Bacterial infections are one of the leading causes of death and disability among children. The host response to infection involves complex interplays between inflammation, coagulation, and fibrinolysis. In meningococcal sepsis, the inflammatory response induce excessive coagulation and downregulation of fibrinolysis, contributing to the need to amputate extremities, multiple organ dysfunction, and eventually death. In this thesis, we characterized children with severe bacterial infections and we studied the following six determinants in relation to outcome: neutrophil extracellular traps (NETs), human leukocyte antigen-DR (HLA-DR) expression on monocyte subsets, glycosylation of the fragment crystallizable (Fc) region of immunoglobulin G (IgG), A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS)-1, ADAMTS-18, and plasminogen-activator-inhibitor-1 (PAI-1). In addition, we explored the role of genetic variation within individuals in the host response to infection.
This thesis shows that community-acquired sepsis continues to cause a devastating effect in high-income countries, mainly by high incidence of disability. Furthermore, this thesis provides considerable insight into the host response to sepsis by studying specific inflammatory, hemostatic, genetic, and environmental factors in relation to outcome. These determinants could help to detect patients at risk for poor outcome at an early stage, and have given us new directions to individualize sepsis treatment.

Additional Metadata
Keywords ADAMTS-1, ADAMTS-18, Bacterial infections, Children, Circadian Rhythm, Coagulation, Critical care, Fc glycosylation, Fibrinolysis, Genetic polymorphisms, Human leukocyte antigen-DR expression, Inflammation, Meningococcal infections, Morbidity, Mortality, Neutrophil extracellular traps, N-glycan, Outcome, Pediatrics, Plasminogen-activator-inhibitor-1, Pneumococcal infections, Sepsis
Promotor J.A. Hazelzet (Jan) , D. Tibboel (Dick) , M. Emonts (Marieke) , G.J.A. Driessen (Gertjan)
Publisher Erasmus University Rotterdam
ISBN 978-94-6380-074-7
Persistent URL hdl.handle.net/1765/111887
Note For copyright reasons there is a partial embargo for this dissertation
Citation
Boeddha, N.P. (2018, November 13). Pediatric Sepsis: Determinants of outcome. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/111887