Causes and Outcomes of Febrile Illness in Health Facilities in Rural South and Southeast Asia

Recruiting

• Conditions: Acute Febrile Illness

• Registration Number: NCT04629053
• Lead Sponsor: University of Oxford

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.

Study Timeline

• Study First Submitted: 2020-11-09
• Study First Submitted QC: 2020-11-09
• Study First Posted: 2020-11-16
• Study Start: 2022-06-21
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-08
• Last Update Posted: 2024-05-09
• Primary Completion: 2024-12-01
• Study Completion: 2024-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 7200

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Prevalence of pathogens	Samples collected over approximately 1 month	Prevalence of a range of pathogens identified from febrile patients, analysed by region and participant age group

Secondary Outcome Measures

Name	Time	Method
Recovery status	Approximately 1 month	Recovery status e.g. full recovery, partial recovery, deterioration, and death at specified time points up to 28 days from enrolment
The association between host biomarkers and other predictors with aetiological diagnoses and clinical outcomes	Samples collected over approximately 1 month	The area under the curve, sensitivity and specificity of host biomarkers and other predictors to identify bacterial infections and to predict severe outcomes.

Trial Locations

Locations (4)

Building Resources Across Communities (BRAC); 🇧🇩 Dhaka, Bangladesh

Laos-Oxford-Mahosot Wellcome Trust Research Unit; 🇱🇦 Vientiane, Lao People's Democratic Republic

Chiangrai Clinical Research Unit (CCRU); 🇹🇭 Chiang Rai, Thailand

Shoklo Malaria Research Unit; 🇹🇭 Mae Sot, Tak, Thailand