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Role of Innate Immunity in Prevention of Health Care Associated Infections in Critically Ill Children- a Prospective Study
Corresponding Author(s) : Anusha Challa
International Journal of Allied Medical Sciences and Clinical Research,
Vol. 5 No. 1 (2017): 2017 Volume 5- Issue -1
Abstract
Introduction
Despite the advances in the critical care management, Health care associated infections (HAI) are leading to increased mortality and morbidity in Paediatric intensive care unit (PICU).Presently acquired immunity is measured routinely and not innate immune response. This study aims to measure Lipopolysaccharide (LPS) induced Tumour necrosis factor (TNF) ? to determine innate immune response in sick children admitted to PICU and association with subsequent development of HAI.
Materials and Methods
A hospital based prospective and observational study was conducted wherein total of 63 children admitted to PICU requiring ventilation or indwelling central line for more than 2 days were included. Whole blood assay of TNF ? levels using ELISA were measured after stimulation with Lipopolysaccharide on day 1,3 and 7 of ICU stay.Statistical analysis of the outcome variables was done by Mann Whitney U test and Wilcoxon signed rank test, ROC curve analysis for relation of TNF ? with HAI and mortality
Results
TNF ? is a significant predictor for HAI on day 1 estimation (p = 0.015). ROC curve showed Day 1 TNF ? levels more than 247 pg/ml and Day 3 TNF ? levels less than 203pg/ml as predictors of HAI and mortality respectively. There is statistically greater reduction in TNF ? between Day 3-Day 7 than Day 1-Day 3 in non survivors (p=0.027). Children who had VAP (p=0.018), HAI (p=0.025), and such reduction was also present in children with HAI caused by multi drug resistant organisms (p=0.0047), gram negative organisms (p=0.0001) and MRSA (p=0.023). This reduction was absent in children who survived and did not develop HAI.
Conclusion
LPS induced TNF ? levels are useful to predict likelihood of development HAI and mortality in critically ill children
Keywords
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World Health Organization. Report on the burden of endemic health care-associated infection worldwide. 2011; [cited on Aug 20,2016] Available from http://apps.who.int/iris/bitstream/10665/80135/1/9789241501507_eng.pdf
[2]. Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nature Reviews Immunology. 13(12), 2013, 862-74.
[3]. Muszynski JA, Nofziger R, Greathouse K, Nateri J, Hanson-Huber L, Steele L, Nicol K, Groner JI, Besner GE, Raffel C, Geyer S. Innate immune function predicts the development of nosocomial infection in critically injured children. Shock (Augusta, Ga.). 42(4), 2014, 313-21
[4]. Inweregbu K, Dave J, Pittard A. Nosocomial infections. Continuing Education in Anaesthesia, Critical Care & Pain. 5(1), 2005, 14-7.
[5]. Monneret G, Venet F. Immune Functional Testing in Clinics: Feasibility and Prediction of Deleterious Outcomes. Critical care medicine. 41(1), 2013, 367-8
[6]. Hall MW, Knatz NL, Vetterly C, Tomarello S, Wewers MD, Volk HD, Carcillo JA. Immunoparalysis and nosocomial infection in children with multiple organ dysfunction syndromes. Intensive care medicine. 37(3), 2011, 525-32.
[7]. Greathouse KC, Hall MW. Critical Illness–Induced Immune Suppression: Current State of the Science. American Journal of Critical Care. 25(1), 2016, 85-92.
[8]. Van Vught LA, Wiewel MA, Hoogendijk AJ, Scicluna BP, Belkasim H, Horn J, Schultz MJ, Van der Poll T. Reduced responsiveness of blood leukocytes to lipopolysaccharide does not predict nosocomial infections in critically ill patients. Critical Care. 19(1), 2015, 1
[9]. Downregulation of Proinflammatory Cytokine Release in Whole Blood From Septic PatientsBlood, 85(5), 1995, 1341-134
[10]. Manzoli TF, Troster EJ, Ferranti JF, Sales MM. Prolonged suppression of monocytic human leukocyte antigen–DR expression correlates with mortality in pediatric septic patients in a pediatric tertiary Intensive Care Unit. Journal of critical care. 33, 2016, 84-9
[11]. Changes of monocyte human leukocyte antigen- DR expression as a reliable predictor of mortality Critical Care 15, 2011, 220
[12]. Venet F, Lukaszewicz AC, Payen D, Hotchkiss R, Monneret G. Monitoring the immune response in sepsis: a rational approach to administration of immunoadjuvant therapies. Current opinion in immunology. 25(4), 2013, 477-83
References
[2]. Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nature Reviews Immunology. 13(12), 2013, 862-74.
[3]. Muszynski JA, Nofziger R, Greathouse K, Nateri J, Hanson-Huber L, Steele L, Nicol K, Groner JI, Besner GE, Raffel C, Geyer S. Innate immune function predicts the development of nosocomial infection in critically injured children. Shock (Augusta, Ga.). 42(4), 2014, 313-21
[4]. Inweregbu K, Dave J, Pittard A. Nosocomial infections. Continuing Education in Anaesthesia, Critical Care & Pain. 5(1), 2005, 14-7.
[5]. Monneret G, Venet F. Immune Functional Testing in Clinics: Feasibility and Prediction of Deleterious Outcomes. Critical care medicine. 41(1), 2013, 367-8
[6]. Hall MW, Knatz NL, Vetterly C, Tomarello S, Wewers MD, Volk HD, Carcillo JA. Immunoparalysis and nosocomial infection in children with multiple organ dysfunction syndromes. Intensive care medicine. 37(3), 2011, 525-32.
[7]. Greathouse KC, Hall MW. Critical Illness–Induced Immune Suppression: Current State of the Science. American Journal of Critical Care. 25(1), 2016, 85-92.
[8]. Van Vught LA, Wiewel MA, Hoogendijk AJ, Scicluna BP, Belkasim H, Horn J, Schultz MJ, Van der Poll T. Reduced responsiveness of blood leukocytes to lipopolysaccharide does not predict nosocomial infections in critically ill patients. Critical Care. 19(1), 2015, 1
[9]. Downregulation of Proinflammatory Cytokine Release in Whole Blood From Septic PatientsBlood, 85(5), 1995, 1341-134
[10]. Manzoli TF, Troster EJ, Ferranti JF, Sales MM. Prolonged suppression of monocytic human leukocyte antigen–DR expression correlates with mortality in pediatric septic patients in a pediatric tertiary Intensive Care Unit. Journal of critical care. 33, 2016, 84-9
[11]. Changes of monocyte human leukocyte antigen- DR expression as a reliable predictor of mortality Critical Care 15, 2011, 220
[12]. Venet F, Lukaszewicz AC, Payen D, Hotchkiss R, Monneret G. Monitoring the immune response in sepsis: a rational approach to administration of immunoadjuvant therapies. Current opinion in immunology. 25(4), 2013, 477-83