Clinical Trial: Causes of Fever in Bangladeshi Patients

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Rickettsial Disease in Febrile Hospitalised Patients in a Tertiary Referral Hospital in Bangladesh

Brief Summary:

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

Detailed Summary:

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 hav
Sponsor: University of Oxford

Current Primary Outcome: The clinical features of severe and uncomplicated scrub typhus and murine typhus in Bangladeshi patients [ Time Frame: 1 year ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

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


Original Secondary Outcome: Same as current

Information By: University of Oxford

Dates:
Date Received: January 8, 2015
Date Started: October 2014
Date Completion: December 2017
Last Updated: April 27, 2016
Last Verified: April 2016