In Gates open research
Introduction: Many acutely ill children in low- and middle-income settings have a high risk of mortality both during and after hospitalisation despite guideline-based care. Understanding the biological mechanisms underpinning mortality may suggest optimal pathways to target for interventions to further reduce mortality. The Childhood Acute Illness and Nutrition (CHAIN) Network ( www.chainnnetwork.org) Nested Case-Cohort Study (CNCC) aims to investigate biological mechanisms leading to inpatient and post-discharge mortality through an integrated multi-omic approach. Methods and analysis; The CNCC comprises a subset of participants from the CHAIN cohort (1278/3101 hospitalised participants, including 350 children who died and 658 survivors, and 270/1140 well community children of similar age and household location) from nine sites in six countries across sub-Saharan Africa and South Asia. Systemic proteome, metabolome, lipidome, lipopolysaccharides, haemoglobin variants, toxins, pathogens, intestinal microbiome and biomarkers of enteropathy will be determined. Computational systems biology analysis will include machine learning and multivariate predictive modelling with stacked generalization approaches accounting for the different characteristics of each biological modality. This systems approach is anticipated to yield mechanistic insights, show interactions and behaviours of the components of biological entities, and help develop interventions to reduce mortality among acutely ill children. Ethics and dissemination. The CHAIN Network cohort and CNCC was approved by institutional review boards of all partner sites. Results will be published in open access, peer reviewed scientific journals and presented to academic and policy stakeholders. Data will be made publicly available, including uploading to recognised omics databases. Trial registration NCT03208725.
Njunge James M, Tickell Kirkby, Diallo Abdoulaye Hama, Sayeem Bin Shahid Abu Sadat Mohammad, Gazi Md Amran, Saleem Ali, Kazi Zaubina, Ali Syed, Tigoi Caroline, Mupere Ezekiel, Lancioni Christina L, Yoshioka Emily, Chisti Mohammod Jobayer, Mburu Moses, Ngari Moses, Ngao Narshion, Gichuki Bonface, Omer Elisha, Gumbi Wilson, Singa Benson, Bandsma Robert, Ahmed Tahmeed, Voskuijl Wieger, Williams Thomas N, Macharia Alex, Makale Johnstone, Mitchel Anna, Williams Jessica, Gogain Joe, Janjic Nebojsa, Mandal Rupasri, Wishart David S, Wu Hang, Xia Lei, Routledge Michael, Gong Yun Yun, Espinosa Camilo, Aghaeepour Nima, Liu Jie, Houpt Eric, Lawley Trevor D, Browne Hilary, Shao Yan, Rwigi Doreen, Kariuki Kevin, Kaburu Timothy, Uhlig Holm H, Gartner Lisa, Jones Kelsey, Koulman Albert, Walson Judd, Berkley James
2022
Case-Cohort, Children, LMIC, Mortality, Omics, Systems Biology
