Causes of Fever in Bangladeshi Patients

January 16, 2019 updated by: University of Oxford

Rickettsial Disease in Febrile Hospitalised Patients in a Tertiary Referral Hospital in Bangladesh

Background:

The clinical features and prevalence of tropical rickettsial illnesses such as murine and scrub typhus in Bangladesh are unknown. Following testing for malaria, patients with undifferentiated fever are frequently treated empirically for typhoid or diagnosed clinically with a viral fever. Since murine and scrub typhus are common causes of fever in other countries in the region, it is likely they are prevalent in Bangladesh. Murine and scrub typhus may be treated cheaply and effectively with doxycycline.

Primary aim:

- Describe the clinical features of scrub and murine typhus in Bangladeshi patients

Secondary aims:

  • Assess the proportion of patients screened for malaria having rickettsial illnesses
  • Understand the pathophysiology of severe scrub typhus and murine typhus
  • Prospective evaluation of rapid diagnostic tests for scrub and murine typhus

Methods:

Scrub typhus and murine typhus rapid tests will be introduced to CMCH in conjunction with existing malaria testing facilities. Consenting febrile adult patients who have had malaria and typhus rapid tests and meeting the entry criteria will be enrolled. Samples will be saved for serology and real time polymerase chain reaction (PCR) testing for O. tsutsugamushi and Rickettsia spp. A thorough history and examination will be undertaken. Hemodynamic status will be assessed by ultrasound upon enrolment. Patients will be followed up for outcome and a second sample will be taken for convalescent serological testing on day 14 where possible.

Analysis The proportion of patients screened for malaria with an acute febrile illness due to scrub typhus and murine typhus will be calculated. The clinical features of scrub and murine typhus, malaria and patients negative for these conditions will be compared. Healthy subject samples will be used to provide normal ranges. The sensitivity and specificity of the rapid tests will be assessed as compared to the gold standard of PCR and serology combined.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Proposed activities:

The primary objective of this study are to assess the clinical features of patients with scrub or murine typhus infections presenting to CMCH. The proportion of cases screened for malaria and typhus who are diagnosed with scrub and murine typhus during the study period will be calculated, and the data made available for future empiric treatment guideline preparation.

Rapid antibody-based tests for scrub typhus and murine typhus will be made available for physicians to request alongside malaria testing in CMCH. Consenting febrile patients admitted to CMCH will be enrolled and history and clinical examination recorded. A sample will be taken for reference diagnostic testing at a later stage (including indirect fluorescent antibody (IFA) and real time PCR for scrub typhus and Rickettsia spp.)16. Samples will also be taken for testing of markers of pathophysiology (endothelial dysfunction neutrophil activation, cell death, cytokines). Where an eschar is found, the scab will be removed for real time-PCR. Where possible, patients will be invited back for a follow up 14 days after enrolment and a sample collected for paired serology assayed by IFA testing. Ultrasound based hemodynamic assessment will be performed to assess volume status and evidence of cardiac dysfunction.

The results of the ultrasound based hemodynamic assessment will be used to provide baseline information on patients with O. tsutsugamushi and Rickettsia spp. infection and other infections. This information may be used to plan further studies on the fluid management of these conditions.

Study design:

This is an observational study with no intervention. Febrile patients admitted to CMCH who have had malaria film and scrub typhus and murine typhus rapid test will be screened for enrolment. If patients meet the entry criteria, they will be enrolled after written informed consent has been given. Enrolled patients will then undergo study procedures (blood tests, physical examinations, follow-up).

Overall Description of study Participants:

The target population of this study is consenting adult patients who have had malaria and typhus rapid tests meeting the eligibility criteria admitted in CMCH. All study patients must meet the applicable inclusion and exclusion criteria.

During the study period, we aim to prospectively recruit consecutive patients until 300 patients are enrolled for whom there are paired admission and convalescent samples.

Data obtained from the malaria patients and patients without malaria or typhus will be used as comparator groups for the patients with typhus. The data from the 300 consecutive patients will be used to prospectively assess the sensitivity and specificity of the typhus diagnostic tests.

In addition, 30 healthy subjects with no recent history of fever will be recruited to provide control samples for the blood and plasma assays.

The total sample size is therefore estimated to be 330 (300 with paired serology and 30 healthy subjects).

Study Type

Observational

Enrollment (Actual)

416

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

  • Bangladesh
      • Chittagong, Bangladesh
        • Chittagong Medical College Hosiptal

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

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The target population of this study is consenting adult patients who have had malaria and typhus rapid tests meeting the eligibility criteria admitted in CMCH. All study patients must meet the applicable inclusion and exclusion criteria.

In addition, 30 healthy subjects with no recent history of fever will be recruited to provide control samples for the blood and plasma assays.

The total sample size is therefore estimated to be 330 (300 patients with paired serology and 30 healthy subjects).

Description

Patients

Inclusion Criteria:

  1. Admitted to CMCH
  2. Have had malaria and typhus rapid tests
  3. Age≥12 years old
  4. Febrile or history of fever for <3 weeks.
  5. Written informed consent from patient or attending adult (for patient who lacks capacity) or parent (for those below 18)

Exclusion Criteria:

  • Consent refused, or no adult (≥18 years) relative or guardian present to give consent in the case the patient lacks capacity to give consent.

Healthy subjects Inclusion

  1. No known acute or chronic medical conditions
  2. Asymptomatic
  3. No febrile illness in the last 2 weeks
  4. Age≥12 years old
  5. Written informed consent from patient or parent (for those below 18)

Exclusion criteria:

1. Consent refused, or no adult (≥18 years) relative or guardian present to give consent in the case the patient is under 18 years.

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
Febrile patients
Febrile patients admitted to CMCH who have had malaria film and scrub typhus and murine typhus rapid test will be screened for enrolment.
Other: Observation
Healthy
Healthy subjects with no recent history of fever will be recruited to provide control samples for the blood and plasma assays.
Other: Observation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The clinical features of severe and uncomplicated scrub typhus and murine typhus in Bangladeshi patients
Time Frame: 1 year
1 year

Secondary Outcome Measures

Outcome Measure
Time Frame
Evaluation of markers of disease severity
Time Frame: 1 year
1 year
Hemodynamic status of patients with typhus
Time Frame: 1 year
1 year
Diagnostic accuracy of rapid diagnostic tests for scrub and murine typhus
Time Frame: 1 year
1 year
Proportion of acute rickettsial illnesses in patients screened for malaria
Time Frame: 1 year
1 year
Identification of vectors harbouring Rickettsia/Orientia spp.
Time Frame: 1 year
1 year

Collaborators and Investigators

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

Sponsor

University of Oxford

Collaborators

University of Amsterdam
Menzies School of Health Research
Mahidol Oxford Tropical Medicine Research Unit
Chittagong Medical College and Hospital

Investigators

  • Principal Investigator: Amir Hossain, Professor Md, Chittagong Medical College and Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

August 1, 2014

Primary Completion (Actual)

September 1, 2015

Study Completion (Actual)

September 1, 2015

Study Registration Dates

First Submitted

January 8, 2015

First Submitted That Met QC Criteria

January 14, 2015

First Posted (Estimate)

January 15, 2015

Study Record Updates

Last Update Posted (Actual)

January 18, 2019

Last Update Submitted That Met QC Criteria

January 16, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BAKMAL1408

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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