Multiomics characterization of acute child illness and mortality in Africa and South Asia

Childhood illnesses from infectious diseases in low- and middle-income countries contribute substantially to the global under-five mortality. Many hospitalized children experience incomplete recovery, readmission, and post-discharge mortality despite guideline-directed care. However, targeted interventions remain elusive due to limited understanding of underlying mechanisms. In this work, we employ multiomic profiling and multivariate modeling to investigate biological drivers of inpatient and post-discharge mortality in 3,101 acutely ill children across nine sites in sub-Saharan Africa and South Asia. In a nested case-cohort (N = 1008), we generate plasma proteomics, serum metabolomics and lipidomics, stool metagenomics, and fecal pathogen data at admission and discharge. Additionally, we profile 270 geographically matched community children for biological baselines. We identify a generalizable mortality signature marked by immune, inflammatory, and metabolic dysregulation with gut dysbiosis. We show that mortality-associated signals persist from admission through discharge, indicating unresolved disease and that malnourished children show greater baseline perturbations, explaining elevated risk. We also find some children with low clinical severity display high predicted mortality risk from targeted biomarkers. Finally, we distill predictive models to a clinically feasible biomarker panel and validate our findings in an independent cohort (N = 100). By linking inpatient and post-discharge mortality to specific biological mechanisms, our findings highlight why current care can fail and demonstrate how biomarker-guided risk stratification can identify vulnerable children currently missed by clinical assessments, enabling targeted interventions to reduce mortality in low- and middle-income countries.

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Publication Details

Journal
Nature Communications
Published
2026-04-13
DOI
https://doi.org/10.1038/s41467-026-69754-w
Primary Topic
Child Nutrition and Water Access
Type
article
Field-Weighted Citation Impact
0.00

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article

Multiomics characterization of acute child illness and mortality in Africa and South Asia

Nebojša Janjić, Hilary P. Browne, Albert Koulman, Moses Mburu et al.
Nature Communications
Child Nutrition and Water Access
article

Multiomics characterization of acute child illness and mortality in Africa and South Asia

Nebojša Janjić, Hilary P. Browne, Albert Koulman, Moses Mburu, Thanaphong Phongpreecha, Nicholas Dawson, Benjamin Jenkins, Abu Sadat Mohammad Sayeem Bin Shahid, Robert Bandsma, Yeasul Kim, Christina Lancioni, Yan Shao, Bonface M. Gichuki, Nima Aghaeepour, Camilo Espinosa, James Alexander Berkley, Caroline Tigoi, Trevor D. Lawley, Judd L. Walson, James M. Njunge, Wieger P. Voskuijl, Abdoulaye Hama Diallo, Zaubina Kazi, Eloïse Berson, Samson Mataraso, Moses M. Ngari, Narshion Ngao, Kirkby D. Tickell, Anna Mitchel, Timothy Rozday, Ali Faisal Saleem, Benson O. Singa, Mohammod Jobayer Chisti, Joseph Gogain, Rupasri Mandal, Chi-Hung Shu, Md Amran Gazi, Mark D. Stares, Jie Liu, Eric R. Houpt, Emily Yoshioka, Jessica Williams, David S. Wishart, Tahmeed Ahmed, Asad Ali, Wilson Gumbi, Ezekiel Mupere, On behalf of The Childhood Acute Illness and Nutrition (CHAIN) Network, Elisha Omer, Lei Xue
article en

Abstract

Childhood illnesses from infectious diseases in low- and middle-income countries contribute substantially to the global under-five mortality. Many hospitalized children experience incomplete recovery, readmission, and post-discharge mortality despite guideline-directed care. However, targeted interventions remain elusive due to limited understanding of underlying mechanisms. In this work, we employ multiomic profiling and multivariate modeling to investigate biological drivers of inpatient and post-discharge mortality in 3,101 acutely ill children across nine sites in sub-Saharan Africa and South Asia. In a nested case-cohort (N = 1008), we generate plasma proteomics, serum metabolomics and lipidomics, stool metagenomics, and fecal pathogen data at admission and discharge. Additionally, we profile 270 geographically matched community children for biological baselines. We identify a generalizable mortality signature marked by immune, inflammatory, and metabolic dysregulation with gut dysbiosis. We show that mortality-associated signals persist from admission through discharge, indicating unresolved disease and that malnourished children show greater baseline perturbations, explaining elevated risk. We also find some children with low clinical severity display high predicted mortality risk from targeted biomarkers. Finally, we distill predictive models to a clinically feasible biomarker panel and validate our findings in an independent cohort (N = 100). By linking inpatient and post-discharge mortality to specific biological mechanisms, our findings highlight why current care can fail and demonstrate how biomarker-guided risk stratification can identify vulnerable children currently missed by clinical assessments, enabling targeted interventions to reduce mortality in low- and middle-income countries.

Nature Communications
Qingdao University (CN), Université Joseph Ki-Zerbo (BF), Johns Hopkins University (US), University of Alberta (CA), University of Malawi (MW), Oregon Health & Science University (US), University of Washington (US), International Centre for Diarrhoeal Disease Research (BD), University of Cambridge (GB), Angkor Hospital for Children (KH), Kamuzu Central Hospital (MW), Hospital for Sick Children (CA), Wellcome Sanger Institute (GB), Aga Khan University Hospital (PK), Kenya Medical Research Institute (KE), Standard Bio (Norway) (NO), Emma Kinderziekenhuis (NL), Wellcome/MRC Institute of Metabolic Science (GB), Amsterdam Institute for Global Health and Development (NL), Stanford Medicine (US), The Childhood Acute Illness and Nutrition Network (KE), Kamuzu University of Health Sciences (MW), University of Virginia (US), Makerere University (UG), Stanford University (US)
Bill and Melinda Gates Foundation, Wellcome Trust, National Institute for Health and Care Research, National Institutes of Health, NIHR Cambridge Biomedical Research Centre
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Child Nutrition and Water Access
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