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
Affiliations
- Albert Koulman
- MRC Epidemiology Unit, University of Cambridge, Cambridge, UK
- Kelsey Jones
- Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK
- James Berkley
- The Childhood Acute Illness and Nutrition Network, Nairobi, Kenya
- Judd Walson
- ORCiD
- Global Health and Epidemiology, University of Washington, Seattle, Seattle, USA
- Eric Houpt
- ORCiD
- Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USA
- David S. Wishart
- Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada
- Christina L. Lancioni
- Department of Pediatrics, Oregon Health and Science University, Portland, OR, USA
- Moses Ngari
- The Childhood Acute Illness and Nutrition Network, Nairobi, Kenya
- Lei Xia
- School of Food Science and Nutrition, University of Leeds, Leeds, UK
- James M. Njunge
- ORCiD
- The Childhood Acute Illness and Nutrition Network, Nairobi, Kenya
- Abdoulaye Hama Diallo
- Department of Public Health, Faculty of Health Sciences, University of Ouagadougou, Ouagadougou, Burkina Faso
- Kirkby Tickell
- Global Health and Epidemiology, University of Washington, Seattle, Seattle, USA
- Md. Amran Gazi
- Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
- Abu Sadat Mohammad Sayeem Bin Shahid
- Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
- Zaubina Kazi
- Department of Pediatrics and Child Health, Aga Khan University Hospital, Karachi, Karachi, Pakistan
- Ali Saleem
- Department of Pediatrics and Child Health, Aga Khan University Hospital, Karachi, Karachi, Pakistan
- Caroline Tigoi
- The Childhood Acute Illness and Nutrition Network, Nairobi, Kenya
- Syed Ali
- Department of Pediatrics and Child Health, Aga Khan University Hospital, Karachi, Karachi, Pakistan
- Emily Yoshioka
- Global Health and Epidemiology, University of Washington, Seattle, Seattle, USA
- Ezekiel Mupere
- Department of Paediatrics and Child Health, College of Health Sciences, Makerere University, Kampala, Uganda
- Moses Mburu
- The Childhood Acute Illness and Nutrition Network, Nairobi, Kenya
- Mohammod Jobayer Chisti
- Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
- Bonface Gichuki
- ORCiD
- The Childhood Acute Illness and Nutrition Network, Nairobi, Kenya
- Narshion Ngao
- The Childhood Acute Illness and Nutrition Network, Nairobi, Kenya
- Wilson Gumbi
- The Childhood Acute Illness and Nutrition Network, Nairobi, Kenya
- Elisha Omer
- The Childhood Acute Illness and Nutrition Network, Nairobi, Kenya
- Robert Bandsma
- Centre for Global Child Health, The Hospital for Sick Children, Toronto, Ontario, Canada
- Benson Singa
- ORCiD
- Kenya Medical Research Institute, Nairobi, Kenya
- Wieger Voskuijl
- ORCiD
- Amsterdam UMC location, University of Amsterdam, Amsterdam, The Netherlands
- Tahmeed Ahmed
- Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
- Alex Macharia
- KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
- Thomas N. Williams
- KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
- Anna Mitchel
- SomaLogic, Boulder, Colorado, USA
- Johnstone Makale
- KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
- Joe Gogain
- SomaLogic, Boulder, Colorado, USA
- Jessica Williams
- SomaLogic, Boulder, Colorado, USA
- Rupasri Mandal
- Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada
- Nebojsa Janjic
- SomaLogic, Boulder, Colorado, USA
- Michael Routledge
- School of Food Science and Nutrition, University of Leeds, Leeds, UK
- Hang Wu
- ORCiD
- School of Food Science and Nutrition, University of Leeds, Leeds, UK
- Camilo Espinosa
- Departments of Anesthesiology, Pain, and Perioperative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA
- Yun Yun Gong
- ORCiD
- School of Food Science and Nutrition, University of Leeds, Leeds, UK
- Jie Liu
- Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USA
- Nima Aghaeepour
- Departments of Anesthesiology, Pain, and Perioperative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA
- Hilary Browne
- Wellcome Sanger Institute, Hinxton, UK
- Trevor D. Lawley
- Wellcome Sanger Institute, Hinxton, UK
- Doreen Rwigi
- The Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya
- Yan Shao
- Wellcome Sanger Institute, Hinxton, UK
- Timothy Kaburu
- ORCiD
- The Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya
- Kevin Kariuki
- ORCiD
- The Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya
- Lisa Gartner
- Translational Gastroenterology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK
- Holm H. Uhlig
- Translational Gastroenterology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK
- Journal volume & issue
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Vol. 6
Abstract
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.
