Predicting referral need for febrile children in low-resource community settings in South and Southeast Asia
Issued Date
2026-01-01
Resource Type
ISSN
10788956
eISSN
1546170X
Scopus ID
2-s2.0-105038704483
Pubmed ID
42056495
Journal Title
Nature Medicine
Rights Holder(s)
SCOPUS
Bibliographic Citation
Nature Medicine (2026)
Suggested Citation
Chandna A., Koshiaris C., Mahajan R., Ahmad R.A., Thi Van Anh D., Choudhury K.S., Keang S., Phung N.T.N., Rattanavong S., Vannachone S., Yuniastuti A., Watson J.A., Vongsouvath M., Vongpromek R., Vinitsorn A., Turner C., Tran B.H., Thongpiam W., Tanunchai P., Souvannasing P., Shomik M., Sambou B., Rekart M., Pongvongsa T., Phamisith C., Phaiphichit C., Perera-Salazar R., Nguyen P.N.T., Menggred C., Malavong S., Luan N.H., Lasry E., Kunlaya K., Khamboocha R., Keomany S., Karyana M., Kain K., Jimenez C., Ghosh P., Dondorp A.M., Day N.P.J., Dat V.Q., Dat T.Q., Chanpheaktra N., Boutthasavong L., Blacksell S.D., Batty E.M., Painter C., Yosia M., Waithira N., Abdad M.Y., Thaipadungpanit J., Turner P., Phuc P.H., Mondal D., Mayxay M., Liem B.T., Ashley E.A., Arguni E., Richard-Greenblatt M., Lubell Y., Burza S. Predicting referral need for febrile children in low-resource community settings in South and Southeast Asia. Nature Medicine (2026). doi:10.1038/s41591-026-04338-1 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/116801
Title
Predicting referral need for febrile children in low-resource community settings in South and Southeast Asia
Author(s)
Chandna A.
Koshiaris C.
Mahajan R.
Ahmad R.A.
Thi Van Anh D.
Choudhury K.S.
Keang S.
Phung N.T.N.
Rattanavong S.
Vannachone S.
Yuniastuti A.
Watson J.A.
Vongsouvath M.
Vongpromek R.
Vinitsorn A.
Turner C.
Tran B.H.
Thongpiam W.
Tanunchai P.
Souvannasing P.
Shomik M.
Sambou B.
Rekart M.
Pongvongsa T.
Phamisith C.
Phaiphichit C.
Perera-Salazar R.
Nguyen P.N.T.
Menggred C.
Malavong S.
Luan N.H.
Lasry E.
Kunlaya K.
Khamboocha R.
Keomany S.
Karyana M.
Kain K.
Jimenez C.
Ghosh P.
Dondorp A.M.
Day N.P.J.
Dat V.Q.
Dat T.Q.
Chanpheaktra N.
Boutthasavong L.
Blacksell S.D.
Batty E.M.
Painter C.
Yosia M.
Waithira N.
Abdad M.Y.
Thaipadungpanit J.
Turner P.
Phuc P.H.
Mondal D.
Mayxay M.
Liem B.T.
Ashley E.A.
Arguni E.
Richard-Greenblatt M.
Lubell Y.
Burza S.
Koshiaris C.
Mahajan R.
Ahmad R.A.
Thi Van Anh D.
Choudhury K.S.
Keang S.
Phung N.T.N.
Rattanavong S.
Vannachone S.
Yuniastuti A.
Watson J.A.
Vongsouvath M.
Vongpromek R.
Vinitsorn A.
Turner C.
Tran B.H.
Thongpiam W.
Tanunchai P.
Souvannasing P.
Shomik M.
Sambou B.
Rekart M.
Pongvongsa T.
Phamisith C.
Phaiphichit C.
Perera-Salazar R.
Nguyen P.N.T.
Menggred C.
Malavong S.
Luan N.H.
Lasry E.
Kunlaya K.
Khamboocha R.
Keomany S.
Karyana M.
Kain K.
Jimenez C.
Ghosh P.
Dondorp A.M.
Day N.P.J.
Dat V.Q.
Dat T.Q.
Chanpheaktra N.
Boutthasavong L.
Blacksell S.D.
Batty E.M.
Painter C.
Yosia M.
Waithira N.
Abdad M.Y.
Thaipadungpanit J.
Turner P.
Phuc P.H.
Mondal D.
Mayxay M.
Liem B.T.
Ashley E.A.
Arguni E.
Richard-Greenblatt M.
Lubell Y.
Burza S.
Author's Affiliation
University of Toronto Faculty of Medicine
Technische Universität Berlin
University of Oxford Medical Sciences Division
Universität Leipzig
London School of Hygiene & Tropical Medicine
The Hospital for Sick Children
Universitas Gadjah Mada
Nuffield Department of Medicine
International Centre for Diarrhoeal Disease Research Bangladesh
Faculty of Tropical Medicine, Mahidol University
Hanoi Medical University
University of Medicine and Pharmacy at HCMC
Mahidol Oxford Tropical Medicine Research Unit
Medecins Sans Frontieres
Oxford University Clinical Research Unit
Amsterdam Institute for Global Health and Development
University of Nicosia Medical School
Kementerian Kesehatan Republik Indonesia
Mahosot Hospital, Lao
Angkor Hospital for Children
University of Health Sciences
Savannakhet Provincial Health Department
Savannakhet Provincial Hospital
Health in Harmony
Salavan Provincial Hospital
Wates District Hospital
Vietnam National Children’s Hospital
Technische Universität Berlin
University of Oxford Medical Sciences Division
Universität Leipzig
London School of Hygiene & Tropical Medicine
The Hospital for Sick Children
Universitas Gadjah Mada
Nuffield Department of Medicine
International Centre for Diarrhoeal Disease Research Bangladesh
Faculty of Tropical Medicine, Mahidol University
Hanoi Medical University
University of Medicine and Pharmacy at HCMC
Mahidol Oxford Tropical Medicine Research Unit
Medecins Sans Frontieres
Oxford University Clinical Research Unit
Amsterdam Institute for Global Health and Development
University of Nicosia Medical School
Kementerian Kesehatan Republik Indonesia
Mahosot Hospital, Lao
Angkor Hospital for Children
University of Health Sciences
Savannakhet Provincial Health Department
Savannakhet Provincial Hospital
Health in Harmony
Salavan Provincial Hospital
Wates District Hospital
Vietnam National Children’s Hospital
Corresponding Author(s)
Other Contributor(s)
Abstract
In resource-constrained community settings, identifying which febrile children require referral remains a major unmet need. Current World Health Organization (WHO) danger signs have limited accuracy, resulting in missed severe illness and unnecessary referrals. Here we developed and validated clinical prediction models to support referral decisions using data from 3,405 children aged 1−59 months presenting with community-acquired acute febrile illnesses to seven hospitals across Bangladesh, Cambodia, Indonesia, Laos and Vietnam. Cambodian data were held out for external validation. The model using simple clinical parameters (sensitivity 74.7% (95% confidence interval (CI): 59.4−88.1); specificity 99.1% (95% CI: 97.7−99.7)) outperformed WHO criteria (sensitivity 55.5% (95% CI: 39.4−72.7); specificity 82.6% (95% CI: 77.1−87.6)) for identification of children at risk of severe disease (death or organ support within 2 days). Including either pulse oximetry or the host biomarker soluble TREM1 (sTREM1) increased sensitivity to 88.9% (95% CI: 76.7−97.8; pulse oximetry) and 89.2% (95% CI: 76.9−97.5; sTREM1), respectively. The pulse oximetry-based model achieved these gains with a threefold reduction in referral rates. These approaches appear cost-effective (pulse oximetry incremental cost effectiveness ratio (ICER) = $26.28; sTREM1 ICER = $196.46) and could improve triage for febrile illness in low-resource settings by enabling more accurate referral decisions. They warrant evaluation in community-based trials.