Prediction of disease severity in young children presenting with acute febrile illness in resource-limited settings: a protocol for a prospective observational study

Arjun Chandna, Endashaw M Aderie, Riris Ahmad, Eggi Arguni, Elizabeth A Ashley, Tanya Cope, Vu Quoc Dat, Nicholas P J Day, Arjen M Dondorp, Victor Illanes, Joanne De Jesus, Carolina Jimenez, Kevin Kain, Keang Suy, Constantinos Koshiaris, Estrella Lasry, Mayfong Mayxay, Dinesh Mondal, Rafael Perera, Tiengkham Pongvongsa, Sayaphet Rattanavong, Michael Rekart, Melissa Richard-Greenblatt, Mohammad Shomik, Phouthalavanh Souvannasing, Veronica Tallo, Claudia Turner, Paul Turner, Naomi Waithira, James A Watson, Mikhael Yosia, Sakib Burza, Yoel Lubell, Arjun Chandna, Endashaw M Aderie, Riris Ahmad, Eggi Arguni, Elizabeth A Ashley, Tanya Cope, Vu Quoc Dat, Nicholas P J Day, Arjen M Dondorp, Victor Illanes, Joanne De Jesus, Carolina Jimenez, Kevin Kain, Keang Suy, Constantinos Koshiaris, Estrella Lasry, Mayfong Mayxay, Dinesh Mondal, Rafael Perera, Tiengkham Pongvongsa, Sayaphet Rattanavong, Michael Rekart, Melissa Richard-Greenblatt, Mohammad Shomik, Phouthalavanh Souvannasing, Veronica Tallo, Claudia Turner, Paul Turner, Naomi Waithira, James A Watson, Mikhael Yosia, Sakib Burza, Yoel Lubell

Abstract

Introduction: In rural and difficult-to-access settings, early and accurate recognition of febrile children at risk of progressing to serious illness could contribute to improved patient outcomes and better resource allocation. This study aims to develop a prognostic clinical prediction tool to assist community healthcare providers identify febrile children who might benefit from referral or admission for facility-based medical care.

Methods and analysis: This prospective observational study will recruit at least 4900 paediatric inpatients and outpatients under the age of 5 years presenting with an acute febrile illness to seven hospitals in six countries across Asia. A venous blood sample and nasopharyngeal swab is collected from each participant and detailed clinical data recorded at presentation, and each day for the first 48 hours of admission for inpatients. Multianalyte assays are performed at reference laboratories to measure a panel of host biomarkers, as well as targeted aetiological investigations for common bacterial and viral pathogens. Clinical outcome is ascertained on day 2 and day 28.Presenting syndromes, clinical outcomes and aetiology of acute febrile illness will be described and compared across sites. Following the latest guidance in prediction model building, a prognostic clinical prediction model, combining simple clinical features and measurements of host biomarkers, will be derived and geographically externally validated. The performance of the model will be evaluated in specific presenting clinical syndromes and fever aetiologies.

Ethics and dissemination: The study has received approval from all relevant international, national and institutional ethics committees. Written informed consent is provided by the caretaker of all participants. Results will be shared with local and national stakeholders, and disseminated via peer-reviewed open-access journals and scientific meetings.

Trial registration number: NCT04285021.

Keywords: infectious diseases; paediatrics; primary care; public health.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1
Figure 1
Study sites. Seven hospitals across six Asian countries where children presenting with acute febrile illness are prospectively enrolled into the study. Lao PDR = Lao People’s Democratic Republic.

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