Causes and Outcomes of Febrile Illness in Health Facilities in Rural South and Southeast Asia (SEACTN-WP-B)

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).

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

Study Overview

• Status: Recruiting
• Conditions: Acute Febrile Illness

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 Type: Observational
• Enrollment (Estimated): 7200

Contacts and Locations

• Study Contact: Name: Yoel Lubell, Prof.; Phone Number: +66-857201350; Email: yoel@tropmedres.ac
• Study Contact Backup: Name: Rusheng Chew, Dr.; Email: chris@tropmedres.ac

Study Locations

• Bangladesh
  • Dhaka, Bangladesh, 1212
    • Not yet recruiting
    • Building Resources Across Communities (BRAC)
    • Contact: Aninda Sen, MBBS | MPH; Phone Number: (+880) 171 131 9050; Email: aninda.sen@brac.net
    • Contact: Amit Neogi, Masters; Phone Number: (+880)179 220 5401; Email: amit.kn@brac.net
• Lao People's Democratic Republic
  • Vientiane, Lao People's Democratic Republic, 01000
    • Recruiting
    • Laos-Oxford-Mahosot Wellcome Trust Research Unit
    • Contact: Koukeo Phommasone, PhD; Phone Number: +(85) 620 558 42842; Email: Koukeo@tropmedres.ac
    • Contact: Elizabeth Ashley, Professor; Phone Number: (+85)621 250 752; Email: liz@tropmedres.ac
• Thailand
  • Chiang Rai, Thailand, 57000
    • Recruiting
    • Chiangrai Clinical Research Unit (CCRU)
    • Contact: Carlo Perrone, MD; Phone Number: (+66) 985 340 823; Email: Carlo@tropmedres.ac
    • Contact: Nidanuch Tasak, Bachelor; Phone Number: (+66)910 719 036; Email: nidanuch@tropmedres.ac
  • Tak
    • Mae Sot, Tak, Thailand, 63110
      • Recruiting
      • Shoklo Malaria Research Unit
      • Contact: Aung Pyae Phyo, Dr; Phone Number: +66064292107; Email: aungpyaephyo@tropmedres.ac
      • Contact: Francois Nosten, Professor; Email: francois@tropmedres.ac

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patients with an acute febrile illness; Patients with acute febrile illness, 4,800 children and 2,400 adults, divided equally across four countries (Laos, Myanmar,Thailand (including the Thai-Myanmar border region), and Bangladesh) and three age groups: >28 days to <5 years; ≥5 years to <15 years, and ≥15 years of age.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: Mahidol Oxford Tropical Medicine Research Unit; Shoklo Malaria Research Unit (SMRU); Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU); Building Resources Across Communities (BRAC), Bangladesh; Chiang Rai Clinical Research Unit (CCRU), Thailand
• Investigators: Principal Investigator: Yoel Lubell, Prof., Mahidol Oxford Tropical Medicine Research Unit

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2022
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: November 9, 2020
• First Submitted That Met QC Criteria: November 9, 2020
• First Posted (Actual): November 16, 2020

Study Record Updates

• Last Update Posted (Estimated): January 15, 2024
• Last Update Submitted That Met QC Criteria: January 12, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Outcomes; Acute Febrile Illness; Causes
• Additional Relevant MeSH Terms: Wounds and Injuries; Body Temperature Changes; Heat Stress Disorders; Hyperthermia; Fever
• Other Study ID Numbers: BAC20003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data collected for this study will be under the custodianship of MORU. With participant's consent, data from this study may be shared in a de-identified form with other groups or researchers in accordance with the MORU Data Sharing Policy.
• IPD Sharing Time Frame: After completion of trial activities and reporting
• IPD Sharing Access Criteria: MORU Data Sharing Policy. (http://www.tropmedres.ac/data-sharing-policy)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No