Biomarkers of post-discharge mortality among children with complicated severe acute malnutrition


Sci Rep

High mortality after discharge from hospital following acute illness has been observed among children with Severe Acute Malnutrition (SAM). However, mechanisms that may be amenable to intervention to reduce risk are unknown. We performed a nested case-control study among HIV-uninfected children aged 2-59 months treated for complicated SAM according to WHO recommendations at four Kenyan hospitals. Blood was drawn from 1778 children when clinically judged stable before discharge from hospital. Cases were children who died within 60 days. Controls were randomly selected children who survived for one year without readmission to hospital. Untargeted proteomics, total protein, cytokines and chemokines, and leptin were assayed in plasma and corresponding biological processes determined. Among 121 cases and 120 controls, increased levels of calprotectin, von Willebrand factor, angiotensinogen, IL8, IL15, IP10, TNFalpha, and decreased levels of leptin, heparin cofactor 2, and serum paraoxonase were associated with mortality after adjusting for possible confounders. Acute phase responses, cellular responses to lipopolysaccharide, neutrophil responses to bacteria, and endothelial responses were enriched among cases. Among apparently clinically stable children with SAM, a sepsis-like profile is associated with subsequent death. This may be due to ongoing bacterial infection, translocated bacterial products or deranged immune response during nutritional recovery.

Njunge, J. M., Gwela, A., Kibinge, N. K., Ngari, M., Nyamako, L., Nyatichi, E., Thitiri, J., Gonzales, G. B., Bandsma, R. H. J., Walson, J. L., Gitau, E. N., Berkley, J. A.

Pages:5981, Volume:9, Edition:4/14/2019, Date,Apr-12


Notes:Njunge, James M|Gwela, Agnes|Kibinge, Nelson K|Ngari, Moses|Nyamako, Lydia|Nyatichi, Emily|Thitiri, Johnstone|Gonzales, Gerard Bryan|Bandsma, Robert H J|Walson, Judd L|Gitau, Evelyn N|Berkley, James A|eng|WT_/Wellcome Trust/United Kingdom|MR/M007367/1/MRC_/Medical Research Council/United Kingdom|Research Support, Non-U.S. Gov’t|England|2019/04/14 06:00|Sci Rep. 2019 Apr 12;9(1):5981. doi: 10.1038/s41598-019-42436-y.

ISBN: 2045-2322 (Electronic)|2045-2322 (Linking) Permanent ID: PMC6461700 Accession Number: 30979939

Author Address: The Childhood Acute Illness & Nutrition (CHAIN) Network, Nairobi, Kenya.|KEMRI/Wellcome Trust Research Programme, Kilifi, Kenya.|The Childhood Acute Illness & Nutrition (CHAIN) Network, Nairobi, Kenya.|KEMRI/Wellcome Trust Research Programme, Kilifi, Kenya.|Department of Gastroenterology, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.|Inflammation Research Centre, Flemish Institute for Biotechnology, Ghent, Belgium.|Centre for Global Child Health, The Hospital for Sick Children, Toronto, Ontario, Canada.|Departments of Global Health, Medicine, Paediatrics and Epidemiology, University of Washington, Seattle, Washington, USA.|African Population and Health Research Centre, Nairobi, Kenya.|Centre for Tropical Medicine & Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.