Multiomics characterization of acute child illness and mortality in Africa and South Asia
Abstract
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.
Article Details
Authors (50)
Camilo A. Espinosa
James M. Njunge
Kirkby D. Tickell
Abdoulaye Hama Diallo
Abu Sadat Mohammad Sayeem Bin Shahid
Md Amran Gazi
Zaubina Kazi
Emily Yoshioka
Caroline Tigoi
Moses Mburu
Moses Ngari
Narshion Ngao
Elisha Omer
Wilson Gumbi
Bonface M. Gichuki
Anna Mitchel
Jessica Williams
Joseph Gogain
Nebojsa Janjic
Rupasri Mandal
Benjamin Jenkins
Hilary P. Browne
Yan Shao
State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, P. R. China
Timothy Rozday
Mark D. Stares
Nicholas J. R. Dawson
Eloïse Berson
Alan Chang
Yeasul Kim
Samson J. Mataraso
Chi-Hung Shu
Thanaphong Phongpreecha
Lei Xue
Ali Saleem
Benson Singa
Tahmeed Ahmed
Wieger P. Voskuijl
David S. Wishart
Eric R. Houpt
Jie Liu
Asad Ali
Ezekiel Mupere
Mohammod Jobayer Chisti
Robert H. J. Bandsma
Trevor D. Lawley
Albert Koulman
Christina L. Lancioni
Nima Aghaeepour
James A. Berkley
KEMRI–Wellcome Trust Research Programme, Center for Graphic Medicine Research, Kilifi, Kenya
Judd L. Walson