Rickettsial Disease Clinical Trial
Official title:
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.
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).
;