Causes of Fever in Bangladeshi Patients

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).

Patients

Inclusion criteria

• Admitted to CMCH
• Have had malaria and typhus rapid tests
• Age≥12 years old
• Febrile or history of fever for <3 weeks.
• 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

• No known acute or chronic medical conditions
• Asymptomatic
• No febrile illness in the last 2 weeks
• Age≥12 years old
• Written informed consent from patient 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 is under 18 years.