Gates Open Research (Nov 2022)

The Childhood Acute Illness and Nutrition (CHAIN) network nested case-cohort study protocol: a multi-omics approach to understanding mortality among children in sub-Saharan Africa and South Asia [version 2; peer review: 2 approved]

  • Albert Koulman,
  • Kelsey Jones,
  • James Berkley,
  • Judd Walson,
  • Eric Houpt,
  • David S. Wishart,
  • Christina L. Lancioni,
  • Moses Ngari,
  • Lei Xia,
  • James M. Njunge,
  • Abdoulaye Hama Diallo,
  • Kirkby Tickell,
  • Md. Amran Gazi,
  • Abu Sadat Mohammad Sayeem Bin Shahid,
  • Zaubina Kazi,
  • Ali Saleem,
  • Caroline Tigoi,
  • Syed Ali,
  • Emily Yoshioka,
  • Ezekiel Mupere,
  • Moses Mburu,
  • Mohammod Jobayer Chisti,
  • Bonface Gichuki,
  • Narshion Ngao,
  • Wilson Gumbi,
  • Elisha Omer,
  • Robert Bandsma,
  • Benson Singa,
  • Wieger Voskuijl,
  • Tahmeed Ahmed,
  • Alex Macharia,
  • Thomas N. Williams,
  • Anna Mitchel,
  • Johnstone Makale,
  • Joe Gogain,
  • Jessica Williams,
  • Rupasri Mandal,
  • Nebojsa Janjic,
  • Michael Routledge,
  • Hang Wu,
  • Camilo Espinosa,
  • Yun Yun Gong,
  • Jie Liu,
  • Nima Aghaeepour,
  • Hilary Browne,
  • Trevor D. Lawley,
  • Doreen Rwigi,
  • Yan Shao,
  • Timothy Kaburu,
  • Kevin Kariuki,
  • Lisa Gartner,
  • Holm H. Uhlig

Journal volume & issue
Vol. 6

Abstract

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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.

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