnosis is unreliable for identifying
scrub typhus, unless a tick eschar is present which is almost pathognomonic for the disease
in Southeast Asia. A combination of culture, paired serology and PCR has been proposed as the
gold-standard method for detection. As a result laboratory confirmation is not widely
available and the diagnosis is missed frequently in clinical practice. Some progress has been
made in developing such a test and one promising candidate is the Scrub Typhus Detect IgM
Rapid Test (InBios International Inc). In laboratory-based evaluations using stored sera
collected from patients recruited in a study in Thailand with confirmed scrub typhus this
test had a sensitivity of ~80% for the detection of the disease compared to serological
methods. We plan to use to this test in this study to estimate the prevalence of scrub typhus
in selected febrile patients presenting to clinics in Myanmar.
Primary objective: To describe the prevalence of scrub typhus defined as a positive rapid
diagnostic test among selected patients presenting with fever to clinics in Myanmar
Secondary objective:
- To assess inter-observer agreement when interpreting the tests
- To assess the ease-of-use of the tests
- To direct future research efforts into rickettsial disease in Myanmar
- To raise awareness of the presence of scrub typhus in Myanmar Inclusion criteria
1. Male or female >1 year of age
2. Fever defined as > 38 °C tympanic temperature
3. Duration of fever >48h
4. Written informed consent (by legally acceptable representative in case of
children), and assent for children age 10-17 year
5. Eschar (60 patients only) Exclusion criteria
- Malaria confirmed by RTD or microscopy
- Skin/soft tissue infection, dysentery or urinary tract infection probable cause of fever
Procedures and Methodology The study will be carried out to describe the prevalence of scrub
typhus defined as a positive rapid diagnostic test among patients presenting with fever to
six participating clinics in Myanmar.
Patients coming with fever to participating clinics will be routinely assessment by attending
physician. Patients meeting the inclusion and exclusion criteria for the study will be
invited and enrolled to the study after getting informed consent.
Rapid diagnostic test and laboratory procedure A scrub typhus rapid test will be performed on
site by using the InBios Scrub Typhus Detect IgM Rapid Test. Tests will be read by two
independent readers and results recorded as positive, negative or invalid. In case of invalid
test result, another test will be performed using a new test strip. If there is any
disagreement between two readers, the lead investigator at the site will decide the test
result and the test will be photographed.
In patients with a skin eschar a sterile surgical blade will be used to gently scrape the
surface of the eschar. Scrapings will be stored in a cryotube containing 95% ethanol and
stored at -80°C for future analysis (PCR genotyping ± whole genome sequencing) to confirm the
presence of Orientia tsutsugamushi.
Treatment Physicians will be advised to formulate a treatment plan according to their usual
practice but it will be recommended that treatment for scrub typhus be added to the regimen
if the test is positive i.e. doxycycline 100mg bd for seven days in adults or 4mg/kg day in
two divided doses in children older than eight years. Doxycycline is contraindicated in
pregnant women and children eight years old or below and these groups should be prescribed
azithromycin (500mg single dose).
Follow up Patients will be reassessed at one week to check for resolution of fever and
symptoms . Any patient with ongoing symptoms will be re-assessed by a physician.
Duration and Study Sites Patients will be recruited 1 year starting from December 2017 to
November 2018 in six sites: Yae township hospital, No.2, 1000 Bedded Military Hospital (Nay
Pyi Taw), No.20, 100 Bedded Military Hospital (Tha Beik Kyin), NAP-MAM clinics (Kawkareik and
Putao township), No.2, 300 Bedded Military Hospital (Ann, Rakhine State).
Risk and benefits This is a low risk study. Finger prick for RDT and scrapping from eschar
(for patients who have eschar) may cause slight discomfort. Some patients may receive
antibiotics they would not have otherwise been prescribed as a result of having the test.
However this is most likely to benefit them as these tests have been shown to be sensitive
and specific for the diagnosis of scrub typhus in similar settings.
Incentives and Compensation There will be no incentives or compensation for study
participation. Confidentiality The study will ensure that the participants' anonymity is
maintained. The participants will be identified only by initials and a study number on the
CRF and the study database.
Publication The research findings will be disseminated to policy-makers and other interested
parties inside Myanmar. If there are any publications resulting from the results all those
who have made a substantial contribution will be co-authors.
