Prediction of Disease Severity in Young Children Presenting With Acute Febrile Illness in Resource-limited Settings

NCT04285021 | Completed DMC

• 1 other identifier: HCR18004
• Study Type: observational
• Target: 3,433
• Locations: 5 countries
• Sites: 6

Brief Summary

Note that this is a study that is co-sponsored by Medecins Sans Frontieres, Spain, and the University of Oxford. The primary objective is to develop a risk prediction algorithm, combining measurements of host biomarkers and clinical features at the point-of-triage, for children with an acute febrile illness in resource-limited settings. The secondary objectives are to determine which host biomarkers, feasible for measurement at the point-of-care, are predictive of disease severity. Additionally to determine the optimal combination of clinical features (including demographics, anthropometric data, historical variables, vital signs, clinical signs and clinical symptoms), feasible for assessment by limited-skill health workers, that is predictive of disease severity. The tertiary objectives are to explore the impact of different methods of outcome classification on development of the risk prediction algorithm, and to explore the performance of the algorithm to predict disease severity in key presenting clinical syndromes and aetiologies.

Conditions

Sepsis

Keywords

Febrile illness; Biomarker; Clinical Severity Scale; Disease severity; Resource-limited setting

Outcome Measures

Primary Outcomes (1)

• Risk prediction algorithm

  To predict disease severity for children with an acute febrile illness in resource-limited settings by combining measurements of host biomarkers and clinical features at the point-of-triage

  12-15 months

Secondary Outcomes (2)

• Biomarkers

  12-15 months

• Clinical features of severity

  12-15 months

Other Outcomes (2)

• Outcome classification for severity

  12-15 months

• Risk prediction algorithm performance

  12-15 months

Eligibility Criteria

• Age: 28 Days - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Children aged \> 28 days and \< 5 years presenting to the study site with an acute febrile illness

You may qualify if:

• The participant may enter the study if ALL of the following apply:
• Caretaker is willing and able to give informed consent for participation in the study;
• Aged \> 28 days and \< 5 years \[day of birth = Day 1\];
• Axillary temperature at presentation ≥ 37.5°C OR axillary temperature at presentation \< 35.5°C OR history of fever in last 24h;
• Onset of illness ≤ two weeks.

You may not qualify if:

• The participant may not enter the study if ANY of the following apply:
• Accident or trauma is the cause for child's presentation;
• Presentation ≤ 72 hours after routine immunisations;
• Known chronic medical condition including immunosuppression (for example, oncological conditions, HIV infection, thalassaemia, current steroid use), active chronic infection (for example, tuberculosis, hepatitis B virus), active cardiorespiratory conditions (for example, symptomatic or currently medicated congenital heart disease, cardiomyopathy or bronchiectasis);
• Admission to any health facility during the current illness;
• Previously enrolled in the study for a different acute illness;
• Receipt of \> 15 minutes of inpatient treatment.

Sponsors & Collaborators

• Medecins Sans Frontieres, Spain: lead
• Mahidol Oxford Tropical Medicine Research Unit: collaborator
• Gadjah Mada University: collaborator
• Lao-Oxford-Mahosot Hospital Wellcome Trust Research Unit: collaborator
• Cambodia Oxford Medical Research Unit: collaborator
• University of Medicine and Pharmacy at Ho Chi Minh City: collaborator
• Research Institute for Tropical Medicine, Philippines: collaborator
• International Centre for Diarrhoeal Disease Research, Bangladesh: collaborator
• Hanoi Medical University: collaborator

Study Sites (6)

MSF Goyalmara Green Roof Hospital

Cox’s Bāzār, Bangladesh

Location

Angkor Hospital for Children

Siem Reap, Krong Siem Reap, Cambodia

Location

Rumah Sakit Umum Daerah Wates

Yogyakarta, DI Yogyakarta, Indonesia

Location

Laos-Oxford-Mahosot Wellcome Trust Research Unit

Vientiane, Laos

Location

Vietnam National Children's Hospital

Hanoi, Vietnam

Location

Dong Nai Children's Hospital

Đông Nãi, Vietnam

Location

Related Publications (2)

• Chandna A, Koshiaris C, Mahajan R, Ahmad RA, Van Anh DT, Choudhury KS, Keang S, Nguyen PNT, Rattanavong S, Vannachone S; Spot Sepsis Investigator Group; Yosia M, Waithira N, Abdad MY, Thaipadungpanit J, Turner P, Phuc PH, Mondal D, Mayxay M, Liem BT, Ashley EA, Arguni E, Perera-Salazar R, Richard-Greenblatt M, Lubell Y, Burza S. Risk stratification of childhood infection using host markers of immune and endothelial activation in Asia (Spot Sepsis): a multi-country, prospective, cohort study. Lancet Child Adolesc Health. 2025 Sep;9(9):634-645. doi: 10.1016/S2352-4642(25)00183-X.

  PMID: 40774784 DERIVED

• Chandna A, Aderie EM, Ahmad R, Arguni E, Ashley EA, Cope T, Dat VQ, Day NPJ, Dondorp AM, Illanes V, De Jesus J, Jimenez C, Kain K, Suy K, Koshiaris C, Lasry E, Mayxay M, Mondal D, Perera R, Pongvongsa T, Rattanavong S, Rekart M, Richard-Greenblatt M, Shomik M, Souvannasing P, Tallo V, Turner C, Turner P, Waithira N, Watson JA, Yosia M, Burza S, Lubell Y. Prediction of disease severity in young children presenting with acute febrile illness in resource-limited settings: a protocol for a prospective observational study. BMJ Open. 2021 Jan 25;11(1):e045826. doi: 10.1136/bmjopen-2020-045826.

  PMID: 33495264 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood will be taken for biomarker assessment from all children, which may include pathogenic identification.

MeSH Terms

Conditions

Sepsis

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Sakib Burza, PhD

  Medecins Sans Frontieres, Spain

  PRINCIPAL INVESTIGATOR

• Yoel Lubell, PhD

  Mahidol Oxford Tropical Medicine Research Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2020
• First Posted: February 26, 2020
• Study Start: March 5, 2020
• Primary Completion: November 30, 2022
• Study Completion: November 30, 2022
• Last Updated: April 24, 2023

Record last verified: 2022-03

Locations

BA (1); CA (1); ID (1); LA (1); VN (2)