Clinical trial NCT04629053: Causes and Outcomes of Febrile Illness in Health Facilities in Rural South and Southeast Asia
Official title: Determining the Causes and Outcomes of Febrile Illness in Health Care Facilities in Rural South and Southeast Asia, as Part of the South and Southeast Asian Community-based Trials Network (SEACTN). Work Package B (WP-B).
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Acute Febrile Illness
Keywords: Acute Febrile Illness
Causes
Outcomes
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: Shoklo Malaria Research Unit (SMRU)
name: Lao-Oxford-Mahosot Hospital Wellcome Trust Research Unit
name: Building Resources Across Communities (BRAC), Bangladesh
name: Mahidol Oxford Tropical Medicine Research Unit
name: Chiang Rai Clinical Research Unit (CCRU), Thailand
First posted: 2020-11-16
Enrollment: 7200
Sex: ALL
Minimum age (years): 29
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients residing in rural areas in Laos, Myanmar, Thailand, the Thai-Myanmar border region, and Bangladesh and presenting with acute febrile illnesses to participating health facilities

Brief summary: This prospective multi-site observational study aims to describe causes and clinical outcomes of acute febrile illness as well as host biomarkers in patients aged \>28 days residing in rural areas in Laos, Myanmar, Thailand, the Thai-Myanmar border region, and Bangladesh and presenting with acute febrile illnesses (≤ 14 days duration) to participating health facilities.

This study is funded by the UK Wellcome Trust. The grant reference number is 215604/Z/19/Z

Detailed description: The majority of people in low- and middle-income countries (LMICs) in South and Southeast Asia live in rural areas. These people are some of the poorest in the region and the exact health issues which concern them have not been well defined, in that they have not been fully studied. Despite this lack of data, there are indications that disease of an infectious aetiology, 'febrile illness,' in particular in the tropics, still accounts for significant morbidity and mortality. This is in contrast to higher-income countries.

The South and Southeast Asian Community-based Trials Network in Rural Febrile Illness project (SEACTN RFI) aims to better understand and quantify the burden of febrile illness, the aetiological causes and the manner in which it affects the people of the area, all on a scale which has not been attempted before. It will collect information to help better understand and predict these outcomes based on a multitude of factors, which will form the basis for interventions within the network in the future. The initial study will be observational, as the current understanding of the local health issues and the health systems in these areas is insufficient to know how best to intervene.

In a separate work package, Work Package A (WP-A), the investigators will be collecting data from within the participating SEACTN communities through village health workers (VHWs) and local health facilities on the incidence, causes and outcomes of febrile illness in these areas.

In Work Package B (WP-B) will recruit patients seeking care at higher level facilities than the WP-A VHWs and health centres. These patients are likely to be more severely ill, in order to obtain a more thorough understanding of the causes and burden of febrile illness in these areas. A broader range of specimens, including venous blood samples and respiratory specimens will be collected. In-depth diagnostic testing including blood cultures, serological assays, pathogen molecular diagnostics, host biomarker assays, and validation of pathogen-blind next generation sequencing approaches will be conducted. The data from WP-A gathered in the community complemented by the WP-B data from higher level health facilities in the same regions will provide a rich understanding of the causes, incidence and outcomes of febrile illness in these areas. These data will be analysed using advanced statistical methodology to create electronic decision-support tools (eDSTs) to aid VHWs in their assessment, triage and treatment of patients. These and other relevant interventions will later be trialled across the SEACTN villages.

Eligibility criteria: Inclusion Criteria:

1. The patient and/or where relevant their parent/guardian/caretaker is willing and able to give informed consent /assent for participation in the study;
2. Aged \> 28 days (day of birth = Day 1);
3. Axillary temperature at presentation (≥ 37.5°C (99.5°F) OR \< 35.5°C (95.9°F)) and no more likely cause than sepsis for hypothermia OR History of fever in the 24 hours prior to presentation;
4. Onset of illness ≤ 14 days

Exclusion Criteria:

1. Accident or trauma is the cause for the patient's presentation;
2. Presentation ≤ 3 days after routine immunisations
3. Is currently under follow-up or has been afebrile for less than 72 hours after completion of a follow-up period.
4. The treating healthcare worker's decision is to send the patient home following initial assessment.

Primary outcomes:
measure: Prevalence of pathogens
timeFrame: Samples collected over approximately 1 month
Secondary outcomes:
measure: Recovery status
timeFrame: Approximately 1 month
measure: The association between host biomarkers and other predictors with aetiological diagnoses and clinical outcomes
timeFrame: Samples collected over approximately 1 month
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: Building Resources Across Communities (BRAC)
city: Vientiane
country: Lao People's Democratic Republic
facility: Laos-Oxford-Mahosot Wellcome Trust Research Unit
city: Mae Sot
country: Thailand
facility: Shoklo Malaria Research Unit
state: Tak
city: Chiang Rai
country: Thailand
facility: Chiangrai Clinical Research Unit (CCRU)
Study officials:
affiliation: Mahidol Oxford Tropical Medicine Research Unit
name: Yoel Lubell, Prof.
role: PRINCIPAL_INVESTIGATOR
References: